WorldWideScience

Sample records for assess tissue vasculature

  1. Using Non-Invasive Multi-Spectral Imaging to Quantitatively Assess Tissue Vasculature

    Energy Technology Data Exchange (ETDEWEB)

    Vogel, A; Chernomordik, V; Riley, J; Hassan, M; Amyot, F; Dasgeb, B; Demos, S G; Pursley, R; Little, R; Yarchoan, R; Tao, Y; Gandjbakhche, A H

    2007-10-04

    This research describes a non-invasive, non-contact method used to quantitatively analyze the functional characteristics of tissue. Multi-spectral images collected at several near-infrared wavelengths are input into a mathematical optical skin model that considers the contributions from different analytes in the epidermis and dermis skin layers. Through a reconstruction algorithm, we can quantify the percent of blood in a given area of tissue and the fraction of that blood that is oxygenated. Imaging normal tissue confirms previously reported values for the percent of blood in tissue and the percent of blood that is oxygenated in tissue and surrounding vasculature, for the normal state and when ischemia is induced. This methodology has been applied to assess vascular Kaposi's sarcoma lesions and the surrounding tissue before and during experimental therapies. The multi-spectral imaging technique has been combined with laser Doppler imaging to gain additional information. Results indicate that these techniques are able to provide quantitative and functional information about tissue changes during experimental drug therapy and investigate progression of disease before changes are visibly apparent, suggesting a potential for them to be used as complementary imaging techniques to clinical assessment.

  2. Three-dimensional volume analysis of vasculature in engineered tissues

    Science.gov (United States)

    YousefHussien, Mohammed; Garvin, Kelley; Dalecki, Diane; Saber, Eli; Helguera, María.

    2013-01-01

    Three-dimensional textural and volumetric image analysis holds great potential in understanding the image data produced by multi-photon microscopy. In this paper, an algorithm that quantitatively analyzes the texture and the morphology of vasculature in engineered tissues is proposed. The investigated 3D artificial tissues consist of Human Umbilical Vein Endothelial Cells (HUVEC) embedded in collagen exposed to two regimes of ultrasound standing wave fields under different pressure conditions. Textural features were evaluated using the normalized Gray-Scale Cooccurrence Matrix (GLCM) combined with Gray-Level Run Length Matrix (GLRLM) analysis. To minimize error resulting from any possible volume rotation and to provide a comprehensive textural analysis, an averaged version of nine GLCM and GLRLM orientations is used. To evaluate volumetric features, an automatic threshold using the gray level mean value is utilized. Results show that our analysis is able to differentiate among the exposed samples, due to morphological changes induced by the standing wave fields. Furthermore, we demonstrate that providing more textural parameters than what is currently being reported in the literature, enhances the quantitative understanding of the heterogeneity of artificial tissues.

  3. Tissue-engineered microenvironment systems for modeling human vasculature.

    Science.gov (United States)

    Tourovskaia, Anna; Fauver, Mark; Kramer, Gregory; Simonson, Sara; Neumann, Thomas

    2014-09-01

    The high attrition rate of drug candidates late in the development process has led to an increasing demand for test assays that predict clinical outcome better than conventional 2D cell culture systems and animal models. Government agencies, the military, and the pharmaceutical industry have started initiatives for the development of novel in-vitro systems that recapitulate functional units of human tissues and organs. There is growing evidence that 3D cell arrangement, co-culture of different cell types, and physico-chemical cues lead to improved predictive power. A key element of all tissue microenvironments is the vasculature. Beyond transporting blood the microvasculature assumes important organ-specific functions. It is also involved in pathologic conditions, such as inflammation, tumor growth, metastasis, and degenerative diseases. To provide a tool for modeling this important feature of human tissue microenvironments, we developed a microfluidic chip for creating tissue-engineered microenvironment systems (TEMS) composed of tubular cell structures. Our chip design encompasses a small chamber that is filled with an extracellular matrix (ECM) surrounding one or more tubular channels. Endothelial cells (ECs) seeded into the channels adhere to the ECM walls and grow into perfusable tubular tissue structures that are fluidically connected to upstream and downstream fluid channels in the chip. Using these chips we created models of angiogenesis, the blood-brain barrier (BBB), and tumor-cell extravasation. Our angiogenesis model recapitulates true angiogenesis, in which sprouting occurs from a "parent" vessel in response to a gradient of growth factors. Our BBB model is composed of a microvessel generated from brain-specific ECs within an ECM populated with astrocytes and pericytes. Our tumor-cell extravasation model can be utilized to visualize and measure tumor-cell migration through vessel walls into the surrounding matrix. The described technology can be used

  4. Partial corrosion casting to assess cochlear vasculature in mouse models of presbycusis and CMV infection.

    Science.gov (United States)

    Carraro, Mattia; Park, Albert H; Harrison, Robert V

    2016-02-01

    Some forms of sensorineural hearing loss involve damage or degenerative changes to the stria vascularis and/or other vascular structures in the cochlea. In animal models, many methods for anatomical assessment of cochlear vasculature exist, each with advantages and limitations. One methodology, corrosion casting, has proved useful in some species, however in the mouse model this technique is difficult to achieve because digestion of non vascular tissue results in collapse of the delicate cast specimen. We have developed a partial corrosion cast method that allows visualization of vasculature along much of the cochlear length but maintains some structural integrity of the specimen. We provide a detailed step-by-step description of this novel technique. We give some illustrative examples of the use of the method in mouse models of presbycusis and cytomegalovirus (CMV) infection.

  5. Assessment of variability in cerebral vasculature for neuro-anatomical surgery planning in rodent brain

    Science.gov (United States)

    Rangarajan, J. R.; Van Kuyck, K.; Himmelreich, U.; Nuttin, B.; Maes, F.; Suetens, P.

    2011-03-01

    Clinical and pre-clinical studies show that deep brain stimulation (DBS) of targeted brain regions by neurosurgical techniques ameliorate psychiatric disorder such as anorexia nervosa. Neurosurgical interventions in preclinical rodent brain are mostly accomplished manually with a 2D atlas. Considering both the large number of animals subjected to stereotactic surgical experiments and the associated imaging cost, feasibility of sophisticated pre-operative imaging based surgical path planning and/or robotic guidance is limited. Here, we spatially normalize vasculature information and assess the intra-strain variability in cerebral vasculature for a neurosurgery planning. By co-registering and subsequently building a probabilistic vasculature template in a standard space, we evaluate the risk of a user defined electrode trajectory damaging a blood vessel on its path. The use of such a method may not only be confined to DBS therapy in small animals, but also could be readily applicable to a wide range of stereotactic small animal surgeries like targeted injection of contrast agents and cell labeling applications.

  6. Stem cell-derived vasculature: A potent and multidimensional technology for basic research, disease modeling, and tissue engineering.

    Science.gov (United States)

    Lowenthal, Justin; Gerecht, Sharon

    2016-05-01

    Proper blood vessel networks are necessary for constructing and re-constructing tissues, promoting wound healing, and delivering metabolic necessities throughout the body. Conversely, an understanding of vascular dysfunction has provided insight into the pathogenesis and progression of diseases both common and rare. Recent advances in stem cell-based regenerative medicine - including advances in stem cell technologies and related progress in bioscaffold design and complex tissue engineering - have allowed rapid advances in the field of vascular biology, leading in turn to more advanced modeling of vascular pathophysiology and improved engineering of vascularized tissue constructs. In this review we examine recent advances in the field of stem cell-derived vasculature, providing an overview of stem cell technologies as a source for vascular cell types and then focusing on their use in three primary areas: studies of vascular development and angiogenesis, improved disease modeling, and the engineering of vascularized constructs for tissue-level modeling and cell-based therapies.

  7. Comparative evaluation of 64-slice CT angiography and digital subtraction angiography in assessing the cervicocranial vasculature

    Directory of Open Access Journals (Sweden)

    Randolf Klingebiel

    2008-08-01

    Full Text Available Randolf Klingebiel1, Max Kentenich3, Hans-Christian Bauknecht3, Florian Masuhr2, Eberhard Siebert1, Markus Busch2, Georg Bohner11Department of Neuroradiology, 2Department of Neurology, 3Department of Radiology, Charité Universitary Medicine Berlin, GermanyBackground: Noninvasive 64-slice computed tomography angiography (64-MSCTA closely approximates conventional catheter angiography (DSA in terms of detail resolution. Objective: Retrospective evaluation of cervicocranial (cc 64-MSCTA in comparison with DSA in patients with presumptive cc vascular disorders.Material and methods: Twenty-four 64-MSCTA studies (32 mm detector width, slice thickness 0.5 mm, 120 kv, 150 mAs, pitch 0.75 of patients with presumptive cc vascular pathology (13 men, 11 women, mean age 38.3 ± 11.3 yrs, range 19–54 yrs were assessed in comparison with DSA studies without abnormal findings in age-matched patients (11 men, 13 women, mean age 39.7 ± 11.9 yrs, range 18–54 yrs. Study readings were performed in a blinded manner by two neuroradiologists with respect to image quality and assessibility of various cc vascular segments by using a five-point scale. Radiation exposure was calculated for 64-MSCTA.Results: Each reader assessed 384/528 different vessel segments (64-MSCTA/DSA. Superior image quality was attributed to DSA with respect to the C1 ICA–C6 ICA, A3 ACA, and P3 PCA segments as well the AICA and SCA. 64-MSCTA was scored superior for C7 ICA and V4 VA segments. A significantly increased number of nonassessable V2- and V3 VA segments in DSA studies was noted. The effective dose for 64-MSCTA amounted to 2.2 mSv.Conclusions: 64-MSCTA provides near-equivalent diagnostic information of the cc vasculature as compared with DSA. According to our results, DSA should be considered primarily when peripheral vessels (A3/P3 or ICA segments close to the skull base (C2-5 are of interest, such as in primary angiitis or stenoocclusive ICA disease, respectively.Keywords: CT

  8. New aspects of fenestrated vasculature and tissue dynamics in the sensory circumventricular organs of adult brains

    Directory of Open Access Journals (Sweden)

    Seiji eMiyata

    2015-10-01

    Full Text Available The blood–brain barrier (BBB generally consists of endothelial tight junction barriers that prevent the free entry of blood-derived substances, thereby maintaining the extracellular environment of the brain. However, the circumventricular organs (CVOs, which are located along the midlines of the brain ventricles, lack these endothelial barriers and have fenestrated capillaries; therefore, they have a number of essential functions, including the transduction of information between the blood circulation and brain. Previous studies have demonstrated the extensive contribution of the CVOs to body fluid and thermal homeostasis, energy balance, the chemoreception of blood-derived substances, and neuroinflammation. In this review, recent advances have been discussed in fenestrated capillary characterization and dynamic tissue reconstruction accompanied by angiogenesis and neurogliogenesis in the sensory CVOs of adult brains. The sensory CVOs, including the organum vasculosum of the lamina terminalis (OVLT, subfornical organ (SFO, and area postrema (AP, have size-selective and heterogeneous vascular permeabilities. Astrocyte-/tanycyte-like neural stem cells (NSCs sense blood- and cerebrospinal fluid-derived information through the transient receptor potential vanilloid 1, a mechanical/osmotic receptor, Toll-like receptor 4, a lipopolysaccharide receptor, and Nax, a Na-sensing Na channel. They also express tight junction proteins and densely and tightly surround mature neurons to protect them from blood-derived neurotoxic substances, indicating that the NSCs of the CVOs perform BBB functions while maintaining the capacity to differentiate into new neurons and glial cells. In addition to neurogliogenesis, the density of fenestrated capillaries is regulated by angiogenesis, which is accompanied by the active proliferation and sprouting of endothelial cells. Vascular endothelial growth factor (VEGF signaling may be involved in angiogenesis and

  9. Development of poly(l-lactic acid) hollow fiber membranes for artificial vasculature in tissue engineering scaffolds

    NARCIS (Netherlands)

    Bettahalli, N.M.S.; Steg, H.; Wessling, M.; Stamatialis, D.

    2011-01-01

    In tissue engineering constructs, vascularization within in vitro cultured tissue is one of the major problems, as proliferating cells act themselves as a barrier for mass transfer. Issues related especially to nutrient and oxygen delivery to the cells limit tissue construct development to smaller t

  10. Functional assessment of hand vasculature using infrared and laser speckle imaging

    Science.gov (United States)

    Gorbach, A. M.; Wang, H.; Wiedenbeck, B.; Liu, W.; Smith, P. D.; Elster, E.

    2009-02-01

    To assess vascular responses of the human hand to inspiratory gasps and hand cooling, two imaging "remote sensing" instruments were utilized: 1) a high-resolution infrared (IR) imaging camera and 2) a full-field laser perfusion imager (FLPI). Data analysis was performed on the data sets collected simultaneously from both instruments. A non-localized drop of both FLPI and IR signals was observed at ~0.5-2.0 min after gasp onset. Spontaneous oscillations, much below the human cardiac and respiratory frequencies, were observed with both imagers. The dominant oscillations for both imaging modalities centered around 0.01Hz. Spectral frequencies, their power, and the duration of temperature oscillations (bursts) for different hand areas changed in time and were spatially heterogeneous. The highest spatial correlation between the two data sets was found between the mean IR derivative image and the mean original FLPI image for the baseline conditions. Heterogeneous images of the human hand were consistently detected non-invasively by both instruments. After cooling, a temperature elevation of ~0.5ºC was seen as a spotted pattern mainly in the thenar and hypothenar areas. A generalized increase in perfusion over the same areas was observed in FLPI images. Both IR and FLPI imagers sensitively identify vasoconstrictor responses induced by inspiratory gasp and hand cooling maneuvers. The specificity to physiological changes and high imaging rate for both instruments, coupled with the current ease of use of optical cameras in clinical settings, make the described combination of two instruments an ideal imaging approach to studying the dynamics of thermal and perfusion heterogeneity in human skin.

  11. Enhanced gene delivery in porcine vasculature tissue following incorporation of adeno-associated virus nanoparticles into porous silicon microparticles.

    Science.gov (United States)

    McConnell, Kellie I; Rhudy, Jessica; Yokoi, Kenji; Gu, Jianhua; Mack, Aaron; Suh, Junghae; La Francesca, Saverio; Sakamoto, Jason; Serda, Rita E

    2014-11-28

    There is an unmet clinical need to increase lung transplant successes, patient satisfaction and to improve mortality rates. We offer the development of a nanovector-based solution that will reduce the incidence of lung ischemic reperfusion injury (IRI) leading to graft organ failure through the successful ex vivo treatment of the lung prior to transplantation. The innovation is in the integrated application of our novel porous silicon (pSi) microparticles carrying adeno-associated virus (AAV) nanoparticles, and the use of our ex vivo lung perfusion/ventilation system for the modulation of pro-inflammatory cytokines initiated by ischemic pulmonary conditions prior to organ transplant that often lead to complications. Gene delivery of anti-inflammatory agents to combat the inflammatory cascade may be a promising approach to prevent IRI following lung transplantation. The rationale for the device is that the microparticle will deliver a large payload of virus to cells and serve to protect the AAV from immune recognition. The microparticle-nanoparticle hybrid device was tested both in vitro on cell monolayers and ex vivo using either porcine venous tissue or a pig lung transplantation model, which recapitulates pulmonary IRI that occurs clinically post-transplantation. Remarkably, loading AAV vectors into pSi microparticles increases gene delivery to otherwise non-permissive endothelial cells.

  12. Hemodynamic Assessment of Compliance of Pre-Stressed Pulmonary Valve-Vasculature in Patient Specific Geometry Using an Inverse Algorithm

    Science.gov (United States)

    Hebbar, Ullhas; Paul, Anup; Banerjee, Rupak

    2016-11-01

    Image based modeling is finding increasing relevance in assisting diagnosis of Pulmonary Valve-Vasculature Dysfunction (PVD) in congenital heart disease patients. This research presents compliant artery - blood interaction in a patient specific Pulmonary Artery (PA) model. This is an improvement over our previous numerical studies which assumed rigid walled arteries. The impedance of the arteries and the energy transfer from the Right Ventricle (RV) to PA is governed by compliance, which in turn is influenced by the level of pre-stress in the arteries. In order to evaluate the pre-stress, an inverse algorithm was developed using an in-house script written in MATLAB and Python, and implemented using the Finite Element Method (FEM). This analysis used a patient specific material model developed by our group, in conjunction with measured pressure (invasive) and velocity (non-invasive) values. The analysis was performed on an FEM solver, and preliminary results indicated that the Main PA (MPA) exhibited higher compliance as well as increased hysteresis over the cardiac cycle when compared with the Left PA (LPA). The computed compliance values for the MPA and LPA were 14% and 34% lesser than the corresponding measured values. Further, the computed pressure drop and flow waveforms were in close agreement with the measured values. In conclusion, compliant artery - blood interaction models of patient specific geometries can play an important role in hemodynamics based diagnosis of PVD.

  13. A Simple Method to Assess In Vivo Proliferation in Lung Vasculature with EdU: The Case of MMC-Induced PVOD in Rat

    Science.gov (United States)

    Fabrice, Antigny; Benoît, Ranchoux; Valérie, Nadeau; Lau, Edmund; Sébastien, Bonnet; Frédéric, Perros

    2015-01-01

    5-Ethynyl-2′-deoxyuridine (EdU) incorporation is becoming the gold standard method for in vitro and in vivo visualization of proliferating cells. The small size of the fluorescent azides used for detection results in a high degree of specimen penetration. It can be used to easily detect DNA replication in large tissue samples or organ explants with low proliferation and turnover of cells formerly believed to be in a “terminal” state of differentiation. Here we describe a protocol for the localization and identification of proliferating cells in quiescent or injured pulmonary vasculature, in a model of pulmonary veno-occlusive disease (PVOD). PVOD is an uncommon form of pulmonary hypertension characterized by progressive obstruction of small pulmonary veins. We previously reported that mitomycin-C (MMC) therapy is associated with PVOD in human. We demonstrated that MMC can induce PVOD in rats, which currently represents the sole animal model that recapitulates human PVOD lesions. Using the EdU assay, we demonstrated that MMC-exposed lungs displayed areas of exuberant microvascular endothelial cell proliferation which mimics pulmonary capillary hemangiomatosis, one of the pathologic hallmarks of human PVOD. In vivo pulmonary cell proliferation measurement represents an interesting methodology to investigate the potential efficacy of therapies aimed at normalizing pathologic angioproliferation. PMID:26345623

  14. A simple method to assess in vivo proliferation in lung vasculature with EdU: the case of MMC-induced PVOD in rat.

    Science.gov (United States)

    Fabrice, Antigny; Benoît, Ranchoux; Valérie, Nadeau; Lau, Edmund; Sébastien, Bonnet; Frédéric, Perros

    2015-01-01

    5-Ethynyl-2'-deoxyuridine (EdU) incorporation is becoming the gold standard method for in vitro and in vivo visualization of proliferating cells. The small size of the fluorescent azides used for detection results in a high degree of specimen penetration. It can be used to easily detect DNA replication in large tissue samples or organ explants with low proliferation and turnover of cells formerly believed to be in a "terminal" state of differentiation. Here we describe a protocol for the localization and identification of proliferating cells in quiescent or injured pulmonary vasculature, in a model of pulmonary veno-occlusive disease (PVOD). PVOD is an uncommon form of pulmonary hypertension characterized by progressive obstruction of small pulmonary veins. We previously reported that mitomycin-C (MMC) therapy is associated with PVOD in human. We demonstrated that MMC can induce PVOD in rats, which currently represents the sole animal model that recapitulates human PVOD lesions. Using the EdU assay, we demonstrated that MMC-exposed lungs displayed areas of exuberant microvascular endothelial cell proliferation which mimics pulmonary capillary hemangiomatosis, one of the pathologic hallmarks of human PVOD. In vivo pulmonary cell proliferation measurement represents an interesting methodology to investigate the potential efficacy of therapies aimed at normalizing pathologic angioproliferation.

  15. A Simple Method to Assess In Vivo Proliferation in Lung Vasculature with EdU: The Case of MMC-Induced PVOD in Rat

    Directory of Open Access Journals (Sweden)

    Antigny Fabrice

    2015-01-01

    Full Text Available 5-Ethynyl-2′-deoxyuridine (EdU incorporation is becoming the gold standard method for in vitro and in vivo visualization of proliferating cells. The small size of the fluorescent azides used for detection results in a high degree of specimen penetration. It can be used to easily detect DNA replication in large tissue samples or organ explants with low proliferation and turnover of cells formerly believed to be in a “terminal” state of differentiation. Here we describe a protocol for the localization and identification of proliferating cells in quiescent or injured pulmonary vasculature, in a model of pulmonary veno-occlusive disease (PVOD. PVOD is an uncommon form of pulmonary hypertension characterized by progressive obstruction of small pulmonary veins. We previously reported that mitomycin-C (MMC therapy is associated with PVOD in human. We demonstrated that MMC can induce PVOD in rats, which currently represents the sole animal model that recapitulates human PVOD lesions. Using the EdU assay, we demonstrated that MMC-exposed lungs displayed areas of exuberant microvascular endothelial cell proliferation which mimics pulmonary capillary hemangiomatosis, one of the pathologic hallmarks of human PVOD. In vivo pulmonary cell proliferation measurement represents an interesting methodology to investigate the potential efficacy of therapies aimed at normalizing pathologic angioproliferation.

  16. Perfusion assessment in rat spinal cord tissue using photoplethysmography and laser Doppler flux measurements

    Science.gov (United States)

    Phillips, Justin P.; Cibert-Goton, Vincent; Langford, Richard M.; Shortland, Peter J.

    2013-03-01

    Animal models are widely used to investigate the pathological mechanisms of spinal cord injury (SCI), most commonly in rats. It is well known that compromised blood flow caused by mechanical disruption of the vasculature can produce irreversible damage and cell death in hypoperfused tissue regions and spinal cord tissue is particularly susceptible to such damage. A fiberoptic photoplethysmography (PPG) probe and instrumentation system were used to investigate the practical considerations of making measurements from rat spinal cord and to assess its suitability for use in SCI models. Experiments to assess the regional perfusion of exposed spinal cord in anesthetized adult rats using both PPG and laser Doppler flowmetry (LDF) were performed. It was found that signals could be obtained reliably from all subjects, although considerable intersite and intersubject variability was seen in the PPG signal amplitude compared to LDF. We present results from 30 measurements in five subjects, the two methods are compared, and practical application to SCI animal models is discussed.

  17. Imaging vasculature and lymphatic flow in mice using quantum dots

    DEFF Research Database (Denmark)

    Ballou, Byron; Ernst, Lauren A.; Andreko, Susan

    2009-01-01

    Quantum dots are ideal probes for fluorescent imaging of vascular and lymphatic tissues. On injection into appropriate sites, red- and near-infrared-emitting quantum dots provide excellent definition of vasculature, lymphoid organs, and lymph nodes draining both normal tissues and tumors. We deta...

  18. Complexity analysis of angiogenesis vasculature

    Science.gov (United States)

    Mahadevan, Vijay; Tyrell, James A.; Tong, Ricky T.; Brown, Edward B.; Jain, Rakesh K.; Roysam, Badrinath

    2005-04-01

    Tumor vasculature has a high degree of irregularity as compared to normal vasculature. The quantification of the morphometric complexity in tumor images can be useful in diagnosis. Also, it is desirable in several other medical applications to have an automated complexity analysis to aid in diagnosis and prognosis under treatment. e.g. in diabetic retinopathy and in arteriosclerosis. In addition, prior efforts at segmentation of the tumor vasculature using matched filtering, template matching and splines have been hampered by the irregularity of these vessels. We try to solve both problems by introducing a novel technique for vessel detection, followed by a tracing-independent complexity analysis based on a combination of ideas. First, the vessel cross-sectional profile is modeled using a continuous and everywhere differentiable family of super-Gaussian curves. This family generates rectangular profiles that can accurately localize the vessel boundaries in microvasculature images. Second, a robust non-linear regression algorithm based on M-estimators is used to estimate the parameters that optimally characterize the vessel"s shape. A framework for the quantitative analysis of the complexity of the vasculature based on the vessel detection is presented. A set of measures that quantify the complexity are proposed viz. Squared Error, Entropy-based and Minimum Description Length-based Shape Complexities. They are completely automatic and can deal with complexities of the entire vessel unlike existing tortuousity measures which deal only with vessel centerlines. The results are validated using carefully constructed phantom and real image data with ground truth information from an expert observer.

  19. Tube-Like Structures with Co-Expression of D2-40 and CD34: Newly Formed Vasculatures?

    Directory of Open Access Journals (Sweden)

    Bin Jiang, Jeffrey Mason, Anahid Jewett, William CS Cho, Yan-gao Man

    2012-01-01

    Full Text Available Background: A great number of in vitro and in vivo studies have suggested that many pathways or factors can stimulate angiogenesis and lymphangiogenesis, which facilitate tumor progression and metastasis. However, the morphological and immunohistochemical profile of newly formed vasculatures has not been elucidated, making it difficult to differentiate them from the pre-existing ones, and to identify their unique molecular profiles for diagnosis and therapeutic interventions.Experimental findings: As cytokeratin (CK-19 is a well-recognized stem cell marker and CK-19-positive cells are frequently detected in the peripheral blood of patients with metastatic cancer, our recent studies have assessed the involvement of CK-19 in the formation of new vasculatures in primary colorectal cancer (CRC tissues. Our studies showed that a subset of lymph node-positive cases harbored some isolated normal epithelial structures with distinct CK-19 immunostaining within an otherwise CK-19-negative background. These structures are exclusively located within or adjacent to lymphoid follicles and are often surrounded by tube-like structures expressing lymphatic endothelial marker D2-40. Similar structures are more frequently seen at the junctions between pre-invasive and invasive CRC with the following features: (1. they consist of a single layer of endothelial cells that express both D2-40 and CD34, (2. their endothelial walls are often incomplete with disseminated cells protruding into the adjacent stroma, and (3. they are exclusively associated with disseminated CK-19-positive cellsHypothesis: Based on these findings, we propose that these tube-like structures represent newly formed vasculatures, which are derived by the convergence of aberrant lymphocyte infiltration and tumor stem cells. Because of their close physical proximity, tumor stem cells within the epithelial and stromal components contribute equally and coordinately to the morphogenesis of new

  20. Assessing local tissue edema in postmastectomy lymphedema.

    Science.gov (United States)

    Mayrovitz, H N

    2007-06-01

    Overall limb lymphedema can be assessed by several methods but none are suitable to determine local edema. Quantifying local edema could provide important information not previously available. Our goal was to determine the suitability of using the tissue dielectric constant (TDC) as and index of local tissue water to detect and quantify edema in postmastectomy patients with unilateral arm lymphedema. Segmental arm volume and TDC were measured in both arms of 18 women with unilateral lymphedema, and in 15 premenopausal and 15 postmenopausal controls. TDC was measured at a frequency of 300 MHz using open-ended coaxial probes with effective measuring depths of 0.5, 1.5, 2.5 and 5.0 mm. For patients and controls, absolute TDC depended on measurement depth but for any depth the TDC of lymphedematous segments was significantly greater than for non-affected contralateral arms (pTDC ratio between arms for patients was 1.64+/-0.30 vs.1.04+/-0.04 for both control groups (pTDC ratio was as low as 1.2 and no control subject's TDC ratio was as great as 1.2. Results suggest that this method is a good quantitative discriminator of the presence of lymphedema in patients with unilateral limb lymphedema.

  1. Real time imaging of peripheral nerve vasculature using optical coherence angiography

    Science.gov (United States)

    Vasudevan, Srikanth; Kumsa, Doe; Takmakov, Pavel; Welle, Cristin G.; Hammer, Daniel X.

    2016-03-01

    The peripheral nervous system (PNS) carries bidirectional information between the central nervous system and distal organs. PNS stimulation has been widely used in medical devices for therapeutic indications, such as bladder control and seizure cessation. Investigational uses of PNS stimulation include providing sensory feedback for improved control of prosthetic limbs. While nerve safety has been well documented for stimulation parameters used in marketed devices, novel PNS stimulation devices may require alternative stimulation paradigms to achieve maximum therapeutic benefit. Improved testing paradigms to assess the safety of stimulation will expedite the development process for novel PNS stimulation devices. The objective of this research is to assess peripheral nerve vascular changes in real-time with optical coherence angiography (OCA). A 1300-nm OCA system was used to image vasculature changes in the rat sciatic nerve in the region around a surface contacting single electrode. Nerves and vasculature were imaged without stimulation for 180 minutes to quantify resting blood vessel diameter. Walking track analysis was used to assess motor function before and 6 days following experiments. There was no significant change in vessel diameter between baseline and other time points in all animals. Motor function tests indicated the experiments did not impair functionality. We also evaluated the capabilities to image the nerve during electrical stimulation in a pilot study. Combining OCA with established nerve assessment methods can be used to study the effects of electrical stimulation safety on neural and vascular tissue in the periphery.

  2. Microfocal angiography of the pulmonary vasculature

    Science.gov (United States)

    Clough, Anne V.; Haworth, Steven T.; Roerig, David T.; Linehan, John H.; Dawson, Christopher A.

    1998-07-01

    X-ray microfocal angiography provides a means of assessing regional microvascular perfusion parameters using residue detection of vascular indicators. As an application of this methodology, we studied the effects of alveolar hypoxia, a pulmonary vasoconstrictor, on the pulmonary microcirculation to determine changes in regional blood mean transit time, volume and flow between control and hypoxic conditions. Video x-ray images of a dog lung were acquired as a bolus of radiopaque contrast medium passed through the lobar vasculature. X-ray time-absorbance curves were acquired from arterial and microvascular regions-of-interest during both control and hypoxic alveolar gas conditions. A mathematical model based on indicator-dilution theory applied to image residue curves was applied to the data to determine changes in microvascular perfusion parameters. Sensitivity of the model parameters to the model assumptions was analyzed. Generally, the model parameter describing regional microvascular volume, corresponding to area under the microvascular absorbance curve, was the most robust. The results of the model analysis applied to the experimental data suggest a significant decrease in microvascular volume with hypoxia. However, additional model assumptions concerning the flow kinematics within the capillary bed may be required for assessing changes in regional microvascular flow and mean transit time from image residue data.

  3. Photon-tissue interaction model for quantitative assessment of biological tissues

    Science.gov (United States)

    Lee, Seung Yup; Lloyd, William R.; Wilson, Robert H.; Chandra, Malavika; McKenna, Barbara; Simeone, Diane; Scheiman, James; Mycek, Mary-Ann

    2014-02-01

    In this study, we describe a direct fit photon-tissue interaction model to quantitatively analyze reflectance spectra of biological tissue samples. The model rapidly extracts biologically-relevant parameters associated with tissue optical scattering and absorption. This model was employed to analyze reflectance spectra acquired from freshly excised human pancreatic pre-cancerous tissues (intraductal papillary mucinous neoplasm (IPMN), a common precursor lesion to pancreatic cancer). Compared to previously reported models, the direct fit model improved fit accuracy and speed. Thus, these results suggest that such models could serve as real-time, quantitative tools to characterize biological tissues assessed with reflectance spectroscopy.

  4. Multidetector CT angiography of renal vasculature: normal anatomy and variants

    Energy Technology Data Exchange (ETDEWEB)

    Tuerkvatan, Aysel; Oezdemir, Mustafa; Cumhur, Turhan; Oelcer, Tuelay [Tuerkiye Yueksek ihtisas Hospital, Department of Radiology, Sihhiye, Ankara (Turkey)

    2009-01-15

    Knowledge of the variations in renal vascular anatomy is important before laparoscopic donor or partial nephrectomy and vascular reconstruction for renal artery stenosis or abdominal aortic aneurysm. Recently, multidetector computed tomographic (MDCT) angiography has become a principal imaging investigation for assessment of the renal vasculature and has challenged the role of conventional angiography. It is an excellent imaging technique because it is a fast and non-invasive tool that provides highly accurate and detailed evaluation of normal renal vascular anatomy and variants. The number, size and course of the renal arteries and veins are easily identified by MDCT angiography. The purpose of this pictorial essay is to illustrate MDCT angiographic appearance of normal anatomy and common variants of the renal vasculature. (orig.)

  5. Prostate-specific membrane antigen expression in tumor-associated vasculature of breast cancers.

    Science.gov (United States)

    Wernicke, Alla Gabriella; Varma, Sonal; Greenwood, Eleni A; Christos, Paul J; Chao, K S Clifford; Liu, He; Bander, Neil H; Shin, Sandra J

    2014-06-01

    Prostate-specific membrane antigen (PSMA) has been found to be expressed in the tumor-associated neovasculature of multiple solid tumor types including breast cancers. However, thus far, the number of cases studied from some tumor types has been limited. In this study, we set out to assess PSMA expression in the tumor-associated vasculature associated with invasive breast carcinomas in a sizable cohort of patients. One hundred and six patients with AJCC stage 0-IV breast cancer were identified. Ninety-two of these patients had primary breast cancer [invasive breast carcinoma with or without co-existing ductal carcinoma in situ (DCIS) (74) or DCIS alone (18)]. In addition, 14 patients with breast cancer metastases to the brain were identified. Immunohistochemical staining for PSMA and CD31 was performed on parallel representative tumor sections in each case. Tumor-associated vascular endothelial cell PSMA immunoreactivity was semi-quantitatively assessed based on two parameters: overall percent of endothelial positivity and staining intensity. PSMA expression for tumor-associated vascular endothelial cells was scored 0 if there was no detectable PSMA expression, 1 if PSMA staining was detectable in 5-50%, and 2 if PSMA expression was positive in >50% of microvessels. CD 31 staining was concurrently reviewed to confirm the presence of vasculature in each case. Tumor-associated vasculature was PSMA-positive in 68/92 (74%) of primary breast cancers and in 14/14 (100%) of breast cancers metastatic to brain. PSMA was not detected in normal breast tissue or carcinoma cells. All but 2 cases (98%) showed absence of PSMA expression in normal breast tissue-associated vasculature. The 10-year overall survival was 88.7% (95% CI = 80.0%, 93.8%) in patients without brain metastases. When overall survival (OS) was stratified based on PSMA score group, patients with PSMA scores of 0, 1, and 2 had 10-year OS of 95.8%, 96.0%, and 79.7%, respectively (p = 0.12). When PSMA scores

  6. Assessment of in situ adipose tissue inflammation by microdialysis

    DEFF Research Database (Denmark)

    Langkilde, Anne; Andersen, Ove; Henriksen, Jens H;

    2015-01-01

    Inflammation, and specifically adipose tissue (AT) inflammation, is part of the pathophysiology of obesity and HIV-associated lipodystrophy. Local AT protein assessment methods are limited, and AT inflammation studies have therefore primarily examined inflammatory gene expression. We therefore...

  7. Gpr177 regulates pulmonary vasculature development.

    Science.gov (United States)

    Jiang, Ming; Ku, Wei-yao; Fu, Jiang; Offermanns, Stefan; Hsu, Wei; Que, Jianwen

    2013-09-01

    Establishment of the functional pulmonary vasculature requires intimate interaction between the epithelium and mesenchyme. Previous genetic studies have led to inconsistent conclusions about the contribution of epithelial Wnts to pulmonary vasculature development. This discrepancy is possibly due to the functional redundancy among different Wnts. Here, we use Shh-Cre to conditionally delete Gpr177 (the mouse ortholog of Drosophila Wntless, Wls), a chaperon protein important for the sorting and secretion of Wnt proteins. Deletion of epithelial Gpr177 reduces Wnt signaling activity in both the epithelium and mesenchyme, resulting in severe hemorrhage and abnormal vasculature, accompanied by branching defects and abnormal epithelial differentiation. We then used multiple mouse models to demonstrate that Wnt/β-catenin signaling is not only required for the proliferation and differentiation of mesenchyme, but also is important for the maintenance of smooth muscle cells through the regulation of the transcription factor Kruppel-like factor 2 (Klf2). Together, our studies define a novel mechanism by which epithelial Wnts regulate the normal development and maintenance of pulmonary vasculature. These findings provide insight into the pathobiology of congenital lung diseases, such as alveolar capillary dysplasia (ACD), that have abnormal alveolar development and dysmorphic pulmonary vasculature.

  8. Histological assessment in peripheral nerve tissue engineering

    Institute of Scientific and Technical Information of China (English)

    Vctor Carriel; Ingrid Garzn; Miguel Alaminos; Maria Cornelissen

    2014-01-01

    The histological analysis of peripheral nerve regeneration is one of the most used methods to demonstrate the success of the regeneration through nerve conduits. Nowadays, it is possible to evaluate different parameters of nerve regeneration by using histological, histochemical, immunohistochemical and ultrastructural techniques. The histochemical methods are very sensible and are useful tools to evaluate the extracellular matrix remodeling and the myelin sheath, but they are poorly speciifc. In contrast, the immunohistochemical methods are highly speciifc and are frequently used for the identiifcation of the regenerated axons, Schwann cells and proteins associated to nerve regeneration or neural linage. The ultrastructural techniques offer the possibility to perform a high resolution morphological and quantitative analysis of the nerve regeneration. However, the use of a single histological method may not be enough to assess the degree of regeneration, and the combination of different histological techniques could be necessary.

  9. Assessment of Regional Myocardial Displacement via Spectral Tissue Doppler Compared with Color Tissue Tracking

    Directory of Open Access Journals (Sweden)

    Zahra Ojaghi-Haghighi

    2008-12-01

    Full Text Available Background: The recent developments in tissue Doppler imaging (TDI now more than ever permit the quantification of the myocardial function. In the current systems, tissue tracking or displacement curves are generated from color tissue Doppler data through the instantaneous temporal integral of velocity-time curves. Methods: The purpose of the present study was to assess regional myocardial displacement via spectral TDI. Maximum myocardial velocities were extracted from spectral pulsed tissue Doppler images using a developed computer program and were integrated throughout the cardiac cycle. Spectral tissue Doppler echocardiography was performed to evaluate longitudinal and radial functions in 20 healthy men, and the calculated end-systolic displacements were subsequently compared with the displacements measured from the same areas via color tissue tracking. Results: According to the Bland-Altman analysis between spectral tissue tracking and color tissue tracking, the significant arithmetic mean was 7.34 mm with SD mean differences of ±2.24 mm in all of the evaluated segments. Despite significant differences (p<0.001, there was a good significant correlation between the two methods (r=0.79, p<0.001. Conclusion: A verification study showed that the proposed approach had the ability to assess regional myocardial displacement using spectral TDI, which can be used in a wider range of equipment than is currently possible.

  10. In-vivo imaging of retinal nerve fiber layer vasculature: imaging – histology comparison

    Directory of Open Access Journals (Sweden)

    Libby Richard T

    2009-08-01

    Full Text Available Abstract Background Although it has been suggested that alterations of nerve fiber layer vasculature may be involved in the etiology of eye diseases, including glaucoma, it has not been possible to examine this vasculature in-vivo. This report describes a novel imaging method, fluorescence adaptive optics (FAO scanning laser ophthalmoscopy (SLO, that makes possible for the first time in-vivo imaging of this vasculature in the living macaque, comparing in-vivo and ex-vivo imaging of this vascular bed. Methods We injected sodium fluorescein intravenously in two macaque monkeys while imaging the retina with an FAO-SLO. An argon laser provided the 488 nm excitation source for fluorescence imaging. Reflectance images, obtained simultaneously with near infrared light, permitted precise surface registration of individual frames of the fluorescence imaging. In-vivo imaging was then compared to ex-vivo confocal microscopy of the same tissue. Results Superficial focus (innermost retina at all depths within the NFL revealed a vasculature with extremely long capillaries, thin walls, little variation in caliber and parallel-linked structure oriented parallel to the NFL axons, typical of the radial peripapillary capillaries (RPCs. However, at a deeper focus beneath the NFL, (toward outer retina the polygonal pattern typical of the ganglion cell layer (inner and outer retinal vasculature was seen. These distinguishing patterns were also seen on histological examination of the same retinas. Furthermore, the thickness of the RPC beds and the caliber of individual RPCs determined by imaging closely matched that measured in histological sections. Conclusion This robust method demonstrates in-vivo, high-resolution, confocal imaging of the vasculature through the full thickness of the NFL in the living macaque, in precise agreement with histology. FAO provides a new tool to examine possible primary or secondary role of the nerve fiber layer vasculature in retinal

  11. Possibility of laboratory assessment of the state of connective tissue

    Directory of Open Access Journals (Sweden)

    G. A. Berezovskaya

    2015-01-01

    Full Text Available This article deals with the possibilities of laboratory assessment of the state of the connective tissue. It contains brief information about its structure, functions and roles of the various components in the development of pathological processes, and provides laboratory diagnostic methods of these changes.

  12. Label-free imaging of developing vasculature in zebrafish with phase variance optical coherence microscopy

    Science.gov (United States)

    Chen, Yu; Fingler, Jeff; Trinh, Le A.; Fraser, Scott E.

    2016-03-01

    A phase variance optical coherence microscope (pvOCM) has been created to visualize blood flow in the vasculature of zebrafish embryos, without using exogenous labels. The pvOCM imaging system has axial and lateral resolutions of 2 μm in tissue, and imaging depth of more than 100 μm. Imaging of 2-5 days post-fertilization zebrafish embryos identified the detailed structures of somites, spinal cord, gut and notochord based on intensity contrast. Visualization of the blood flow in the aorta, veins and intersegmental vessels was achieved with phase variance contrast. The pvOCM vasculature images were confirmed with corresponding fluorescence microscopy of a zebrafish transgene that labels the vasculature with green fluorescent protein. The pvOCM images also revealed functional information of the blood flow activities that is crucial for the study of vascular development.

  13. CLARITY reveals dynamics of ovarian follicular architecture and vasculature in three-dimensions

    Science.gov (United States)

    Feng, Yi; Cui, Peng; Lu, Xiaowei; Hsueh, Brian; Möller Billig, Fredrik; Zarnescu Yanez, Livia; Tomer, Raju; Boerboom, Derek; Carmeliet, Peter; Deisseroth, Karl; Hsueh, Aaron J. W.

    2017-01-01

    Optimal distribution of heterogeneous organelles and cell types within an organ is essential for physiological processes. Unique for the ovary, hormonally regulated folliculogenesis, ovulation, luteal formation/regression and associated vasculature changes lead to tissue remodeling during each reproductive cycle. Using the CLARITY approach and marker immunostaining, we identified individual follicles and corpora lutea in intact ovaries. Monitoring lifetime changes in follicle populations showed age-dependent decreases in total follicles and percentages of advanced follicles. Follicle development from primordial to preovulatory stage was characterized by 3 × 105-fold increases in volume, decreases in roundness, and decreased clustering of same stage follicles. Construction of follicle-vasculature relationship maps indicated age- and gonadotropin-dependent increases in vasculature and branching surrounding follicles. Heterozygous mutant mice with deletion of hypoxia-response element in the vascular endothelial growth factor A (VEGFA) promoter showed defective ovarian vasculature and decreased ovulatory responses. Unilateral intrabursal injection of axitinib, an inhibitor of VEGF receptors, retarded neo-angiogenesis that was associated with defective ovulation in treated ovaries. Our approach uncovers unique features of ovarian architecture and essential roles of vasculature in organizing follicles to allow future studies on normal and diseased human ovaries. Similar approaches could also reveal roles of neo-angiogenesis during embryonic development and tumorigenesis. PMID:28333125

  14. Assessment of FUS-Tissue Interactions In Vivo

    Science.gov (United States)

    Haritonova, Alyona V.

    Focused ultrasound (FUS) has been proposed for a variety of minimally invasive therapeutic applications, including tumor ablation, neuromodulation, targeted drug delivery and blood brain barrier opening. To date, FUS beams have been primarily monitored through MR and ultrasound diagnostic imaging modalities. The recent introduction of real-time dual-mode ultrasound array (DMUA) systems offers a new paradigm for the guidance of therapeutic focused ultrasound. The DMUA approach allows for inherent registration between the therapeutic and imaging coordinate systems. In this thesis we investigated the use of ultrasound-based thermography to assess FUS-tissue interactions. Specifically, we focused on two aspects of image-guided therapy: 1) monitoring and localization of FUS-tissue interactions, and 2) tissue damage assessment. Towards this end, we presented first experimental results of ultrasound-guided transcranial FUS in a rat brain, both ex vivo and in vivo. DMUA imaging was used to monitor and localize FUS-tissue thermal interactions in real-time. The transcranial echo data allowed for a reliable estimation of temperature change in brain tissue, which had never been done before using ultrasound image guidance. Despite some measurable distortion and loss in focusing gain, transcranial FUS beams at 3.2 MHz were localized axially and laterally. This confirms the results obtained using DMUA-based transcranial ultrasound thermography. A high degree of focusing with the DMUA was then successfully leveraged to perform localized tissue damage assessment in both ex vivo and in vivo. The experimental results presented in this thesis demonstrate some of the unique aspects of image guidance using DMUAs, especially when FUS is subject to significant distortions as in transcranial applications.

  15. Assessment of right ventricular systolic function by tissue Doppler echocardiography

    DEFF Research Database (Denmark)

    Kjærgaard, Jesper

    2012-01-01

    myocardial velocities, but no changes in SR, strain or isovolumic acceleration could be observed [II and III]. Tissue Doppler echocardiography of the RV free wall in non-massive pulmonary embolism quantifies degree of RV dysfunction, and supports the existence of the McConnell sign of mid-ventricular RV...... structure including significant dilatation, but is well tolerated with only mild reduction in measures of global RV systolic function as estimated by 2D echocardiography in an experimental animal model. Regional RV myocardial function is also only mildly reduced. Also no differences in global or regional RV......This thesis summarizes a series of studies performed in order to assess the clinical usefulness of a novel echocardiographic technology that allows non-invasive assessment of regional right ventricular myocardial velocities and deformation: tissue Doppler echocardiography. While the technology...

  16. Assessing diabetic foot ulcer development risk with hyperspectral tissue oximetry

    Science.gov (United States)

    Yudovsky, Dmitry; Nouvong, Aksone; Schomacker, Kevin; Pilon, Laurent

    2011-02-01

    Foot ulceration remains a serious health concern for diabetic patients and has a major impact on the cost of diabetes treatment. Early detection and preventive care, such as offloading or improved hygiene, can greatly reduce the risk of further complications. We aim to assess the use of hyperspectral tissue oximetry in predicting the risk of diabetic foot ulcer formation. Tissue oximetry measurements are performed during several visits with hyperspectral imaging of the feet in type 1 and 2 diabetes mellitus subjects that are at risk for foot ulceration. The data are retrospectively analyzed at 21 sites that ulcerated during the course of our study and an ulceration prediction index is developed. Then, an image processing algorithm based on this index is implemented. This algorithm is able to predict tissue at risk of ulceration with a sensitivity and specificity of 95 and 80%, respectively, for images taken, on average, 58 days before tissue damage is apparent to the naked eye. Receiver operating characteristic analysis is also performed to give a range of sensitivity/specificity values resulting in a Q-value of 89%.

  17. Multiscale imaging and computational modeling of blood flow in the tumor vasculature.

    Science.gov (United States)

    Kim, Eugene; Stamatelos, Spyros; Cebulla, Jana; Bhujwalla, Zaver M; Popel, Aleksander S; Pathak, Arvind P

    2012-11-01

    The evolution in our understanding of tumor angiogenesis has been the result of pioneering imaging and computational modeling studies spanning the endothelial cell, microvasculature and tissue levels. Many of these primary data on the tumor vasculature are in the form of images from pre-clinical tumor models that provide a wealth of qualitative and quantitative information in many dimensions and across different spatial scales. However, until recently, the visualization of changes in the tumor vasculature across spatial scales remained a challenge due to a lack of techniques for integrating micro- and macroscopic imaging data. Furthermore, the paucity of three-dimensional (3-D) tumor vascular data in conjunction with the challenges in obtaining such data from patients presents a serious hurdle for the development and validation of predictive, multiscale computational models of tumor angiogenesis. In this review, we discuss the development of multiscale models of tumor angiogenesis, new imaging techniques capable of reproducing the 3-D tumor vascular architecture with high fidelity, and the emergence of "image-based models" of tumor blood flow and molecular transport. Collectively, these developments are helping us gain a fundamental understanding of the cellular and molecular regulation of tumor angiogenesis that will benefit the development of new cancer therapies. Eventually, we expect this exciting integration of multiscale imaging and mathematical modeling to have widespread application beyond the tumor vasculature to other diseases involving a pathological vasculature, such as stroke and spinal cord injury.

  18. What optimization principle explains the zebrafish vasculature?

    Science.gov (United States)

    Chang, Shyr-Shea; Baek, Kyung In; Hsiai, Tzung; Roper, Marcus

    2016-11-01

    Many multicellular organisms depend on biological transport networks; from the veins of leaves to the animal circulatory system, to redistribute nutrients internally. Since natural selection rewards efficiency, those networks are thought to minimize the cost of maintaining the flow inside. But optimizing these costs creates tradeoffs with other functions, e.g. mixing or uniform distribution of nutrients. We develop an extended Lagrange multiplier approach that allows the optimization of general network functionals. We also follow the real zebrafish vasculature and blood flows during organism development. Taken together, our work shows that the challenge of uniform oxygen perfusion, and not transport efficiency, explain zebrafish vascular organization. Ruth L. Kirschstein National Research Service Award (T32-GM008185).

  19. Genetic determinants of hyaloid and retinal vasculature in zebrafish

    Directory of Open Access Journals (Sweden)

    Hyde David R

    2007-10-01

    Full Text Available Abstract Background The retinal vasculature is a capillary network of blood vessels that nourishes the inner retina of most mammals. Developmental abnormalities or microvascular complications in the retinal vasculature result in severe human eye diseases that lead to blindness. To exploit the advantages of zebrafish for genetic, developmental and pharmacological studies of retinal vasculature, we characterised the intraocular vasculature in zebrafish. Results We show a detailed morphological and developmental analysis of the retinal blood supply in zebrafish. Similar to the transient hyaloid vasculature in mammalian embryos, vessels are first found attached to the zebrafish lens at 2.5 days post fertilisation. These vessels progressively lose contact with the lens and by 30 days post fertilisation adhere to the inner limiting membrane of the juvenile retina. Ultrastructure analysis shows these vessels to exhibit distinctive hallmarks of mammalian retinal vasculature. For example, smooth muscle actin-expressing pericytes are ensheathed by the basal lamina of the blood vessel, and vesicle vacuolar organelles (VVO, subcellular mediators of vessel-retinal nourishment, are present. Finally, we identify 9 genes with cell membrane, extracellular matrix and unknown identity that are necessary for zebrafish hyaloid and retinal vasculature development. Conclusion Zebrafish have a retinal blood supply with a characteristic developmental and adult morphology. Abnormalities of these intraocular vessels are easily observed, enabling application of genetic and chemical approaches in zebrafish to identify molecular regulators of hyaloid and retinal vasculature in development and disease.

  20. Local oestrogenic/androgenic balance in the cerebral vasculature.

    Science.gov (United States)

    Krause, D N; Duckles, S P; Gonzales, R J

    2011-09-01

    Reproductive effects of sex steroids are well-known; however it is increasingly apparent that these hormones have important actions on non-reproductive tissues such as the vasculature. The latter effects can be relevant throughout the lifespan, not just limited to reproductive years, and are not necessarily restricted to one gender or the other. Our work has established that cerebral blood vessels are a non-reproductive target tissue for sex steroids. We have found that oestrogen and androgens alter vascular tone, endothelial function, oxidative stress and inflammatory responses in cerebral vessels. Often the actions of oestrogen and androgens oppose each other. Moreover, it is clear that cerebral vessels are directly targeted by sex steroids, as they express specific receptors for these hormones. Interestingly, cerebral blood vessels also express enzymes that metabolize sex steroids. These findings suggest that local synthesis of 17ß-estradiol and dihydrotestosterone can occur within the vessel wall. One of the enzymes present, aromatase, converts testosterone to 17ß-estradiol, which would alter the local balance of androgenic and oestrogenic influences. Thus cerebral vessels are affected by circulating sex hormones as well as locally synthesized sex steroids. The presence of vascular endocrine effector mechanisms has important implications for male-female differences in cerebrovascular function and disease. Moreover, the cerebral circulation is a target for gonadal hormones as well as anabolic steroids and therapeutic drugs used to manipulate sex steroid actions. The long-term consequences of these influences are yet to be determined.

  1. Noise-immune complex correlation for vasculature imaging based on standard and Jones-matrix optical coherence tomography

    Science.gov (United States)

    Makita, Shuichi; Kurokawa, Kazuhiro; Hong, Young-Joo; Li, En; Miura, Masahiro; Yasuno, Yoshiaki

    2016-03-01

    A new optical coherence angiography (OCA) method, called correlation mapping OCA (cmOCA), is presented by using the SNR-corrected complex correlation. An SNR-correction theory for the complex correlation calculation is presented. The method also integrates a motion-artifact-removal method for the sample motion induced decorrelation artifact. The theory is further extended to compute more reliable correlation by using multi- channel OCT systems, such as Jones-matrix OCT. The high contrast vasculature imaging of in vivo human posterior eye has been obtained. Composite imaging of cmOCA and degree of polarization uniformity indicates abnormalities of vasculature and pigmented tissues simultaneously.

  2. Vascular metallomics: copper in the vasculature.

    Science.gov (United States)

    Easter, Renee N; Qilin Chan; Lai, Barry; Ritman, Erik L; Caruso, Joseph A; Zhenyu Qin

    2010-02-01

    Owing to recent progress in analytical techniques, metallomics are evolving from detecting distinct trace metals in a defined state to monitor the dynamic changes in the abundance and location of trace metals in vitro and in vivo. Vascular metallomics is an emerging field that studies the role of trace metals in vasculature. This review will introduce common metallomics techniques including atomic absorption spectrometry, inductively coupled plasma-atomic emission spectrometry, inductively coupled plasma-mass spectrometry and X-ray fluorescence spectrometry with a summary table to compare these techniques. Moreover, we will summarize recent research findings that have applied these techniques to human population studies in cardiovascular diseases, with a particular emphasis on the role of copper in these diseases. In order to address the issue of interdisciplinary studies between metallomics and vascular biology, we will review the progress of efforts to understand the role of copper in neovascularization. This recent advance in the metallomics field may be a powerful tool to elucidate the signaling pathways and specific biological functions of these trace metals. Finally, we summarize the evidence to support the notion that copper is a dynamic signaling molecule. As a future direction, vascular metallomics studies may lead to the identification of targets for diagnosis and therapy in cardiovascular disease.

  3. Functional photoacoustic microscopy of diabetic vasculature

    Science.gov (United States)

    Krumholz, Arie; Wang, Lidai; Yao, Junjie; Wang, Lihong V.

    2012-06-01

    We used functional photoacoustic microscopy to image diabetes-induced damage to the microvasculature. To produce an animal model for Type 1 diabetes, we used streptozotocin (STZ), which is particularly toxic to the insulin-producing beta cells of the pancreas in mammals. A set number of ND4 Swiss Webster mice received intraperitoneal injections of STZ for five consecutive days at 50 mg/kg. Most mice developed a significant rise in blood glucose level (~400 mg/dL) within three weeks of the first injection. Changes in vasculature and hemodynamics were monitored for six weeks. The mouse ear was imaged with an optical-resolution photoacoustic microscope at a main blood vessel branch from the root of the ear. There are noticeable and measurable changes associated with the disease, including decreased vessel diameter and possible occlusion due to vessel damage and polyurea. We also observed an increase in the blood flow speed in the vein and a decrease in the artery, which could be due to compensation for the dehydration and vessel diameter changes. Functional and metabolic parameters such as hemoglobin oxygen saturation, oxygen extraction fraction, and oxygen consumption rate were also measured, but showed no significant change.

  4. Peptides as targeting probes against tumor vasculature for diagnosis and drug delivery.

    Science.gov (United States)

    Li, Zhi Jie; Cho, Chi Hin

    2012-09-19

    Tumor vasculature expresses a distinct set of molecule signatures on the endothelial cell surface different from the resting blood vessels of other organs and tissues in the body. This makes them an attractive target for cancer therapy and molecular imaging. The current technology using the in vivo phage display biopanning allows us to quickly isolate and identify peptides potentially homing to various tumor blood vessels. Tumor-homing peptides in conjugation with chemotherapeutic drugs or imaging contrast have been extensively tested in various preclinical and clinical studies. These tumor-homing peptides have valuable potential as targeting probes for tumor molecular imaging and drug delivery. In this review, we summarize the recent advances about the applications of tumor-homing peptides selected by in vivo phage display library screening against tumor vasculature. We also introduce the characteristics of the latest discovered tumor-penetrating peptides in their potential clinical applications.

  5. CAVAREV-an open platform for evaluating 3D and 4D cardiac vasculature reconstruction

    Energy Technology Data Exchange (ETDEWEB)

    Rohkohl, Christopher; Hornegger, Joachim [Pattern Recognition Lab, Department of Computer Science, Friedrich-Alexander University Erlangen-Nuremberg, Martensstr. 3, 91058 Erlangen (Germany); Lauritsch, Guenter [Siemens AG, Healthcare Sector, Siemensstr. 1, 91301 Forchheim (Germany); Keil, Andreas, E-mail: christopher.rohkohl@informatik.uni-erlangen.d, E-mail: guenter.lauritsch@siemens.co, E-mail: andreas.keil@cs.tum.ed, E-mail: joachim.hornegger@informatik.uni-erlangen.d [Computer Aided Medical Procedures and Augmented Reality, TU Muenchen, Boltzmannstr. 3, 85748 Garching (Germany)

    2010-05-21

    The 3D reconstruction of cardiac vasculature, e.g. the coronary arteries, using C-arm CT (rotational angiography) is an active and challenging field of research. There are numerous publications on different reconstruction techniques. However, there is still a lack of comparability of achieved results for several reasons: foremost, datasets used in publications are not open to public and thus experiments are not reproducible by other researchers. Further, the results highly depend on the vasculature motion, i.e. cardiac and breathing motion patterns which are also not comparable across publications. We aim to close this gap by providing an open platform, called Cavarev (CArdiac VAsculature Reconstruction EValuation). It features two simulated dynamic projection datasets based on the 4D XCAT phantom with contrasted coronary arteries which was derived from patient data. In the first dataset, the vasculature undergoes a continuous periodic motion. The second dataset contains aperiodic heart motion by including additional breathing motion. The geometry calibration and acquisition protocol were obtained from a real-world C-arm system. For qualitative evaluation of the reconstruction results, the correlation of the morphology is used. Two segmentation-based quality measures are introduced which allow us to assess the 3D and 4D reconstruction quality. They are based on the spatial overlap of the vasculature reconstruction with the ground truth. The measures enable a comprehensive analysis and comparison of reconstruction results independent from the utilized reconstruction algorithm. An online platform (www.cavarev.com) is provided where the datasets can be downloaded, researchers can manage and publish algorithm results and download a reference C++ and Matlab implementation.

  6. Application of tissue clearing and light sheet fluorescence microscopy to assess optic nerve regeneration in unsectioned tissues.

    Science.gov (United States)

    Luo, Xueting; Yungher, Benjamin; Park, Kevin K

    2014-01-01

    Optic nerve crush injury, as a model to study central nervous system (CNS) injury, is widely used to assess potential therapeutic strategies, aimed at promoting axon regeneration and neuronal survival. Traditional methods to evaluate optic nerve regeneration rely on histological sectioning. However, tissue sectioning results in inevitable loss of three-dimensional (3D) information, such as axonal trajectories and terminations. Here we describe a protocol for whole-tissue assessment of optic nerve regeneration in adult mice without the need for histological sectioning.

  7. Effects of the tumor vasculature targeting agent NGR-TNF on the tumor microenvironment in murine lymphomas.

    NARCIS (Netherlands)

    Laarhoven, H.W.M. van; Gambarota, G.; Heerschap, A.; Lok, J.; Verhagen, I.; Corti, A.; Toma, S.; Gallo Stampino, C.; Kogel, A.J. van der; Punt, C.J.A.

    2006-01-01

    TNF-alpha may improve drug delivery to tumors by alteration of vascular permeability. However, toxicity precludes its systemic administration in patients. NGR-TNF comprises TNF coupled to the peptide CNGRC, which is a ligand for CD13. CD13 is expressed on tumor vasculature. Therefore, to assess the

  8. In situ FTIR assessment of desiccation-tolerant tissues

    NARCIS (Netherlands)

    Wolkers, W.F.; Hoekstra, F.A.

    2003-01-01

    This essay shows how Fourier transform infrared (FTIR) microspectroscopy can be applied to study thermodynamic parameters and conformation of endogenous biomolecules in desiccation-tolerant biological tissues. Desiccation tolerance is the remarkable ability of some organisms to survive complete dehy

  9. Tissue viability assessment via laser-based fluorescence monitor

    Science.gov (United States)

    Curtis, Craig H.; Peyghambarian, Nasser; Dereniak, Eustace L.; Frink, Edward

    1996-04-01

    A preliminary study of the degree to which recently introduced inhalation anesthetics influence the intracellular energetic metabolism of isolated perfused rat livers is undertaken via NADH fluorometry. During liver transplantation, anesthesiologists desire to maintain a high level of metabolic energy status in newly transplanted liver tissue. Ischemic storage of donor liver tissue prior to transplantation is known to inhibit mitochondrial electron transfer, which results in decreased levels of ATP and increased levels of NADH in the stored tissue. The ability of transplanted liver tissue to regenerate ATP at normal levels is desirable for early post- operative recovery of liver function. Previous studies have examined the differential effects inhalation anesthetics have on the energetic metabolism of tissue at the cellular level; the trend of such agents is to induce a dose-dependent increase in NADH fluorescence in accordance with their strengths as general anesthetics. The present study evaluates the differential effects exhibited by new inhalation anesthetics on the return of function of energetic metabolism in liver tissue. The third-harmonic (355 nm) output of a Nd:YAG laser is spatially filtered and used as the excitation source for surface fluorometric measurements of isolated buffer-perfused rat livers. Lastly, maximum fluorescence emission versus spot-size are measured.

  10. The vasoactive potential of kisspeptin-10 in the peripheral vasculature.

    Directory of Open Access Journals (Sweden)

    Iain Sawyer

    Full Text Available Splice products of the Kiss1 protein (kisspeptins have been shown to be involved in a diverse range of functions, including puberty, metastasis and vasoconstriction in large human arteries. Circulating Kisspeptin-10 (Kp-10 plasma levels are low in normal individuals but are elevated during various disease states as well as pregnancy. Here, we investigated the potential of Kp-10, the shortest biologically active kisspeptin, to influence microvascular effects, concentrating on the cutaneous vasculature. Kp-10 caused a dose-dependent increase in oedema formation (0.3-10 nmol/injection site, assessed by Evans Blue albumin dye extravasation, in the dorsal skin of CD1 mice. Oedema formation was shown to be inhibited by the histamine H(1 receptor antagonist mepyramine. The response was characterised by a ring of pallor at the injection site in keeping with vasoconstrictor activity. Therefore, changes in dorsal skin blood flow were assessed by clearance of intradermally injected (99mtechnetium. Kp-10 was found to significantly reduce clearance, in keeping with decreased blood flow and providing further evidence for vasoconstrictor activity. The decreased clearance was partially inhibited by co-treatment with the cyclo-oxygenase inhibitor indomethacin. Finally evidence for the kisspeptin receptor gene (Kiss1R, but not the kisspeptin peptide gene (Kiss1, mRNA expression was observed in heart, aorta and kidney samples from normal and angiotensin II induced hypertensive mice, with similar mRNA levels observed in each. We have evidence for two peripheral vasoactive roles for kisspeptin-10. Firstly, plasma extravasation indicative of ability to induce oedema formation and secondly decreased peripheral blood flow, indicating microvascular constriction. Thus Kp-10 has vasoactive properties in the peripheral microvasculature.

  11. How to assess the plasma delivery of RONS into tissue fluid and tissue

    Science.gov (United States)

    Oh, Jun-Seok; Szili, Endre J.; Gaur, Nishtha; Hong, Sung-Ha; Furuta, Hiroshi; Kurita, Hirofumi; Mizuno, Akira; Hatta, Akimitsu; Short, Robert D.

    2016-08-01

    The efficacy of helium (He) and argon (Ar) plasma jets are being investigated for different healthcare applications including wound and cancer therapy, sterilisation and surface disinfections. Current research points to a potential link between the generation of reactive oxygen and nitrogen species (RONS) and outcomes in a range of biological and medical applications. As new data accrue, further strengthening this link, it becomes important to understand the controlled delivery of RONS into solutions, tissue fluids and tissues. This paper investigates the use of He and Ar plasma jets to deliver three RONS (hydrogen peroxide—H2O2, nitrite—\\text{NO}2- and nitrate—\\text{NO}3- ) and molecular oxygen (O2) directly into deionised (DI) water, or indirectly into DI water through an agarose target. The DI water is used in place of tissue fluid and the agarose target serves as a surrogate of tissue. Direct plasma jet treatments deliver more RONS and O2 than the through-agarose treatments for equivalent treatments times. The former only deliver RONS whilst the plasma jets are ignited; the latter continues to deliver RONS into the DI water long after the plasmas are extinguished. The He plasma jet is more effective at delivering H2O2 and \\text{NO}2- directly into DI water, but the Ar plasma jet is more effective at nitrating the DI water in both direct and through-agarose treatments. DI water directly treated with the plasma jets is deoxygenated, with the He plasma jet purging more O2 than the Ar plasma jet. This effect is known as ‘sparging’. In contrast, for through-agarose treatments both jets oxygenated the DI water. These results indicate that in the context of direct and indirect plasma jet treatments of real tissue fluids and tissue, the choice of process gas (He or Ar) could have a profound effect on the concentrations of RONS and O2. Irrespective of operating gas, sparging of tissue fluid (in an open wound) for long prolonged periods during direct plasma

  12. Facilitated assessment of tissue loss following traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Anders eHånell

    2012-03-01

    Full Text Available All experimental models of traumatic brain injury (TBI result in a progressive loss of brain tissue. The extent of tissue loss reflects the injury severity and can be measured to evaluate the potential neuroprotective effect of experimental treatments. Quantitation of tissue volumes is commonly performed using evenly spaced brain sections stained using routine histochemical methods and digitally captured. The brain tissue areas are then measured and the corresponding volumes are calculated using the distance between the sections. Measurements of areas are usually performed using a general purpose image analysis software and the results are then transferred to another program for volume calculations. To facilitate the measurement of brain tissue loss we developed novel algorithms which automatically separate the areas of brain tissue from the surrounding image background and identify the ventricles. We implemented these new algorithms by creating a new computer program (SectionToVolume which also has functions for image organization, image adjustments and volume calculations. We analyzed brain sections from mice subjected to severe focal TBI using both SectionToVolume and ImageJ, a commonly used image analysis program. The volume measurements made by the two programs were highly correlated and analysis using SectionToVolume required considerably less time. The inter-rater reliability was high. Given the extensive use of brain tissue loss measurements in TBI research, SectionToVolume will likely be a useful tool for TBI research. We therefore provide both the source code and the program as attachments to this article.

  13. Multimodal nanoprobes evaluating physiological pore size of brain vasculatures in ischemic stroke models.

    Science.gov (United States)

    Zheng, Shuyan; Bai, Ying-Ying; Changyi, Yinzhi; Gao, Xihui; Zhang, Wenqing; Wang, Yuancheng; Zhou, Lu; Ju, Shenghong; Li, Cong

    2014-11-01

    Ischemic stroke accounts for 80% strokes and originates from a reduction of cerebral blood flow (CBF) after vascular occlusion. For treatment, the first action is to restore CBF by thrombolytic agent recombinant tissue-type plasminogen activator (rt-PA). Although rt-PA benefits clinical outcome, its application is limited by short therapeutic time window and risk of brain hemorrhage. Different to thrombolytic agents, neuroprotectants reduce neurological injuries by blocking ischemic cascade events such as excitotoxicity and oxidative stress. Nano-neuroprotectants demonstrate higher therapeutic effect than small molecular analogues due to their prolonged circulation lifetime and disrupted blood-brain barrier (BBB) in ischemic region. Even enhanced BBB permeability in ischemic territories is verified, the pore size of ischemic vasculatures determining how large and how efficient the therapeutics can pass is barely studied. In this work, nanoprobes (NPs) with different diameters are developed. In vivo multimodal imaging indicates that NP uptakes in ischemic region depended on their diameters and the pore size upper limit of ischemic vasculatures is determined as 10-11 nm. Additionally, penumbra defined as salvageable ischemic tissues performed a higher BBB permeability than infarct core. This work provides a guideline for developing nano-neuroprotectants by taking advantage of the locally enhanced BBB permeability in ischemic brain tissues.

  14. Automated tissue classification framework for reproducible chronic wound assessment.

    Science.gov (United States)

    Mukherjee, Rashmi; Manohar, Dhiraj Dhane; Das, Dev Kumar; Achar, Arun; Mitra, Analava; Chakraborty, Chandan

    2014-01-01

    The aim of this paper was to develop a computer assisted tissue classification (granulation, necrotic, and slough) scheme for chronic wound (CW) evaluation using medical image processing and statistical machine learning techniques. The red-green-blue (RGB) wound images grabbed by normal digital camera were first transformed into HSI (hue, saturation, and intensity) color space and subsequently the "S" component of HSI color channels was selected as it provided higher contrast. Wound areas from 6 different types of CW were segmented from whole images using fuzzy divergence based thresholding by minimizing edge ambiguity. A set of color and textural features describing granulation, necrotic, and slough tissues in the segmented wound area were extracted using various mathematical techniques. Finally, statistical learning algorithms, namely, Bayesian classification and support vector machine (SVM), were trained and tested for wound tissue classification in different CW images. The performance of the wound area segmentation protocol was further validated by ground truth images labeled by clinical experts. It was observed that SVM with 3rd order polynomial kernel provided the highest accuracies, that is, 86.94%, 90.47%, and 75.53%, for classifying granulation, slough, and necrotic tissues, respectively. The proposed automated tissue classification technique achieved the highest overall accuracy, that is, 87.61%, with highest kappa statistic value (0.793).

  15. Automated Tissue Classification Framework for Reproducible Chronic Wound Assessment

    Directory of Open Access Journals (Sweden)

    Rashmi Mukherjee

    2014-01-01

    Full Text Available The aim of this paper was to develop a computer assisted tissue classification (granulation, necrotic, and slough scheme for chronic wound (CW evaluation using medical image processing and statistical machine learning techniques. The red-green-blue (RGB wound images grabbed by normal digital camera were first transformed into HSI (hue, saturation, and intensity color space and subsequently the “S” component of HSI color channels was selected as it provided higher contrast. Wound areas from 6 different types of CW were segmented from whole images using fuzzy divergence based thresholding by minimizing edge ambiguity. A set of color and textural features describing granulation, necrotic, and slough tissues in the segmented wound area were extracted using various mathematical techniques. Finally, statistical learning algorithms, namely, Bayesian classification and support vector machine (SVM, were trained and tested for wound tissue classification in different CW images. The performance of the wound area segmentation protocol was further validated by ground truth images labeled by clinical experts. It was observed that SVM with 3rd order polynomial kernel provided the highest accuracies, that is, 86.94%, 90.47%, and 75.53%, for classifying granulation, slough, and necrotic tissues, respectively. The proposed automated tissue classification technique achieved the highest overall accuracy, that is, 87.61%, with highest kappa statistic value (0.793.

  16. Persistent fetal vasculature: ocular features, management of cataract and outcomes

    Directory of Open Access Journals (Sweden)

    Marcia Beatriz Tartarella

    2013-06-01

    Full Text Available PURPOSES: To describe ocular features, management of cataract and functional outcomes in patients with persistent fetal vasculature. METHODS: Retrospective, descriptive case series of patients with persistent fetal vasculature. Data were recorded from the Congenital Cataract Section of Federal University of São Paulo, Brazil from 2001 to 2012. All patients were evaluated for sex, age at diagnosis, systemic findings, laterality, age at surgery, and initial and final follow-up visual acuities. Follow-up and complications after cataract surgery were recorded. Ultrasound was performed in all cases and ocular eco-Doppler was performed in most. RESULTS: The study comprised 53 eyes from 46 patients. Age at diagnosis ranged from 5 days of life to 10 years-old (mean 22.7 months. Twenty-seven patients were male (58.7%. Persistent fetal vasculature was bilateral in 7 patients (15.2%. Forty-two eyes (79.2% had combined (anterior and posterior forms PFV presentation, 5 eyes (9.4% had only anterior persistent fetal vasculature presentation and 6 eyes (11.3% had posterior persistent fetal vasculature presentation. Thirty-eight eyes (71.7% were submitted to cataract surgery. Lensectomy combined with anterior vitrectomy was performed in 18 eyes (47.4%. Phacoaspiration with intraocular lens implantation was performed in 15 eyes (39.5%, and without lens implantation in 5 eyes (13.2%. Mean follow-up after surgery was 44 months. Postoperative complications were posterior synechiae (3 cases, retinal detachment (2 cases, phthisis (3 cases, posterior capsular opacification (8 cases, inflammatory pupillary membrane (5 cases, glaucoma (4 cases, intraocular lens implantation displacement (1 case and vitreous hemorrhage (2 cases. Complications were identified in 19 (50% of the 38 operated eyes. Visual acuity improved after cataract surgery in 83% of the eyes. CONCLUSIONS: Patients with persistent fetal vasculature have variable clinical presentation. There is an

  17. A survey on the visualization and reconstruction of vasculatures

    Science.gov (United States)

    Hong, Qingqi

    2014-01-01

    Visualization and reconstruction of blood vessel from standard medical datasets play an important role in many clinical situations. This paper presents a survey on the visualization and reconstruction of vascular structures. Firstly, the visualization techniques of vasculatures are introduced, which includes volume rendering and surface rendering of vasculatures. Then, we focus on the reconstruction techniques of vascular structures, which can be classified into two categories: explicit reconstruction and implicit reconstruction of vascular structures. With reconstructed vascular geometry, it is quite easy to produce smooth visualization of vessel surfaces. In addition, finding the accurate geometric representation of vascular structures is crucial in developing computer aided vascular surgery systems.

  18. Detecting abnormal vasculature from photoacoustic signals using wavelet-packet features

    Science.gov (United States)

    Zalev, Jason; Kolios, Michael C.

    2011-03-01

    Photoacoustic systems can produce high-resolution, high-contrast images of vascular structures. To reconstruct images at very high-resolution, signals must be collected from many transducer locations, which can be time consuming due to limitations in transducer array technology. A method is presented to quickly discriminate between normal and abnormal tissue based on the structural morphology of vasculature. To demonstrate that the approach may be useful for cancer detection, a special simulator that produces photoacoustic signals from 3D models of vascular tissue is developed. Results show that it is possible to differentiate tissue classes even when it is not possible to resolve individual blood vessels. Performance of the algorithm remains strong as the number of transducer locations decreases and in the presence of noise.

  19. Force-based assessment of tissue handling skills

    NARCIS (Netherlands)

    Horeman, T.

    2014-01-01

    In laparoscopic surgery, special instruments with long and slender shafts are inserted through small incisions in the abdominal wall. A laparoscope is used for a clear vision inside the inflated abdominal cavity while laparoscopic graspers and cutters are used for manipulation of tissue. The use of

  20. Assessing infection risk in implanted tissue-engineered devices

    NARCIS (Netherlands)

    Kuijer, Roel; Jansen, Edwin J. P.; Emans, Pieter J.; Bulstra, Sjoerd K.; Riesle, Jens; Pieper, Jeroen; Grainger, David W.; Busscher, Henk J.

    2007-01-01

    Peri-operative contamination is the major cause of biomaterial-associated infections, highly complicating surgical patient outcomes. While this risk in traditional implanted biomaterials is well-recognised, newer cell-seeded, biologically conducive tissue-engineered (TE) constructs now targeted for

  1. Assessing laser-tissue damage with bioluminescent imaging.

    Science.gov (United States)

    Wilmink, Gerald J; Opalenik, Susan R; Beckham, Joshua T; Davidson, Jeffrey M; Jansen, E Duco

    2006-01-01

    Effective medical laser procedures are achieved by selecting laser parameters that minimize undesirable tissue damage. Traditionally, human subjects, animal models, and monolayer cell cultures have been used to study wound healing, tissue damage, and cellular effects of laser radiation. Each of these models has significant limitations, and consequently, a novel skin model is needed. To this end, a highly reproducible human skin model that enables noninvasive and longitudinal studies of gene expression was sought. In this study, we present an organotypic raft model (engineered skin) used in combination with bioluminescent imaging (BLI) techniques. The efficacy of the raft model was validated and characterized by investigating the role of heat shock protein 70 (hsp70) as a sensitive marker of thermal damage. The raft model consists of human cells incorporated into an extracellular matrix. The raft cultures were transfected with an adenovirus containing a murine hsp70 promoter driving transcription of luciferase. The model enables quantitative analysis of spatiotemporal expression of proteins using BLI. Thermal stress was induced on the raft cultures by means of a constant temperature water bath or with a carbon dioxide (CO2) laser (lambda=10.6 microm, 0.679 to 2.262 Wcm2, cw, unfocused Gaussian beam, omegaL=4.5 mm, 1 min exposure). The bioluminescence was monitored noninvasively with an IVIS 100 Bioluminescent Imaging System. BLI indicated that peak hsp70 expression occurs 4 to 12 h after exposure to thermal stress. A minimum irradiance of 0.679 Wcm2 activated the hsp70 response, and a higher irradiance of 2.262 Wcm2 was associated with a severe reduction in hsp70 response due to tissue ablation. Reverse transcription polymerase chain reaction demonstrated that hsp70 mRNA levels increased with prolonged heating exposures. Enzyme-linked immunosorbent protein assays confirmed that luciferase was an accurate surrogate for hsp70 intracellular protein levels. Hematoxylin

  2. Assessing laser-tissue damage with bioluminescent imaging

    Science.gov (United States)

    Wilmink, Gerald J.; Opalenik, Susan R.; Beckham, Josh T.; Davidson, Jeffrey M.; Jansen, Eric D.

    2006-07-01

    Effective medical laser procedures are achieved by selecting laser parameters that minimize undesirable tissue damage. Traditionally, human subjects, animal models, and monolayer cell cultures have been used to study wound healing, tissue damage, and cellular effects of laser radiation. Each of these models has significant limitations, and consequently, a novel skin model is needed. To this end, a highly reproducible human skin model that enables noninvasive and longitudinal studies of gene expression was sought. In this study, we present an organotypic raft model (engineered skin) used in combination with bioluminescent imaging (BLI) techniques. The efficacy of the raft model was validated and characterized by investigating the role of heat shock protein 70 (hsp70) as a sensitive marker of thermal damage. The raft model consists of human cells incorporated into an extracellular matrix. The raft cultures were transfected with an adenovirus containing a murine hsp70 promoter driving transcription of luciferase. The model enables quantitative analysis of spatiotemporal expression of proteins using BLI. Thermal stress was induced on the raft cultures by means of a constant temperature water bath or with a carbon dioxide (CO2) laser (λ=10.6 µm, 0.679 to 2.262 W/cm2, cw, unfocused Gaussian beam, ωL=4.5 mm, 1 min exposure). The bioluminescence was monitored noninvasively with an IVIS 100 Bioluminescent Imaging System. BLI indicated that peak hsp70 expression occurs 4 to 12 h after exposure to thermal stress. A minimum irradiance of 0.679 W/cm2 activated the hsp70 response, and a higher irradiance of 2.262 W/cm2 was associated with a severe reduction in hsp70 response due to tissue ablation. Reverse transcription polymerase chain reaction demonstrated that hsp70 mRNA levels increased with prolonged heating exposures. Enzyme-linked immunosorbent protein assays confirmed that luciferase was an accurate surrogate for hsp70 intracellular protein levels. Hematoxylin and

  3. Segmentation of digitized histological sections for quantification of the muscularized vasculature in the mouse hind limb.

    Science.gov (United States)

    Xu, Yiwen; Pickering, J Geoffrey; Nong, Zengxuan; Ward, Aaron D

    2017-04-01

    Immunohistochemical tissue staining enhances microvasculature characteristics, including the smooth muscle in the medial layer of the vessel walls that is responsible for regulation of blood flow. The vasculature can be imaged in a comprehensive fashion using whole-slide scanning. However, since each such image potentially contains hundreds of small vessels, manual vessel delineation and quantification is not practically feasible. In this work, we present a fully automatic segmentation and vasculature quantification algorithm for whole-slide images. We evaluated its performance on tissue samples drawn from the hind limbs of wild-type mice, stained for smooth muscle using 3,3'-Diaminobenzidine (DAB) immunostain. The algorithm was designed to be robust to vessel fragmentation due to staining irregularity, and artefactual staining of nonvessel objects. Colour deconvolution was used to isolate the DAB stain for detection of vessel wall fragments. Complete vessels were reconstructed from the fragments by joining endpoints of topological skeletons. Automatic measures of vessel density, perimeter, wall area and local wall thickness were taken. The segmentation algorithm was validated against manual measures, resulting in a Dice similarity coefficient of 89%. The relationships observed between these measures were as expected from a biological standpoint, providing further reinforcement of the accuracy of this system. This system provides a fully automated and accurate means of measuring the arteriolar and venular morphology of vascular smooth muscle.

  4. Combination of thermographic and ultrasonographic assessments for early detection of deep tissue injury.

    Science.gov (United States)

    Higashino, Takuya; Nakagami, Gojiro; Kadono, Takafumi; Ogawa, Yuki; Iizaka, Shinji; Koyanagi, Hiroe; Sasaki, Sanae; Haga, Nobuhiko; Sanada, Hiromi

    2014-10-01

    Early detection and intervention of deep tissue injury are important to lead good outcome. Although the efficiency of ultrasonographic assessment of deep tissue injury has been reported previously, it requires a certain level of skill for accurate assessment. In this study, we present an investigation of the combination of thermographic and ultrasonographic assessments for early detection of deep tissue injury. We retrospectively reviewed 28 early-stage pressure ulcers (21 patients) presenting at the University of Tokyo Hospital between April 2009 and February 2010, surveying the associated thermographic and ultrasonographic findings. The wound temperature patterns were divided into low, even and high compared with the surrounding skin. Ultrasonographic findings were classified into unclear layer structure, hypoechoic lesion, discontinuous fascia and heterogeneous hypoechoic area. All 13 ulcers that were associated with low temperature showed good outcome; three ulcers had even temperatures and 12 ulcers showed high temperature on thermographic assessment. The two deep tissue injuries were rated high on thermographic assessment and showed heterogeneous hypoechoic area findings on ultrasonographic assessment. No non-deep tissue injury lesion was associated with these two findings simultaneously. The combination of thermographic and ultrasonographic assessments is expected to increase the accuracy of the early detection of deep tissue injuries.

  5. 3D reconstruction of digitized histological sections for vasculature quantification in the mouse hind limb

    Science.gov (United States)

    Xu, Yiwen; Pickering, J. Geoffrey; Nong, Zengxuan; Gibson, Eli; Ward, Aaron D.

    2014-03-01

    In contrast to imaging modalities such as magnetic resonance imaging and micro computed tomography, digital histology reveals multiple stained tissue features at high resolution (0.25μm/pixel). However, the two-dimensional (2D) nature of histology challenges three-dimensional (3D) quantification and visualization of the different tissue components, cellular structures, and subcellular elements. This limitation is particularly relevant to the vasculature, which has a complex and variable structure within tissues. The objective of this study was to perform a fully automated 3D reconstruction of histology tissue in the mouse hind limb preserving the accurate systemic orientation of the tissues, stained with hematoxylin and immunostained for smooth muscle α actin. We performed a 3D reconstruction using pairwise rigid registrations of 5μm thick, paraffin-embedded serial sections, digitized at 0.25μm/pixel. Each registration was performed using the iterative closest points algorithm on blood vessel landmarks. Landmarks were vessel centroids, determined according to a signed distance map of each pixel to a decision boundary in hue-saturation-value color space; this decision boundary was determined based on manual annotation of a separate training set. Cell nuclei were then automatically extracted and corresponded to refine the vessel landmark registration. Homologous nucleus landmark pairs appearing on not more than two adjacent slides were chosen to avoid registrations which force curved or non-sectionorthogonal structures to be straight and section-orthogonal. The median accumulated target registration errors ± interquartile ranges for the vessel landmark registration, and the nucleus landmark refinement were 43.4+/-42.8μm and 2.9+/-1.7μm, respectively (p<0.0001). Fully automatic and accurate 3D rigid reconstruction of mouse hind limb histology imaging is feasible based on extracted vasculature and nuclei.

  6. Microwave tomography for functional imaging of extremity soft tissues: feasibility assessment

    Energy Technology Data Exchange (ETDEWEB)

    Semenov, Serguei [Keele University, School of Medicine, ISTM, Stoke-on-Trent, ST4 7QB (United Kingdom); Kellam, James [Carolinas Medical Center, Charlotte, NC 28203 (United States); Althausen, Peter [Reno Orthopaedic Clinic, Reno, NV 89503 (United States); Williams, Thomas [Carolinas Medical Center, Charlotte, NC 28203 (United States); Abubakar, Aria [Schlumberger-Doll, Ridgefield, CT 06877 (United States); Bulyshev, Alexander [MA-Inc, Hampton, VA (United States); Sizov, Yuri [TRINITI, Moscow Region (Russian Federation)

    2007-09-21

    It is important to assess the viability of extremity soft tissues, as this component is often the determinant of the final outcome of fracture treatment. Microwave tomography (MWT) and sensing might be able to provide a fast and mobile assessment of such properties. MWT imaging of extremities possesses a complicated, nonlinear, high dielectric contrast inverse problem of diffraction tomography. There is a high dielectric contrast between bone and soft tissue in the extremities. A contrast between soft tissue abnormalities is less pronounced when compared with the high bone-soft tissue contrast. The goal of this study was to assess the feasibility of MWT for functional imaging of extremity soft tissues, i.e. to detect a relatively small contrast within soft tissues in closer proximity to high contrast boney areas. Both experimental studies and computer simulation were performed. Experiments were conducted using live pigs with compromised blood flow and compartment syndrome within an extremity. A whole 2D tomographic imaging cycle at 1 GHz was computer simulated and images were reconstructed using the Newton, MR-CSI and modified Born methods. Results of experimental studies demonstrate that microwave technology is sensitive to changes in the soft tissue blood content and elevated compartment pressure. It was demonstrated that MWT is feasible for functional imaging of extremity soft tissues, circulatory-related changes, blood flow and elevated compartment pressure.

  7. Suitability of single tissue dielectric constant measurements to assess local tissue water in normal and lymphedematous skin.

    Science.gov (United States)

    Mayrovitz, Harvey N; Davey, Suzanne; Shapiro, Elizabeth

    2009-04-01

    Previous reports described the use of average tissue dielectric constant (TDC) measurements to assess local tissue water and its change. Our goal was to determine if a single TDC measurement could be used in place of the average of multiple measurements. The comparison criteria used to test this was the extent to which single and averaged measurements yielded similar TDC values in both normal and lymphedematous tissue. Measurements were made in two groups of women; a control group (n = 20) and a group with unilateral arm lymphedema (n = 10). In the control group, TDC was measured to multiple depths (0.5-5.0 mm) on both ventral forearms and to a depth of 2.5 mm on the lateral thorax on both body sides. In the lymphedematous group, TDC was measured on both ventral forearms to a depth of 2.5 mm. Results showed that the 95% confidence interval for differences between single and averaged TDC values was less than +/-1 TDC unit and that the limits of agreement between methods was less than +/-2.5 TDC units (+/-6.5%) for each condition, site and depth measured. This finding suggests that where this level of agreement is acceptable suitable clinical assessments can be made using a single TDC measurement.

  8. Gold nanoparticle induced vasculature damage in radiotherapy: Comparing protons, megavoltage photons, and kilovoltage photons

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yuting, E-mail: yutingl188@gmail.com; Paganetti, Harald; Schuemann, Jan [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 (United States); McMahon, Stephen J. [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 and Center for Cancer Research and Cell Biology, Queen’s University Belfast, 97 Lisburn Road, Belfast BT97AE, Northern Ireland (United Kingdom)

    2015-10-15

    Purpose: The purpose of this work is to investigate the radiosensitizing effect of gold nanoparticle (GNP) induced vasculature damage for proton, megavoltage (MV) photon, and kilovoltage (kV) photon irradiation. Methods: Monte Carlo simulations were carried out using tool for particle simulation (TOPAS) to obtain the spatial dose distribution in close proximity up to 20 μm from the GNPs. The spatial dose distribution from GNPs was used as an input to calculate the dose deposited to the blood vessels. GNP induced vasculature damage was evaluated for three particle sources (a clinical spread out Bragg peak proton beam, a 6 MV photon beam, and two kV photon beams). For each particle source, various depths in tissue, GNP sizes (2, 10, and 20 nm diameter), and vessel diameters (8, 14, and 20 μm) were investigated. Two GNP distributions in lumen were considered, either homogeneously distributed in the vessel or attached to the inner wall of the vessel. Doses of 30 Gy and 2 Gy were considered, representing typical in vivo enhancement studies and conventional clinical fractionation, respectively. Results: These simulations showed that for 20 Au-mg/g GNP blood concentration homogeneously distributed in the vessel, the additional dose at the inner vascular wall encircling the lumen was 43% of the prescribed dose at the depth of treatment for the 250 kVp photon source, 1% for the 6 MV photon source, and 0.1% for the proton beam. For kV photons, GNPs caused 15% more dose in the vascular wall for 150 kVp source than for 250 kVp. For 6 MV photons, GNPs caused 0.2% more dose in the vascular wall at 20 cm depth in water as compared to at depth of maximum dose (Dmax). For proton therapy, GNPs caused the same dose in the vascular wall for all depths across the spread out Bragg peak with 12.7 cm range and 7 cm modulation. For the same weight of GNPs in the vessel, 2 nm diameter GNPs caused three times more damage to the vessel than 20 nm diameter GNPs. When the GNPs were attached

  9. Unilateral persistent fetal vasculature coexisting with anterior segment dysgenesis.

    Science.gov (United States)

    Khokhar, Sudarshan; Gupta, Shikha; Arora, Tarun; Gogia, Varun; Dada, Tanuj

    2013-08-01

    Persistent fetal vasculature (PFV) is a common congenital developmental anomaly of the eye which results from failure of the embryological primary vitreous and hyaloid vasculature to regress by the time of birth (Int Ophthalmol Clin 48: 53-62, 2008). Typically, it is divided into anterior, posterior or combined types and is characterized by the presence of a vascular stalk located between the optic disc and the posterior lens capsule (Int Ophthalmol Clin 48: 53-62, 2008). Although it has been reported to manifest itself differently, in our case it presented in a microphthalmic eye as anterior segment dysgenesis with broad-based mid-peripheral synechiae, posterior embryotoxon, iridoschisis, ectropion uveae, hypotony and subluxated cataractous lens with a taut anterior hyaloid face which are rare associations with PFV.

  10. Remodeling Tumor Vasculature to Enhance Delivery of Intermediate-Sized Nanoparticles.

    Science.gov (United States)

    Jiang, Wen; Huang, Yuhui; An, Yi; Kim, Betty Y S

    2015-09-22

    Restoration of dysfunctional tumor vasculature can reestablish the pressure gradient between intravascular and interstitial space that is essential for transporting nanomedicines into solid tumors. Morphologic and functional normalization of tumor vessels improves tissue perfusion to facilitate intratumoral nanoparticle delivery. However, this remodeling process also reduces tumor vessel permeability, which can impair nanoparticle transport. Although nanoparticles sized below 10 nm maximally benefited from tumor vessel normalization therapy for enhanced nanomedicine delivery, the small particle size severely limits its applicability. Here, we show that intermediate-sized nanoparticles (20-40 nm) can also benefit from tumor vasculature remodeling. We demonstrate that a window of opportunity exists for a two-stage transport strategy of different nanoparticle sizes. Overall, tumor vessel remodeling enhances the transvascular delivery of intermediate-size nanoparticles of up to 40 nm. Once within the tumor matrix, however, smaller nanoparticles experience a significantly lesser degree of diffusional hindrance, resulting in a more homogeneous distribution within the tumor interstitium. These findings suggest that antiangiogenic therapy and nanoparticle design can be combined in a multistage fashion, with two sets of size-inclusion criteria, to achieve optimal nanomedicine delivery into solid tumors.

  11. Differentiation of the brain vasculature: the answer came blowing by the Wnt

    Directory of Open Access Journals (Sweden)

    Plate Karl H

    2010-01-01

    Full Text Available Abstract Vascularization of the vertebrate brain takes place during embryonic development from a preformed perineural vascular plexus. As a consequence of the intimate contact with neuroectodermal cells the vessels, which are entering the brain exclusively via sprouting angiogenesis, acquire and maintain unique barrier properties known as the blood-brain barrier (BBB. The endothelial BBB depends upon the close association of endothelial cells with pericytes, astrocytes, neurons and microglia, which are summarized in the term neuro-vascular unit. Although it is known since decades that the CNS tissue provides the cues for BBB induction and differentiation in endothelial cells, the molecular mechanism remained obscure. Only recently, the canonical Wnt/β-catenin pathway and the Wnt7a/7b growth factors have been implicated in brain angiogenesis on the one hand and in BBB induction on the other. This breakthrough in understanding the differentiation of the brain vasculature prompted us to review these findings embedded in the emerging concepts of Wnt signaling in the vasculature. In particular, interactions with other pathways that are crucial for vascular development such as VEGF, Notch, angiopoietins and Sonic hedgehog are discussed. Finally, we considered the potential role of the Wnt pathway in vascular brain pathologies in which BBB function is hampered, as for example in glioma, stroke and Alzheimer's disease.

  12. Modulation of the tumor vasculature and oxygenation to improve therapy

    DEFF Research Database (Denmark)

    Siemann, Dietmar W; Horsman, Michael R

    2015-01-01

    nutritional support to tumor cells. As a consequence the expanding neoplastic cell population initiates its own vascular network which is both structurally and functionally abnormal. This aberrant vasculature impacts all aspects of the tumor microenvironment including the cells, extracellular matrix...... important are the functional consequences experienced by the tumor cells residing in such environments: adaptation to hypoxia, cell quiescence, modulation of transporters and critical signaling molecules, immune escape, and enhanced metastatic potential. Together these factors lead to therapeutic barriers...

  13. Segmentation and separation of venous vasculatures in liver CT images

    Science.gov (United States)

    Wang, Lei; Hansen, Christian; Zidowitz, Stephan; Hahn, Horst K.

    2014-03-01

    Computer-aided analysis of venous vasculatures including hepatic veins and portal veins is important in liver surgery planning. The analysis normally consists of two important pre-processing tasks: segmenting both vasculatures and separating them from each other by assigning different labels. During the acquisition of multi-phase CT images, both of the venous vessels are enhanced by injected contrast agent and acquired either in a common phase or in two individual phases. The enhanced signals established by contrast agent are often not stably acquired due to non-optimal acquisition time. Inadequate contrast and the presence of large lesions in oncological patients, make the segmentation task quite challenging. To overcome these diffculties, we propose a framework with minimal user interactions to analyze venous vasculatures in multi-phase CT images. Firstly, presented vasculatures are automatically segmented adopting an efficient multi-scale Hessian-based vesselness filter. The initially segmented vessel trees are then converted to a graph representation, on which a series of graph filters are applied in post-processing steps to rule out irrelevant structures. Eventually, we develop a semi-automatic workow to refine the segmentation in the areas of inferior vena cava and entrance of portal veins, and to simultaneously separate hepatic veins from portal veins. Segmentation quality was evaluated with intensive tests enclosing 60 CT images from both healthy liver donors and oncological patients. To quantitatively measure the similarities between segmented and reference vessel trees, we propose three additional metrics: skeleton distance, branch coverage, and boundary surface distance, which are dedicated to quantifying the misalignment induced by both branching patterns and radii of two vessel trees.

  14. Characterization and assessment of hyperelastic and elastic properties of decellularized human adipose tissues.

    Science.gov (United States)

    Omidi, Ehsan; Fuetterer, Lydia; Reza Mousavi, Seyed; Armstrong, Ryan C; Flynn, Lauren E; Samani, Abbas

    2014-11-28

    Decellularized adipose tissue (DAT) has shown potential as a regenerative scaffold for plastic and reconstructive surgery to augment or replace damaged or missing adipose tissue (e.g. following lumpectomy or mastectomy). The mechanical properties of soft tissue substitutes are of paramount importance in restoring the natural shape and appearance of the affected tissues, and mechanical mismatching can lead to unpredictable scar tissue formation and poor implant integration. The goal of this work was to assess the linear elastic and hyperelastic properties of decellularized human adipose tissue and compare them to those of normal breast adipose tissue. To assess the influence of the adipose depot source on the mechanical properties of the resultant decellularized scaffolds, we performed indentation tests on DAT samples sourced from adipose tissue isolated from the breast, subcutaneous abdominal region, omentum, pericardial depot and thymic remnant, and their corresponding force-displacement data were acquired. Elastic and hyperelastic parameters were estimated using inverse finite element algorithms. Subsequently, a simulation was conducted in which the estimated hyperelastic parameters were tested in a real human breast model under gravity loading in order to assess the suitability of the scaffolds for implantation. Results of these tests showed that in the human breast, the DAT would show similar deformability to that of native normal tissue. Using the measured hyperelastic parameters, we were able to assess whether DAT derived from different depots exhibited different intrinsic nonlinearities. Results showed that DAT sourced from varying regions of the body exhibited little intrinsic nonlinearity, with no statistically significant differences between the groups.

  15. Anthropometry of fetal vasculature in the chorionic plate.

    Science.gov (United States)

    Gordon, Z; Elad, D; Almog, R; Hazan, Y; Jaffa, A J; Eytan, O

    2007-12-01

    Normal fetal development is dependent on adequate placental blood perfusion. The functional role of the placenta takes place mainly in the capillary system; however, ultrasound imaging of fetal blood flow is commonly performed on the umbilical artery, or on its first branches over the chorionic plate. The objective of this study was to evaluate the structural organization of the feto-placental vasculature of the chorionic plate. Casting of the placental vasculature was performed on 15 full-term placentas using a dental polymer mixed with colored ink. Observations of the cast models revealed that the branching architecture of the chorionic vessel is a combination of dichotomous and monopodial patterns, where the first two to three generations are always of a dichotomous nature. Analysis of the daughter-to-mother diameter ratios in the chorionic vessels provided a maximum in the range of 0.6-0.8 for the dichotomous branches, whereas in monopodial branches it was in the range of 0.1-0.3. Similar to previous studies, this study reveals that the vasculature architecture is mostly monopodial for the marginal cord insertion and mostly dichotomous for the central insertion. The more marginal the umbilical cord insertion is on the chorionic plate, the more monopodial branching patterns are created to compensate the dichotomous pattern deficiency to perfuse peripheral placental territories.

  16. Effects of dietary amines on the gut and its vasculature.

    Science.gov (United States)

    Broadley, Kenneth J; Akhtar Anwar, M; Herbert, Amy A; Fehler, Martina; Jones, Elen M; Davies, Wyn E; Kidd, Emma J; Ford, William R

    2009-06-01

    Trace amines, including tyramine and beta-phenylethylamine (beta-PEA), are constituents of many foods including chocolate, cheeses and wines and are generated by so-called 'friendly' bacteria such as Lactobacillus, Lactococcus and Enterococcus species, which are found in probiotics. We therefore examined whether these dietary amines could exert pharmacological effects on the gut and its vasculature. In the present study we examined the effects of tyramine and beta-PEA on the contractile activity of guinea-pig and rat ileum and upon the isolated mesenteric vasculature and other blood vessels. Traditionally, these amines are regarded as sympathomimetic amines, exerting effects through the release of noradrenaline from sympathetic nerve endings, which should relax the gut. A secondary aim was therefore to confirm this mechanism of action. However, contractile effects were observed in the gut and these were independent of noradrenaline, acetylcholine, histamine and serotonin receptors. They were therefore probably due to the recently described trace amine-associated receptors. These amines relaxed the mesenteric vasculature. In contrast, the aorta and coronary arteries were constricted, a response that was also independent of a sympathomimetic action. From these results, we propose that after ingestion, trace amines could stimulate the gut and improve intestinal blood flow. Restriction of blood flow elsewhere diverts blood to the gut to aid digestion. Thus, trace amines in the diet may promote the digestive process through stimulation of the gut and improved gastrointestinal circulation.

  17. The Pleiotropic Role of L1CAM in Tumor Vasculature

    Science.gov (United States)

    Angiolini, Francesca; Cavallaro, Ugo

    2017-01-01

    Angiogenesis, the formation of new vessels, is a key step in the development, invasion, and dissemination of solid tumors and, therefore, represents a viable target in the context of antitumor therapy. Indeed, antiangiogenic approaches have given promising results in preclinical models and entered the clinical practice. However, in patients, the results obtained so far with antiangiogenic drugs have not completely fulfilled expectations, especially because their effect has been transient with tumors developing resistance and evasion mechanisms. A better understanding of the mechanisms that underlie tumor vascularization and the functional regulation of cancer vessels is a prerequisite for the development of novel and alternative antiangiogenic treatments. The L1 cell adhesion molecule (L1CAM), a cell surface glycoprotein previously implicated in the development and plasticity of the nervous system, is aberrantly expressed in the vasculature of various cancer types. L1CAM plays multiple pro-angiogenic roles in the endothelial cells of tumor-associated vessels, thus emerging as a potential therapeutic target. In addition, L1CAM prevents the maturation of cancer vasculature and its inhibition promotes vessel normalization, a process that is thought to improve the therapeutic response of tumors to cytotoxic drugs. We here provide an overview on tumor angiogenesis and antiangiogenic therapies and summarize the current knowledge on the biological role of L1CAM in cancer vasculature. Finally, we highlight the clinical implications of targeting L1CAM as a novel antiangiogenic and vessel-normalizing approach. PMID:28134764

  18. Tissue quality assessment using a novel direct elasticity assessment device (the E-finger: a cadaveric study of prostatectomy dissection.

    Directory of Open Access Journals (Sweden)

    Daniel W Good

    Full Text Available Minimally invasive radical prostatectomy (RP (robotic and laparoscopic, have brought improvements in the outcomes of RP due to improved views and increased degrees of freedom of surgical devices. Robotic and laparoscopic surgeries do not incorporate haptic feedback, which may result in complications secondary to inadequate tissue dissection (causing positive surgical margins, rhabdosphincter damage, etc. We developed a micro-engineered device (6 mm2 sized [E-finger] capable of quantitative elasticity assessment, with amplitude ratio, mean ratio and phase lag representing this. The aim was to assess the utility of the device in differentiating peri-prostatic tissue types in order to guide prostate dissection.Two embalmed and 2 fresh frozen cadavers were used in the study. Baseline elasticity values were assessed in bladder, prostate and rhabdosphincter of pre-dissected embalmed cadavers using the micro-engineered device. A measurement grid was created to span from the bladder, across the prostate and onto the rhabdosphincter of fresh frozen cadavers to enable a systematic quantitative elasticity assessment of the entire area by 2 independent assessors. Tissue was sectioned along each row of elasticity measurement points, and stained with haematoxylin and eosin (H&E. Image analysis was performed with Image Pro Premier to determine the histology at each measurement point.Statistically significant differences in elasticity were identified between bladder, prostate and sphincter in both embalmed and fresh frozen cadavers (p = < 0.001. Intra-class correlation (ICC reliability tests showed good reliability (average ICC = 0.851. Sensitivity and specificity for tissue identification was 77% and 70% respectively to a resolution of 6 mm2.This cadaveric study has evaluated the ability of our elasticity assessment device to differentiate bladder, prostate and rhabdosphincter to a resolution of 6 mm2. The results provide useful data for which to continue to

  19. Evaluation of optical imaging and spectroscopy approaches for cardiac tissue depth assessment

    Energy Technology Data Exchange (ETDEWEB)

    Lin, B; Matthews, D; Chernomordik, V; Gandjbakhche, A; Lane, S; Demos, S G

    2008-02-13

    NIR light scattering from ex vivo porcine cardiac tissue was investigated to understand how imaging or point measurement approaches may assist development of methods for tissue depth assessment. Our results indicate an increase of average image intensity as thickness increases up to approximately 2 mm. In a dual fiber spectroscopy configuration, sensitivity up to approximately 3 mm with an increase to 6 mm when spectral ratio between selected wavelengths was obtained. Preliminary Monte Carlo results provided reasonable fit to the experimental data.

  20. Pigment epithelium-derived factor enhances tumor response to radiation through vasculature normalization in allografted lung cancer in mice.

    Science.gov (United States)

    Xu, Z; Dong, Y; Peng, F; Yu, Z; Zuo, Y; Dai, Z; Chen, Y; Wang, J; Hu, X; Zhou, Q; Ma, H; Bao, Y; Gao, G; Chen, M

    2015-03-01

    This study aimed to explore the potential therapeutic effects of the combination of pigment epithelium-derived factor (PEDF) and radiation on lung cancer. The Lewis lung cancer (LLC) allografts in nude mice were treated with radiation, PEDF and PEDF combined with radiation. The morphologic changes of tumor vasculature and the hypoxic fraction of tumor tissues were evaluated. Significant inhibition of tumor growth was observed when radiation was applied between the 3rd and 7th day (the vasculature normalization window) after the initiation of PEDF treatment. During the vasculature normalization window, the tumor blood vessels in PEDF-treated mice were less tortuous and more uniform than those in the LLC allograft tumor treated with phosphate-buffered saline. Meanwhile, the thickness of the basement membrane was remarkably reduced and pericyte coverage was significantly increased with the PEDF treatment. We also found that tumor hypoxic fraction decreased during the 3rd to the 7th day after PEDF treatment, suggesting improved intratumoral oxygenation. Taken together, our results show that PEDF improved the effects of radiation therapy on LLC allografts by inducing a vascular normalization window from the 3rd to the 7th day after PEDF treatment. Our findings provide a basis for treating lung cancer with the combination of PEDF and radiation.

  1. Perilipin+ embryonic preadipocytes actively proliferate along growing vasculatures for adipose expansion.

    Science.gov (United States)

    Hong, Ki Yong; Bae, Hosung; Park, Intae; Park, Dae-Young; Kim, Kyun Hoo; Kubota, Yoshiaki; Cho, Eui-Sic; Kim, Hail; Adams, Ralf H; Yoo, Ook-Joon; Koh, Gou Young

    2015-08-01

    Despite the growing interest in adipose tissue as a therapeutic target of metabolic diseases, the identity of adipocyte precursor cells (preadipocytes) and the formation of adipose tissue during embryonic development are still poorly understood. Here, we clarified the identity and dynamic processes of preadipocytes in mouse white adipose tissue during embryogenesis through direct examination, lineage tracing and culture systems. Surprisingly, we found that lipid-lacking but perilipin(+) or adiponectin(+) proliferating preadipocytes started to emerge at embryonic day 16.5, and these cells underwent active proliferation until birth. Moreover, these preadipocytes resided as clusters and were distributed along growing adipose vasculatures. Importantly, the embryonic preadipocytes exhibited considerable coexpression of stem cell markers, such as CD24, CD29 and PDGFRα, and a small portion of preadipocytes were derived from PDGFRβ(+) mural cells, in contrast to the adult preadipocytes present in the stromal vascular fraction. Further analyses with in vitro and ex vivo culture systems revealed a stepwise but dynamic regulation of preadipocyte formation and differentiation during prenatal adipogenesis. To conclude, we unraveled the identity and characteristics of embryonic preadipocytes, which are crucial for the formation and expansion of adipose tissue during embryogenesis.

  2. Anatomic Eponyms in Neuroradiology: Brain, Cerebral Vasculature, and Calvarium.

    Science.gov (United States)

    Bunch, Paul M; Zamani, Amir A

    2016-06-01

    Medical eponyms are ubiquitous, numerous, and at times controversial. They are often useful for succinctly conveying complex concepts, and familiarity with eponyms is important for proper usage and appropriate communication. In this historical review, we identify 18 anatomic eponyms used to describe structures of the brain, cerebral vasculature, and calvarium. For each structure, we first offer a biographical sketch of the individual for whom the structure is named. This is followed by a description of the anatomic structure and a brief discussion of its clinical relevance.

  3. Contractile Changes in the Vasculature After Subchronic Smoking

    DEFF Research Database (Denmark)

    Haanes, Kristian Agmund; Kruse, Lars Schack; Johansson, Helle Wulf;

    2016-01-01

    : Wild type (WT) and SP-D KO mice were exposed to cigarette smoke (CS) or room air for 12 weeks. The pulmonary artery, left anterior descending coronary artery, and basilar artery (BA) were isolated and mounted in wire myographs. Contractile concentration response curves to endothelin-1 and UDP were...... displayed no smoke induced changes, but were surprisingly similar to the CSE WT. CONCLUSION: The contractility to UDP was altered in the brain and heart vasculature of CSE mice. SP-D KO (both control and CSE) and CSE WT had similar changes in contractility compared to control WT. IMPLICATIONS: These results...

  4. Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis

    Science.gov (United States)

    Zhang, Boyang; Montgomery, Miles; Chamberlain, M. Dean; Ogawa, Shinichiro; Korolj, Anastasia; Pahnke, Aric; Wells, Laura A.; Massé, Stéphane; Kim, Jihye; Reis, Lewis; Momen, Abdul; Nunes, Sara S.; Wheeler, Aaron R.; Nanthakumar, Kumaraswamy; Keller, Gordon; Sefton, Michael V.; Radisic, Milica

    2016-06-01

    We report the fabrication of a scaffold (hereafter referred to as AngioChip) that supports the assembly of parenchymal cells on a mechanically tunable matrix surrounding a perfusable, branched, three-dimensional microchannel network coated with endothelial cells. The design of AngioChip decouples the material choices for the engineered vessel network and for cell seeding in the parenchyma, enabling extensive remodelling while maintaining an open-vessel lumen. The incorporation of nanopores and micro-holes in the vessel walls enhances permeability, and permits intercellular crosstalk and extravasation of monocytes and endothelial cells on biomolecular stimulation. We also show that vascularized hepatic tissues and cardiac tissues engineered by using AngioChips process clinically relevant drugs delivered through the vasculature, and that millimetre-thick cardiac tissues can be engineered in a scalable manner. Moreover, we demonstrate that AngioChip cardiac tissues implanted with direct surgical anastomosis to the femoral vessels of rat hindlimbs establish immediate blood perfusion.

  5. Assessment of myocardial strain and strain rate by tissue doppler echocar-diography

    Directory of Open Access Journals (Sweden)

    Ekimova N.A.

    2013-03-01

    Full Text Available The objective of the article is to review the current data on the method of quantitative evaluation of cardiac mechanics — assessment of myocardial strain and strain rate according to the results of the tissue Doppler echocardiography and prospects of its clinical application.

  6. High Field Sodium MRI Assessment of Stem Cell Chondrogenesis in a Tissue-Engineered Matrix.

    Science.gov (United States)

    Majumdar, Shreyan; Pothirajan, Padmabharathi; Dorcemus, Deborah; Nukavarapu, Syam; Kotecha, Mrignayani

    2016-04-01

    The development of non-invasive assessment techniques in vitro and in vivo is essential for monitoring and evaluating the growth of engineered cartilage tissues. Magnetic resonance imaging (MRI) is the leading non-invasive imaging modality used for assessing engineered cartilage. Typical MRI uses water proton relaxation times (T1 and T2) and apparent diffusion coefficient (ADC) to assess tissue growth. These techniques, while excellent in providing the first assurance of tissue growth, are unspecific to monitor the progress of engineered cartilage extracellular matrix components. In the current article, we present high field (11.7 T, (1)H freq. = 500 MHz) sodium MRI assessment of tissue-engineered cartilage at the early stage of tissue growth in vitro. We observed the chondrogenesis of human bone marrow derived stromal cells seeded in a gradient polymer-hydrogel matrix made out of poly(85 lactide-co-15 glycolide)--PuraMatrix™ for 4 weeks. We calculated the sodium concentration in the engineered constructs using a model of sodium MRI voxels that takes into account scaffold volume, cell density and amount of glycosaminoglycan (GAG). The sodium concentration was then converted to the fixed charge density (FCD) and compared with FCD derived from biochemical GAG analysis. Despite the small amount of GAG present in the engineered constructs, the sodium MRI derived FCD is found to be correlated (Pearson correlation coefficient R = 0.79) with the FCD derived from biochemical analysis. We conclude that sodium MRI could prove to be an invaluable tool in assessing engineered cartilage quantitatively during the repair or regeneration of cartilage defects.

  7. Control of the adaptive immune response by tumor vasculature

    Directory of Open Access Journals (Sweden)

    Laetitia eMauge

    2014-03-01

    Full Text Available The endothelium is nowadays described as an entire organ that regulates various processes: vascular tone, coagulation, inflammation, and immune cell trafficking, depending on the vascular site and its specific microenvironment as well as on endothelial cell-intrinsic mechanisms like epigenetic changes. In this review, we will focus on the control of the adaptive immune response by the tumor vasculature. In physiological conditions, the endothelium acts as a barrier regulating cell trafficking by specific expression of adhesion molecules enabling adhesion of immune cells on the vessel, and subsequent extravasation. This process is also dependent on chemokine and integrin expression, and on the type of junctions defining the permeability of the endothelium. Endothelial cells can also regulate immune cell activation. In fact, the endothelial layer can constitute immunological synapses due to its close interactions with immune cells, and the delivery of co-stimulatory or co-inhibitory signals. In tumor conditions, the vasculature is characterized by abnormal vessel structure and permeability, and by specific phenotype of endothelial cells. All these abnormalities lead to a modulation of intratumoral immune responses and contribute to the development of intratumoral immunosuppression, which is a major mechanism for promoting the development, progression and treatment resistance of tumors. The in-depth analysis of these various abnormalities will help defining novel targets for the development of antitumoral treatments. Furthermore, eventual changes of the endothelial cell phenotype identified by plasma biomarkers could secondarily be selected to monitor treatment efficacy.

  8. Robust model-based vasculature detection in noisy biomedical images.

    Science.gov (United States)

    Mahadevan, Vijay; Narasimha-Iyer, Harihar; Roysam, Badrinath; Tanenbaum, Howard L

    2004-09-01

    This paper presents a set of algorithms for robust detection of vasculature in noisy retinal video images. Three methods are studied for effective handling of outliers. The first method is based on Huber's censored likelihood ratio test. The second is based on the use of a alpha-trimmed test statistic. The third is based on robust model selection algorithms. All of these algorithms rely on a mathematical model for the vasculature that accounts for the expected variations in intensity/texture profile, width, orientation, scale, and imaging noise. These unknown parameters are estimated implicitly within a robust detection and estimation framework. The proposed algorithms are also useful as nonlinear vessel enhancement filters. The proposed algorithms were evaluated over carefully constructed phantom images, where the ground truth is known a priori, as well as clinically recorded images for which the ground truth was manually compiled. A comparative evaluation of the proposed approaches is presented. Collectively, these methods outperformed prior approaches based on Chaudhuri et al. (1989) matched filtering, as well as the verification methods used by prior exploratory tracing algorithms, such as the work of Can et aL (1999). The Huber censored likelihood test yielded the best overall improvement, with a 145.7% improvement over the exploratory tracing algorithm, and a 43.7% improvement in detection rates over the matched filter.

  9. Assessment of MRI Issues at 3 Tesla for a New Metallic Tissue Marker.

    Science.gov (United States)

    Cronenweth, Charlotte M; Shellock, Frank G

    2015-01-01

    Purpose. To assess the MRI issues at 3 Tesla for a metallic tissue marker used to localize removal areas of tissue abnormalities. Materials and Methods. A newly designed, metallic tissue marker (Achieve Marker, CareFusion, Vernon Hills, IL) used to mark biopsy sites, particularly in breasts, was assessed for MRI issues which included standardized tests to determine magnetic field interactions (i.e., translational attraction and torque), MRI-related heating, and artifacts at 3 Tesla. Temperature changes were determined for the marker using a gelled-saline-filled phantom. MRI was performed at a relatively high specific absorption rate (whole body averaged SAR, 2.9-W/kg). MRI artifacts were evaluated using T1-weighted, spin echo and gradient echo pulse sequences. Results. The marker displayed minimal magnetic field interactions (2-degree deflection angle and no torque). MRI-related heating was only 0.1°C above background heating (i.e., the heating without the tissue marker present). Artifacts seen as localized signal loss were relatively small in relation to the size and shape of the marker. Conclusions. Based on the findings, the new metallic tissue marker is acceptable or "MR Conditional" (using current labeling terminology) for a patient undergoing an MRI procedure at 3 Tesla or less.

  10. Assessing beef carcass tissue weights using computed tomography spirals of primal cuts.

    Science.gov (United States)

    Navajas, E A; Glasbey, C A; Fisher, A V; Ross, D W; Hyslop, J J; Richardson, R I; Simm, G; Roehe, R

    2010-01-01

    More than 800 beef primal cuts from 44 Aberdeen Angus and Limousin-cross steers carcasses were scanned using spiral computed tomography (CT) and dissected. Thresholds for the segmentation of fat, muscle and bone in the CT spirals were estimated with the objective of assessing the weight of these tissues in the primal cuts and in the entire carcasses. Thresholds were estimated using half of the dataset (DBE) and then validated in the other half (DBV). Automatic image analysis procedures were used to assess tissue weights. The R(2) of the regression between primal tissue weight by dissection and CT were high in both datasets for fat (DBE, 0.89; DBV, 0.92), muscle (DBE, 0.99; DBV, 0.99) and bone (DBE, 0.95; DBV, 0.97). The estimation of total carcass tissue weights were also very accurate for the three tissues (R(2) values of 0.95 to 0.96), indicating that CT scanning may deliver very accurate information on beef carcass composition faster and with lower cost than physical dissection and without damaging or depreciating the primal joints.

  11. Quantitative Assessment of First Annular Pulley and Adjacent Tissues Using High-Frequency Ultrasound

    Science.gov (United States)

    Lin, Yi-Hsun; Yang, Tai-Hua; Wang, Shyh-Hau; Su, Fong-Chin

    2017-01-01

    Due to a lack of appropriate image resolution, most ultrasound scanners are unable to sensitively discern the pulley tissues. To extensively investigate the properties of the A1 pulley system and the surrounding tissues for assessing trigger finger, a 30 MHz ultrasound system was implemented to perform in vitro experiments using the hypodermis, A1 pulley, and superficial digital flexor tendon (SDFT) dissected from cadavers. Ultrasound signals were acquired from both the transverse and sagittal planes of each tissue sample. The quantitative ultrasonic parameters, including sound speed, attenuation coefficient, integrated backscatter (IB) and Nakagami parameter (m), were subsequently estimated to characterize the tissue properties. The results demonstrated that the acquired ultrasound images have high resolution and are able to sufficiently differentiate the variations of tissue textures. Moreover, the attenuation slope of the hypodermis is larger than those of the A1 pulley and SDFT. The IB of A1 pulley is about the same as that of the hypodermis, and is very different from SDFT. The m parameter of the A1 pulley is also very different from those of hypodermis and SDFT. This study demonstrated that high-frequency ultrasound images in conjunction with ultrasonic parameters are capable of characterizing the A1 pulley system and surrounding tissues. PMID:28067854

  12. Tissue distribution of adoptively transferred adherent lymphokine-activated killer cells assessed by different cell labels

    DEFF Research Database (Denmark)

    Basse, P; Herberman, R B; Hokland, M;

    1992-01-01

    Assessment of the tissue distribution of adoptively transferred adherent lymphokine-activated killer A-LAK) cells by use of 51Cr indicated that these effector cells, after an initial phase in the lungs, distributed in high numbers to liver and spleen (30% and 10% of injected dose, respectively......). However, when this experiment was repeated with 125IdUrd as cell label, fewer than 2% and 0.5% of the injected cells distributed into liver and spleen respectively. To analyse this discrepancy, we compared the tissue distribution of 51Cr- and 125IdUrd-labelled A-LAK cells with that indicated...

  13. A visual description of the dissection of the cerebral surface vasculature and associated meninges and the choroid plexus from rat brain.

    Science.gov (United States)

    Bowyer, John F; Thomas, Monzy; Patterson, Tucker A; George, Nysia I; Runnells, Jeffrey A; Levi, Mark S

    2012-11-14

    This video presentation was created to show a method of harvesting the two most important highly vascular structures, not residing within the brain proper, that support forebrain function. They are the cerebral surface (superficial) vasculature along with associated meninges (MAV) and the choroid plexus which are necessary for cerebral blood flow and cerebrospinal fluid (CSF) homeostasis. The tissue harvested is suitable for biochemical and physiological analysis, and the MAV has been shown to be sensitive to damage produced by amphetamine and hyperthermia. As well, the major and minor cerebral vasculatures harvested in MAV are of potentially high interest when investigating concussive types of head trauma. The MAV dissected in this presentation consists of the pial and some of the arachnoid membrane (less dura) of the meninges and the major and minor cerebral surface vasculature. The choroid plexus dissected is the structure that resides in the lateral ventricles as described by Oldfield and McKinley. The methods used for harvesting these two tissues also facilitate the harvesting of regional cortical tissue devoid of meninges and larger cerebral surface vasculature, and is compatible with harvesting other brain tissues such as striatum, hypothalamus, hippocampus, etc. The dissection of the two tissues takes from 5 to 10 min total. The gene expression levels for the dissected MAV and choroid plexus, as shown and described in this presentation can be found at GSE23093 (MAV) and GSE29733 (choroid plexus) at the NCBI GEO repository. This data has been, and is being, used to help further understand the functioning of the MAV and choroid plexus and how neurotoxic events such as severe hyperthermia and AMPH adversely affect their function.

  14. Selective alpha-particle mediated depletion of tumor vasculature with vascular normalization.

    Directory of Open Access Journals (Sweden)

    Jaspreet Singh Jaggi

    Full Text Available BACKGROUND: Abnormal regulation of angiogenesis in tumors results in the formation of vessels that are necessary for tumor growth, but compromised in structure and function. Abnormal tumor vasculature impairs oxygen and drug delivery and results in radiotherapy and chemotherapy resistance, respectively. Alpha particles are extraordinarily potent, short-ranged radiations with geometry uniquely suitable for selectively killing neovasculature. METHODOLOGY AND PRINCIPAL FINDINGS: Actinium-225 ((225Ac-E4G10, an alpha-emitting antibody construct reactive with the unengaged form of vascular endothelial cadherin, is capable of potent, selective killing of tumor neovascular endothelium and late endothelial progenitors in bone-marrow and blood. No specific normal-tissue uptake of E4G10 was seen by imaging or post-mortem biodistribution studies in mice. In a mouse-model of prostatic carcinoma, (225Ac-E4G10 treatment resulted in inhibition of tumor growth, lower serum prostate specific antigen level and markedly prolonged survival, which was further enhanced by subsequent administration of paclitaxel. Immunohistochemistry revealed lower vessel density and enhanced tumor cell apoptosis in (225Ac-E4G10 treated tumors. Additionally, the residual tumor vasculature appeared normalized as evident by enhanced pericyte coverage following (225Ac-E4G10 therapy. However, no toxicity was observed in vascularized normal organs following (225Ac-E4G10 therapy. CONCLUSIONS: The data suggest that alpha-particle immunotherapy to neovasculature, alone or in combination with sequential chemotherapy, is an effective approach to cancer therapy.

  15. The Effect Of Portfolio Assessment Application On Academic Achievement and Test Anxiety in Teaching Animal Tissue

    Directory of Open Access Journals (Sweden)

    M. Handan GÜNEŞ

    2015-06-01

    Full Text Available In this study, the effect of portfolio assessment application on student success in teaching animal tissue covered in General Biology 1 and General Biology Laboratory 1 courses in Science and Technology Education curriculum was investigated. For this purpose, portfolio assessment application was administered to the second grade students who were attending Education Faculty, Science and Technology Education Department. A multiple choice achievement test was applied as pre-test and post-test to control (n=28 and experimental group (n=29 students who were randomly chosen from A and B class. Additionally, a test anxiety scale was applied to the students to obtain their opinions about test anxiety. Research results revealed that portfolio assessment application has positive effects on improving the success level of teacher candidates and reducing their test anxiety level in both education process and assessment and evaluation processes. Study results also revealed that portfolio assessment may be effective in teaching subjects too.

  16. Photoperiod sensitivity of the Arabidopsis circadian clock is tissue-specific.

    Science.gov (United States)

    Shimizu, Hanako; Araki, Takashi; Endo, Motomu

    2015-01-01

    Tissue-specific functions of the circadian clock in Arabidopsis have recently been revealed. The vasculature clock shows distinctive gene expression profiles compared to the clock in other tissues under light-dark cycles. However, it has not yet been established whether the vasculature clock also shows unique gene expression patterns that correlate with temperature cycles, another important environmental cue. Here, we detected diel phase of TIMING OF CAB EXPRESSION 1 (TOC1) expression in the vasculature and whole leaf under long-day light-dark cycles and temperature cycles. We found that the vasculature clock had advanced TOC1 phase under light-dark cycles but not under temperature cycles, suggesting that the vasculature clock has lower sensitivity against temperature signals. Furthermore, the phase advancement of TOC1 was seen only under long-day condition but not under short-day condition. These results support our previous conclusion that the circadian clock in vasculature preferentially senses photoperiodic signals.

  17. Distribution of abdominal adipose tissue as a predictor of hepatic steatosis assessed by MRI

    Energy Technology Data Exchange (ETDEWEB)

    Ducluzeau, P.-H. [Department of endocrinology-Diabetology-Nutrition, Universitary Hospital of Angers, Faculty of Medicine of Angers (France); Manchec-Poilblanc, P., E-mail: Manchecp@yahoo.f [Department of Radiology, Universitary Hospital of Angers, Faculty of Medicine of Angers (France); Roullier, V. [Department of Radiology, Universitary Hospital of Angers, Faculty of Medicine of Angers (France); LISA, Laboratoire d' Ingenierie des Systemes Automatises, Universitary Hospital of Angers, Faculty of Medicine of Angers (France); Cesbron, E. [Department of digestive and liver disease, Universitary hospital of Angers, Faculty of Medicine of Angers (France); Lebigot, J. [Department of Radiology, Universitary Hospital of Angers, Faculty of Medicine of Angers (France); Bertrais, S. [HIFIH Laboratory, UPRES EA 3859, IFR 132, Universitary Hospital of Angers, Faculty of Medicine of Angers (France); Aube, C. [Department of Radiology, Universitary Hospital of Angers, Faculty of Medicine of Angers (France); HIFIH Laboratory, UPRES EA 3859, IFR 132, Universitary Hospital of Angers, Faculty of Medicine of Angers (France)

    2010-09-15

    Aim: To evaluate the relationship between the distribution of visceral and subcutaneous adipose tissue and hepatic steatosis assessed using magnetic resonance imaging (MRI). Materials and methods: One T1-weighted, in-/out-of-phase, single-section sequence at the L3/L4 level and one multi-echo gradient MRI (MGRE) sequence were performed on 65 patients [19 females and 46 males; age 57 {+-} 9.5 years; body mass index (BMI) 31 {+-} 5.1 kg/m{sup 2}]. Visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) surfaces, and hepatic steatosis were automatically calculated using in-house software. Weight, height, BMI, waist circumference, hip circumference, and waist:hip ratio were recorded. The probability of having a steatosis greater than 10% on MRI was evaluated by receiver operating characteristic (ROC) curves. Results: The anthropometric parameter best correlated to hepatic steatosis was the waist-to-hip ratio (r = 0.301). VAT and proportion of VAT were correlated to liver fat content (r = 0.307 and r = 0.249, respectively). No significant correlations were found for BMI, hip circumference, and SAT. The area under the receiver operating characteristics (AUROCs) for the relationship between liver steatosis and BMI, waist circumference, waist:hip ratio, VAT surface, and proportion of VAT, were respectively 0.52, 0.63, 0.71, 0.73 and 0.75. Conclusion: Adipose tissue distribution is more relevant than total fat mass when assessing the possibility of liver steatosis in overweight patients.

  18. An end-to-end assessment of range uncertainty in proton therapy using animal tissues

    Science.gov (United States)

    Zheng, Yuanshui; Kang, Yixiu; Zeidan, Omar; Schreuder, Niek

    2016-11-01

    Accurate assessment of range uncertainty is critical in proton therapy. However, there is a lack of data and consensus on how to evaluate the appropriate amount of uncertainty. The purpose of this study is to quantify the range uncertainty in various treatment conditions in proton therapy, using transmission measurements through various animal tissues. Animal tissues, including a pig head, beef steak, and lamb leg, were used in this study. For each tissue, an end-to-end test closely imitating patient treatments was performed. This included CT scan simulation, treatment planning, image-guided alignment, and beam delivery. Radio-chromic films were placed at various depths in the distal dose falloff region to measure depth dose. Comparisons between measured and calculated doses were used to evaluate range differences. The dose difference at the distal falloff between measurement and calculation depends on tissue type and treatment conditions. The estimated range difference was up to 5, 6 and 4 mm for the pig head, beef steak, and lamb leg irradiation, respectively. Our study shows that the TPS was able to calculate proton range within about 1.5% plus 1.5 mm. Accurate assessment of range uncertainty in treatment planning would allow better optimization of proton beam treatment, thus fully achieving proton beams’ superior dose advantage over conventional photon-based radiation therapy.

  19. Correlation of breast tissue histology and optical signatures to improve margin assessment techniques

    Science.gov (United States)

    Kennedy, Stephanie; Caldwell, Matthew; Bydlon, Torre; Mulvey, Christine; Mueller, Jenna; Wilke, Lee; Barry, William; Ramanujam, Nimmi; Geradts, Joseph

    2016-06-01

    Optical spectroscopy is sensitive to morphological composition and has potential applications in intraoperative margin assessment. Here, we evaluate ex vivo breast tissue and corresponding quantified hematoxylin & eosin images to correlate optical scattering signatures to tissue composition stratified by patient characteristics. Adipose sites (213) were characterized by their cell area and density. All other benign and malignant sites (181) were quantified using a grid method to determine composition. The relationships between mean reduced scattering coefficient (), and % adipose, % collagen, % glands, adipocyte cell area, and adipocyte density were investigated. These relationships were further stratified by age, menopausal status, body mass index (BMI), and breast density. We identified a positive correlation between and % collagen and a negative correlation between and age and BMI. Increased collagen corresponded to increased variability. In postmenopausal women, was similar regardless of fibroglandular content. Contributions from collagen and glands to were independent and equivalent in benign sites; glands showed a stronger positive correlation than collagen to in malignant sites. Our data suggest that scattering could differentiate highly scattering malignant from benign tissues in postmenopausal women. The relationship between scattering and tissue composition will support improved scattering models and technologies to enhance intraoperative optical margin assessment.

  20. Rapid full-field OCT assessment of clinical tissue specimens (Conference Presentation)

    Science.gov (United States)

    Dalimier, Eugénie; Harms, Fabrice; Brossollet, Charles; Benoit, Emilie; Martins, Franck; Boccara, Claude A.

    2016-03-01

    FFOCT (Full Field Optical Coherence Tomography) is a novel optical technology that gives access to very high resolution tomography images of biological tissues within minutes, non-invasively. This makes it an attractive tool to bridge the gap between medical imaging modalities (MRI, ultrasound, CT) used for cancer lesion identification or targeting and histological diagnosis. Clinical tissue specimens, such as surgical cancer margins or biopsies, can potentially be assessed rapidly, by the clinician, in the aim to help him decide on the course of action. A fast FFOCT prototype was built, that provides 1cm2 images with 1 µm resolution in 1 minute, and can accommodate samples up to 50mm diameter. Specific work was carried out to implement a large sample holder, high-speed image acquisition system, optimized scanning, and accelerated GPU tiles stitching. Results obtained on breast, urology, and digestive tissues show the efficiency of the technique for the detection of cancer on clinical tissue specimens, and reinforce the clinical relevance of the technique. The technical and clinical results show that the fast FFOCT system can successfully be used for a fast assessment of cancer excision margins or biopsies providing a very valuable tool in the clinical environment.

  1. Biologic Effects of Dopamine on Tumor Vasculature in Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Myrthala Moreno-Smith

    2013-05-01

    Full Text Available Chronic sympathetic nervous system activation results in increased angiogenesis and tumor growth in orthotopic mouse models of ovarian carcinoma. However, the mechanistic effects of such activation on the tumor vasculature are not well understood. Dopamine (DA, an inhibitory catecholamine, regulates the functions of normal and abnormal blood vessels. Here, we examined whether DA, an inhibitory catecholamine, could block the effects of chronic stress on tumor vasculature and tumor growth. Exogenous administration of DA not only decreased tumor microvessel density but also increased pericyte coverage of tumor vessels following daily restraint stress in mice. Daily restraint stress resulted in significantly increased tumor growth in the SKOV3ip1 and HeyA8 ovarian cancer models. DA treatment blocked stress-mediated increases in tumor growth and increased pericyte coverage of tumor endothelial cells. Whereas the antiangiogenic effect of DA is mediated by dopamine receptor 2 (DR2, our data indicate that DA, through DR1, stimulates vessel stabilization by increasing pericyte recruitment to tumor endothelial cells. DA significantly stimulated migration of mouse 10T1/2 pericyte-like cells in vitro and increased cyclic adenosine mono-phosphate (cAMP levels in these cells. Moreover, DA or the DR1 agonist SKF 82958 increased platinum concentration in SKOV3ip1 tumor xenografts following cisplatin administration. In conclusion, DA stabilizes tumor blood vessels through activation of pericyte cAMP-protein kinase A signaling pathway by DR1. These findings could have implications for blocking the stimulatory effects of chronic stress on tumor growth.

  2. Ultrasound imaging beyond the vasculature with new generation contrast agents.

    Science.gov (United States)

    Perera, Reshani H; Hernandez, Christopher; Zhou, Haoyan; Kota, Pavan; Burke, Alan; Exner, Agata A

    2015-01-01

    Current commercially available ultrasound contrast agents are gas-filled, lipid- or protein-stabilized microbubbles larger than 1 µm in diameter. Because the signal generated by these agents is highly dependent on their size, small yet highly echogenic particles have been historically difficult to produce. This has limited the molecular imaging applications of ultrasound to the blood pool. In the area of cancer imaging, microbubble applications have been constrained to imaging molecular signatures of tumor vasculature and drug delivery enabled by ultrasound-modulated bubble destruction. Recently, with the rise of sophisticated advancements in nanomedicine, ultrasound contrast agents, which are an order of magnitude smaller (100-500 nm) than their currently utilized counterparts, have been undergoing rapid development. These agents are poised to greatly expand the capabilities of ultrasound in the field of targeted cancer detection and therapy by taking advantage of the enhanced permeability and retention phenomenon of many tumors and can extravasate beyond the leaky tumor vasculature. Agent extravasation facilitates highly sensitive detection of cell surface or microenvironment biomarkers, which could advance early cancer detection. Likewise, when combined with appropriate therapeutic agents and ultrasound-mediated deployment on demand, directly at the tumor site, these nanoparticles have been shown to contribute to improved therapeutic outcomes. Ultrasound's safety profile, broad accessibility and relatively low cost make it an ideal modality for the changing face of healthcare today. Aided by the multifaceted nano-sized contrast agents and targeted theranostic moieties described herein, ultrasound can considerably broaden its reach in future applications focused on the diagnosis and staging of cancer.

  3. A method for assessing mitochondrial bioenergetics in whole white adipose tissues.

    Science.gov (United States)

    Dunham-Snary, Kimberly J; Sandel, Michael W; Westbrook, David G; Ballinger, Scott W

    2014-01-01

    Obesity is a primary risk factor for numerous metabolic diseases including metabolic syndrome, type II diabetes (T2DM), cardiovascular disease and cancer. Although classically viewed as a storage organ, the field of white adipose tissue biology is expanding to include the consideration of the tissue as an endocrine organ and major contributor to overall metabolism. Given its role in energy production, the mitochondrion has long been a focus of study in metabolic dysfunction and a link between the organelle and white adipose tissue function is likely. Herein, we present a novel method for assessing mitochondrial bioenergetics from whole white adipose tissue. This method requires minimal manipulation of tissue, and eliminates the need for cell isolation and culture. Additionally, this method overcomes some of the limitations to working with transformed and/or isolated primary cells and allows for results to be obtained more expediently. In addition to the novel method, we present a comprehensive statistical analysis of bioenergetic data as well as guidelines for outlier analysis.

  4. Simultaneous confocal fluorescence microscopy and optical coherence tomography for drug distribution and tissue integrity assessment

    Science.gov (United States)

    Rinehart, Matthew T.; LaCroix, Jeffrey; Henderson, Marcus; Katz, David; Wax, Adam

    2011-03-01

    The effectiveness of microbicidal gels, topical products developed to prevent infection by sexually transmitted diseases including HIV/AIDS, is governed by extent of gel coverage, pharmacokinetics of active pharmaceutical ingredients (APIs), and integrity of vaginal epithelium. While biopsies provide localized information about drug delivery and tissue structure, in vivo measurements are preferable in providing objective data on API and gel coating distribution as well as tissue integrity. We are developing a system combining confocal fluorescence microscopy with optical coherence tomography (OCT) to simultaneously measure local concentrations and diffusion coefficients of APIs during transport from microbicidal gels into tissue, while assessing tissue integrity. The confocal module acquires 2-D images of fluorescent APIs multiple times per second allowing analysis of lateral diffusion kinetics. The custom Fourier domain OCT module has a maximum a-scan rate of 54 kHz and provides depth-resolved tissue integrity information coregistered with the confocal fluorescence measurements. The combined system is validated by imaging phantoms with a surrogate fluorophore. Time-resolved API concentration measured at fixed depths is analyzed for diffusion kinetics. This multimodal system will eventually be implemented in vivo for objective evaluation of microbicide product performance.

  5. Assessing allele-specific expression across multiple tissues from RNA-seq read data

    Science.gov (United States)

    Pirinen, Matti; Lappalainen, Tuuli; Zaitlen, Noah A.; Dermitzakis, Emmanouil T.; Donnelly, Peter; McCarthy, Mark I.; Rivas, Manuel A.

    2015-01-01

    Motivation: RNA sequencing enables allele-specific expression (ASE) studies that complement standard genotype expression studies for common variants and, importantly, also allow measuring the regulatory impact of rare variants. The Genotype-Tissue Expression (GTEx) project is collecting RNA-seq data on multiple tissues of a same set of individuals and novel methods are required for the analysis of these data. Results: We present a statistical method to compare different patterns of ASE across tissues and to classify genetic variants according to their impact on the tissue-wide expression profile. We focus on strong ASE effects that we are expecting to see for protein-truncating variants, but our method can also be adjusted for other types of ASE effects. We illustrate the method with a real data example on a tissue-wide expression profile of a variant causal for lipoid proteinosis, and with a simulation study to assess our method more generally. Availability and implementation: http://www.well.ox.ac.uk/~rivas/mamba/. R-sources and data examples http://www.iki.fi/mpirinen/ Contact: matti.pirinen@helsinki.fi or rivas@well.ox.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25819081

  6. Development of heart failure assessed by tissue Doppler imaging in hypertensive Dahl rats

    OpenAIRE

    宮田, 聖子||ミヤタ, セイコ||Miyata, Seiko; 山田, 亜紀||ヤマダ, アキ||Yamada, Aki||Iwami Yamada, Aki; 橋本, 克徳||ハシモト, カツノリ||Hashimoto, Katsunori; 黒木, 祥子||クロキ, ショウコ||Kuroki, Shoko; 岩本, 隆司||イワモト, タカシ||Iwamoto, Takashi; 野田, 明子||ノダ, アキコ||Noda, Akiko

    2014-01-01

    Objective: Tissue Doppler imaging (TDI) has been recognized as a useful tool to assess regional myocardial function. The purpose of this study was to evaluate the development of heart failure in hypertensive Dahl rats using echocardiography with TDI. Methods: Dahl salt-sensitive (DS) rats were placed on 8% NaCl diet from 7 weeks old. As an age-matched control, DS rats were consistently placed on normal diet. In these rats, echocardiography was performed successively. We evaluated interventric...

  7. Automated high-throughput assessment of prostate biopsy tissue using infrared spectroscopic chemical imaging

    Science.gov (United States)

    Bassan, Paul; Sachdeva, Ashwin; Shanks, Jonathan H.; Brown, Mick D.; Clarke, Noel W.; Gardner, Peter

    2014-03-01

    Fourier transform infrared (FT-IR) chemical imaging has been demonstrated as a promising technique to complement histopathological assessment of biomedical tissue samples. Current histopathology practice involves preparing thin tissue sections and staining them using hematoxylin and eosin (H&E) after which a histopathologist manually assess the tissue architecture under a visible microscope. Studies have shown that there is disagreement between operators viewing the same tissue suggesting that a complementary technique for verification could improve the robustness of the evaluation, and improve patient care. FT-IR chemical imaging allows the spatial distribution of chemistry to be rapidly imaged at a high (diffraction-limited) spatial resolution where each pixel represents an area of 5.5 × 5.5 μm2 and contains a full infrared spectrum providing a chemical fingerprint which studies have shown contains the diagnostic potential to discriminate between different cell-types, and even the benign or malignant state of prostatic epithelial cells. We report a label-free (i.e. no chemical de-waxing, or staining) method of imaging large pieces of prostate tissue (typically 1 cm × 2 cm) in tens of minutes (at a rate of 0.704 × 0.704 mm2 every 14.5 s) yielding images containing millions of spectra. Due to refractive index matching between sample and surrounding paraffin, minimal signal processing is required to recover spectra with their natural profile as opposed to harsh baseline correction methods, paving the way for future quantitative analysis of biochemical signatures. The quality of the spectral information is demonstrated by building and testing an automated cell-type classifier based upon spectral features.

  8. Assessment of bioburden on human and animal tissues: part 2--results of testing of human tissue and qualification of a composite sample for routine bioburden determination.

    Science.gov (United States)

    Kowalski, John B; Merritt, Karen; Gocke, David; Osborne, Joel

    2012-08-01

    A quantitative method was developed and validated to assess bioburden on tissue from human donors and to compare bioburden determination results to swab culture results from the same donor. An initial study with allograft tissue from 101 donors showed a wide range of bioburden levels; values from no colony-forming units (CFU) detected to >28,000 CFU were observed. Tissues from donors that had swab cultures negative for objectionable microorganisms generally had lower bioburden than tissues from donors where objectionable microorganisms were recovered by swab culturing. In a follow-up study with 1,445 donors, a wide range of bioburden levels was again observed on tissues from donors that were swab culture negative for objectionable microorganisms. Tissues from 885 (61%) of these donors had no recoverable bioburden (donors had recoverable bioburden which ranged from 1 to >24,000 CFU. Identification of bioburden isolates showed a diversity of genera and species. In compliance with the recent revision of the American Association of Tissue Banks K2.210 Standard, the quantitative bioburden determination method was validated with a composite tissue sample that contains bone and soft tissue sections tested together in one extraction vessel. A recovery efficiency of 68% was validated and the composite sample was shown to be representative of all of the tissues recovered from a donor. The use of the composite sample in conjunction with the quantitative bioburden determination method will facilitate an accurate assessment of the numbers and types of contaminating microorganisms on allografts prior to disinfection/sterilization. This information will ensure that disinfection/sterilization processes are properly validated and the capability of the overall allograft process is understood on a donor by donor basis.

  9. Assessment of histological changes in antemortem gingival tissues fixed at various time intervals: A method of estimation of postmortem interval

    Science.gov (United States)

    Mahalakshmi, V.; Gururaj, N.; Sathya, R.; Sabarinath, T. R.; Sivapathasundharam, B.; Kalaiselvan, S.

    2016-01-01

    Introduction: Conventional methods to estimate the time of death are adequate, but a histological method is yet unavailable to assess postmortem interval (PMI). The autolytic changes that occur in an unfixed antemortem gingival tissue which reflects histologically at an early stage are similar to changes that occur in postmortem tissue. These histological changes can be used and applied in a postmortem tissue as a method to assess PMI. Aims: The aim of the study is to assess the histological changes in a gingival tissue left unfixed for various time intervals and to correlate the findings with duration. Materials and Methods: Sixty gingival tissues obtained from patients following therapeutic extractions, impactions, gingivectomy and crown lengthening procedures were used. Each tissue obtained was divided into two pieces and labeled as “A”, the control group and “ B” the study group. Tissues labeled “A” were fixed in 10% formalin immediately and tissues labeled“B” were placed in closed containers and fixed after 15, 30, 45 min, 1, 2, and 4 h time interval. Of the sixty tissues in the study group “ B”, ten tissues were used for each time interval under investigation. All the fixed tissues were processed, stained, assessed, and analyzed statistically using Pearson correlation and regression analysis. Results: Histological changes appear at 15 min in an unfixed antemortem tissue. At 2 h interval, all layers with few cells in basal cell layer are involved. At 4 h interval, loss of stratification and complete homogenization of cells in the superficial layers with prominent changes in basal layer is evident. There was a positive correlation (<1.0) between the time interval and the appearance of the histological changes. Conclusion: Histological changes such as complete homogenization of cells in superficial layers and loss of epithelial architecture at 4 h in unfixed antemortem tissue may be used as a criterion to estimate PMI, after further studies

  10. Assessment of histological changes in antemortem gingival tissues fixed at various time intervals: A method of estimation of postmortem interval

    Directory of Open Access Journals (Sweden)

    V Mahalakshmi

    2016-01-01

    Full Text Available Introduction: Conventional methods to estimate the time of death are adequate, but a histological method is yet unavailable to assess postmortem interval (PMI. The autolytic changes that occur in an unfixed antemortem gingival tissue which reflects histologically at an early stage are similar to changes that occur in postmortem tissue. These histological changes can be used and applied in a postmortem tissue as a method to assess PMI. Aims: The aim of the study is to assess the histological changes in a gingival tissue left unfixed for various time intervals and to correlate the findings with duration. Materials and Methods: Sixty gingival tissues obtained from patients following therapeutic extractions, impactions, gingivectomy and crown lengthening procedures were used. Each tissue obtained was divided into two pieces and labeled as “A”, the control group and “ B” the study group. Tissues labeled “A” were fixed in 10% formalin immediately and tissues labeled“B” were placed in closed containers and fixed after 15, 30, 45 min, 1, 2, and 4 h time interval. Of the sixty tissues in the study group “ B”, ten tissues were used for each time interval under investigation. All the fixed tissues were processed, stained, assessed, and analyzed statistically using Pearson correlation and regression analysis. Results: Histological changes appear at 15 min in an unfixed antemortem tissue. At 2 h interval, all layers with few cells in basal cell layer are involved. At 4 h interval, loss of stratification and complete homogenization of cells in the superficial layers with prominent changes in basal layer is evident. There was a positive correlation (<1.0 between the time interval and the appearance of the histological changes.Conclusion: Histological changes such as complete homogenization of cells in superficial layers and loss of epithelial architecture at 4 h in unfixed antemortem tissue may be used as a criterion to estimate PMI, after

  11. In situ label-free cell viability assessment of nucleus pulposus tissue.

    Science.gov (United States)

    Dittmar, Roman; van Dijk, Bart G M; van Zandvoort, Marc A M J; Ito, Keita

    2014-04-01

    Regenerative medicine approaches aiming at treating degenerating intervertebral discs, a major cause of back pain, are increasingly tested in ex-vivo disc explant models mimicking in-vivo conditions. For assessing the efficacy of regenerative therapies, cell viability is commonly measured requiring specific labels to stain cells. Here, we demonstrate and evaluate how cellular auto-fluorescence can be utilized to non-invasively assess viability in disc tissue in-situ using label-free two-photon microscopy. Live and dead bovine disc cells (0% and 100% cell viability) from the nucleus pulposus were seeded into collagen gels and auto-fluorescence was characterized. Subsequently, nucleus pulposus explants were cultured for 6 days in media with different glucose supplementation (0, 0.25, 0.5, and 1 g/L) to induce different degrees of cell death. Then, samples were split and viability was assessed using label-free two-photon microscopy and conventional staining. Results show that live and dead nucleus pulposus cells systematically emit auto-fluorescent light with distinct characteristics. Cell viability values obtained with label-free microscopy did not significantly differ from those acquired with staining. In summary, monitoring auto-fluorescence facilitates accurate cell viability assessment in nucleus tissue requiring no additional dyes. Thus, this technique may be suitable for pre-clinical testing of regenerative therapies in nucleus pulposus cultures. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:545-550, 2014.

  12. Generation and Assessment of Functional Biomaterial Scaffolds for Applications in Cardiovascular Tissue Engineering and Regenerative Medicine

    Science.gov (United States)

    Hinderer, Svenja; Brauchle, Eva

    2015-01-01

    Current clinically applicable tissue and organ replacement therapies are limited in the field of cardiovascular regenerative medicine. The available options do not regenerate damaged tissues and organs, and, in the majority of the cases, show insufficient restoration of tissue function. To date, anticoagulant drug‐free heart valve replacements or growing valves for pediatric patients, hemocompatible and thrombus‐free vascular substitutes that are smaller than 6 mm, and stem cell‐recruiting delivery systems that induce myocardial regeneration are still only visions of researchers and medical professionals worldwide and far from being the standard of clinical treatment. The design of functional off‐the‐shelf biomaterials as well as automatable and up‐scalable biomaterial processing methods are the focus of current research endeavors and of great interest for fields of tissue engineering and regenerative medicine. Here, various approaches that aim to overcome the current limitations are reviewed, focusing on biomaterials design and generation methods for myocardium, heart valves, and blood vessels. Furthermore, novel contact‐ and marker‐free biomaterial and extracellular matrix assessment methods are highlighted. PMID:25778713

  13. Effect of noise pollution on testicular tissue and hormonal assessment in rat.

    Science.gov (United States)

    Farzadinia, P; Bigdeli, M; Akbarzadeh, S; Mohammadi, M; Daneshi, A; Bargahi, A

    2016-11-01

    Many studies have focused on the effect of noise stress on the health. So far, few studies have been conducted on the effect of noise on reproductive system. The aim of study was to investigate the effect of noise pollution on morphometric parameters of testicular tissue and hormonal assessment (ACTH, cortisol and testosterone). In this study, 40 male rats were exposed to control, 95, 105 and 115 dB noise intensity for sixty days. At the end of study, blood sampling was performed and ACTH, cortisol and testosterone concentrations were assessed. The results showed that noise stress decreased testosterone levels in the 115 dB-treated group, while it increased the ACTH and cortisol levels. Histological sections of testis showed that the mean diameter of the seminiferous tubules and thickness of the germinal epithelium reduced compared to the control group. Also the ratio of the interstitial tissue area to the total testicular tissue area was increased significantly. Our study shows that noise stress may have negative influences on male fertility.

  14. Assessment of strain and strain rate in embryonic chick heart in vivo using tissue Doppler optical coherence tomography

    Science.gov (United States)

    Li, Peng; Liu, Aiping; Shi, Liang; Yin, Xin; Rugonyi, Sandra; Wang, Ruikang K.

    2011-11-01

    We present a method to assess the in vivo radial strain and strain rate of the myocardial wall, which is of great importance to understand the biomechanics of cardiac development, using tissue Doppler optical coherence tomography (tissue-DOCT). Combining the structure and velocity information acquired from tissue-DOCT, the velocity distribution in the myocardial wall is plotted, from which the radial strain and strain rate are evaluated. The results demonstrate that tissue-DOCT can be used as a useful tool to describe tissue deformation, especially, the biomechanical characteristics of the embryonic heart.

  15. Quantitative assessment of optical properties in healthy cartilage and repair tissue by optical coherence tomography and histology (Conference Presentation)

    Science.gov (United States)

    Jansen, Sanne M. A.; Cernohorsky, Paul; de Bruin, Daniel M.; van der Pol, Edwin; Savci-Heijink, Cemile D.; Strackee, Simon D.; Faber, Dirk J.; van Leeuwen, Ton G.

    2016-02-01

    Quantification of the OCT signal is an important step toward clinical implementation of a diagnostic tool in cartilage imaging. Discrimination of structural cartilage differences in patients with osteoarthritis is critical, yet challenging. This study assesses the variation in the optical attenuation coefficient (μOCT) between healthy cartilage, repair tissue, bone and layers within repair tissue in a controlled setting. OCT and histology was used to assess goat talus articular surfaces in which central osteochondral defects were created. Exact matches of OCT and histology were selected for research. μOCT measurements were taken from healthy cartilage, repair tissue and bone. Measured μOCT in healthy cartilage was higher compared to both repair tissue and bone tissue. Two possible mechanisms for the difference in attenuation were investigated. We studied morphological parameters in terms of nucleus count, nucleus size and inter-nucleus distance. Collagen content in healthy cartilage and repair tissue was assessed using polarization microscopy. Quantitative analysis of the nuclei did not demonstrate a difference in nucleus size and count between healthy cartilage and repair tissue. In healthy cartilage, cells were spaced farther apart and had a lower variation in local nuclear density compared to repair tissue. Polarization microscopy suggested higher collagen content in healthy cartilage compared to repair tissue. μOCT measurements can distinguish between healthy cartilage, repair tissue and bone. Results suggest that cartilage OCT attenuation measurements could be of great impact in clinical diagnostics of osteoarthritis.

  16. Fractal analysis of the retinal vasculature and chronic kidney disease.

    Science.gov (United States)

    Sng, Chelvin C A; Sabanayagam, Charumathi; Lamoureux, Ecosse L; Liu, Erica; Lim, Su Chi; Hamzah, Haslina; Lee, Jeannette; Tai, E Shyong; Wong, Tien Y

    2010-07-01

    BACKGROUND. Fractal analysis provides a global index of the geometric complexity and optimality of vascular networks. In this study, we investigated the relationship between fractal measurements of the retinal vasculature and chronic kidney disease (CKD). METHODS. This was a population-based case-control study which included participants from the Singapore Prospective Study Program. We identified 261 participants with CKD, defined as estimated glomerular filtration rate of fractal dimension (D(f)) was quantified from digitized fundus photographs using a computer-based programme. RESULTS. The mean D(f) was 1.43 +/- 0.048 in the participants with CKD and 1.44 +/- 0.042 in controls (P = 0.013). Suboptimal D(f) in the lowest (first) and highest (fifth) quintiles were associated with an increased prevalence of CKD after adjusting for age, systolic blood pressure, diabetes and other risk factors [odds ratio (OR) 2.10, 95% confidence interval (CI) 1.15, 3.83 and OR 1.84, 95% CI 1.06, 3.17; compared to the fourth quintile, respectively). This association was present even in participants without diabetes or hypertension. CONCLUSIONS. Our study found that an abnormal retinal vascular network is associated with an increased risk of CKD, supporting the hypothesis that deviations from optimal microvascular architecture may be related to kidney damage.

  17. Importance Rat Liver Morphology and Vasculature in Surgical Research.

    Science.gov (United States)

    Vdoviaková, Katarína; Vdoviaková, Katarína; Petrovová, Eva; Krešáková, Lenka; Maloveská, Marcela; Teleky, Jana; Jenčová, Janka; Živčák, Jozef; Jenča, Andrej

    2016-12-02

    BACKGROUND The laboratory rat is one of the most popular experimental models for the experimental surgery of the liver. The objective of this study was to investigate the morphometric parameters, physiological data, differences in configuration of liver lobes, biliary system, and vasculature (arteries, veins, and lymphatic vessels) of the liver in laboratory rats. In addition, this study supports the anatomic literature and identified similarities and differences with human and other mammals. MATERIAL AND METHODS Forty laboratory rats were dissected to prepare corrosion casts of vascular system specimens (n=20), determine the lymph vessels and lymph nodes (n=10), and for macroscopic anatomical dissection (n=10) of the rat liver. The results are listed in percentages. The anatomical nomenclature of the liver morphology, its arteries, veins, lymph nodes, and lymphatic vessels are in accordance with Nomina Anatomica Veterinaria. RESULTS We found many variations in origin, direction, and division of the arterial, venous, and lymphatic systems in rat livers, and found differences in morphometric parameters compared to results reported by other authors. The portal vein was formed by 4 tributaries in 23%, by 3 branches in 64%, and by 2 tributaries in 13%. The liver lymph was drained to the 2 different lymph nodes. The nomenclature and morphological characteristics of the rat liver vary among authors. CONCLUSIONS Our results may be useful for the planing of experimental surgery and for cooperation with other investigation methods to help fight liver diseases in human populations.

  18. Chemokine-guided angiogenesis directs coronary vasculature formation in zebrafish.

    Science.gov (United States)

    Harrison, Michael R M; Bussmann, Jeroen; Huang, Ying; Zhao, Long; Osorio, Arthela; Burns, C Geoffrey; Burns, Caroline E; Sucov, Henry M; Siekmann, Arndt F; Lien, Ching-Ling

    2015-05-26

    Interruption of the coronary blood supply severely impairs heart function with often fatal consequences for patients. However, the formation and maturation of these coronary vessels is not fully understood. Here we provide a detailed analysis of coronary vessel development in zebrafish. We observe that coronary vessels form in zebrafish by angiogenic sprouting of arterial cells derived from the endocardium at the atrioventricular canal. Endothelial cells express the CXC-motif chemokine receptor Cxcr4a and migrate to vascularize the ventricle under the guidance of the myocardium-expressed ligand Cxcl12b. cxcr4a mutant zebrafish fail to form a vascular network, whereas ectopic expression of Cxcl12b ligand induces coronary vessel formation. Importantly, cxcr4a mutant zebrafish fail to undergo heart regeneration following injury. Our results suggest that chemokine signaling has an essential role in coronary vessel formation by directing migration of endocardium-derived endothelial cells. Poorly developed vasculature in cxcr4a mutants likely underlies decreased regenerative potential in adults.

  19. Supracrestal gingival tissue: assessing relation with periodontal biotypes in a healthy periodontium.

    Science.gov (United States)

    Arora, Ritika; Narula, Satish C; Sharma, Rajinder K; Tewari, Shikha

    2013-01-01

    This cross-sectional study assessed the variability in supracrestal gingival tissue (SGT) dimensions in a healthy periodontium. SGT dimensions were evaluated for differences across various locations, tooth types, and periodontal biotypes. All measurements were made with a vernier caliper to the nearest 0.1 mm. A total of 1,932 sites in 366 teeth were statistically analyzed. Median overall SGT was recorded as 3.50 mm with a range from 1.80 to 6.20 mm. The thick-flat biotype exhibited greater median SGT than the thinscalloped biotype. When planning crown lengthening surgery, periodontal biotype may have a significant role in determining SGT dimensions.

  20. Total average diastolic longitudinal displacement by colour tissue doppler imaging as an assessment of diastolic function

    DEFF Research Database (Denmark)

    de Knegt, Martina Chantal; Biering-Sørensen, Tor; Søgaard, Peter;

    2016-01-01

    BACKGROUND: The current method for a non-invasive assessment of diastolic dysfunction is complex with the use of algorithms of many different echocardiographic parameters. Total average diastolic longitudinal displacement (LD), determined by colour tissue Doppler imaging (TDI) via the measurement...... by TDI, and the degree of diastolic dysfunction, based on current guidelines. Of these 206 patients, 157 had cardiac anomalies that could potentially affect diastolic LD such as severe systolic heart failure (n = 45), LV hypertrophy (n = 49), left ventricular (LV) dilation (n = 30), and mitral...

  1. Assessment of Breast, Brain and Skin Pathological Tissue Using Full Field OCM

    Science.gov (United States)

    Dalimier, Eugénie; Assayag, Osnath; Harms, Fabrice; Boccara, A. Claude

    The aim of this chapter is to assess whether the images of the breast, brain, and skin tissue obtained by FFOCM contain sufficient detail to allow pathologists to make a diagnosis of cancer and other pathologies comparable to what was obtained by conventional histological techniques. More precisely, it is necessary to verify on FFOCM images if it is possible to differentiate a healthy area from a pathological area. The reader interested in other organs or in animal studies may find a large number of 2D or 3D images in the atlas [2].

  2. Predicting effects of blood flow rate and size of vessels in a vasculature on hyperthermia treatments using computer simulation

    Directory of Open Access Journals (Sweden)

    Shih Tzu-Ching

    2010-03-01

    Full Text Available Abstract Background Pennes Bio Heat Transfer Equation (PBHTE has been widely used to approximate the overall temperature distribution in tissue using a perfusion parameter term in the equation during hyperthermia treatment. In the similar modeling, effective thermal conductivity (Keff model uses thermal conductivity as a parameter to predict temperatures. However the equations do not describe the thermal contribution of blood vessels. A countercurrent vascular network model which represents a more fundamental approach to modeling temperatures in tissue than do the generally used approximate equations such as the Pennes BHTE or effective thermal conductivity equations was presented in 1996. This type of model is capable of calculating the blood temperature in vessels and describing a vasculature in the tissue regions. Methods In this paper, a countercurrent blood vessel network (CBVN model for calculating tissue temperatures has been developed for studying hyperthermia cancer treatment. We use a systematic approach to reveal the impact of a vasculature of blood vessels against a single vessel which most studies have presented. A vasculature illustrates branching vessels at the periphery of the tumor volume. The general trends present in this vascular model are similar to those shown for physiological systems in Green and Whitmore. The 3-D temperature distributions are obtained by solving the conduction equation in the tissue and the convective energy equation with specified Nusselt number in the vessels. Results This paper investigates effects of size of blood vessels in the CBVN model on total absorbed power in the treated region and blood flow rates (or perfusion rate in the CBVN on temperature distributions during hyperthermia cancer treatment. Also, the same optimized power distribution during hyperthermia treatment is used to illustrate the differences between PBHTE and CBVN models. Keff (effective thermal conductivity model delivers the

  3. The safety assessment of food ingredients derived from plant cell, tissue and organ cultures: a review.

    Science.gov (United States)

    Murthy, Hosakatte Niranjana; Georgiev, Milen I; Park, So-Young; Dandin, Vijayalaxmi S; Paek, Kee-Yoeup

    2015-06-01

    Plant cell, tissue and organ cultures (PCTOC) have become an increasingly attractive alternative for the production of various high molecular weight molecules which are used as flavourings, fragrances, colouring agents and food additives. Although PCTOC products are cultivated in vitro in a contamination free environment, the raw material produced from PCTOC may contain many components apart from the target compound. In some cases, PCTOC raw materials may also carry toxins, which may be naturally occurring or accumulated during the culture process. Assessment of the safety of PCTOC products is, therefore, a priority of the biotech industries involved in their production. The safety assessment involves the evaluation of starting material, production process and the end product. Before commercialisation, PCTOC products should be evaluated for their chemical and biological properties, as well as for their toxicity. In this review, measures and general criteria for biosafety evaluation of PCTOC products are addressed and thoroughly discussed.

  4. Reliability of Margin Assessment after Surgery for Extremity Soft Tissue Sarcoma: The SSG Experience

    Directory of Open Access Journals (Sweden)

    Clement S. Trovik

    2012-01-01

    Full Text Available Surgery remains the mainstay of soft tissue sarcoma (STS treatment and has been the primary treatment for the majority of patients in Scandinavia during the last 30 years although the use of adjuvant radiotherapy has increased. Patient and treatment characteristics have been recorded in the Scandinavian Sarcoma Group (SSG Register since 1987. When the effect of new radiotherapy guidelines from 1998 was evaluated, the reliability of surgical margin assessments among different Scandinavian institutions was investigated. Margins were reevaluated by a panel of sarcoma surgeons, studying pathology and surgical reports from 117 patients, randomly selected among 470 recorded patients treated between 1998–2003. In 80% of cases, the panel agreed with the original classification. Disagreement was most frequent when addressing the distinction between marginal and wide margins. Considered the element of judgment inherent in all margin assessment, we find this reliability acceptable for using the Register for studies of local control of STS.

  5. Fast full-field OCT assessment of clinical tissue specimens (Conference Presentation)

    Science.gov (United States)

    Dalimier, Eugénie; Harms, Fabrice; Brossolet, Charles; Benoit, Emilie; Martins, Franck; Boccara, Claude

    2016-03-01

    Full-field optical coherence tomography (FFOCT) offers a non-invasive method of obtaining images of biological tissues at ultrahigh resolution (1µm in all 3 directions) approaching traditional histological sections. Previous clinical studies have shown the high efficiency of this imaging technique for the detection of cancer on various organs. This promises great potential of the technique for an ex-vivo quick analysis of surgical resections or biopsy specimens, in the aim to help the surgeon/radiologist decide on the course of action. Here we will present some of the latest technical developments on a FFOCT system which can produce 1cm2 images with 1 µm resolution in 1 minute. Larger samples, up to 50mm diameter, can also be imaged. Details on the large sample handling, high-speed image acquisition, optimized scanning, and accelerated GPU tiles stitching will be given. Results on the clinical applications for breast, urology, and digestive tissues will also be given. They highlight the relevance of the system characteristics for the detection of cancer on ex-vivo specimens. FFOCT now appears clearly as a very fast and non-destructive imaging technique that provides a quick assessment of the tissue morphology. With the benefit of both new technical developments and clinical validation, it turned into a mature technique to be implemented in the clinical environment. In particular, the technique holds potential for the fast ex-vivo analysis of excision margins or biopsies in the operating room.

  6. ASSESSMENT OF DIASTOLIC FUNCTION IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY BY DOPPLER TISSUE IMAGING

    Institute of Scientific and Technical Information of China (English)

    Jing Li; Yan-ling Liu; Hao Wang; Xiu-zhang Lü; Hong-chang Yang; Fu-jian Duan; Zhen-hui Zhu

    2004-01-01

    Objective To determine the clinical application of pulsed Doppler tissue imaging in assessing the left ventricular diastolic function and in discriminating between normal subjects and patients with hypertrophic cardiomyopathy with various stages of diastolic dysfunction.Methods We measured the peak diastolic velocities of mitral annulus in 81 patients with hypertrophic cardiomyopathy with various stages of diastolic dysfunction and 50 normal volunteers by Doppler tissue imaging using the apical window at 2-chamber and long apical views, respectively. The myocardial velocities were determined with use of variance F statistical analysis.Results Early diastolic myocardial velocities ofmitral annulus were higher in normal subjects than in patients with hypertrophic cardiomyopathy with either delayed relaxation, pseudonormal filling, or restrictive filling. However, peak myocardial velocities of mitral annulus during atrial contraction were similar in normal subjects and patients with hypertrophic cardiomyopathy.Conclusion Doppler tissue imaging can directly reflect upon left diastolic ventricular function. Early phase of diastole was the best discriminator between control subjects and patients with hypertrophic cardiomyopathy.

  7. Impact of a Combined High Cholesterol Diet and High Glucose Environment on Vasculature

    Science.gov (United States)

    Cui, Taixing; Tang, Dongqi; Wang, Xing Li

    2013-01-01

    Aims Vascular complications are the leading cause of mortality and morbidity in patients with diabetes. However, proper animal models of diabetic vasculopathy that recapitulate the accelerated progression of vascular lesions in human are unavailable. In the present study, we developed a zebrafish model of diabetic vascular complications and the methodology for quantifying vascular lesion formation real-time in the living diabetic zebrafish. Methods and Results Wild type zebrafish (AB) and transgenic zebrafish lines of fli1:EGFP, lyz:EGFP, gata1:dsRed, double transgenic zebrafish of gata1:dsRed/fli1:EGFP were exposed to high cholesterol diet and 3% glucose (HCD-HG) for 10 days. The zebrafish model with HCD-HG treatment was characterized by significantly increased tissue levels of insulin, glucagon, glucose, total triglyceride and cholesterol. Confocal microscopic analysis further revealed that the diabetic larvae developed clearly thickened endothelial layers, distinct perivascular lipid depositions, substantial accumulations of inflammatory cells in the injured vasculature, and a decreased velocity of blood flow. Moreover, the vascular abnormalities were improved by the treatment of pioglitazone and metformin. Conclusion A combination of high cholesterol diet and high glucose exposure induces a rapid onset of vascular complications in zebrafish similar to the early atherosclerotic vascular injuries in mammalian diabetic models, suggesting that zebrafish may be used as a novel animal model for diabetic vasculopathy. PMID:24349075

  8. Assessment of the interstitial fluid in the subcutaneous tissue of healthy adults using ultrasonography

    Directory of Open Access Journals (Sweden)

    Terumi Ueda-Iuchi

    2015-11-01

    Full Text Available Objective: Lymphoedema involves swelling, especially in the subcutaneous tissues. For lymphoedema management to be successful, it is necessary to remove the interstitial fluid. Subcutaneous echogenicity may be associated with interstitial fluid, but echogenicity is not an indicator for the evaluation of management because we do not directly compare echogenicity with the interstitial fluid. We aimed to identify an outcome indicator for the evaluation of interstitial fluid using ultrasonography. We assessed the correlation between echogenicity and transverse relaxation rate (R2 on magnetic resonance imaging. Methods: This was an observational study. Healthy adults with leg swelling after activity for >8 h were recruited. The legs of 13 women were evaluated using ultrasonography, magnetic resonance imaging and measurements of the limb circumference before and after an intervention to reduce the swelling. Results: Echogenicity in the oedema group was greater than that of the controls. Echogenicity decreased with reductions in oedema. The range of the strongest correlations with the changes in R2 occurred at echogenicity values of 48–144 (Pearson’s correlation coefficient: r = −0.63 and p < 0.01. Thus, it was possible to evaluate the interstitial fluid using echogenicity. Conclusion: The outcome indicators for the evaluation of interstitial fluid using ultrasonography were echogenicities in the range of 48–144, and these values were valid for assessing the interstitial fluid in the subcutaneous tissue.

  9. An Assessment of Cell Culture Plate Surface Chemistry for in Vitro Studies of Tissue Engineering Scaffolds

    Directory of Open Access Journals (Sweden)

    Alexander Röder

    2015-11-01

    Full Text Available The use of biopolymers as a three dimensional (3D support structure for cell growth is a leading tissue engineering approach in regenerative medicine. Achieving consistent cell seeding and uniform cell distribution throughout 3D scaffold culture in vitro is an ongoing challenge. Traditionally, 3D scaffolds are cultured within tissue culture plates to enable reproducible cell seeding and ease of culture media change. In this study, we compared two different well-plates with different surface properties to assess whether seeding efficiencies and cell growth on 3D scaffolds were affected. Cell attachment and growth of murine calvarial osteoblast (MC3T3-E1 cells within a melt-electrospun poly-ε-caprolactone scaffold were assessed when cultured in either “low-adhesive” non-treated or corona discharged-treated well-plates. Increased cell adhesion was observed on the scaffold placed in the surface treated culture plates compared to the scaffold in the non-treated plates 24 h after seeding, although it was not significant. However, higher cell metabolic activity was observed on the bases of all well-plates than on the scaffold, except for day 21, well metabolic activity was higher in the scaffold contained in non-treated plate than the base. These results indicate that there is no advantage in using non-treated plates to improve initial cell seeding in 3D polymeric tissue engineering scaffolds, however non-treated plates may provide an improved metabolic environment for long-term studies.

  10. Assessment of cryopreserved donor skin viability: the experience of the regional tissue bank of Siena.

    Science.gov (United States)

    Pianigiani, E; Tognetti, L; Ierardi, F; Mariotti, G; Rubegni, P; Cevenini, G; Perotti, R; Fimiani, M

    2016-06-01

    Skin allografts from cadaver donors are an important resource for treating extensive burns, slow-healing wounds and chronic ulcers. A high level of cell viability of cryopreserved allografts is often required, especially in burn surgery, in Italy. Thus, we aimed to determine which conditions enable procurement of highly viable skin in our Regional Skin Bank of Siena. For this purpose, we assessed cell viability of cryopreserved skin allografts procured between 2011 and 2013 from 127 consecutive skin donors, before and after freezing (at day 15, 180, and 365). For each skin donor, we collected data concerning clinical history (age, sex, smoking, phototype, dyslipidemia, diabetes, cause of death), donation process (multi-tissue or multi-organ) and timing of skin procurement (assessment of intervals such as death-harvesting, harvesting-banking, death-banking). All these variables were analysed in the whole case study (127 donors) and in different groups (e.g. multi-organ donors, non refrigerated multi-tissue donors, refrigerated multi-tissue donors) for correlations with cell viability. Our results indicated that cryopreserved skin allografts with higher cell viability were obtained from female, non smoker, heartbeating donors died of cerebral haemorrhage, and were harvested within 2 h of aortic clamping and banked within 12 h of harvesting (13-14 h from clamping). Age, cause of death and dyslipidaemia or diabetes did not appear to influence cell viability. To maintain acceptable cell viability, our skin bank needs to reduce the time interval between harvesting and banking, especially for refrigerated donors.

  11. Smartphone-Based Accurate Analysis of Retinal Vasculature towards Point-of-Care Diagnostics

    Science.gov (United States)

    Xu, Xiayu; Ding, Wenxiang; Wang, Xuemin; Cao, Ruofan; Zhang, Maiye; Lv, Peilin; Xu, Feng

    2016-01-01

    Retinal vasculature analysis is important for the early diagnostics of various eye and systemic diseases, making it a potentially useful biomarker, especially for resource-limited regions and countries. Here we developed a smartphone-based retinal image analysis system for point-of-care diagnostics that is able to load a fundus image, segment retinal vessels, analyze individual vessel width, and store or uplink results. The proposed system was not only evaluated on widely used public databases and compared with the state-of-the-art methods, but also validated on clinical images directly acquired with a smartphone. An Android app is also developed to facilitate on-site application of the proposed methods. Both visual assessment and quantitative assessment showed that the proposed methods achieved comparable results to the state-of-the-art methods that require high-standard workstations. The proposed system holds great potential for the early diagnostics of various diseases, such as diabetic retinopathy, for resource-limited regions and countries. PMID:27698369

  12. Normal Doppler velocimetry of renal vasculature in Persian cats.

    Science.gov (United States)

    Carvalho, Cibele F; Chammas, Maria C

    2011-06-01

    Renal diseases are common in older cats. Decreased renal blood flow may be the first sign of dysfunction and can be evaluated by Doppler ultrasound. But previous studies suggest that the resistive index (RI) has a low sensitivity for detecting renal disease. Doppler waveforms of renal and intrarenal arteries demonstrate decreased blood flow before there are any changes in the RI. The purpose of this study was to evaluate the normal Doppler flowmetrics parameters of renal arteries (RAs), interlobar arteries (IAs) and abdominal aorta (AO) in adult healthy, Persian cats. Twenty-five Persian cats (13 females and 12 males with mean age of 30 months and an age range 12-60 months) with normal clinical examinations and biochemical tests and normal systemic blood pressure were given B-mode ultrasonographies in order to exclude all nephropathies, including polycystic kidney disease. All measurements were performed on both kidneys. Both kidneys (n=50) were examined by color mapping of the renal vasculature. Pulsed Doppler was used to examine both RAs, the IAs at cranial, middle and caudal sites, and the AO. The RI was calculated for all of the vessels. Early systolic acceleration (ESA) of RA and IA was obtained with Doppler spectral analysis. Furthermore, the ratio indices between RA/AO, and IA/RA velocities were calculated. The mean values of peak systolic velocity (PSV) and the diameter for AO were 53.17±13.46 cm/s and 0.38±0.08 cm, respectively. The mean RA diameter for all 50 kidneys was 0.15±0.02 cm. Considering the velocimetric values in both RAs, the mean PSV and RI that were obtained were 41.17±9.40 cm/s and 0.54±0.07. The RA had a mean ESA of 1.12±1.14 m/s(2) and the calculated upper limit of the reference value was 3.40 m/s(2). The mean renal-aortic ratio was 0.828±0.296. The IA showed PSV and RI values of 32.16±9.33 cm/s and 0.52±0.06, respectively. The mean ESA of all IAs was 0.73±0.61 m/s(2). The calculated upper limit of the reference value was 2.0m

  13. Control strategies for afterload reduction with an artificial vasculature device.

    Science.gov (United States)

    Giridharan, Guruprasad A; Cheng, Rolando Chip; Glower, Jacob S; Ewert, Daniel L; Sobieski, Michael A; Slaughter, Mark S; Koenig, Steven C

    2012-01-01

    Ventricular assist devices (VADs) have been used successfully as a bridge to transplant in heart failure patients by unloading ventricular volume and restoring the circulation. An artificial vasculature device (AVD) is being developed that may better facilitate myocardial recovery than VAD by controlling the afterload experienced by the native heart and controlling the pulsatile energy entering into the arterial system from the device, potentially reconditioning the arterial system properties. The AVD is a valveless, 80 ml blood chamber with a servo-controlled pusher plate connected to the ascending aorta by a vascular graft. Control algorithms for the AVD were developed to maintain any user-defined systemic input impedance (IM) including resistance, elastance, and inertial components. Computer simulation and mock circulation models of the cardiovascular system were used to test the efficacy of two control strategies for the AVD: 1) average impedance position control (AIPC)-to maintain an average value of resistance during left ventricular (LV) systole and 2) instantaneous impedance force feedback (IIFF) and position control (IIPC)-to maintain a desired value or profile of resistance and compliance. Computer simulations and mock loop tests were performed to predict resulting cardiovascular pressures, volumes, flows, and the resistance and compliance experienced by the native LV during ejection for simulated normal, failing, and recovering LV. These results indicate that the LV volume and pressure decreased, and the LV stroke volume increased with decreasing IM, resulting in an increased ejection fraction. Although the AIPC algorithm is more stable and can tolerate higher levels of sensor errors and noise, the IIFF and IIPC control algorithms are better suited to maintain any instantaneous IM or an IM profile. The developed AVD impedance control algorithms may be implemented with current VADs to promote myocardial recovery and facilitate weaning.

  14. Radiographic assessment of facial soft tissue thickness in South Indian population--An anthropologic study.

    Science.gov (United States)

    Kotrashetti, Vijayalakshmi S; Mallapur, M D

    2016-04-01

    Facial reconstruction is a technique used in forensic anthropology to identify an unknown person. Various methods used for facial reconstruction are drawings, sculpture and computer aided image building which is mainly based on facial soft tissue thickness measurement. Several methods have been established for measuring facial soft tissue thickness (FSTT) with each one having certain limitations. There is limited data available on FSTT among South Indian population. Hence the present study was ventured to determine the FSTT among South Indian adults and also to find FSTT difference between male and female. 308 subjects of South Indian origin (18-27 years) having full set of permanent dentition who require orthodontic treatment were included in the study. Subjects were assessed for Body Mass Index (BMI) and diagnostic digital x-ray of lateral cephalogram (LC), Lateral oblique (LO) view and posterior-anterior (PA) view was obtained. The digital image was transferred to Adobe Photoshop CS4 software and 23 different soft tissue points were measured. Mean FSTT was more in males compared to females except for three landmarks. Statistically significant difference was observed in 20 landmarks when height and weight was compared in males, whereas in females only 12 landmarks showed significant difference. BMI showed good correlation with FSTT in both males and females, which was confirmed by linear regression. The best regressor in terms of estimating FSTT in association with age/sex/BMI were nasion, sub nasale, labial superioris, labrale inferius, gnathion, inferior border of zygomatic, right and left gonion. Stepwise discriminant analysis using all variables showed 94.8% of overall accuracy in sex determination. The observation of present study suggests that LO and PA view along with LC gives information regarding mean FSTT among South Indian population. Even though BMI plays a dominant role in determining FSTT, but age, sex, height and weight should also be considered

  15. Assessment of left ventricular function by tissue Doppler imaging in patients with ankylosing spondylitis

    Directory of Open Access Journals (Sweden)

    Osman Kuloglu

    2012-05-01

    Full Text Available Ankylosing spondylitis (ASpis a chronic, inflammatory and systemic disease affecting pericardium, myocardium and the conduction system of the heart. In this study, we aimed to analyse left ventricular systolic and diastolic functions using tissue Doppler imaging (TDI. 30 patients with ASp and 30 healthy volunteers having the similar demographic characteristics were included. Left ventricular systolic and diastolic functions were assessed by using two dimensional (2D echocardiography, M-mode, pulsed-wave (PW and tissue Doppler echocardiography. The peak systolic velocity (Sm, early diastolic myocardial peak velocity (m, late diastolic myocardial peak velocity (Am, isovolumic acceleration (IVA, myocardial precontraction time (PCTm, myocardial contraction time (CTm, myocardial relaxation time (RTm, and myocardial performance index (MPI were measured at septal and lateral mitral annulus. In conventional echocardiography, end-diastolic interventricular septum and posterior wall diameters were higher in patients with ASp than the control group. The ratio of E/A was significantly lower and deceleration time was significantly prolonged in patients with ASp, but mitral E and A velocities, isovolumic relaxation time and MPI were similar in patient and control group (P>0.05. Left ventricular lateral and septal wall tissue Doppler echocardiography showed that Em, Em/Am ratio and CTm were significantly lower, IVRTm was longer and MPI was higher in patients with ASp. No significant differences were detected between the groups for IVA, Sm, Am, PCTm, PCTm/CTm ratio (P>0.05. We have demonstrated that in patients with ASp, diastolic functions were impaired but systolic functions were preserved by using TDI.

  16. Nonwoven-based gelatin/polycaprolactone membrane proves suitability in a preclinical assessment for treatment of soft tissue defects.

    Science.gov (United States)

    Schulz, Simon; Angarano, Marco; Fabritius, Martin; Mülhaupt, Rolf; Dard, Michel; Obrecht, Marcel; Tomakidi, Pascal; Steinberg, Thorsten

    2014-07-01

    Standard preclinical assessments in vitro often have limitations regarding their transferability to human beings, mainly evoked by their nonhuman and tissue-different/nontissue-specific source. Here, we aimed at employing tissue-authentic simple and complex interactive fibroblast-epithelial cell systems and their in vivo-relevant biomarkers for preclinical in vitro assessment of nonwoven-based gelatin/polycaprolactone membranes (NBMs) for treatment of soft tissue defects. NBMs were composed of electrospun gelatin and polycaprolactone nanofiber nonwovens. Scanning electron microscopy in conjunction with actin/focal contact integrin fluorescence revealed successful adhesion and proper morphogenesis of keratinocytes and fibroblasts, along with cells' derived extracellular matrix deposits. The "feel-good factor" of cells under study on the NBM was substantiated by forming a confluent connective tissue entity, which was concomitant with a stratified epithelial equivalent. Immunohistochemistry proved tissue authenticity over time by abundance of the biomarker vimentin in the connective tissue entity, and chronological increase of keratins KRT1/10 and involucrin expression in epithelial equivalents. Suitability of the novel NBM as wound dressing was evidenced by an almost completion of epithelial wound closure in a pilot mini-pig study, after a surgical intervention-caused gingival dehiscence. In summary, preclinical assessment by tissue-authentic cell systems and the animal pilot study revealed the NBM as an encouraging therapeutic medical device for prospective clinical applications.

  17. Assessing reproductive status in elasmobranch fishes using steroid hormones extracted from skeletal muscle tissue.

    Science.gov (United States)

    Prohaska, Bianca K; Tsang, Paul C W; Driggers, William B; Hoffmayer, Eric R; Wheeler, Carolyn R; Brown, A Christine; Sulikowski, James A

    2013-01-01

    Elasmobranch fishes (sharks, skates, and rays) are particularly susceptible to anthropogenic threats, making a thorough understanding of their life history characteristics essential for proper management. Historically, elasmobranch reproductive data have been collected by lethal sampling, an approach that is problematic for threatened and endangered species. However, recent studies have demonstrated that non-lethal approaches can be as effective as lethal ones for assessment of the reproductive status of an animal. For example, plasma has been used to examine concentrations of steroid hormones. Additionally, skeletal muscle tissue, which can be obtained non-lethally and with minimal stress, can also be used to quantify concentrations of steroid hormones. Skeletal muscle progesterone, testosterone, and estradiol concentrations were determined to be statistically significant indicators of reproductive status in the oviparous Leucoraja erinacea, the yolk-dependent viviparous Squalus acanthias, and the yolk-sac placental viviparous Rhizoprionodon terraenovae. The results of the present study demonstrate that steroid hormones present in non-lethally harvested skeletal muscle tissue can be used as reliable indicators of reproductive status in elasmobranchs.

  18. A new technique for assessing arterial pressure wave forms and central pressure with tissue Doppler

    Science.gov (United States)

    Haluska, Brian A; Jeffriess, Leanne; Mottram, Phillip M; Carlier, Stephane G; Marwick, Thomas H

    2007-01-01

    Background Non-invasive assessment of arterial pressure wave forms using applanation tonometry of the radial or carotid arteries can be technically challenging and has not found wide clinical application. 2D imaging of the common carotid arteries is routinely used and we sought to determine whether arterial waveform measurements could be derived from tissue Doppler imaging (TDI) of the carotid artery. Methods We studied 91 subjects (52 men, age 52 ± 14 years) with and without cardiovascular disease. Tonometry was performed on the carotid artery simultaneously with pulsed wave Doppler of the LVOT and acquired digitally. Longitudinal 2D images of the common carotid artery with and without TDI were also acquired digitally and both TDI and tonometry were calibrated using mean and diastolic cuff pressure and analysed off line. Results Correlation between central pressure by TDI and tonometry was excellent for maximum pressure (r = 0.97, p < 0.0001). The mean differences between central pressures derived by TDI and tonometry were minimal (systolic 5.36 ± 5.5 mmHg; diastolic 1.2 ± 1.2 mmHg). Conclusion Imaging of the common carotid artery motion with tissue Doppler may permit acquisition of a waveform analogous to that from tonometry. This method may simplify estimation of central arterial pressure and calculation of total arterial compliance. PMID:17266772

  19. Holographic Assessment of Lymphoma Tissue (HALT) for Global Oncology Field Applications.

    Science.gov (United States)

    Pathania, Divya; Im, Hyungsoon; Kilcoyne, Aoife; Sohani, Aliyah R; Fexon, Lioubov; Pivovarov, Misha; Abramson, Jeremy S; Randall, Thomas C; Chabner, Bruce A; Weissleder, Ralph; Lee, Hakho; Castro, Cesar M

    2016-01-01

    Low-cost, rapid and accurate detection technologies are key requisites to cope with the growing global cancer challenges. The need is particularly pronounced in resource-limited settings where treatment opportunities are often missed due to the absence of timely diagnoses. We herein describe a Holographic Assessment of Lymphoma Tissue (HALT) system that adopts a smartphone as the basis for molecular cancer diagnostics. The system detects malignant lymphoma cells labeled with marker-specific microbeads that produce unique holographic signatures. Importantly, we optimized HALT to detect lymphomas in fine-needle aspirates from superficial lymph nodes, procedures that align with the minimally invasive biopsy needs of resource-constrained regions. We equipped the platform to directly address the practical needs of employing novel technologies for "real world" use. The HALT assay generated readouts in <1.5 h and demonstrated good agreement with standard cytology and surgical pathology.

  20. Phase variance optical coherence microscopy for label-free imaging of the developing vasculature in zebrafish embryos

    Science.gov (United States)

    Chen, Yu; Trinh, Le A.; Fingler, Jeff; Fraser, Scott E.

    2016-12-01

    A phase variance optical coherence microscope (pvOCM) has been created to image blood flow in the microvasculature of zebrafish embryos, without the use of exogenous labels. The pvOCM imaging system has axial and lateral resolutions of 2.8 μm in tissue and imaging depth of more than 100 μm. Images of 2 to 5 days postfertilization zebrafish embryos identified the detailed anatomical structure based on OCM intensity contrast. Phase variance contrast offered visualization of blood flow in the arteries, veins, and capillaries. The pvOCM images of the vasculature were confirmed by direct comparisons with fluorescence microscopy images of transgenic embryos in which the vascular endothelium is labeled with green fluorescent protein. The ability of pvOCM to capture activities of regional blood flow permits it to reveal functional information that is of great utility for the study of vascular development.

  1. Three-dimensional imaging of the developing vasculature within stem cell-seeded scaffolds cultured in ovo

    Directory of Open Access Journals (Sweden)

    Anna eWoloszyk

    2016-04-01

    Full Text Available Successful tissue engineering requires functional vascularization of the three-dimensional constructs with the aim to serve as implants for tissue replacement and regeneration. The survival of the implant is only possible if the supply of oxygen and nutrients by developing capillaries from the host is established. The chorioallantoic membrane assay is a valuable tool to study the ingrowth and distribution of vessels into scaffolds composed by appropriate biomaterials and stem cell populations that are used in cell-based regenerative approaches. The developing vasculature of chicken embryos within cell-seeded scaffolds can be visualized with microcomputed tomography after intravenous injection of MicroFil®, which is a radiopaque contrast agent. Here, we provide a step-by-step protocol for the seeding of stem cells into silk fibroin scaffolds, the chorioallantoic membrane culture conditions, the procedure of MicroFil® perfusion, and finally the microcomputed tomography scanning. Three-dimensional imaging of the vascularized tissue engineered constructs provides an important analytical tool for studying the potential of cell seeded scaffolds to attract vessels and form vascular networks, as well as for analyzing the number, density, length, branching, and diameter of vessels. This in ovo method can greatly help to screen implants that will be used for tissue regeneration purposes before their in vivo testing, thereby reducing the amount of animals needed for pre-clinical studies.

  2. Experimental Study of Assessment on Ventricular Activation Origin and Contraction Sequence by Doppler Tissue Imaging

    Institute of Scientific and Technical Information of China (English)

    冀瑞平; 王新房; 郑宗锷; 刘望彭; 李治安; 刘俐

    2002-01-01

    To evaluate the possibility and accuracy of Doppler tissue image (DTI) on assessment of normal and abnormal ventricular activation and contraction sequence, 9 open chest canine hearts were analyzed by acceleration mode, M-mode, and spectrum mode DTI. Our results showed that: (1) Acceleration mode DTI could show the origin of activation and conduction sequence on line; (2) Mmode DTI revealed that the activation in mid-interventricular septum was earlier than that in mid-left ventricular posterior wall at sinus activation; (3) Spectrum DTI showed the ventricular endocardium was activated earlier than the ventricular epicardium in all segments at sinus rhythm. The earliest site of activation of the normal ventricular wall was at middle interventricular septum; the latest site was at basal-posterior wall; the contraction sequence was different at the different walls; (4) During abnormal ventricular activation, mid-left ventricular posterior wall was activated earliest in accordance with the pacing sites. Abnormal ventricular activation was slower than sinus activation, and the contraction sequence varied at different sites of ventricular wall. It is concluded that DTI can be used to localize the origin of normal or abnormal myocardial activation and to assess the contraction sequence conveniently, accurately and non-invasively.

  3. Effects of Mitral Balloon Valvuloplasty on Left Ventricular Systolic Functions: Assessment with Color Tissue Doppler

    Directory of Open Access Journals (Sweden)

    Cevat Kırma

    2010-04-01

    Full Text Available Objective: Left ventricular (LV systolic functions are generally depressed in Mitral Stenosis (MS. Recovery of LV systolic functions demonstrated with 2D echocardiography in some patients by mitral balloon valvuloplasty (MBV. Systolic mitral annular velocity (S' by Tissue Doppler Imaging (TDI predicts LV systolic function. We aimed to evaluate early effects of MBV on LV systolic function by TDI.Methods: Forty-eight consecutive patients included to the study (39 female, 36±10 years. A full transthoracic echocardiographic study (TTE including left ventricular ejection fraction assessment by teicholz method and mitral annular color TDI assessment was performed 24 hours before and after MBV in all patients. MBV performed by Inoue technique under guidance of TTE. Analysis of mitral lateral annular S' wave velocity was performed immediately after echocardiographic examination. Results: MBV performed successfully in 43 patients (Group A, and severe mitral regurgitation developed in 5 patients(Group B. Mitral valve area, and S’ wave velocity increased, mean and maximum mitral gradient, and left atrial diameter, and systolic pulmonary artery pressure (PAP were reduced significantly by MBV in group A patients (p<0.01, =0.046, <0.01, <0.01, <0.01, <0.01, respectively. But, only mitral valve area increased significantly ingroup B patients (p<0.01. LVEF by teicholz did not change significantly in both groups. Conclusion: Improvements of LV systolic functions after successfull MBV can easily showed by color TDI where2D echocardiography could not indicate.

  4. Assessment of Regional Myocardial Function in Patients with Hypertrophic Cardiomyopathy by Tissue Strain Imaging

    Institute of Scientific and Technical Information of China (English)

    XIONG Runqing; XIE Mingxing; WANG Xinfang; L(U) Qing

    2006-01-01

    The value of tissue strain imaging (SI) in regional myocardial systolic anddiastolic function assessment was studied. In 18 patients with nonobstructive hypertrophic cardiomyopathy (HCM) and 20 age-matched healthy subjects, regional myocardial longitudinal peak systolic strain in eject time (represented by εet) was measured at basal, mid and apical segments of septal, lateral and posterior walls of the left ventricle (LV) and compared between groups. εet had no significant difference between segments in control group (P>0.05), which displayed a decreasing trend from basal segments to apical ones. εet in the HCM group was significantly decreased (P<0. 05) as compared with that in the healthy group. In the HCM group, εet in the midseptum was significantly less than at the basal and apical septum, and was also less than at the rest LV walls in the same group (P<0.01). The systolic reversed εet was noticed in 35 % of the hypertrophic segments in HCM group. Significantly negative correlation existed between the absolute value of εet and wall thickness in the midseptum (r=- 0.83). The post-systolic strain(PSS) segment number the and amplitudes in healthy group were significantly less than those in HCM group (P<0.05). Both regional myocardial systolic and diastolic functions were impaired in hypertrophic or non-hypertrophic segments in patients with the HCM, especially in hypertrophic segments. Strain imaging technique is a sensitive and accura tool in myocardial dysfunction assessment.

  5. Assessing the effect of a high-fat diet on rodents' adipose tissue using Brillouin and Raman spectroscopy

    Science.gov (United States)

    Troyanova-Wood, Maria; Gobbell, Cassidy; Meng, Zhaokai; Yakovlev, Vladislav V.

    2016-03-01

    The purpose of this study is to evaluate the effect of a high-lipid diet on elasticity of adipose tissue. We employed dual Raman/Brillouin microspectroscopy to analyze brown and white adipose tissues obtained from adult rats. The rats were divided into two groups, one of which received a high-fat feed, while the other served as a control. We hypothesized that the changes in the elasticity of adipose tissues between the two groups can be successfully assessed using Brillouin spectroscopy. We found that the brown adipose tissue possessed a lesser Brillouin shift than the white adipose within each group and that the elastic modulus of both adipose tissues increases in the high-fat diet group. The Raman spectra provided supplementary chemical information and indicated an increase in the lipid-to-protein ratio in the brown adipose, but not in the white adipose.

  6. Threshold-dependent sample sizes for selenium assessment with stream fish tissue

    Science.gov (United States)

    Hitt, Nathaniel P.; Smith, David R.

    2015-01-01

    Natural resource managers are developing assessments of selenium (Se) contamination in freshwater ecosystems based on fish tissue concentrations. We evaluated the effects of sample size (i.e., number of fish per site) on the probability of correctly detecting mean whole-body Se values above a range of potential management thresholds. We modeled Se concentrations as gamma distributions with shape and scale parameters fitting an empirical mean-to-variance relationship in data from southwestern West Virginia, USA (63 collections, 382 individuals). We used parametric bootstrapping techniques to calculate statistical power as the probability of detecting true mean concentrations up to 3 mg Se/kg above management thresholds ranging from 4 to 8 mg Se/kg. Sample sizes required to achieve 80% power varied as a function of management thresholds and Type I error tolerance (α). Higher thresholds required more samples than lower thresholds because populations were more heterogeneous at higher mean Se levels. For instance, to assess a management threshold of 4 mg Se/kg, a sample of eight fish could detect an increase of approximately 1 mg Se/kg with 80% power (given α = 0.05), but this sample size would be unable to detect such an increase from a management threshold of 8 mg Se/kg with more than a coin-flip probability. Increasing α decreased sample size requirements to detect above-threshold mean Se concentrations with 80% power. For instance, at an α-level of 0.05, an 8-fish sample could detect an increase of approximately 2 units above a threshold of 8 mg Se/kg with 80% power, but when α was relaxed to 0.2, this sample size was more sensitive to increasing mean Se concentrations, allowing detection of an increase of approximately 1.2 units with equivalent power. Combining individuals into 2- and 4-fish composite samples for laboratory analysis did not decrease power because the reduced number of laboratory samples was compensated for by increased

  7. Preliminary assessment of facial soft tissue thickness utilizing three-dimensional computed tomography models of living individuals.

    Science.gov (United States)

    Parks, Connie L; Richard, Adam H; Monson, Keith L

    2014-04-01

    Facial approximation is the technique of developing a representation of the face from the skull of an unknown individual. Facial approximation relies heavily on average craniofacial soft tissue depths. For more than a century, researchers have employed a broad array of tissue depth collection methodologies, a practice which has resulted in a lack of standardization in craniofacial soft tissue depth research. To combat such methodological inconsistencies, Stephan and Simpson 2008 [15] examined and synthesized a large number of previously published soft tissue depth studies. Their comprehensive meta-analysis produced a pooled dataset of averaged tissue depths and a simplified methodology, which the researchers suggest be utilized as a minimum standard protocol for future craniofacial soft tissue depth research. The authors of the present paper collected craniofacial soft tissue depths using three-dimensional models generated from computed tomography scans of living males and females of four self-identified ancestry groups from the United States ranging in age from 18 to 62 years. This paper assesses the differences between: (i) the pooled mean tissue depth values from the sample utilized in this paper and those published by Stephan 2012 [21] and (ii) the mean tissue depth values of two demographically similar subsets of the sample utilized in this paper and those published by Rhine and Moore 1984 [16]. Statistical test results indicate that the tissue depths collected from the sample evaluated in this paper are significantly and consistently larger than those published by Stephan 2012 [21]. Although a lack of published variance data by Rhine and Moore 1984 [16] precluded a direct statistical assessment, a substantive difference was also concluded. Further, the dataset presented in this study is representative of modern American adults and is, therefore, appropriate for use in constructing contemporary facial approximations.

  8. Computerized cuff pressure algometry: A new method to assess deep-tissue hypersensitivity in fibromyalgia.

    Science.gov (United States)

    Jespersen, Anders; Dreyer, Lene; Kendall, Sally; Graven-Nielsen, Thomas; Arendt-Nielsen, Lars; Bliddal, Henning; Danneskiold-Samsoe, Bente

    2007-09-01

    The aim of this study was to evaluate the use of computerized cuff pressure algometry (CPA) in fibromyalgia (FM) and to correlate deep-tissue sensitivity assessed by CPA with other disease markers of FM. Forty-eight women with FM and 16 healthy age-matched women were included. A computer-controlled, pneumatic tourniquet cuff was placed over the gastrocnemius muscle. The cuff was inflated, and the subject rated the pain intensity continuously on an electronic Visual Analogue Scale (VAS). The subject stopped the inflation at the pressure-pain tolerance and the corresponding VAS-score was determined (pressure-pain limit). The pressure at which VAS firstly exceeded 0 was defined as the pressure-pain threshold. Other disease markers (FM only): Isokinetic knee muscle strength, tenderpoint-count, myalgic score, Beck Depression Inventory, and Fibromyalgia Impact Questionnaire. Student's T-test was used to compare pressure-pain threshold and pressure-pain tolerance and the Mann-Whitney test to compare pressure-pain limit. Pearson's correlation was used to detect linear relationships. Pressure-pain threshold and pressure-pain tolerance assessed by CPA were significantly lower in FM compared to healthy controls. There was no difference in pressure-pain limit. CPA-parameters were significantly correlated to isokinetic muscle strength where more hypersensitivity resulted in lower strength. Pressure-pain threshold and pressure-pain tolerance assessed by CPA were significantly lower in patients with FM indicating muscle hyperalgesia. CPA was associated with knee muscle strength but not with measures thought to be influenced by psychological distress and mood.

  9. Adipose tissue angiogenesis: impact on obesity and type-2 diabetes.

    Science.gov (United States)

    Corvera, Silvia; Gealekman, Olga

    2014-03-01

    The growth and function of tissues are critically dependent on their vascularization. Adipose tissue is capable of expanding many-fold during adulthood, therefore requiring the formation of new vasculature to supply growing and proliferating adipocytes. The expansion of the vasculature in adipose tissue occurs through angiogenesis, where new blood vessels develop from those pre-existing within the tissue. Inappropriate angiogenesis may underlie adipose tissue dysfunction in obesity, which in turn increases type-2 diabetes risk. In addition, genetic and developmental factors involved in vascular patterning may define the size and expandability of diverse adipose tissue depots, which are also associated with type-2 diabetes risk. Moreover, the adipose tissue vasculature appears to be the niche for pre-adipocyte precursors, and factors that affect angiogenesis may directly impact the generation of new adipocytes. Here we review recent advances on the basic mechanisms of angiogenesis, and on the role of angiogenesis in adipose tissue development and obesity. A substantial amount of data points to a deficit in adipose tissue angiogenesis as a contributing factor to insulin resistance and metabolic disease in obesity. These emerging findings support the concept of the adipose tissue vasculature as a source of new targets for metabolic disease therapies. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

  10. Assessment of alginate hydrogel degradation in biological tissue using viscosity-sensitive fluorescent dyes

    Science.gov (United States)

    Shkand, Tatiana V.; Chizh, Mykola O.; Sleta, Iryna V.; Sandomirsky, Borys P.; Tatarets, Anatoliy L.; Patsenker, Leonid D.

    2016-12-01

    The main goal of this study is to investigate a combination of viscosity-sensitive and viscosity-insensitive fluorescent dyes to distinguish different rheological states of hydrogel based biostructural materials and carriers in biological tissues and to assess their corresponding location areas. The research is done in the example of alginate hydrogel stained with viscosity-sensitive dyes Seta-470 and Seta-560 as well as the viscosity-insensitive dye Seta-650. These dyes absorb/emit at 469/518, 565/591 and 651/670 nm, respectively. The rheological state of the alginate, the area of the fluorescence signal and the mass of the dense alginate versus the calcium gluconate concentration utilized for alginate gelation were studied in vitro. The most pronounced change in the fluorescence signal area was found at the same concentrations of calcium gluconate (below ~1%) as the change in the alginate plaque mass. The stained alginate was also implanted in situ in rat hip and myocardium and monitored using fluorescence imaging. In summary, our data indicate that the viscosity sensitive dye in combination with the viscosity-insensitive dye allow tracking the biodegradation of the alginate hydrogel and determining the rheological state of hydrogel in biological tissue, which both should have relevance for research and clinical applications. Using this method we estimated the half-life of the dense alginate hydrogel in a rat hip to be in the order of 4 d and about 6-8 d in rat myocardium. The half-life of the dense hydrogel in the myocardium was found to be long enough to prevent aneurysm rupture of the left ventricle wall, one of the more severe complications of the early post-infarction period.

  11. Heterogeneity of tumor vasculature and antiangiogenic intervention: insights from MR angiography and DCE-MRI.

    Directory of Open Access Journals (Sweden)

    Wenlian Zhu

    Full Text Available PURPOSE: Solid tumor vasculature is highly heterogeneous, which presents challenges to antiangiogenic intervention as well as the evaluation of its therapeutic efficacy. The aim of this study is to evaluate the spatial tumor vascular changes due to bevacizumab/paclitaxel therapy using a combination approach of MR angiography and DCE-MRI method. EXPERIMENTAL DESIGN: Tumor vasculature of MCF-7 breast tumor mouse xenografts was studied by a combination of MR angiography and DCE-MRI with albumin-Gd-DTPA. Tumor macroscopic vasculature was extracted from the early enhanced images. Tumor microvascular parameters were obtained from the pharmacokinetic modeling of the DCE-MRI data. A spatial analysis of the microvascular parameters based on the macroscopic vasculature was used to evaluate the changes of the heterogeneous vasculature induced by a 12 day bevacizumab/paclitaxel treatment in mice bearing MCF-7 breast tumor. RESULTS: Macroscopic vessels that feed the tumors were not affected by the bevacizumab/paclitaxel combination therapy. A higher portion of the tumors was within close proximity of these macroscopic vessels after the treatment, concomitant with tumor growth retardation. There was a significant decrease in microvascular permeability and vascular volume in the tumor regions near these vessels. CONCLUSION: Bevacizumab/paclitaxel combination therapy did not block the blood supply to the MCF-7 breast tumor. Such finding is consistent with the modest survival benefits of adding bevacizumab to current treatment regimens for some types of cancers.

  12. Vegfa signaling promotes zebrafish intestinal vasculature development through endothelial cell migration from the posterior cardinal vein.

    Science.gov (United States)

    Koenig, Andrew L; Baltrunaite, Kristina; Bower, Neil I; Rossi, Andrea; Stainier, Didier Y R; Hogan, Benjamin M; Sumanas, Saulius

    2016-03-01

    The mechanisms underlying organ vascularization are not well understood. The zebrafish intestinal vasculature forms early, is easily imaged using transgenic lines and in-situ hybridization, and develops in a stereotypical pattern thus making it an excellent model for investigating mechanisms of organ specific vascularization. Here, we demonstrate that the sub-intestinal vein (SIV) and supra-intestinal artery (SIA) form by a novel mechanism from angioblasts that migrate out of the posterior cardinal vein and coalesce to form the intestinal vasculature in an anterior to posterior wave with the SIA forming after the SIV. We show that vascular endothelial growth factor aa (vegfaa) is expressed in the endoderm at the site where intestinal vessels form and therefore likely provides a guidance signal. Vegfa/Vegfr2 signaling is required for early intestinal vasculature development with mutation in vegfaa or loss of Vegfr2 homologs causing nearly complete inhibition of the formation of the intestinal vasculature. Vegfc and Vegfr3 function, however, are dispensable for intestinal vascularization. Interestingly, ubiquitous overexpression of Vegfc resulted in an overgrowth of the SIV, suggesting that Vegfc is sufficient to induce SIV development. These results argue that Vegfa signaling directs endothelial cells to migrate out of existing vasculature and coalesce to form the intestinal vessels. It is likely that a similar mechanism is utilized during vascularization of other organs.

  13. Low-dose phase-based X-ray imaging techniques for in situ soft tissue engineering assessments.

    Science.gov (United States)

    Izadifar, Zohreh; Honaramooz, Ali; Wiebe, Sheldon; Belev, George; Chen, Xiongbiao; Chapman, Dean

    2016-03-01

    In tissue engineering, non-invasive imaging of biomaterial scaffolds and tissues in living systems is essential to longitudinal animal studies for assessments without interrupting the repair process. Conventional X-ray imaging is inadequate for use in soft tissue engineering due to the limited absorption difference between the soft tissue and biomaterial scaffolds. X-ray phase-based imaging techniques that derive contrast from refraction or phase effects rather than absorption can provide the necessary contrast to see low-density biomaterial scaffolds and tissues in large living systems. This paper explores and compares three synchrotron phase-based X-ray imaging techniques-computed tomography (CT)-diffraction enhanced imaging (DEI), -analyzer based imaging (ABI), and -phase contrast imaging (PCI)-for visualization and characterization of low-density biomaterial scaffolds and tissues in situ for non-invasive soft tissue engineering assessments. Intact pig joints implanted with polycaprolactone scaffolds were used as the model to assess and compare the imaging techniques in terms of different qualitative and quantitative criteria. For long-term in vivo live animal imaging, different strategies for reducing the imaging radiation dose and scan time-reduced number of CT projections, region of interest, and low resolution imaging-were examined with the presented phase-based imaging techniques. The results demonstrated promising capabilities of the phase-based techniques for visualization of biomaterial scaffolds and soft tissues in situ. The low-dose imaging strategies were illustrated effective for reducing the radiation dose to levels appropriate for live animal imaging. The comparison among the imaging techniques suggested that CT-DEI has the highest efficiency in retaining image contrast at considerably low radiation doses.

  14. Spreading Depression, Spreading Depolarizations, and the Cerebral Vasculature

    DEFF Research Database (Denmark)

    Ayata, Cenk; Lauritzen, Martin

    2015-01-01

    slowly at a rate of only millimeters per minute by way of grey matter contiguity, irrespective of functional or vascular divisions, and lasts up to a minute in otherwise normal tissue. As such, SD is a radically different breed of electrophysiological activity compared with everyday neural activity...

  15. Localized tissue water changes accompanying one manual lymphatic drainage (MLD) therapy session assessed by changes in tissue dielectric constant inpatients with lower extremity lymphedema.

    Science.gov (United States)

    Mayrovitz, H N; Davey, S; Shapiro, E

    2008-06-01

    Previous reports described the utility of assessing local tissue water via tissue dielectric constant (TDC) measurements. Our goal was to determine the suitability of this method to evaluate lymphedema changes. For this purpose, we measured changes in TDC produced by one MLD treatment in 27 legs of 18 patients with lower extremity lymphedema. TDC values were measured to a depth of 2.5 mm at the greatest leg swelling site before and after one MLD treatment. Girth at the target site was measured with a calibrated tape measure. TDC values, which range from 1 for zero water to 78.5 for all water within the sampled volume, were measured four times and the average used to estimate local changes. Results showed that in every case the posttreatment TDC was reduced from its pretreatment value with percentage reductions (mean SD) of -9.8 +/- 5.64% (p TDC measurements reflect changes to a depth of about 2.5 mm whereas girth measurements reflect conditions of the entire cross-section, TDC assessment may be more sensitive to localized lymphedema changes. This finding suggests that TDC measurements are useful as complementary and perhaps as independent assessment methods of edema/lymphedema and treatment-related changes.

  16. Assessment of deep tissue hyperalgesia in the groin – a method comparison of electrical vs. pressure stimulation

    DEFF Research Database (Denmark)

    Aasvang, E K; Werner, M U; Kehlet, H

    2014-01-01

    BACKGROUND: Deep pain complaints are more frequent than cutaneous in post-surgical patients, and a prevalent finding in quantitative sensory testing studies. However, the preferred assessment method - pressure algometry - is indirect and tissue unspecific, hindering advances in treatment and prev......BACKGROUND: Deep pain complaints are more frequent than cutaneous in post-surgical patients, and a prevalent finding in quantitative sensory testing studies. However, the preferred assessment method - pressure algometry - is indirect and tissue unspecific, hindering advances in treatment...... thresholds to pressure algometry, by performing identical test-retest sequences 10 days apart, in deep tissues in the groin region. Electrical stimulation was performed by five up-and-down staircase series of single impulses of 0.04 ms duration, starting from 0 mA in increments of 0.2 mA until a threshold......: The presented tissue-specific direct deep tissue electrical stimulation technique has equal or superior reliability compared with the indirect tissue-unspecific stimulation by pressure algometry. This method may facilitate advances in mechanism based preventive and treatment strategies in acute and chronic post...

  17. A novel in vivo vascular imaging approach for hierarchical quantification of vasculature using contrast enhanced micro-computed tomography.

    Directory of Open Access Journals (Sweden)

    Laura Nebuloni

    Full Text Available The vasculature of body tissues is continuously subject to remodeling processes originating at the micro-vascular level. The formation of new blood vessels (angiogenesis is essential for a number of physiological and pathophysiological processes such as tissue regeneration, tumor development and the integration of artificial tissues. There are currently no time-lapsed in vivo imaging techniques providing information on the vascular network at the capillary level in a non-destructive, three-dimensional and high-resolution fashion. This paper presents a novel imaging framework based on contrast enhanced micro-computed tomography (micro-CT for hierarchical in vivo quantification of blood vessels in mice, ranging from largest to smallest structures. The framework combines for the first time a standard morphometric approach with densitometric analysis. Validation tests showed that the method is precise and robust. Furthermore, the framework is sensitive in detecting different perfusion levels after the implementation of a murine ischemia-reperfusion model. Correlation with both histological data and micro-CT analysis of vascular corrosion casts confirmed accuracy of the method. The newly developed time-lapsed imaging approach shows high potential for in vivo monitoring of a number of different physiological and pathological conditions in angiogenesis and vascular development.

  18. The vasculature of nurse cells infected with non-encapsulated Trichinella species.

    Science.gov (United States)

    Khositharattanakool, Pathamet; Morakote, Nimit; Uparanukraw, Pichart

    2013-07-04

    The vasculature surrounding the nurse cells of encapsulated Trichinella spiralis has been described previously. It has been postulated the function of these vessels is to support the growth of the parasite. We describe here for the first time the vasculature surrounding the nurse cells of non-encapsulated T. pseudospiralis and T. papuae. Similar to the vasculature of uninfected muscle cells, the vessels surrounding non-encapsulated Trichinella nurse cells are dense and branched longitudinally along the long axis of the muscle cells; they also appear to be similar in diameter. The netting pattern of enlarged vessels found around T. spiralis (encapsulated) nurse cells is not present in non-encapsulated Trichinella infections. The vessels surrounding non-encapsulated Trichinella nurse cells seem to exist prior to parasite invasion of the muscle cell.

  19. Vascular endothelial growth factor co-ordinates proper development of lung epithelium and vasculature.

    Science.gov (United States)

    Zhao, Liqing; Wang, Ke; Ferrara, Napoleone; Vu, Thiennu H

    2005-07-01

    The vasculature forms an intrinsic functional component of the lung and its development must be tightly regulated and coordinated with lung epithelial morphogenesis. Vascular endothelial growth factor (VEGF) and its receptors are highly expressed in a complementary pattern in the lungs during embryonic development. VEGF is expressed by epithelium and the receptors in the surrounding mesenchyme. To determine the function of VEGF in lung formation, we inhibited its activity using a soluble receptor in lung renal capsule grafts. Inhibition of VEGF results in inhibition of vascular development and significant alteration in epithelial development. Epithelial proliferation is inhibited, sacculation is impaired, and the epithelium undergoes apoptosis. Interestingly, when VEGF is attenuated, epithelial differentiation still proceeds, as shown by acquisition of both proximal and distal markers. These data show that VEGF co-ordinates epithelial and vascular development. It is required for the development of the lung vasculature and the vasculature is necessary for epithelial proliferation and morphogenesis, but not for cell differentiation.

  20. Assessing Antioxidant Capacity in Brain Tissue: Methodologies and Limitations in Neuroprotective Strategies

    Directory of Open Access Journals (Sweden)

    Jennifer E. Slemmer

    2014-10-01

    Full Text Available The number of putative neuroprotective compounds with antioxidant activity described in the literature continues to grow. Although these compounds are validated using a variety of in vivo and in vitro techniques, they are often evaluated initially using in vitro cell culture techniques in order to establish toxicity and effective concentrations. Both in vivo and in vitro methodologies have their respective advantages and disadvantages, including, but not limited to, cost, time, use of resources and technical limitations. This review expands on the inherent benefits and drawbacks of in vitro and in vivo methods for assessing neuroprotection, especially in light of proper evaluation of compound efficacy and neural bioavailability. For example, in vivo studies can better evaluate the effects of protective compounds and/or its metabolites on various tissues, including the brain, in the whole animal, whereas in vitro studies can better discern the cellular and/or mechanistic effects of compounds. In particular, we aim to address the question of appropriate and accurate extrapolation of findings from in vitro experiment-where compounds are often directly applied to cellular extracts, potentially at higher concentrations than would ever cross the blood-brain barrier—to the more complex scenario of neuroprotection due to pharmacodynamics in vivo.

  1. Soft tissue artifact assessment during treadmill walking in subjects with total knee arthroplasty.

    Science.gov (United States)

    Barre, Arnaud; Thiran, Jean-Philippe; Jolles, Brigitte M; Theumann, Nicolas; Aminian, Kamiar

    2013-11-01

    Accurate measurement of knee kinematics during functional activities suffers mainly from soft tissue artifact (STA): the combination of local surface deformations and rigid movement of markers relative to the underlying bone (also called rigid STA movement: RSTAM). This study proposes to assess RSTAM on the thigh, shank, and knee joint and to observe possible features between subjects. Nineteen subjects with knee arthroplasty were asked to walk on a treadmill while a biplane fluoroscopic system (X-rays) and a stereophotogrammetric system (skin markers) recorded their knee movement. The RSTAM was defined as the rigid movement of the cluster of skin markers relative to the prosthesis. The results showed that RSTAM amplitude represents approximately 80-100% of the STA. The vertical axis of the anatomical frame of the femur was influenced the most by RSTAM. Combined with tibial error, internal/external rotation angle and distraction-compression were the knee kinematics parameters most affected by RSTAM during the gait cycle, with average rms values of 3.8° and 11.1 mm. This study highlighted higher RSTAM during the swing phase particularly in the thigh segment and suggests new features for RSTAM such as the particular shape of some RSTAM waveforms and the absence of RSTAM in certain kinematics during the gait phases. The comparison of coefficient of multiple correlations showed some similarities of RSTAM between subjects, while some correlations were found with gait speed and BMI. These new insights could potentially allow the development of new methods of compensation to avoid STA.

  2. Science and the lay perspective: lay people's involvement in assessing tissue engineering.

    Science.gov (United States)

    Zoeller, Katharina

    2014-10-01

    Tissue engineering (TE) is a scientific field that will have an influence on our daily lives. It has the potential to revolutionize medical treatments, but it has also an impact on our human image and is associated with potential risks and ethical aspects. Among the publicly controversial issues are embryonic and induced pluripotent stem cells, cloning, uncertainties regarding risks and informed consent issues. To maintain public confidence in the science of TE, a good solution is public dialogues with patients and other interested lay people that gives the public the chance to independently evaluate TE issues and build their own opinion based on information from different perspectives. The article describes public participation projects in TE on stem cell research and gene therapy and presents the case study of the EU-Gene Activated Matrices for Bone and Cartilage Regeneration on Arthritis (GAMBA) panels, a dialogue with patient and citizen panels in three European countries. In the GAMBA panels, lay participants assessed the basic research project aimed at finding ways of healing osteoarthritis through a matrix composed of adult stem cells, gene vectors, nanoparticles, and biomaterials. The results of the dialogues in different countries, such as Denmark, Japan, Ireland, Switzerland, and Germany, are compared and the evaluation criteria for high quality dialogues are presented, including multiperspectivity, openness of results, a clear mandate, impartial facilitation of the panels, and transparency.

  3. Use of cis-[18F] fluoro-proline for assessment of exercise-related collagen synthesis in musculoskeletal connective tissue

    DEFF Research Database (Denmark)

    Skovgaard, Dorthe; Kjaer, Andreas; Heinemeier, Katja Maria

    2011-01-01

    Protein turnover in collagen rich tissue is influenced by exercise, but can only with difficulty be studied in vivo due to use of invasive procedure. The present study was done to investigate the possibility of applying the PET-tracer, cis-[(18)F]fluoro-proline (cis-Fpro), for non-invasive assess......Protein turnover in collagen rich tissue is influenced by exercise, but can only with difficulty be studied in vivo due to use of invasive procedure. The present study was done to investigate the possibility of applying the PET-tracer, cis-[(18)F]fluoro-proline (cis-Fpro), for non......-invasive assessment of collagen synthesis in rat musculoskeletal tissues at rest and following short-term (3 days) treadmill running. Musculoskeletal collagen synthesis was studied in rats at rest and 24 h post-exercise. At each session, rats were PET scanned at two time points following injection of cis-FPro: (60...

  4. Real time assessment of RF cardiac tissue ablation with optical spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Demos, S G; Sharareh, S

    2008-03-20

    An optical spectroscopy approach is demonstrated allowing for critical parameters during RF ablation of cardiac tissue to be evaluated in real time. The method is based on incorporating in a typical ablation catheter transmitting and receiving fibers that terminate at the tip of the catheter. By analyzing the spectral characteristics of the NIR diffusely reflected light, information is obtained on such parameters as, catheter-tissue proximity, lesion formation, depth of penetration of the lesion, formation of char during the ablation, formation of coagulum around the ablation site, differentiation of ablated from healthy tissue, and recognition of micro-bubble formation in the tissue.

  5. Long-term impact of systemic bacterial infection on the cerebral vasculature and microglia

    Directory of Open Access Journals (Sweden)

    Püntener Ursula

    2012-06-01

    Full Text Available Abstract Background Systemic infection leads to generation of inflammatory mediators that result in metabolic and behavioural changes. Repeated or chronic systemic inflammation leads to a state of innate immune tolerance: a protective mechanism against overactivity of the immune system. In this study, we investigated the immune adaptation of microglia and brain vascular endothelial cells in response to systemic inflammation or bacterial infection. Methods Mice were given repeated doses of lipopolysaccharide (LPS or a single injection of live Salmonella typhimurium. Inflammatory cytokines were measured in serum, spleen and brain, and microglial phenotype studied by immunohistochemistry. To assess priming of the innate immune response in the brain, mice were infected with Salmonella typhimurium and subsequently challenged with a focal unilateral intracerebral injection of LPS. Results Repeated systemic LPS challenges resulted in increased brain IL-1β, TNF-α and IL-12 levels, despite attenuated systemic cytokine production. Each LPS challenge induced significant changes in burrowing behaviour. In contrast, brain IL-1β and IL-12 levels in Salmonella typhimurium-infected mice increased over three weeks, with high interferon-γ levels in the circulation. Behavioural changes were only observed during the acute phase of the infection. Microglia and cerebral vasculature display an activated phenotype, and focal intracerebral injection of LPS four weeks after infection results in an exaggerated local inflammatory response when compared to non-infected mice. Conclusions These studies reveal that the innate immune cells in the brain do not become tolerant to systemic infection, but are primed instead. This may lead to prolonged and damaging cytokine production that may have a profound effect on the onset and/or progression of pre-existing neurodegenerative disease.

  6. Left ventricular regional and global diastolic function assessed using Quantitative Tissue velocity Imaging in patients with hypertrophic cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    王良玉; 王新房; 谢明星; 蔡志雄; 陈纪平

    2003-01-01

    Objectives The study was performed to assess the left ventricular (LV) regional and global diastolic function、 left ventricular wall motion features in patients with Hypertrophic cardiomyopathy by Quantitative Tissue Velocity Imaging (QTVI).Methods 42 patients with hypertrophic cardiomyopathy and 36 age-matched normal subjects underwent QTVI study. Off-line LV regional muscular tissue velocity Imaging along LV aplcal long-axis view were obtained. Regional diastolic function was assessed in using peak tissue velocities of LV regional muscular tissue during early diastole (Ve)and LA contraction (Va) , Ve/Va ratio, derived from Tissue Velocity Imaging. Global diastolic function was reflected by isovolumic relaxation time(IRT) and mitral valve peak flow velocity ( E/A ) calculated with pulsed wave doppler.The end-diastolic interventricular septal thickness (IVSt) was measured by conventional 2 - dimension the segments of hypertrophic interventricular septum (IVS) reduced wlhile E/A ratio significantly reduced and IRT markedly prolonged in HCM patients than in duced in the segments of hypertrophic interventricular septum compared with other LV segments in HCM paE/A in HCM patients with abnormal E/A ratio (r = 0.Va and IVSt in non- obstruction HCM patients (B group , r = - 0.61 ) Conclusions QTVI offers a newer method in clinical practice which has a higher sensibility and accuracy in evaluating the LV regional and global diastolic function in HCM patients.

  7. Quantitative assessment of photoacoustic tomography systems integrating clinical ultrasound transducers using novel tissue-simulating phantoms

    Science.gov (United States)

    Vogt, William C.; Jia, Congxian; Wear, Keith A.; Garra, Brian S.; Pfefer, Joshua

    2015-03-01

    Photoacoustic Tomography (PAT) systems based on commercial ultrasound instruments have the benefit of dualmodality imaging, which increases their appeal from a clinical standpoint. However, factors that influence PAT system performance have not been thoroughly investigated and standardized test methods have not been established for image quality evaluation. To address these issues we have adapted phantom-based approaches from ultrasound imaging standards and implemented them to assess a PAT system developed for vascular imaging. Our system comprises a tunable near-infrared pulsed laser and a commercial ultrasound imaging system, including four interchangeable linear array clinical ultrasound transducers with varying center frequencies, acoustic bandwidths and geometries. Phantoms consisted of a customized polyvinyl chloride (PVC) plastisol gel that simulates both optical and acoustic properties of breast tissue. One phantom incorporates a sub-resolution filament array suitable for bimodal ultrasound-photoacoustic imaging, while another contains an array of hemoglobin-filled cylindrical inclusions at various depths. Key performance characteristics were evaluated, including spatial resolution, signal uniformity, contrast, and penetration depth. These characteristics were evaluated at 750 nm at radiant exposures below ANSI safety limits. Effects of transducer properties on imaging performance were evaluated. Axial and lateral resolution ranged from 0.27-0.83 mm and 0.28-1.8 mm, respectively, and penetration depths from 1.9-4.2 cm were achieved. These results demonstrate variation in PAT system performance based on clinical transducer selection, as well as the utility of realistic phantom-based test methods in performing benchtop evaluations of system performance.

  8. Pulsed Doppler Tissue Imaging for Assessment of Left Ventricular Systolic and Diastolic Synchronicity in Normal Subjects

    Institute of Scientific and Technical Information of China (English)

    Yang Li; Wu Wei; Wang Jingfeng; Zhang Xiaoling

    2006-01-01

    Objectives To quantitatively analyze the longitudinal myocardial systolic and diastolic velocities and time intervals of the left ventricle in normal subjects, and to explore the value of pulsed Doppler tissue imaging (DTI) for the assessment of left ventricular systolic and diastolic synchronicity.Methods Twenty and six healthy subjects were studied by pulsed DTI. The septal and lateral, anterior and inferior walls of the left ventricle were displayed respectively, and basal and middle segments of each wall were selected for myocardial motion spectrum sampling. DTI parameters were: peak systolic myocardial velocity (s), regional pre-ejection period (PEP), time to the peak of s wave (Ts), regional ejection time (ET); peak early diastolic velocity (e),peak late diastolic velocity (a), e/a ratio, time to the beginning of e wave (QE), time to the peak of e wave (Te) and regional isovolumic relaxation time (IVRT).Results The e and e/a were significantly different among basal segments, and s and e/a were significantly different among middle segments, with the highest value in lateral segments and the lowest value in septal segments. The s, e and a were all significantly higher in basal segments than middle segments. None of the systolic time intervals (PEP, Ts and ET) and diastolic time intervals (QE, Te and IVRT) were significantly different among basal segments and middle segments,neither were they when basal segment was compared with middle segment. Conclusions In normal subjects, the longitudinal myocardial systolic and diastolic velocities of the left ventricle are not homogeneous, but the contraction and relaxation are highly synchronized. Pulsed DTI can be used to quantitatively analyze the systolic and diastolic synchronicity of the heart.

  9. Performance assessment of automated tissue characterization for prostate H and E stained histopathology

    Science.gov (United States)

    DiFranco, Matthew D.; Reynolds, Hayley M.; Mitchell, Catherine; Williams, Scott; Allan, Prue; Haworth, Annette

    2015-03-01

    Reliable automated prostate tumor detection and characterization in whole-mount histology images is sought in many applications, including post-resection tumor staging and as ground-truth data for multi-parametric MRI interpretation. In this study, an ensemble-based supervised classification algorithm for high-resolution histology images was trained on tile-based image features including histogram and gray-level co-occurrence statistics. The algorithm was assessed using different combinations of H and E prostate slides from two separate medical centers and at two different magnifications (400x and 200x), with the aim of applying tumor classification models to new data. Slides from both datasets were annotated by expert pathologists in order to identify homogeneous cancerous and non-cancerous tissue regions of interest, which were then categorized as (1) low-grade tumor (LG-PCa), including Gleason 3 and high-grade prostatic intraepithelial neoplasia (HG-PIN), (2) high-grade tumor (HG-PCa), including various Gleason 4 and 5 patterns, or (3) non-cancerous, including benign stroma and benign prostatic hyperplasia (BPH). Classification models for both LG-PCa and HG-PCa were separately trained using a support vector machine (SVM) approach, and per-tile tumor prediction maps were generated from the resulting ensembles. Results showed high sensitivity for predicting HG-PCa with an AUC up to 0.822 using training data from both medical centres, while LG-PCa showed a lower sensitivity of 0.763 with the same training data. Visual inspection of cancer probability heatmaps from 9 patients showed that 17/19 tumors were detected, and HG-PCa generally reported less false positives than LG-PCa.

  10. Automatic quantification of neo-vasculature from micro-CT

    Science.gov (United States)

    Mallya, Yogish; Narayanan, A. K.; Zagorchev, Lyubomir

    2009-02-01

    Angiogenesis is the process of formation of new blood vessels as outgrowths of pre-existing ones. It occurs naturally during development, tissue repair, and abnormally in pathologic diseases such as cancer. It is associated with proliferation of blood vessels/tubular sprouts that penetrate deep into tissues to supply nutrients and remove waste products. The process starts with migration of endothelial cells. As the cells move towards the target area they form small tubular sprouts recruited from the parent vessel. The sprouts grow in length due to migration, proliferation, and recruitment of new endothelial cells and the process continues until the target area becomes fully vascular. Accurate quantification of sprout formation is very important for evaluation of treatments for ischemia as well as angiogenesis inhibitors and plays a key role in the battle against cancer. This paper presents a technique for automatic quantification of newly formed blood vessels from Micro-CT volumes of tumor samples. A semiautomatic technique based on interpolation of Bezier curves was used to segment out the cancerous growths. Small vessels as determined by their diameter within the segmented tumors were enhanced and quantified with a multi-scale 3-D line detection filter. The same technique can be easily extended for quantification of tubular structures in other 3-D medical imaging modalities. Experimental results are presented and discussed.

  11. Bioprinted 3D Primary Liver Tissues Allow Assessment of Organ-Level Response to Clinical Drug Induced Toxicity In Vitro

    Science.gov (United States)

    Funk, Juergen; Robbins, Justin B.; Crogan-Grundy, Candace; Presnell, Sharon C.; Singer, Thomas; Roth, Adrian B.

    2016-01-01

    Modeling clinically relevant tissue responses using cell models poses a significant challenge for drug development, in particular for drug induced liver injury (DILI). This is mainly because existing liver models lack longevity and tissue-level complexity which limits their utility in predictive toxicology. In this study, we established and characterized novel bioprinted human liver tissue mimetics comprised of patient-derived hepatocytes and non-parenchymal cells in a defined architecture. Scaffold-free assembly of different cell types in an in vivo-relevant architecture allowed for histologic analysis that revealed distinct intercellular hepatocyte junctions, CD31+ endothelial networks, and desmin positive, smooth muscle actin negative quiescent stellates. Unlike what was seen in 2D hepatocyte cultures, the tissues maintained levels of ATP, Albumin as well as expression and drug-induced enzyme activity of Cytochrome P450s over 4 weeks in culture. To assess the ability of the 3D liver cultures to model tissue-level DILI, dose responses of Trovafloxacin, a drug whose hepatotoxic potential could not be assessed by standard pre-clinical models, were compared to the structurally related non-toxic drug Levofloxacin. Trovafloxacin induced significant, dose-dependent toxicity at clinically relevant doses (≤ 4uM). Interestingly, Trovafloxacin toxicity was observed without lipopolysaccharide stimulation and in the absence of resident macrophages in contrast to earlier reports. Together, these results demonstrate that 3D bioprinted liver tissues can both effectively model DILI and distinguish between highly related compounds with differential profile. Thus, the combination of patient-derived primary cells with bioprinting technology here for the first time demonstrates superior performance in terms of mimicking human drug response in a known target organ at the tissue level. PMID:27387377

  12. Bioprinted 3D Primary Liver Tissues Allow Assessment of Organ-Level Response to Clinical Drug Induced Toxicity In Vitro.

    Directory of Open Access Journals (Sweden)

    Deborah G Nguyen

    Full Text Available Modeling clinically relevant tissue responses using cell models poses a significant challenge for drug development, in particular for drug induced liver injury (DILI. This is mainly because existing liver models lack longevity and tissue-level complexity which limits their utility in predictive toxicology. In this study, we established and characterized novel bioprinted human liver tissue mimetics comprised of patient-derived hepatocytes and non-parenchymal cells in a defined architecture. Scaffold-free assembly of different cell types in an in vivo-relevant architecture allowed for histologic analysis that revealed distinct intercellular hepatocyte junctions, CD31+ endothelial networks, and desmin positive, smooth muscle actin negative quiescent stellates. Unlike what was seen in 2D hepatocyte cultures, the tissues maintained levels of ATP, Albumin as well as expression and drug-induced enzyme activity of Cytochrome P450s over 4 weeks in culture. To assess the ability of the 3D liver cultures to model tissue-level DILI, dose responses of Trovafloxacin, a drug whose hepatotoxic potential could not be assessed by standard pre-clinical models, were compared to the structurally related non-toxic drug Levofloxacin. Trovafloxacin induced significant, dose-dependent toxicity at clinically relevant doses (≤ 4uM. Interestingly, Trovafloxacin toxicity was observed without lipopolysaccharide stimulation and in the absence of resident macrophages in contrast to earlier reports. Together, these results demonstrate that 3D bioprinted liver tissues can both effectively model DILI and distinguish between highly related compounds with differential profile. Thus, the combination of patient-derived primary cells with bioprinting technology here for the first time demonstrates superior performance in terms of mimicking human drug response in a known target organ at the tissue level.

  13. In vitro assessment of the soft tissue/implant interface using porcine gingival explants.

    Science.gov (United States)

    Abdulmajeed, Aous A; Willberg, Jaana; Syrjänen, Stina; Vallittu, Pekka K; Närhi, Timo O

    2015-01-01

    The biologic seal of peri-implant soft tissue is crucial for long-term prognosis of oral implants. This in vitro study describes a novel tissue culture model using porcine gingival explants to evaluate the soft tissue/implant interface. Two different types of substrates were investigated: (a) plain polymer: BisGMA-TEGDMA (50-50 %) and (b) unidirectional fiber-reinforced composite (FRC). Porcine gingival explants were obtained from a local slaughterhouse. The experimental implants (n = 4) were inserted into the middle of freshly excised porcine gingival explants and cultured at the air/liquid interface up to 14 days. Porcine gingival explants with no implants served as baseline controls. The specimens were fixed and processed for the preparation of undecalcified samples. Histological analysis of the soft tissue/implant interface was carried out using a light-microscope. Microscopic evaluation suggests that the gingival explants established epithelial and connective tissue attachment to both implant types over the incubation period. FRC surfaces seemed to have a favorable tissue response with a sign of an outward epithelial migration. However, tissue degeneration was observed at the end of the experiment. In conclusion, this in vitro model maintains mucosal viability and ability to histologically evaluate soft tissue attachment to biomaterials rendering it a time efficient and cost effective model that may reduce the need for animal experiments.

  14. Tissue Doppler assessment of right ventricular function in female patients with limited form of systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Ayman Ahmed Abdelaziz

    2013-09-01

    Conclusions: Patients with limited form of SSc present with pulsed-tissue Doppler imaging indices indicative of right ventricle dysfunction, which had significant correlations with disease duration. Tissue Doppler is a valuable non-invasive tool for detecting RV myocardial involvement in patients with limited SSc.

  15. Assessment of the interaction of Portland cement-based materials with blood and tissue fluids using an animal model

    Science.gov (United States)

    Schembri Wismayer, P.; Lung, C. Y. K.; Rappa, F.; Cappello, F.; Camilleri, J.

    2016-01-01

    Portland cement used in the construction industry improves its properties when wet. Since most dental materials are used in a moist environment, Portland cement has been developed for use in dentistry. The first generation material is mineral trioxide aggregate (MTA), used in surgical procedures, thus in contact with blood. The aim of this study was to compare the setting of MTA in vitro and in vivo in contact with blood by subcutaneous implantation in rats. The tissue reaction to the material was also investigated. ProRoot MTA (Dentsply) was implanted in the subcutaneous tissues of Sprague-Dawley rats in opposite flanks and left in situ for 3 months. Furthermore the material was also stored in physiological solution in vitro. At the end of the incubation time, tissue histology and material characterization were performed. Surface assessment showed the formation of calcium carbonate for both environments. The bismuth was evident in the tissues thus showing heavy element contamination of the animal specimen. The tissue histology showed a chronic inflammatory cell infiltrate associated with the MTA. MTA interacts with the host tissues and causes a chronic inflammatory reaction when implanted subcutaneously. Hydration in vivo proceeds similarly to the in vitro model with some differences particularly in the bismuth oxide leaching patterns. PMID:27683067

  16. Tissue Doppler Imaging as Part of Assessing the Diastolic Functions of the Left Ventricular Myocardium in Athletes

    Directory of Open Access Journals (Sweden)

    Alina Yu. Tatarinova

    2013-12-01

    Full Text Available The article presents the results of assessing the morphofunctional condition of the left ventricular myocardium within 231 athletes who specialise in various sports. All of them underwent a transthoracic echocardiogram that included colour and tissue Doppler imaging. There are no significant differences in the diastolic function indicators of the left ventricular myocardium between different types of sports. Athletes that exhibit slight hypertrophy of the left ventricular myocardium do not exhibit signs of diastolic dysfunction. Tissue Doppler imaging helps identify signs of diastolic dysfunction in athletes who have a formally normal transmitral flow.

  17. Interaction of isoflavones and endophyte-infected tall fescue seed extract on vasoactivity of bovine mesenteric vasculature

    Science.gov (United States)

    It was hypothesized that isoflavones may attenuate ergot alkaloid-induced vasoconstriction and possibly alleviate diminished contractility of vasculature after exposure to ergot alkaloids. The objective of this study was to determine if prior incubation of bovine mesenteric vasculature with the isof...

  18. Endothelial cells internalize and degrade RGD-modified proteins developed for tumor vasculature targeting

    NARCIS (Netherlands)

    Schraaa, AJ; Kok, RJ; Berendsen, AD; Moorlag, HE; Bos, EJ; Meijer, DKF; de Leij, LFMH; Molema, G

    2002-01-01

    Tumor vasculature can be targeted by peptides containing an RGD (Arg-Gly-Asp) sequence, which bind to a p, and alpha(v)beta(5) integrins on angiogenic endothelial cells. By covalently attaching cyclic RGD-peptides (cRGDfK) to a protein backbone, we prepared a multivalent peptide-protein conjugate wi

  19. RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature

    NARCIS (Netherlands)

    Temming, K; Molema, G; Kok, RJ

    2005-01-01

    During the past decade, RGD-peptides have become a popular tool for the targeting of drugs and imaging agents to a(v)beta(3)-integrin expressing tumour vasculature. RGD-peptides have been introduced by recombinant means into therapeutic proteins and viruses. Chemical means have been applied to coupl

  20. Sex-based differential regulation of oxidative stress in the vasculature by nitric oxide

    Directory of Open Access Journals (Sweden)

    Rommel C. Morales

    2015-04-01

    Conclusions: Our results provide evidence that regulation of the redox environment at baseline and following exposure to •NO is sex-dependent in the vasculature. These data suggest that sex-based differential redox regulation may be one mechanism by which •NO is more effective at inhibiting neointimal hyperplasia in male versus female rodents.

  1. Genetic Regulation of Angiogenesis and Lymphangiogenesis: Visualization and characterization of the vasculature

    NARCIS (Netherlands)

    F.L. Bos (Frank)

    2011-01-01

    textabstractAelius Galenus (AD 129 – 199) was one of the first persons to explore the blood vasculature. During his work as physician and surgeon, he recognized distinct differences in blood vessels. During surgery, he observed that vessels were filled with either dark or bright blood. He believed t

  2. A New Presentation and Exploration of Human Cerebral Vasculature Correlated with Surface and Sectional Neuroanatomy

    Science.gov (United States)

    Nowinski, Wieslaw L.; Thirunavuukarasuu, Arumugam; Volkau, Ihar; Marchenko, Yevgen; Aminah, Bivi; Gelas, Arnaud; Huang, Su; Lee, Looi Chow; Liu, Jimin; Ng, Ting Ting; Nowinska, Natalia G.; Qian, Guoyu Yu; Puspitasari, Fiftarina; Runge, Val M.

    2009-01-01

    The increasing complexity of human body models enabled by advances in diagnostic imaging, computing, and growing knowledge calls for the development of a new generation of systems for intelligent exploration of these models. Here, we introduce a novel paradigm for the exploration of digital body models illustrating cerebral vasculature. It enables…

  3. Dynamic fluorescence imaging for multiparametric measurement of tumor vasculature

    Science.gov (United States)

    Choi, Myunghwan; Choi, Kyungsun; Ryu, Seung-Wook; Lee, Jungwhoi; Choi, Chulhee

    2011-04-01

    Angiogenesis is essential for tumor growth and a promising target for cancer therapy. Blood vessel monitoring is an indispensable tool for evaluation and development of anti-angiogenic drugs. Here, we report a new noninvasive in vivo imaging tool, named dynamic fluorescence imaging (DyFI), for the simultaneous measurement of multiple vascular parameters including vascular density, perfusion rate, and permeability using spatiotemporal profiles of indocyanine green. Using DyFI in a tumor xenograft model, we quantitatively measured multiple vascular parameters in tumors and normal tissues with high spatial resolution. The multimodality of this method allowed us to find negative spatial correlations between perfusion and permeability. Moreover, DyFI was effective for revealing the early effects of an anti-angiogenic drug. We suggest that DyFI could be a useful tool for the preclinical development of anti-angiogenic drugs.

  4. Ectopic expression a tomato KNOX Gene Tkn4 affects the formation and the differentiation of meristems and vasculature.

    Science.gov (United States)

    Yan, Fang; Hu, Guojian; Ren, Zhenxin; Deng, Wei; Li, Zhengguo

    2015-12-01

    The KNOTTED-LIKE HOMEODOMAIN genes are involved in maintenance of the shoot apical meristem which produces the whole above-ground body of vascular plants. In this report, a tomato homolog gene, named as Tkn4 (a nucleus targeted transcription factor) was identified and characterized. By performing RT-PCR, the transcript level of Tkn4 was separately found in stem, root, stamen, stigma, fruit and sepal but hardly visible in the leaf. Besides, Tkn4 was induced by a series of plant hormones. Overexpression of Tkn4 gene in tomato resulted in dwarf phenotype and strongly repressed the formation of shoot apical meristem, lateral meristem and cambiums in transgenic lines. The transgenic lines had wrinkled leaves and anatomic analysis showed that there was no obvious palisade tissues in the leaves and the layer of cells changed in vascular tissue (xylem and phloem). To explore the regulation network of Tkn4, RNA-sequencing was performed in overexpression lines and wild type plants, by which many genes related to the synthesis and the signal transduction of cytokinin, auxin, gibberellin, ethylene, abscisic acid, and tracheary element differentiation or extracellular matrix synthesis were significantly regulated. Taken together, our results demonstrate that Tkn4 plays important roles in regulating the biosynthesis and signal transduction of diverse plant hormones, and the formation and differentiation of meristems and vasculature in tomato.

  5. Optical imaging of the chorioretinal vasculature in the living human eye.

    Science.gov (United States)

    Kim, Dae Yu; Fingler, Jeff; Zawadzki, Robert J; Park, Susanna S; Morse, Lawrence S; Schwartz, Daniel M; Fraser, Scott E; Werner, John S

    2013-08-27

    Detailed visualization of microvascular changes in the human retina is clinically limited by the capabilities of angiography imaging, a 2D fundus photograph that requires an intravenous injection of fluorescent dye. Whereas current angiography methods enable visualization of some retinal capillary detail, they do not adequately reveal the choriocapillaris or other microvascular features beneath the retina. We have developed a noninvasive microvascular imaging technique called phase-variance optical coherence tomography (pvOCT), which identifies vasculature three dimensionally through analysis of data acquired with OCT systems. The pvOCT imaging method is not only capable of generating capillary perfusion maps for the retina, but it can also use the 3D capabilities to segment the data in depth to isolate vasculature in different layers of the retina and choroid. This paper demonstrates some of the capabilities of pvOCT imaging of the anterior layers of choroidal vasculature of a healthy normal eye as well as of eyes with geographic atrophy (GA) secondary to age-related macular degeneration. The pvOCT data presented permit digital segmentation to produce 2D depth-resolved images of the retinal vasculature, the choriocapillaris, and the vessels in Sattler's and Haller's layers. Comparisons are presented between en face projections of pvOCT data within the superficial choroid and clinical angiography images for regions of GA. Abnormalities and vascular dropout observed within the choriocapillaris for pvOCT are compared with regional GA progression. The capability of pvOCT imaging of the microvasculature of the choriocapillaris and the anterior choroidal vasculature has the potential to become a unique tool to evaluate therapies and understand the underlying mechanisms of age-related macular degeneration progression.

  6. iPSC-derived cancer stem cells provide a model of tumor vasculature

    Science.gov (United States)

    Prieto-Vila, Marta; Yan, Ting; Calle, Anna Sanchez; Nair, Neha; Hurley, Laura; Kasai, Tomonari; Kakuta, Hiroki; Masuda, Junko; Murakami, Hiroshi; Mizutani, Akifumi; Seno, Masaharu

    2016-01-01

    To grow beyond a size of approximately 1-2 mm3, tumor cells activate many processes to develop blood vasculature. Growing evidences indicate that the formation of the tumor vascular network is very complex, and is not restricted to angiogenesis. Cancer cell-derived tumor vasculatures have been recently described. Among them, endothelial differentiation of tumor cells have been directly related to cancer stem cells, which are cells within a tumor that possess the capacity to self-renew, and to exhibit multipotential heterogeneous lineages of cancer cells. Vasculogenic mimicry has been described to be formed by cancer cells expressing stemness markers. Thus, cancer stem cells have been proposed to contribute to vasculogenic mimicry, though its relation is yet to be clarified. Here, we analyzed the tumor vasculature by using a model of mouse cancer stem cells, miPS-LLCcm cells, which we have previously established from mouse induced pluripotent stem cells and we introduced the DsRed gene in miPS-LLCcm to trace them in vivo. Various features of vasculature were evaluated in ovo, in vitro, and in vivo. The tumors formed in allograft nude mice exhibited angiogenesis in chick chorioallantoic membrane assay. In those tumors, along with penetrated host endothelial vessels, we detected endothelial differentiation from cancer stem cells and formation of vasculogenic mimicry. The angiogenic factors such as VEGF-A and FGF2 were expressed predominantly in the cancer stem cells subpopulation of miPS-LLCcm cells. Our results suggested that cancer stem cells play key roles in not only the recruitment of host endothelial vessels into tumor, but also in maturation of endothelial linage of cancer stem cell’s progenies. Furthermore, the undifferentiated subpopulation of the miPS-LLCcm participates directly in the vasculogenic mimicry formation. Collectively, we show that miPS-LLCcm cells have advantages to further study tumor vasculature and to develop novel targeting strategies in

  7. Use of cis-[18F]fluoro-proline for assessment of exercise-related collagen synthesis in musculoskeletal connective tissue.

    Directory of Open Access Journals (Sweden)

    Dorthe Skovgaard

    Full Text Available Protein turnover in collagen rich tissue is influenced by exercise, but can only with difficulty be studied in vivo due to use of invasive procedure. The present study was done to investigate the possibility of applying the PET-tracer, cis-[(18F]fluoro-proline (cis-Fpro, for non-invasive assessment of collagen synthesis in rat musculoskeletal tissues at rest and following short-term (3 days treadmill running. Musculoskeletal collagen synthesis was studied in rats at rest and 24 h post-exercise. At each session, rats were PET scanned at two time points following injection of cis-FPro: (60 and 240 min p.i. SUV were calculated for Achilles tendon, calf muscle and tibial bone. The PET-derived results were compared to mRNA expression of collagen type I and III. Tibial bone had the highest SUV that increased significantly (p<0.001 from the early (60 min to the late (240 min PET scan, while SUV in tendon and muscle decreased (p<0.001. Exercise had no influence on SUV, which was contradicted by an increased gene expression of collagen type I and III in muscle and tendon. The clearly, visible uptake of cis-Fpro in the collagen-rich musculoskeletal tissues is promising for multi-tissue studies in vivo. The tissue-specific differences with the highest basal uptake in bone are in accordance with earlier studies relying on tissue incorporation of isotopic-labelled proline. A possible explanation of the failure to demonstrate enhanced collagen synthesis following exercise, despite augmented collagen type I and III transcription, is that SUV calculations are not sensitive enough to detect minor changes in collagen synthesis. Further studies including kinetic compartment modeling must be performed to establish whether cis-Fpro can be used for non-invasive in-vivo assessment of exercise-induced changes in musculoskeletal collagen synthesis.

  8. Assessment of image quality in soft tissue and bone visualization tasks for a dedicated extremity cone-beam CT system

    Energy Technology Data Exchange (ETDEWEB)

    Demehri, S. [Johns Hopkins University, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Johns Hopkins Outpatient Center, JHOC 5168, Musculoskeletal Radiology, Baltimore, MD (United States); Muhit, A.; Zbijewski, W.; Stayman, J.W. [Johns Hopkins University, Department of Biomedical Engineering, Baltimore, MD (United States); Yorkston, J.; Packard, N.; Senn, R.; Yang, D.; Foos, D. [Carestream Health, Rochester, NY (United States); Thawait, G.K.; Fayad, L.M.; Chhabra, A.; Carrino, J.A. [Johns Hopkins University, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Siewerdsen, J.H. [Johns Hopkins University, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Johns Hopkins University, Department of Biomedical Engineering, Baltimore, MD (United States)

    2015-06-01

    To assess visualization tasks using cone-beam CT (CBCT) compared to multi-detector CT (MDCT) for musculoskeletal extremity imaging. Ten cadaveric hands and ten knees were examined using a dedicated CBCT prototype and a clinical multi-detector CT using nominal protocols (80kVp-108mAs for CBCT; 120kVp- 300mAs for MDCT). Soft tissue and bone visualization tasks were assessed by four radiologists using five-point satisfaction (for CBCT and MDCT individually) and five-point preference (side-by-side CBCT versus MDCT image quality comparison) rating tests. Ratings were analyzed using Kruskal-Wallis and Wilcoxon signed-rank tests, and observer agreement was assessed using the Kappa-statistic. Knee CBCT images were rated ''excellent'' or ''good'' (median scores 5 and 4) for ''bone'' and ''soft tissue'' visualization tasks. Hand CBCT images were rated ''excellent'' or ''adequate'' (median scores 5 and 3) for ''bone'' and ''soft tissue'' visualization tasks. Preference tests rated CBCT equivalent or superior to MDCT for bone visualization and favoured the MDCT for soft tissue visualization tasks. Intraobserver agreement for CBCT satisfaction tests was fair to almost perfect (κ ∝ 0.26-0.92), and interobserver agreement was fair to moderate (κ ∝ 0.27-0.54). CBCT provided excellent image quality for bone visualization and adequate image quality for soft tissue visualization tasks. (orig.)

  9. MRI in the assessment of the supportive soft tissues of the cervical spine in acute trauma in children

    Energy Technology Data Exchange (ETDEWEB)

    Keiper, M.D.; Zimmerman, R.A.; Bilaniuk, L.T. [Department of Radiology, Children`s Hospital of Philadelphia, PA (United States)

    1998-06-01

    We carried out a retrospective analysis of imaging and clinical findings in 52 children with a history of cervical spinal trauma. No patient had evidence of a fracture on plain films or CT. All had MRI at 1.5 T because of persistent or delayed symptoms, unexplained findings of injury or instability, or as further assessment of the extent of soft-tissue injury. Clinical follow-up ranged from 6 months to 3.5 years. MRI was evaluated for its influence on therapy and outcome. MRI was positive in 16 (31 %) of 52 patients. Posterior soft-tissue or ligamentous injury was the most common finding in the 10 patients with mild to moderate trauma, while acute disc bulges and longitudinal ligament disruption, each seen in one case, were uncommon. MRI was superior to CT for assessment of the extent of soft-tissue injury and for identification of spinal cord injuries and intracanalicular hemorrhage in the six patients with more severe trauma. MRI specifically influenced the management of all four patients requiring surgery by extending the level of posterior stabilization. No patients with normal MRI or any of the 10 with radiographically stable soft-tissue injury on MRI, developed delayed clinical or radiographic evidence of instability or deformity. (orig.) With 2 figs., 2 tabs., 24 refs.

  10. Two-photon excited fluorescence of intrinsic fluorophores enables label-free assessment of adipose tissue function

    Science.gov (United States)

    Alonzo, Carlo Amadeo; Karaliota, Sevasti; Pouli, Dimitra; Liu, Zhiyi; Karalis, Katia P.; Georgakoudi, Irene

    2016-08-01

    Current methods for evaluating adipose tissue function are destructive or have low spatial resolution. These limit our ability to assess dynamic changes and heterogeneous responses that occur in healthy or diseased subjects, or during treatment. Here, we demonstrate that intrinsic two-photon excited fluorescence enables functional imaging of adipocyte metabolism with subcellular resolution. Steady-state and time-resolved fluorescence from intracellular metabolic co-factors and lipid droplets can distinguish the functional states of excised white, brown, and cold-induced beige fat. Similar optical changes are identified when white and brown fat are assessed in vivo. Therefore, these studies establish the potential of non-invasive, high resolution, endogenous contrast, two-photon imaging to identify distinct adipose tissue types, monitor their functional state, and characterize heterogeneity of induced responses.

  11. Assessment of the Effectiveness of Extracorporeal Shock Wave Therapy (ESWT) For Soft Tissue Injuries (ASSERT): An Online Database Protocol

    OpenAIRE

    Maffulli, G; Hemmings, Steph; Maffulli, Nicola

    2014-01-01

    Background Soft tissue injuries and tendinopathies account for large numbers of chronic musculoskeletal disorders. Extracorporeal shockwave therapy (ESWT) is popular, and effective in the management of chronic tendon conditions in the elbow, shoulder, and pain at and around the heel. Methods/Design Ethical approval was granted from the South East London Research Ethics Committee to implement a database for the Assessment of Effectiveness of Extracorporeal Shock Wave Therapy for Soft Tis...

  12. Tissue motion and strain in the human brain assessed by intraoperative ultrasound in glioma patients.

    Science.gov (United States)

    Selbekk, Tormod; Brekken, Reidar; Solheim, Ole; Lydersen, Stian; Hernes, Toril A N; Unsgaard, Geirmund

    2010-01-01

    The objective of the study was to investigate tissue motion and strain imposed by cardiovascular pulsation in pathologic and normal brain parenchyma, as quantified from in vivo ultrasound data. Ultrasound acquired during surgery of 16 patients with glial tumors was retrospectively processed and analyzed. The tissue velocity was quantified at depths of 1cm, 2cm and 3cm from brain cortex to investigate spatial dependency with depth. Comparison of strain and velocity in tumor and adjacent normal parenchyma was performed by selecting two regions-of-interest in the hyperechoic tumor and two regions in the low-echogenic areas interpreted as mainly normal tissue with some degree of tumor cell infiltration. The absolute maximum tissue velocity is seen to increase with increasing depths in 14 of 16 cases (87.5%). The maximum tissue velocities in the four regions close to the ultrasound visible tumor border are not statistically different (p=0.163 to p=0.975). The strain magnitudes are significantly higher in the regions with expected normal brain parenchyma than in regions with expected glial tumor tissue, both for the two regions being closest to the tumor border (p=0.0004) and for the two regions further away from the tumor border (p=0.0009). We conclude that the velocity of the brain parenchyma imposed by arterial pulsation during a cardiac cycle is generally increasing with increasing depth from cortex. The maximum velocity appears to be similar in regions with expected normal brain and tumor tissue, thus, does not seem to be affected by pathology. Strain magnitude is, however, a suitable parameter for discrimination of glial tumor and normal brain parenchyma. (E-mail: Tormod.Selbekk@sintef.no).

  13. Assessment of recovery from ocular irritancy using a human tissue equivalent model.

    Science.gov (United States)

    Espersen, R J; Olsen, P; Nicolaisen, G M; Jensen, B L; Rasmussen, E S

    1997-01-01

    The SKIN(2) ZK1200 tissue equivalent model has been used in an exploratory study of recovery from ocular irritation. Nine substances from the ECETOC eye irritation reference chemicals data bank were tested. The cellular viability of the tissue model was measured using the MTT assay immediately after chemical exposure and after incubation periods corresponding to observation times used in the Draize tests. The cellular viability of the tissue specimens exposed to moderate irritants, with modified maximum average score (MMAS) values between 15 and 40 (= 5), returned to control levels within 1-7 days. Tissue specimens exposed to 1 and 10% benzalkonium chloride showed significantly reduced MTT activities at day 14 and day 21. Mild ocular irritants, with MMAS values below 3 (n = 2), did not induce significant depressions of the MTT activities of the tissue specimens after 60 min exposure. A relatively good correlation (r = 0.73) was obtained between the exposure times used in vitro and Draize MMAS values. Moreover, the incubation periods needed for the exposed SKIN(2) ZK1200 to regain control MTT activities showed a good agreement (r > 0.90) with days-to-clear ocular irritancy in the Draize test.

  14. Noncontact diffuse optical assessment of blood flow changes in head and neck free tissue transfer flaps

    Science.gov (United States)

    Huang, Chong; Radabaugh, Jeffrey P.; Aouad, Rony K.; Lin, Yu; Gal, Thomas J.; Patel, Amit B.; Valentino, Joseph; Shang, Yu; Yu, Guoqiang

    2015-07-01

    Knowledge of tissue blood flow (BF) changes after free tissue transfer may enable surgeons to predict the failure of flap thrombosis at an early stage. This study used our recently developed noncontact diffuse correlation spectroscopy to monitor dynamic BF changes in free flaps without getting in contact with the targeted tissue. Eight free flaps were elevated in patients with head and neck cancer; one of the flaps failed. Multiple BF measurements probing the transferred tissue were performed during and post the surgical operation. Postoperative BF values were normalized to the intraoperative baselines (assigning "1") for the calculation of relative BF change (rBF). The rBF changes over the seven successful flaps were 1.89±0.15, 2.26±0.13, and 2.43±0.13 (mean±standard error), respectively, on postoperative days 2, 4, and 7. These postoperative values were significantly higher than the intraoperative baseline values (pflap vascularity after the tissue transfer. By contrast, rBF changes observed from the unsuccessful flaps were 1.14 and 1.34, respectively, on postoperative days 2 and 4, indicating less flow recovery. Measurement of BF recovery after flap anastomosis holds the potential to act early to salvage ischemic flaps.

  15. The extrinsic apoptotic signaling pathway in gastric adenocarcinomas assessed by tissue microarray.

    Science.gov (United States)

    Gomes, Thiago S; Oshima, Celina T F; Segreto, Helena R C; Barrazueta, Luis M; Costa, Henrique O; Lima, Flavio O; Forones, Nora M; Ribeiro, Daniel A

    2011-10-15

    The purpose of this investigation was to analyze the immunoexpression of FasL, Fas, FADD, cleaved caspase 8, and cleaved caspase 3 in gastric cancer. Formalin-fixed and paraffin-embedded gastric adenocarcinoma tissues from 87 patients, including adjacent normal tissues, were included on tissue microarray by immunohistochemistry. The tumor and the adjacent normal tissues were positive for FasL in 66.7% and 90.6%, for Fas in 52.8% and 52.4%, for FADD in 67.4% and 82.3%, for cleaved caspase 8 in 27.9% and 37.7%, and for cleaved caspase 3 in 33.7% and 8.3%, respectively. FasL and the FADD from tumor were statistically different in relation to the histological type. Cleaved caspase 8 was statistically different in relation to clinical stage (p=0.031). The FADD from normal tissue was statistically different in relation to age (p=0.039), sex (p=0.055), clinical stage (p=0.019), and Fas was different in relation to tumor size (p=0.012). In the tumor, we observed a correlation between FasL and Fas, FasL and FADD, and FasL and cleaved caspase 3. In the adjacent normal tissue, a correlation was observed between FasL and Fas, FasL and FADD. There was no association of another marker with sex, age, clinical stage, and survival. Our results suggest that these proteins mediate the early extrinsic apoptotic pathway in gastric cancer and adjacent normal mucosa. FasL protein binds to Fas protein and subsequently binds to death receptor FADD signaling activation of the extrinsic apoptotic pathway. In this phase, there was inhibition of caspase 8 and, consequently, decreased apoptosis.

  16. Soft tissue assessment in midface advancement: the use of regional flaps to enhance facial projection.

    Science.gov (United States)

    Chavanne, Juan Martin; Steinberg, Diego; Houssay, Alfredo; Margaride, Luis A

    2009-09-01

    Classically, soft tissue repair when indicated is done before or after the skeletal mobilization especially in those cases that present midface deficiency with severe midline soft tissue restriction by scars or congenital affectation. The distraction osteogenesis method has contributed to improve substantially this problem elongating bones, muscles, and ligaments, but some situations need specific and more precise reconstruction of the subunits to gain in aesthetics. The labial-columella junction, the tip of the nose, and the more projecting point of the cheeks are one of these exigent anatomic areas, where only sophisticated reconstruction by flaps can improve facial proportions and projections.

  17. Histological assessment of titanium and polypropylene fiber mesh implantation with and without fibrin tissue glue

    NARCIS (Netherlands)

    Hallers, E.J.O. ten; Jansen, J.A.; Marres, H.A.M.; Rakhorst, G.; Verkerke, G.J.

    2007-01-01

    Polypropylene (PP) and titanium (Ti) meshes are well-known surgical implants that provoke a relative low foreign body reaction. Firm stabilization of the implant is important to prevent migration and subsequent failure of the operation. Fibrin tissue glues are commercially available adhesives and ar

  18. Fully automated assessment of inflammatory cell counts and cytokine expression in bronchial tissue.

    NARCIS (Netherlands)

    Sont, J.K.; Boer, W.I.; Schadewijk, W.A. van; Grunberg, K.; Krieken, J.H.J.M. van; Hiemstra, P.S.; Sterk, P.J.

    2003-01-01

    Automated image analysis of bronchial tissue offers the opportunity to quantify stained area and staining intensity in a standardized way to obtain robust estimates of inflammatory cell counts and cytokine expression from multiple large areas of histopathologic sections. We compared fully automated

  19. Instrumental and laboratory assessment of stressful remodelling processes in bone tissue at total hip replacement

    Directory of Open Access Journals (Sweden)

    E.V. Karjakina

    2010-06-01

    Full Text Available Research objective is to estimate stressful remodelling features of bone tissue according to the densitometry data and to the level of biochemical markers of bone resorption and formation in total hip replacement (THR. Bone tissue mineral density (BTMD, condition of calcium-phosphoric metabolism and biochemical markers of bone formation (osteocalcin and bone isoenzyme of alkaline phosphatase and resorption (С-terminal bodypeptide of the I type collagen have been determined in 52 patients with coxarthrosis of ll-lll stages with marked joint dysfunction before and after THR. The control group included 24 donors. The data were considered to be reliable when the probability index was р<0,05. The reliable (р<0,05 change of BTMD was determined only in 3-6 months after the operation, whereas the change of biochemical markers of remodeling had already been done after 1,5-3 months, allowing to define the group of patients with obvious negative bone balance: strong predominance of resorption processes without compensation of the subsequent adequate osteogenesis, that subsequently could lead to significant bone tissue deficiency in the area adjacent to the endoprosthesis. Changes of indices of calcium-phosphoric metabolism were not certain during the investigation term. ln conclusion it is to state that biochemical markers of remodeling in comparison with BTMD allow to estimate objectively features of adaptive bone tissue remodeling after THR in earlier periods and to define group of patients with sharp intensification of metabolism and obvious negative bone balance

  20. [A computerized manual for assessing the dosage absorbed by breast tissue in mammography].

    Science.gov (United States)

    Bagni, B; Pedrazzini, L

    1988-11-01

    The computerized translation of "Handbook of glandular tissue doses in mammography" (HHS publication FDA 85-8239) is presented. It is registered on floppy disk and suitable for use in MS-DOS on IBM personal computer, Olivetti or compatible. The manual collects data published by many authors and suggests a method to estimate the dose released to the glandular tissue (considered at risk for breast cancer) in the most commonly used conditions for mammography. Besides translation manual, the program holds an algorithm developed by the authors, which allows the dose to the glandular tissue to be evaluated, given the following data: projection: craniocaudal or mediolateral; compression level: firm or moderate; breast size: small, medium or large; breast composition: percentage of glandular tissue content (by weight); X-ray beam quality: HVL mm Al. The algorithm is obtained from a bidimensional fit of the original data and is based on the terms contained in the manual. The program flow is guided by menus that make the procedure suitable for inexperienced operators too, both for consulting and printing and for computing program.

  1. Prostate tissue ablation with MRI guided transurethral therapeutic ultrasound and intraoperative assessment of the integrity of the neurovascular bundle

    Science.gov (United States)

    Sammet, Steffen; Partanen, Ari; Yousuf, Ambereen; Wardrip, Craig; Niekrasz, Marek; Antic, Tatjana; Razmaria, Aria; Sokka, Sham; Karczmar, Gregory; Oto, Aytekin

    2017-03-01

    OBJECTIVES: Evaluation of the precision of prostate tissue ablation with MRI guided therapeuticultrasound by intraoperative objective assessment of the neurovascular bundle in canines in-vivo. METHODS: In this ongoing IACUC approved study, eight male canines were scanned in a clinical 3T Achieva MRI scanner (Philips) before, during, and after ultrasound therapy with a prototype MR-guided ultrasound therapy system (Philips). The system includes a therapy console to plan treatment, to calculate real-time temperature maps, and to control ultrasound exposures with temperature feedback. Atransurethral ultrasound applicator with eight transducer elements was used to ablate canine prostate tissue in-vivo. Ablated prostate tissue volumes were compared to the prescribed target volumes to evaluate technical effectiveness. The ablated volumes determined by MRI (T1, T2, diffusion, dynamic contrast enhanced and 240 CEM43 thermal dose maps) were compared to H&E stained histological slides afterprostatectomy. Potential nerve damage of the neurovascular bundle was objectively assessed intraoperativelyduring prostatectomy with a CaverMap Surgical Aid nerve stimulator (Blue Torch Medical Technologies). RESULTS: Transurethral MRI -guided ultrasound therapy can effectively ablate canine prostate tissue invivo. Coronal MR-imaging confirmed the correct placement of the HIFU transducer. MRI temperature maps were acquired during HIFU treatment, and subsequently used for calculating thermal dose. Prescribed target volumes corresponded to the 240 CEM43 thermal dose maps during HIFU treatment in all canines. Ablated volumes on high resolution anatomical, diffusion weighted, and contrast enhanced MR images matched corresponding histological slides after prostatectomy. MRI guidance with realtime temperature monitoring showed no damage to surrounding tissues, especially to the neurovascular bundle (assessed intra-operatively with a nerve stimulator) or to the rectum wall. CONCLUSIONS: Our study

  2. Tissue Iron Distribution Assessed by MRI in Patients with Iron Loading Anemias

    Science.gov (United States)

    Gutiérrez, Lucía; House, Michael J.; Vasavda, Nisha; Drašar, Emma; Gonzalez-Gascon y Marin, Isabel; Kulasekararaj, Austin G.; St Pierre, Tim G.; Thein, Swee L.

    2015-01-01

    Bone marrow, spleen, liver and kidney proton transverse relaxation rates (R2), together with cardiac R2* from patients with sickle cell disease (SCD), paroxysmal nocturnal hemoglobinuria (PNH) and non-transfusion dependent thalassemia (NTDT) have been compared with a control group. Increased liver and bone marrow R2 values for the three groups of patients in comparison with the controls have been found. SCD and PNH patients also present an increased spleen R2 in comparison with the controls. The simultaneous measurement of R2 values for several tissue types by magnetic resonance imaging (MRI) has allowed the identification of iron distribution patterns in diseases associated with iron imbalance. Preferential liver iron loading is found in the highly transfused SCD patients, while the low transfused ones present a preferential iron loading of the spleen. Similar to the highly transfused SCD group, PNH patients preferentially accumulate iron in the liver. A reduced spleen iron accumulation in comparison with the liver and bone marrow loading has been found in NTDT patients, presumably related to the differential increased intestinal iron absorption. The correlation between serum ferritin and tissue R2 is moderate to good for the liver, spleen and bone marrow in SCD and PNH patients. However, serum ferritin does not correlate with NTDT liver R2, spleen R2 or heart R2*. As opposed to serum ferritin measurements, tissue R2 values are a more direct measurement of each tissue’s iron loading. This kind of determination will allow a better understanding of the different patterns of tissue iron biodistribution in diseases predisposed to tissue iron accumulation. PMID:26406992

  3. Optical assessment of intravascular and intracellular parameters related to tissue viability

    Science.gov (United States)

    Mayevsky, Avraham; Sherman, Efrat; Cohen-Kashi, Meir; Dekel, Nava; Pewzner, Eliyahu

    2007-02-01

    Tissue viability represents the balance between O II supply and demand. In our previous paper (Mayevsky et al; Proc.SPIE 6083 : z1-z10, 2006) the HbO II was added to the multiparametric tissue spectroscope (Mayevsky et al J.Biomedical Optics 9:1028-1045,2004). This parameter provides relative values of microcirculatory blood oxygenation (MC-HbO II) evaluated by the 2 wavelength reflectometry principle. The advantage of this approach as compared to pulse oximetry is that the measurement is not dependent of the existence of the pulse of the heart. Also in the MC-HbO II the information is collected from small vessels providing O II to the mitochondria as compared to the pulse oximeter indicating blood oxygenation by the respiratory and cardiovascular systems. In the present study we compared the level of blood oxygenation measured by the pulse oximeter to that measured by the CritiView in the brain exposed to various systemic and localized perturbations of O II supply or demand. We exposed gerbils to anoxia, hypoxia, ischemia and terminal anoxia. In addition we measured mitochondrial NADH (surface fluorometry), tissue reflectance, tissue blood flow (laser Doppler flowmetry) from the same site of MC-HbO II measurement. A clear connection was found between the two blood oxygenation parameters only when systemic perturbations were used (anoxia, hypoxia and terminal anoxia). Under local events (ischemia) the MC-HbO II was responsive while the systemic oxygenation was unchanged. We concluded that MC-HbO II has a significant value in interpretation of tissue energy metabolism under pathophysiological conditions.

  4. Embryonic stem cell-derived neural progenitors transplanted to the hippocampus migrate on host vasculature

    Directory of Open Access Journals (Sweden)

    Chelsea M. Lassiter

    2016-05-01

    Full Text Available This study describes the migration of transplanted ESNPs either injected directly into the hippocampus of a mouse, seeded onto hippocampal slices, or under in vitro culture conditions. We show that transplanted mouse ESNPs associate with, and appear to migrate on the surface of the vasculature, and that human ESNPs also associate with blood vessels when seeded on hippocampal slices, and migrate towards BECs in vitro using a Boyden chamber assay. This initial adhesion to vessels is mediated, at least in part, via the integrin α6β1, as observed for SVZ neural progenitor cells. Our data are consistent with CXCL12, expressed by the astroglial-vasculature niche, playing an important role in the migration of transplanted neural progenitors within and outside of the hippocampus.

  5. The shell vasculature of Trachemys turtles investigated by modern 3D imaging techniques

    DEFF Research Database (Denmark)

    Hansen, Kasper; Thygesen, Jesper; Nielsen, Tobias Wang;

    Many freshwater turtles are extremely tolerant to the lack of oxygen and can survive the winter submerged in anoxic mud in ice-covered lakes. The pronounced anoxia-tolerance resides with a considerable depression of cellular metabolism and the ability to use the shell to buffer the acidosis arising...... from anaerobic metabolism (1). Infusion of microspheres has shown that the shell receives almost half of the cardiac output in turtles made anoxic at low temperatures (2). However, the vasculature of the turtle shell remains to be described. To visualise the vasculature within the carapace and plastron...... of the turtle Trachemys scripta, we perfused terminally anaesthetised turtles with different contrast enhancing agents (Microfil [lead n/a]), barium sulphate [250 mg/kg], and iodine [15-250 mg/kg]), and the animals were then scanned by both single source as well as dual energy Computed Tomographic systems...

  6. A model for gas and nutrient exchange in the chorionic vasculature system of the mouse placenta

    Science.gov (United States)

    Mirbod, Parisa; Sled, John

    2015-11-01

    The aim of this study is to develop an analytical model for the oxygen and nutrient transport from the umbilical cord to the small villous capillaries. The nutrient and carbon dioxide removal from the fetal cotyledons in the mouse placental system has also been considered. This model describes the mass transfer between the fetal and the maternal red blood cells in the chorionic arterial vasculature system. The model reveals the detail fetal vasculature system and its geometry and the precise mechanisms of mass transfer through the placenta. The dimensions of the villous capillaries, the total length of the villous trees, the total villi surface area, and the total resistance to mass transport in the fetal villous trees has also been defined. This is the first effort to explain the reason why there are at least 7 lobules in the mouse placenta from the fluid dynamics point of view.

  7. A fish-feeding laboratory bioassay to assess the antipredatory activity of secondary metabolites from the tissues of marine organisms.

    Science.gov (United States)

    Marty, Micah J; Pawlik, Joseph R

    2015-01-11

    Marine chemical ecology is a young discipline, having emerged from the collaboration of natural products chemists and marine ecologists in the 1980s with the goal of examining the ecological functions of secondary metabolites from the tissues of marine organisms. The result has been a progression of protocols that have increasingly refined the ecological relevance of the experimental approach. Here we present the most up-to-date version of a fish-feeding laboratory bioassay that enables investigators to assess the antipredatory activity of secondary metabolites from the tissues of marine organisms. Organic metabolites of all polarities are exhaustively extracted from the tissue of the target organism and reconstituted at natural concentrations in a nutritionally appropriate food matrix. Experimental food pellets are presented to a generalist predator in laboratory feeding assays to assess the antipredatory activity of the extract. The procedure described herein uses the bluehead, Thalassoma bifasciatum, to test the palatability of Caribbean marine invertebrates; however, the design may be readily adapted to other systems. Results obtained using this laboratory assay are an important prelude to field experiments that rely on the feeding responses of a full complement of potential predators. Additionally, this bioassay can be used to direct the isolation of feeding-deterrent metabolites through bioassay-guided fractionation. This feeding bioassay has advanced our understanding of the factors that control the distribution and abundance of marine invertebrates on Caribbean coral reefs and may inform investigations in diverse fields of inquiry, including pharmacology, biotechnology, and evolutionary ecology.

  8. The importance of tissue handling of surgically removed breast cancer for an accurate assessment of the Ki-67 index

    Science.gov (United States)

    Arima, Nobuyuki; Nishimura, Reiki; Osako, Tomofumi; Nishiyama, Yasuyuki; Fujisue, Mamiko; Okumura, Yasuhiro; Nakano, Masahiro; Tashima, Rumiko; Toyozumi, Yasuo

    2016-01-01

    Aim Insufficient attention for the Ki-67 immunohistochemistry has been given to the importance of tissue handling for surgical breast cancer specimens. We sought to investigate the effect of fixation status on the Ki-67. Methods We examined the effect of fixative, time to and duration of fixation using surgical specimens, and finally, compared the paired Ki-67 index in the tumour between core needle and surgical specimen. Results The Ki-67 was significantly higher when 10% neutral buffered formalin was used (p=0.0276). Insufficient fixation caused a drastic reduction in the Ki-67 index (p=0.0177), but not significant in oestrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). Sixteen hours delayed time to fixation also caused a reduction of the Ki-67 (p=0.0284), but not significant in ER. Prolonged fixation significantly led to a gradual reduction in the Ki-67 in a time-dependent manner, but not in both ER and HER2. Finally, cutting the tumour before fixation improved fixation status and consequently caused an increased level of the Ki-67 index (p=0.0181), which resulted in a strong correlation of the Ki-67 between core needle and surgical specimen (r=0.8595). Conclusions Tissue handling of surgical specimen is critical for assessing the Ki-67 compared with ER and HER2. We should pay more attention to tissue fixation status for the standard assessment of the Ki-67 index. PMID:26420767

  9. Surgical Anatomy of the Gastrointestinal Tract and Its Vasculature in the Laboratory Rat

    OpenAIRE

    Katarína Vdoviaková; Eva Petrovová; Marcela Maloveská; Lenka Krešáková; Jana Teleky; Mario Zefanias Joao Elias; Darina Petrášová

    2015-01-01

    The aim of this study was to describe and illustrate the morphology of the stomach, liver, intestine, and their vasculature to support the planning of surgical therapeutic methods in abdominal cavity. On adult Wistar rats corrosion casts were prepared from the arterial system and Duracryl Dental and PUR SP were used as a casting medium and was performed macroscopic anatomical dissection of the stomach, liver, and intestine was performed. The rat stomach was a large, semilunar shaped sac with ...

  10. EGFR Regulates the Development and Microarchitecture of Intratumoral Angiogenic Vasculature Capable of Sustaining Cancer Cell Intravasation

    Directory of Open Access Journals (Sweden)

    Petra Minder

    2015-08-01

    Full Text Available Many malignant characteristics of cancer cells are regulated through pathways induced by the tyrosine kinase activity of the epidermal growth factor receptor (EGFR. Herein, we show that besides directly affecting the biology of cancer cells per se, EGFR also regulates the primary tumor microenvironment. Specifically, our findings demonstrate that both the expression and signaling activity of EGFR are required for the induction of a distinct intratumoral vasculature capable of sustaining tumor cell intravasation, a critical rate-limiting step in the metastatic cascade. An intravasation-sustaining mode of intratumoral angiogenic vessels depends on high levels of tumor cell EGFR and the interplay between EGFR-regulated production of interleukin 8 by tumor cells, interleukin-8–induced influx of tumor-infiltrating neutrophils delivering their unique matrix metalloproteinase-9, and neutrophil matrix metalloproteinase-9–dependent release of the vascular permeability and endothelial growth factor, VEGF. Our data indicate that through VEGF-mediated disruption of endothelial layer integrity and increase of intratumoral vasculature permeability, EGFR activity significantly facilitates active intravasation of cancer cells. Therefore, this study unraveled an important but overlooked function of EGFR in cancer, namely, its ability to create an intravasation-sustaining microenvironment within the developing primary tumor by orchestrating several interrelated processes required for the initial steps of cancer metastasis through vascular routes. Our findings also suggest that EGFR-targeted therapies might be more effective when implemented in cancer patients with early-staged primary tumors containing a VEGF-dependent angiogenic vasculature. Accordingly, early EGFR inhibition combined with various anti-VEGF approaches could synergistically suppress tumor cell intravasation through inhibiting the highly permeable angiogenic vasculature induced by EGFR

  11. In-vivo photoacoustic microscopy of nanoshell extravasation from solid tumor vasculature

    OpenAIRE

    Li, Meng-Lin; Wang, James Chunjay; Schwartz, Jon A.; Gill-Sharp, Kelly L.; Stoica, George; Lihong V. Wang

    2009-01-01

    In this study, high resolution backward-mode photoacoustic microscopy (PAM) is used to noninvasively image progressive extravasation and accumulation of nanoshells within a solid tumor in vivo. PAM takes advantage of the strong near-infrared absorption of nanoshells and their extravasation tendency from leaky tumor vasculatures for imaging. Subcutaneous tumors are grown on immunocompetent BALB/c mice. Polyethylene glycol (PEGylated) nanoshells with a peak optical absorption at ∼800nm are intr...

  12. Engineering thick tissues - the vascularisation problem

    Directory of Open Access Journals (Sweden)

    H C H Ko

    2007-07-01

    Full Text Available The ability to create thick tissues is a major tissue engineering challenge, requiring the development of a suitable vascular supply. Current trends are seeing the utilization of cells seeded into hybrid matrix/scaffold systems to create in vitro vascular analogues. Approaches that aim to create vasculature in vitro include the use of biological extracellular matrices such as collagen hydrogels, porous biodegradable polymeric scaffolds with macro- and micro-lumens and micro-channels, co-culture of cells, incorporation of growth factors, culture in dynamic bioreactor environments, and combinations of these. Of particular interest are those approaches that aim to create bioengineered tissues in vitro that can be readily connected to the host's vasculature following implantation in order to maintain cell viability.

  13. Astrocyte-derived vascular endothelial growth factor stabilizes vessels in the developing retinal vasculature.

    Directory of Open Access Journals (Sweden)

    Andrew Scott

    Full Text Available Vascular endothelial growth factor (VEGF plays a critical role in normal development as well as retinal vasculature disease. During retinal vascularization, VEGF is most strongly expressed by not yet vascularized retinal astrocytes, but also by retinal astrocytes within the developing vascular plexus, suggesting a role for retinal astrocyte-derived VEGF in angiogenesis and vessel network maturation. To test the role of astrocyte-derived VEGF, we used Cre-lox technology in mice to delete VEGF in retinal astrocytes during development. Surprisingly, this only had a minor impact on retinal vasculature development, with only small decreases in plexus spreading, endothelial cell proliferation and survival observed. In contrast, astrocyte VEGF deletion had more pronounced effects on hyperoxia-induced vaso-obliteration and led to the regression of smooth muscle cell-coated radial arteries and veins, which are usually resistant to the vessel-collapsing effects of hyperoxia. These results suggest that VEGF production from retinal astrocytes is relatively dispensable during development, but performs vessel stabilizing functions in the retinal vasculature and might be relevant for retinopathy of prematurity in humans.

  14. Computational Assessment of Neural Probe and Brain Tissue Interface under Transient Motion

    Directory of Open Access Journals (Sweden)

    Michael Polanco

    2016-06-01

    Full Text Available The functional longevity of a neural probe is dependent upon its ability to minimize injury risk during the insertion and recording period in vivo, which could be related to motion-related strain between the probe and surrounding tissue. A series of finite element analyses was conducted to study the extent of the strain induced within the brain in an area around a neural probe. This study focuses on the transient behavior of neural probe and brain tissue interface with a viscoelastic model. Different stages of the interface from initial insertion of neural probe to full bonding of the probe by astro-glial sheath formation are simulated utilizing analytical tools to investigate the effects of relative motion between the neural probe and the brain while friction coefficients and kinematic frequencies are varied. The analyses can provide an in-depth look at the quantitative benefits behind using soft materials for neural probes.

  15. Computational Assessment of Neural Probe and Brain Tissue Interface under Transient Motion.

    Science.gov (United States)

    Polanco, Michael; Bawab, Sebastian; Yoon, Hargsoon

    2016-06-16

    The functional longevity of a neural probe is dependent upon its ability to minimize injury risk during the insertion and recording period in vivo, which could be related to motion-related strain between the probe and surrounding tissue. A series of finite element analyses was conducted to study the extent of the strain induced within the brain in an area around a neural probe. This study focuses on the transient behavior of neural probe and brain tissue interface with a viscoelastic model. Different stages of the interface from initial insertion of neural probe to full bonding of the probe by astro-glial sheath formation are simulated utilizing analytical tools to investigate the effects of relative motion between the neural probe and the brain while friction coefficients and kinematic frequencies are varied. The analyses can provide an in-depth look at the quantitative benefits behind using soft materials for neural probes.

  16. Dynamic tissue phantoms and their use in assessment of a noninvasive optical plethysmography imaging device

    Science.gov (United States)

    Thatcher, Jeffrey E.; Plant, Kevin D.; King, Darlene R.; Block, Kenneth L.; Fan, Wensheng; DiMaio, J. Michael

    2014-05-01

    Non-contact photoplethysmography (PPG) has been studied as a method to provide low-cost and non-invasive medical imaging for a variety of near-surface pathologies and two dimensional blood oxygenation measurements. Dynamic tissue phantoms were developed to evaluate this technology in a laboratory setting. The purpose of these phantoms was to generate a tissue model with tunable parameters including: blood vessel volume change; pulse wave frequency; and optical scattering and absorption parameters. A non-contact PPG imaging system was evaluated on this model and compared against laser Doppler imaging (LDI) and a traditional pulse oximeter. Results indicate non-contact PPG accurately identifies pulse frequency and appears to identify signals from optically dense phantoms with significantly higher detection thresholds than LDI.

  17. Assessment of SAR in the tissues near a cochlear implant exposed to radiofrequency electromagnetic fields

    Energy Technology Data Exchange (ETDEWEB)

    Sibella, F; Parazzini, M; Paglialonga, A; Ravazzani, P [Istituto di Ingegneria Biomedica, Consiglio Nazionale delle Ricerche, Piazza Leonardo da Vinci, 32, 20133 Milano (Italy)], E-mail: federica.sibella@polimi.it, E-mail: marta.parazzini@polimi.it, E-mail: alessia.paglialonga@polimi.it, E-mail: paolo.ravazzani@polimi.it

    2009-04-21

    Cochlear implants (CI) are electronic devices used to restore partial hearing to people with severe hearing impairment. This paper aims to investigate if the introduction of a CI has an effect on SAR distribution in a head model exposed to radiofrequency electromagnetic fields (RF EMF) at mobile communication frequencies. The head model was obtained by image segmentation, the implant was modelled as a geometric structure and the exposure source was modelled as a uniform plane wave at 900 MHz, 1750 MHz and 1950 MHz, incident on the side of the head with the CI. Vertical and horizontal polarizations were simulated. Results show that the presence of a CI inside the cochlea produces negligible variations in the averaged SAR values, both in the head and in the cochlear tissues, although very localized differences in point SAR were found in the cochlea. Globally, these results suggest that finding harmful effects in the cochlear tissues will be unlikely. (note)

  18. An assessment of mercury in estuarine sediment and tissue in Southern New Jersey using public domain data

    Science.gov (United States)

    Ng, Kara; Szabo, Zoltan; Reilly, Pamela A.; Barringer, Julia; Smalling, Kelly

    2016-01-01

    Mercury (Hg) is considered a contaminant of global concern for coastal environments due to its toxicity, widespread occurrence in sediment, and bioaccumulation in tissue. Coastal New Jersey, USA, is characterized by shallow bays and wetlands that provide critical habitat for wildlife but share space with expanding urban landscapes. This study was designed as an assessment of the magnitude and distribution of Hg in coastal New Jersey sediments and critical species using publicly available data to highlight potential data gaps. Mercury concentrations in estuary sediments can exceed 2 μg/g and correlate with concentrations of other metals. Based on existing data, the concentrations of Hg in mussels in southern New Jersey are comparable to those observed in other urbanized Atlantic Coast estuaries. Lack of methylmercury data for sediments, other media, and tissues are data gaps needing to be filled for a clearer understanding of the impacts of Hg inputs to the ecosystem.

  19. Using Design of Experiments Methods for Assessing Peak Contact Pressure to Material Properties of Soft Tissue in Human Knee

    Directory of Open Access Journals (Sweden)

    Marjan Bahraminasab

    2013-01-01

    Full Text Available Contact pressure in the knee joint is a key element in the mechanisms of knee pain and osteoarthritis. Assessing the contact pressure in tibiofemoral joint is a challenging mechanical problem due to uncertainty in material properties. In this study, a sensitivity analysis of tibiofemoral peak contact pressure to the material properties of the soft tissue was carried out through fractional factorial and Box-Behnken designs. The cartilage was modeled as linear elastic material, and in addition to its elastic modulus, interaction effects of soft tissue material properties were added compared to previous research. The results indicated that elastic modulus of the cartilage is the most effective factor. Interaction effects of axial/radial modulus with elastic modulus of cartilage, circumferential and axial/radial moduli of meniscus were other influential factors. Furthermore this study showed how design of experiment methods can help designers to reduce the number of finite element analyses and to better interpret the results.

  20. Prognostic factors and assessment of staging systems for head and neck soft tissue sarcomas in adults

    OpenAIRE

    Van Damme, J.P.; Schmitz, S.; Machiels, J.P.; Galant, C.; Grégoire, V.; Lengelé, B.; Hamoir, M.

    2010-01-01

    Abstract Objectives The primary objectives of this study were to analyse the outcome of patients diagnosed with head and neck soft tissue sarcomas (HNSTS) and to identify relevant prognostic factors. As well as this, we compared the prognostic value of two staging systems proposed by the American Joint Committee on Cancer (AJCC) and the Memorial Sloan-Kettering Cancer Center (MSKCC). Methods From 07/1988 to 01/2008, the charts of 42 adult patients w...

  1. DNA damage in preserved specimens and tissue samples: a molecular assessment

    Directory of Open Access Journals (Sweden)

    Cantin Elizabeth

    2008-10-01

    Full Text Available Abstract The extraction of genetic information from preserved tissue samples or museum specimens is a fundamental component of many fields of research, including the Barcode of Life initiative, forensic investigations, biological studies using scat sample analysis, and cancer research utilizing formaldehyde-fixed, paraffin-embedded tissue. Efforts to obtain genetic information from these sources are often hampered by an inability to amplify the desired DNA as a consequence of DNA damage. Previous studies have described techniques for improved DNA extraction from such samples or focused on the effect of damaging agents – such as light, oxygen or formaldehyde – on free nucleotides. We present ongoing work to characterize lesions in DNA samples extracted from preserved specimens. The extracted DNA is digested to single nucleosides with a combination of DNase I, Snake Venom Phosphodiesterase, and Antarctic Phosphatase and then analyzed by HPLC-ESI-TOF-MS. We present data for moth specimens that were preserved dried and pinned with no additional preservative and for frog tissue samples that were preserved in either ethanol, or formaldehyde, or fixed in formaldehyde and then preserved in ethanol. These preservation methods represent the most common methods of preserving animal specimens in museum collections. We observe changes in the nucleoside content of these samples over time, especially a loss of deoxyguanosine. We characterize the fragmentation state of the DNA and aim to identify abundant nucleoside lesions. Finally, simple models are introduced to describe the DNA fragmentation based on nicks and double-strand breaks.

  2. Clinical assessments of the erbium:YAG laser for soft tissue surgery and scaling.

    Science.gov (United States)

    Watanabe, H; Ishikawa, I; Suzuki, M; Hasegawa, K

    1996-04-01

    We evaluated the clinical usefulness of an erbium:YAG laser for soft tissue surgery, and scaling. Thirty-one patients with soft tissue lesions (13 males and 18 females from 24 to 71 years old), and 60 patients with calculus deposits (21 males and 39 females from 19 to 72 years old) were treated with the laser. The clinical parameters evaluated were pain, redness, swelling of the gingiva, and the subjective patient comfort parameters including uneasiness with the sound and vibration associated with laser treatment. Additionally, hemorrhage and wound healing during and after the surgery, the roughness of the root surface after scaling, and the effectiveness of scaling using the laser were examined. Laser surgery caused less hemorrhage and resulted in better wound healing when compared with conventional methods. It was easy to remove calculi from the root surface with the laser in 95% of the cases. Although the scaled site showed some irregularity, it was not clinically significant in 98% of the cases. Only a few patients complained about the unpleasant sound and vibration. There were no complications or side effects during this clinical trial. Thus, this study suggests that an Er:YAG laser is useful for soft tissue surgery and scaling.

  3. Risk assessment of mouse gastric tissue cancer induced by dichlorvos and dimethoate.

    Science.gov (United States)

    Wang, Qing-Lu; Zhang, Yu-Jun; Zhou, Cai-Xia; Zhang, Jie; Dou, Ye; Li, Qiao-Qiao

    2013-04-01

    Cancer hazards from pesticide residues in food have been much discussed in the past decade. In this study, we showed that dichlorvos and dimethoate affect hemoglobin content and hematocrit value, but had no effect on red blood cell counts and total plasma protein in mice. A 40-mg/kg/day dose of dichlorvos upregulated the expression of p16, Bcl-2 and c-myc genes in mouse gastric tissue. By contrast, expression of the p16, Bcl-2 and c-myc genes induced by low doses (5, 10 and 20 mg/kg/day) of dichlorvos demonstrated no change in the control check group (CK; 200 μl sterile saline perfused group; 0 mg/kg/day). Different doses of dimethoate all upregulated the expression of p16, Bcl-2 and c-myc genes in mouse gastric tissue. The results further demonstrated that mouse gastric tissue, exposed in the long-term to low doses of dichlorvos and dimethoate, has the potential to become cancerous.

  4. Assessment of photoacoustic computed tomography to classify tissue in a polycystic-kidney disease mouse model

    Science.gov (United States)

    Liu, Bo; Gattone, Vincent H., II; Kruger, Robert A.; Stantz, Keith M.

    2006-02-01

    Purpose: The purpose of this study is to evaluate PCT Imaging technique to classify tissue and extract kidney cysts in pcy mice model of human adolescent nephronophthisis. Method: Four mice with late stages of nephronophthisis with polycystic kidney disease-PKD and one normal mouse were scanned in the PCT Small Animal Scanner. Both vivo and ex-vivo images of mice kidney were taken at wavelength from 680 nm to 940 nm. The ex-vivo PCT images were compared with histology photographs to check the sensitivity of detecting cysts. Histograms of kidney images were generated over slices and fitted to Gaussian-curve model for volumetric analysis. The portions of cysts in kidneys were estimated and kidney images were segmented by three different colors to present the distribution of different tissues. Result: A good correspondence between PCT imaging findings and PKD histology result was observed. Histogram curves from images of pcy kidneys and normal kidneys were fitted to Gaussian-curve model. Portions of cysts, parenchyma and area of high level hemoglobin were estimated according to the curve fit result. A growth of cysts associated with relatively volume decrease of parenchyma and tissues with high perfusion of hemoglobin was observed. Conclusion: The PCT enabled visualization of renal cysts for mouse model and had the potential for volumetric measurements of kidney.

  5. Utilization of laser Doppler flowmetry and tissue spectrophotometry for burn depth assessment using a miniature swine model.

    Science.gov (United States)

    Lotter, Oliver; Held, Manuel; Schiefer, Jennifer; Werner, Ole; Medved, Fabian; Schaller, Hans-Eberhard; Rahmanian-Schwarz, Afshin; Jaminet, Patrick; Rothenberger, Jens

    2015-01-01

    Currently, the diagnosis of burn depth is primarily based on a visual assessment and can be dependent on the surgeons' experience. The goal of this study was to determine the ability of laser Doppler flowmeter combined with a tissue spectrophotometer to discriminate burn depth in a miniature swine burn model. Burn injuries of varying depth, including superficial-partial, deep-partial, and full thickness, were created in seven Göttingen minipigs using an aluminium bar (100 °C), which was applied to the abdominal skin for periods of 1, 3, 6, 12, 30, and 60 seconds with gravity alone. The depth of injury was evaluated histologically using hematoxylin and eosin staining. All burns were assessed 3 hours after injury using a device that combines a laser light and a white light to determine blood flow, hemoglobin oxygenation, and relative amount of hemoglobin. The blood flow (41 vs. 124 arbitrary units [AU]) and relative amount of hemoglobin (32 vs. 52 AU) were significantly lower in full thickness compared with superficial-partial thickness burns. However, no significant differences in hemoglobin oxygenation were observed between these depths of burns (61 vs. 60%). These results show the ability of laser Doppler flowmeter and tissue spectrophotometer in combination to discriminate between various depths of injury in the minipig model, suggesting that this device may offer a valuable tool for burn depth assessment influencing burn management.

  6. Plasma DNA tissue mapping by genome-wide methylation sequencing for noninvasive prenatal, cancer, and transplantation assessments

    Science.gov (United States)

    Sun, Kun; Jiang, Peiyong; Chan, K. C. Allen; Wong, John; Cheng, Yvonne K. Y.; Liang, Raymond H. S.; Chan, Wai-kong; Ma, Edmond S. K.; Chan, Stephen L.; Cheng, Suk Hang; Chan, Rebecca W. Y.; Tong, Yu K.; Ng, Simon S. M.; Wong, Raymond S. M.; Hui, David S. C.; Leung, Tse Ngong; Leung, Tak Y.; Lai, Paul B. S.; Chiu, Rossa W. K.; Lo, Yuk Ming Dennis

    2015-01-01

    Plasma consists of DNA released from multiple tissues within the body. Using genome-wide bisulfite sequencing of plasma DNA and deconvolution of the sequencing data with reference to methylation profiles of different tissues, we developed a general approach for studying the major tissue contributors to the circulating DNA pool. We tested this method in pregnant women, patients with hepatocellular carcinoma, and subjects following bone marrow and liver transplantation. In most subjects, white blood cells were the predominant contributors to the circulating DNA pool. The placental contributions in the plasma of pregnant women correlated with the proportional contributions as revealed by fetal-specific genetic markers. The graft-derived contributions to the plasma in the transplant recipients correlated with those determined using donor-specific genetic markers. Patients with hepatocellular carcinoma showed elevated plasma DNA contributions from the liver, which correlated with measurements made using tumor-associated copy number aberrations. In hepatocellular carcinoma patients and in pregnant women exhibiting copy number aberrations in plasma, comparison of methylation deconvolution results using genomic regions with different copy number status pinpointed the tissue type responsible for the aberrations. In a pregnant woman diagnosed as having follicular lymphoma during pregnancy, methylation deconvolution indicated a grossly elevated contribution from B cells into the plasma DNA pool and localized B cells as the origin of the copy number aberrations observed in plasma. This method may serve as a powerful tool for assessing a wide range of physiological and pathological conditions based on the identification of perturbed proportional contributions of different tissues into plasma. PMID:26392541

  7. Endothelial follistatin-like 1 regulates the maturation of the pulmonary vasculature by modulating BMP/SMAD signaling

    NARCIS (Netherlands)

    Tania, Navessa Padma; Maarsingh, Harm; Bos, Sophie T.; Mattiotti, Andrea; Prakash, Stuti; Timens, Wim; Schmidt, Martina; Van Den Hoff, Maurice; Gosens, Reinoud

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a progressive disease that is characterized by vascular remodeling and sustained vasoconstriction which consequently lead to high blood pressure in the pulmonary vasculature and right ventricle remodeling. Altered bone morphogenetic protein (BMP) signaling ha

  8. BaroFuse, a novel pressure-driven, adjustable-throughput perfusion system for tissue maintenance and assessment

    Directory of Open Access Journals (Sweden)

    Austin Rountree

    2016-12-01

    Conclusions: The very low flow rates and simplicity of design and operation of the BaroFuse device allow for the efficient generation of large number of kinetic profiles in OCR and other endpoints lasting from hours to days. The use of flow enhances the ability to make measurements on primary tissue where some elements of native three-dimensional structure are preserved. We offer the BaroFuse as a powerful tool for physiological studies and for pharmaceutical assessment of drug effects as well as personalized medicine.

  9. Ventricular synchronicity: observations comparing pulse flow and tissue Doppler assessment in a Chinese healthy adult cohort

    Institute of Scientific and Technical Information of China (English)

    QUAN Xin; ZHU Tian-gang; GUO Shi; MA Jian-xin; WANG Xin; GUO Ji-hong

    2012-01-01

    Background Mechanical asynchrony is an important parameter in predicting the response to cardiac resynchronization therapy,but detailed knowledge about cardiac timing in healthy persons is scarce.Therefore,in the current study,we sought to investigate the physiological status of interventricular synchronicity using pulse wave flow and tissue Doppler imaging in a healthy Chinese population.Methods Eighty-eight healthy volunteers underwent standard flow and tissue Doppler echocardiographic examinations.Ventricular inflow and outflow pulse wave flow Doppler patterns were recorded together with annulus pulse tissue Doppler imaging.Time intervals from the beginning of the QRS complex to the onset,peak and end of each wave were measured.Results The onsets of systole between left and right ventricles were highly synchronized by both imaging modalities.However,the left ventricle reached the peak flow ejection and peak mechanical contraction earlier than the right ventricle,(165.61±26.23) ms vs.(204.3±34.55) ms (P <0.01) and (133.62±26.19) ms vs.(191.25±38.47) ms (P <0.01).Time to peak early diastolic relaxation was earlier in the left ventricle than in the right heart,(500.23±56.52) me vs.(524.94±47.42) ms (P <0.01).Conclusions Left and right ventricles were well synchronized at the onsets of systole and diastole even though interventricular peak systolic and peak early diastolic dyssynchrony was observed in healthy people by pulse wave Doppler imaging.In addition,diastolic timing events were slightly affected by age and gender.

  10. Endoplasmic reticulum stress responses differ in meninges and associated vasculature, striatum, and parietal cortex after a neurotoxic amphetamine exposure.

    Science.gov (United States)

    Thomas, Monzy; George, Nysia I; Saini, Upasana T; Patterson, Tucker A; Hanig, Joseph P; Bowyer, John F

    2010-08-01

    Amphetamine (AMPH) is used to treat attention deficit and hyperactivity disorders, but it can produce neurotoxicity and adverse vascular effects at high doses. The endoplasmic reticulum (ER) stress response (ERSR) entails the unfolded protein response, which helps to avoid or minimize ER dysfunction. ERSR is often associated with toxicities resulting from the accumulation of unfolded or misfolded proteins and has been associated with methamphetamine toxicity in the striatum. The present study evaluates the effect of AMPH on several ERSR elements in meninges and associated vasculature (MAV), parietal cortex, and striatum. Adult, male Sprague-Dawley rats were exposed to saline, environmentally induced hyperthermia (EIH) or four consecutive doses of AMPH that produce hyperthermia. Expression changes (mRNA and protein levels) of key ERSR-related genes in MAV, striatum, and parietal cortex at 3 h or 1 day postdosing were monitored. AMPH increased the expression of some ERSR-related genes in all tissues. Atf4 (activating transcription factor 4, an indicator of Perk pathway activation), Hspa5/Grp78 (Glucose regulated protein 78, master regulator of ERSR), Pdia4 (protein disulfide isomerase, protein-folding enzyme), and Nfkb1 (nuclear factor of kappa b, ERSR sensor) mRNA increased significantly in MAV and parietal cortex 3 h after AMPH. In striatum, Atf4 and Hspa5/Grp78 mRNA significantly increased 3 h after AMPH, but Pdia4 and Nfkb11 did not. Thus, AMPH caused a robust activation of the Perk pathway in all tissues, but significant Ire1 pathway activation occurred only after AMPH treatment in the parietal cortex and striatum. Ddit3/Chop, a downstream effector of the ERSR pathway related to the neurotoxicity, was only increased in striatum and parietal cortex. Conversely, Pdia4, an enzyme protective in the ERSR, was only increased in MAV. The overall ERSR manifestation varied significantly between MAV, striatum, and parietal cortex after a neurotoxic exposure to AMPH.

  11. Multi-timescale Modeling of Activity-Dependent Metabolic Coupling in the Neuron-Glia-Vasculature Ensemble

    KAUST Repository

    Jolivet, Renaud

    2015-02-26

    Glucose is the main energy substrate in the adult brain under normal conditions. Accumulating evidence, however, indicates that lactate produced in astrocytes (a type of glial cell) can also fuel neuronal activity. The quantitative aspects of this so-called astrocyte-neuron lactate shuttle (ANLS) are still debated. To address this question, we developed a detailed biophysical model of the brain’s metabolic interactions. Our model integrates three modeling approaches, the Buxton-Wang model of vascular dynamics, the Hodgkin-Huxley formulation of neuronal membrane excitability and a biophysical model of metabolic pathways. This approach provides a template for large-scale simulations of the neuron-glia-vasculature (NGV) ensemble, and for the first time integrates the respective timescales at which energy metabolism and neuronal excitability occur. The model is constrained by relative neuronal and astrocytic oxygen and glucose utilization, by the concentration of metabolites at rest and by the temporal dynamics of NADH upon activation. These constraints produced four observations. First, a transfer of lactate from astrocytes to neurons emerged in response to activity. Second, constrained by activity-dependent NADH transients, neuronal oxidative metabolism increased first upon activation with a subsequent delayed astrocytic glycolysis increase. Third, the model correctly predicted the dynamics of extracellular lactate and oxygen as observed in vivo in rats. Fourth, the model correctly predicted the temporal dynamics of tissue lactate, of tissue glucose and oxygen consumption, and of the BOLD signal as reported in human studies. These findings not only support the ANLS hypothesis but also provide a quantitative mathematical description of the metabolic activation in neurons and glial cells, as well as of the macroscopic measurements obtained during brain imaging.

  12. Infarct myocardium tissue heterogeneity assessment using pre-contrast and post-contrast T1 maps acquired with Modified Look-Locker Inversion Recovery (MOLLI) imaging

    NARCIS (Netherlands)

    Chen, Z.; Voigt, T.; Wiethoff, A.; Shetty, A.K.; Crichton, S.; Murday, D.; Rinaldi, A.; Nagel, E.; Puntmann, V.O.; Schaeffter, T.; Razavi, R.S.

    2012-01-01

    We aim to explore tissue heterogeneity assessment using T1 maps generated with the modified Look Locker (MOLLI) sequence in patients with previous myocardial infarct. Conclusion: Differences between healthy myocardium and scarred tissues can be reliably distinguished from the R1 values derived from

  13. Assessment of bone tissue during treatment dentoalveolar anomalies in children with scoliosis

    Directory of Open Access Journals (Sweden)

    Samoilenko A.V.

    2012-01-01

    Full Text Available The purpose of the study was to develop a rational method of treatment dentoalveolar anomalies aimed at reducing relapses dentoalveolar anomalies, duration of treatment, depending on bone density in patients with scoliosis. Scoliosis is often associated with osteopenia and impaired metabolism of connective tissue that manifested reduced bone mineral density and changes in metabolic status, impaired synthesis of the major structural components of connective tissue, resulting integral reaction to a combination of two abnormal situations - osteopenia and scoliotic deformity. Prevalence dentoalveolar anomalies abnormalities among patients with scoliosis reaches 81.6%, in most cases accompanied by gingivitis. Therefore, the need for orthodontic treatment in these patients is quite high. When scoliosis orthodontic treatment has an impact on pathologically changed bone, so the retention period of orthodontic treatment need prescriptions that enhance the adaptive capacity of the body and promote reparative bone formation and development of pathogenetically substantiated complex preventive measures aimed at improving the effectiveness of treatment and prevention of dentoalveolar anomalies recurrence. A biometric study of control and diagnostic models of the jaws, biochemical oral fluid, determining bone density by ultrasonic osteography, the timing of orthodontic treatment in patients, with jaw abnormalities suffering from scoliosis and various sites of varying severity. We have developed medical centers showed high efficiency, which showed an increase density and improve bone metabolism.

  14. Assessment of the Selenoprotein M (SELM over-expression on human hepatocellular carcinoma tissues by immunohistochemistry

    Directory of Open Access Journals (Sweden)

    E. Guerriero

    2014-10-01

    Full Text Available Selenium is an essential trace mineral of fundamental importance to human healthy and exerts its biological function through selenoproteins. In particular, Selenoprotein M (SELM is located in the endoplasmic reticulum and contains the common redox motif of cysteine-X-X-selenocysteine type. It attracts great attention due to its high expression in brain and its potential roles as antioxidant, neuroprotective, and cytosolic calcium regulator. Recently, our group found SELM over-expression  in human hepatocellular carcinoma (HCC cell lines. In this report some paraffin-embedded tissues from liver biopsy of patients with hepatitis C virus (HCV-related cirrhosis and HCC were immunohistochemically stained and SELM expression scoring was evaluated. Our results evidence for the first time an increase of SELM expression in HCC liver tissues, and its gradual expression raise associated with an increased malignancy grade. Therefore, we propose to use i SELM as putative marker for HCC as well as ii simple immunohistochemistry technique to distinguish between the different grades of malignancy. 

  15. Resonant Raman detectors for noninvasive assessment of carotenoid antioxidants in human tissue

    Science.gov (United States)

    Gellermann, Werner; Sharifzadeh, Mohsen; Ermakova, Maia R.; Ermakov, Igor V.; Bernstein, P. S.

    2003-07-01

    Carotenoid antioxidants form an important part of the human body's anti-oxidant system and are thought to play an important role in disease prevention. Studies have shown an inverse correlation between high dietary intake of carotenoids and risk of certain cancers, heart disease and degenerative diseases. For example, the carotenoids lutein and zeaxanthin, which are present in high concentrations in the human retina, are thought to prevent age-related macular degeneration, the leading cause of blindness in the elderly in the Western world. We have developed various clinical prototype instruments, based on resonance Raman spectroscopy, that are able to measure carotenoid levels directly in the tissue of interest. At present we use the Raman technology to quantify carotenoid levels in the human retina, in skin, and in the oral cavity. We use resonant excitation of the π-conjugated molecules in the visible wavelength range and detect the molecules' carbon-carbon stretch frequencies. The spectral properties of the various carotenoids can be explored to selectively measure in some cases individual carotenoid species linked ot the prevention of cancer, in human skin. The instrumentation involves home-built, compact, high-throughput Raman systems capable of measuring physiological carotenoid concentrations in human subjects rapidly and quantitatively. The instruments have been demonstrated for field use and screening of tissue carotenoid status in large populations. In Epidemiology, the technology holds promise as a novel, noninvasive and objective biomarker of fruit and vegetable uptake.

  16. Perfluorocarbon-loaded lipid nanocapsules as oxygen sensors for tumor tissue pO₂ assessment.

    Science.gov (United States)

    Lemaire, L; Bastiat, G; Franconi, F; Lautram, N; Duong Thi Dan, T; Garcion, E; Saulnier, P; Benoit, J P

    2013-08-01

    The assessment of tumor oxygenation is a crucial factor in cancer therapy and may be carried out using fluorine MRI once fluorine probes have been distributed within the tumor. However, the deposit of those highly fluorinated compounds often jeopardizes anatomical image quality and requires emulsification of the probes. Due to the high density and the high lipophilicity of perfluorocarbons, nanoemulsion of these molecules usually requires high-energy processes. In the present work, we discuss the synthesis and the physico-chemical characterization of perfluorocarbon nanocapsules using a low-energy phase-inversion process. The nanocapsules were tested on a mouse tumor brain model to assess oxygenation.

  17. Assessment of heavy metals in seawater and fish tissues at Pulau Indah, Selangor, Malaysia

    Energy Technology Data Exchange (ETDEWEB)

    Md Yunus, Sabarina, E-mail: sabarina2020@salam.uitm.edu.m; Hamzah, Zaini; Wood, Ab. Khalik; Ahmad [Faculty of Applied Sciences, Universiti Teknologi MARA, 40450 Shah Alam, Selangor (Malaysia)

    2015-04-29

    This study focuses on the levels of heavy metals in seawater and selected fish tissue at Pulau Indah, Selangor, Malaysia. Pulau Indah primarily contains Westport (Malaysia’s major port), and a host of full scales factories. Therefore, it is important to monitor the levels of pollution in this water body and the aquatic organisms in the long term effects, due to the human activities in this area. Water samples in this study were taken from 8 locations along the coastal area. The water samples were collected using water sampler and sampling locations were determined using a Global Positioning system (GPS). Similarly, in situ water quality parameters including temperature, dissolve oxygen (DO), salinity, total suspended solid (TSS), pH and turbidity were measured by using portable multi probes meter. Then, the samples were acidified until pH 2 and filtered. Fish samples were purchased from local fisherman along the Pulau Indah coastal area and samples were digested using concentrated nitric acid in wet digestion method. The levels of selected heavy metals in four species of fish and seawater from Pulau Indah coastal area were determined using Inductive Coupled Plasma Mass Spectrometer (ICPMS) after dilution to the samples. In general, the quality of water at Pulau Indah is lower than Malaysia Marine Water Quality Standard except for few locations were higher than the maximum permissible levels. The concentration of heavy metals which are lead (Pb), copper (Cu), zinc (Zn) and uranium (U) in water samples are in the range of 0.36-5.43 µg/L, 75.20-621.58 µg/L, 11.92-30.52 µg/L, and 4.00-4.65 µg/L respectively. While the results of the four selected fish showed the following order of abundance Zn> U> Cu> Pb. Transfer factor (TF) of heavy metals in fish tissue of selected fish species from the water was discussed. However, the observed metal concentration in the sample tissue did not exceed the allowable limit of Malaysian Food Act (1983) and Regulation (1985

  18. Assessment of Telomere Length in Archived Formalin-Fixed, Paraffinized Human Tissue Is Confounded by Chronological Age and Storage Duration

    Science.gov (United States)

    2016-01-01

    Telomeres shorten with physiological aging but undergo substantial restoration during cancer immortalization. Increasingly, cancer studies utilize the archive of formalin-fixed, paraffin-embedded (FFPE) tissues in diagnostic pathology departments. Conceptually, such studies would be confounded by physiological telomere attrition and loss of DNA integrity from prolonged tissue storage. Our study aimed to investigate these two confounding factors. 145 FFPE tissues of surgically-resected, non-diseased appendixes were retrieved from our pathology archive, from years 2008 to 2014. Cases from 2013 to 2014 were categorized by patient chronological age (0–20 years, 21–40 years, 41–60 years, > 60 years). Telomere lengths of age categories were depicted by telomere/chromosome 2 centromere intensity ratio (TCR) revealed by quantitative fluorescence in situ hybridization. Material from individuals aged 0–20 years from years 2013/2014, 2011/2012, 2009/2010, and 2008 were compared for storage effect. Telomere integrity was assessed by telomere fluorescence intensity (TFI). Epithelial TCRs (mean ± SD) for the respective age groups were 4.84 ± 2.08, 3.64 ± 1.21, 2.03 ± 0.37, and 1.93 ± 0.45, whereas corresponding stromal TCRs were 5.16 ± 2.55, 3.84 ± 1.36, 2.49 ± 1.20, and 2.93 ± 1.24. A trend of inverse correlation with age in both epithelial and stromal tissues is supported by r = -0.69, p archived beyond 2 years are suboptimal for telomere analysis. PMID:27598341

  19. A Novel Semiautomated Fractional Limb Volume Tool for Rapid and Reproducible Fetal Soft Tissue Assessment.

    Science.gov (United States)

    Mack, Lauren M; Kim, Sung Yoon; Lee, Sungmin; Sangi-Haghpeykar, Haleh; Lee, Wesley

    2016-07-01

    The purpose of this study was to document the reproducibility and efficiency of a semiautomated image analysis tool that rapidly provides fetal fractional limb volume measurements. Fifty pregnant women underwent 3-dimensional sonographic examinations for fractional arm and thigh volumes at a mean menstrual age of 31.3 weeks. Manual and semiautomated fractional limb volume measurements were calculated, with the semiautomated measurements calculated by novel software (5D Limb Vol; Samsung Medison, Seoul, Korea). The software applies an image transformation method based on the major axis length, minor axis length, and limb center coordinates. A transformed image is used to perform a global optimization technique for determination of an optimal limb soft tissue boundary. Bland-Altman analysis defined bias with 95% limits of agreement (LOA) between methods, and timing differences between manual versus automated methods were compared by a paired t test. Bland-Altman analysis indicated an acceptable bias with 95% LOA between the manual and semiautomated methods: mean arm volume ± SD, 1.7% ± 4.6% (95% LOA, -7.3% to 10.7%); and mean thigh volume, 0.0% ± 3.8% (95% LOA, -7.5% to 7.5%). The computer-assisted software completed measurements about 5 times faster compared to manual tracings. In conclusion, semiautomated fractional limb volume measurements are significantly faster to calculate when compared to a manual procedure. These results are reproducible and are likely to reduce operator dependency. The addition of computer-assisted fractional limb volume to standard biometry may improve the precision of estimated fetal weight by adding a soft tissue component to the weight estimation process.

  20. Development and assessment of a cutaneous tissue stretch device as a novel scar therapy

    Institute of Scientific and Technical Information of China (English)

    Jonathan Kanevsky; Joshua Vorstenbosch; Julian Diaz-Abele; Tyler Safran; Markus Prinz; Youssef Tahiri; Mirko Gilardino; Satya Prakash

    2016-01-01

    Aim: Scar prevention and reduction is an area of therapeutic opportunity and unmet medical need. With no current effective scar therapy, patients are often disappointed in their appearance post surgery and re-present to surgeons, only to be turned away. The purpose of this study was to develop and test a device that produces intermittent parallel stretch on new scars and to analyze its potential to reduce scarring.Methods: Mice were randomized into 5 scar stretch treatment groups: 1 control, 1 sham, and 3 stretch models (0.5×, 1×, or 2× device strength) and treated for 10 days. Scars were scored using the Vancouver Scar Scale. Scar tissue samples were compared by histology and transforming growth factor beta 1 (TGF-β1) expression between control and treatment groups.Results: Scar scores of 0.5× and 1× groups were signiifcantly lower than the control group (P < 0.05). Scar scores from the 1× treatment group were also signiifcantly lower than the 0.5× group (P < 0.05). Sham, control scar and 2× groups showed more collagen deposition and a thicker dermal scar than the 0.5× and 1× groups. Unstretched scars had fewer ifbroblasts with more collagen deposition than the 0.5× and 2× groups. TGF-β1 levels were signiifcantly lower in the 0.5× (342.1 ± 9.2) and 1× (254.1 ± 3.1) groups than in the control group (P < 0.05). TGF-β1 levels in the 1× treatment group were also signiifcantly lower than the 0.5× treatment group (P < 0.05).Conclusion:Intermittent cutaneous tissue stretch parallel to scars during the proliferative phase of wound healing decreases ifbrosis on a macroscopic, microscopic and biochemical level.

  1. Assessment of doses caused by electrons in thin layers of tissue-equivalent materials, using MCNP.

    Science.gov (United States)

    Heide, Bernd

    2013-10-01

    Absorbed doses caused by electron irradiation were calculated with Monte Carlo N-Particle transport code (MCNP) for thin layers of tissue-equivalent materials. The layers were so thin that the calculation of energy deposition was on the border of the scope of MCNP. Therefore, in this article application of three different methods of calculation of energy deposition is discussed. This was done by means of two scenarios: in the first one, electrons were emitted from the centre of a sphere of water and also recorded in that sphere; and in the second, an irradiation with the PTB Secondary Standard BSS2 was modelled, where electrons were emitted from an (90)Sr/(90)Y area source and recorded inside a cuboid phantom made of tissue-equivalent material. The speed and accuracy of the different methods were of interest. While a significant difference in accuracy was visible for one method in the first scenario, the difference in accuracy of the three methods was insignificant for the second one. Considerable differences in speed were found for both scenarios. In order to demonstrate the need for calculating the dose in thin small zones, a third scenario was constructed and simulated as well. The third scenario was nearly equal to the second one, but a pike of lead was assumed to be inside the phantom in addition. A dose enhancement (caused by the pike of lead) of ∼113 % was recorded for a thin hollow cylinder at a depth of 0.007 cm, which the basal-skin layer is referred to in particular. Dose enhancements between 68 and 88 % were found for a slab with a radius of 0.09 cm for all depths. All dose enhancements were hardly noticeable for a slab with a cross-sectional area of 1 cm(2), which is usually applied to operational radiation protection.

  2. Assessment of metal contamination in water, sediment, and tissues of Arius thalassinus fish from the Red Sea coast of Yemen and the potential human risk assessment.

    Science.gov (United States)

    Saleh, Yousef S; Marie, Mohamed-Assem S

    2015-04-01

    Heavy metal pollution is one of the most serious environmental issues globally. To evaluate the metal pollution in the Red Sea coast of Hodeida, Yemen Republic, the concentrations of Fe, Cu, Ni, Pb, and Cd in water, sediment, and some vital organs of sea catfish, Arius thalassinus collected from polluted and unpolluted sites, were determined. The risk of these metals to humans through fish consumption was then assessed. The results showed that the concentration order of metals in water, sediment, and fish tissues were Fe > Cu > Ni > Pb > Cd. The levels of studied metals in water, sediment, and fish tissues were significantly higher in the polluted site than those of the unpolluted site, with few exceptions. Linear correlation incorporating paired variables (water-sediment, water-fish, and fish-fish) exhibited several significant correlations indicating a common metal pollution. The risk assessment performed revealed that fish consumption was safe for consumers. This field investigation provides a baseline data on metal pollution in this region.

  3. Visual and automated assessment of matrix metalloproteinase-14 tissue expression for the evaluation of ovarian cancer prognosis.

    Science.gov (United States)

    Trudel, Dominique; Desmeules, Patrice; Turcotte, Stéphane; Plante, Marie; Grégoire, Jean; Renaud, Marie-Claude; Orain, Michèle; Bairati, Isabelle; Têtu, Bernard

    2014-10-01

    The purpose of this study was to evaluate whether the membrane type 1 matrix metalloproteinase-14 (or MT1-MMP) tissue expression, as assessed visually on digital slides and by digital image analysis, could predict outcomes in women with ovarian carcinoma. Tissue microarrays from a cohort of 211 ovarian carcinoma women who underwent a debulking surgery between 1993 and 2006 at the CHU de Québec (Canada) were immunostained for matrix metalloproteinase-14. The percentage of MMP-14 staining was assessed visually and with the Calopix software. Progression was evaluated using the CA-125 and/or the RECIST criteria according to the GCIG criteria. Dates of death were obtained by record linkage with the Québec mortality files. Adjusted hazard ratios of death and progression with their 95% confidence intervals were estimated using the Cox model. Comparisons between the two modalities of MMP-14 assessment were done using the box plots and the Kruskal-Wallis test. The highest levels of MMP-14 immunostaining were associated with nonserous histology, early FIGO stage, and low preoperative CA-125 levels (P40% of MMP-14-positive cells) was inversely associated with progression using visual assessment (hazard ratio=0.39; 95% confidence interval: 0.18-0.82). A similar association was observed with the highest quartile of MMP-14-positive area assessed by digital image analysis (hazard ratio=0.48; 95% confidence interval: 0.28-0.82). After adjustment for standard prognostic factors, these associations were no longer significant in the ovarian carcinoma cohort. However, in women with serous carcinoma, the highest quartile of MMP-14-positive area was associated with progression (adjusted hazard ratio=0.48; 95% confidence interval: 0.24-0.99). There was no association with overall survival. The digital image analysis of MMP-14-positive area matched the visual assessment using three categories (>40% vs 21-40 vs <20%). Higher levels of MMP-14 immunostaining were associated with standard

  4. Tumor growth inhibition through targeting liposomally bound curcumin to tumor vasculature.

    Science.gov (United States)

    Mondal, Goutam; Barui, Sugata; Saha, Soumen; Chaudhuri, Arabinda

    2013-12-28

    Increasing number of Phase I/II clinical studies have demonstrated clinical potential of curcumin for treatment of various types of human cancers. Despite significant anti-tumor efficacies and bio-safety profiles of curcumin, poor systemic bioavailability is retarding its clinical success. Efforts are now being directed toward developing stable formulations of curcumin using various drug delivery systems. To this end, herein we report on the development of a new tumor vasculature targeting liposomal formulation of curcumin containing a lipopeptide with RGDK-head group and two stearyl tails, di-oleyolphosphatidylcholine (DOPC) and cholesterol. We show that essentially water insoluble curcumin can be solubilized in fairly high concentrations (~500 μg/mL) in such formulation. Findings in the Annexin V/Propidium iodide (PI) binding based flow cytometric assays showed significant apoptosis inducing properties of the present curcumin formulation in both endothelial (HUVEC) and tumor (B16F10) cells. Using syngeneic mouse tumor model, we show that growth of solid melanoma tumor can be inhibited by targeting such liposomal formulation of curcumin to tumor vasculature. Results in immunohistochemical staining of the tumor cryosections are consistent with tumor growth inhibition being mediated by apoptosis of tumor endothelial cells. Findings in both in vitro and in vivo mechanistic studies are consistent with the supposition that the presently described liposomal formulation of curcumin inhibits tumor growth by blocking VEGF-induced STAT3 phosphorylation in tumor endothelium. To the best of our knowledge, this is the first report on inhibiting tumor growth through targeting liposomal formulation of curcumin to tumor vasculatures.

  5. Assessment of electrochemical properties of a biogalvanic system for tissue characterisation

    Science.gov (United States)

    Chandler, J.H.; Culmer, P.R.; Jayne, D.G.; Neville, A.

    2015-01-01

    Biogalvanic characterisation is a promising method for obtaining health-specific tissue information. However, there is a dearth of understanding in the literature regarding the underlying galvanic cell, electrode reactions and their controlling factors which limits the application of the technique. This work presents a parametric electrochemical investigation into a zinc–copper galvanic system using salt (NaCl) solution analogues at physiologically-relevant concentrations (1.71, 17.1 & 154 mM). The potential difference at open cell, closed cell maximum current and the internal resistance (based on published characterisation methods) were measured. Additionally, independent and relative polarisation scans of the electrodes were performed to improve understanding of the system. Our findings suggest that the prominent reaction at the cathode is that of oxygen-reduction, not hydrogen-evolution. Results indicate that cell potentials are influenced by the concentration of dissolved oxygen at low currents and maximum closed cell currents are limited by the rate of oxygen diffusion to the cathode. Characterised internal resistance values for the salt solutions did not correspond to theoretical values at the extremes of concentration (1.71 and 154 mM) due to electrode resistance and current limitation. Existing biogalvanic models do not consider these phenomena and should be improved to advance the technique and its practical application. PMID:25460609

  6. Synthesis, characterization and in vitro cytotoxicity assessment of hydroxyapatite from different bioresources for tissue engineering application

    Indian Academy of Sciences (India)

    Sudip Mondal; Rajashree Bardhan; Biswanath Mondal; Apurba Dey; Sudit S Mukhopadhyay; Syamal Roy; Rajan Guha; Koushik Roy

    2012-08-01

    In the present study, hydroxyapatite (HAp) is synthesized from different biosources like eggshell, fish scale and bovine bone in a cost effective and ecofriendly way. HAp materials were synthesized from eggshell by wet precipitation method whereas thermal decomposition method was applied in case of fish scale and bovine bone. The phase purity and crystallinity of different calcined HAp powder were determined by XRD and FTIR analyses. The thermogravimetric analysis was carried out to show thermal stability of HAp powder. Average grain sizes of sintered samples were in submicron range. The morphology of the powders were observed under scanning electron microscopy (SEM). The dried powders were wet ball milled for several hours and surfactants like Triton-X small fillers (2 / 4 mm long rod-shaped) were made for in vitro testing. In order to verify the biocompatibility of HAp powders, cytotoxicity evaluation was carried out in RAW macrophage like cell line media for an incubation period of 72 h. The cell attachment studies on HAp compacts show an excellent affinity between cells and compact surface. These results proved high biocompatibility of HAp powders obtained fromdifferent biosources for tissue engineering applications.

  7. Assessment of electrochemical properties of a biogalvanic system for tissue characterisation.

    Science.gov (United States)

    Chandler, J H; Culmer, P R; Jayne, D G; Neville, A

    2015-02-01

    Biogalvanic characterisation is a promising method for obtaining health-specific tissue information. However, there is a dearth of understanding in the literature regarding the underlying galvanic cell, electrode reactions and their controlling factors which limits the application of the technique. This work presents a parametric electrochemical investigation into a zinc–copper galvanic system using salt (NaCl) solution analogues at physiologically-relevant concentrations (1.71, 17.1 & 154 mM). The potential difference at open cell, closed cell maximum current and the internal resistance (based on published characterisation methods) were measured. Additionally, independent and relative polarisation scans of the electrodes were performed to improve understanding of the system. Our findings suggest that the prominent reaction at the cathode is that of oxygen-reduction, not hydrogen-evolution. Results indicate that cell potentials are influenced by the concentration of dissolved oxygen at low currents and maximum closed cell currents are limited by the rate of oxygen diffusion to the cathode. Characterised internal resistance values for the salt solutions did not correspond to theoretical values at the extremes of concentration (1.71 and 154 mM) due to electrode resistance and current limitation. Existing biogalvanic models do not consider these phenomena and should be improved to advance the technique and its practical application.

  8. Tissue elasticity quantification by acoustic radiation force impulse for the assessment of renal allograft function.

    Science.gov (United States)

    He, Wan-Yuan; Jin, Yun-Jie; Wang, Wen-Ping; Li, Chao-Lun; Ji, Zheng-Biao; Yang, Cheng

    2014-02-01

    Acoustic radiation force impulse (ARFI) quantification, a novel ultrasound-based elastography method, has been used to measure liver fibrosis. However, few studies have been performed on the use of ARFI quantification in kidney examinations. We evaluated renal allograft stiffness using ARFI quantification in patients with stable renal function (n = 52) and those with biopsy-proven allograft dysfunction (n = 50). ARFI quantification, given as shear wave velocity (SWV), was performed. The resistance index (RI) was calculated by pulsed-wave Doppler ultrasound, and clinical and laboratory data were collected. Morphologic changes in transplanted kidneys were diagnosed by an independent pathologist. Mean SWV was more significantly negatively correlated with estimated glomerular filtration rate (eGFR) (r = -0.657, p renal allograft dysfunction were 72.0% and 86.5% (cutoff value = 2.625), respectively. The latter values were better than those of RI, which were 62.0% and 69.2% (cutoff value = 0.625), respectively. The coefficient of variation for repeat SWV measurements of the middle part of transplanted kidney was 8.64%, and inter-observer agreement on SWV was good (Bland-Altman method, ICC = 0.890). In conclusion, tissue elasticity quantification by ARFI is more accurate than the RI in diagnosing renal allograft function.

  9. A geometric flow for segmenting vasculature in proton-density weighted MRI.

    Science.gov (United States)

    Descoteaux, Maxime; Collins, D Louis; Siddiqi, Kaleem

    2008-08-01

    Modern neurosurgery takes advantage of magnetic resonance images (MRI) of a patient's cerebral anatomy and vasculature for planning before surgery and guidance during the procedure. Dual echo acquisitions are often performed that yield proton-density (PD) and T2-weighted images to evaluate edema near a tumor or lesion. In this paper we develop a novel geometric flow for segmenting vasculature in PD images, which can also be applied to the easier cases of MR angiography data or Gadolinium enhanced MRI. Obtaining vasculature from PD data is of clinical interest since the acquisition of such images is widespread, the scanning process is non-invasive, and the availability of vessel segmentation methods could obviate the need for an additional angiographic or contrast-based sequence during preoperative imaging. The key idea is to first apply Frangi's vesselness measure [Frangi, A., Niessen, W., Vincken, K.L., Viergever, M.A., 1998. Multiscale vessel enhancement filtering. In: International Conference on Medical Image Computing and Computer Assisted Intervention, vol. 1496 of Lecture Notes in Computer Science, pp. 130-137] to find putative centerlines of tubular structures along with their estimated radii. This measure is then distributed to create a vector field which allows the flux maximizing flow algorithm of Vasilevskiy and Siddiqi [Vasilevskiy, A., Siddiqi, K., 2002. Flux maximizing geometric flows. IEEE Transactions on Pattern Analysis and Machine Intelligence 24 (12), 1565-1578] to be applied to recover vessel boundaries. We carry out a qualitative validation of the approach on PD, MR angiography and Gadolinium enhanced MRI volumes and suggest a new way to visualize the segmentations in 2D with masked projections. We validate the approach quantitatively on a single-subject data set consisting of PD, phase contrast (PC) angiography and time of flight (TOF) angiography volumes, with an expert segmented version of the TOF volume viewed as the ground truth. We then

  10. Changes of the vasculature and innervation in the anterior segment of the RCS rat eye.

    Science.gov (United States)

    May, Christian Albrecht

    2011-12-01

    Investigating the anterior eye segment vasculature and innervation of dystrophic RCS rats, two major unique findings were observed: in the iris, young adult animals with retinal dystrophy showed an increase in substance P nerve fibres and a dilation of arterioles and capillaries. This finding continued during ageing. In the pars plana region, the surface covered by venules decreased continuously with age. In older animals, this decrease was parallelled by a local decrease of sympathetic TH-positive nerve fibres supplying these venules. For both conditions, no comparable data exists so far in the literature. They might point to a unique situation in the anterior eye segment of the dystrophic RCS rat.

  11. Ultrastructural analyses of the novel chimeric hemostatic agent generated via nanotechnology, ABS nanohemostat, at the renal tissue level.

    Science.gov (United States)

    Huri, Emre; Dogantekin, Engin; Hayran, Murvet; Malkan, Umit Yavuz; Ergun, Mine; Firat, Aysegul; Beyazit, Yavuz; Ustun, Huseyin; Kekilli, Murat; Dadali, Mumtaz; Astarci, Muzeyyen; Haznedaroglu, Ibrahim C

    2016-01-01

    Ankaferd Blood Stopper (ABS), a hemostatic agent of plant origin, has been registered for the prevention of clinical hemorrhages. Currently there is no data regarding the ultrastructural analysis of ABS at the tissue level. The aim of this study is to assess renal tissue effects via scanning electron microscopy (SEM) analyses for the ABS and ABS nanohemostat (formed by the combination of self-assembling peptide amphiphile molecules and ABS). SEM experiments were performed with FEI Nova NanoSEM 230, using the ETD detector at low vacuum mode with 30 keV beam energy. SEM analyses revealed that significant erythroid aggregation are present inside the capillary bed of the renal tissue. However, neither the signs of necrosis nor any other sign of tissue damage are evident in the surrounding renal tissue supplied by the microcapillary vasculature. Our study is important for several reasons. Firstly, in our study we used ABS nanohemostat which was recently developed. This study adds valuable information to the literature regarding ABS nanohemostat. Secondly, this study is the first ultrastructural analysis of ABS that was performed at the tissue level. Thirdly, we disclosed that ABS nanohemostat could induce vital erythroid aggregation at the renal tissue level as detected by SEM. Lastly, we detected that ABS nanohemostat causes no harm to the tissues including necrosis and any other detrimental effects.

  12. Noninvasive NIR measurement of tissue pH to assess hemorrhagic shock in swine

    Science.gov (United States)

    Soller, Babs R.; Zhang, Songbiao; Micheels, Ronald H.; Puyana, Juan C.

    1999-07-01

    Body-worn noninvasive physilogical sensors are needed to continuously monitor soldiers for hemorrhage and to provide real-time information for minimally skilled medics to treat the injured. In the hospital intramucosal pHi of the gut is used to monitor shock and its treatment. We hypothesize that abdominal wall muscle (AWM) pH can be measured noninvasively using near infrared (NIR) spectroscopy and partial least squares analysis (PLS) and will correlate with pHi. METHODS: AWM pH was measured with microelectrodes and gastric pHi was measured with a tonometric catheter simultaneously while NIR spectra were collected using prototype LED spectrometers placed on the pig's flanks. Animals were subject to hemorrhagic shock at 45 mm Hg for 45 minutes, then resuscitated with blood and lactated ringers. Relationships between electrode pH, pHi and NIR spectra were developed using PLS with cross validation. RESULTS: NIR spectral changes noninvasively acquired through the skin were shown to be from the muscle, not from changes in skin blood flow. Trending ability (R2) model accuracy (RMSD), and relative error were calculated for individual pigs. Using electrode pH as the reference, average R2 was 0.88 with a predicted accuracy of 0.17 pH units, a 9.3% relative error. Slightly degraded results were observed when pHi was used as a reference. CONCLUSIONS: NIR measurement of tissue pH can be used to noninvasively monitor for shock and guide its treatment in a swine model. These measurements correlate with gastric pHi, a clinically accepted measure of shock, providing an approach to develop similar methodology for humans.

  13. Quantitative Assessment of Breast Parenchymal Uptake on 18F-FDG PET/CT: Correlation with Age, Background Parenchymal Enhancement, and Amount of Fibroglandular Tissue on MRI.

    Science.gov (United States)

    Leithner, Doris; Baltzer, Pascal A; Magometschnigg, Heinrich F; Wengert, Georg J; Karanikas, Georgios; Helbich, Thomas H; Weber, Michael; Wadsak, Wolfgang; Pinker, Katja

    2016-10-01

    Background parenchymal enhancement (BPE), and the amount of fibroglandular tissue (FGT) assessed with MRI have been implicated as sensitive imaging biomarkers for breast cancer. The purpose of this study was to quantitatively assess breast parenchymal uptake (BPU) on (18)F-FDG PET/CT as another valuable imaging biomarker and examine its correlation with BPE, FGT, and age.

  14. Assessment of global DNA methylation in the first trimester fetal tissues exposed to maternal cigarette smoking

    DEFF Research Database (Denmark)

    Fa, Svetlana; Larsen, Trine Vilsbøll; Bilde, Katrine;

    2016-01-01

    AIMS: Maternal cigarette smoking during pregnancy increases the risk of negative health consequences for the exposed child. Epigenetic mechanisms constitute a likely link between the prenatal exposure to maternal cigarette smoking and the increased risk in later life for diverse pathologies....... Maternal smoking induces gene-specific DNA methylation alterations as well as global DNA hypermethylation in the term placentas and hypomethylation in the cord blood. Early pregnancy represents a developmental time where the fetal epigenome is remodeled and accordingly can be expected to be highly prone...... to exposures with an epigenetic impact. We have assessed the influence of maternal cigarette smoking during the first trimester for fetal global DNA methylation. METHODS AND RESULTS: We analyzed the human fetal intestines and livers as well as the placentas from the first trimester pregnancies. Global DNA...

  15. Assessment of tissue heterogeneity using diffusion tensor and diffusion kurtosis imaging for grading gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Raja, Rajikha; Sinha, Neelam [International Institute of Information Technology-Bangalore, Bangalore (India); Saini, Jitender; Mahadevan, Anita; Rao, K.V.L. Narasinga; Swaminathan, Aarthi [National Institute of Mental Health and Neurosciences, Bangalore (India)

    2016-12-15

    In this work, we aim to assess the significance of diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) parameters in grading gliomas. Retrospective studies were performed on 53 subjects with gliomas belonging to WHO grade II (n = 19), grade III (n = 20) and grade IV (n = 14). Expert marked regions of interest (ROIs) covering the tumour on T2-weighted images. Statistical texture measures such as entropy and busyness calculated over ROIs on diffusion parametric maps were used to assess the tumour heterogeneity. Additionally, we propose a volume heterogeneity index derived from cross correlation (CC) analysis as a tool for grading gliomas. The texture measures were compared between grades by performing the Mann-Whitney test followed by receiver operating characteristic (ROC) analysis for evaluating diagnostic accuracy. Entropy, busyness and volume heterogeneity index for all diffusion parameters except fractional anisotropy and anisotropy of kurtosis showed significant differences between grades. The Mann-Whitney test on mean diffusivity (MD), among DTI parameters, resulted in the highest discriminability with values of P = 0.029 (0.0421) for grade II vs. III and P = 0.0312 (0.0415) for III vs. IV for entropy (busyness). In DKI, mean kurtosis (MK) showed the highest discriminability, P = 0.018 (0.038) for grade II vs. III and P = 0.022 (0.04) for III vs. IV for entropy (busyness). Results of CC analysis illustrate the existence of homogeneity in volume (uniformity across slices) for lower grades, as compared to higher grades. Hypothesis testing performed on volume heterogeneity index showed P values of 0.0002 (0.0001) and 0.0003 (0.0003) between grades II vs. III and III vs. IV, respectively, for MD (MK). In summary, the studies demonstrated great potential towards automating grading gliomas by employing tumour heterogeneity measures on DTI and DKI parameters. (orig.)

  16. Assessment of Soft Tissue Changes by Cephalometry and Two-Dimensional Photogrammetry in Bilateral Sagittal Split Ramus Osteotomy Cases

    Directory of Open Access Journals (Sweden)

    Jan Rustemeyer

    2011-07-01

    Full Text Available Objectives: We aimed to compare the standard methods of cephalometry and two-dimensional photogrammetry, to evaluate the reliability and accuracy of both methods.Material and Methods: Twenty-six patients (mean age 25.5, standard deviation (SD 5.2 years with Class II relationship and 23 patients with Class III relationship (mean age 26.4, SD 4.7 years who had undergone bilateral sagittal split ramus osteotomy were selected, with a median follow-up of 8 months between pre- and postsurgical evaluation. Pre- and postsurgical cephalograms and lateral photograms were traced and changes were recorded.Results: Pre- and postsurgical measurements of hard tissue angles and distances revealed higher correlations with cephalometrically performed soft tissue measurements of facial convexity (Class II: N-PG, r = - 0.50, P = 0.047; Class III: ANB, r = 0.73, P = 0.005; NaPg , r = 0.71, P = 0.007; and labiomental angle (Class II: SNB, r = 0.72, P = 0.002; ANB, r = - 0.72, P = 0.002; N-B, r = - 0.68, P = 0.004; ANS-Gn, r = 0.71, P = 0.002; Class III: ANS-Gn, r = 0.65, P = 0.043 compared with two-dimensional photogrammetry. However, two-dimensional photogrammetry revealed higher correlation between lower lip length and cephalometrically assessed angular hard tissue changes (Class II: SNB, r = 0.98, P = 0.007; N-B, r = 0.89, P = 0.037; N-Pg, r = 0.90, P = 0.033; Class III: SNB, r = - 0.54, P = 0.060; NAPg, r = - 0.65, P = 0.041; N-Pg, r = 0.58, P = 0.039.Conclusions: Our findings suggest that cephalometry and two-dimensional photogrammetry offer the possibility to complement one another.

  17. An automated method for analysis of microcirculation videos for accurate assessment of tissue perfusion

    Directory of Open Access Journals (Sweden)

    Demir Sumeyra U

    2012-12-01

    Full Text Available Abstract Background Imaging of the human microcirculation in real-time has the potential to detect injuries and illnesses that disturb the microcirculation at earlier stages and may improve the efficacy of resuscitation. Despite advanced imaging techniques to monitor the microcirculation, there are currently no tools for the near real-time analysis of the videos produced by these imaging systems. An automated system tool that can extract microvasculature information and monitor changes in tissue perfusion quantitatively might be invaluable as a diagnostic and therapeutic endpoint for resuscitation. Methods The experimental algorithm automatically extracts microvascular network and quantitatively measures changes in the microcirculation. There are two main parts in the algorithm: video processing and vessel segmentation. Microcirculatory videos are first stabilized in a video processing step to remove motion artifacts. In the vessel segmentation process, the microvascular network is extracted using multiple level thresholding and pixel verification techniques. Threshold levels are selected using histogram information of a set of training video recordings. Pixel-by-pixel differences are calculated throughout the frames to identify active blood vessels and capillaries with flow. Results Sublingual microcirculatory videos are recorded from anesthetized swine at baseline and during hemorrhage using a hand-held Side-stream Dark Field (SDF imaging device to track changes in the microvasculature during hemorrhage. Automatically segmented vessels in the recordings are analyzed visually and the functional capillary density (FCD values calculated by the algorithm are compared for both health baseline and hemorrhagic conditions. These results were compared to independently made FCD measurements using a well-known semi-automated method. Results of the fully automated algorithm demonstrated a significant decrease of FCD values. Similar, but more variable FCD

  18. Targeting the tumour vasculature: exploitation of low oxygenation and sensitivity to NOS inhibition by treatment with a hypoxic cytotoxin.

    Science.gov (United States)

    Baker, Jennifer H E; Kyle, Alastair H; Bartels, Kirsten L; Methot, Stephen P; Flanagan, Erin J; Balbirnie, Andrew; Cran, Jordan D; Minchinton, Andrew I

    2013-01-01

    Many cancer research efforts focus on exploiting genetic-level features that may be targeted for therapy. Tissue-level features of the tumour microenvironment also represent useful therapeutic targets. Here we investigate the presence of low oxygen tension and sensitivity to NOS inhibition of tumour vasculature as potential tumour-specific features that may be targeted by hypoxic cytotoxins, a class of therapeutics currently under investigation. We have previously demonstrated that tirapazamine (TPZ) mediates central vascular dysfunction in tumours. TPZ is a hypoxic cytotoxin that is also a competitive inhibitor of NOS. Here we further investigated the vascular-targeting activity of TPZ by combining it with NOS inhibitor L-NNA, or with low oxygen content gas breathing. Tumours were analyzed via multiplex immunohistochemical staining that revealed irreversible loss of perfusion and enhanced tumour cell death when TPZ was combined with either low oxygen or a NOS inhibitor. Tumour growth rate was reduced by TPZ + NOS inhibition, and tumours previously resistant to TPZ-mediated vascular dysfunction were sensitized by low oxygen breathing. Additional mapping analysis suggests that tumours with reduced vascular-associated stroma may have greater sensitivity to these effects. These results indicate that poorly oxygenated tumour vessels, also being abnormally organized and with inadequate smooth muscle, may be successfully targeted for significant anti-cancer effects by inhibition of NOS and hypoxia-activated prodrug toxicity. This strategy illustrates a novel use of hypoxia-activated cytotoxic prodrugs as vascular targeting agents, and also represents a novel mechanism for targeting tumour vessels.

  19. Infrared thermography for indirect assessment of activation of brown adipose tissue in lean and obese male subjects.

    Science.gov (United States)

    El Hadi, Hamza; Frascati, Andrea; Granzotto, Marnie; Silvestrin, Valentina; Ferlini, Elisabetta; Vettor, Roberto; Rossato, Marco

    2016-12-01

    Brown adipose tissue (BAT) plays a key role in adaptive thermogenesis in mammals, and it has recently been considered as an attractive therapeutic target for tackling human obesity by increasing energy expenditure. Thermal imaging using infrared thermography (IRT) has emerged as a potential safe, rapid and inexpensive technique for detecting BAT in humans. However, little attention has been given to the reliability of this method in obese subjects. To this end, we evaluated the capacity of IRT to detect activated supraclavicular (SCV) BAT in 14 lean and 16 mildly obese young adults after acute cold exposure. Using IRT we measured the temperature of the skin overlying the SCV and sternal areas at baseline and after acute cold stimulation. Additionally, energy expenditure was measured by indirect calorimetry and body composition was estimated using bioelectrical impedance analysis. Energy expenditure and SCV skin temperature significantly increased in lean subjects upon cold exposure, while no significant changes were detected in the obese group. Furthermore, cold-induced variations in SCV skin temperature of obese subjects showed a negative correlation with body mass index. This study suggests that in lean individuals BAT is a rapidly activated thermogenic tissue possibly involved in the regulation of energy balance, and can be indirectly assessed using IRT. In obese subjects, BAT seems less prone to be activated by cold exposure, with the degree of adiposity representing a limiting factor for the indirect detection of BAT activation by measuring the skin temperature overlying BAT.

  20. Assessment of the relationships among posture, maxillomandibular denture complex, and soft-tissue profile of aesthetic adult Korean women.

    Science.gov (United States)

    Choi, B; Baek, S H; Yang, W S; Kim, S

    2000-11-01

    The objective of this study was to assess the relationships among the posture, the maxillomandibular denture complex, and the soft-tissue profile of aesthetic adult Korean women. From an initial group of 346 women, the authors examined 28 beautiful adult Korean women who had normal vertical and sagittal skeletal relationships and normal occlusion. There were no differences in the inclinations of the incisors to the occlusal planes in the maxilla and the mandible in the data for Korean women vs. Arnett's data for white women. However, the overbite and overjet in Korean women were slightly smaller than in white women. AB to maxillary occlusal plane angle (MxOP) represented the anteroposterior denture base discrepancy to the occlusal plane. Angulation of the maxillary occlusal plane to the Frankfurt (FH) plane and the true vertical line at submasale (TVL) (Sn) was a little steeper in Korean women than in white women. The FH plane was almost parallel to the true horizontal line in Korean women who had normal vertical and sagittal skeletal relationships and normal occlusion. With regard to soft-tissue variables, the upper lip length (Sn-Stms), interlabial gap, upper incisor exposure, nasolabial angle, lip and nose tip projection value, and TVL (Sn)-to-upper lip line (UL) angle showed interracial differences. The results of this study can assist in the diagnosis and treatment planning of orthognathic surgery.

  1. Assessment of Control Tissue for Gene and Protein Expression Studies: A Comparison of Three Alternative Lung Sources

    Directory of Open Access Journals (Sweden)

    Margaret R. Passmore

    2012-01-01

    Full Text Available The use of an appropriate control group in human research is essential in investigating the level of a pathological disorder. This study aimed to compare three alternative sources of control lung tissue and to determine their suitability for gene and protein expression studies. Gene and protein expression levels of the vascular endothelial growth factor (VEGF and gelatinase families and their receptors were measured using real-time reverse transcription polymerase chain reaction (RT-PCR and immunohistochemistry. The gene expression levels of VEGFA, placental growth factor (PGF, and their receptors, fms-related tyrosine kinase 1 (FLT1, and kinase insert domain receptor (KDR as well as matrix metalloproteinase-2 (MMP-2 and the inhibitors, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1 and TIMP-2 were significantly higher in lung cancer resections. The gene expression level of MMP-9 was significantly lower in the corresponding samples. Altered protein expression was also detected, depending on the area assessed. The results of this study show that none of the three control groups studied are completely suitable for gene and protein studies associated with the VEGF and gelatinase families, highlighting the need for researchers to be selective in which controls they opt for.

  2. Multimodal assessment of spatial distribution of drug-tracer uptake by brain tissue after intra-arterial injections

    Science.gov (United States)

    Singh-Moon, Rajinder; Chaudhuri, Durba; Wang, Mei; Straubinger, Robert; Bigio, Irving J.; Joshi, Shailendra

    2014-02-01

    It is challenging to track the rapid changes in drug concentrations after intra-arterial (IA) administration to elucidate the pharmacokinetics of this method of drug delivery. Traditional pharmacokinetic parameters (such as protein binding) that are highly relevant to intravenous (IV) administration do not seem to apply to IA injections. Regional drug delivery is affected by the biomechanics of drug injection, resting blood flow, and local tissue extraction. In-vivo and ex-vivo, optical methods for spatial mapping of drug deposition can assist in visualizing drug distributions and aid in the screening of potential drugs and carrier candidates. We present a multimodal approach for the assessment of drug distribution in postmortem tissue specimens using diffuse reflectance spectroscopy, multispectral imaging, and confocal microscopy and demonstrate feasibility of distinguishing route of administration advantages of liposome-dye conjugate delivery. The results of this study suggest that insight on drug dynamics gained by this aggregated approach can be used to help screen and/or optimize potential drug candidates and drug delivery protocols.

  3. Cosmos 1887: morphology, histochemistry, and vasculature of the growing rat tibia

    Science.gov (United States)

    Doty, S. B.; Morey-Holton, E. R.; Durnova, G. N.; Kaplansky, A. S.

    1990-01-01

    Light microscopy, electron microscopy, and enzyme histochemistry were used to study the effects of spaceflight on metaphyseal and cortical bone of the rat tibia. Cortical cross-sectional area and perimeter were not altered by a 12.5-day spaceflight in 3-month-old male rats. The endosteal osteoblast population and the vasculature near the periosteal surface in flight rats compared with ground controls showed more pronounced changes in cortical bone than in metaphyseal bone. The osteoblasts demonstrated greater numbers of transitional Golgi vesicles, possibly caused by a decreased cellular metabolic energy source, but no difference in the large Golgi saccules or the cell membrane-associated alkaline phosphatase activity. The periosteal vasculature in the diaphysis of flight rats often showed lipid accumulations within the lumen of the vessels, occasional degeneration of the vascular wall, and degeneration of osteocytes adjacent to vessels containing intraluminal deposits. These changes were not found in the metaphyseal region of flight animals. The focal vascular changes may be due to ischemia of bone or a developing fragility of the vessel walls as a result of spaceflight.

  4. Biomimetic carriers mimicking leukocyte plasma membrane to increase tumor vasculature permeability

    Science.gov (United States)

    Palomba, R.; Parodi, A.; Evangelopoulos, M.; Acciardo, S.; Corbo, C.; De Rosa, E.; Yazdi, I. K.; Scaria, S.; Molinaro, R.; Furman, N. E. Toledano; You, J.; Ferrari, M.; Salvatore, F.; Tasciotti, E.

    2016-10-01

    Recent advances in the field of nanomedicine have demonstrated that biomimicry can further improve targeting properties of current nanotechnologies while simultaneously enable carriers with a biological identity to better interact with the biological environment. Immune cells for example employ membrane proteins to target inflamed vasculature, locally increase vascular permeability, and extravasate across inflamed endothelium. Inspired by the physiology of immune cells, we recently developed a procedure to transfer leukocyte membranes onto nanoporous silicon particles (NPS), yielding Leukolike Vectors (LLV). LLV are composed of a surface coating containing multiple receptors that are critical in the cross-talk with the endothelium, mediating cellular accumulation in the tumor microenvironment while decreasing vascular barrier function. We previously demonstrated that lymphocyte function-associated antigen (LFA-1) transferred onto LLV was able to trigger the clustering of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells. Herein, we provide a more comprehensive analysis of the working mechanism of LLV in vitro in activating this pathway and in vivo in enhancing vascular permeability. Our results suggest the biological activity of the leukocyte membrane can be retained upon transplant onto NPS and is critical in providing the particles with complex biological functions towards tumor vasculature.

  5. Swept-source OCT Angiography of the Retinal Vasculature using Intensity Differentiation Based OMAG Algorithms

    Science.gov (United States)

    Huang, Yanping; Zhang, Qinqin; Thorell, Mariana Rossi; An, Lin; Durbin, Mary; Laron, Michal; Sharma, Utkarsh; Gregori, Giovanni; Rosenfeld, Philip J.; Wang, Ruikang K

    2014-01-01

    Background and Objective To demonstrate the feasibility of using a 1050 nm swept-source OCT (SS-OCT) system to achieve noninvasive retinal vasculature imaging in human eyes. Materials and Methods Volumetric datasets were acquired using a ZEISS 1 µm SS-OCT prototype that operated at an A-line rate of 100 kHz. A scanning protocol designed to allow for motion contrast processing, referred to as OCT angiography or optical microangiography (OMAG), was used to scan ~3 mm × 3 mm area in the central macular region of the retina within ~4.5 seconds. Intensity differentiation based OMAG algorithm was used to extract 3-D retinal functional microvasculature information. Results Intensity signal differentiation generated capillary-level resolution en face OMAG images of the retina. The parafoveal capillaries were clearly visible, thereby allowing visualization of the foveal avascular zone (FAZ) in normal subjects. Conclusion The capability of OMAG to produce retinal vascular images was demonstrated using the ZEISS 1 µm SS-OCT prototype. This technique can potentially have clinical value for studying retinal vasculature abnormalities. PMID:25230403

  6. Residual motion compensation in ECG-gated interventional cardiac vasculature reconstruction

    Science.gov (United States)

    Schwemmer, C.; Rohkohl, C.; Lauritsch, G.; Müller, K.; Hornegger, J.

    2013-06-01

    Three-dimensional reconstruction of cardiac vasculature from angiographic C-arm CT (rotational angiography) data is a major challenge. Motion artefacts corrupt image quality, reducing usability for diagnosis and guidance. Many state-of-the-art approaches depend on retrospective ECG-gating of projection data for image reconstruction. A trade-off has to be made regarding the size of the ECG-gating window. A large temporal window is desirable to avoid undersampling. However, residual motion will occur in a large window, causing motion artefacts. We present an algorithm to correct for residual motion. Our approach is based on a deformable 2D-2D registration between the forward projection of an initial, ECG-gated reconstruction, and the original projection data. The approach is fully automatic and does not require any complex segmentation of vasculature, or landmarks. The estimated motion is compensated for during the backprojection step of a subsequent reconstruction. We evaluated the method using the publicly available CAVAREV platform and on six human clinical datasets. We found a better visibility of structure, reduced motion artefacts, and increased sharpness of the vessels in the compensated reconstructions compared to the initial reconstructions. At the time of writing, our algorithm outperforms the leading result of the CAVAREV ranking list. For the clinical datasets, we found an average reduction of motion artefacts by 13 ± 6%. Vessel sharpness was improved by 25 ± 12% on average.

  7. Pulmonary MR imaging with ultra-short TEs: Utility for disease severity assessment of connective tissue disease patients

    Energy Technology Data Exchange (ETDEWEB)

    Ohno, Yoshiharu, E-mail: yosirad@kobe-u.ac.jp [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Nishio, Mizuho [Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Koyama, Hisanobu [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Takenaka, Daisuke [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Department of Radiology, Hyogo Cancer Center, Akashi, Hyogo (Japan); Takahashi, Masaya [Advanced Imaging Research Center, Department of Radiology, University of Texas Southwestern Medical Center, Houston, TX (United States); Yoshikawa, Takeshi; Matsumoto, Sumiaki [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Obara, Makoto; Cauteren, Marc van [Philips Electronics Japan, Tokyo (Japan); Sugimura, Kazuro [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan)

    2013-08-15

    Purpose: To evaluate the utility of pulmonary magnetic resonance (MR) imaging with ultra-short echo times (UTEs) at a 3.0 T MR system for pulmonary functional loss and disease severity assessments of connective tissue disease (CTD) patients with interstitial lung disease (ILD). Materials and methods: This prospective study was approved by the institutional review board, and written informed consent was obtained from 18 CTD patients (eight men and ten women) and eight normal subjects with suspected chest disease (three men and five women). All subjects underwent thin-section MDCT, pulmonary MR imaging with UTEs, pulmonary function test and serum KL-6. Regional T2* maps were generated from each MR data set, and mean T2* values were determined from ROI measurements. From each thin-section MDCT data set, CT-based disease severity was evaluated with a visual scoring system. Mean T2* values for normal and CTD subjects were statistically compared by using Student's t-test. To assess capability for pulmonary functional loss and disease severity assessments, mean T2* values were statistically correlated with pulmonary functional parameters, serum KL-6 and CT-based disease severity. Results: Mean T2* values for normal and CTD subjects were significantly different (p = 0.0019) and showed significant correlations with %VC, %DL{sub CO}, serum KL-6 and CT-based disease severity of CTD patients (p < 0.05). Conclusion: Pulmonary MR imaging with UTEs is useful for pulmonary functional loss and disease severity assessments of CTD patients with ILD.

  8. A pilot study of morphometric analysis of choroidal vasculature in vivo, using en face optical coherence tomography.

    Directory of Open Access Journals (Sweden)

    Mahsa Sohrab

    Full Text Available PURPOSE: To study the ability of volumetric spectral domain optical coherence tomography (SD-OCT to perform quantitative measurement of the choroidal vasculature in vivo. METHODS: Choroidal vascular density and vessel size were quantified using en face choroidal scans from various depths below the retinal pigment epithelium (RPE in 58 eyes of 58 patients with either epiretinal membranes (ERM, early age-related macular degeneration (AMD, or reticular pseudo-drusen (RPD. For each patient, we used the macular volume scan (6×6 mm cube for vessel quantification, while high-definition (HD cross-section raster scans were used to qualitatively assess vascularity of the choroidal sub-layers, and measure choroidal thickness. RESULTS: Of the 58 patients, more were female (66% versus 34% male, of whom 14 (24% had ERM, 11 (19% early AMD, and 33 (57% RPD. Compared to intact choriocapillaris in all ERM (100%, none of the RPD and only 5/11 (45% early AMD eyes had visible choriocapillaris on either cross section or C-scans (p-value<0.001. When comparing select regions from the most superficial C-scans, early AMD group had lowest vascular density and RPD had highest (p-value 0.04. Qualitative evaluation of C-scans from all three groups revealed a more granular appearance of the choriocapillaris in ERM versus increased stroma and larger vessels in the RPD eyes. CONCLUSIONS: SD-OCT can be used to qualitatively and quantitatively assess choroidal vascularity in vivo. Our findings correlate to previously reported histopathologic studies. Lack of choriocapillaris on HD cross-sections or C-scans in all RPD and about half of early AMD eyes suggests earlier choroidal involvement in AMD and specifically, RPD.

  9. Mass transfer trends occurring in engineered ex vivo tissue scaffolds.

    Science.gov (United States)

    Moore, Marc; Sarntinoranont, Malisa; McFetridge, Peter

    2012-08-01

    In vivo the vasculature provides an effective delivery system for cellular nutrients; however, artificial scaffolds have no such mechanism, and the ensuing limitations in mass transfer result in limited regeneration. In these investigations, the regional mass transfer properties that occur through a model scaffold derived from the human umbilical vein (HUV) were assessed. Our aim was to define the heterogeneous behavior associated with these regional variations, and to establish if different decellularization technologies can modulate transport conditions to improve microenvironmental conditions that enhance cell integration. The effect of three decellularization methods [Triton X-100 (TX100), sodium dodecyl sulfate (SDS), and acetone/ethanol (ACE/EtOH)] on mass transfer, cellular migration, proliferation, and metabolic activity were assessed. Results show that regional variation in tissue structure and composition significantly affects both mass transfer and cell function. ACE/EtOH decellularization was shown to increase albumin mass flux through the intima and proximate-medial region (0-250 μm) when compared with sections decellularized with TX100 or SDS; although, mass flux remained constant over all regions of the full tissue thickness when using TX100. Scaffolds decellularized with TX100 were shown to promote cell migration up to 146% further relative to SDS decellularized samples. These results show that depending on scaffold derivation and expectations for cellular integration, specificities of the decellularization chemistry affect the scaffold molecular architecture resulting in variable effects on mass transfer and cellular response.

  10. A meta-analysis to assess the effect of the composition of dietary fat on α-tocopherol blood and tissue concentration in pigs.

    Science.gov (United States)

    Prévéraud, D P; Desmarchelier, C; Rouffineau, F; Devillard, E; Borel, P

    2015-03-01

    A meta-analysis based on the results from 13 selected publications was performed to assess the effect of dietary fat supplementation (quantity and fatty acid composition) on α-tocopherol (TOL) concentration in 4 pig tissues (blood, liver, muscle, and adipose tissue). Dietary fat supplementation was defined by the quantity of fat added to the basal diet and its fatty acid profile. After standardization of tissue TOL concentration (as the dependent variable), statistical analyses were performed using multiple nonlinear regression, data partitioning, and partial least squares regression with 7 predictor variables including added vitamin E (VE), added fat, PUFA (% fat), MUFA (% fat), SFA (% fat), omega-3 fatty acids (-3; % fat), and omega-6 fatty acids (-6; % fat). The statistical analyses first showed that the VE level in the diet was the main factor that modulates tissue TOL concentration. The dose-response relationship followed a logarithmic curve, with a saturation of tissue TOL concentration in all the studied tissues. Moreover, the amount of dietary fat, at least up to 20%, was not linearly correlated with tissue TOL concentration, considering that the main fatty acid classes, MUFA and, to a lesser extent, SFA, were positively associated with tissue TOL concentrations. Finally, this study suggests that the inclusion of -3 fatty acids in the diet may decrease tissue and, more precisely, blood TOL concentration.

  11. Three-dimensional imaging of the mouse heart and vasculature using micro-CT and whole-body perfusion of iodine or phosphotungstic acid.

    Science.gov (United States)

    Dunmore-Buyze, P Joy; Tate, Elsbeth; Xiang, Fu-li; Detombe, Sarah A; Nong, Zengxuan; Pickering, J Geoffrey; Drangova, Maria

    2014-01-01

    Recent studies have investigated histological staining compounds as micro-computed tomography (micro-CT) contrast agents, delivered by soaking tissue specimens in stain and relying on passive diffusion for agent uptake. This study describes a perfusion approach using iodine or phosphotungstic acid (PTA) stains, delivered to an intact mouse, to capitalize on the microvasculature as a delivery conduit for parenchymal staining and direct contact for staining artery walls. Twelve C57BL/6 mice, arterially perfused with either 25% Lugol's solution or 5% PTA solution were scanned intact and reconstructed with 26 µm isotropic voxels. The animals were fixed and the heart and surrounding vessels were excised, embedded and scanned; isolated heart images were reconstructed with 13 µm isotropic voxels. Myocardial enhancement and artery diameters were measured. Both stains successfully enhanced the myocardium and vessel walls. Interestingly, Lugol's solution provided a significantly higher enhancement of the myocardium than PTA [2502 ± 437 vs 656 ± 178 Hounsfield units (HU); p Lugol's, 1036 ± 635 HU; PTA, 738 ± 124 HU; p = 0.29), but coronary arteries were more effectively segmented from the PTA-stained hearts, enabling segmented imaging of fifth- order coronary artery branches. The combination of whole mouse perfusion delivery and use of heavy metal-containing stains affords high-resolution imaging of the mouse heart and vasculature by micro-CT. The differential imaging patterns of Lugol's- and PTA-stained tissues reveals new opportunities for micro-analyses of cardiac and vascular tissues.

  12. 23.4% saline decreases brain tissue volume in severe hepatic encephalopathy as assessed by a quantitative computed tomography marker

    Science.gov (United States)

    Liotta, Eric M; Lizza, Bryan D; Romanova, Anna L; Guth, James C; Berman, Michael D; Carroll, Timothy J; Francis, Brandon; Ganger, Daniel; Ladner, Daniela P; Maas, Matthew B; Naidech, Andrew M

    2016-01-01

    Objective Cerebral edema is common in severe hepatic encephalopathy and may be life-threatening. Bolus 23.4% hypertonic saline (HTS) improves surveillance neuromonitoring scores, although its mechanism of action is not clearly established. We investigated the hypothesis that bolus HTS decreases cerebral edema in severe hepatic encephalopathy utilizing a quantitative technique to measure brain and CSF volume changes. Design Retrospective analysis of serial computed tomography (CT) scans and clinical data for a case-control series was performed. Setting Intensive care units of a tertiary care hospital. Patients Patients with severe hepatic encephalopathy treated with 23.4% HTS and control patients who did not receive 23.4% HTS. Methods We used clinically obtained CT scans to measure volumes of the ventricles, intracranial CSF, and brain using a previously validated semi-automated technique (Analyze Direct; Overland Park, KS). Volumes before and after 23.4% HTS were compared with Wilcoxon signed-rank test. Associations between total CSF volume, ventricular volume, serum sodium, and Glasgow Coma Scale Scores were assessed using Spearman correlation. Results Eleven patients with 18 administrations of 23.4% HTS met inclusion criteria. Total CSF (median 47.6 [35.1–69.4] to 61.9 [47.7–87.0] mL, pbrain tissue volume. Total CSF and ventricular volume change may be useful quantitative measures to assess cerebral edema in severe hepatic encephalopathy. PMID:26308431

  13. Noninvasive Spatially Offset and Transmission Raman Mapping of Breast Tissue: A Multimodal Approach Towards the In Vivo Assessment of Tissue Pathology

    Science.gov (United States)

    2013-06-01

    construct geometry’s that cannot be molded. 3) Soybeans are being considered as an inclusion because they have very similar spectral properties to tissue...scattering properties of fatty tissue,2-4 were added to increase the scattering potential. 0.25ml or 1.25ml per 50ml of water were added to produce...target relative to the source and detector. b) PTFE to Intralipid Raman photon ratio as a function of phantom rotation, average of all fibers

  14. An Assessment of the Utility of Tissue Smears in Rapid Cancer Profiling with Desorption Electrospray Ionization Mass Spectrometry (DESI-MS)

    Science.gov (United States)

    Woolman, Michael; Tata, Alessandra; Bluemke, Emma; Dara, Delaram; Ginsberg, Howard J.; Zarrine-Afsar, Arash

    2017-01-01

    Mass spectrometry imaging with desorption electrospray ionization mass spectrometry (DESI-MS) is used to characterize cancer from ex vivo slices of tissues. The process is time-consuming. The use of tissue smears for DESI-MS analysis has been proposed as it eliminates the time required to snap-freeze and section the tissue. To assess the utility of tissue smears for rapid cancer characterization, principal component analysis (PCA) was performed to evaluate the concordance between DESI-MS profiles of breast cancer from tissue slices and smears prepared on various surfaces. PCA suggested no statistical discrimination between DESI-MS profiles of tissue sections and tissue smears prepared on glass, polytetrafluoroethylene (PTFE), and porous PTFE. However, the abundances of cancer biomarker ions varied between sections and smears, with DESI-MS analysis of tissue sections yielding higher ion abundances of cancer biomarkers compared with smears. Coefficient of variance (CV) analysis suggests DESI-MS profiles from tissue smears are as reproducible as the ones from tissue sections. The limit of detection with smear samples from single pixel analysis is comparable to tissue sections that average the signal from a tissue area of 0.01 mm2. The smears prepared on the PTFE surface possessed a higher degree of homogeneity compared with the smears prepared on the glass surface. This allowed single MS scans ( 1 s) from random positions across the surface of the smear to be used in rapid cancer typing with good reproducibility, providing pathologic information for cancer typing at speeds suitable for clinical utility.

  15. Oxygen saturation, red blood cell tissue fraction and speed resolved perfusion - A new optical method for microcirculatory assessment.

    Science.gov (United States)

    Jonasson, Hanna; Fredriksson, Ingemar; Pettersson, Anders; Larsson, Marcus; Strömberg, Tomas

    2015-11-01

    We have developed a new fiber-optic system that combines diffuse reflectance spectroscopy (DRS) and laser Doppler Flowmetry (LDF) for a multi-modal assessment of the microcirculation. Quantitative data is achieved with an inverse Monte Carlo algorithm based on an individually adaptive skin model. The output parameters are calculated from the model and given in absolute units: hemoglobin oxygen saturation (%), red blood cell (RBC) tissue fraction (%), and the speed resolved RBC perfusion separated into three speed regions; 0-1mm/s, 1-10mm/s and above 10mm/s (% mm/s). The aim was to explore microcirculatory parameters using the new optical method, integrating DRS and LDF in a joint skin model, during local heating of the dorsal foot and venous and arterial occlusion of the forearm in 23 healthy subjects (age 20-28years). There were differences in the three speed regions in regard to blood flow changes due to local heating, where perfusion for high speeds increased the most. There was also a high correlation between changes in oxygenation and changes in perfusion for higher speeds. Oxygen saturation at baseline was 44% on foot, increasing to 83% at plateau after heating. The larger increase in perfusion for higher speeds than for lower speeds together with the oxygenation increase during thermal provocation, shows a local thermoregulatory blood flow in presumably arteriolar dermal vessels. In conclusion, there are improved possibilities to assess microcirculation using integrated DRS and LDF in a joint skin model by enabling both oxygenation and speed resolved blood flow assessment simultaneously and in the same skin site. Output parameters in absolute units may also yield new insights about the microcirculatory system.

  16. Functional transient receptor potential vanilloid 1 and transient receptor potential vanilloid 4 channels along different segments of the renal vasculature

    DEFF Research Database (Denmark)

    Chen, L; Kaßmann, M; Sendeski, M;

    2015-01-01

    with functional TRPV1 having a narrow, discrete distribution in the resistance vasculature and TRPV4 having more universal, widespread distribution along different vascular segments. We suggest that TRPV1/4 channels are potent therapeutic targets for site-specific vasodilation in the kidney....... that TRPV1/4 plays a role in endothelium-dependent vasodilation of renal blood vessels. METHODS: We studied the distribution of functional TRPV1/4 along different segments of the renal vasculature. Mesenteric arteries were studied as control vessels. RESULTS: The TRPV1 agonist capsaicin relaxed mouse...

  17. Stimulation of NTS A1 adenosine receptors evokes counteracting effects on hindlimb vasculature.

    Science.gov (United States)

    McClure, Joseph M; O'Leary, Donal S; Scislo, Tadeusz J

    2005-12-01

    Our previous studies concluded that stimulation of the nucleus of the solitary tract (NTS) A2a receptors evokes preferential hindlimb vasodilation mainly via inducing increases in preganglionic sympathetic nerve activity (pre-ASNA) directed to the adrenal medulla. This increase in pre-ASNA causes the release of epinephrine and subsequent activation of beta-adrenergic receptors that are preferentially located in the skeletal muscle vasculature. Selective activation of NTS A1 adenosine receptors evokes variable, mostly pressor effects and increases pre-ASNA, as well as lumbar sympathetic activity, which is directed to the hindlimb. These counteracting factors may have opposite effects on the hindlimb vasculature resulting in mixed vascular responses. Therefore, in chloralose-urethane-anesthetized rats, we evaluated the contribution of vasodilator versus vasoconstrictor effects of stimulation of NTS A1 receptors on the hindlimb vasculature. We compared the changes in iliac vascular conductance evoked by microinejctions into the NTS of the selective A1 receptor agonist N6-cyclopentyladenosine (330 pmol in 50 nl volume) in intact animals with the responses evoked after beta-adrenergic blockade, bilateral adrenalectomy, bilateral lumbar sympathectomy, and combined adrenalectomy + lumbar sympathectomy. In intact animals, stimulation of NTS A1 receptors evoked variable effects: increases and decreases in mean arterial pressure and iliac conductance with prevailing pressor and vasoconstrictor effects. Peripheral beta-adrenergic receptor blockade and bilateral adrenalectomy eliminated the depressor component of the responses, markedly potentiated iliac vasoconstriction, and tended to increase the pressor responses. Lumbar sympathectomy tended to decrease the pressor and vasoconstrictor responses. After bilateral adrenalectomy plus lumbar sympathectomy, a marked vasoconstriction in iliac vascular bed still persisted, suggesting that the vasoconstrictor component of the

  18. Non-invasive temperature assessment at different tissue types based on average grey-level from B-mode ultrasonic images

    Science.gov (United States)

    Alvarenga, A. V.; Teixeira, C. A.; Von Krüger, M. A.; Pereira, W. C. A.

    2012-05-01

    The average grey-levels calculated from B-Mode images were assessed for non-invasive temperature estimation in a porcine tissue sample containing two different tissue types, fat and muscle. The porcine sample was subjected to heating and cooling procedures with temperature varying from 35°C to 42°C. The sample was continuously imaged with an ultrasound scanner, and simultaneously the temperature was measured at each 5 seconds using Type-T thermocouples. The result shows that the average grey-level (AVGL)/temperature relations are different for the two studied regions, where the muscle tissue tends to present a bigger AVGL variation than the fat tissue considering the same temperature variation. Besides, the average grey-level/temperature functions estimated for each tissue region presented fitting errors inferior to ± 0.21°C, indicating that it might be possible to track temperature changes from both tissues using AVGL. This result is innovative since it suggests that using the same B-mode image and an average grey-level/temperature function to each region it is possible to estimate non-invasively temperature variations from different tissue regions in the same tissue sample. Future work includes the investigation of the spatial limits of these average grey-level/temperature functions.

  19. Glucose-Dependent Insulinotropic Polypeptide Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB

    DEFF Research Database (Denmark)

    Berglund, Lisa M; Lyssenko, Valeriya; Ladenvall, Claes;

    2016-01-01

    Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with extrapancreatic effects beyond glycemic control. Here we demonstrate unexpected effects of GIP signaling in the vasculature. GIP induces the expression of the pro-atherogenic cytokine osteopontin (OPN) in mouse arteries......, via local release of endothelin-1 (ET-1) and activation of cAMP response element binding protein (CREB). Infusion of GIP increases plasma OPN levels in healthy individuals. Plasma ET-1 and OPN levels are positively correlated in patients with critical limb ischemia. Fasting GIP levels are higher......; and expression associates to parameters characteristic of unstable and inflammatory plaques (increased lipid accumulation, macrophage infiltration and reduced smooth muscle cell content). While GIPR expression is predominantly endothelial in healthy arteries from human, mouse, rat and pig; remarkable up-regulation...

  20. Right Ventricular Tissue Doppler Assessment in Space During Circulating Volume Modification using the Braslet-M Device

    Science.gov (United States)

    Hamilton, D. R.; Sargsyan, A. E.; Fincke, E. M.; Magnus, S. H.; Lonchakov, Y. V.; Alferova, I. V.; Dulchavsky, S. A.; Ebert, D.; Garcia, K.; Martin, D.; Matveev, V. P.; Voronkov, Y. I.; Melton, S. L.; Duncan, J. M.; Bogomolov, V. V.

    2009-01-01

    This joint U.S. - Russian work aims to establish a methodology for assessing cardiac function in microgravity in association with manipulation of central circulating volume. Russian Braslet-M occlusion cuffs were used to temporarily increase the volume of blood in the lower extremities, which effectively reduces the volume returning to the heart in the central circulation. A novel methodology was tested on the International Space Station (ISS) to assess the volume status of crewmembers by evaluating the responses to application and release of the Braslet-on-occlusion cuffs, as well as to modified Valsalva and Mueller maneuvers. Baseline echocardiographic tissue Doppler imaging (TDI) of the right ventricular free wall with no Braslet applied shows early diastolic E' (16 cm/sec), late diastolic A' (14 cm/sec), and systolic (12 cm/sec) velocities compatible with normal subjects on Earth. TDI of the RV free wall with Braslet applied shows that early diastolic E' decreased by 50% (8 cm/sec), late diastolic A' increased by 45%, and systolic S' remains unchanged. TDI of the RV free wall approximately 8 beats after the Braslet was released shows early diastolic E' (8 cm/sec), late diastolic A' (12 cm/sec), and systolic S' (13 cm/sec) velocities. During this portion of the release, early diastolic E' did not recover to baseline values but late diastolic A' and systolic S' recovered to pre-Braslet values. The pre-systolic cross-sectional area of the internal jugular vein with Braslet off was 1.07 cm(sup 2) and 1.13 cm(sup 2) 10 min after the Braslet was applied. The presystolic cross-sectional area of the common femoral vein with Braslet off was 0.50 cm(sup 2), and was 0.54 cm(sup 2) 10 min after the Braslet was applied. The right ventricular myocardial performance Tei index also was calculated for comparison with typical values found in healthy subjects on Earth. Baseline and Braslet-on values for Tei index were 0.25 and 0.22 respectively. Braslet Tei indices are within

  1. Characterization of breast tissue composition and breast cancer risk assessment using non-invasive transillumination breast spectroscopy (TIBS)

    Science.gov (United States)

    Blackmore, Kristina M.; Weersink, Robert; Lilge, Lothar

    2005-09-01

    Tissue undergoing transformation into a state that is more favourable for tumor growth may present itself with different tissue optical properties and contain different amounts of the major tissue chromophores. Here, we decomposed transillumination spectra obtain in women from various risk levels of developing breast cancer.

  2. Assessment of Subclinical Left Ventricular Dysfunction in Patients with Chronic Mitral Regurgitation Using Torsional Parameters Described by Tissue Doppler Imaging

    Directory of Open Access Journals (Sweden)

    Zahra Ojaghi-Haghighi

    2015-10-01

    Full Text Available Background: Left ventricular (LV twist is due to oppositely directed apical and basal rotation and has been proposed as a sensitive marker of LV function. We sought to assess the impact of chronic pure mitral regurgitation (MR on the torsional mechanics of the left human ventricle using tissue Doppler imaging.Methods: Nineteen severe MR patients with a normal LV ejection fraction and 16 non-MR controls underwent conventional echocardiography and apical and basal short-axis color Doppler myocardial imaging (CDMI. LV rotation at the apical and basal short-axis levels was calculated from the averaged tangential velocities of the septal and lateral regions, corrected for the LV radius over time. LV twist was defined as the difference in LV rotation between the two levels, and the LV twist and twisting/untwisting rate profiles were analyzed throughout the cardiac cycle.Results: LV twist and LV torsion were significantly lower in the MR group than in the non-MR group (10.38˚ ± 4.04˚ vs.13.95˚ ± 4.27˚; p value = 0.020; and 1.29 ± 0.54 ˚/cm vs. 1.76 ± 0.56 ˚/cm; p value = 0.021, respectively, both suggesting incipient LV dysfunction in the MR group. Similarly, the untwisting rate was lower in the MR group (-79.74 ± 35.97 ˚/s vs.-110.96 ± 34.65 ˚/s; p value = 0.020, but there was statistically no significant difference in the LV twist rate.Conclusion: The evaluation of LV torsional parameters in MR patients with a normal LV ejection fraction suggests the potential role of these sensitive variables in assessing the early signs of ventricular dysfunction in asymptomatic patients

  3. Doppler Tissue Imaging Assessment of Left Ventricular Systolic Dyssynchrony in Severe Heart Failure Patients With a Normal QRS Duration

    Institute of Scientific and Technical Information of China (English)

    Xiaozhu Chen; Jieting Wang; Suyun Song; Juan Fu; Xinxia Zhang

    2008-01-01

    Objectives To assess the prevalence of systolic dyssynchrony of the left ventricular(LV)wails in patients of heart failure(HF)with a normal QRS duration by Doppler tissue imaging(DTI).Methods 20 patients of HF with a normal QRS duration and 20 healthy individuals were investigated with DTI to quantitatively analyze their pulsed-wave Doppler spectrum of basal and middle segments in six walls of left ventricle.The time between the onset of the QRS complex of the surface ECG and the onset of the systolic wave of pulsed-wave Doppler spectrum was measured(TS).LV systolic synchronization was assessed by the maximal difference(MD)in time of TS,the standard deviation(SD)and the coefficient of variation(CV)of TS in the all 12 LV segments.Results When a TS-MD of TS>53.08 ms,a TS-SD of TS>18.08 ms and a TS-CV of TS>0.91(+1.65 SD of normal controls) was used to define significant systolic dyssynchrony,the prevalence of systolic dyssynchrony was 55.0%,55.0% and 55.0%,respectively,in the HF patients group,significantly gher than those in the normai control and the locations of delayed contraction of these patients were different.Conclusions LV systolic dyssynchrony could be commonly demonstrated by DTI in HF patients with a normal QRS duration.This finding will support the view about the possibility that more HF patients could benefit from cardiac resynchronization therapy.

  4. Assessing the three-dimensional collagen network in soft tissues using contrast agents and high resolution micro-CT: Application to porcine iliac veins.

    Science.gov (United States)

    Nierenberger, Mathieu; Rémond, Yves; Ahzi, Saïd; Choquet, Philippe

    2015-07-01

    The assessment of the three-dimensional architecture of collagen fibers inside vessel walls constitutes one of the bases for building structural models for the description of the mechanical behavior of these tissues. Multiphoton microscopy allows for such observations, but is limited to volumes of around a thousand of microns. In the present work, we propose to observe the collagenous network of vascular tissues using micro-CT. To get a contrast, three staining solutions (phosphotungstic acid, phosphomolybdic acid and iodine potassium iodide) were tested. Two of these stains were showed to lead to similar results and to a satisfactory contrast within the tissue. A detailed observation of a small porcine iliac vein sample allowed assessing the collagen fibers orientations within the medial and adventitial layers of the vein. The vasa vasorum network, which is present inside the adventitia of the vein, was also observed. Finally, the demonstrated micro-CT staining technique for the three-dimensional observation of thin soft tissues samples, like vein walls, contributes to the assessment of their structure at different scales while keeping a global overview of the tissue.

  5. Non-invasive MRI Assessments of Tissue Microstructures and Macromolecules in the Eye upon Biomechanical or Biochemical Modulation.

    Science.gov (United States)

    Ho, Leon C; Sigal, Ian A; Jan, Ning-Jiun; Yang, Xiaoling; van der Merwe, Yolandi; Yu, Yu; Chau, Ying; Leung, Christopher K; Conner, Ian P; Jin, Tao; Wu, Ed X; Kim, Seong-Gi; Wollstein, Gadi; Schuman, Joel S; Chan, Kevin C

    2016-08-26

    The microstructural organization and composition of the corneoscleral shell (CSS) determine the biomechanical behavior of the eye, and are important in diseases such as glaucoma and myopia. However, limited techniques can assess these properties globally, non-invasively and quantitatively. In this study, we hypothesized that multi-modal magnetic resonance imaging (MRI) can reveal the effects of biomechanical or biochemical modulation on CSS. Upon intraocular pressure (IOP) elevation, CSS appeared hyperintense in both freshly prepared ovine eyes and living rat eyes using T2-weighted MRI. Quantitatively, transverse relaxation time (T2) of CSS increased non-linearly with IOP at 0-40 mmHg and remained longer than unloaded tissues after being unpressurized. IOP loading also increased fractional anisotropy of CSS in diffusion tensor MRI without apparent change in magnetization transfer MRI, suggestive of straightening of microstructural fibers without modification of macromolecular contents. Lastly, treatments with increasing glyceraldehyde (mimicking crosslinking conditions) and chondroitinase-ABC concentrations (mimicking glycosaminoglycan depletion) decreased diffusivities and increased magnetization transfer in cornea, whereas glyceraldehyde also increased magnetization transfer in sclera. In summary, we demonstrated the changing profiles of MRI contrast mechanisms resulting from biomechanical or biochemical modulation of the eye non-invasively. Multi-modal MRI may help evaluate the pathophysiological mechanisms in CSS and the efficacy of corneoscleral treatments.

  6. Biomarker responsiveness in different tissues of caged Ruditapes philippinarum and its use within an integrated sediment quality assessment

    Energy Technology Data Exchange (ETDEWEB)

    Ramos-Gomez, Julia, E-mail: julia.ramosgomez@uca.es [UNITWIN/UNESCO/WiCoP, Departamento de Quimica Fisica, Universidad de Cadiz, Facultad de Ciencias del Mar y Ambientales, Campus Universitario de Puerto Real, 11510 Puerto Real, Cadiz (Spain); Coz, Alberto; Viguri, Javier R. [Dpto. Ingenieria Quimica y Quimica Inorganica, ETSIIT, Universidad de Cantabria, Avda. los Castros, s/n 39005 Santander (Spain); Luque, Angel [Departamento de Biologia, Universidad de Las Palmas de Gran Canaria, 35017 Las Palmas de Gran Canaria, Gran Canaria, The Canary Islands (Spain); Martin-Diaz, M. Laura [UNITWIN/UNESCO/WiCoP, Departamento de Quimica Fisica, Universidad de Cadiz, Facultad de Ciencias del Mar y Ambientales, Campus Universitario de Puerto Real, 11510 Puerto Real, Cadiz (Spain); Centro Andaluz de Ciencia y Tecnologia Marinas (CACYTMAR), Universidad de Cadiz, Campus Universitario de Puerto Real, 11510 Puerto Real, Cadiz (Spain); DelValls, T. Angel [UNITWIN/UNESCO/WiCoP, Departamento de Quimica Fisica, Universidad de Cadiz, Facultad de Ciencias del Mar y Ambientales, Campus Universitario de Puerto Real, 11510 Puerto Real, Cadiz (Spain)

    2011-07-15

    Biomarkers comprising activities of biotransformation enzymes (ethoxyresorufin-O-deethylase -EROD-, dibenzylfluorescein dealkylase -DBF-, glutathione S-transferase -GST), antioxidant enzymes (glutathione reductase -GR- and glutathione peroxidase -GPX), lipid peroxidation -LPO- and DNA strand breaks were analyzed in the clam Ruditapes philippinarum caged at Cadiz Bay, Santander Bay and Las Palmas de Gran Canaria (LPGC) Port (Spain). Sediments were characterized. Digestive gland was the most sensitive tissue to sediment contamination. In Cadiz Bay, changes in LPO regarding day 0 were related with metals. In LPGC Port, DBF, EROD, and GST activity responses suggested the presence of undetermined contaminants which might have led to DNA damage. In Santander Bay, PAHs were related with EROD activity, organic and metal contamination was found to be associated with GR and GST activities and DNA damage presented significant (p < 0.05) induction. R. philippinarum was sensitive to sediment contamination at biochemical level. Biomarkers allowed chemical exposure and sediment quality assessment. - Highlights: > Ruditapes philippinarum is sensitive to sediment contamination at biochemical level. > Digestive gland biomarkers showed the best correlations with sediment contaminants. > Presence of potentially toxic chemicals not analyzed in this research was unmasked. > Multivariate analysis allowed the identification of toxic xenobiotic and possible sources. > Inner area of Santander Bay presented the highest sediment toxicity. - Integration of Ruditapes philippinarum biomarker results and sediment chemistry distinguished xenobiotic exposure and sediment toxicity in coastal areas of Spain.

  7. Analyzing the "CareGap": assessing gaps in adherence to clinical guidelines in adult soft tissue sarcoma.

    Science.gov (United States)

    Waks, Zeev; Goldbraich, Esther; Farkash, Ariel; Torresani, Michele; Bertulli, Rossella; Restifo, Nicola; Locatelli, Paolo; Casali, Paolo; Carmeli, Boaz

    2013-01-01

    Clinical decision support systems (CDSSs) are gaining popularity as tools that assist physicians in optimizing medical care. These systems typically comply with evidence-based medicine and are designed with input from domain experts. Nonetheless, deviations from CDSS recommendations are abundant across a broad spectrum of disorders, raising the question as to why this phenomenon exists. Here, we analyze this gap in adherence to a clinical guidelines-based CDSS by examining the physician treatment decisions for 1329 adult soft tissue sarcoma patients in northern Italy using patient-specific parameters. Dubbing this analysis "CareGap", we find that deviations correlate strongly with certain disease features such as local versus metastatic clinical presentation. We also notice that deviations from the guideline-based CDSS suggestions occur more frequently for patients with shorter survival time. Such observations can direct physicians' attention to distinct patient cohorts that are prone to higher deviation levels from clinical practice guidelines. This illustrates the value of CareGap analysis in assessing quality of care for subsets of patients within a larger pathology.

  8. DDTs in rice frogs (Rana limnocharis) from an agricultural site, South China: tissue distribution, biomagnification, and potential toxic effects assessment.

    Science.gov (United States)

    Wu, Jiang-Ping; Zhang, Ying; Luo, Xiao-Jun; Chen, She-Jun; Mai, Bi-Xian

    2012-04-01

    Contamination with agricultural pesticides such as dichlorodiphenyltrichloroethane (DDT) and its metabolites, dichlorodiphenyldichloroethylene (DDE) and dichlorodiphenyldichloroethane (DDD), is among several proposed stressors contributing to the global declines in amphibian populations and species biodiversity. These chemicals were examined in insects and in the muscle, liver, and eggs of rice frogs (Rana limnocharis) from the paddy fields of an agricultural site in South China. The ΣDDT (sum of DDT, DDE, and DDD) concentrations ranged from 154 to 915, 195 to 1,400, and 165 to 1,930 ng/g lipid weight in the muscle, liver, and eggs, respectively. All the DDTs (DDT, DDE, and DDD) showed higher affinity for the liver relative to muscle tissue and can be maternally transferred to eggs in female frogs. The average biomagnification factors for DDTs ranged from 1.6 to 1.9 and 1.5 to 2.9 in female and male frogs, respectively, providing clear evidence of their biomagnification from insects to frogs. Compared with the reported DDT levels demonstrated to have toxic effects on frogs, DDTs in the present frogs are unlikely to constitute an immediate health risk. However, the adverse impacts of high DDT residues in eggs on the hatching success and their potential toxicity to the newly metamorphosed larval frogs should be assessed further.

  9. Implementation of an absolute brain 1H-MRS quantification method to assess different tissue alterations in multiple sclerosis.

    Science.gov (United States)

    Bagory, Matthieu; Durand-Dubief, Françoise; Ibarrola, Danielle; Comte, Jean-Christophe; Cotton, François; Confavreux, Christian; Sappey-Marinier, Dominique

    2012-10-01

    Magnetic resonance spectroscopy has emerged as a sensitive modality to detect early and diffuse alterations in multiple sclerosis. Recently, the hypothesis of neurodegenerative pathogenesis has highlightened the interest for measurement of metabolites concentrations, to gain specificity, in a large brain volume encompassing different tissue alterations. Therefore, we proposed in this paper the implementation of an absolute quantification method based on localized spectroscopy at short (30 ms) and long (135 ms) echo time of a volume including normal appearing white matter, cortical gray matter, and lesions. First, methodological developments were implemented including external calibration, and corrections of phased-array coil sensitivity and cerebrospinal fluid volume contribution. Second, these improvements were validated and optimized using an original methodology based on simulations of brain images with lesions. Finally, metabolic alterations were assessed in 65 patients including 26 relapsing-remitting, 17 primary-progressive (PP), 22 secondary-progressive (SP) patients, and in 23 normal subjects. Results showed increases of choline, creatine, and myo-inositol concentrations in PP and SP patients compared to controls, whereas the concentration of N-acetyl compounds remained constant. The major finding of this study was the identification of Cho concentration and Cho/tNA ratio as putative markers of progressive onset, suggesting interesting perspectives in detection and followup of neurodegenerative processes.

  10. The three-dimensional organisation of the post-trabecular aqueous outflow pathway and limbal vasculature in the mouse.

    Science.gov (United States)

    van der Merwe, Elizabeth L; Kidson, Susan H

    2014-08-01

    The mouse eye has been used as a model for studies on the microanatomy of the outflow pathways but most of what is known comes from histological sections. These studies have focused mainly on the morphological features of the trabecular meshwork, Schlemm's canal and aqueous channels that link to the superficial episcleral vasculature. However, the anatomical architecture of the aqueous outflow vessels and their relationship to each other and to the general vascular circulation is not well understood. The aim of this study was to provide a detailed description of the microarchitecture of the aqueous outflow vessels and their relationship to the superficial limbal/episcleral vasculature throughout the entire limbus. The aqueous outflow vessels and blood and lymphatic vessels were imaged in PECAM-1 and LYVE-1 immunostained whole anterior segments of adult mice and three-dimensional (3-D) reconstructions of the optical sections were generated to reveal the aqueous, blood and lymphatic architecture. The arterial supply, venous drainage, organisation of perilimbal vasculature, collector channels/aqueous veins and the morphology of Schlemm's canal were revealed in their entirety and the relationships between these structures is described. Schlemm's canal was PECAM-1 positive but there was no affinity for the lymphatic marker LYVE-1. We show that Schlemm's canal is a continuous circular structure and more often seen as a single, broad, varicose vessel with short regions appearing as a plexus. Aqueous veins link Schlemm's canal to the superficial vasculature and there were no direct links seen between the canal and the lymphatic vessels.

  11. iNKT Cell Emigration out of the Lung Vasculature Requires Neutrophils and Monocyte-Derived Dendritic Cells in Inflammation

    Science.gov (United States)

    Thanabalasuriar, A; Neupane, A.S; Wang, J; Krummel, M.F; Kubes, P

    2017-01-01

    iNKT cells are a subset of innate T cells that recognize glycolipids presented on CD1d molecules and protect against a variety of bacterial infections including S. pneumoniae. Using lung intravital imaging, we examined the behavior and mechanism of pulmonary iNKT cell activation in response to the potent iNKT cell ligand α-galactosylceramide or during S. pneumoniae infection. In untreated mice the major fraction of iNKT cells resided in the vasculature, but a small critical population resided in the extravascular space in proximity to monocyte-derived DCs. Administration of either α-GalCer or S. pneumoniae, induced CD1d dependent rapid recruitment of neutrophils out of the vasculature. This neutrophil exodus paved the way for extravasation of iNKT cells from the lung vasculature via CCL17. Depletion of monocyte-derived DCs abrogated both the neutrophil and subsequent iNKT cell extravasation. Moreover, impairing iNKT cell migration out of the lung vasculature by blocking CCL17 greatly increased susceptibility to S. pneumoniae infection, suggesting a critical role for the secondary wave of iNKT cells in host defense. PMID:27653688

  12. Deregulated ephrin-B2 expression in the mammary gland interferes with the development of both the glandular epithelium and vasculature and promotes metastasis formation.

    Science.gov (United States)

    Haldimann, Mirjam; Custer, Domenica; Munarini, Nadia; Stirnimann, Christoph; Zürcher, Gisela; Rohrbach, Valeria; Djonov, Valentin; Ziemiecki, Andrew; Andres, Anne-Catherine

    2009-09-01

    Eph receptor tyrosine kinases and their membrane-bound ephrin ligands play key roles during morphogenesis and adult tissue homeostasis. Receptor-ligand interactions result in forward and reverse signalling from the receptor and ligand respectively. To delineate the role(s) of forward and reverse signalling in mammary gland biology we have established transgenic mice exhibiting mammary epithelial-specific overexpression of either the native ephrin-B2 or a dominant negative ephrin-B2 mutant incapable of reverse signalling. During pregnancy and lactation overexpression of the native ephrin-B2 resulted in precocious differentiation, whereas overexpression of mutated ephrin-B2 caused delayed epithelial differentiation and in disturbed tissue architecture. Both transgenes affected also mammary vascularisation. Whereas ephrin-B2 induced superfluous but organised capillaries, mutant ephrin-B2 overexpression resulted in an irregular vasculature with blind-ending capillaries. Mammary tumours were not observed in either transgenic line, however, the crossing with NeuT transgenic animals revealed that mutated ephrin-B2 expression significantly accelerated tumour growth and imposed a metastatic phenotype.

  13. Large field, high resolution full-field optical coherence tomography: a pre-clinical study of human breast tissue and cancer assessment.

    Science.gov (United States)

    Assayag, Osnath; Antoine, Martine; Sigal-Zafrani, Brigitte; Riben, Michael; Harms, Fabrice; Burcheri, Adriano; Grieve, Kate; Dalimier, Eugénie; Le Conte de Poly, Bertrand; Boccara, Claude

    2014-10-01

    We present a benchmark pilot study in which high-resolution Full-Field Optical Coherence Tomography (FF-OCT) was used to image human breast tissue and is evaluated to assess its ability to aid the pathologist's management of intra-operative diagnoses. FF-OCT imaging safety was investigated and agreement between FF-OCT and routinely prepared histopathological images was evaluated. The compact setup used for this study provides 1 mm3 resolution and 200 mm imaging depth, and a 2.25 cm2 specimen is scanned in about 7 minutes. 75 breast specimens were imaged from 22 patients (21 women, 1 man) with a mean age of 58 (range: 25-83). Pathologists blind diagnosed normal/benign or malignant tissue based on FF-OCT images alone, diagnosis from histopathology followed for comparison. The contrast in the FF-OCT images is generated by intrinsic tissue scattering properties, meaning that no tissue staining or preparation is required. Major architectural features and tissue structures of benign breast tissue, including adipocytes, fibrous stroma, lobules and ducts were characterized. Subsequently, features resulting from pathological modification were characterized and a diagnosis decision tree was developed. Using FF-OCT images, two breast pathologists were able to distinguish normal/benign tissue from lesional with a sensitivity of 94% and 90%, and specificity of 75% and 79% respectively.

  14. Tissue-specific in vivo genetic toxicity of nine polycyclic aromatic hydrocarbons assessed using the Muta™Mouse transgenic rodent assay

    Science.gov (United States)

    Long, Alexandra S.; Lemieux, Christine L.; Arlt, Volker M.; White, Paul A.

    2016-01-01

    Test batteries to screen chemicals for mutagenic hazard include several endpoints regarded as effective for detecting genotoxic carcinogens. Traditional in vivo methods primarily examine clastogenic endpoints in haematopoietic tissues. Although this approach is effective for identifying systemically distributed clastogens, some mutagens may not induce clastogenic effects; moreover, genotoxic effects may be restricted to the site of contact and/or related tissues. An OECD test guideline for transgenic rodent (TGR) gene mutation assays was released in 2011, and the TGR assays permit assessment of mutagenicity in any tissue. This study assessed the responses of two genotoxicity endpoints following sub-chronic oral exposures of male Muta™Mouse to 9 carcinogenic polycyclic aromatic hydrocarbons (PAHs). Clastogenicity was assessed via induction of micronuclei in peripheral blood, and mutagenicity via induction of lacZ transgene mutations in bone marrow, glandular stomach, small intestine, liver, and lung. Additionally, the presence of bulky PAH-DNA adducts was examined. Five of the 9 PAHs elicited positive results across all endpoints in at least one tissue, and no PAHs were negative or equivocal across all endpoints. All PAHs were positive for lacZ mutations in at least one tissue (sensitivity = 100%), and for 8 PAHs, one or more initial sites of chemical contact (i.e., glandular stomach, liver, small intestine) yielded a greater response than bone marrow. Five PAHs were positive in the micronucleus assay (sensitivity = 56%). Furthermore, all PAHs produced DNA adducts in at least one tissue. The results demonstrate the utility of the TGR assay for mutagenicity assessment, especially for compounds that may not be systemically distributed. PMID:26603514

  15. Temporal dynamics of cerebral blood flow, cortical damage, apoptosis, astrocyte-vasculature interaction and astrogliosis in the pericontusional region after traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Sonia eVillapol

    2014-06-01

    Full Text Available Traumatic brain injury (TBI results in a loss of brain tissue at the moment of impact in the cerebral cortex. Subsequent secondary injury involves the release of molecular signals with dramatic consequences for the integrity of damaged tissue, leading to the evolution of a pericontusional-damaged area minutes to days after in the initial injury. The mechanisms behind the progression of tissue loss remain under investigation. In this study, we analyzed the spatial-temporal profile of blood flow, apoptotic and astrocytic-vascular events in the cortical regions around the impact site at time points ranging from 5 hours to 2 months after TBI. We performed a mild-moderate controlled cortical impact injury in young adult mice and analyzed the glial and vascular response to injury. We observed a dramatic decrease in perilesional cerebral blood flow (CBF immediately following the cortical impact that lasted until days later. CBF finally returned to baseline levels by 30 days post-injury (dpi. The initial impact also resulted in an immediate loss of tissue and cavity formation that gradually increased in size until 3 dpi. An increase in dying cells localized in the pericontusional region and a robust astrogliosis were also observed at 3 dpi. A strong vasculature interaction with astrocytes was established at 7 dpi. Glial scar formation began at 7 dpi and seemed to be compact by 60 dpi. Altogether, these results suggest that TBI results in a progression from acute neurodegeneration that precedes astrocytic activation, reformation of the neurovascular unit to glial scar formation. Understanding the multiple processes occurring after TBI is critical to the ability to develop neuroprotective therapeutics to ameliorate the short and long-term consequences of brain injury.

  16. Can Archival Tissue Reveal Answers to Modern Research Questions?: Computer-Aided Histological Assessment of Neuroblastoma Tumours Collected over 60 Years.

    Science.gov (United States)

    Chetcuti, Albert; Mackie, Nicole; Tafavogh, Siamak; Graf, Nicole; Henwood, Tony; Charlton, Amanda; Catchpoole, Daniel

    2014-02-28

    Despite neuroblastoma being the most common extracranial solid cancer in childhood, it is still a rare disease. Consequently, the unavailability of tissue for research limits the statistical power of studies. Pathology archives are possible sources of rare tissue, which, if proven to remain consistent over time, could prove useful to research of rare disease types. We applied immunohistochemistry to investigate whether long term storage caused any changes to antigens used diagnostically for neuroblastoma. We constructed and quantitatively assessed a tissue microarray containing neuroblastoma archival material dating between 1950 and 2007. A total of 119 neuroblastoma tissue cores were included spanning 6 decades. Fourteen antibodies were screened across the tissue microarray (TMA). These included seven positive neuroblastoma diagnosis markers (NB84, Chromogranin A, NSE, Ki-67, INI1, Neurofilament Protein, Synaptophysin), two anticipated to be negative (S100A, CD99), and five research antibodies (IL-7, IL-7R, JAK1, JAK3, STAT5). The staining of these antibodies was evaluated using Aperio ImageScope software along with novel pattern recognition and quantification algorithms. This analysis demonstrated that marker signal intensity did not decrease over time and that storage for 60 years had little effect on antigenicity. The construction and assessment of this neuroblastoma TMA has demonstrated the feasibility of using archival samples for research.

  17. Quantitative three-dimensional methodology to assess volumetric and profilometric outcome of subepithelial connective tissue grafting at pontic sites: a prospective pilot study.

    Science.gov (United States)

    González-Martín, Oscar; Veltri, Mario; Moráguez, Osvaldo; Belser, Urs C

    2014-01-01

    The aim of this study was to describe a technique for the assessment of soft tissue volumetric and profilometric changes. The technique has been applied at the alveolar contour of mild to moderate horizontal ridge defects after soft tissue augmentation at pontic sites. A quantitative three-dimensional (3D) analysis based on laser scanning was used for the measurement of volume gain and horizontal changes of alveolar profile 5 months after a subepithelial connective tissue graft using a pouch approach in five patients. All the surgical sites healed uneventfully. A mean soft tissue volume increase of 35.9 mm3 was measured 5 months after the grafting procedure. The linear measurements showed that, in the area where the augmentation was performed, the distance between the preoperative vestibular profile and the postoperative one ranged from 0.16 to 2 mm. The described quantitative measurements based on 3D laser scanning appear to be an effective method for assessment of soft tissue changes in future studies. Additionally, within the limitation of a small sample size, the present data suggest that the investigated surgical technique can be considered when corrections of mild to moderate alveolar horizontal ridge atrophies at maxillary lateral incisor edentulous gaps are necessary.

  18. Can Archival Tissue Reveal Answers to Modern Research Questions?: Computer-Aided Histological Assessment of Neuroblastoma Tumours Collected over 60 Years

    Directory of Open Access Journals (Sweden)

    Albert Chetcuti

    2014-02-01

    Full Text Available Despite neuroblastoma being the most common extracranial solid cancer in childhood, it is still a rare disease. Consequently, the unavailability of tissue for research limits the statistical power of studies. Pathology archives are possible sources of rare tissue, which, if proven to remain consistent over time, could prove useful to research of rare disease types. We applied immunohistochemistry to investigate whether long term storage caused any changes to antigens used diagnostically for neuroblastoma. We constructed and quantitatively assessed a tissue microarray containing neuroblastoma archival material dating between 1950 and 2007. A total of 119 neuroblastoma tissue cores were included spanning 6 decades. Fourteen antibodies were screened across the tissue microarray (TMA. These included seven positive neuroblastoma diagnosis markers (NB84, Chromogranin A, NSE, Ki-67, INI1, Neurofilament Protein, Synaptophysin, two anticipated to be negative (S100A, CD99, and five research antibodies (IL-7, IL-7R, JAK1, JAK3, STAT5. The staining of these antibodies was evaluated using Aperio ImageScope software along with novel pattern recognition and quantification algorithms. This analysis demonstrated that marker signal intensity did not decrease over time and that storage for 60 years had little effect on antigenicity. The construction and assessment of this neuroblastoma TMA has demonstrated the feasibility of using archival samples for research.

  19. The effectiveness of diagnostic imaging methods for the assessment of soft tissue and articular disorders of the shoulder and elbow

    Energy Technology Data Exchange (ETDEWEB)

    Shahabpour, M. [Department of Radiology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels (Belgium)], E-mail: Maryam@shahabpour.uzbrussel; Kichouh, M.; Laridon, E. [Department of Radiology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels (Belgium); Gielen, J.L. [Department of Radiology, Universitair Ziekenhuis Antwerpen, Universiteit Antwerpen, Wilrijkstraat 10, 2650 Edegem (Belgium); De Mey, J. [Department of Radiology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels (Belgium)

    2008-02-15

    There are no clear guidelines for diagnostic imaging of articular and soft tissue pathologies of the shoulder and elbow. Several methods are used, including magnetic resonance imaging (MRI), magnetic resonance arthrography (MRA) and ultrasound (US). Their cost-effectiveness is still unclear. We performed a meta-analysis of the relevant literature and discussed the role of MR imaging of the shoulder and elbow compared with other diagnostic imaging modalities. For the shoulder impingement syndrome and rotator cuff tears, MRI and US have a comparable accuracy for detection of full-thickness rotator cuff tears. MRA and US might be more accurate for the detection of partial-thickness tears than MRI. Given the large difference in cost of MR and US, ultrasound may be the most cost-effective diagnostic method for identification of full-thickness tears in a specialist hospital setting (Evidence level 3). Both MRA and CT arthrography (CTA) are effective methods for the detection of labrum tears. More recently, multidetector CTA has offered the advantages of thinner slices than with MRA in a shorter examination time. Still, MRA has the advantage towards CTA to directly visualize the affected structures with a better evaluation of extent and location and to detect associated capsuloligamentous injuries. For the elbow pathologies, plain MRI or MRA have the advantage towards CTA to detect occult bone injuries. CTA is better for the assessment of the thin cartilage of the elbow. Both US and MRI are reliable methods to detect chronic epicondylitis; US is more available and far more cost-effective (Evidence level 2). MRA can differentiate complete from partial tears of the medial collateral ligament. US or MRI can detect partial and complete biceps tendon tears and/or bursitis. MRI can provide important diagnostic information in lesions of the ulnar, radial, or median nerve.

  20. QUANTITATIVE INVIVO ASSESSMENT OF THE TISSUE-RESPONSE TO DERMAL SHEEP COLLAGEN IN ABDOMINAL-WALL DEFECTS

    NARCIS (Netherlands)

    HUNT, JA; VANDERLAAN, JS; SCHAKENRAAD, J; WILLIAMS, DF

    1993-01-01

    We quantified the tissue response, tissue organization and patency of biodegradable patches for the repair of abdominal wall defects. We used dermal sheep collagen, cross-linked with hexamethylenediisocyanate in a model. The collagen patches were implanted either untreated or plasma polymerized with

  1. Narrow-band pass filter array for integrated opto-electronic spectroscopy detectors to assess esophageal tissue

    NARCIS (Netherlands)

    Ferreira, D.S.; Mirkovic, J.; Wolffenbuttel, R.F.; Correia, J.H.; Feld, M.S.; Minas, G.

    2011-01-01

    A strategy for spectroscopy tissue diagnosis using a small number of wavelengths is reported. The feasibility to accurately quantify tissue information using only 16 wavelengths is demonstrated with several wavelength reduction simulations of the existing esophageal data set. These results are an im

  2. A pilot quantitative study of topographic correlation between reticular pseudodrusen and the choroidal vasculature using en face optical coherence tomography.

    Directory of Open Access Journals (Sweden)

    Dilraj S Grewal

    Full Text Available PURPOSE: To analyze the topographic correlation between reticular pseudodrusen (RPD visualized on infrared reflectance (IR and choroidal vasculature using en-face volumetric spectral-domain optical coherence tomography (SD-OCT. METHODS: A masked observer marked individual RPD on IR images using ImageJ (NIH, Bethesda, MD. Using the macular volume scan (Cirrus, Carl Zeiss Meditec Inc, Dublin, CA, the RPE slab function was used to generate a C-scan of the most superficial choroidal vasculature. An independent masked grader created a topographic binary map of the choroidal vasculature by thresholding the en-face image, which was overlaid onto the IR map of RPD. For each IR image, ImageJ was used to generate a random set of dots as "control lesions". RESULTS: 17 eyes of 11 patients (78±13.7 years with RPD were analyzed. The average number of RPD lesions identified on IR images was 414±71.5, of which 49.6±4.3% were located overlying the choroidal vasculature, compared to 45.4±4.0% in controls (p = 0.014. 50.4±4.3% of lesions overlay the choroidal stroma, of which 76.5±3.1% were ≤3 pixels from the choroidal vessels. The percentage of RPD lesions located within ≤3 pixels from the choroidal vasculature was significantly greater than the percentage located ≥7 pixels away. (p<0.0001. Compared to controls (71.6±3.8%, RPD were more likely to be located ≤3 pixels away from choroidal vessels (p = 0.014. In contrast, control lesions were more likely to be ≥7 pixels away from choroidal vessels than RPD (9.1±1.9% vs. 4.8±1.2%, respectively, p = 0.002. CONCLUSIONS: Our analysis shows that RPD lesions follow the underlying choroidal vasculature. Approximately half the RPD directly overlay the choroidal vessels and the majority of the remaining lesions were ≤3 pixels (≤30 microns from the vessel edge, supporting the hypothesis that RPD maybe related to pathologic changes at the choroidal level.

  3. Assessment of the 2-d gel-based proteomics application of clinically archived formalin-fixed paraffin embedded tissues.

    Science.gov (United States)

    Davalieva, Katarina; Kiprijanovska, Sanja; Polenakovic, Momir

    2014-04-01

    Hospital tissue repositories possess a vast and valuable supply of disease samples with matched retrospective clinical information. Detection and characterization of disease biomarkers in formalin-fixed paraffin-embedded (FFPE) tissues will greatly aid the understanding of the diseases mechanisms and help in the development of diagnostic and prognostic markers. In this study, the possibility of using full-length proteins extracted from clinically archived FFPE tissues in two-dimensional (2-D) gel-based proteomics was evaluated. The evaluation was done based on two types of tumor tissues (breast and prostate) and two extraction protocols. The comparison of the 2-D patterns of FFPE extracts obtained by two extraction protocols with the matching frozen tissue extracts showed that only 7-10% of proteins from frozen tissues can be matched to proteins from FFPE tissues. Most of the spots in the 2-D FFPE's maps had pl 4-6, while the percentages of proteins with pl above 6 were 3-5 times lower in comparison to the fresh/frozen tissue. Despite the three-fold lower number of the detected spots in FFPE maps compared to matched fresh/frozen maps, 67-78% of protein spots in FFPE could not be matched to the corresponding spots in the fresh/frozen tissue maps indicating irreversible protein modifications. In conclusion, the inability to completely reverse the cross-linked complexes and overcome protein fragmentation with the present day FFPE extraction methods stands in the way of effective use of these samples in 2-D gel based proteomics studies.

  4. SEX STEROIDS MODULATE UTERINE-PLACENTAL VASCULATURE: IMPLICATIONS FOR OBSTETRICS AND NEONATAL OUTCOMES

    Directory of Open Access Journals (Sweden)

    Manuel eMaliqueo

    2016-04-01

    Full Text Available Adequate blood supply to the uterine-placental region is crucial to ensure the transport of oxygen and nutrients to the growing fetus. Multiple factors intervene to achieve appropriate uterine blood flow and the structuring of the placental vasculature during the early stages of pregnancy. Among these factors, oxygen concentrations, growth factors, cytokines and steroid hormones are the most important. Sex steroids are present in extremely high concentrations in the maternal circulation and are important paracrine and autocrine regulators of a wide range of maternal and placental functions. In this regard, progesterone and estrogens act as modulators of uterine vessels and decrease the resistance of the spiral uterine arteries. On the other hand, androgens have the opposite effect, increasing the vascular resistance of the uterus. Moreover, progesterone and estrogens modulate the synthesis and release of angiogenic factors by placental cells, which regulates trophoblastic invasion and uterine artery remodeling. In this scenario, it is not surprising that women with pregnancy-related pathologies, such as early miscarriages, preterm delivery, preeclampsia and fetal growth restriction, exhibit altered sex steroid concentrations.

  5. Segmentation methods for breast vasculature in dual-energy contrast-enhanced digital breast tomosynthesis

    Science.gov (United States)

    Lau, Kristen C.; Lee, Hyo Min; Singh, Tanushriya; Maidment, Andrew D. A.

    2015-03-01

    Dual-energy contrast-enhanced digital breast tomosynthesis (DE CE-DBT) uses an iodinated contrast agent to image the three-dimensional breast vasculature. The University of Pennsylvania has an ongoing DE CE-DBT clinical study in patients with known breast cancers. The breast is compressed continuously and imaged at four time points (1 pre-contrast; 3 post-contrast). DE images are obtained by a weighted logarithmic subtraction of the high-energy (HE) and low-energy (LE) image pairs. Temporal subtraction of the post-contrast DE images from the pre-contrast DE image is performed to analyze iodine uptake. Our previous work investigated image registration methods to correct for patient motion, enhancing the evaluation of vascular kinetics. In this project we investigate a segmentation algorithm which identifies blood vessels in the breast from our temporal DE subtraction images. Anisotropic diffusion filtering, Gabor filtering, and morphological filtering are used for the enhancement of vessel features. Vessel labeling methods are then used to distinguish vessel and background features successfully. Statistical and clinical evaluations of segmentation accuracy in DE-CBT images are ongoing.

  6. Anticancer Role of PPARγ Agonists in Hematological Malignancies Found in the Vasculature, Marrow, and Eyes

    Directory of Open Access Journals (Sweden)

    P. J. Simpson-Haidaris

    2010-01-01

    Full Text Available The use of targeted cancer therapies in combination with conventional chemotherapeutic agents and/or radiation treatment has increased overall survival of cancer patients. However, longer survival is accompanied by increased incidence of comorbidities due, in part, to drug side effects and toxicities. It is well accepted that inflammation and tumorigenesis are linked. Because peroxisome proliferator-activated receptor (PPAR-γ agonists are potent mediators of anti-inflammatory responses, it was a logical extension to examine the role of PPARγ agonists in the treatment and prevention of cancer. This paper has two objectives: first to highlight the potential uses for PPARγ agonists in anticancer therapy with special emphasis on their role when used as adjuvant or combined therapy in the treatment of hematological malignancies found in the vasculature, marrow, and eyes, and second, to review the potential role PPARγ and/or its ligands may have in modulating cancer-associated angiogenesis and tumor-stromal microenvironment crosstalk in bone marrow.

  7. Insulin regulates its own delivery to skeletal muscle by feed-forward actions on the vasculature

    Science.gov (United States)

    Wang, Hong; Upchurch, Charles T.; Liu, Zhenqi

    2011-01-01

    Insulin, at physiological concentrations, regulates the volume of microvasculature perfused within skeletal and cardiac muscle. It can also, by relaxing the larger resistance vessels, increase total muscle blood flow. Both of these effects require endothelial cell nitric oxide generation and smooth muscle cell relaxation, and each could increase delivery of insulin and nutrients to muscle. The capillary microvasculature possesses the greatest endothelial surface area of the body. Yet, whether insulin acts on the capillary endothelial cell is not known. Here, we review insulin's actions at each of three levels of the arterial vasculature as well as recent data suggesting that insulin can regulate a vesicular transport system within the endothelial cell. This latter action, if it occurs at the capillary level, could enhance insulin delivery to muscle interstitium and thereby complement insulin's actions on arteriolar endothelium to increase insulin delivery. We also review work that suggests that this action of insulin on vesicle transport depends on endothelial cell nitric oxide generation and that insulin's ability to regulate this vesicular transport system is impaired by inflammatory cytokines that provoke insulin resistance. PMID:21610226

  8. Suppression of pulmonary vasculature in lung perfusion MRI using correlation analysis

    Energy Technology Data Exchange (ETDEWEB)

    Risse, Frank; Semmler, Wolfhard [Deutsches Krebsforschungszentrum, Department of Medical Physics in Radiology, Heidelberg (Germany); Kuder, Tristan A. [Deutsches Krebsforschungszentrum, Department of Medical Physics in Radiology, Heidelberg (Germany); Deutsches Krebsforschungszentrum, Department of Radiology, Heidelberg (Germany); Kauczor, Hans-Ulrich [University of Heidelberg, Department of Diagnostic Radiology, Heidelberg (Germany); Fink, Christian [University Medical Center Mannheim, Medical Faculty Mannheim - University of Heidelberg, Department of Clinical Radiology and Nuclear Medicine, Mannheim (Germany); Universitaetsmedizin Mannheim, Institut fuer Klinische Radiologie und Nuklearmedizin, Mannheim (Germany)

    2009-11-15

    The purpose of the study was to evaluate the feasibility of suppressing the pulmonary vasculature in lung perfusion MRI using cross-correlation analysis (CCA). Perfusion magnetic resonance imaging (MRI) (3D FLASH, TR/TE/flip angle: 0.8 ms/2.1 ms/40 ) of the lungs was performed in seven healthy volunteers at 1.5 Tesla after injection of Gd-DTPA. CCA was performed pixel-wise in lung segmentations using the signal time-course of the main pulmonary artery and left atrium as references. Pixels with high correlation coefficients were considered as arterial or venous and excluded from further analysis. Quantitative perfusion parameters [pulmonary blood flow (PBF) and volume (PBV)] were calculated for manual lung segmentations separately, with the entire left and right lung with all intrapulmonary vessels (IPV) included, excluded manually or excluded using CCA. The application of CCA allowed reliable suppression of hilar and large IPVs. Using vascular suppression by CCA, perfusion parameters were significantly reduced (p {<=} 0.001). The reduction was 8% for PBF and 13% for PBV compared with manual exclusion and 15% for PBF and 25% for PBV when all vessel structures were included. The application of CCA improves the visualisation and quantification of lung perfusion in MRI. Overestimation of perfusion parameters caused by pulmonary vessels is significantly reduced. (orig.)

  9. Surgical Anatomy of the Gastrointestinal Tract and Its Vasculature in the Laboratory Rat

    Directory of Open Access Journals (Sweden)

    Katarína Vdoviaková

    2016-01-01

    Full Text Available The aim of this study was to describe and illustrate the morphology of the stomach, liver, intestine, and their vasculature to support the planning of surgical therapeutic methods in abdominal cavity. On adult Wistar rats corrosion casts were prepared from the arterial system and Duracryl Dental and PUR SP were used as a casting medium and was performed macroscopic anatomical dissection of the stomach, liver, and intestine was performed. The rat stomach was a large, semilunar shaped sac with composite lining. On the stomach was very marked fundus, which formed a blind sac (saccus cecus. The rat liver was divided into six lobes, but without gall bladder. Intestine of the rat was simple, but cecum had a shape as a stomach. The following variations were observed in the origin of the cranial mesenteric artery. On the corrosion cast specimens we noticed the presence of the anastomosis between middle colic artery (a. colica media and left colic artery (a. colica sinistra. We investigated the second anastomosis between middle colic artery and left colic artery. The results of this study reveal that the functional anatomical relationship between the rat stomach, liver and intestine is important for the development of surgical research in human and veterinary medicine.

  10. The diagnostic and prognostic value of ¹⁸F-FDG PET/CT in the initial assessment of high-grade bone and soft tissue sarcoma. A retrospective study of 89 patients

    DEFF Research Database (Denmark)

    Fuglø, Hanna Maria; Jørgensen, Simon Møller; Loft, Annika;

    2012-01-01

    To evaluate the feasibility of (18)F-FDG PET/CT for initial assessment in high-grade bone sarcomas (BS) and soft tissue sarcomas (STS).......To evaluate the feasibility of (18)F-FDG PET/CT for initial assessment in high-grade bone sarcomas (BS) and soft tissue sarcomas (STS)....

  11. Tissue distribution and excretion of the five components of Portulaca oleracea L. extract in rat assessed by UHPLC

    Directory of Open Access Journals (Sweden)

    Wenjie Zhang

    2015-09-01

    Full Text Available The aim of the present study was to investigate the tissue distribution and excretion of five components of Portulaca oleracea L. extract (POE in rat following oral administration. A rapid, sensitive and specific ultra-high performance liquid chromatography (UHPLC method with puerarin as the internal standard was used for the quantitative analysis of five components of POE, including caffeic acid (CA, p-coumaric acid (p-CA, ferulic acid (FA, quercitrin (QUER and hesperidin (HP in rat tissues including the liver, intestine, stomach, muscle, heart, lung, brain, kidney and spleen, urine and feces. The results show that onlyp-CA and FA were found in nearly all tissues with low cumulative ratios, and CA was higher in the intestine and stomach with a slightly higher cumulative ratio in the urine and feces after 24 h. HP and QUER were found at low levels in the tissues with low cumulative ratios.

  12. Mapping differential elemental accumulation in fish tissues: assessment of metal and trace element concentrations in wels catfish (Silurus glanis) from the Danube River by ICP-MS.

    Science.gov (United States)

    Jovičić, Katarina; Nikolić, Dragica M; Višnjić-Jeftić, Željka; Đikanović, Vesna; Skorić, Stefan; Stefanović, Srđan M; Lenhardt, Mirjana; Hegediš, Aleksandar; Krpo-Ćetković, Jasmina; Jarić, Ivan

    2015-03-01

    Studies of metal accumulation in fish are mainly focused on the muscle tissue, while the metal accumulation patterns in other tissues have been largely neglected. Muscle is not always a good indicator of the whole fish body contamination. Elemental accumulation in many fish tissues and organs and their potential use in monitoring programs have not received proper attention. In the present study, As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Se, and Zn concentrations were assessed by inductively coupled plasma mass spectrometry (ICP-MS) in the following 14 tissues of the wels catfish (Silurus glanis) from the Danube River: muscle, gills, spleen, liver, kidneys, intestine, gizzard, heart, brain, gallbladder, swim bladder, vertebra, operculum, and gonads. A high level of differential elemental accumulation among the studied tissues was observed. The maximum overall metal accumulation was observed in the vertebra, followed by the kidneys and liver, with the metal pollution index (MPI) values of 0.26, 0.25, and 0.24, respectively. The minimum values were observed in the gallbladder, muscle, brain, and swim bladder, with MPI values of 0.03, 0.06, 0.07, and 0.09, respectively. Average metal concentrations in the fish muscle were below the maximum allowed concentrations for human consumption. The mean As, Cd, Pb, Cu, Fe, and Zn concentrations in the muscle were 0.028, 0.001, 0.001, 0.192, 3.966, and 3.969 μg/g wet weight, respectively. We believe that the presented findings could be of interest for the scientific community and freshwater ecosystem managers. There is a need for further research that would assess less studied tissues in different fish species.

  13. A pilot study using Tissue Velocity Ultrasound Imaging (TVI to assess muscle activity pattern in patients with chronic trapezius myalgia

    Directory of Open Access Journals (Sweden)

    Brodin Lars-Åke

    2008-09-01

    Full Text Available Abstract Background Different research techniques indicate alterations in muscle tissue and in neuromuscular control of aching muscles in patients with chronic localized pain. Ultrasound can be used for analysis of muscle tissue dynamics in clinical practice. Aim This study introduces a new muscle tissue sensitive ultrasound technique in order to provide a new methodology for providing a description of local muscle changes. This method is applied to investigate trapezius muscle tissue response – especially with respect to specific regional deformation and deformation rates – during concentric shoulder elevation in patients with chronic trapezius myalgia and healthy controls before and after pain provocation. Methods Patients with trapezius myalgia and healthy controls were analyzed using an ultrasound system equipped with tissue velocity imaging (TVI. The patients performed a standardized 3-cm concentric shoulder elevation before and after pain provocation/exercise at a standardized elevation tempo (30 bpm. A standardized region of interest (ROI, an ellipsis with a size that captures the upper and lower fascia of the trapezius muscle (4 cm width at rest, was placed in the first frame of the loop registration of the elevation. The ROI was re-anchored frame by frame following the same anatomical landmark in the basal fascia during all frames of the concentric phase. In cardiac measurement, tissue velocities are measured in the axial projection towards and against the probe where red colour represents shortening and red lengthening. In the case of measuring the trapezius muscle, tissue deformation measurements are made orthogonally, thus, indirectly. Based on the assumption of muscle volume incompressibility, blue represents tissue contraction and red relaxation. Within the ROI, two variables were calculated as a function of time: deformation and deformation rate. Hereafter, max, mean, and quadratic mean values (RMS of each variable were

  14. The evaluation of renal ischaemic damage: the value of CD10 monoclonal antibody staining and of biochemical assessments of tissue viability

    Directory of Open Access Journals (Sweden)

    Griffiths A Paul

    2007-05-01

    Full Text Available Abstract Background It is well recognised that there is often a disparity between the structural changes observed in the kidney following renal injury and the function of the organ. For this reason, we carried out studies to explore possible means of studying and quantifying the severity of renal ischaemic damage using a laboratory model. Methods To do this, freshly isolated rabbit kidney tissue was subjected to warm (37°C or cold (1°C ischaemia for 20 hours. Following this, the tissue was stained using Haematoxylin and Eosin (H+E, Periodic Schiff reagent (PAS and the novel monoclonal antibody CD10 stain. Additionally, ischaemic damage to the kidneys was assessed by biochemical tests of tissue viability using formazan-based colorimetry. Results CD 10 antibody intensely stained the brush border of control kidney tissue with mild or no cytoplasmic staining. Cell injury was accompanied by a redistribution of CD10 into the lumen and cell cytoplasm. There was good correlation between a score of histological damage using the CD 10 monoclonal antibody stain and the biochemical assessment of viability. Similarly, a score of histological damage using traditional PAS staining correlated well with that using the CD10 antibody stain. In particular, the biochemical assay and the monoclonal antibody staining techniques were able to demonstrate the efficacy of Soltran (this solution is used cold to preserve freshly isolated human kidneys prior to transplantation in preserving renal tissue at cold temperatures compared to other randomly selected solutions. Conclusion We conclude that the techniques described using the CD10 monoclonal antibody stain may be helpful in the diagnosis and assessment of ischaemic renal damage. In addition, biochemical tests of viability may have an important role in routine histopathological work by giving additional information about cellular viability which may have implications on the function of the organ.

  15. Protection of blood retinal barrier and systemic vasculature by insulin-like growth factor binding protein-3.

    Directory of Open Access Journals (Sweden)

    Yagna P R Jarajapu

    Full Text Available Previously, we showed that insulin growth factor (IGF-1 binding protein-3 (IGFBP-3, independent of IGF-1, reduces pathological angiogenesis in a mouse model of the oxygen-induced retinopathy (OIR. The current study evaluates novel endothelium-dependent functions of IGFBP-3 including blood retinal barrier (BRB integrity and vasorelaxation. To evaluate vascular barrier function, either plasmid expressing IGFBP-3 under the regulation of an endothelial-specific promoter or a control plasmid was injected into the vitreous humor of mouse pups (P1 and compared to the non-injected eyes of the same pups undergoing standard OIR protocol. Prior to sacrifice, the mice were given an injection of horseradish peroxidase (HRP. IGFBP-3 plasmid-injected eyes displayed near-normal vessel morphology and enhanced vascular barrier function. Further, in vitro IGFBP-3 protects retinal endothelial cells from VEGF-induced loss of junctional integrity by antagonizing the dissociation of the junctional complexes. To assess the vasodilatory effects of IGFBP-3, rat posterior cerebral arteries were examined in vitro. Intraluminal IGFBP-3 decreased both pressure- and serotonin-induced constrictions by stimulating nitric oxide (NO release that were blocked by L-NAME or scavenger receptor-B1 neutralizing antibody (SRB1-Ab. Both wild-type and IGF-1-nonbinding mutant IGFBP-3 (IGFBP-3NB stimulated eNOS activity/NO release to a similar extent in human microvascular endothelial cells (HMVECs. NO release was neither associated with an increase in intracellular calcium nor decreased by Ca(2+/calmodulin-dependent protein kinase II (CamKII blockade; however, dephosphorylation of eNOS-Thr(495 was observed. Phosphatidylinositol 3-kinase (PI3K activity and Akt-Ser(473 phosphorylation were both increased by IGFBP-3 and selectively blocked by the SRB1-Ab or PI3K blocker LY294002. In conclusion, IGFBP-3 mediates protective effects on BRB integrity and mediates robust NO release to stimulate

  16. Three-dimensional echocardiography with tissue harmonic imaging shows excellent reproducibility in assessment of left ventricular volumes

    DEFF Research Database (Denmark)

    Kim, Won Yong; Søgaard, Peter; Egeblad, Henrik;

    2001-01-01

    We studied the reproducibility of repeated measurements of left ventricular (LV) volumes by 2-dimensional (biplane method of disks) and 3-dimensional echocardiography (coaxial scanning) with tissue harmonic imaging. Ten healthy subjects underwent estimation of LV volumes by transthoracic echocard......We studied the reproducibility of repeated measurements of left ventricular (LV) volumes by 2-dimensional (biplane method of disks) and 3-dimensional echocardiography (coaxial scanning) with tissue harmonic imaging. Ten healthy subjects underwent estimation of LV volumes by transthoracic...

  17. Effects of Sleep Deprivation on Phase Synchronization as Assessed by Wavelet Phase Coherence Analysis of Prefrontal Tissue Oxyhemoglobin Signals

    Science.gov (United States)

    Bu, Lingguo; Zhang, Ming; Li, Jianfeng; Li, Fangyi; Liu, Heshan; Li, Zengyong

    2017-01-01

    Purpose To reveal the physiological mechanism of the decline in cognitive function after sleep deprivation, a within-subject study was performed to assess sleep deprivation effects on phase synchronization, as revealed by wavelet phase coherence (WPCO) analysis of prefrontal tissue oxyhemoglobin signals. Materials and Methods Twenty subjects (10 male and 10 female, 25.5 ± 3.5 years old) were recruited to participate in two tests: one without sleep deprivation (group A) and the other with 24 h of sleep deprivation (group B). Before the test, each subject underwent a subjective evaluation using visual analog scales. A cognitive task was performed by judging three random numbers. Continuous recordings of the near-infrared spectroscopy (NIRS) signals were obtained from both the left and right prefrontal lobes during rest, task, and post-task periods. The WPCO of cerebral Delta [HbO2] signals were analyzed for these three periods for both groups A and B. Results Six frequency intervals were defined: I: 0.6–2 Hz (cardiac activity), II: 0.145–0.6 Hz (respiratory activity), III: 0.052–0.145 Hz (myogenic activity), IV: 0.021–0.052 Hz (neurogenic activity), V: 0.0095–0.021 Hz (nitric oxide related endothelial activity) and VI: 0.005–0.0095 Hz (non-nitric oxide related endothelial activity). WPCO in intervals III (F = 5.955, p = 0.02) and V (F = 4.7, p = 0.037) was significantly lower in group B than in group A at rest. During the task period, WPCO in intervals III (F = 5.175, p = 0.029) and IV (F = 4.585, p = 0.039) was significantly lower in group B compared with group A. In the post-task recovery period, the WPCO in interval III (F = 6.125, p = 0.02) was significantly lower in group B compared with group A. Reaction time was significantly prolonged, and the accuracy rate and F1 score both declined after sleep deprivation. Conclusions The decline in WPCO after sleep deprivation indicates reduced phase synchronization between left and right prefrontal

  18. Noncontact diffuse optical assessment of blood flow changes in head and neck free tissue transfer flaps (Conference Presentation)

    Science.gov (United States)

    Huang, Chong; Radabaugh, Jeffrey P.; Aouad, Rony K.; Lin, Yu; Gal, Thomas J.; Patel, Amit B.; Valentino, Joseph; Shang, Yu; Yu, Guoqiang

    2016-02-01

    Head and neck cancer accounts for 3 to 5% of all cancers in the United States. Primary or salvage surgeries are extensive and often lead to major head and neck defects that require complex reconstructions with local, regional, or free tissue transfer flaps. Knowledge of tissue blood flow (BF) changes after free tissue transfer may enable surgeons to predict the failure of flap thrombosis at an early stage. This study used our recently developed noncontact diffuse correlation spectroscopy to monitor dynamic BF changes in free flaps without getting in contact with the targeted tissue. Eight free flaps were elevated in patients with head and neck cancer; one of the flaps failed. Multiple BF measurements probing the transferred tissue were performed during and post the surgical operation. Postoperative BF values were normalized to the intraoperative baselines (assigning '1') for the calculation of relative BF change (rBF). The rBF changes over the seven successful flaps were 1.89 +/- 0.15, 2.26 +/- 0.13, and 2.43 +/- 0.13 (mean +/- standard error) respectively on postoperative days 2, 4, and 7. These postoperative values were significantly higher than the intraoperative baseline values (p flap vascularity after the tissue transfer. By contrast, rBF changes observed from the unsuccessful flap were 1.14 and 1.34 respectively on postoperative days 2 and 4, indicating a less flow recovery. Measurement of BF recovery after flap anastomosis holds the potential to act early to salvage ischemic flaps.

  19. Children as donors: a national study to assess procurement of organs and tissues in pediatric intensive care units.

    Science.gov (United States)

    Siebelink, Marion J; Albers, Marcel J I J; Roodbol, Petrie F; Van de Wiel, Harry B M

    2012-12-01

    A shortage of size-matched organs and tissues is the key factor limiting transplantation in children. Empirical data on procurement from pediatric donors is sparse. This study investigated donor identification, parental consent, and effectuation rates, as well as adherence to the national protocol. A national retrospective cohort study was conducted in all eight Dutch pediatric intensive care units. Records of deceased children were analyzed by an independent donation officer. Seventy-four (11%) of 683 deceased children were found to be suitable for organ donation and 132 (19%) for tissue donation. Sixty-two (84%) potential organ donors had been correctly identified; the parental consent and effectuation rate was 42%. Sixty-three (48%) potential tissue donors had been correctly identified; the parental consent and effectuation rate was 27%. Correct identification increased with age (logistic regression, organs: P = .024; tissues: P = .011). Although an overall identification rate of 84% of potential organ donors may seem acceptable, the variation observed suggests room for improvement, as does the overall low rate of identification of pediatric tissue donors. Efforts to address the shortage of organs and tissues for transplantation in children should focus on identifying potential donors and on the reasons why parents do not consent.

  20. hESC Differentiation toward an Autonomic Neuronal Cell Fate Depends on Distinct Cues from the Co-Patterning Vasculature

    Directory of Open Access Journals (Sweden)

    Lisette M. Acevedo

    2015-06-01

    Full Text Available To gain insight into the cellular and molecular cues that promote neurovascular co-patterning at the earliest stages of human embryogenesis, we developed a human embryonic stem cell model to mimic the developing epiblast. Contact of ectoderm-derived neural cells with mesoderm-derived vasculature is initiated via the neural crest (NC, not the neural tube (NT. Neurovascular co-patterning then ensues with specification of NC toward an autonomic fate requiring vascular endothelial cell (EC-secreted nitric oxide (NO and direct contact with vascular smooth muscle cells (VSMCs via T-cadherin-mediated homotypic interactions. Once a neurovascular template has been established, NT-derived central neurons then align themselves with the vasculature. Our findings reveal that, in early human development, the autonomic nervous system forms in response to distinct molecular cues from VSMCs and ECs, providing a model for how other developing lineages might coordinate their co-patterning.

  1. Functional Importance of L- and P/Q-Type Voltage-Gated Calcium Channels in Human Renal Vasculature

    DEFF Research Database (Denmark)

    Hansen, Pernille B; Poulsen, Christian B; Walter, Steen

    2011-01-01

    in kidney function. It was hypothesized that human renal vascular excitation-contraction coupling involves different subtypes of channels. In human renal artery and dissected intrarenal blood vessels from nephrectomies, PCR analysis showed expression of L-type (Ca(v) 1.2), P/Q-type (Ca(v) 2.1), and T-type......, and L- and P/Q-type channels are of functional importance for the depolarization-induced vasoconstriction. The contribution of P/Q-type channels to contraction in the human vasculature is a novel mechanism for the regulation of renal blood flow and suggests that clinical treatment with calcium blockers......Calcium channel blockers are widely used for treatment of hypertension, because they decrease peripheral vascular resistance through inhibition of voltage-gated calcium channels. Animal studies of renal vasculature have shown expression of several types of calcium channels that are involved...

  2. Noninvasive monitoring of cardiac function in a chronic ischemic heart failure model in the rat: Assessment with tissue Doppler and non-Doppler 2D strain echocardiography

    Directory of Open Access Journals (Sweden)

    Baumann Gert

    2011-05-01

    Full Text Available Abstract Objectives Feasibility of noninvasive monitoring of cardiac function after surgically induced ischemic cardiomyopathy with tissue Doppler and non-Doppler 2D strain echocardiography in rats. Background The optimal method for quantitative assessment of global and regional ventricular function in rats with chronic heart failure for research purposes remains unclear. Methods 20 rats underwent suture ligation of the left anterior descending coronary artery via a left thoracotomy to induce ischemic cardiomyopathy. Echocardiographic examination with estimation of left ventricular wall thickness, diameters, fractional shortening, ejection fraction, wall velocities as well as radial strain were performed before and 4 weeks after surgery. Results Mean LVEF decreased from 70 ± 6% to 40 ± 8% (p Conclusion It is feasible to assess dimensions, global function, and regional contractility with echocardiography in rats suffering from chronic heart failure after myocardial infarction. Particularly regional function can be exactly evaluated if tissue Doppler and 2D strain is used.

  3. Brain-derived neurotrophic factor promotes vasculature-associated migration of neuronal precursors toward the ischemic striatum.

    Science.gov (United States)

    Grade, Sofia; Weng, Yuan C; Snapyan, Marina; Kriz, Jasna; Malva, João O; Saghatelyan, Armen

    2013-01-01

    Stroke induces the recruitment of neuronal precursors from the subventricular zone (SVZ) into the ischemic striatum. In injured areas, de-routed neuroblasts use blood vessels as a physical scaffold to their migration, in a process that resembles the constitutive migration seen in the rostral migratory stream (RMS). The molecular mechanism underlying injury-induced vasculature-mediated migration of neuroblasts in the post-stroke striatum remains, however, elusive. Using adult mice we now demonstrate that endothelial cells in the ischemic striatum produce brain-derived neurotrophic factor (BDNF), a neurotrophin that promotes the vasculature-mediated migration of neuronal precursors in the RMS, and that recruited neuroblasts maintain expression of p75NTR, a low-affinity receptor for BDNF. Reactive astrocytes, which are widespread throughout the damaged area, ensheath blood vessels and express TrkB, a high-affinity receptor for BDNF. Despite the absence of BDNF mRNA, we observed strong BDNF immunolabeling in astrocytes, suggesting that these glial cells trap extracellular BDNF. Importantly, this pattern of expression is reminiscent of the adult RMS, where TrkB-expressing astrocytes bind and sequester vasculature-derived BDNF, leading to the entry of migrating cells into the stationary phase. Real-time imaging of cell migration in acute brain slices revealed a direct role for BDNF in promoting the migration of neuroblasts to ischemic areas. We also demonstrated that cells migrating in the ischemic striatum display higher exploratory behavior and longer stationary periods than cells migrating in the RMS. Our findings suggest that the mechanisms involved in the injury-induced vasculature-mediated migration of neuroblasts recapitulate, at least partially, those observed during constitutive migration in the RMS.

  4. Brain-derived neurotrophic factor promotes vasculature-associated migration of neuronal precursors toward the ischemic striatum.

    Directory of Open Access Journals (Sweden)

    Sofia Grade

    Full Text Available Stroke induces the recruitment of neuronal precursors from the subventricular zone (SVZ into the ischemic striatum. In injured areas, de-routed neuroblasts use blood vessels as a physical scaffold to their migration, in a process that resembles the constitutive migration seen in the rostral migratory stream (RMS. The molecular mechanism underlying injury-induced vasculature-mediated migration of neuroblasts in the post-stroke striatum remains, however, elusive. Using adult mice we now demonstrate that endothelial cells in the ischemic striatum produce brain-derived neurotrophic factor (BDNF, a neurotrophin that promotes the vasculature-mediated migration of neuronal precursors in the RMS, and that recruited neuroblasts maintain expression of p75NTR, a low-affinity receptor for BDNF. Reactive astrocytes, which are widespread throughout the damaged area, ensheath blood vessels and express TrkB, a high-affinity receptor for BDNF. Despite the absence of BDNF mRNA, we observed strong BDNF immunolabeling in astrocytes, suggesting that these glial cells trap extracellular BDNF. Importantly, this pattern of expression is reminiscent of the adult RMS, where TrkB-expressing astrocytes bind and sequester vasculature-derived BDNF, leading to the entry of migrating cells into the stationary phase. Real-time imaging of cell migration in acute brain slices revealed a direct role for BDNF in promoting the migration of neuroblasts to ischemic areas. We also demonstrated that cells migrating in the ischemic striatum display higher exploratory behavior and longer stationary periods than cells migrating in the RMS. Our findings suggest that the mechanisms involved in the injury-induced vasculature-mediated migration of neuroblasts recapitulate, at least partially, those observed during constitutive migration in the RMS.

  5. Large Field, High Resolution Full Field Optical Coherence Tomography: A Pre-clinical study of human breast tissue and cancer assessment

    CERN Document Server

    Assayag, Osnath; Sigal-Zafrani, Brigitte; Riben, Michael; Harms, Fabrice; Burcheri, Adriano; de Poly, Bertrand Le Conte; Boccara, Claude

    2012-01-01

    We present a benchmark pilot study in which high-resolution Full-Field Optical Coherence Tomography (FF-OCT) is used to image human breast tissue and is evaluated to assess its ability to aid the pathologist's management of intra-operative diagnoses. Our aim included evaluating the safety of FF-OCT on human tissue and determining the concordance between the images obtained with routinely prepared histopathological material. The compact device used for this study provides a 2 {\\mu}m-lateral and a 1 {\\mu}m-axial resolution, and is able to scan a 1.5cm^2 specimen in about 7 minutes. 75 breast specimens obtained from 22 patients have been imaged. Because the contrast in the images is generated by endogenous tissue components, no biological, contrast agents or specimen preparation is required. We characterized the major architectural features and tissue structures of benign breast tissue, including adipocytes, fibrous stroma, lobules and ducts. We subsequently characterized features resulting from their pathologic...

  6. Functional Response of Tumor Vasculature to PaCO2: Determination of Total and Microvascular Blood Volume by MRI

    Directory of Open Access Journals (Sweden)

    Scott D. Packard

    2003-07-01

    Full Text Available In order to identify differences in functional activity, we compared the reactivity of glioma vasculature and the native cerebral vasculature to both dilate and constrict in response to altered PaCO2. Gliomas were generated by unilateral implantation of U87MGdEGFR human glioma tumor cells into the striatum of adult female athymic rats. Relative changes in total and microvascular cerebral blood volume were determined by steady state contrast agent-enhanced magnetic resonance imaging for transitions from normocarbia to hypercarbia and hypocarbia. Although hypercarbia induced a significant increase in both total and microvascular blood volume in normal brain and glioma, reactivity of glioma vasculature was significantly blunted in comparison to normal striatum; glioma total CBV increased by 0.6±0.1%/mm Hg CO2 whereas normal striatum increased by 1.5±0.2%/mm Hg CO2, (P < .0001, group t-test. Reactivity of microvascular blood volume was also significantly blunted. In contrast, hypocarbia decreased both total and microvascular blood volumes more in glioma than in normal striatum. These results indicate that cerebral blood vessels derived by tumor-directed angiogenesis do retain reactivity to CO2. Furthermore, reduced reactivity of tumor vessels to a single physiological perturbation, such as hypercarbia, should not be construed as a generalized reduction of functional activity of the tumor vascular bed.

  7. Vascular endothelial growth factor-D over-expressing tumor cells induce differential effects on uterine vasculature in a mouse model of endometrial cancer

    Directory of Open Access Journals (Sweden)

    Stacker Steven A

    2010-07-01

    Full Text Available Abstract Background It has been hypothesised that increased VEGF-D expression may be an independent prognostic factor for endometrial cancer progression and lymph node metastasis; however, the mechanism by which VEGF-D may promote disease progression in women with endometrial cancer has not been investigated. Our aim was to describe the distribution of lymphatic vessels in mouse uterus and to examine the effect of VEGF-D over-expression on these vessels in a model of endometrial cancer. We hypothesised that VEGF-D over-expression would stimulate growth of new lymphatic vessels into the endometrium, thereby contributing to cancer progression. Methods We initially described the distribution of lymphatic vessels (Lyve-1, podoplanin, VEGFR-3 and VEGF-D expression in the mouse uterus during the estrous cycle, early pregnancy and in response to estradiol-17beta and progesterone using immunohistochemistry. We also examined the effects of VEGF-D over-expression on uterine vasculature by inoculating uterine horns in NOD SCID mice with control or VEGF-D-expressing 293EBNA tumor cells. Results Lymphatic vessels positive for the lymphatic endothelial cell markers Lyve-1, podoplanin and VEGFR-3 profiles were largely restricted to the connective tissue between the myometrial circular and longitudinal muscle layers; very few lymphatic vessel profiles were observed in the endometrium. VEGF-D immunostaining was present in all uterine compartments (epithelium, stroma, myometrium, although expression was generally low. VEGF-D immunoexpression was slightly but significantly higher in estrus relative to diestrus; and in estradiol-17beta treated mice relative to vehicle or progesterone treated mice. The presence of VEGF-D over-expressing tumor cells did not induce endometrial lymphangiogenesis, although changes were observed in existing vessel profiles. For myometrial lymphatic and endometrial blood vessels, the percentage of profiles containing proliferating

  8. First Quantitative Imaging of Organic Fluorine within Angiogenic Tissues by Particle Induced Gamma-Ray Emission (PIGE Analysis: First PIGE Organic Fluorine Imaging

    Directory of Open Access Journals (Sweden)

    Gérard Déléris

    2011-03-01

    Full Text Available PET (Positron Emission Tomography allows imaging of the in vivo distribution of biochemical compounds labeled with a radioactive tracer, mainly 18F-FDG (2-deoxy-2-[18F] fluoro-D-glucose. 18F only allows a relatively poor spatial resolution (2-3 mm which does not allow imaging of small tumors or specific small size tissues, e.g. vasculature. Unfortunately, angiogenesis is a key process in various physiologic and pathologic processes and is, for instance, involved in modern anticancer approaches. Thus ability to visualize angiogenesis could allow early diagnosis and help to monitor the response of cancer to specific chemotherapies. Therefore, indirect analytical techniques are required to assess the localization of fluorinated compounds at a micrometric scale. Multimodality imaging approaches could provide accurate information on the metabolic activity of the target tissue. In this article, PIGE method (Particle Induced Gamma-ray Emission was used to determine fluorinated tracers by the nuclear reaction of 19F(p,p′γ19F in tissues. The feasibility of this approach was assessed on polyfluorinated model glucose compounds and novel peptide-based tracer designed for angiogenesis imaging. Our results describe the first mapping of the biodistribution of fluorinated compounds in both vascularized normal tissue and tumor tissue.

  9. First Quantitative Imaging of Organic Fluorine within Angiogenic Tissues by Particle Induced Gamma-Ray Emission (PIGE) Analysis: First PIGE Organic Fluorine Imaging.

    Science.gov (United States)

    Lavielle, Sébastien; Gionnet, Karine; Ortega, Richard; Devès, Guillaume; Kilarski, Victor; Wehbe, Katia; Bikfalvi, Andreas; Déléris, Gérard

    2011-03-09

    PET (Positron Emission Tomography) allows imaging of the in vivo distribution of biochemical compounds labeled with a radioactive tracer, mainly 18F-FDG (2-deoxy-2-[18F] fluoro-D-glucose). 18F only allows a relatively poor spatial resolution (2-3 mm) which does not allow imaging of small tumors or specific small size tissues, e.g. vasculature. Unfortunately, angiogenesis is a key process in various physiologic and pathologic processes and is, for instance, involved in modern anticancer approaches. Thus ability to visualize angiogenesis could allow early diagnosis and help to monitor the response of cancer to specific chemotherapies. Therefore, indirect analytical techniques are required to assess the localization of fluorinated compounds at a micrometric scale. Multimodality imaging approaches could provide accurate information on the metabolic activity of the target tissue. In this article, PIGE method (Particle Induced Gamma-ray Emission) was used to determine fluorinated tracers by the nuclear reaction of 19F(p,p'γ)19F in tissues. The feasibility of this approach was assessed on polyfluorinated model glucose compounds and novel peptide-based tracer designed for angiogenesis imaging. Our results describe the first mapping of the biodistribution of fluorinated compounds in both vascularized normal tissue and tumor tissue.

  10. Assessment of apoptosis and oxidative stress in retina tissue of rats with diabetic retinopathy after grape polyphenols intervention

    Institute of Scientific and Technical Information of China (English)

    Sheng-Li Zhang

    2016-01-01

    Objective:To study the effect of grape polyphenols intervention on apoptosis and oxidative stress in retina tissue of rats with diabetic retinopathy (DR).Methods: SPF male SD rats were selected as experimental animals and divided into control group, diabetes group and grape polyphenols group, intraperitoneal injection of streptozotocin was adopted to establish diabetic rat models, and grape polyphenols group received intragastric administration of grape polyphenols. 60 d after model establishment, the rats were executed, and the retina tissue was collected to determine apoptosis molecules and oxidative stress indexes.Results:Bax, Caspase-3, c-fos, c-jun, ROS, MDA, 8-OHdG, PARP, Cyclophilin D, Nrf-2, ARE, ERK and PI3K content in retina tissue of diabetes group were significantly higher than those of control group while Bcl-2, CAT, SOD, GSH-Px, HO-1 and NQO1 content were significantly lower than those of control group; Bax, Caspase-3, c-fos, c-jun, ROS, MDA, 8-OHdG, PARP and Cyclophilin D content in retina tissue of grape polyphenols group were significantly lower than those of diabetes group while Bcl-2, CAT, SOD, GSH-Px, HO-1, NQO1, Nrf-2, ARE, ERK and PI3K content were significantly higher those of diabetes group.Conclusions:Grape polyphenols intervention can relieve the apoptosis and oxidative stress in retina tissue of rats with diabetic retinopathy.

  11. Vasculature of the parotoid glands of four species of toads (bufonidae: bufo).

    Science.gov (United States)

    Hutchinson, Deborah A; Savitzky, Alan H

    2004-05-01

    The parotoid glands of toads (Bufonidae) consist of large aggregations of granular glands located between the otic region of the skull and the scapular region. To determine the circulatory pattern of these glands, we perfused the vascular systems of Bufo alvarius, B. marinus, B. terrestris, and B. valliceps with either India ink or Microfil, a fine latex. The perfused glands were studied by gross dissection, microscopic examination, and histology. The vascular patterns of the parotoid glands were compared to the arrangement of vessels in the dorsal skin of Rana sphenocephala (Ranidae), a frog that lacks parotoid glands. The parotoid glands of the four species of toads are supplied with blood by the lateral and dorsal cutaneous arteries and are drained by one or more branches of the internal jugular vein. The dorsal cutaneous artery supplies most of the blood to the parotoid glands in B. terrestris and B. valliceps. In B. alvarius and B. marinus, both the lateral and dorsal cutaneous arteries serve major roles in the blood supply of the glands. These patterns of blood flow have not been described previously for parotoid glands and conflict with earlier accounts for B. alvarius and B. marinus. The arteries and veins associated with the parotoid glands of toads are present in R. sphenocephala, but are arranged differently. In R. sphenocephala, the lateral cutaneous artery supplies the dorsal and lateral skin posterior to the shoulder region, whereas the dorsal cutaneous artery supplies the skin of the shoulder region. In toads, both the lateral and dorsal cutaneous arteries supply the skin of the shoulder region and ramify into subcutaneous capillaries that surround the secretory units of the parotoid glands. Extensive vasculature presumably is important for delivering cholesterol and other precursor molecules to the parotoid glands, where those compounds are converted into toxins.

  12. Evaluation of Hepatic Vasculature in Fatty Liver Patients with Duplex Doppler Sonography

    Directory of Open Access Journals (Sweden)

    Nahid Sedighi

    2010-05-01

    Full Text Available Background/Objective: Duplex Doppler ultrasonography (US has been newly suggested as an important diagnostic technique in the non-invasive evaluation of hepatic vasculature and some hepatic parenchymal diseases. New findings suggest that diffuse fatty infiltration of the liver can alter normal hepatic vein and artery Doppler indices. The following study has been performed to evaluate the effect of fatty infiltration on portal vein indices."nPatients and Methods: Forty-eight patients with various degrees of fatty infiltration of the liver and 48 normal subjects without any signs of hepatic fatty infiltration in ultrasonography were examined using standard color Doppler sonography. Maximum and minimum peak velocity and resistance index were compared in the two groups."nResults: The mean of maximum peak velocity in the portal vein was 25.9±9.9 and 34.3±18.3 in the case and control group, respectively (P=0.006. The mean of minimum peak velocity in the portal vein was 19.2±9.9 and 18.7±8.7 in the case and control group, respectively (P=0.795. The mean of resistance index was 0.25±0.09 and 0.41±0.15 in the case and control group, respectively (P<0.001."nConclusion: The mean of maximum peak velocity and the mean of resistance index in the portal vein was significantly lower in patients with fatty infiltration compared to those who had no abnormality in the liver ultrasonography .

  13. Ontogenetic changes in the shoot primary vasculature of Anagallis arvensis L.

    Directory of Open Access Journals (Sweden)

    Dorota Kwiatkowska

    2014-01-01

    Full Text Available Ontogenetic changes in the primary vasculature of Anagallis shoots are strictly related to phyllotaxis. During the ontogeny of Anagallis, whorled and spiral phyllotactic patterns appear alternately in a regular sequence. The initial decussate phyllotaxis is transformed into the spiral Fibonacci, and then further into trimerous pattern. This in turn may change into the spiral Lucas phyllotaxis. Sporadically the immediate transition from the decussate to trimerous phyllotaxis takes place. The vascular system in Anagallis is always closed, despite that both whorled and spiral phyllotaxes are present. Also the number of vascular traces diverging to the leaf is constant. In the course of a single phyllotactic transition, there is an increase in the number of vascular sympodia and in the number of leaf traces present in the vascular cylinder. Usually only one single sympodium and one or two traces are added to the system. The immediate addition of two sympodia occurs only during infrequent transition from the decussate to trimerous pattern. The increase in the number of sympodia is most often simultaneous with the phyllotactic transition, however, when the trimerous pattern is transformed into the spiral Lucas, the increase is delayed, sometimes for as much as ten plastochrons. In shoots with changing phyllotaxis, a sector within the vascular cylinder can be distinguished, in which the leaf traces are arranged as if the previous phyllotactic pattern continued, whereas rearrangement of traces takes place at the same level but in the complementary sector. This is in agreement with the concept of discontinuous circumferential changes in the shoot apex being responsible for qualitative transformations of phyllotaxis.

  14. Metals in tissues of seabass and seabream reared in sites with oxic and anoxic substrata and risk assessment for consumers.

    Science.gov (United States)

    Kalantzi, I; Pergantis, S A; Black, K D; Shimmield, T M; Papageorgiou, N; Tsapakis, M; Karakassis, I

    2016-03-01

    Twenty-eight metals and elements were measured in the muscle, liver, gills, bone and intestine of farmed seabass and gilthead seabream from four Mediterranean fish farms. The influence of fish species and the effect of environmental conditions on the metal accumulation in fish tissues was investigated. Most concentrations were lower in muscle and higher in liver and bone than in other body tissues. Seabass accumulates more elements in its tissues than seabream. Fish reared in coarse, oxic sites accumulate more elements with higher concentrations in muscle, bone and intestine and with lower concentrations in liver and gills than fish reared in silty, anoxic sites. This may be attributed to feed type and sediment properties. According to the metal pollution index, hazard quotient, selenium health benefit values, carcinogenic risk of arsenic, maximum safe consumption and the permitted limits, the consumption of both farmed species should be considered as safe for human health.

  15. The assessment of cardiac functions by tissue Doppler-derived myocardial performance index in patients with Behcet's disease.

    Science.gov (United States)

    Tavil, Yusuf; Ozturk, Mehmet Akif; Sen, Nihat; Kaya, Mehmet Gungor; Hizal, Fatma; Poyraz, Fatih; Turfan, Murat; Onder, Meltem; Gurer, Mehmet Ali; Cengel, Atiye

    2008-03-01

    Vascular involvement is one of the major characteristics of Behcet's disease (BD). However, there are controversial findings regarding cardiac involvement in BD. Although early reports demonstrated that there is diastolic dysfunction in BD, conflicting results were found in the following trials. Hence, a new method for more objectively estimating the cardiac functions is needed. For this aim, we used high-usefulness tissue Doppler echocardiography for detailed analysis of cardiac changes in BD patients because this method was superior to other conventional echocardiographic techniques. The study population included 42 patients with BD (19 men, 23 women; mean age, 35 +/- 10 years, mean disease duration, 2.7 +/- 1.6 years) and 30 healthy subjects (14 men, 16 women; mean age, 38 +/- 7 years). Cardiac functions were determined using echocardiography, comprising standard two-dimensional and conventional Doppler and tissue Doppler imaging (TDI). Peak systolic myocardial velocity at mitral annulus, early diastolic mitral annular velocity (Em), late diastolic mitral annular velocity (Am), Em/Am, and myocardial performance index (MPI) were calculated by TDI. The conventional echocardiographic parameters and tissue Doppler measurements were similar between the groups. Tissue Doppler derived mitral relaxation time was longer (75 +/- 13 vs 63 +/- 16 msn, p = 0.021) in patients with BD. There was statistically significant difference between the two groups regarding left ventricular MPI (0.458 +/- 0.072 vs 0.416 +/- 0.068%, p = 0.016), which were calculated from tissue Doppler systolic time intervals. There was also significant correlation between the disease duration and MPI (r = 0.38, p = 0.017). We have demonstrated that tissue Doppler-derived myocardial left ventricular relaxation time and MPI were impaired in BD patients, although systolic and diastolic function parameters were comparable in the patients and controls.

  16. SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hou, P; Park, P; Li, H; Zhu, X; Mahajan, A; Grosshans, D [M.D. Anderson Cancer Center, Houston, TX (United States)

    2015-06-15

    Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated with PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted.

  17. Oxygen-enhanced MRI for patients with connective tissue diseases: Comparison with thin-section CT of capability for pulmonary functional and disease severity assessment

    Energy Technology Data Exchange (ETDEWEB)

    Ohno, Yoshiharu, E-mail: yosirad@kobe-u.ac.jp [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Nishio, Mizuho [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Koyama, Hisanobu [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Yoshikawa, Takeshi; Matsumoto, Sumiaki [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Seki, Shinichiro [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Tsubakimoto, Maho [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Nakagami-Gun, Okinawa (Japan); Sugimura, Kazuro [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan)

    2014-02-15

    Purpose: To prospectively and directly compare oxygen-enhanced (O{sub 2}-enhanced) MRI with thin-section CT for pulmonary functional loss and disease severity assessment in connective tissue disease (CTD) patients with interstitial lung disease (ILD). Materials and methods: Thin-section CT, O{sub 2}-enhanced MRI, pulmonary function test and serum KL-6 were administered to 36 CTD patients with ILD (23 men, 13 women; mean age: 63.9 years) and nine CTD patients without ILD (six men, and three women; mean age: 62.0 years). A relative-enhancement ratio (RER) map was generated from O{sub 2}-enhanced MRI and mean relative enhancement ratio (MRER) for each subject was calculated from all ROI measurements. CT-assessed disease severity was evaluated with a visual scoring system from each of the thin-section CT data. MRER and CT-assessed disease severities of CTD patients with and without ILD were then statistically compared. To assess capability for pulmonary functional loss and disease severity assessment in CTD patients, correlations of MRER and CT-assessed disease severity with pulmonary functional parameters and serum KL-6 in all subjects were statistically determined. Results: MRER and CT-assessed disease severity showed significant differences between CTD patients with (MRER: 0.15 ± 0.08, CT-assessed disease severity: 13.0 ± 7.4%) and without ILD (MRER: 0.25 ± 0.06, p = 0.0011; CT-assessed disease severity: 1.6 ± 1.6%, p < 0.0001). MRER and CT-assessed disease severity correlated significantly with pulmonary functional parameters and serum KL-6 in all subjects (0.61 ≤ r ≤ 0.79, p < 0.05). Conclusion: O{sub 2}-enhanced MRI was found to be as useful as thin-section CT for pulmonary functional loss and disease severity assessment of CTD patients with ILD.

  18. Morph-X-Select: Morphology-based tissue aptamer selection for ovarian cancer biomarker discovery

    Science.gov (United States)

    Wang, Hongyu; Li, Xin; Volk, David E.; Lokesh, Ganesh L.-R.; Elizondo-Riojas, Miguel-Angel; Li, Li; Nick, Alpa M.; Sood, Anil K.; Rosenblatt, Kevin P.; Gorenstein, David G.

    2016-01-01

    High affinity aptamer-based biomarker discovery has the advantage of simultaneously discovering an aptamer affinity reagent and its target biomarker protein. Here, we demonstrate a morphology-based tissue aptamer selection method that enables us to use tissue sections from individual patients and identify high-affinity aptamers and their associated target proteins in a systematic and accurate way. We created a combinatorial DNA aptamer library that has been modified with thiophosphate substitutions of the phosphate ester backbone at selected 5′dA positions for enhanced nuclease resistance and targeting. Based on morphological assessment, we used image-directed laser microdissection (LMD) to dissect regions of interest bound with the thioaptamer (TA) library and further identified target proteins for the selected TAs. We have successfully identified and characterized the lead candidate TA, V5, as a vimentin-specific sequence that has shown specific binding to tumor vasculature of human ovarian tissue and human microvascular endothelial cells. This new Morph-X-Select method allows us to select high-affinity aptamers and their associated target proteins in a specific and accurate way, and could be used for personalized biomarker discovery to improve medical decision-making and to facilitate the development of targeted therapies to achieve more favorable outcomes. PMID:27839510

  19. Application of non-lethal stable isotope analysis to assess feeding patterns of juvenile pallid sturgeon Scaphirhynchus albus: a comparison of tissue types and sample preservation methods

    Science.gov (United States)

    Andvik, R.T.; VanDeHey, J.A.; Fincel, M.J.; French, William E.; Bertrand, K.N.; Chipps, Steven R.; Klumb, R.A.; Graeb, B.D.S.

    2010-01-01

    Traditional techniques for stable isotope analysis (SIA) generally require sacrificing animals to collect tissue samples; this can be problematic when studying diets of endangered species such as the pallid sturgeon Scaphirhynchus albus. Our objectives were to (i) determine if pectoral fin tissue (non-lethal) could be a substitute for muscle tissue (lethal) in SIA of juvenile pallid sturgeon, and (ii) evaluate the influence of preservation techniques on stable isotope values. In the laboratory, individual juvenile pallid sturgeon were held for up to 186 day and fed chironomids, fish, or a commercially available pellet diet. Significant, positive relationships (r² ≥ 0.8) were observed between fin and muscle tissues for both δ15N and δ13C; in all samples isotopes were enriched in fins compared to muscle tissue. Chironomid and fish based diets of juvenile pallid sturgeon were distinguishable for fast growing fish (0.3 mm day−1) using stable δ15N and δ13C isotopes. Frozen and preserved fin tissue δ15N isotopes were strongly related (r2 = 0.89) but δ13C isotopes were weakly related (r2 = 0.16). Therefore, freezing is recommended for preservation of fin clips to avoid the confounding effect of enrichment by ethanol. This study demonstrates the utility of a non-lethal technique to assess time integrated food habits of juvenile pallid sturgeon and should be applicable to other threatened or endangered species.

  20. Cardiac dysfunction assessed by echocardiographic tissue Doppler imaging is an independent predictor of mortality in the general population

    DEFF Research Database (Denmark)

    Mogelvang, Rasmus; Sogaard, Peter; Pedersen, Sune A

    2009-01-01

    BACKGROUND: Tissue Doppler imaging (TDI) detects left ventricular dysfunction in patients with heart failure and normal ejection fraction, but the prognostic significance of left ventricular dysfunction by TDI in the general population is unknown. METHODS AND RESULTS: Within the Copenhagen City...

  1. In situ hybridization with labeled probes: assessment of african Swine Fever virus in formalin-fixed paraffin-embedded tissues.

    Science.gov (United States)

    Ballester, Maria; Rodríguez, Fernando

    2015-01-01

    In situ hybridization (ISH) has become a very valuable molecular diagnostic tool to detect specific DNA or RNA sequences in biological samples through the use of complementary DNA- or RNA-labeled probes. Here, we describe an optimized in situ hybridization protocol to detect African swine fever virus (ASFV) DNA in formalin-fixed, paraffin-embedded tissues using digoxigenin-labeled probes.

  2. Speckle-Tracking Sonographic Assessment of Longitudinal Motion of the Flexor Tendon and Subsynovial Tissue in Carpal Tunnel Syndrome

    NARCIS (Netherlands)

    van Doesburg, Margriet H. M.; Yoshii, Yuichi; Henderson, Jacqueline; Villarraga, Hector R.; Moran, Steven L.; Amadio, Peter C.

    2012-01-01

    Objectives-The aim of this study was to image both tendon and subsynovial connective tissue movement in patients with carpal tunnel syndrome and healthy control volunteers, using sonography with speckle tracking. To estimate accuracy of this tracking method, we used in vivo measurements during surge

  3. Tissue-Doppler assessment of cardiac left ventricular function during short-term adjuvant epirubicin therapy for breast cancer

    DEFF Research Database (Denmark)

    Appel, Jon M; Sogaard, Peter; Mortensen, Christiane E;

    2011-01-01

    It has been hypothesized that the extent of acute anthracycline-induced cardiotoxicity reflects the risk for late development of heart failure. The aim of this study was to examine if short-term changes in cardiac function can be detected even after low-dose adjuvant epirubicin therapy for breast...... cancer when using Doppler tissue imaging of longitudinal left ventricular function....

  4. Children as donors : a national study to assess procurement of organs and tissues in pediatric intensive care units

    NARCIS (Netherlands)

    Siebelink, Marion J.; Albers, Marcel J. I. J.; Roodbol, Petrie F.; Van de Wiel, Harry B. M.

    2012-01-01

    A shortage of size-matched organs and tissues is the key factor limiting transplantation in children. Empirical data on procurement from pediatric donors is sparse. This study investigated donor identification, parental consent, and effectuation rates, as well as adherence to the national protocol.

  5. Imaging Tumor Vasculature Noninvasively with Positron Emission Tomography and RGD Peptides Labeled with Copper 64 Using the Bifunctonal Chelates DOTA, Oxo-DO3A. and PCTA

    Directory of Open Access Journals (Sweden)

    Donald T.T. Yapp

    2013-06-01

    Full Text Available Two novel bifunctional chelates, 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15,11,13-triene-3,6,9-triacetic acid (PCTA and 1-oxa-4,7,10-triazacyclododecane-4,7,10-triacetic acid (Oxo-DO3A, were found to radiolabel antibodies with copper 64 (64Cu well for positron emission tomography (PET. In this study, the same chelators were used to radiolabel peptides with 64Cu for PET imaging of angiogenesis. PCTA, Oxo-DO3A, and 1,4,7,10-tetraazacyclododecane-N,N‘,N“,N”’-tetraacetic acid (DOTA were conjugated to cyclic-(RGDyK, and their binding affinities were confirmed. Conditions for 64Cu radiolabeling were optimized for maximum yield and specific activity. The in vitro stability of the radiolabeled compounds was challenged with serum incubation. PET studies were carried out in a non-αvβ3-expressing tumor model to evaluate the compounds' specificity for proliferating tumor vasculature and their in vivo pharmacokinetics. The PCTA and Oxo-DO3A bioconjugates were labeled with 64Cu at higher effective specific activity and radiochemical yield than the DOTA bioconjugate. In the imaging studies, all the 64Cu bioconjugates could be used to visualize the tumor and the radiotracer uptake was blocked with cyclic-(RGDyK. Target uptake of each bioconjugate was similar, but differences in other tissues were observed. 64Cu-PCTA-RGD showed the best clearance from nontarget tissue and the highest tumor to nontarget ratios. PCTA was the most promising bifunctional chelate for 64Cu peptide imaging and warrants further investigation.

  6. Using the Monte Carlo method for assessing the tissue and organ doses of patients in dental radiography

    Science.gov (United States)

    Makarevich, K. O.; Minenko, V. F.; Verenich, K. A.; Kuten, S. A.

    2016-05-01

    This work is dedicated to modeling dental radiographic examinations to assess the absorbed doses of patients and effective doses. For simulating X-ray spectra, the TASMIP empirical model is used. Doses are assessed on the basis of the Monte Carlo method by using MCNP code for voxel phantoms of ICRP. The results of the assessment of doses to individual organs and effective doses for different types of dental examinations and features of X-ray tube are presented.

  7. Use of a laser displacement sensor with a non-contact electromagnetic vibration device for assessment of simulated periodontal tissue conditions.

    Science.gov (United States)

    Kobayashi, Hiroshi; Yamaoka, Masaru; Hayashi, Makoto; Ogiso, Bunnai

    2016-01-01

    A non-contact electromagnetic vibration device (NEVD) was previously developed to monitor the condition of periodontal tissues by assessing mechanical parameters. This system requires placement of an accelerometer on the target tooth, to detect vibration. Using experimental tooth models, we evaluated the performance of an NEVD system with a laser displacement sensor (LDS), which does not need an accelerometer. Simulated teeth (polyacetal rods) were submerged at various depths in simulated bone (polyurethane or polyurethane foam) containing simulated periodontal ligament (tissue conditioner). Then, mechanical parameters (resonant frequency, elastic modulus, and viscosity coefficient) were assessed using the NEVD with the following detection methods: Group 1, measurement with an accelerometer; Group 2, measurement with an LDS in the presence of the accelerometer; and Group 3, measurement with an LDS in the absence of the accelerometer. Statistical analyses were performed using nonparametric methods (n = 5) (P < 0.05). The three mechanical parameters significantly increased with increasing depth. In addition, the mechanical parameters significantly differed between the polyurethane and polyurethane foam models. Although Groups 1 and 2 did not significantly differ, most all mechanical parameters in Group 3 were significantly larger and more distinguishable than those in Groups 1 and 2. The LDS was more accurate in measuring mechanical parameters and better able to differentiate periodontal tissue conditions. (J Oral Sci 58, 93-99, 2016).

  8. Left ventricular dyssynchrony assessed by two three-dimensional imaging modalities: phase analysis of gated myocardial perfusion SPECT and tri-plane tissue Doppler imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ajmone Marsan, Nina [Leiden University Medical Center, Department of Cardiology, Albinusdreef 2, ZA, Leiden (Netherlands); Policlinico S. Matteo, Department of Cardiology, Pavia (Italy); Henneman, Maureen M.; Ypenburg, Claudia; Bleeker, Gabe B.; Bax, Jeroen J. [Leiden University Medical Center, Department of Cardiology, Albinusdreef 2, ZA, Leiden (Netherlands); Chen, Ji; Garcia, Ernest V. [Emory University School of Medicine, Department of Radiology, Atlanta, Georgia (United States); Dibbets, Petra; Stokkel, Marcel P. [Leiden University Medical Center, Department of Nuclear Medicine, Leiden (Netherlands); Ghio, Stefano; Tavazzi, Luigi [Policlinico S. Matteo, Department of Cardiology, Pavia (Italy); Wall, Ernst E. van der [Leiden University Medical Center, Department of Cardiology, Albinusdreef 2, ZA, Leiden (Netherlands); The Interuniversity Cardiology Institute of the Netherlands, Utrecht (Netherlands)

    2008-01-15

    To compare left ventricular (LV) dyssynchrony assessment by phase analysis from gated myocardial perfusion SPECT (GMPS) with LV dyssynchrony assessment by tri-plane tissue Doppler imaging (TDI). Baseline LV dyssynchrony assessed with standard deviation (SD) of time-to-peak systolic velocity of 12 LV segments (Ts-SD) with TDI has proven to be a powerful predictor of response to CRT. Information on LV dyssynchrony can also be provided by GMPS with phase analysis of regional LV maximal count changes throughout the cardiac cycle. Forty heart failure patients, referred for evaluation of potential eligibility for CRT, underwent both 3D echocardiography, with tri-plane TDI, and resting GMPS. From tri-plane TDI, Ts-SD was used as a validated parameter of LV dyssynchrony and compared with different indices (histogram bandwidth, phase SD, histogram skewness and kurtosis) derived from phase analysis of GMPS. Histogram bandwidth and phase SD showed good correlation with Ts-SD (r=0.77 and r=0.74, p<0.0001, respectively). Patients with substantial LV dyssynchrony assessed with tri-plane TDI (Ts-SD {>=}33 ms) had also significantly higher values of histogram bandwidth and phase SD. The results of this study support the use of phase analysis by GMPS to evaluate LV dyssynchrony. Histogram bandwidth and phase SD showed the best correlation with Ts-SD assessed with tri-plane TDI and appeared the most optimal variables for assessment of LV dyssynchrony with GMPS. (orig.)

  9. Impact of tissue atrophy on high-pass filtered MRI signal phase-based assessment in large-scale group-comparison studies: A simulation study

    Science.gov (United States)

    Schweser, Ferdinand; Dwyer, Michael G.; Deistung, Andreas; Reichenbach, Jürgen R.; Zivadinov, Robert

    2013-10-01

    The assessment of abnormal accumulation of tissue iron in the basal ganglia nuclei and in white matter plaques using the gradient echo magnetic resonance signal phase has become a research focus in many neurodegenerative diseases such as multiple sclerosis or Parkinson’s disease. A common and natural approach is to calculate the mean high-pass-filtered phase of previously delineated brain structures. Unfortunately, the interpretation of such an analysis requires caution: in this paper we demonstrate that regional gray matter atrophy, which is concomitant with many neurodegenerative diseases, may itself directly result in a phase shift seemingly indicative of increased iron concentration even without any real change in the tissue iron concentration. Although this effect is relatively small results of large-scale group comparisons may be driven by anatomical changes rather than by changes of the iron concentration.

  10. Real-time and label free determination of ligand binding-kinetics to primary cancer tissue specimens; a novel tool for the assessment of biomarker targeting

    DEFF Research Database (Denmark)

    Clausen, Thomas Mandel; Ayres Pereira, Marina; Oo, Htoo Zarni;

    2016-01-01

    In clinical oncology, diagnosis and evaluation of optimal treatment strategies are mostly based on histopathological examination combined with immunohistochemical (IHC) expression analysis of cancer-associated antigens in formalin fixed paraffin-embedded (FFPE) tissue biopsies. However, informative...... of epitopes available, this readout offers a quantitative and unbiased readout for in situ binding-avidity and amount of binding epitopes. In summary, this method adds a new and important dimension to classical IHC-based molecular pathology by adding information about the binding characteristics...... IHC analysis depends on both the specificity and affinity of the binding reagent, which are inherently difficult to quantify in situ. Here we describe a label-free method that allows for the direct and real-time assessment of molecular binding kinetics in situ on FFPE tissue specimens using quartz...

  11. Assessing the Impact of EDTA Chelating Effect on some Macro- and Microminerals in Prussian Carp (Carassius Gibelio Tissues

    Directory of Open Access Journals (Sweden)

    Marioara Nicula

    2011-10-01

    Full Text Available Chelators are used in chemical analysis, in medical aplications, as water softeners, as decontamination agents on radioactive surfaces and they are ingredients in many commercial products such as shampoos and food preservatives. Such a synthetic chelator is EDTA (ethylenediaminetetraacetic acid. It is considered one of the tools that promises to control the heavy metal pollution in aquaculture. EDTA attaches itself to heavy metals and carries the metals from the fish body. EDTA can also slow free-radical activity produced by heavy metals in the body. Because its ability to sequester metal ions, we tried to estimate the potential risks of a chronic exposure to EDTA on tissue mobilization of some metals which have an essential role in realization of different cell functions in Prussian carp specimens. Ca, Mg, Fe, Zn. Mn and Cu, were the mineral elements we have targeted in this study. It was found that these minerals have a trend of their tissues distribution and concentration in the body of the control specimens (higher or lower related to other similar works and EDTA presence in water led to a significant decreasing of their level in all tissues analyzed in a dose-dependent manner.

  12. Acoustic Assessment of a Konjac–Carrageenan Tissue-Mimicking Material at 5–60 MHz

    Science.gov (United States)

    Kenwright, David A.; Sadhoo, Neelaksh; Rajagopal, Srinath; Anderson, Tom; Moran, Carmel M.; Hadoke, Patrick W.; Gray, Gillian A.; Zeqiri, Bajram; Hoskins, Peter R.

    2014-01-01

    The acoustic properties of a robust tissue-mimicking material based on konjac–carrageenan at ultrasound frequencies in the range 5–60 MHz are described. Acoustic properties were characterized using two methods: a broadband reflection substitution technique using a commercially available preclinical ultrasound scanner (Vevo 770, FUJIFILM VisualSonics, Toronto, ON, Canada), and a dedicated high-frequency ultrasound facility developed at the National Physical Laboratory (NPL, Teddington, UK), which employed a broadband through-transmission substitution technique. The mean speed of sound across the measured frequencies was found to be 1551.7 ± 12.7 and 1547.7 ± 3.3 m s−1, respectively. The attenuation exhibited a non-linear dependence on frequency, f (MHz), in the form of a polynomial function: 0.009787f2 + 0.2671f and 0.01024f2 + 0.3639f, respectively. The characterization of this tissue-mimicking material will provide reference data for designing phantoms for preclinical systems, which may, in certain applications such as flow phantoms, require a physically more robust tissue-mimicking material than is currently available. PMID:25438864

  13. Real-time and label free determination of ligand binding-kinetics to primary cancer tissue specimens; a novel tool for the assessment of biomarker targeting

    Directory of Open Access Journals (Sweden)

    Thomas Mandel Clausen

    2016-07-01

    Full Text Available In clinical oncology, diagnosis and evaluation of optimal treatment strategies are mostly based on histopathological examination combined with immunohistochemical (IHC expression analysis of cancer-associated antigens in formalin fixed paraffin-embedded (FFPE tissue biopsies. However, informative IHC analysis depends on both the specificity and affinity of the binding reagent, which are inherently difficult to quantify in situ. Here we describe a label-free method that allows for the direct and real-time assessment of molecular binding kinetics in situ on FFPE tissue specimens using quartz crystal microbalance (QCM enabled biosensor technology. We analysed the interaction between the rVAR2 protein and its placental-like chondroitin sulfate (pl-CS receptor in primary human placenta tissue and in breast and prostate tumour specimens in situ. rVAR2 interacted with FFPE human placenta and cancer tissue with an affinity in the nanomolar range, and showed no detectable interaction with pl-CS negative normal tissue. We further validated the method by including analysis with the androgen receptor N-20 antibody (anti-AR. As the KD value produced by this method is independent of the number of epitopes available, this readout offers a quantitative and unbiased readout for in situ binding-avidity and amount of binding epitopes. In summary, this method adds a new and important dimension to classical IHC-based molecular pathology by adding information about the binding characteristics in biologically relevant conditions. This can potentially be used to select optimal biologics for diagnostic and for therapeutic applications as well as guide the development of novel high affinity binding drugs.

  14. A critical assessment of SELDI-TOF-MS for biomarker discovery in serum and tissue of patients with an ovarian mass

    Directory of Open Access Journals (Sweden)

    Wegdam Wouter

    2012-07-01

    Full Text Available Abstract Background Less than 25% of patients with a pelvic mass who are presented to a gynecologist will eventually be diagnosed with epithelial ovarian cancer. Since there is no reliable test to differentiate between different ovarian tumors, accurate classification could facilitate adequate referral to a gynecological oncologist, improving survival. The goal of our study was to assess the potential value of a SELDI-TOF-MS based classifier for discriminating between patients with a pelvic mass. Methods Our study design included a well-defined patient population, stringent protocols and an independent validation cohort. We compared serum samples of 53 ovarian cancer patients, 18 patients with tumors of low malignant potential, and 57 patients with a benign ovarian tumor on different ProteinChip arrays. In addition, from a subset of 84 patients, tumor tissues were collected and microdissection was used to isolate a pure and homogenous cell population. Results Diagonal Linear Discriminant Analysis (DLDA and Support Vector Machine (SVM classification on serum samples comparing cancer versus benign tumors, yielded models with a classification accuracy of 71-81% (cross-validation, and 73-81% on the independent validation set. Cancer and benign tissues could be classified with 95-99% accuracy using cross-validation. Tumors of low malignant potential showed protein expression patterns different from both benign and cancer tissues. Remarkably, none of the peaks differentially expressed in serum samples were found to be differentially expressed in the tissue lysates of those same groups. Conclusion Although SELDI-TOF-MS can produce reliable classification results in serum samples of ovarian cancer patients, it will not be applicable in routine patient care. On the other hand, protein profiling of microdissected tumor tissue may lead to a better understanding of oncogenesis and could still be a source of new serum biomarkers leading to novel methods for

  15. Three-dimensional bioprinting of thick vascularized tissues.

    Science.gov (United States)

    Kolesky, David B; Homan, Kimberly A; Skylar-Scott, Mark A; Lewis, Jennifer A

    2016-03-22

    The advancement of tissue and, ultimately, organ engineering requires the ability to pattern human tissues composed of cells, extracellular matrix, and vasculature with controlled microenvironments that can be sustained over prolonged time periods. To date, bioprinting methods have yielded thin tissues that only survive for short durations. To improve their physiological relevance, we report a method for bioprinting 3D cell-laden, vascularized tissues that exceed 1 cm in thickness and can be perfused on chip for long time periods (>6 wk). Specifically, we integrate parenchyma, stroma, and endothelium into a single thick tissue by coprinting multiple inks composed of human mesenchymal stem cells (hMSCs) and human neonatal dermal fibroblasts (hNDFs) within a customized extracellular matrix alongside embedded vasculature, which is subsequently lined with human umbilical vein endothelial cells (HUVECs). These thick vascularized tissues are actively perfused with growth factors to differentiate hMSCs toward an osteogenic lineage in situ. This longitudinal study of emergent biological phenomena in complex microenvironments represents a foundational step in human tissue generation.

  16. Pharmacokinetic modeling of ascorbate diffusion through normal and tumor tissue.

    Science.gov (United States)

    Kuiper, Caroline; Vissers, Margreet C M; Hicks, Kevin O

    2014-12-01

    Ascorbate is delivered to cells via the vasculature, but its ability to penetrate into tissues remote from blood vessels is unknown. This is particularly relevant to solid tumors, which often contain regions with dysfunctional vasculature, with impaired oxygen and nutrient delivery, resulting in upregulation of the hypoxic response and also the likely depletion of essential plasma-derived biomolecules, such as ascorbate. In this study, we have utilized a well-established multicell-layered, three-dimensional pharmacokinetic model to measure ascorbate diffusion and transport parameters through dense tissue in vitro. Ascorbate was found to penetrate the tissue at a slightly lower rate than mannitol and to travel via the paracellular route. Uptake parameters into the cells were also determined. These data were fitted to the diffusion model, and simulations of ascorbate pharmacokinetics in normal tissue and in hypoxic tumor tissue were performed with varying input concentrations, ranging from normal dietary plasma levels (10-100 μM) to pharmacological levels (>1 mM) as seen with intravenous infusion. The data and simulations demonstrate heterogeneous distribution of ascorbate in tumor tissue at physiological blood levels and provide insight into the range of plasma ascorbate concentrations and exposure times needed to saturate all regions of a tumor. The predictions suggest that supraphysiological plasma ascorbate concentrations (>100 μM) are required to achieve effective delivery of ascorbate to poorly vascularized tumor tissue.

  17. Three-dimensional bioprinting of thick vascularized tissues

    Science.gov (United States)

    Kolesky, David B.; Homan, Kimberly A.; Skylar-Scott, Mark A.; Lewis, Jennifer A.

    2016-03-01

    The advancement of tissue and, ultimately, organ engineering requires the ability to pattern human tissues composed of cells, extracellular matrix, and vasculature with controlled microenvironments that can be sustained over prolonged time periods. To date, bioprinting methods have yielded thin tissues that only survive for short durations. To improve their physiological relevance, we report a method for bioprinting 3D cell-laden, vascularized tissues that exceed 1 cm in thickness and can be perfused on chip for long time periods (>6 wk). Specifically, we integrate parenchyma, stroma, and endothelium into a single thick tissue by coprinting multiple inks composed of human mesenchymal stem cells (hMSCs) and human neonatal dermal fibroblasts (hNDFs) within a customized extracellular matrix alongside embedded vasculature, which is subsequently lined with human umbilical vein endothelial cells (HUVECs). These thick vascularized tissues are actively perfused with growth factors to differentiate hMSCs toward an osteogenic lineage in situ. This longitudinal study of emergent biological phenomena in complex microenvironments represents a foundational step in human tissue generation.

  18. A lab-on-a-chip system integrating tissue sample preparation and multiplex RT-qPCR for gene expression analysis in point-of-care hepatotoxicity assessment.

    Science.gov (United States)

    Lim, Geok Soon; Chang, Joseph S; Lei, Zhang; Wu, Ruige; Wang, Zhiping; Cui, Kemi; Wong, Stephen

    2015-10-21

    A truly practical lab-on-a-chip (LOC) system for point-of-care testing (POCT) hepatotoxicity assessment necessitates the embodiment of full-automation, ease-of-use and "sample-in-answer-out" diagnostic capabilities. To date, the reported microfluidic devices for POCT hepatotoxicity assessment remain rudimentary as they largely embody only semi-quantitative or single sample/gene detection capabilities. In this paper, we describe, for the first time, an integrated LOC system that is somewhat close to a practical POCT hepatotoxicity assessment device - it embodies both tissue sample preparation and multiplex real-time RT-PCR. It features semi-automation, is relatively easy to use, and has "sample-in-answer-out" capabilities for multiplex gene expression analysis. Our tissue sample preparation module incorporating both a microhomogenizer and surface-treated paramagnetic microbeads yielded high purity mRNA extracts, considerably better than manual means of extraction. A primer preloading surface treatment procedure and the single-loading inlet on our multiplex real-time RT-PCR module simplify off-chip handling procedures for ease-of-use. To demonstrate the efficacy of our LOC system for POCT hepatotoxicity assessment, we perform a preclinical animal study with the administration of cyclophosphamide, followed by gene expression analysis of two critical protein biomarkers for liver function tests, aspartate transaminase (AST) and alanine transaminase (ALT). Our experimental results depict normalized fold changes of 1.62 and 1.31 for AST and ALT, respectively, illustrating up-regulations in their expression levels and hence validating their selection as critical genes of interest. In short, we illustrate the feasibility of multiplex gene expression analysis in an integrated LOC system as a viable POCT means for hepatotoxicity assessment.

  19. A compact instrument to measure perfusion of vasculature in transplanted maxillofacial free flaps

    Science.gov (United States)

    Kolodziejski, Noah J.; Stapels, Christopher J.; McAdams, Daniel R.; Fernandez, Daniel E.; Podolsky, Matthew J.; Farkas, Dana; Ward, Brent B.; Vartarian, Mark; Feinberg, Stephen E.; Lee, Seung Yup; Parikh, Urmi; Mycek, Mary-Ann; Christian, James F.

    2016-03-01

    The vascularization and resulting perfusion of transferred tissues are critical to the success of grafts in buried free flap transplantations. To enable long-term clinical monitoring of grafted tissue perfusion during neovascularization and endothelialization, we are developing an implantable instrument for the continuous monitoring of perfusion using diffuse correlation spectroscopy (DCS), and augmented with diffuse reflectance spectroscopy (DRS). This work discusses instrument construction, integration, and preliminary results using a porcine graft model.

  20. Delivery of Encapsulated Drugs to Cancer Cells and Tissue: The Impact of Ultrasound

    OpenAIRE

    Afadzi, Mercy

    2013-01-01

    Encapsulated drugs have improved tumor to normal tissue uptake compared to free drugs, however, the concentration of drugs at the tumor site is still low and heterogeneous due to the tumor microenvironment which serves as barriers for the delivery to the target site. Combining ultrasound (US) with encapsulated drugs might enhance the transport of the encapsulated drug across the vasculature and into tumor tissues. US can also increase local drug release and the uptake of the drug into cancer ...

  1. Subtracted dynamic MR perfusion source images (sMRP-SI) provide collateral blood flow assessment in MCA occlusions and predict tissue fate

    Energy Technology Data Exchange (ETDEWEB)

    Villringer, Kersten; Serrano-Sandoval, Rafael; Galinovic, Ivana; Ostwaldt, Ann-Christin; Brunecker, Peter; Fiebach, Jochen B. [Charite-Universitaetsmedizin, Academic Neuroradiology, Center for Stroke Research (CSB), Berlin (Germany); Grittner, Ulrike [Charite, Universitaetsmedizin Berlin, Center for Stroke Research, Berlin (Germany); Charite, Department for Biostatistics and Clinical Epidemiology, Berlin (Germany); Schneider, Alice [Charite, Universitaetsmedizin Berlin, Center for Stroke Research, Berlin (Germany); Rocco, Andrea [Charite, Department of Neurology and Center for Stroke Research, Berlin (Germany)

    2016-05-15

    Collateral blood flow is accepted as a predictive factor of tissue fate in ischemic stroke. Thus, we aimed to evaluate a new method derived from MR perfusion source images to assess collateral flow in patients with ICA/MCA occlusions. A total of 132 patients of the prospective 1000+ study were examined. MR perfusion source images were assessed according to Δimg{sub n} = img{sub n} + 1 - img{sub n} - 1 using the five-grade Higashida collateral flow rating system. Higashida scores were correlated to mismatch (MM) volume, mismatch ratio, day 6 FLAIR lesion volumes and day 90 mRS. Patients with Higashida scores 3 and 4 had significantly lower admission NIHSS, smaller FLAIR day 6 lesion volumes (p < 0.001) and higher rates of better long-term outcome (mRS 0-2, p = 0.002). There was a linear trend for the association of Higashida grade 1 (p = 0.002) and 2 (p = 0.001) with unfavourable outcome (day 90 mRS 3-6), but no significant association was found for MM volume, MM ratio and day 90 mRS. Inter-rater agreement was 0.58 (95 % CI 0.43-0.73) on day 1, 0.70 (95 % CI 0.58-0.81) on day 2. sMRP-SI Higashida score offers a non-invasive collateral vessel and tissue perfusion assessment of ischemic tissue. The predictive value of Higashida rating proved superior to MM with regard to day 90 mRS. (orig.)

  2. Modulation of retinal image vasculature analysis to extend utility and provide secondary value from optical coherence tomography imaging.

    Science.gov (United States)

    Cameron, James R; Ballerini, Lucia; Langan, Clare; Warren, Claire; Denholm, Nicholas; Smart, Katie; MacGillivray, Thomas J

    2016-04-01

    Retinal image analysis is emerging as a key source of biomarkers of chronic systemic conditions affecting the cardiovascular system and brain. The rapid development and increasing diversity of commercial retinal imaging systems present a challenge to image analysis software providers. In addition, clinicians are looking to extract maximum value from the clinical imaging taking place. We describe how existing and well-established retinal vasculature segmentation and measurement software for fundus camera images has been modulated to analyze scanning laser ophthalmoscope retinal images generated by the dual-modality Heidelberg SPECTRALIS(®) instrument, which also features optical coherence tomography.

  3. The detailed assessment of left and right ventricular functions by tissue Doppler imaging in patients with familial Mediterranean fever.

    Science.gov (United States)

    Tavil, Yusuf; Ureten, Kemal; Oztürk, Mehmet Akif; Sen, Nihat; Kaya, Mehmet Güngör; Cemri, Mustafa; Cengel, Atiye

    2008-02-01

    In the contrary to other rheumatologic disorders, there have been limited numbers of studies investigating the cardiac involvement in patients with familial Mediterranean fever (FMF), although the disease may carry a potential for cardiovascular disorders because of sustained inflammation during its course. In the present study, we used high usefulness tissue Doppler echocardiography for detailed analysis of cardiac changes in FMF patients. The study population included 30 patients with FMF (11 men, 19 women; mean age, 35 +/- 7 years, mean disease duration, 15.4 +/- 7.6 years) and 30 healthy subjects as controls (12 men, 18 women; mean age, 33 +/- 7 years). The diagnosis of FMF was established according to the Tell-Hashomer criteria. Left and right ventricular functions were measured using echocardiography comprising standard two-dimensional, M-mode, and conventional Doppler as well as tissue Doppler imaging. The conventional echocardiographic paratemeters were similar apart from left ventricular relaxation time was longer (107 +/- 25 vs 85 +/- 10 ms, p < 0.001, respectively) in patients with FMF. According to the tissue Doppler measurements, while systolic velocities of both ventricles were not different, diastolic filling velocities of left ventricle including E'(m) (12.6 +/- 3.4 vs 14.7 +/- 3.3 cm/s, p = 0.04), A'(m) (10.1 +/- 2.6 vs 8.6 +/- 2.0 cm/s, p = 0.015), and E'(m)/ A'(m) (1.24 +/- 0.4 vs 1.71 +/- 0.5 cm/s, p = 0.012) values were statistically different between the groups. Left ventricular myocardial performance indices and right ventricular diastolic functions were found similar between two groups. In addition, there were no significant correlations between the disease duration, clinical features, and echocardiographic parameters. In conclusion, we have demonstrated that although systolic functions were comparable in the patients and controls, left ventricular diastolic function indices were impaired in FMF patients by using tissue Doppler analysis.

  4. Assessment of normal tissue complications following prostate cancer irradiation: Comparison of radiation treatment modalities using NTCP models

    Energy Technology Data Exchange (ETDEWEB)

    Takam, Rungdham; Bezak, Eva; Yeoh, Eric E.; Marcu, Loredana [School of Chemistry and Physics, University of Adelaide, Adelaide SA 5000 (Australia) and Department of Medical Physics, Royal Adelaide Hospital, Adelaide SA 5000 (Australia); School of Medicine, University of Adelaide, Adelaide SA 5000 (Australia) and Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide SA 5000 (Australia); School of Chemistry and Physics, University of Adelaide, Adelaide SA 5000 (Australia) and Faculty of Science, University of Oradea, Oradea 410086 (Romania)

    2010-09-15

    Purpose: Normal tissue complication probability (NTCP) of the rectum, bladder, urethra, and femoral heads following several techniques for radiation treatment of prostate cancer were evaluated applying the relative seriality and Lyman models. Methods: Model parameters from literature were used in this evaluation. The treatment techniques included external (standard fractionated, hypofractionated, and dose-escalated) three-dimensional conformal radiotherapy (3D-CRT), low-dose-rate (LDR) brachytherapy (I-125 seeds), and high-dose-rate (HDR) brachytherapy (Ir-192 source). Dose-volume histograms (DVHs) of the rectum, bladder, and urethra retrieved from corresponding treatment planning systems were converted to biological effective dose-based and equivalent dose-based DVHs, respectively, in order to account for differences in radiation treatment modality and fractionation schedule. Results: Results indicated that with hypofractionated 3D-CRT (20 fractions of 2.75 Gy/fraction delivered five times/week to total dose of 55 Gy), NTCP of the rectum, bladder, and urethra were less than those for standard fractionated 3D-CRT using a four-field technique (32 fractions of 2 Gy/fraction delivered five times/week to total dose of 64 Gy) and dose-escalated 3D-CRT. Rectal and bladder NTCPs (5.2% and 6.6%, respectively) following the dose-escalated four-field 3D-CRT (2 Gy/fraction to total dose of 74 Gy) were the highest among analyzed treatment techniques. The average NTCP for the rectum and urethra were 0.6% and 24.7% for LDR-BT and 0.5% and 11.2% for HDR-BT. Conclusions: Although brachytherapy techniques resulted in delivering larger equivalent doses to normal tissues, the corresponding NTCPs were lower than those of external beam techniques other than the urethra because of much smaller volumes irradiated to higher doses. Among analyzed normal tissues, the femoral heads were found to have the lowest probability of complications as most of their volume was irradiated to lower

  5. Accuracy and safety verification of ovarian reserve assessment technique for ovarian tissue transplantation using optical coherence tomography in mice ovary

    Science.gov (United States)

    Takae, Seido; Tsukada, Kosuke; Sato, Yorino; Okamoto, Naoki; Kawahara, Tai; Suzuki, Nao

    2017-03-01

    Except for histological study, there are currently no suitable techniques available for the detection and identification of primordial follicles in ovary of primary ovarian insufficiency patients who have undetectable AMH levels. Also, the ability to locate and quantify follicles on ovarian cortex strips, without fixation, is valuable for patients who could undergo subsequent successful ovarian tissue transplantation. Although optical coherence tomography (OCT) is a well-established high resolution imaging technique without fixation commonly applied in biomedicine, few reports are available on ovarian tissue imaging. In present study, we established standard OCT follicle images at each developmental stage, including the primordial follicle, and demonstrated the efficacy of OCT to estimate IVF outcome in transplanted mice ovary like ovarian reserve tests. Unfortunately, the current commercial OCT could not be used to accurate follicle count the number of follicles for whole ovary, because the maximum depth of examination was 100 μm. And we demonstrated the safety of OCT examination, it did not affect IVF outcome and birth defect rate, and reproductive ability. Although there is room for improvement, these findings will be first step to bring OCT examination a step closer to clinical application for measuring true ovarian reserve and localizing follicles.

  6. Performance Assessment of Bi-Directional Knotless Tissue-Closure Devices in Juvenile Chinook Salmon Surgically Implanted with Acoustic Transmitters, 2009 - Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Woodley, Christa M.; Wagner, Katie A.; Bryson, Amanda J.

    2012-11-09

    The purpose of this report is to assess the performance of bi-directional knotless tissue-closure devices for use in tagging juvenile salmon. This study is part of an ongoing effort at Pacific Northwest National Laboratory (PNNL) to reduce unwanted effects of tags and tagging procedures on the survival and behavior of juvenile salmonids, by assessing and refining suturing techniques, suture materials, and tag burdens. The objective of this study was to compare the performance of the knotless (barbed) suture, using three different suture patterns (treatments: 6-point, Wide “N”, Wide “N” Knot), to the current method of suturing (MonocrylTM monofilament, discontinuous sutures with a 2×2×2×2 knot) used in monitoring and research programs with a novel antiseptic barrier on the wound (“Second Skin”).

  7. Assessment of tissue perfusion changes in port wine stains after vascular targeted photodynamic therapy: a short-term follow-up study.

    Science.gov (United States)

    Ren, Jie; Li, Pengcheng; Zhao, Hongyou; Chen, Defu; Zhen, Jie; Wang, Ying; Wang, Yucheng; Gu, Ying

    2014-03-01

    The occlusion effect of vascular targeted photodynamic therapy (V-PDT) for malformed vessels in port wine stains (PWS) often last for some time after the treatment. A relatively longer period after V-PDT is needed to accurately assess the final response of PWS microcirculation to the treatment. In this study, we intended to use laser speckle imaging (LSI) to assess the tissue perfusion changes of PWS at follow-up after V-PDT and preliminarily analyze the relationship between perfusion change and color bleaching. Seventeen patients with 40 PWS lesions were scanned by LSI before and 3-6 months after they received V-PDT. The speckle flow indices of PWS lesions and normal skin before and at follow-up after V-PDT were recorded. We also performed analyses on the correlation between perfusion changes and color bleaching. Before V-PDT, the 40 PWS lesions showed higher perfusion than the normal skin (1,421 ± 463 and 1,115 ± 386 perfusion unit (PU), respectively, P perfusion level compared to the preoperative values (1,282 ± 460 and 1,421 ± 463 PU, respectively, P perfusion change rates coincide well with the color bleaching rates (correlation coefficient, 0.73). In conclusion, the LSI system is capable of imaging PWS perfusion precisely, and it has shown promising results in assessing the changes of tissue perfusion of V-PDT for PWS, with objective and quantitative data, real-time images, and a shorter detection time. It may also provide an effectiveness assessment method for the treatment of PWS.

  8. Molecular risk assessment of BIG 1-98 participants by expression profiling using RNA from archival tissue

    Directory of Open Access Journals (Sweden)

    Giobbie-Hurder Anita

    2010-02-01

    Full Text Available Abstract Background The purpose of the work reported here is to test reliable molecular profiles using routinely processed formalin-fixed paraffin-embedded (FFPE tissues from participants of the clinical trial BIG 1-98 with a median follow-up of 60 months. Methods RNA from fresh frozen (FF and FFPE tumor samples of 82 patients were used for quality control, and independent FFPE tissues of 342 postmenopausal participants of BIG 1-98 with ER-positive cancer were analyzed by measuring prospectively selected genes and computing scores representing the functions of the estrogen receptor (eight genes, ER_8, the progesterone receptor (five genes, PGR_5, Her2 (two genes, HER2_2, and proliferation (ten genes, PRO_10 by quantitative reverse transcription PCR (qRT-PCR on TaqMan Low Density Arrays. Molecular scores were computed for each category and ER_8, PGR_5, HER2_2, and PRO_10 scores were combined into a RISK_25 score. Results Pearson correlation coefficients between FF- and FFPE-derived scores were at least 0.94 and high concordance was observed between molecular scores and immunohistochemical data. The HER2_2, PGR_5, PRO_10 and RISK_25 scores were significant predictors of disease free-survival (DFS in univariate Cox proportional hazard regression. PRO_10 and RISK_25 scores predicted DFS in patients with histological grade II breast cancer and in lymph node positive disease. The PRO_10 and PGR_5 scores were independent predictors of DFS in multivariate Cox regression models incorporating clinical risk indicators; PRO_10 outperformed Ki-67 labeling index in multivariate Cox proportional hazard analyses. Conclusions Scores representing the endocrine responsiveness and proliferation status of breast cancers were developed from gene expression analyses based on RNA derived from FFPE tissues. The validation of the molecular scores with tumor samples of participants of the BIG 1-98 trial demonstrates that such scores can serve as independent prognostic

  9. Impacts of acute severe pulmonary regurgitation on right ventricular geometry and contractility assessed by tissue-Doppler echocardiography

    DEFF Research Database (Denmark)

    Kjaergaard, Jesper; Iversen, Kasper K; Vejlstrup, Niels G;

    2010-01-01

    Little is known of the impact of acute right ventricular (RV) volume overload on RV function. We assessed the impact of acute severe pulmonary regurgitation (PR) on global and regional RV function by applying novel quantitative echocardiographic markers of myocardial performance in an animal model....

  10. Impacts of acute severe pulmonary regurgitation on right ventricular geometry and contractility assessed by tissue-Doppler echocardiography

    DEFF Research Database (Denmark)

    Kjaergaard, Jesper; K. Iversen, Kasper; G Vejlstrup, Niels;

    2010-01-01

    AIMS: Little is known of the impact of acute right ventricular (RV) volume overload on RV function. We assessed the impact of acute severe pulmonary regurgitation (PR) on global and regional RV function by applying novel quantitative echocardiographic markers of myocardial performance in an animal...

  11. Quality assessment of estrogen receptor and progesterone receptor testing in breast cancer using a tissue microarray-based approach

    NARCIS (Netherlands)

    T.J.A. Dekker; S. ter Borg; J. Hooijer; S.L. Meijer (Sybren); J. Wesseling (Jelle); J.E. Boers (James); E. Schuuring; J. Bart; J. van Gorp (Joost); P. Bult (Peter); S. Riemersma (Sietske); C.H.M. van Deurzen (Carolien); H.F. Sleddens (Hein); W.E. Mesker; J.R. Kroep (Judith); V.T.H.B.M. Smit (Vincent); M.J. Vijver (Marc )

    2015-01-01

    textabstractAssessing hormone receptor status is an essential part of the breast cancer diagnosis, as this biomarker greatly predicts response to hormonal treatment strategies. As such, hormone receptor testing laboratories are strongly encouraged to participate in external quality control schemes t

  12. Quality assessment of estrogen receptor and progesterone receptor testing in breast cancer using a tissue microarray-based approach

    NARCIS (Netherlands)

    Dekker, T. J. A.; ter Borg, S.; Hooijer, G. K. J.; Meijer, S. L.; Wesseling, J.; Boers, J. E.; Schuuring, E.; Bart, J.; van Gorp, J.; Bult, P.; Riemersma, S. A.; van Deurzen, C. H. M.; Sleddens, H. F. B. M.; Mesker, W. E.; Kroep, J. R.; Smit, V. T. H. B. M.; van de Vijver, M. J.

    2015-01-01

    Assessing hormone receptor status is an essential part of the breast cancer diagnosis, as this biomarker greatly predicts response to hormonal treatment strategies. As such, hormone receptor testing laboratories are strongly encouraged to participate in external quality control schemes to achieve op

  13. Inhibition of Vascular Endothelial Growth Factor A and Hypoxia-Inducible Factor 1α Maximizes the Effects of Radiation in Sarcoma Mouse Models Through Destruction of Tumor Vasculature

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hae-June [Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Yoon, Changhwan [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Park, Do Joong [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Surgery, Seoul National University Bundang Hospital, Sungnam (Korea, Republic of); Kim, Yeo-Jung [Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Schmidt, Benjamin [Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Lee, Yoon-Jin [Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Tap, William D. [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Eisinger-Mathason, T.S. Karin [Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Choy, Edwin [Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Kirsch, David G. [Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina (United States); Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Simon, M. Celeste [Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Howard Hughes Medical Institute (United States); and others

    2015-03-01

    Purpose: To examine the addition of genetic or pharmacologic inhibition of hypoxia-inducible factor 1α (HIF-1α) to radiation therapy (RT) and vascular endothelial growth factor A (VEGF-A) inhibition (ie trimodality therapy) for soft-tissue sarcoma. Methods and Materials: Hypoxia-inducible factor 1α was inhibited using short hairpin RNA or low metronomic doses of doxorubicin, which blocks HIF-1α binding to DNA. Trimodality therapy was examined in a mouse xenograft model and a genetically engineered mouse model of sarcoma, as well as in vitro in tumor endothelial cells (ECs) and 4 sarcoma cell lines. Results: In both mouse models, any monotherapy or bimodality therapy resulted in tumor growth beyond 250 mm{sup 3} within the 12-day treatment period, but trimodality therapy with RT, VEGF-A inhibition, and HIF-1α inhibition kept tumors at <250 mm{sup 3} for up to 30 days. Trimodality therapy on tumors reduced HIF-1α activity as measured by expression of nuclear HIF-1α by 87% to 95% compared with RT alone, and cytoplasmic carbonic anhydrase 9 by 79% to 82%. Trimodality therapy also increased EC-specific apoptosis 2- to 4-fold more than RT alone and reduced microvessel density by 75% to 82%. When tumor ECs were treated in vitro with trimodality therapy under hypoxia, there were significant decreases in proliferation and colony formation and increases in DNA damage (as measured by Comet assay and γH2AX expression) and apoptosis (as measured by cleaved caspase 3 expression). Trimodality therapy had much less pronounced effects when 4 sarcoma cell lines were examined in these same assays. Conclusions: Inhibition of HIF-1α is highly effective when combined with RT and VEGF-A inhibition in blocking sarcoma growth by maximizing DNA damage and apoptosis in tumor ECs, leading to loss of tumor vasculature.

  14. Assessment of murine brain tissue shrinkage caused by different histological fixatives using magnetic resonance and computed tomography imaging.

    Science.gov (United States)

    Wehrl, Hans F; Bezrukov, Ilja; Wiehr, Stefan; Lehnhoff, Mareike; Fuchs, Kerstin; Mannheim, Julia G; Quintanilla-Martinez, Leticia; Kohlhofer, Ursula; Kneilling, Manfred; Pichler, Bernd J; Sauter, Alexander W

    2015-05-01

    Especially for neuroscience and the development of new biomarkers, a direct correlation between in vivo imaging and histology is essential. However, this comparison is hampered by deformation and shrinkage of tissue samples caused by fixation, dehydration and paraffin embedding. We used magnetic resonance (MR) imaging and computed tomography (CT) imaging to analyze the degree of shrinkage on murine brains for various fixatives. After in vivo imaging using 7 T MRI, animals were sacrificed and the brains were dissected and immediately placed in different fixatives, respectively: zinc-based fixative, neutral buffered formalin (NBF), paraformaldehyde (PFA), Bouin-Holland fixative and paraformaldehyde-lysine-periodate (PLP). The degree of shrinkage based on mouse brain volumes, radiodensity in Hounsfield units (HU), as well as non-linear deformations were obtained. The highest degree of shrinkage was observed for PLP (68.1%, P brain shrinkage and only small deformations and is therefore recommended for in vivo ex vivo comparison studies.

  15. Spectroscopic imaging system for high-throughput viability assessment of ovarian spheroids or microdissected tumor tissues (MDTs) in a microfluidic chip

    Science.gov (United States)

    St-Georges-Robillard, A.; Masse, M.; Kendall-Dupont, J.; Strupler, M.; Patra, B.; Jermyn, M.; Mes-Masson, A.-M.; Leblond, F.; Gervais, T.

    2016-02-01

    There is a growing effort in the biomicrosystems community to develop a personalized treatment response assay for cancer patients using primary cells, patient-derived spheroids, or live tissues on-chip. Recently, our group has developed a technique to cut tumors in 350 μm diameter microtissues and keep them alive on-chip, enabling multiplexed in vitro drug assays on primary tumor tissue. Two-photon microscopy, confocal microscopy and flow cytometry are the current standard to assay tissue chemosensitivity on-chip. While these techniques provide microscopic and molecular information, they are not adapted for high-throughput analysis of microtissues. We present a spectroscopic imaging system that allows rapid quantitative measurements of multiple fluorescent viability markers simultaneously by using a liquid crystal tunable filter to record fluorescence and transmittance spectra. As a proof of concept, 24 spheroids composed of ovarian cancer cell line OV90 were formed in a microfluidic chip, stained with two live cell markers (CellTrackerTM Green and Orange), and imaged. Fluorescence images acquired were normalized to the acquisition time and gain of the camera, dark noise was removed, spectral calibration was applied, and spatial uniformity was corrected. Spectral un-mixing was applied to separate each fluorophore's contribution. We have demonstrated that rapid and simultaneous viability measurements on multiple spheroids can be achieved, which will have a significant impact on the prediction of a tumor's response to multiple treatment options. This technique may be applied as well in drug discovery to assess the potential of a drug candidate directly on human primary tissue.

  16. Tissue concentrations as the dose metric to assess potential toxic effects of metals in field-collected fish: Copper and cadmium.

    Science.gov (United States)

    Meador, James P

    2015-06-01

    The present study examined the available literature linking whole-body tissue concentrations with toxic effects in fish species for copper and cadmium. The variability in effect concentration for both copper and cadmium among species occurred within an order of magnitude for all responses, whereas the range for lethal toxicity based on water exposure spanned approximately 4 to 5 orders of magnitude. Fish tissue concentrations causing adverse effects were just above background concentrations, occurring between 1 μg/g and 10 μg/g for copper and 0.1 μg/g to 4 μg/g for cadmium. The results also show that salmonids are especially sensitive to cadmium, which appears to be a function of chemical potency. No studies were found that indicated adverse effects without increases in whole-body concentration of these metals. This narrow range for dose-response implies that a toxicological spillover point occurs when the detoxification capacity of various tissues within the animal are exceeded, and this likely occurs at a similar whole-body concentration for all naïvely exposed fish species. Elevated whole-body concentrations in fish from the field may be indicative of possible acclimation to metals that may or may not result in effects for target species. Acclimation concentrations may be useful in that they signal excessive metal concentrations in water, sediment, or prey species for a given site and indicate likely toxic effects for species unable to acclimate to excess metal exposure. Using tissue residues as the dose metric for these metals provides another line of evidence for assessing impaired ecosystems and greater confidence that hazard concentrations are protective for all fish species.

  17. Current methods of assessing the accuracy of three-dimensional soft tissue facial predictions: technical and clinical considerations.

    Science.gov (United States)

    Khambay, B; Ullah, R

    2015-01-01

    Since the introduction of three-dimensional (3D) orthognathic planning software, studies have reported on their predictive ability. The aim of this study was to highlight the limitations of the current methods of analysis. The predicted 3D soft tissue image was compared to the postoperative soft tissue. For the full face, the maximum and 95th and 90th percentiles, the percentage of 3D mesh points ≤ 2 mm, and the root mean square (RMS) error, were calculated. For specific anatomical regions, the percentage of 3D mesh points ≤ 2 mm and the distance between the two meshes at 10 landmarks were determined. For the 95th and 90th percentiles, the maximum difference ranged from 7.7 mm to 2.2 mm and from 3.7 mm to 1.5 mm, respectively. The absolute mean distance ranged from 0.98 mm to 0.56 mm and from 0.91 mm to 0.50 mm, respectively. The percentage of mesh with ≤ 2 mm for the full face was 94.4-85.2% and 100-31.3% for anatomical regions. The RMS error ranged from 2.49 mm to 0.94 mm. The majority of mean linear distances between the surfaces were ≤ 0.8 mm, but increased for the mean absolute distance. At present the use of specific anatomical regions is more clinically meaningful than the full face. It is crucial to understand these and adopt a protocol for conducting such studies.

  18. An immunocytochemical study of the germinal layer vasculature in the developing fetal brain using Ulex europaeus 1 lectin.

    Science.gov (United States)

    Gould, S J; Howard, S

    1988-10-01

    The characteristics of the germinal matrix vasculature were studied in the developing fetal brain using immunocytochemical methods. A preliminary comparative immunocytochemical study was made on six fetal brains to compare endothelial staining by Ulex europaeus I lectin with that of antibody to Factor VIII related antigen. Ulex was found to stain germinal layer vessels better than Factor VIII related antigen. Subsequently, the germinal layers of a further 15 fetal and preterm infant brains ranging from 13 to 35 weeks' gestation were stained with Ulex europaeus I to demonstrate the vasculature. With increasing gestation, there was a gradual increase in vessel density, particularly of capillaries. This was not a uniform process. A plexus of capillaries was prominent immediately beneath the ependyma while the more central parts of the germinal matrix contained fewer, but often larger diameter, vessels. The variation in vessel density which was a feature of the later gestation brains may have implications for local blood flow and may be a factor in haemorrhage at this site.

  19. The tissue velocity imaging and strain rate imaging in the assessment of interatrial electromechanical conduction in patients with sick sinus syndrome before and after pacemaker implantation.

    Science.gov (United States)

    Zheng, Xiaozhi; Ji, Ping; Mao, Hongwei; Hu, Jianqun

    2011-05-01

    Tissue velocity imaging (TVI) and strain rate imaging (SRI) were recently introduced to quantify myocardial mechanical activity in patients receiving cardiac resynchronization therapy. To clear whether atrial-demand-based (AAI) (R) atrial pacing can fully simulate the electromechanical conduction of physiological state and to clarify which one is more appropriate for the assessment of electromechanical activity of the heart between TVI and SRI, 30 normal subjects and 31 patients with sick sinus syndrome (SSS) before and after AAI(R) pacemaker implantation (PI) were investigated in this study. The results showed that the time intervals (ms), P-SRa assessed by SRI (not P-Va assessed by TVI) prolonged step by step from the lateral wall of the right atrium (RA), the interatrial septum (IAS) and the left atrium (LA) in normal subjects(5.01±0.62, 17.05±3.54 and 45.09±12.26, pIAS and LA in patients with SSS before PI (p>0.05), and they were significant longer than those of normal subjects (pIAS to LA. At the same time, the peak velocities and the peak strain rates during atrial contraction also returned to normal values from lower levels. These data suggested that AAI(R) atrial pacing can successfully reverse the abnormal interatrial electromechanical conduction in patients with SSS, and SRI is more appropriate for the assessment of the electromechanical activity of atrial wall than TVI.

  20. The influence of DNA degradation in formalin-fixed, paraffin-embedded (FFPE) tissue on locus-specific methylation assessment by MS-HRM.

    Science.gov (United States)

    Daugaard, Iben; Kjeldsen, Tina E; Hager, Henrik; Hansen, Lise Lotte; Wojdacz, Tomasz K

    2015-12-01

    Readily accessible formalin-fixed paraffin embedded (FFPE) tissues are a highly valuable source of genetic material for molecular analyses in both research and in vitro diagnostics but frequently genetic material in those samples is highly degraded. With locus-specific methylation changes being widely investigated for use as biomarkers in various aspects of clinical disease management, we aimed to evaluate to what extent standard laboratory procedures can approximate the quality of the DNA extracted from FFPE samples prior to methylation analyses. DNA quality in 107 FFPE non-small cell lung cancer (NSCLC) samples was evaluated using spectrophotometry and gel electrophoresis. Subsequently, the quality assessment results were correlated with the results of locus specific methylation assessment with methylation sensitive high resolution melting (MS-HRM). The correlation of template quality with PCR amplification performance and HRM based methylation detection indicated a significant influence of DNA quality on PCR amplification but not on methylation assessment. In conclusion, standard laboratory procedures fairly well approximate DNA degradation of FFPE samples and DNA degradation does not seem to considerably affect locus-specific methylation assessment by MS-HRM.

  1. Injectable silk foams for soft tissue regeneration.

    Science.gov (United States)

    Bellas, Evangelia; Lo, Tim J; Fournier, Eric P; Brown, Joseph E; Abbott, Rosalyn D; Gil, Eun S; Marra, Kacey G; Rubin, J Peter; Leisk, Gary G; Kaplan, David L

    2015-02-18

    Soft tissue fillers are needed for restoration of a defect or augmentation of existing tissues. Autografts and lipotransfer have been under study for soft tissue reconstruction but yield inconsistent results, often with considerable resorption of the grafted tissue. A minimally invasive procedure would reduce scarring and recovery time as well as allow the implant and/or grafted tissue to be placed closer to existing vasculature. Here, the feasibility of an injectable silk foam for soft tissue regeneration is demonstrated. Adipose-derived stem cells survive and migrate through the foam over a 10-d period in vitro. The silk foams are also successfully injected into the subcutaneous space in a rat and over a 3-month period integrating with the surrounding native tissue. The injected foams are palpable and soft to the touch through the skin and returning to their original dimensions after pressure is applied and then released. The foams readily absorb lipoaspirate making the foams useful as a scaffold or template for existing soft tissue filler technologies, useful either as a biomaterial alone or in combination with the lipoaspirate.

  2. Left ventricular dyssynchrony assessed by two three-dimensional imaging modalities: phase analysis of gated myocardial perfusion SPECT and tri-plane tissue Doppler imaging

    Science.gov (United States)

    Ajmone Marsan, Nina; Henneman, Maureen M.; Chen, Ji; Ypenburg, Claudia; Dibbets, Petra; Ghio, Stefano; Bleeker, Gabe B.; Stokkel, Marcel P.; van der Wall, Ernst E.; Tavazzi, Luigi; Garcia, Ernest V.

    2007-01-01

    Purpose To compare left ventricular (LV) dyssynchrony assessment by phase analysis from gated myocardial perfusion SPECT (GMPS) with LV dyssynchrony assessment by tri-plane tissue Doppler imaging (TDI). Baseline LV dyssynchrony assessed with standard deviation (SD) of time-to-peak systolic velocity of 12 LV segments (Ts-SD) with TDI has proven to be a powerful predictor of response to CRT. Information on LV dyssynchrony can also be provided by GMPS with phase analysis of regional LV maximal count changes throughout the cardiac cycle. Methods Forty heart failure patients, referred for evaluation of potential eligibility for CRT, underwent both 3D echocardiography, with tri-plane TDI, and resting GMPS. From tri-plane TDI, Ts-SD was used as a validated parameter of LV dyssynchrony and compared with different indices (histogram bandwidth, phase SD, histogram skewness and kurtosis) derived from phase analysis of GMPS. Results Histogram bandwidth and phase SD showed good correlation with Ts-SD (r=0.77 and r=0.74, p<0.0001, respectively). Patients with substantial LV dyssynchrony assessed with tri-plane TDI (Ts-SD ≥33 ms) had also significantly higher values of histogram bandwidth and phase SD. Conclusions The results of this study support the use of phase analysis by GMPS to evaluate LV dyssynchrony. Histogram bandwidth and phase SD showed the best correlation with Ts-SD assessed with tri-plane TDI and appeared the most optimal variables for assessment of LV dyssynchrony with GMPS. PMID:17874098

  3. Pharmacology of the Adenosine A3 Receptor in the Vasculature and Essential Hypertension

    Science.gov (United States)

    Ho, Ming-Fen; Low, Leanne M.; Rose’Meyer, Roselyn B.

    2016-01-01

    Background Essential hypertension is considered to be a multifactorial disorder and its aetiology has yet to be clearly identified. As the adenosine receptors have a significant role in mediating vasodilation, alterations in their structures or signalling pathways may be involved in the development of hypertension. This study aimed to measure the expression of adenosine A3 receptors in a range of cardiovascular tissues and determine whether they could be altered with essential hypertension, and to functionally test responses to adenosine A3 receptor agonists in coronary blood vessels using the isolated perfused heart preparation. Methods mRNA samples from cardiovascular tissues and a range of blood vessels were collected from 10 week old male spontaneously hypertensive rats and age-gender matched Wistar rats (n = 8). The Langendorff heart perfusion preparation was used to characterise adenosine A3 receptor mediated coronary vasodilation in the rat heart. Results Adenosine A3 receptor agonists induced coronary vasodilation. The expression of adenosine A3 receptors in cardiovascular tissues was altered in a tissue-specific pattern. Specifically, down-regulation of adenosine A3 receptor expression occurred in hypertensive hearts, which might be associated with attenuated vasodilator responses observed in coronary vessels to adenosine A3 receptor agonists. Conclusions This study demonstrated alterations in the expression of adenosine A3 receptors occurred in a tissue specific mode, and reduced adenosine A3 receptor mediated coronary vasodilation in hearts from spontaneously hypertensive rats. Our findings with regard to changes in the adenosine A3 receptor in hypertensive hearts suggest that adenosine A3 receptor might play a role in the physiopathology of essential hypertension and potentially open the way to pharmacologic manipulation of vasomotor activity by the use of adenosine A3 receptor agonists. PMID:26907173

  4. Assessment of legacy and emerging persistent organic pollutants in Weddell seal tissue (Leptonychotes weddellii) near McMurdo Sound, Antarctica

    Energy Technology Data Exchange (ETDEWEB)

    Trumble, Stephen J.; Robinson, Eleanor M. [Baylor University, One Bear Place 97388, Waco, TX 76798-7388 (United States); Noren, Shawn R. [Institute of Marine Science, University of California, Santa Cruz, CA (United States); Usenko, Sascha, E-mail: Sascha_Usenko@baylor.edu [Baylor University, One Bear Place 97388, Waco, TX 76798-7388 (United States); Davis, Jay [U.S. Fish and Wildlife Service, Western Washington Fish and Wildlife Office, Lacey, WA 98503 (United States); Kanatous, Shane B. [Department of Biology, Colorado State University, Fort Collins, CO 80523-1878 (United States)

    2012-11-15

    Muscle samples were collected from pup, juvenile and adult Weddell seals (Leptonychotes weddellii) near McMurdo Sound, Antarctica during the austral summer of 2006. Blubber samples were collected from juvenile and adult seals. Samples were analyzed for emerging and legacy persistent organic pollutants (POPs) including current and historic-use organochlorine pesticides, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs). Of the 41 target analytes, 28 contaminants were recovered from the Weddell seal blubber, in this order of prevalence: p,p Prime -DDE, p,p Prime -DDT, trans-nonachlor, mirex, cis-nonachlor, PCB 153, PCB 138, dieldrin, heptachlor epoxide, nonachlor III, PCB 187, oxychlordane, cis-chlordane, PCB 118, PBDE 47, PCB 156, PCB 149, PCB 180, PCB 101, PCB 170, PCB 105, o,p Prime -DDT, PCB 99, trans-chlordane, PCB 157, PCB 167, PCB 189, and PCB 114. Fewer POPs were found in the muscle samples, but were similar in the order of prevalence to that of the blubber: p,p Prime -DDE, o,p Prime -DDT, trans-nonachlor, nonachlor III, oxychlordane, p,p Prime -DDT, dieldrin, mirex, cis-nonachlor, PCB 138, and PCB 105. Besides differences in toxicant concentrations reported between the muscle and blubber, we found differences in POP levels according to age class and suggest that differences in blubber storage and/or mobilization of lipids result in age class differences in POPs. To our knowledge, such ontogenetic associations are novel. Importantly, data from this study suggest that p,p Prime -DDT is becoming less prevalent temporally, resulting in an increased proportion of its metabolite p,p Prime -DDE in the tissues of this top predator. In addition, this study is among the first to identify a PBDE congener in Weddell seals near the McMurdo Station. This may provide evidence of increased PBDE transport and encroachment in Antarctic wildlife. -- Highlights: Black-Right-Pointing-Pointer PBDE measuring in Weddell seal blubber. Black

  5. Robust volume assessment of brain tissues for 3-dimensional fourier transformation MRI via a novel multispectral technique.

    Directory of Open Access Journals (Sweden)

    Jyh-Wen Chai

    Full Text Available A new TRIO algorithm method integrating three different algorithms is proposed to perform brain MRI segmentation in the native coordinate space, with no need of transformation to a standard coordinate space or the probability maps for segmentation. The method is a simple voxel-based algorithm, derived from multispectral remote sensing techniques, and only requires minimal operator input to depict GM, WM, and CSF tissue clusters to complete classification of a 3D high-resolution multislice-multispectral MRI data. Results showed very high accuracy and reproducibility in classification of GM, WM, and CSF in multislice-multispectral synthetic MRI data. The similarity indexes, expressing overlap between classification results and the ground truth, were 0.951, 0.962, and 0.956 for GM, WM, and CSF classifications in the image data with 3% noise level and 0% non-uniformity intensity. The method particularly allows for classification of CSF with 0.994, 0.961 and 0.996 of accuracy, sensitivity and specificity in images data with 3% noise level and 0% non-uniformity intensity, which had seldom performed well in previous studies. As for clinical MRI data, the quantitative data of brain tissue volumes aligned closely with the brain morphometrics in three different study groups of young adults, elderly volunteers, and dementia patients. The results also showed very low rates of the intra- and extra-operator variability in measurements of the absolute volumes and volume fractions of cerebral GM, WM, and CSF in three different study groups. The mean coefficients of variation of GM, WM, and CSF volume measurements were in the range of 0.03% to 0.30% of intra-operator measurements and 0.06% to 0.45% of inter-operator measurements. In conclusion, the TRIO algorithm exhibits a remarkable ability in robust classification of multislice-multispectral brain MR images, which would be potentially applicable for clinical brain volumetric analysis and explicitly promising

  6. Assessment of multicomponent hydrogel scaffolds of poly(acrylic acid-2-hydroxy ethyl methacrylate)/gelatin for tissue engineering applications.

    Science.gov (United States)

    Jaiswal, Maneesh; Koul, Veena

    2013-03-01

    The article describes the design of the multicomponent hydrogel system of poly(acrylic acid-HEMA)/gelatin for tissue engineering application. Derivative of polycaprolactone-diol (polycaprolactone diacrylate (PCL-DAr)) was used to cross-link acrylate monomers whereas gelatin was kept free for cell proliferation. Epigallocatechin gallate (EGCG), an anti-oxidant phytochemical, was loaded by diffusion method. Its in vitro release study in PBS (pH 6.5) at 37 ± 0.2°C (75 rpm) revealed a sustained release profile upto 20 days. Fitting of drug release data in Korsmeyer-Peppas model equation revealed probable release mechanism through the value of release coefficient (n), which was found to depend on formulations composition. Drug-polymer interaction, thermal behavior, and surface morphology were investigated by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, thermogravimetric analysis (TGA), and scanning electron microscopic (SEM). Swelling behavior of hydrogel in PBS (pH 6.5 and 7.4, 0.2 M) and in distilled water was found to increase with increasing AAc/HEMA ratio. Compression modulus decreased from 203 ± 3.7 KPa to 11.6 ± 1.1KPa, at 30% strain, whereas displacement values significantly increased from 3.2 ± 0.2 to 4.7 ± 0.6 mm at 20 N force (p < 0.05), with increasing AAc/HEMA ratio. Percentage cell viability was analyzed using indirect 3-[4, 5-dimethylthiazolyl-2]-2,5-diphenyltetrazo-liumbromide (MTT) assay with fibroblast L929 cells; showed ≥92.3% cell viability after 24 h incubation. Cell proliferation on the scaffold surface was found to increase with incorporation of HEMA in P(AAc)/G cross-linked hydrogel matrix upto a certain extent. These biocompatible, elastic, and swellable hydrogels can serve as a matrix for drug delivery and tissue engineering applications.

  7. Tissue-specific direct microtransfer of nanomaterials into Drosophila embryos as a versatile in vivo test bed for nanomaterial toxicity assessment

    Directory of Open Access Journals (Sweden)

    Vega-Alvarez S

    2014-04-01

    Full Text Available Sasha Vega-Alvarez,1 Adriana Herrera,2 Carlos Rinaldi,2–4 Franklin A Carrero-Martínez1,5 1Department of Biology, 2Department of Chemical Engineering, University of Puerto Rico-Mayagüez, Mayagüez, Puerto Rico; 3J Crayton Pruitt Family Department of Biomedical Engineering, 4Department of Chemical Engineering, University of Florida, Gainesville, FL, USA; 5Department of Anatomy and Neuroscience, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico Abstract: Nanomaterials are the subject of intense research, focused on their synthesis, modification, and biomedical applications. Increased nanomaterial production and their wide range of applications imply a higher risk of human and environmental exposure. Unfortunately, neither environmental effects nor toxicity of nanomaterials to organisms are fully understood. Cost-effective, rapid toxicity assays requiring minimal amounts of materials are needed to establish both their biomedical potential and environmental safety standards. Drosophila exemplifies an efficient and cost-effective model organism with a vast repertoire of in vivo tools and techniques, all with high-throughput scalability and screening feasibility throughout its life cycle. Here we report tissue specific nanomaterial assessment through direct microtransfer into target tissues. We tested several nanomaterials with potential biomedical applications such as single-wall carbon nanotubes, multiwall carbon nanotubes, silver, gold, titanium dioxide, and iron oxide nanoparticles. Assessment of nanomaterial toxicity was conducted by evaluating progression through developmental morphological milestones in Drosophila. This cost-effective assessment method is amenable to high-throughput screening. Keywords: nanotoxicity, Drosophila, microtransfer, nanoparticle, iron oxide, silver, gold, titanium dioxide, carbon nanotube

  8. A combined approach for the assessment of cell viability and cell functionality of human fibrochondrocytes for use in tissue engineering.

    Directory of Open Access Journals (Sweden)

    Ingrid Garzón

    Full Text Available Temporo-mandibular joint disc disorders are highly prevalent in adult populations. Autologous chondrocyte implantation is a well-established method for the treatment of several chondral defects. However, very few studies have been carried out using human fibrous chondrocytes from the temporo-mandibular joint (TMJ. One of the main drawbacks associated to chondrocyte cell culture is the possibility that chondrocyte cells kept in culture tend to de-differentiate and to lose cell viability under in in-vitro conditions. In this work, we have isolated human temporo-mandibular joint fibrochondrocytes (TMJF from human disc and we have used a highly-sensitive technique to determine cell viability, cell proliferation and gene expression of nine consecutive cell passages to determine the most appropriate cell passage for use in tissue engineering and future clinical use. Our results revealed that the most potentially viable and functional cell passages were P5-P6, in which an adequate equilibrium between cell viability and the capability to synthesize all major extracellular matrix components exists. The combined action of pro-apoptotic (TRAF5, PHLDA1 and anti-apoptotic genes (SON, HTT, FAIM2 may explain the differential cell viability levels that we found in this study. These results suggest that TMJF should be used at P5-P6 for cell therapy protocols.

  9. Experimental exposure of African catfish Clarias Gariepinus (Burchell, 1822 to phenol: Clinical evaluation, tissue alterations and residue assessment

    Directory of Open Access Journals (Sweden)

    Mai D. Ibrahem

    2012-04-01

    Full Text Available There is lack of information regarding; the toxicological and pathological consequences of phenol stressed Clarias gariepinus; as well as; the susceptibility of the stressed fish to disease occurrence. Static renewal bioassay was experimentally conducted to evaluate the toxic effects of phenol on the African catfish C. gariepinus. Ninety-six-hour acute toxicity tests revealed that the median lethal concentration of phenol (LC50 is 35 mg/L by immersion. Four experimental fish groups were assigned for 3 weeks exposure test; three were exposed 20%, 50% and 70% LC50, the fourth control fish group received a vehicle of dechlorinated water. Abnormal signs including cessation of feeding, nervous manifestations; skin expressed perfuses mucous, black patches with skin erosion and ulcerations in the later stages. All observations were correlated to the time and dose of exposure. Post mortem examination revealed adhesion of the internal organs. For tissue alterations; Skin, gills, brain, liver and kidney showed variable degrees of degenerative changes and necrosis. Muscle residues shown in mean ± SE were 4.3 ± 0.05 and 6.65 ± 0.05 ppm in groups that received 20 and 50% LD50, respectively. Infection with Aeromonas hydrophila resulted in high percent of mortalities with a non significant difference between the challenged fish groups. The study cleared that phenol is toxic to C. gariepinus under experimental conditions.

  10. Right ventricular function assessed by tissue Doppler echocardiography in older subjects without evidence for structural cardiac disease.

    Science.gov (United States)

    Laszlo, Roman; Baumann, Tobias; Konz, Hanna; Dallmeier, Dhayana; Klenk, Jochen; Denkinger, Michael; Koenig, Wolfgang; Rothenbacher, Dietrich; Steinacker, Juergen Michael

    2016-05-31

    The aim of our study was to obtain right ventricular (RV) tissue Doppler imaging (TDI) data in older subjects (n = 95, mean age: 74.5 ± 4.6 years) without evidence of hemodynamically significant structural heart disease recruited from a large population-based cohort (ActiFE-Ulm study). Our data indicate that aging may be accompanied by decreasing RV diastolic function and at most little alterations of RV systolic function. Mean values of all parameters were still within the guideline-suggested reference range with most of them closer to the abnormality thresholds. On an individual basis, respective thresholds were also exceeded in some subjects (almost all parameters subjects, presumed pathological measures might still be compatible with physiological age-related alterations. Therefore, they always have to be interpreted across the clinical context and in relation to other parameters of morphology and function obtained by other ultrasound imaging techniques (M-mode, B-mode, etc.) in the context of echocardiographic evaluation of the right heart.

  11. In Vitro Assessment of Antibacterial Activity and Cytocompatibility of Quercetin-Containing PLGA Nanofibrous Scaffolds for Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Zhi-Cai Xing

    2012-01-01

    Full Text Available Flavonoids, such as quercetin, have been reported to exhibit a wide range of biological activities related to their antioxidant capacity. The aim of this study was to investigate the protective effect of quercetin on cell adhesion, and the viability and proliferation of KB epithelial cells. Quercetin- (1, 5 wt%-containing poly (l-lactide-co-glycolide (PLGA nanofibrous scaffolds (PLGA/Q 1, PLGA/Q 5 were prepared by electrospinning technique and their antibacterial properties were examined. Two types of bacteria strains, Staphylococcus aureus (SA and Klebsiella pneumoniae (KP, were used to evaluate the antibacterial properties of the scaffolds. The results showed that the quercetin-containing PLGA nanofibrous scaffolds exhibited significant antibacterial effects against the two bacterial strains. KB epithelial cells were also used to evaluate the cytocompatibility of the scaffolds. From the results, it was found that the PLGA nanofibrous scaffolds with 1 wt% of quercetin had good cell compatibility. It is considered that the PLGA nanofibrous scaffolds with 1 wt% quercetin have potential to be used in tissue engineering.

  12. Cellulose-based porous scaffold for bone tissue engineering applications: Assessment of hMSC proliferation and differentiation.

    Science.gov (United States)

    Demitri, Christian; Grazia Raucci, Maria; Giuri, Antonella; De Benedictis, Vincenzo Maria; Giugliano, Daniela; Calcagnile, Paola; Sannino, Alessandro; Ambrosio, Luigi

    2015-10-31

    Physical foaming combined with microwave-induced curing was used in this study to develop an innovative device for bone tissue regeneration. In the first step of the process, a stable physical foaming was induced using a surfactant (i.e. pluronic) as blowing agent of a homogeneous blend of Sodium salt of carboxymethylcellulose (CMCNa) and polyethylene glycol diacrylate (PEGDA700) solution. In the second step, the porous structure of the scaffold was chemically stabilized by radical polymerization induced by a homogeneous rapid heating of the sample in a microwave reactor. In this step 2,2-Azobis[2-(2-imidazolin-2 yl)propane]Dihydrochloride was used as thermoinitiator (TI). CMCNa and PEGDA were mixed with different blends to correlate the properties of final product with the composition. The chemical properties of each sample were evaluated by spectroscopy analysis ATR-IR (before and after curing) in order to maximize reaction yield, and optimize kinetic parameters (i.e. time curing, microwave power). The stability of the materials was evaluated in vitro by degradation test in Phosphate Buffered Saline (PBS). Biological analyses were performed to evaluate the effect of scaffold materials on cellular behaviour in terms of proliferation and early osteogenic differentiation of human Mesenchymal Stem Cells (hMSC). This article is protected by copyright. All rights reserved.

  13. Common protein biomarkers assessed by reverse phase protein arrays show considerable intratumoral heterogeneity in breast cancer tissues.

    Science.gov (United States)

    Malinowsky, Katharina; Raychaudhuri, Mithu; Buchner, Theresa; Thulke, Sabrina; Wolff, Claudia; Höfler, Heinz; Becker, Karl-Friedrich; Avril, Stefanie

    2012-01-01

    Proteins are used as prognostic and predictive biomarkers in breast cancer. However, the variability of protein expression within the same tumor is not well studied. The aim of this study was to assess intratumoral heterogeneity in protein expression levels by reverse-phase-protein-arrays (RPPA) (i) within primary breast cancers and (ii) between axillary lymph node metastases from the same patient. Protein was extracted from 106 paraffin-embedded samples from 15 large (≥3 cm) primary invasive breast cancers, including different zones within the primary tumor (peripheral, intermediate, central) as well as 2-5 axillary lymph node metastases in 8 cases. Expression of 35 proteins including 15 phosphorylated proteins representing the HER2, EGFR, and uPA/PAI-1 signaling pathways was assessed using reverse-phase-protein-arrays. All 35 proteins showed considerable intratumoral heterogeneity within primary breast cancers with a mean coefficient of variation (CV) of 31% (range 22-43%). There were no significant differences between phosphorylated (CV 32%) and non-phosphorylated proteins (CV 31%) and in the extent of intratumoral heterogeneity within a defined tumor zone (CV 28%, range 18-38%) or between different tumor zones (CV 24%, range 17-38%). Lymph node metastases from the same patient showed a similar heterogeneity in protein expression (CV 27%, range 18-34%). In comparison, the variation amongst different patients was higher in primary tumors (CV 51%, range 29-98%) and lymph node metastases (CV 65%, range 40-146%). Several proteins showed significant differential expression between different tumor stages, grades, histological subtypes and hormone receptor status. Commonly used protein biomarkers of breast cancer, including proteins from HER2, uPA/PAI-1 and EGFR signaling pathways showed higher than previously reported intratumoral heterogeneity of expression levels both within primary breast cancers and between lymph node metastases from the same patient. Assessment

  14. Connective tissue growth factor is overexpressed in human hepatocellular carcinoma and promotes cell invasion and growth

    Institute of Scientific and Technical Information of China (English)

    Ming Xiu; Ya-Hui Liu; David R Brigstock; Fang-Hui He; Rui-Juan Zhang; Run-Ping Gao

    2012-01-01

    AIM:To determine the expression characteristics of connective tissue growth factor (CTGF/CCN2) in human hepatocellular carcinoma (HCC) in histology and to elucidate the roles of CCN2 on hepatoma cell cycle progression and metastasis in vitro.METHODS:Liver samples from 36 patients (who underwent hepatic resection for the first HCC between 2006 and 2011) and 6 normal individuals were examined for transforming growth factor β1 (TGF-β1) or CCN2 mRNA by in situ hybridization.Computer image analysis was performed to measure integrated optimal density of CCN2 mRNA-positive cells in carcinoma foci and the surrounding stroma.Fibroblast-specific protein-1 (FSP-1) and E-cadherin were examined to evaluate the process of epithelial to mesenchymal transition,α-smooth muscle actin and FSP-1 were detected to identify hepatic stellate cells,and CD34 was measured to evaluate the extent of vascularization in liver tissues by immunohistochemical staining.CCN2 was assessed for its stimulation of HepG2 cell migration and invasion using commercial kits while flow cytometry was used to determine CCN2 effects on HepG2 cell-cycle.RESULTS:In situ hybridization analysis showed that TGF-β1 mRNA was mainly detected in connective tissues and vasculature around carcinoma foci.In comparison to normal controls,CCN2 mRNA was enhanced 1.9-fold in carcinoma foci (12.36 ± 6.08 vs 6.42 ± 2.35)or 9.4-fold in the surrounding stroma (60.27 ± 28.71 vs 6.42 ± 2.35),with concomitant expression of CCN2 and TGF-β1 mRNA in those areas.Epithelial-mesenchymal transition phenotype related with CCN2 was detected in 12/36 (33.3%) of HCC liver samples at the edges between carcinoma foci and vasculature.Incubation of HepG2 cells with CCN2 (100 ng/mL) resulted in more of the cells transitioning into S phase (23.85 ± 2.35vs 10.94 ± 0.23),and induced a significant migratory (4.0-fold) and invasive (5.7-fold) effect.TGF-β1-induced cell invasion was abrogated by a neutralizing CCN2 antibody showing that CCN2

  15. Stimulated infrared thermography applied to differentiate scar tissue from peri-scar tissue: a preliminary study.

    Science.gov (United States)

    Riquet, Damien; Houel, Nicolas; Bodnar, Jean-Luc

    2016-08-01

    Every human injury leads to a scar formation. The healing process leads to the formation of new tissue: the scar, which is different from the original tissue. This process is influenced by mechanical strength and the local vasculature is modified. The purpose of this study is to show that there are various temperatures between the scar and the peri-scar area associated with the healing process that can be estimated using the thermal infrared camera. In the study, 12 scars were stimulated by cold. Several changes of temperature were observed between scar and peri-scar area for 10 min. Scars appeared significantly colder with a Wilcoxon test (p = 0.01). Results showed that stimulated infrared thermography can be used to monitor the temperature difference between the scar and peri-scar tissue.

  16. Monitoring plant tissue nitrogen isotopes to assess nearshore inputs of nitrogen to Lake Crescent, Olympic National Park, Washington

    Science.gov (United States)

    Cox, Stephen E.; Moran, Patrick W.; Huffman, Raegan L.; Fradkin, Steven C.

    2016-05-31

    Mats of filamentous-periphytic algae present in some nearshore areas of Lake Crescent, Olympic National Park, Washington, may indicate early stages of eutrophication from nutrient enrichment of an otherwise highly oligotrophic lake. Natural abundance ratios of stable isotopes of nitrogen (δ15N) measured in plant tissue growing in nearshore areas of the lake indicate that the major source of nitrogen used by these primary producing plants is derived mainly from atmospherically fixed nitrogen in an undeveloped forested ecosystem. Exceptions to this pattern occurred in the Barnes Point area where elevated δ15N ratios indicate that effluent from septic systems also contribute nitrogen to filamentous-periphytic algae growing in the littoral zone of that area. Near the Lyre River outlet of Lake Crescent, the δ15N of filamentous-periphytic algae growing in close proximity to the spawning areas of a unique species of trout show little evidence of elevated δ15N indicating that nitrogen from on-site septic systems is not a substantial source of nitrogen for these plants. The δ15N data corroborate estimates that nitrogen input to Lake Crescent from septic sources is comparatively small relative to input from motor vehicle exhaust and vegetative sources in undeveloped forests, including litterfall, pollen, and symbiotic nitrogen fixation. The seasonal timing of blooms of filamentous-periphytic algal near the lake shoreline is also consistent with nitrogen exported from stands of red alder trees (Alnus rubra). Isotope biomonitoring of filamentous-periphytic algae may be an effective approach to monitoring the littoral zone for nutrient input to Lake Crescent from septic sources.

  17. Assessment of legacy and emerging persistent organic pollutants in Weddell seal tissue (Leptonychotes weddellii) near McMurdo Sound, Antarctica.

    Science.gov (United States)

    Trumble, Stephen J; Robinson, Eleanor M; Noren, Shawn R; Usenko, Sascha; Davis, Jay; Kanatous, Shane B

    2012-11-15

    Muscle samples were collected from pup, juvenile and adult Weddell seals (Leptonychotes weddellii) near McMurdo Sound, Antarctica during the austral summer of 2006. Blubber samples were collected from juvenile and adult seals. Samples were analyzed for emerging and legacy persistent organic pollutants (POPs) including current and historic-use organochlorine pesticides, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs). Of the 41 target analytes, 28 contaminants were recovered from the Weddell seal blubber, in this order of prevalence: p,p'-DDE, p,p'-DDT, trans-nonachlor, mirex, cis-nonachlor, PCB 153, PCB 138, dieldrin, heptachlor epoxide, nonachlor III, PCB 187, oxychlordane, cis-chlordane, PCB 118, PBDE 47, PCB 156, PCB 149, PCB 180, PCB 101, PCB 170, PCB 105, o,p'-DDT, PCB 99, trans-chlordane, PCB 157, PCB 167, PCB 189, and PCB 114. Fewer POPs were found in the muscle samples, but were similar in the order of prevalence to that of the blubber: p,p'-DDE, o,p'-DDT, trans-nonachlor, nonachlor III, oxychlordane, p,p'-DDT, dieldrin, mirex, cis-nonachlor, PCB 138, and PCB 105. Besides differences in toxicant concentrations reported between the muscle and blubber, we found differences in POP levels according to age class and suggest that differences in blubber storage and/or mobilization of lipids result in age class differences in POPs. To our knowledge, such ontogenetic associations are novel. Importantly, data from this study suggest that p,p'-DDT is becoming less prevalent temporally, resulting in an increased proportion of its metabolite p,p'-DDE in the tissues of this top predator. In addition, this study is among the first to identify a PBDE congener in Weddell seals near the McMurdo Station. This may provide evidence of increased PBDE transport and encroachment in Antarctic wildlife.

  18. Assessment of BRAF V600E Status in Colorectal Carcinoma: Tissue-Specific Discordances between Immunohistochemistry and Sequencing.

    Science.gov (United States)

    Estrella, Jeannelyn S; Tetzlaff, Michael T; Bassett, Roland L; Patel, Keyur P; Williams, Michelle D; Curry, Jonathan L; Rashid, Asif; Hamilton, Stanley R; Broaddus, Russell R

    2015-12-01

    Although sequencing provides the gold standard for identifying colorectal carcinoma with BRAF V600E mutation, immunohistochemistry (IHC) with the recently developed mouse monoclonal antibody VE1 for BRAF V600E protein has shown promise as a more widely available and rapid method. However, we identified anecdotal discordance between VE1 IHC and sequencing results and therefore analyzed VE1 staining by two different IHC methods (Leica Bond and Ventana BenchMark) in whole tissue sections from 480 colorectal carcinomas (323 BRAF wild-type, 142 BRAF V600E mutation, and 15 BRAF non-V600E mutation). We also compared the results with melanomas and papillary thyroid carcinomas (PTC). With the Bond method, among 142 BRAF V600E-mutated colorectal carcinomas, 77 (54%) had diffuse VE1 staining and 48 (33%) had heterogeneous staining, but 17 (12%) were negative. Among 323 BRAF wild-type colorectal carcinomas, 196 (61%) were negative, but 127 (39%) had staining, including 7 with diffuse staining. When positivity was defined as staining in ≥ 20% of tumor cells, VE1 IHC had sensitivity of 75% and specificity of 93% for BRAF V600E mutation. With the Ventana method, among 57 BRAF V600E-mutated colorectal carcinomas, 36 (63%) had diffuse VE1 staining, whereas 6 (11%) had no or weak (Ventana VE1 IHC in melanoma and PTC were highly concordant with sequencing results. We conclude that VE1 IHC produces suboptimal results in colorectal carcinoma and should not be used to guide patient management.

  19. Common protein biomarkers assessed by reverse phase protein arrays show considerable intratumoral heterogeneity in breast cancer tissues.

    Directory of Open Access Journals (Sweden)

    Katharina Malinowsky

    Full Text Available Proteins are used as prognostic and predictive biomarkers in breast cancer. However, the variability of protein expression within the same tumor is not well studied. The aim of this study was to assess intratumoral heterogeneity in protein expression levels by reverse-phase-protein-arrays (RPPA (i within primary breast cancers and (ii between axillary lymph node metastases from the same patient. Protein was extracted from 106 paraffin-embedded samples from 15 large (≥3 cm primary invasive breast cancers, including different zones within the primary tumor (peripheral, intermediate, central as well as 2-5 axillary lymph node metastases in 8 cases. Expression of 35 proteins including 15 phosphorylated proteins representing the HER2, EGFR, and uPA/PAI-1 signaling pathways was assessed using reverse-phase-protein-arrays. All 35 proteins showed considerable intratumoral heterogeneity within primary breast cancers with a mean coefficient of variation (CV of 31% (range 22-43%. There were no significant differences between phosphorylated (CV 32% and non-phosphorylated proteins (CV 31% and in the extent of intratumoral heterogeneity within a defined tumor zone (CV 28%, range 18-38% or between different tumor zones (CV 24%, range 17-38%. Lymph node metastases from the same patient showed a similar heterogeneity in protein expression (CV 27%, range 18-34%. In comparison, the variation amongst different patients was higher in primary tumors (CV 51%, range 29-98% and lymph node metastases (CV 65%, range 40-146%. Several proteins showed significant differential expression between different tumor stages, grades, histological subtypes and hormone receptor status. Commonly used protein biomarkers of breast cancer, including proteins from HER2, uPA/PAI-1 and EGFR signaling pathways showed higher than previously reported intratumoral heterogeneity of expression levels both within primary breast cancers and between lymph node metastases from the same patient

  20. Air pollution assessment based on elemental concentration of leaves tissue and foliage dust along an urbanization gradient in Vienna.

    Science.gov (United States)

    Simon, Edina; Braun, Mihály; Vidic, Andreas; Bogyó, Dávid; Fábián, István; Tóthmérész, Béla

    2011-05-01

    Foliage dust contains heavy metal that may have harmful effects on human health. The elemental contents of tree leaves and foliage dust are especially useful to assess air environmental pollution. We studied the elemental concentrations in foliage dust and leaves of Acer pseudoplatanus along an urbanization gradient in Vienna, Austria. Samples were collected from urban, suburban and rural areas. We analysed 19 elements in both kind of samples: aluminium, barium, calcium, copper, iron, potassium, magnesium, sodium, phosphor, sulphur, strontium and zinc. We found that the elemental concentrations of foliage dust were significantly higher in the urban area than in the rural area for aluminium, barium, iron, lead, phosphor and selenium. Elemental concentrations of leaves were significantly higher in urban than in rural area for manganese and strontium. Urbanization changed significantly the elemental concentrations of foliage dust and leaves and the applied method can be useful for monitoring the environmental load.

  1. Therapy-induced carboplatin-DNA adduct levels in human ovarian tumours in relation to assessment of adduct measurement in mouse tissues.

    Science.gov (United States)

    Jarvis, Ian W H; Meczes, Emma L; Thomas, Huw D; Edmondson, Richard J; Veal, Gareth J; Boddy, Alan V; Ottley, Christopher J; Pearson, D Graham; Tilby, Michael J

    2012-01-01

    Despite an increasing understanding of the molecular mechanisms by which platinum drug DNA adducts interact with cellular processes, the relationship between adduct formation in tumours and clinical response remains unclear. We have determined carboplatin-DNA adduct levels in biopsies removed from ovarian cancer patients following treatment. Reliability of DNA adduct measurements in tissues samples were assessed using experimental animals. Platinum-DNA adduct levels were measured using inductively coupled plasma mass spectrometry (ICP-MS) and plasma drug concentrations determined by atomic absorption spectrometry (AAS). Adduct levels in tissues and plasma pharmacokinetics were determined in Balb/c mice exposed to platinum drugs. Comparisons of adduct levels in tumour and normal tissue were made in nu/nu mice carrying human neuroblastoma xenografts. At 30 min post-cisplatin administration, adduct levels in DNA from kidney and liver were approximately 10- and 6-fold higher than spleen or tumour. By 60 min, levels in liver and kidney, but not spleen or tumour, had fallen considerably. Carboplatin showed high adduct levels only in kidney. Adduct levels in tumour xenografts were comparable to those induced in vitro with similar drug exposures. In clinical samples removed 6h after drug administration, adduct levels ranged from 1.9 to 4.3 and 0.2 to 3.6 nmol Pt/g DNA for tumour biopsies and peripheral blood mononuclear cells, respectively. No correlation was apparent between these two data sets. The present results demonstrate that reliable measurements of adducts in clinical tumours are feasible. Future results should provide insight into drug resistance.

  2. Study of the Myocardial Contraction and Relaxation Velocities through Doppler Tissue Imaging Echocardiography: A New Alternative in the Assessment of the Segmental Ventricular Function

    Directory of Open Access Journals (Sweden)

    Silva Carlos Eduardo Suaide

    2002-01-01

    Full Text Available OBJECTIVE: Doppler tissue imaging (DTI enables the study of the velocity of contraction and relaxation of myocardial segments. We established standards for the peak velocity of the different myocardial segments of the left ventricle in systole and diastole, and correlated them with the electrocardiogram. METHODS: We studied 35 healthy individuals (27 were male with ages ranging from 12 to 59 years (32.9 ± 10.6. Systolic and diastolic peak velocities were assessed by Doppler tissue imaging in 12 segments of the left ventricle, establishing their mean values and the temporal correlation with the cardiac cycle. RESULTS: The means (and standard deviation of the peak velocities in the basal, medial, and apical regions (of the septal, anterior, lateral, and posterior left ventricle walls were respectively, in cm/s, 7.35(1.64, 5.26(1.88, and 3.33(1.58 in systole and 10.56(2.34, 7.92(2.37, and 3.98(1.64 in diastole. The mean time in which systolic peak velocity was recorded was 131.59ms (±19.12ms, and diastolic was 459.18ms (±18.13ms based on the peak of the R wave of the electrocardiogram. CONCLUSION: In healthy individuals, maximum left ventricle segment velocities decreased from the bases to the ventricular apex, with certain proportionality between contraction and relaxation (P<0.05. The use of Doppler tissue imaging may be very helpful in detecting early alterations in ventricular contraction and relaxation.

  3. Assessment of Tissue Eosinophilia as a Prognosticator in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma—An Image Analysis Study

    Directory of Open Access Journals (Sweden)

    Megha Jain

    2014-01-01

    Full Text Available Association of tissue eosinophilia with oral squamous cell carcinoma has shown variable results ranging from favourable to unfavourable or even having no influence on prognosis. Also, very few studies have been done to know the role of eosinophils in premalignancy. So the present study investigated role of eosinophilic infiltration in oral precancer and cancer and its possible use as a prognosticator. 60 histopathologically proven cases (20 cases each of metastatic and nonmetastatic oral squamous cell carcinoma and oral leukoplakia with dysplasia of various grades were included. Congo red is used as a special stain for eosinophils. Each specimen slide was viewed under high power in 10 consecutive microscopic fields for counting of eosinophils. As a result, a significant increase in eosinophil count was found in oral carcinomas compared to dysplasia. Nonmetastatic cases showed higher counts than metastatic carcinomas. So, it is concluded that eosinophilia is a favourable histopathological prognostic factor in oral cancer. Moreover, higher eosinophil counts in carcinoma group compared to dysplasia group proved that they might have a role in stromal invasion thus suggesting that quantitative assessment of tissue eosinophilia should become a part of the routine histopathological diagnosis for oral precancer and OSCC.

  4. The impact of ageing on adipose structure, function and vasculature in the B6D2F1 mouse: evidence of significant multisystem dysfunction.

    Science.gov (United States)

    Donato, Anthony J; Henson, Grant D; Hart, Corey R; Layec, Gwenael; Trinity, Joel D; Bramwell, R Colton; Enz, Ryley A; Morgan, R Garrett; Reihl, Kelly D; Hazra, Sugata; Walker, Ashley E; Richardson, Russell S; Lesniewski, Lisa A

    2014-09-15

    The critical influence of the white adipose tissue (WAT) on metabolism is well-appreciated in obesity, but adipose tissue dysfunction as a mechanism underlying age-associated metabolic dysfunction requires elucidation. To explore this possibility, we assessed metabolism and measures of epididymal (e)WAT mitochondria and artery function in young (6.1 ± 0.4 months) and old (29.6 ± 0.2 months) B6D2F1 mice. There were no group differences in average daily oxygen consumption, fasted blood glucose or plasma free fatty acids, but fasted plasma insulin and the homeostatic model assessment of insulin resistance (HOMA-IR%) were higher in the old (∼50-85%, P Tissue mass (P adipose markers (P adipose tissue characterized by both mitochondrial and arterial dysfunction.

  5. Assessment of Proton Microbeam Analysis of 11B for Quantitative Microdistribution Analysis of Boronated Neutron Capture Agent Analogs in Biological Tissues

    Energy Technology Data Exchange (ETDEWEB)

    Bench, G; Grant, P G; Ueda, D L; Autry-Conwell, S A; Hou, Y; Boggan, J E

    2002-12-04

    Purpose: To assess the {sup 11}B(p, {alpha}){sup 8}Be* nuclear reaction for quantitatively mapping the in-vivo sub-cellular distribution of boron within gliosarcoma tumors treated with boronated neutron capture therapy agent (NCTA) analogs. Materials and Methods: Intracranial tumors were produced in Fisher 344 rats using a 9L gliosarcoma model. Fourteen days later, the majority of rats were treated with f-boronophenylalanine and sacrificed 30 or 180 minutes after intravenous injection. Freeze dried tumor cryosections were imaged using the {sup 11}B(p, {alpha}){sup 8}Be* nuclear reaction and proton microbeams obtained from the nuclear microprobe at Lawrence Livermore National Laboratory. Results/Discussion: With{sup 11}B(p, {alpha}){sup 8}Be* analysis, {sup 11}B distributions within cells can be quantitatively imaged with spatial resolutions down to 1.5 {micro}m, minimum detection limits of 0.8 mg/kg and acquisition times of several hours. These capabilities offer advantages over alpha track autoradiography, electron energy loss spectroscopy and secondary ion mass spectrometry (SIMS) for 'B quantitation in tissues. However, the spatial resolution, multi-isotope capability and analysis times achieved with SIMS are superior to those achieved with {sup 11}B(p, {alpha}){sup 8}Be* analysis. Conclusions: When accuracy in quantitation is crucial, the assessing the microdistribution of {sup 11}B. {sup 11}B(p, {alpha}){sup 8}Be* reaction is well suited for Otherwise, SIMS may well be better suited to image the microdistribution of boron associated with NCTAs in biological tissues.

  6. Effects of Liver Fibrosis Progression on Tissue Relaxation Times in Different Mouse Models Assessed by Ultrahigh Field Magnetic Resonance Imaging.

    Science.gov (United States)

    Müller, Andreas; Hochrath, Katrin; Stroeder, Jonas; Hittatiya, Kanishka; Schneider, Günther; Lammert, Frank; Buecker, Arno; Fries, Peter

    2017-01-01

    Recently, clinical studies demonstrated that magnetic resonance relaxometry with determination of relaxation times T1 and T2(⁎) may aid in staging and management of liver fibrosis in patients suffering from viral hepatitis and steatohepatitis. In the present study we investigated T1 and T2(⁎) in different models of liver fibrosis to compare alternate pathophysiologies in their effects on relaxation times and to further develop noninvasive quantification methods of liver fibrosis. MRI was performed with a fast spin echo sequence for measurement of T1 and a multigradient echo sequence for determination of T2(⁎). Toxic liver fibrosis was induced by injections of carbon tetrachloride (1.4 mL CCl4 per kg bodyweight and week, for 3 or 6 weeks) in BALB/cJ mice. Chronic sclerosing cholangitis was mimicked using the ATP-binding cassette transporter B4 knockout (Abcb4 (-/-)) mouse model. Untreated BALB/cJ mice served as controls. To assess hepatic fibrosis, we ascertained collagen contents and fibrosis scores after Sirius red staining. T1 and T2(⁎) correlate differently to disease severity and etiology of liver fibrosis. T2(⁎) shows significant decrease correlating with fibrosis in CCl4 treated animals, while demonstrating significant increase with disease severity in Abcb4 (-/-) mice. Measurements of T1 and T2(⁎) may therefore facilitate discrimination between different stages and causes of liver fibrosis.

  7. Effects of Liver Fibrosis Progression on Tissue Relaxation Times in Different Mouse Models Assessed by Ultrahigh Field Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Andreas Müller

    2017-01-01

    Full Text Available Recently, clinical studies demonstrated that magnetic resonance relaxometry with determination of relaxation times T1 and T2⁎ may aid in staging and management of liver fibrosis in patients suffering from viral hepatitis and steatohepatitis. In the present study we investigated T1 and T2⁎ in different models of liver fibrosis to compare alternate pathophysiologies in their effects on relaxation times and to further develop noninvasive quantification methods of liver fibrosis. MRI was performed with a fast spin echo sequence for measurement of T1 and a multigradient echo sequence for determination of T2⁎. Toxic liver fibrosis was induced by injections of carbon tetrachloride (1.4 mL CCl4 per kg bodyweight and week, for 3 or 6 weeks in BALB/cJ mice. Chronic sclerosing cholangitis was mimicked using the ATP-binding cassette transporter B4 knockout (Abcb4 -/- mouse model. Untreated BALB/cJ mice served as controls. To assess hepatic fibrosis, we ascertained collagen contents and fibrosis scores after Sirius red staining. T1 and T2⁎ correlate differently to disease severity and etiology of liver fibrosis. T2⁎ shows significant decrease correlating with fibrosis in CCl4 treated animals, while demonstrating significant increase with disease severity in Abcb4 -/- mice. Measurements of T1 and T2⁎ may therefore facilitate discrimination between different stages and causes of liver fibrosis.

  8. Effects of Liver Fibrosis Progression on Tissue Relaxation Times in Different Mouse Models Assessed by Ultrahigh Field Magnetic Resonance Imaging

    Science.gov (United States)

    Müller, Andreas; Hochrath, Katrin; Stroeder, Jonas; Hittatiya, Kanishka; Schneider, Günther; Lammert, Frank; Buecker, Arno

    2017-01-01

    Recently, clinical studies demonstrated that magnetic resonance relaxometry with determination of relaxation times T1 and T2⁎ may aid in staging and management of liver fibrosis in patients suffering from viral hepatitis and steatohepatitis. In the present study we investigated T1 and T2⁎ in different models of liver fibrosis to compare alternate pathophysiologies in their effects on relaxation times and to further develop noninvasive quantification methods of liver fibrosis. MRI was performed with a fast spin echo sequence for measurement of T1 and a multigradient echo sequence for determination of T2⁎. Toxic liver fibrosis was induced by injections of carbon tetrachloride (1.4 mL CCl4 per kg bodyweight and week, for 3 or 6 weeks) in BALB/cJ mice. Chronic sclerosing cholangitis was mimicked using the ATP-binding cassette transporter B4 knockout (Abcb4 −/−) mouse model. Untreated BALB/cJ mice served as controls. To assess hepatic fibrosis, we ascertained collagen contents and fibrosis scores after Sirius red staining. T1 and T2⁎ correlate differently to disease severity and etiology of liver fibrosis. T2⁎ shows significant decrease correlating with fibrosis in CCl4 treated animals, while demonstrating significant increase with disease severity in Abcb4 −/− mice. Measurements of T1 and T2⁎ may therefore facilitate discrimination between different stages and causes of liver fibrosis. PMID:28194423

  9. Unilateral anterior persistent fetal vasculature in a child with blepharophimosis-ptosis-epicanthus inversus syndrome: A surgical challenge

    Directory of Open Access Journals (Sweden)

    Vasudha Kemmanu

    2016-01-01

    Full Text Available Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES is a rare autosomal dominant genetic disease. It is clinically characterized by four major features; blepharophimosis, ptosis, epicanthus inversus, and telecanthus. We report a case of a 1-year-old female with BPES with unilateral anterior persistent fetal vasculature (PFV. On examination, she was found to have all the clinical features of BPES, along with calcified and partially absorbed cataract with elongated ciliary processes in her left eye. B-scan of left eye showed attached retina with no evidence of posterior PFV. Systemic examination was normal. She underwent cataract surgery with primary posterior capsulotomy with intraocular lens implantation under general anesthesia. Literature search did not reveal any previous reports of unilateral anterior PFV and BPES. The clinical features, other associations, and the difficulties in the surgical management of this condition are discussed.

  10. Unilateral anterior persistent fetal vasculature in a child with blepharophimosis-ptosis-epicanthus inversus syndrome: A surgical challenge

    Science.gov (United States)

    Kemmanu, Vasudha; Rathod, Pragnya; Anaspure, Hemant; Yadav, Naresh K

    2016-01-01

    Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal dominant genetic disease. It is clinically characterized by four major features; blepharophimosis, ptosis, epicanthus inversus, and telecanthus. We report a case of a 1-year-old female with BPES with unilateral anterior persistent fetal vasculature (PFV). On examination, she was found to have all the clinical features of BPES, along with calcified and partially absorbed cataract with elongated ciliary processes in her left eye. B-scan of left eye showed attached retina with no evidence of posterior PFV. Systemic examination was normal. She underwent cataract surgery with primary posterior capsulotomy with intraocular lens implantation under general anesthesia. Literature search did not reveal any previous reports of unilateral anterior PFV and BPES. The clinical features, other associations, and the difficulties in the surgical management of this condition are discussed. PMID:27488160

  11. Assessment of some heavy metals in the tissues (gills, liver and muscle) of Clarias gariepinus from Calabar River, Cross River State, South-eastern Nigeria

    Institute of Scientific and Technical Information of China (English)

    Akaninyene Paul Joseph; Victor Oscar Eyo; Andem BasseyAndem; Joseph Udo Idung

    2016-01-01

    Objective: To assess the pollution status of Calabar River in relation to the levels of heavy metal in the tissue of the African catfish [Clarias gariepinus (C. gariepinus)]. Methods: A total of 45 samples of C. gariepinus were purchased from fishermen on landing at Nsidung beach along Calabar River within three months (15 samples monthly) from June to August, 2014. The samples were then put into a cold box containing ice blocks immediately after buying from the fishermen. The fish samples were transported immediately to the Chemistry Laboratory, University of Calabar for digestion and heavy metal analysis. Portions of the muscle, gills and liver were removed from the fresh samples and oven dried at temperature of 120 °C to constant weight and digested using standard methods. The digested tissue portions were analyzed for lead, iron, manganese, cobalt, chromium and cadmium concentrations using atomic absorption spectrophotometer. Results: Mercury was not detected at all in the muscle, liver and gills of C. gariepinus. The mean ± SD of metals in liver of C. gariepinus were: (0.080 ± 0.014), (0.110 ± 0.014), (6.480 ± 1.279) and (0.295 ± 0.021) mg/kg for Cd, Cr, Fe and Mn, respectively. In the gills, heavy metals values were: (0.065 ± 0.021), (0.115 ± 0.035), (5.843 ± 0.558), and (0.345 ± 0.007) mg/kg for Cd, Cr, Fe and Mn, respectively. In the muscles, heavy metals values were (0.045 ± 0.021), (0.115 ± 0.353), (5.150 ± 1.075), and (0.187 ± 0.045) mg/kg for Cd, Cr, Fe and Mn, respectively. The general trend of metals accumulation in tissues of C. gariepinus showed a decreasing trend of Fe > Mn > Cr > Cd. Also, the metal accumulation in the three tissues showed a decreasing trend of liver > gills > muscle. Conclusions: The metal concentrations in the muscle, gills and liver of C. gariepinus were all below the World Health Organization acceptable range, and as such fishery resources from Calabar River are safe for consumption.

  12. Assessment of some heavy metals in the tissues (gills, liver and muscle of Clarias gariepinus from Calabar River, Cross River State, South-eastern Nigeria

    Directory of Open Access Journals (Sweden)

    Akaninyene Paul Joseph

    2016-06-01

    Full Text Available Objective: To assess the pollution status of Calabar River in relation to the levels of heavy metal in the tissue of the African catfish [Clarias gariepinus (C. gariepinus]. Methods: A total of 45 samples of C. gariepinus were purchased from fishermen on landing at Nsidung beach along Calabar River within three months (15 samples monthly from June to August, 2014. The samples were then put into a cold box containing ice blocks immediately after buying from the fishermen. The fish samples were transported immediately to the Chemistry Laboratory, University of Calabar for digestion and heavy metal analysis. Portions of the muscle, gills and liver were removed from the fresh samples and oven dried at temperature of 120 °C to constant weight and digested using standard methods. The digested tissue portions were analyzed for lead, iron, manganese, cobalt, chromium and cadmium concentrations using atomic absorption spectrophotometer. Results: Mercury was not detected at all in the muscle, liver and gills of C. gariepinus. The mean ± SD of metals in liver of C. gariepinus were: (0.080 ± 0.014, (0.110 ± 0.014, (6.480 ± 1.279 and (0.295 ± 0.021 mg/kg for Cd, Cr, Fe and Mn, respectively. In the gills, heavy metals values were: (0.065 ± 0.021, (0.115 ± 0.035, (5.843 ± 0.558, and (0.345 ± 0.007 mg/kg for Cd, Cr, Fe and Mn, respectively. In the muscles, heavy metals values were (0.045 ± 0.021, (0.115 ± 0.353, (5.150 ± 1.075, and (0.187 ± 0.045 mg/kg for Cd, Cr, Fe and Mn, respectively. The general trend of metals accumulation in tissues of C. gariepinus showed a decreasing trend of Fe > Mn > Cr > Cd. Also, the metal accumulation in the three tissues showed a decreasing trend of liver > gills > muscle. Conclusions: The metal concentrations in the muscle, gills and liver of C. gariepinus were all below the World Health Organization acceptable range, and as such fishery resources from Calabar River are safe for consumption.

  13. Air pollution assessment based on elemental concentration of leaves tissue and foliage dust along an urbanization gradient in Vienna

    Energy Technology Data Exchange (ETDEWEB)

    Simon, Edina, E-mail: edina.simon@gmail.com [Department of Ecology, University of Debrecen, H-4010 Debrecen, P.O. Box 71 (Hungary); Braun, Mihaly [Department of Inorganic and Analytical Chemistry, University of Debrecen, H-4010 Debrecen, P.O. Box 21 (Hungary); Vidic, Andreas [Department fuer Naturschutzbiologie, Vegetations- und Landschaftsoekologie, Universitat Wien, Althanstrasse 14, 1090 Wien (Austria); Bogyo, David [Department of Ecology, University of Debrecen, H-4010 Debrecen, P.O. Box 71 (Hungary); Fabian, Istvan [Department of Inorganic and Analytical Chemistry, University of Debrecen, H-4010 Debrecen, P.O. Box 21 (Hungary); Tothmeresz, Bela [Department of Ecology, University of Debrecen, H-4010 Debrecen, P.O. Box 71 (Hungary)

    2011-05-15

    Foliage dust contains heavy metal that may have harmful effects on human health. The elemental contents of tree leaves and foliage dust are especially useful to assess air environmental pollution. We studied the elemental concentrations in foliage dust and leaves of Acer pseudoplatanus along an urbanization gradient in Vienna, Austria. Samples were collected from urban, suburban and rural areas. We analysed 19 elements in both kind of samples: aluminium, barium, calcium, copper, iron, potassium, magnesium, sodium, phosphor, sulphur, strontium and zinc. We found that the elemental concentrations of foliage dust were significantly higher in the urban area than in the rural area for aluminium, barium, iron, lead, phosphor and selenium. Elemental concentrations of leaves were significantly higher in urban than in rural area for manganese and strontium. Urbanization changed significantly the elemental concentrations of foliage dust and leaves and the applied method can be useful for monitoring the environmental load. - Highlights: > We studied the elements in dust and leaves along an urbanization gradient, Austria. > We analysed 19 elements: Al, Ba, Ca, Cd, Cu, Fe, K, Mg, Na, P, Pb, S, Sr and Zn. > Elemental concentrations were higher in urban area than in the rural area. > Studied areas were separated by CDA based on the elemental concentrations. > Dust and leaves can be useful for monitoring the environmental load. - Studying the elements (Al, Ba, Ca, Cu, Fe, K, Mg, Na, P, S, Sr, Zn) in dust and leaves along an urbanization gradient in Wien, Austria we found that the elemental concentrations of foliage dust were significantly higher in the urban area than in the rural area for Al, Ba, Fe, Pb, P and Se, and concentrations of leaves were significantly higher in urban than in rural area for Mn and Sr.

  14. Vascular tissue is the first site of damage in the TCDD-exposed fish embryo

    Energy Technology Data Exchange (ETDEWEB)

    Cantrell, S.; Tillitt, D. [Midwest Science Center, Columbia, MO (United States); Hannink, M. [Univ. of Missouri, Columbia, MO (United States). Biochemistry Dept.

    1995-12-31

    The planar halogenated hydrocarbons (PHHs) are a group of environmental contaminants that exert adverse biological effects in most vertebrate organisms. Embryonic development is the most sensitive life stage to the effects of these compounds. The reason for the enhanced sensitivity to PHHs during early life stages is unknown. To study TCDD-induced embryotoxicity, a fish species the medaka was the organism of choice. The authors localized the initial site of tissue damage in the developing embryo and investigated the mechanism of TCDD-induced tissue damage. There were three parts to this study, (1) observation of morphological anomalies in the TCDD-treated embryo, (2) immunohistochemical detection of DNA damage in the tissues of TCDD-treated embryos, and (3) test the ability of an antioxidant to delay the onset of initial tissue damage. Morphological observations show that the first visual lesions that occur in the TCDD treated embryo occur at stage 36, about day 6 post fertilization. The lesions are localized in the cardiac vasculature. Immunohistochemical staining, using the terminal nucleotide transferase assay (TdT-assay) which detects DNA damage showed that the initial site of tissue damage was in the vasculature in the cardiac region. Tissue damage was detected in neural tissue and muscle tissue at later time points. TCDD is known to induce oxidative stress in a variety of organisms, therefore; the authors tested to see if oxidative stress may play a role in TCDD-induced embryotoxicity. The TCDD-treated embryos were cultured in the antioxidant N-acetyl cysteine (NAC) and the morphological observations and TdT-assay were repeated. They found that NAC was able to delay the onset of tissue damage and NAC was able to reduce total mortality in the embryo. The results from this study indicate that the cardiac vasculature is the initial site of tissue damage.

  15. Tumor Angiogenesis Therapy Using Targeted Delivery of Paclitaxel to the Vasculature of Breast Cancer Metastases

    Directory of Open Access Journals (Sweden)

    Shijun Zhu

    2014-01-01

    Full Text Available Breast cancer aberrantly expresses tissue factor (TF in cancer tissues and cancer vascular endothelial cells (VECs. TF plays a central role in cancer angiogenesis, growth, and metastasis and, as such, is a target for therapy and drug delivery. TF is the cognate receptor of factor VIIa (fVIIa. We have coupled PTX (paclitaxel, also named Taxol with a tripeptide, phenylalanine-phenylalanine-arginine chloromethyl ketone (FFRck and conjugated it with fVIIa. The key aim of the work is to evaluate the antiangiogenic effects of PTX-FFRck-fVIIa against a PTX-resistant breast cancer cell line. Matrigel mixed with VEGF and MDA-231 was injected subcutaneously into the flank of athymic nude mice. Animals were treated by tail vein injection of the PTX-FFRck-fVIIa conjugate, unconjugated PTX, or PBS. The PTX-FFRck-fVIIa conjugate significantly reduces microvessel density in matrigel (p<0.01–0.05 compared to PBS and unconjugated PTX. The breast cancer lung metastasis model in athymic nude mice was developed by intravenous injection of MDA-231 cells expressing luciferase. Animals were similarly treated intravenously with the PTX-FFRck-fVIIa conjugate or PBS. The conjugate significantly inhibits lung metastasis as compared to the control, highlighting its potential to antagonize angiogenesis in metastatic carcinoma. In conclusion, PTX conjugated to fVIIa is a promising therapeutic approach for improving selective drug delivery and inhibiting angiogenesis.

  16. Quantitative assessment of selective in-plane shielding of tissues in computed tomography through evaluation of absorbed dose and image quality

    Energy Technology Data Exchange (ETDEWEB)

    Geleijns, J.; Veldkamp, W.J.H. [Leiden University Medical Center, Radiology Department, ZA Leiden (Netherlands); Salvado Artells, M.; Lopez Tortosa, M. [Universitat Rovira i Virgili, Facultat de Medicina i Ciencies de la Salut, Departament de Ciencies Mediques Basiques, Reus, Tarragona (Spain); Calzado Cantera, A. [Universidad Complutense de Madrid, Departamento de Radiologia, Madrid (Spain)

    2006-10-15

    This study aimed at assessment of efficacy of selective in-plane shielding in adults by quantitative evaluation of the achieved dose reduction and image quality. Commercially available accessories for in-plane shielding of the eye lens, thyroid and breast, and an anthropomorphic phantom were used for the evaluation of absorbed dose and image quality. Organ dose and total energy imparted were assessed by means of a Monte Carlo technique taking into account tube voltage, tube current, and scanner type. Image quality was quantified as noise in soft tissue. Application of the lens shield reduced dose to the lens by 27% and to the brain by 1%. The thyroid shield reduced thyroid dose by 26%; the breast shield reduced dose to the breasts by 30% and to the lungs by 15%. Total energy imparted (unshielded/shielded) was 88/86 mJ for computed tomography (CT) brain, 64/60 mJ for CT cervical spine, and 289/260 mJ for CT chest scanning. An increase in image noise could be observed in the ranges were bismuth shielding was applied. The observed reduction of organ dose and total energy imparted could be achieved more efficiently by a reduction of tube current. The application of in-plane selective shielding is therefore discouraged. (orig.)

  17. Automated segmentation of cerebral vasculature with aneurysms in 3DRA and TOF-MRA using geodesic active regions: An evaluation study

    NARCIS (Netherlands)

    H. Bogunović; J.M. Pozo; M.C. Villa-Uriol; C.B.L.M. Majoie; R. van den Berg; H.A.F.G. van Andel; J.M. Macho; J. Blasco; L.S. Román; A.F. Frangi

    2011-01-01

    Purpose: To evaluate the suitability of an improved version of an automatic segmentation method based on geodesic active regions (GAR) for segmenting cerebral vasculature with aneurysms from 3D x-ray reconstruction angiography (3DRA) and time of flight magnetic resonance angiography (TOF-MRA) images

  18. Advanced three-dimensional imaging reveals the arterial vasculature in the head region of the air-breathing swamp eel, Monopterus albus

    DEFF Research Database (Denmark)

    Lauridsen, Henrik; Pedersen, Michael; Huong, Do T

    Air-breathing fish exhibit many anatomical modifications that allow for oxygen uptake directly from air. This is certainly the case for the tropical swamp eels, Synbranchidae, where various structural adaptations of the vasculature within the buccopharyngeal region mediate an amphibious lifestyle...

  19. Application of electrical stimulation for functional tissue engineering in vitro and in vivo

    Science.gov (United States)

    Radisic, Milica (Inventor); Park, Hyoungshin (Inventor); Langer, Robert (Inventor); Freed, Lisa (Inventor); Vunjak-Novakovic, Gordana (Inventor)

    2013-01-01

    The present invention provides new methods for the in vitro preparation of bioartificial tissue equivalents and their enhanced integration after implantation in vivo. These methods include submitting a tissue construct to a biomimetic electrical stimulation during cultivation in vitro to improve its structural and functional properties, and/or in vivo, after implantation of the construct, to enhance its integration with host tissue and increase cell survival and functionality. The inventive methods are particularly useful for the production of bioartificial equivalents and/or the repair and replacement of native tissues that contain electrically excitable cells and are subject to electrical stimulation in vivo, such as, for example, cardiac muscle tissue, striated skeletal muscle tissue, smooth muscle tissue, bone, vasculature, and nerve tissue.

  20. Pulsed ultrasound enhances the delivery of nitric oxide from bubble liposomes to ex vivo porcine carotid tissue

    Directory of Open Access Journals (Sweden)

    Sutton JT

    2014-10-01

    Full Text Available JT Sutton,1 JL Raymond,1 MC Verleye,2 GJ Pyne-Geithman,3 CK Holland4 1University of Cincinnati, Biomedical Engineering Program, Cincinnati, OH, 2University of Notre Dame Department of Chemical Engineering, Notre Dame, IN, 3University of Cincinnati, College of Medicine, Department of Neurosurgery and the University of Cincinnati Neuroscience Institute, and Mayfield Clinic, Cincinnati, OH, 4University of Cincinnati, College of Medicine, Internal Medicine, Division of Cardiovascular Diseases, Cincinnati, OH, USA Abstract: Ultrasound-mediated drug delivery is a novel technique for enhancing the penetration of drugs into diseased tissue beds noninvasively. By encapsulating drugs into microsized and nanosized liposomes, the therapeutic can be shielded from degradation within the vasculature until delivery to a target site by ultrasound exposure. Traditional in vitro or ex vivo techniques to quantify this delivery profile include optical approaches, cell culture, and electrophysiology. Here, we demonstrate an approach to characterize the degree of nitric oxide (NO delivery to porcine carotid tissue by direct measurement of ex vivo vascular tone. An ex vivo perfusion model was adapted to assess ultrasound-mediated delivery of NO. This potent vasodilator was coencapsulated with inert octafluoropropane gas to produce acoustically active bubble liposomes. Porcine carotid arteries were excised post mortem and mounted in a physiologic buffer solution. Vascular tone was assessed in real time by coupling the artery to an isometric force transducer. NO-loaded bubble liposomes were infused into the lumen of the artery, which was exposed to 1 MHz pulsed ultrasound at a peak-to-peak acoustic pressure amplitude of 0.34 MPa. Acoustic cavitation emissions were monitored passively. Changes in vascular tone were measured and compared with control and sham NO bubble liposome exposures. Our results demonstrate that ultrasound-triggered NO release from bubble liposomes

  1. Occurrence of specific environmental risk factors in brain tissues of sudden infant death and sudden intrauterine unexpected death victims assessed with gas chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Termopoli, Veronica; Famiglini, Giorgio; Palma, Pierangela; Magrini, Laura; Cappiello, Achille

    2015-03-01

    Sudden infant death syndrome (SIDS) and sudden intrauterine unexpected death syndrome (SIUDS) are an unresolved teaser in the social-medical and health setting of modern medicine and are the result of multifactorial interactions. Recently, prenatal exposure to environmental contaminants has been associated with negative pregnancy outcomes, and verification of their presence in fetal and newborn tissues is of crucial importance. A gas chromatography-tandem mass spectrometry (MS/MS) method, using a triple quadrupole analyzer, is proposed to assess the presence of 20 organochlorine pesticides, two organophosphate pesticides, one carbamate (boscalid), and a phenol (bisphenol A) in human brain tissues. Samples were collected during autopsies of infants and fetuses that died suddenly without any evident cause. The method involves a liquid-solid extraction using n-hexane as the extraction solvent. The extracts were purified with Florisil cartridges prior to the final determination. Recovery experiments using lamb brain spiked at three different concentrations in the range of 1-50 ng g(-1) were performed, with recoveries ranging from 79 to 106%. Intraday and interday repeatability were evaluated, and relative standard deviations lower than 10% and 18%, respectively, were obtained. The selectivity and sensitivity achieved in multiple reaction monitoring mode allowed us to achieve quantification and confirmation in a real matrix at levels as low as 0.2-0.6 ng g(-1). Two MS/MS transitions were acquired for each analyte, using the Q/q ratio as the confirmatory parameter. This method was applied to the analysis of 14 cerebral cortex samples (ten SIUDS and four SIDS cases), and confirmed the presence of several selected compounds.

  2. Feasibility and limitations of the round robin test for assessment of in vitro chondrogenesis evaluation protocol in a tissue-engineered medical product.

    Science.gov (United States)

    Yokoi, Masako; Hattori, Koji; Narikawa, Koichi; Ohgushi, Hajime; Tadokoro, Mika; Hoshi, Kazuto; Takato, Tsuyoshi; Myoui, Akira; Nanno, Katsuhiko; Kato, Yukio; Kanawa, Masami; Sugawara, Katsura; Kobo, Tomoko; Ushida, Takashi

    2012-07-01

    Tissue-engineered medical products (TEMPs) should be evaluated before implantation. Therefore, it is indispensable to establish evaluation protocols in regenerative medicine. Whether or not such evaluation protocols are reasonable is generally verified through a 'round robin' test. However, the round robin test for TEMPs intrinsically includes a deficiency, because 'identical' specimens can not be prepared for TEMPs. The aim of the study was to assess the feasibility and limitations of the round robin test for TEMPs by using a prepared evaluation protocol. We adopted tissue-engineered cartilage constructs as delivered specimens and a protocol of measuring sGAG content as an evaluation protocol proposed to ISO TC150/SC7, which is an invasive, but usually applied, method, although non-invasive methods are keenly required in evaluating TEMPs. The results showed that: (a) the coefficient of variation (CV) of the measured sGAG contents in intralaboratory tests was ~5% at most; (b) the CV of sGAG content in the scheme where each participating laboratory measured different constructs was comparable with that in the scheme where each participating laboratory measured one half of a construct along with the organizing laboratory; (c) the CV caused by factors other than the specimen was ~15%, comparable to that in reproducible experiments in biomedical fields. Based on these results, the study concludes that a round robin test for a TEMP could be valuable, under the condition that the delivered TEMPs are sufficiently reproducible so that the CV of the measured values is < 5% in the organizing laboratory.

  3. Initial clinical experience with near-infrared spectroscopy in assessing cerebral tissue oxygen saturation in cerebral vasospasm before and after intra-arterial verapamil injection.

    Science.gov (United States)

    Meng, Lingzhong; Settecase, Fabio; Xiao, Jifang; Yu, Zhaoxia; Flexman, Alana M; Higashida, Randall T

    2016-04-01

    Cerebral vasospasm is a devastating complication after subarachnoid hemorrhage. The use of cerebral tissue oxygen saturation (SctO2) to non-invasively assess changes in cerebral tissue perfusion induced by intra-arterial (IA) verapamil treatment has not been described to our knowledge. A total of 21 consecutive post-craniotomy patients scheduled for possible IA verapamil treatment of cerebral vasospasm were recruited. The effect of IA verapamil injection on SctO2 being continuously monitored on both the left and right forehead was investigated. Comparisons between changes in SctO2 monitored on the ipsilateral and contralateral forehead in relationship to the side of internal carotid artery (ICA) injection were performed. A total of 47 IA verapamil injections (15 left ICA, 18 right ICA, and 14 vertebral artery injections) during 18 neurointerventional procedures in 13 patients were analyzed. IA verapamil administration led to both increases and decreases in SctO2. Changes in SctO2 ipsilateral to the ICA injection side were more pronounced (p=0.02 and 0.07 for left and right ICA injections, respectively) and favored compared to contralateral SctO2 changes. We were unable to obtain reliable measurements on the side ipsilateral to the craniotomy during four procedures in three patients, presumably secondary to pneumocephalus. The local cerebral vasodilating effect of IA verapamil injection is suggested by the differential changes in SctO2 ipsilateral and contralateral to the ICA injection side. The inconsistent changes in SctO2 and the limitations of applying cerebral oximetry in this patient population needs to be recognized.

  4. 3D printing of functional biomaterials for tissue engineering.

    Science.gov (United States)

    Zhu, Wei; Ma, Xuanyi; Gou, Maling; Mei, Deqing; Zhang, Kang; Chen, Shaochen

    2016-08-01

    3D printing is emerging as a powerful tool for tissue engineering by enabling 3D cell culture within complex 3D biomimetic architectures. This review discusses the prevailing 3D printing techniques and their most recent applications in building tissue constructs. The work associated with relatively well-known inkjet and extrusion-based bioprinting is presented with the latest advances in the fields. Emphasis is put on introducing two relatively new light-assisted bioprinting techniques, including digital light processing (DLP)-based bioprinting and laser based two photon polymerization (TPP) bioprinting. 3D bioprinting of vasculature network is particularly discussed for its foremost significance in maintaining tissue viability and promoting functional maturation. Limitations to current bioprinting approaches, as well as future directions of bioprinting functional tissues are also discussed.

  5. Risk assessment tool for incontinence-associated dermatitis in elderly patients combining tissue tolerance and perineal environment predictors: a prospective clinical study

    Directory of Open Access Journals (Sweden)

    Ichikawa-Shigeta Y

    2014-10-01

    Full Text Available Yoshie Ichikawa-Shigeta,1 Hiromi Sanada,2 Chizuko Konya,3 Saldy Yusuf,1 Supriadi,1 Junko Sugama11Department of Clinical Nursing, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, Japan; 2Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; 3Department of Adult Nursing, Kanazawa Medical University, Ishikawa, JapanBackground: Elderly patients with incontinence are at risk of developing incontinence-associated dermatitis (IAD. Although perineal risk factors of IAD have been identified, the contribution of tissue tolerance to IAD remains poorly understood.Objective: This study aimed to identify predictors of IAD development in three categories of potential risk factors: perineal environment, tissue tolerance, and toileting ability.Methods: This was a prospective clinical study, conducted at a long-term medical facility in Japan between November 2011 and April 2012. The subjects were elderly female patients with urine and/or fecal incontinence, and constantly wearing absorbent products. The patients were monitored during 42 days for the onset of IAD and the emergence of potential risk factors of IAD related to tissue tolerance (skin hydration status, maceration, erythema index [EI], etc, perineal environment (urination, stool properties, etc, and toileting ability (mobility and cognitive awareness. The risk factors were identified by univariate and multiple logistic regression analysis. Receiver operating characteristic (ROC curve analysis was conducted to evaluate the predictive validity of the risk factors.Results: Among the 46 patients enrolled, IAD developed in 25 (54.3%. The factors significantly associated with IAD development were loose or liquid stools (odds ratio [OR]: 20.612, 95% confidence interval [CI]: 1.118–379.852, P=0.042, malodorous urine (OR: 37.094, 95% CI: 3.480–395.399, P=0.003, and EI ≥46 (OR: 35.191, 95% CI: 5

  6. Assessment of gastrointestinal pH, fluid and lymphoid tissue in the guinea pig, rabbit and pig, and implications for their use in drug development.

    Science.gov (United States)

    Merchant, Hamid A; McConnell, Emma L; Liu, Fang; Ramaswamy, Chandrasekaran; Kulkarni, Rucha P; Basit, Abdul W; Murdan, Sudaxshina

    2011-01-18

    Laboratory animals are often used in drug delivery and research. However, basic information about their gastrointestinal pH, fluid volume, and lymphoid tissue is not completely known. We have investigated these post-mortem in healthy guinea pigs, rabbits and pigs, to assess their suitability for pre-clinical studies by comparing the results with reported human literature. The mean gastric pH (fed ad libitum) was 2.9 and 4.4 in guinea pig and pig, respectively. In contrast, a very low pH (1.6) was recorded in the rabbits. The small intestinal pH was found in the range of 6.4-7.4 in the guinea pigs and rabbits, whereas lower pH (6.1-6.7) was recorded in the pig, which may have consequences for ionisable or pH responsive systems when tested in pig. A relatively lower pH than in the small intestine was found in the caecum (6.0-6.4) and colon (6.1-6.6) of the guinea pig, rabbit and the pig. The water content in the gastrointestinal tract of guinea pig, rabbit and pig was 51g, 153g and 1546g, respectively. When normalized to the body weight, the guinea pig, had larger amounts of water compared to the rabbit and the pig (guinea pig>rabbit>pig); in contrast, a reverse order was found when normalized to per unit length of the gut (guinea pigpig). The lymphoid tissue distribution (lymphoid follicles, Peyer's patches and long strips) along the length of the gut in these animals is presented; in particular, an abundance of lymphoid tissue was found in pig's stomach, small intestine and caecum, and rabbit's appendix. Their ample presence indicated the potential utility of these animal species in oral and colonic vaccination. These differences in the gastrointestinal parameters of the guinea pig, rabbit and pig reiterates the crucial importance of correctly selecting animal models for pre-clinical studies.

  7. Tissue tests

    NARCIS (Netherlands)

    Sonneveld, C.; Voogt, W.

    2009-01-01

    Tissue tests are widely used in horticulture practice and have in comparison with soil or substrate testing advantages as well disadvantages in comparison with soil testing. One of the main advantages of tissue tests is the certainty that analysed nutrients in plant tissues are really present in the

  8. 3D bioprinting of vascularized, heterogeneous cell-laden tissue constructs.

    Science.gov (United States)

    Kolesky, David B; Truby, Ryan L; Gladman, A Sydney; Busbee, Travis A; Homan, Kimberly A; Lewis, Jennifer A

    2014-05-21

    A new bioprinting method is reported for fabricating 3D tissue constructs replete with vasculature, multiple types of cells, and extracellular matrix. These intricate, heterogeneous structures are created by precisely co-printing multiple materials, known as bioinks, in three dimensions. These 3D micro-engineered environments open new -avenues for drug screening and fundamental studies of wound healing, angiogenesis, and stem-cell niches.

  9. A multiplex endpoint RT-PCR assay for quality assessment of RNA extracted from formalin-fixed paraffin-embedded tissues

    Directory of Open Access Journals (Sweden)

    Dobrovic Alexander

    2010-12-01

    Full Text Available Abstract Background RNA extracted from formalin-fixed paraffin-embedded (FFPE samples is chemically modified and degraded, which compromises its use in gene expression studies. Most of the current approaches for RNA quality assessment are not suitable for FFPE derived RNA. Results We have developed a single-tube multiplex endpoint RT-PCR assay specifically designed to evaluate RNA extracted from FFPE tissues for mRNA integrity and performance in reverse transcription - quantitative real-time PCR (RT-qPCR assays. This single-tube quality control (QC assay minimises the amount of RNA used in quality control. mRNA integrity and the suitability of RNA for RT-PCR is evaluated by the multiplex endpoint RT-PCR assay using the TBP gene mRNA as the target sequence. The RT-PCR amplicon sizes, 92, 161, 252 and 300 bp, cover a range of amplicon sizes suitable for a wide range of RT-qPCR assays. The QC assay was used to evaluate RNA prepared by two different protocols for extracting total RNA from needle microdissected FFPE breast tumour samples. The amplification products were analysed by gel electrophoresis where the spectrum of amplicon sizes indicated the level of RNA degradation and thus the suitability of the RNA for PCR. The ability of the multiplex endpoint RT-PCR QC assay to identify FFPE samples with an adequate RNA quality was validated by examining the Cq values of an RT-qPCR assay with an 87 bp amplicon. Conclusions The multiplex endpoint RT-PCR assay is well suited for the determination of the quality of FFPE derived RNAs, to identify which RT-PCR assays they are suitable for, and is also applicable to assess non-FFPE RNA for gene expression studies. Furthermore, the assay can also be used for the evaluation of RNA extraction protocols from FFPE samples.

  10. Use of diffusion tensor imaging to assess the impact of normobaric hyperoxia within at-risk pericontusional tissue after traumatic brain injury.

    Science.gov (United States)

    Veenith, Tonny V; Carter, Eleanor L; Grossac, Julia; Newcombe, Virginia F; Outtrim, Joanne G; Nallapareddy, Sridhar; Lupson, Victoria; Correia, Marta M; Mada, Marius M; Williams, Guy B; Menon, David K; Coles, Jonathan P

    2014-10-01

    Ischemia and metabolic dysfunction remain important causes of neuronal loss after head injury, and we have shown that normobaric hyperoxia may rescue such metabolic compromise. This study examines the impact of hyperoxia within injured brain using diffusion tensor imaging (DTI). Fourteen patients underwent DTI at baseline and after 1 hour of 80% oxygen. Using the apparent diffusion coefficient (ADC) we assessed the impact of hyperoxia within contusions and a 1 cm border zone of normal appearing pericontusion, and within a rim of perilesional reduced ADC consistent with cytotoxic edema and metabolic compromise. Seven healthy volunteers underwent imaging at 21%, 60%, and 100% oxygen. In volunteers there was no ADC change with hyperoxia, and contusion and pericontusion ADC values were higher than volunteers (P<0.01). There was no ADC change after hyperoxia within contusion, but an increase within pericontusion (P<0.05). We identified a rim of perilesional cytotoxic edema in 13 patients, and hyperoxia resulted in an ADC increase towards normal (P=0.02). We demonstrate that hyperoxia may result in benefit within the perilesional rim of cytotoxic edema. Future studies should address whether a longer period of hyperoxia has a favorable impact on the evolution of tissue injury.

  11. Automatic classification of scar tissue in late gadolinium enhancement cardiac MRI for the assessment of left-atrial wall injury after radiofrequency ablation.

    Science.gov (United States)

    Perry, Daniel; Morris, Alan; Burgon, Nathan; McGann, Christopher; Macleod, Robert; Cates, Joshua

    2012-02-23

    Radiofrequency ablation is a promising procedure for treating atrial fibrillation (AF) that relies on accurate lesion delivery in the left atrial (LA) wall for success. Late Gadolinium Enhancement MRI (LGE MRI) at three months post-ablation has proven effective for noninvasive assessment of the location and extent of scar formation, which are important factors for predicting patient outcome and planning of redo ablation procedures. We have developed an algorithm for automatic classification in LGE MRI of scar tissue in the LA wall and have evaluated accuracy and consistency compared to manual scar classifications by expert observers. Our approach clusters voxels based on normalized intensity and was chosen through a systematic comparison of the performance of multivariate clustering on many combinations of image texture. Algorithm performance was determined by overlap with ground truth, using multiple overlap measures, and the accuracy of the estimation of the total amount of scar in the LA. Ground truth was determined using the STAPLE algorithm, which produces a probabilistic estimate of the true scar classification from multiple expert manual segmentations. Evaluation of the ground truth data set was based on both inter- and intra-observer agreement, with variation among expert classifiers indicating the difficulty of scar classification for a given a dataset. Our proposed automatic scar classification algorithm performs well for both scar localization and estimation of scar volume: for ground truth datasets considered easy, variability from the ground truth was low; for those considered difficult, variability from ground truth was on par with the variability across experts.

  12. Overexpression of Colligin 2 in Glioma Vasculature is Associated with Overexpression of Heat Shock Factor 2.

    Science.gov (United States)

    Mustafa, Dana A M; Sieuwerts, Anieta M; Zheng, Ping Pin; Kros, Johan M

    2010-10-20

    In previous studies we found expression of the protein colligin 2 (heat shock protein 47 (HSP47), SERPINH1) in glioma neovasculature while not in normal brain tissue. Generally, the regulation of heat shock gene expression in eukaryotes is mediated by heat shock factors (HSF). In mammals, three heat shock transcription factors, HSF-1, -2, and -4, have been isolated. Here we investigated the relation between the expression of colligin 2 and these heat shock factors at the mRNA level using real-time reverse transcriptase PCR (qRT-PCR) in different grades of astrocytic tumorigenesis, viz., low-grade glioma and glioblastoma. Endometrium samples, representing physiological angiogenesis, were included as controls. Since colligin 2 is a chaperon for collagens, the gene expression of collagen I (COL1A1) was also investigated. The blood vessel density of the samples was monitored by expression of the endothelial marker CD31 (PECAM1). Because NG2-immunopositive pericytic cells are involved in glioma neovascularization, the expression of NG2 (CSPG4) was also measured.We demonstrate overexpression of HSF2 in both stages of glial tumorigenesis (reaching significance only in low-grade glioma) and also minor elevated levels of HSF1 as compared to normal brain. There were no differences in expression of HSF4 between low-grade glioma and normal brain while HSF4 was downregulated in glioblastoma. In the endometrium samples, none of the HSFs were upregulated. In the low-grade gliomas SERPINH appeared to be slightly overexpressed with a parallel 4-fold upregulation of COL1A1, while in glioblastoma there was over 5-fold overexpression of SERPINH1 and more than 150-fold overexpression of COL1A1. In both the lowgrade gliomas and the glioblastomas overexpression of CSPG4 was found and overexpression of PECAM1 was only found in the latter. Our data suggest that the upregulated expression of colligin 2 in glioma is accompanied by upregulation of COL1A1, CSPG4, HSF2 and to a lesser extent

  13. Assessing Tumor Angiogenesis with Dynamic Contrast Enhanced Magnetic Resonance Imaging

    Science.gov (United States)

    Esparza-Coss, Emilio; Jackson, Edward F.

    2006-09-01

    Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is a method able of assessing microvascular changes at high spatial resolution and without ionizing radiation. The microcirculation and structure of tumors are fundamentally chaotic in that tumor-derived factors stimulate the endothelial cells to form new small vessels (angiogenesis) and this vasculature deviates markedly from normal hierarchical branching patterns. The tumor-induced microvascular changes lead to blood flow that is both spatially and temporally more heterogeneous than the efficient and uniform perfusion of normal organs and tissues. DCE-MRI allows for the assessment of perfusion and permeability of the tumor microvasculature, including the network of vessels with diameters less than 100 μm, which are beyond the resolution of conventional angiograms. The microvessel permeability to small molecular weight contrast media as well as measures of tumor response can be assessed with different analysis techniques ranging from simple measures of enhancement to pharmacokinetic models. In this work, such DCE-MRI analysis techniques are discussed.

  14. High-intensity Focused Ultrasound Ablation of Soft-tissue Tumors and Assessment of Treatment Response with Multiparametric Magnetic Resonance Imaging: Preliminary Study Using Rabbit VX2 Tumor Model

    Directory of Open Access Journals (Sweden)

    Kyung Won Kim

    2014-06-01

    Conclusion: Extracorporeal HIFU treatment for soft-tissue tumor may be a feasible approach with adjustment of input energy level. For post-treatment assessment, functional MRI techniques including DCE-MRI and ADC map may be useful and complementary to conventional MRI.

  15. Crawling phagocytes recruited in the brain vasculature after pertussis toxin exposure through IL6, ICAM1 and ITGαM.

    Science.gov (United States)

    Richard, Jean-François; Roy, Monica; Audoy-Rémus, Julie; Tremblay, Pierrot; Vallières, Luc

    2011-11-01

    The cerebral vasculature is constantly patrolled by rod-shaped leukocytes crawling on the luminal endothelial surface. These cells are recruited in greater numbers after exposure to bacterial lipopolysaccharide (LPS) by a mechanism involving tumor necrosis factor (TNF), interleukin-1β (IL1β) and angiopoietin-2 (Angpt2). Here, we report that the population of crawling leukocytes, consisting mainly of granulocytes, is also increased in the brains of mice suffering from experimental autoimmune encephalomyelitis (EAE) or injected with pertussis toxin (PTX), which is commonly used to induce EAE. However, this recruitment occurs through an alternative mechanism, independent of Angpt2. In a series of experiments using DNA microarrays, knockout mice and neutralizing antibodies, we found that PTX acts indirectly on the endothelium in part through IL6, which is essential for the post-transcriptional upregulation of intercellular adhesion molecule 1 (ICAM1) in response to PTX but not to LPS. We also found that phagocytes adhere to brain capillaries through the interaction of integrin αM (ITGαM) with ICAM1 and an unidentified ligand. In conclusion, this study supports the concept that PTX promotes EAE, at least in part, by inducing vascular changes necessary for the recruitment of patrolling leukocytes.

  16. Gold Nanoparticle–Mediated Targeted Delivery of Recombinant Human Endostatin Normalizes Tumour Vasculature and Improves Cancer Therapy

    Science.gov (United States)

    Li, Wei; Zhao, Xiaoxu; Du, Bin; Li, Xin; Liu, Shuhao; Yang, Xiao-Yan; Ding, Hui; Yang, Wende; Pan, Fan; Wu, Xiaobo; Qin, Li; Pan, Yunlong

    2016-01-01

    Tumour vasculature is generally disordered because of the production of excessive angiogenic factors by tumour cells, which results in tumour progression and reduces the effectiveness of radiotherapy or chemotherapy. Transient anti-angiogenic therapies that regulate tumour vascular morphology and function and improve the efficiency of antitumour therapy are under investigation. Recombinant human endostatin (Endostar/rhES) is a vascular angiogenesis–disrupting agent that has been used to treat non-small cell lung cancer (NSCLC) in the clinical setting. In this study, we used gold nanoparticles (AuNPs) as a drug-delivery system (DDS) for targeted tumour delivery of rhES for short therapy, which resulted in transient tumour vascular normalization, reduced permeability and hypoxia, strengthened blood vessel integrity, and increased blood-flow perfusion. Moreover, combination therapy with 5-FU over this timeframe was substantially more effective than 5-FU monotherapy. In conclusion, our research demonstrates the potential use of AuNPs as a drug-delivery platform for transporting rhES into a tumour to induce transient tumour vascular normalization and enhance the antitumour efficacy of cytotoxic drugs. PMID:27470938

  17. Biomimetic proteolipid vesicles for targeting inflamed tissues

    Science.gov (United States)

    Molinaro, R.; Corbo, C.; Martinez, J. O.; Taraballi, F.; Evangelopoulos, M.; Minardi, S.; Yazdi, I. K.; Zhao, P.; De Rosa, E.; Sherman, M. B.; de Vita, A.; Toledano Furman, N. E.; Wang, X.; Parodi, A.; Tasciotti, E.

    2016-09-01

    A multitude of micro- and nanoparticles have been developed to improve the delivery of systemically administered pharmaceuticals, which are subject to a number of biological barriers that limit their optimal biodistribution. Bioinspired drug-delivery carriers formulated by bottom-up or top-down strategies have emerged as an alternative approach to evade the mononuclear phagocytic system and facilitate transport across the endothelial vessel wall. Here, we describe a method that leverages the advantages of bottom-up and top-down strategies to incorporate proteins derived from the leukocyte plasma membrane into lipid nanoparticles. The resulting proteolipid vesicles--which we refer to as leukosomes--retained the versatility and physicochemical properties typical of liposomal formulations, preferentially targeted inflamed vasculature, enabled the selective and effective delivery of dexamethasone to inflamed tissues, and reduced phlogosis in a localized model of inflammation.

  18. Topical anaesthetic effects on skin vasculature with potential implications for laser treatment.

    Science.gov (United States)

    Tollan, Clare Josephine; MacLaren, William; Mackay, Iain R

    2016-05-01

    Laser treatment of vascular lesions is affected by parameters including the diameter and depth of the vessels and flow within the vessels. Topical anaesthetics are in common use prior to laser treatment but may have effects on vessel parameters and, subsequently, the efficacy of laser treatment. Eleven patients with capillary vascular malformations were investigated for vessel diameter before and after elective application of a topical anaesthetic, Eutectic Mixture of Local Anaesthetics (EMLA) (AstraZeneca) or Ametop (S&N Health), prior to pulsed dye laser treatment. EMLA contains 2.5% lidocaine ad 2.5% prilocaine, and Ametop gel contains 4% tetracaine. Patients' capillary malformations were assessed using confocal laser scanning microscopy (CLSM) (Vivascope 1500 Mavig GmbH, Munich). Six of the 11 patients recruited had EMLA topical anaesthetic, and five had Ametop. Four hundred twenty-one diameters were measured. The mean vessel diameter was 50.87 μm. Previous laser treatments undergone by each patient were noted to exclude this as a confounding variable, and no significant difference was found between topical anaesthetic groups. Statistical calculations were made using GenStat and Minitab. There is no evidence that Ametop affects mean diameter (p value is 0.361). EMLA reduces the mean diameter of vessels (p = 0.002), with a 27% reduction in post-EMLA diameter. This study demonstrates that the use of EMLA cream has a statistically significant reduction vessel diameter. As it is known that vessel diameter is important for the response of laser treatment, the use of EMLA may affect outcome.

  19. Synergistic and additive effects of hydrostatic pressure and growth factors on tissue formation.

    Directory of Open Access Journals (Sweden)

    Benjamin D Elder

    Full Text Available BACKGROUND: Hydrostatic pressure (HP is a significant factor in the function of many tissues, including cartilage, knee meniscus, temporomandibular joint disc, intervertebral disc, bone, bladder, and vasculature. Though studies have been performed in assessing the role of HP in tissue biochemistry, to the best of our knowledge, no studies have demonstrated enhanced mechanical properties from HP application in any tissue. METHODOLOGY/PRINCIPAL FINDINGS: The objective of this study was to determine the effects of hydrostatic pressure (HP, with and without growth factors, on the biomechanical and biochemical properties of engineered articular cartilage constructs, using a two-phased approach. In phase I, a 3x3 full-factorial design of HP magnitude (1, 5, 10 MPa and frequency (0, 0.1, 1 Hz was used, and the best two treatments were selected for use in phase II. Static HP at 5 MPa and 10 MPa resulted in significant 95% and 96% increases, respectively, in aggregate modulus (H(A, with corresponding increases in GAG content. These regimens also resulted in significant 101% and 92% increases in Young's modulus (E(Y, with corresponding increases in collagen content. Phase II employed a 3x3 full-factorial design of HP (no HP, 5 MPa static, 10 MPa static and growth factor application (no GF, BMP-2+IGF-I, TGF-beta1. The combination of 10 MPa static HP and TGF-beta1 treatment had an additive effect on both H(A and E(Y, as well as a synergistic effect on collagen content. This group demonstrated a 164% increase in H(A, a 231% increase in E(Y, an 85% increase in GAG/wet weight (WW, and a 173% increase in collagen/WW, relative to control. CONCLUSIONS/SIGNIFICANCE: To our knowledge, this is the first study to demonstrate increases in the biomechanical properties of tissue from pure HP application, using a cartilage model. Furthermore, it is the only study to demonstrate additive or synergistic effects between HP and growth factors on tissue functional properties

  20. Tissue types (image)

    Science.gov (United States)

    There are 4 basic types of tissue: connective tissue, epithelial tissue, muscle tissue, and nervous tissue. Connective tissue ... and binds them together (bone, blood, and lymph tissues). Epithelial tissue provides a covering (skin, the linings of ...

  1. Does the sequence of pulmonary vasculature ligation have any oncological impact during an anatomical lung resection for non-small-cell lung cancer?

    Science.gov (United States)

    Toufektzian, Levon; Attia, Rizwan; Polydorou, Nicolaos; Veres, Lukacs

    2015-02-01

    A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'in patients with primary lung carcinoma, does the sequence of pulmonary vasculature ligation during anatomical lung resection influence the oncological outcomes?' A total of 48 papers were found using the reported search, of which 7 represented the best evidence to answer the question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Among six prospective studies included, five of them randomized patients to either pulmonary vein or artery occlusion first during anatomical lung resection, while one study was retrospective. Two reports did not find any difference between pulmonary vein and artery occlusion first during long-term follow-up in terms of either disease recurrence (51 vs 53%, P = 0.7), or 5-year overall survival (54 vs 50%, P = 0.82). One report did not find any difference with regard to circulating tumour cells either after thoracotomy (5.0 vs 3.9, P = 0.4), or after the completion of lobectomy (38.0 vs 70.0, P = 0.23). One report found a higher expression of CD44v6 (P = 0.008) and CK19 (P = 0.05) in patients undergoing pulmonary arterial occlusion first. One report found that pulmonary vein occlusion before that of the pulmonary arterial branches has a favourable outcome on circulating carcino-embryonic antigen (CEA) mRNA in the peripheral blood, while another one did not find a significant difference in circulating levels of CEA mRNA (P = 0.075) and CK19 mRNA (P = 0.086) with either method. Another study reported no correlation between circulating pin1 mRNA levels in peripheral blood after the completion of the resection and the sequence of ligation of pulmonary vessels (9.95 ± 0.91 vs 14.71 ± 1.64, P > 0.05). Based on the two studies assessing the long-term outcome of patients with primary lung cancer undergoing anatomical curative

  2. Biomimetic injectable HUVEC-adipocytes/collagen/alginate microsphere co-cultures for adipose tissue engineering.

    Science.gov (United States)

    Yao, Rui; Zhang, Renji; Lin, Feng; Luan, Jie

    2013-05-01

    Engineering adipose tissue that has the ability to engraft and establish a vascular supply is a laudable goal that has broad clinical relevance, particularly for tissue reconstruction. In this article, we developed novel microtissues from surface-coated adipocyte/collagen/alginate microspheres and human umbilical vein endothelial cells (HUVECs) co-cultures that resembled the components and structure of natural adipose tissue. Firstly, collagen/alginate hydrogel microspheres embedded with viable adipocytes were obtained to mimic fat lobules. Secondly, collagen fibrils were allowed to self-assemble on the surface of the microspheres to mimic collagen fibrils surrounding the fat lobules in the natural adipose tissue and facilitate HUVEC attachment and co-cultures formation. Thirdly, the channels formed by the gap among the microspheres served as the room for in vitro prevascularization and in vivo blood vessel development. The endothelial cell layer outside the microspheres was a starting point of rapid vascular ingrowth. Adipose tissue formation was analyzed for 12 weeks at 4-week intervals by subcutaneous injection into the head of node mice. The vasculature in the regenerated tissue showed functional anastomosis with host blood vessels. Long-term stability of volume and weight of the injection was observed, indicating that the vasculature formed within the constructs benefited the formation, maturity, and maintenance of adipose tissue. This study provides a microsurgical method for adipose regeneration and construction of biomimetic model for drug screening studies.

  3. Equal modulation of endothelial cell function by four distinct tissue-specific mesenchymal stem cells.

    Science.gov (United States)

    Lin, Ruei-Zeng; Moreno-Luna, Rafael; Zhou, Bin; Pu, William T; Melero-Martin, Juan M

    2012-09-01

    Mesenchymal stem cells (MSCs) can generate multiple end-stage mesenchymal cell types and constitute a promising population of cells for regenerative therapies. Additionally, there is increasing evidence supporting other trophic activities of MSCs, including the ability to enable formation of vasculature in vivo. Although MSCs were originally isolated from the bone marrow, the presence of these cells in the stromal vascular fraction of multiple adult tissues has been recently recognized. However, it is unknown whether the capacity to modulate vasculogenesis is ubiquitous to all MSCs regardless of their tissue of origin. Here, we demonstrated that tissue-resident MSCs isolated from four distinct tissues have equal capacity to modulate endothelial cell function, including formation of vascular networks in vivo. MSCs were isolated from four murine tissues, including bone marrow, white adipose tissue, skeletal muscle, and myocardium. In culture, all four MSC populations secreted a plethora of pro-angiogenic factors that unequivocally induced proliferation, migration, and tube formation of endothelial colony-forming cells (ECFCs). In vivo, co-implantation of MSCs with ECFCs into mice generated an extensive network of blood vessels with ECFCs specifically lining the lumens and MSCs occupying perivascular positions. Importantly, there were no differences among all four MSCs evaluated. Our studies suggest that the capacity to modulate the formation of vasculature is a ubiquitous property of all MSCs, irrespective of their original anatomical location. These results validate multiple tissues as potential sources of MSCs for future cell-based vascular therapies.

  4. Combined multi-modal photoacoustic tomography, optical coherence tomography (OCT) and OCT angiography system with an articulated probe for in vivo human skin structure and vasculature imaging

    Science.gov (United States)

    Liu, Mengyang; Chen, Zhe; Zabihian, Behrooz; Sinz, Christoph; Zhang, Edward; Beard, Paul C.; Ginner, Laurin; Hoover, Erich; Minneman, Micheal P.; Leitgeb, Rainer A.; Kittler, Harald; Drexler, Wolfgang

    2016-01-01

    Cutaneous blood flow accounts for approximately 5% of cardiac output in human and plays a key role in a number of a physiological and pathological processes. We show for the first time a multi-modal photoacoustic tomography (PAT), optical coherence tomography (OCT) and OCT angiography system with an articulated probe to extract human cutaneous vasculature in vivo in various skin regions. OCT angiography supplements the microvasculature which PAT alone is unable to provide. Co-registered volumes for vessel network is further embedded in the morphologic image provided by OCT. This multi-modal system is therefore demonstrated as a valuable tool for comprehensive non-invasive human skin vasculature and morphology imaging in vivo. PMID:27699106

  5. Assessment of left ventricular segmental function after autologous bone marrow stem cells transplantation in patients with acute myocardial infarction by tissue tracking and strain imaging

    Institute of Scientific and Technical Information of China (English)

    RUAN Wen; PAN Cui-zhen; HUANG Guo-qian; LI Yan-lin; GE Jun-bo; SHU Xian-hong

    2005-01-01

    Background Emerging evidence suggests that stem cells can be used to improve cardiac function in patients after acute myocardial infarction. In this randomized trial, we aimed to use Doppler tissue tracking and strain imaging to assess left ventricular segmental function after intracoronary transfer of autologous bone-marrow stem cells (BMCs) for 6 months' follow up. Methods Twenty patients with acute myocardial infarction and anterior descending coronary artery occlusion proven by angiography were double-blindedly randomized into intracoronary injection of bone-marrow cell (treated, n=9) or diluted serum (control, n=11) groups. GE vivid 7 and Q-analyze software were used to perform echocardiogram in both groups 1 week, 3 months and 6 months after treatment. Three apical views of tissue Doppler imaging were acquired to measure peak systolic displacement (Ds) and peak systolic strain (εpeak) from 12 segments of LV walls. Left ventricular ejection fraction (LVEF), end-diastolic volume (EDV) and end-systolic volume (ESV) were obtained by Simposon's biplane method. Results (1) 3 months later, Ds and εpeak over the infract-related region clearly increased in the BMCs group [Ds: (4.49±2.71) mm vs (7.56±2.95) mm, P0.05; εpeak : (-13.84±6.05)% vs (-15.04±6.75)%, P>0.05]. At the same time, Ds over the normal region also increased, but the Ds enhancement was markedly higher in the BMCs group than that in the control group [(3.21±3.17) mm vs (0.76±1.94) mm, P0.05). (2) LVEF in treated and control groups were almost the same at baseline (1st week after PCI) [(53.37±8.92)% vs (53.51±5.84)%, P>0.05]. But 6 months later, LVEF in the BMCs group were clearly higher than that in the control group [(59.33±12.91)% vs (50.30±8.30)%, P0.05; ESV: (57.12±18.66) ml vs (62.09±17.68) ml, P>0.05]. Three months later, EDV and ESV in the control group were markedly greater than those in the BMCs group [EDV: (154.89±46.34) ml vs (104.85±33.21) ml, P0.05). Conclusions Emergency

  6. Data on biodistribution and radiation absorbed dose profile of a novel 64Cu-labeled high affinity cell-specific peptide for positron emission tomography imaging of tumor vasculature

    Directory of Open Access Journals (Sweden)

    Joseph R. Merrill

    2016-06-01

    Full Text Available New peptide-based diagnostic and therapeutic approaches hold promise for highly selective targeting of cancer leading to more precise and effective diagnostic and therapeutic modalities. An important feature of these approaches is to reach the tumor tissue while limiting or minimizing the dose to normal organs. In this context, efforts to design and engineer materials with optimal in vivo targeting and clearance properties are important. This Data In Brief article reports on biodistribution and radiation absorbed dose profile of a novel high affinity radiopeptide specific for bone marrow-derived tumor vasculature. Background information on the design, preparation, and in vivo characterization of this peptide-based targeted radiodiagnostic is described in the article “Synthesis and comparative evaluation of novel 64Cu-labeled high affinity cell-specific peptides for positron emission tomography of tumor vasculature” (Merrill et al., 2016 [1]. Here we report biodistribution measurements in mice and calculate the radiation absorbed doses to normal organs using a modified Medical Internal Radiation Dosimetry (MIRD methodology that accounts for physical and geometric factors and cross-organ beta doses.

  7. Assessment

    Institute of Scientific and Technical Information of China (English)

    Geoff Brindley

    2005-01-01

    @@ Introduction TERMINOLOGY AND KEY CONCEPTS The term assessment refers to a variety of ways of collecting information on a learner's language ability or achievement. Although testing and assessment are often used interchangeably, the latter is an umbrella term encompassing measurement instruments administered on a ‘one-off’ basis such as tests, as well as qualitative methods of monitoring and recording student learning such as observation, simulations of project work. Assessment is also distinguished from evaluation which is concerned with the overall language programme and not just with what individual students have learnt. Proficiency assessment refers to the assessment of general language abilities acquired by the learner independent of a course of study.This kind of assessment is often done through the administration of standardised commercial language-proficency tests. On the other hand, assessment of achievement aims to establish what a student had learned in relation to a particular course or curriculum (thus frequently carried out by the teacher) .Achievement assesssment may be based either on the specific content of the course or on the course objectives (Hughes 1989).

  8. Cardiac functions assessment in children with celiac disease and its correlation with the degree of mucosal injury: Doppler tissue imaging study

    Directory of Open Access Journals (Sweden)

    Abeer Fathy

    2016-01-01

    Full Text Available Background/Aims: Celiac disease (CD-associated cardiologic disorders is a growing concern. However, data regarding cardiac affection in children with CD are few. This study aimed at assessing the subclinical impact of CD on the global myocardial performance in Saudi children with CD using Doppler tissue imaging (DTI. Patients and Methods: Conventional two-dimensional echocardiography was performed among 20 Saudi children with CDas well as 20 age and sex-matched healthy controls. DTI were used to determine right ventricular (RV and left ventricular (LV Tei indexes. These findings were correlated with the Modified Marsh Classification of the histologic findings in CD. Results: LV and RV Tei indexes were significantly higher in children with CD than the control group (mean ± standard deviation: 0.47 ± 0.05 vs. 0.31 ± 0.18; P< 0.0005 and 0.51 ± 0.04 vs. 0.32 ± 0.05; P< 0.0001, respectively. RV Tei index was found to be positively correlated with the Modified Marsh Classification of CD (r = 0.7753, P< 0.0001. LV Tei index tended to be more affected in patients with more severe histologic findings, however, such relation did not reach statistical significance (r = 0.2479, P = 0.292. Fractional shortening did not correlate with the Modified Marsh Classification of histologic findings in CD patients (r= −0.11, P = 0.641. Conclusions: Subclinical myocardial dysfunction of both ventricles occurs in children with CD. The DTI method appears to be more sensitive than conventional two-dimensional echocardiography in the early detection of myocardial dysfunction in children with CD.

  9. Application of microtechnologies for the vascularization of engineered tissues

    Directory of Open Access Journals (Sweden)

    Gauvin Robert

    2011-10-01

    Full Text Available Abstract Recent advances in medicine and healthcare allow people to live longer, increasing the need for the number of organ transplants. However, the number of organ donors has not been able to meet the demand, resulting in an organ shortage. The field of tissue engineering has emerged to produce organs to overcome this limitation. While tissue engineering of connective tissues such as skin and blood vessels have currently reached clinical studies, more complex organs are still far away from commercial availability due to pending challenges with in vitro engineering of 3D tissues. One of the major limitations of engineering large tissue structures is cell death resulting from the inability of nutrients to diffuse across large distances inside a scaffold. This task, carried out by the vasculature inside the body, has largely been described as one of the foremost important challenges in engineering 3D tissues since it remains one of the key steps for both in vitro production of tissue engineered construct and the in vivo integration of a transplanted tissue. This short review highlights the important challenges for vascularization and control of the microcirculatory system within engineered tissues, with particular emphasis on the use of microfabrication approaches.

  10. Decreased brain venous vasculature visibility on susceptibility-weighted imaging venography in patients with multiple sclerosis is related to chronic cerebrospinal venous insufficiency

    Directory of Open Access Journals (Sweden)

    Hojnacki David

    2011-10-01

    Full Text Available Abstract Background The potential pathogenesis between the presence and severity of chronic cerebrospinal venous insufficiency (CCSVI and its relation to clinical and imaging outcomes in brain parenchyma of multiple sclerosis (MS patients has not yet been elucidated. The aim of the study was to investigate the relationship between CCSVI, and altered brain parenchyma venous vasculature visibility (VVV on susceptibility-weighted imaging (SWI in patients with MS and in sex- and age-matched healthy controls (HC. Methods 59 MS patients, 41 relapsing-remitting and 18 secondary-progressive, and 33 HC were imaged on a 3T GE scanner using pre- and post-contrast SWI venography. The presence and severity of CCSVI was determined using extra-cranial and trans-cranial Doppler criteria. Apparent total venous volume (ATVV, venous intracranial fraction (VIF and average distance-from-vein (DFV were calculated for various vein mean diameter categories: .9 mm. Results CCSVI criteria were fulfilled in 79.7% of MS patients and 18.2% of HC (p Conclusions MS patients with higher number of venous stenoses, indicative of CCSVI severity, showed significantly decreased venous vasculature in the brain parenchyma. The pathogenesis of these findings has to be further investigated, but they suggest that reduced metabolism and morphological changes of venous vasculature may be taking place in patients with MS.

  11. Fine processes of Nestin-GFP-positive radial glia-like stem cells in the adult dentate gyrus ensheathe local synapses and vasculature.

    Science.gov (United States)

    Moss, Jonathan; Gebara, Elias; Bushong, Eric A; Sánchez-Pascual, Irene; O'Laoi, Ruadhan; El M'Ghari, Imane; Kocher-Braissant, Jacqueline; Ellisman, Mark H; Toni, Nicolas

    2016-05-03

    Adult hippocampal neurogenesis relies on the activation of neural stem cells in the dentate gyrus, their division, and differentiation of their progeny into mature granule neurons. The complex morphology of radial glia-like (RGL) stem cells suggests that these cells establish numerous contacts with the cellular components of the neurogenic niche that may play a crucial role in the regulation of RGL stem cell activity. However, the morphology of RGL stem cells remains poorly described. Here, we used light microscopy and electron microscopy to examine Nestin-GFP transgenic mice and provide a detailed ultrastructural reconstruction analysis of Nestin-GFP-positive RGL cells of the dentate gyrus. We show that their primary processes follow a tortuous path from the subgranular zone through the granule cell layer and ensheathe local synapses and vasculature in the inner molecular layer. They share the ensheathing of synapses and vasculature with astrocytic processes and adhere to the adjacent processes of astrocytes. This extensive interaction of processes with their local environment could allow them to be uniquely receptive to signals from local neurons, glia, and vasculature, which may regulate their fate.

  12. Tissue Distribution of Polychlorinated Biphenyls and Organochlorine Pesticides and Potential Toxicity to Alaskan Northern Fur Seals Assessed Using PCBs Congener Specific Mode of Action Schemes

    Science.gov (United States)

    The concentrations of 145 polychlorinated biphenyl (PCB) congeners were measured using gas chromatography-ion trap mass spectrometry in 8 different tissues (blubber, brain, heart, kidney, liver, lung, muscle, and reproductive tissues) of 10 Alaskan northern fur seals. The mean concentrations of bot...

  13. Tissue Classification

    DEFF Research Database (Denmark)

    Van Leemput, Koen; Puonti, Oula

    2015-01-01

    Computational methods for automatically segmenting magnetic resonance images of the brain have seen tremendous advances in recent years. So-called tissue classification techniques, aimed at extracting the three main brain tissue classes (white matter, gray matter, and cerebrospinal fluid), are now...... well established. In their simplest form, these methods classify voxels independently based on their intensity alone, although much more sophisticated models are typically used in practice. This article aims to give an overview of often-used computational techniques for brain tissue classification...

  14. Quantitative sodium MRI of the human brain at 9.4 T provides assessment of tissue sodium concentration and cell volume fraction during normal aging.

    Science.gov (United States)

    Thulborn, Keith; Lui, Elaine; Guntin, Jonathan; Jamil, Saad; Sun, Ziqi; Claiborne, Theodore C; Atkinson, Ian C

    2016-02-01

    Sodium ion homeostasis is a fundamental property of viable tissue, allowing the tissue sodium concentration to be modeled as the tissue cell volume fraction. The modern neuropathology literature using ex vivo tissue from selected brain regions indicates that human brain cell density remains constant during normal aging and attributes the volume loss that occurs with advancing age to changes in neuronal size and dendritic arborization. Quantitative sodium MRI performed with the enhanced sensitivity of ultrahigh-field 9.4 T has been used to investigate tissue cell volume fraction during normal aging. This cross-sectional study (n = 49; 21-80 years) finds that the in vivo tissue cell volume fraction remains constant in all regions of the brain with advancing age in individuals who remain cognitively normal, extending the ex vivo literature reporting constant neuronal cell density across the normal adult age range. Cell volume fraction, as measured by quantitative sodium MRI, is decreased in diseases of cell loss, such as stroke, on a time scale of minutes to hours, and in response to treatment of brain tumors on a time scale of days to weeks. Neurodegenerative diseases often have prodromal periods of decades in which regional neuronal cell loss occurs prior to clinical presentation. If tissue cell volume fraction can detect such early pathology, this quantitative parameter may permit the objective measurement of preclinical disease progression. This current study in cognitively normal aging individuals provides the basis for the pursuance of investigations directed towards such neurodegenerative diseases.

  15. Real-time and label free determination of ligand binding-kinetics to primary cancer tissue specimens; a novel tool for the assessment of biomarker targeting

    DEFF Research Database (Denmark)

    Clausen, Thomas Mandel; Pereira, Marina Ayres; Oo, Htoo Zarni;

    2016-01-01

    crystal microbalance (QCM) enabled biosensor technology. We analysed the interaction between the rVAR2 protein and its placental-like chondroitin sulfate (pl-CS) receptor in primary human placenta tissue and in breast and prostate tumour specimens in situ. rVAR2 interacted with FFPE human placenta...... and cancer tissue with an affinity in the nanomolar range, and showed no detectable interaction with pl-CS negative normal tissue. We further validated the method by including analysis with the androgen receptor N-20 antibody (anti-AR). As the KD value produced by this method is independent of the number...

  16. Tissue engineered periodontal products.

    Science.gov (United States)

    Bartold, P M; Gronthos, S; Ivanovski, S; Fisher, A; Hutmacher, D W

    2016-02-01

    Attainment of periodontal regeneration is a significant clinical goal in the management of advanced periodontal defects arising from periodontitis. Over the past 30 years numerous techniques and materials have been introduced and evaluated clinically and have included guided tissue regeneration, bone grafting materials, growth and other biological factors and gene therapy. With the exception of gene therapy, all have undergone evaluation in humans. All of the products have shown efficacy in promoting periodontal regeneration in animal models but the results in humans remain variable and equivocal concerning attaining complete biological regeneration of damaged periodontal structures. In the early 2000s, the concept of tissue engineering was proposed as a new paradigm for periodontal regeneration based on molecular and cell biology. At this time, tissue engineering was a new and emerging field. Now, 14 years later we revisit the concept of tissue engineering for the periodontium and assess how far we have come, where we are currently situated and what needs to be done in the future to make this concept a reality. In this review, we cover some of the precursor products, which led to our current position in periodontal tissue engineering. The basic concepts of tissue engineering with special emphasis on periodontal tissue engineering products is discussed including the use of mesenchymal stem cells in bioscaffolds and the emerging field of cell sheet technology. Finally, we look into the future to consider what CAD/CAM technology and nanotechnology will have to offer.

  17. Cardiac adipose tissue and its relationship to diabetes mellitus and cardiovascular disease

    Institute of Scientific and Technical Information of China (English)

    Adam; M; Noyes; Kirandeep; Dua; Ramprakash; Devadoss; Lovely; Chhabra

    2014-01-01

    Type-2 diabetes mellitus(T2DM) plays a central role in the development of cardiovascular disease(CVD). However, its relationship to epicardial adipose tissue(EAT) and pericardial adipose tissue(PAT) in particular is important in the pathophysiology of coronary artery disease. Owing to its close proximity to the heart and coronary vasculature, EAT exerts a direct metabolic impact by secreting proinflammatory adipokines and free fatty acids, which promote CVD locally. In this review, we have discussed the relationship between T2 DM and cardiac fat deposits, particularly EAT and PAT, which together exert a big impact on the cardiovascular health.

  18. Targeting Breast Cancer Vasculature

    Science.gov (United States)

    2006-03-01

    that are expressed by various types of EC. A global analysis of gene expression patterns makes it possible to simultaneously identify and classify large...corrected by subtracting the immediate surrounding background. The corrected intensities were normalized for each cDNA by global normalization per ImaGene...NG2 €xpression is limited to pedcytes, endothelial c€lls do not € xpress detectabl€ lev€ls of NGz The ECM of biood vessels con:ists of a sub-endothelial

  19. Three-dimensional bioprinting in tissue engineering and regenerative medicine.

    Science.gov (United States)

    Gao, Guifang; Cui, Xiaofeng

    2016-02-01

    With the advances of stem cell research, development of intelligent biomaterials and three-dimensional biofabrication strategies, highly mimicked tissue or organs can be engineered. Among all the biofabrication approaches, bioprinting based on inkjet printing technology has the promises to deliver and create biomimicked tissue with high throughput, digital control, and the capacity of single cell manipulation. Therefore, this enabling technology has great potential in regenerative medicine and translational applications. The most current advances in organ and tissue bioprinting based on the thermal inkjet printing technology are described in this review, including vasculature, muscle, cartilage, and bone. In addition, the benign side effect of bioprinting to the printed mammalian cells can be utilized for gene or drug delivery, which can be achieved conveniently during precise cell placement for tissue construction. With layer-by-layer assembly, three-dimensional tissues with complex structures can be printed using converted medical images. Therefore, bioprinting based on thermal inkjet is so far the most optimal solution to engineer vascular system to the thick and complex tissues. Collectively, bioprinting has great potential and broad applications in tissue engineering and regenerative medicine. The future advances of bioprinting include the integration of different printing mechanisms to engineer biphasic or triphasic tissues with optimized scaffolds and further understanding of stem cell biology.

  20. Effects of chronic severe pulmonary regurgitation and percutaneous valve repair on right ventricular geometry and contractility ass