Perfusion MRI (dynamic susceptibility contrast imaging) with different measurement approaches for the evaluation of blood flow and blood volume in human gliomas

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Thomsen, H. (Den Sundhedsfaglige Kandidatuddannelse, Aarhus Universitet Bygning 1264, Aarhus (Denmark); University College Nordjylland, Aalborg (Denmark)), Email: hnt@ucn.dk; Steffensen, E. (Aalborg Hospital/Aarhus University Hospital, Department of Radiology, Aalborg (Denmark)); Larsson, E. M. (Aalborg Hospital/Aarhus University Hospital, Department of Radiology, Aalborg (Denmark); Uppsala University Hospital, Department of Radiology, Uppsala (Sweden))

2012-02-15

Background. Perfusion magnetic resonance imaging (MRI) is increasingly used in the evaluation of brain tumors. Relative cerebral blood volume (rCBV) is usually obtained by dynamic susceptibility contrast (DSC) MRI using normal appearing white matter as reference region. The emerging perfusion technique arterial spin labelling (ASL) presently provides measurement only of cerebral blood flow (CBF), which has not been widely used in human brain tumor studies. Purpose. To assess if measurement of blood flow is comparable with measurement of blood volume in human biopsy-proven gliomas obtained by DSC-MRI using two different regions for normalization and two different measurement approaches. Material and Methods. Retrospective study of 61 patients with different types of gliomas examined with DSC perfusion MRI. Regions of interest (ROIs) were placed in tumor portions with maximum perfusion on rCBF and rCBV maps, with contralateral normal appearing white matter and cerebellum as reference regions. Larger ROIs were drawn for histogram analyses. The type and grade of the gliomas were obtained by histopathology. Statistical comparison was made between diffuse astrocytomas, anaplastic astrocytomas, and glioblastomas. Results. rCBF and rCBV measurements obtained with the maximum perfusion method were correlated when normalized to white matter (r = 0.60) and to the cerebellum (r = 0.49). Histogram analyses of rCBF and rCBV showed that mean and median values as well as skewness and peak position were correlated (0.61 < r < 0.93), whereas for kurtosis and peak height, the correlation coefficient was about 0.3 when comparing rCBF and rCBV values for the same reference region. Neither rCBF nor rCBV quantification provided a statistically significant difference between the three types of gliomas. However, both rCBF and rCBV tended to increase with tumor grade and to be lower in patients who had undergone resection/treatment. Conclusion. rCBF measurements normalized to white matter

Distinct bone marrow blood vessels differentially regulate haematopoiesis.

Science.gov (United States)

Itkin, Tomer; Gur-Cohen, Shiri; Spencer, Joel A; Schajnovitz, Amir; Ramasamy, Saravana K; Kusumbe, Anjali P; Ledergor, Guy; Jung, Yookyung; Milo, Idan; Poulos, Michael G; Kalinkovich, Alexander; Ludin, Aya; Kollet, Orit; Shakhar, Guy; Butler, Jason M; Rafii, Shahin; Adams, Ralf H; Scadden, David T; Lin, Charles P; Lapidot, Tsvee

2016-04-21

Bone marrow endothelial cells (BMECs) form a network of blood vessels that regulate both leukocyte trafficking and haematopoietic stem and progenitor cell (HSPC) maintenance. However, it is not clear how BMECs balance these dual roles, and whether these events occur at the same vascular site. We found that mammalian bone marrow stem cell maintenance and leukocyte trafficking are regulated by distinct blood vessel types with different permeability properties. Less permeable arterial blood vessels maintain haematopoietic stem cells in a low reactive oxygen species (ROS) state, whereas the more permeable sinusoids promote HSPC activation and are the exclusive site for immature and mature leukocyte trafficking to and from the bone marrow. A functional consequence of high permeability of blood vessels is that exposure to blood plasma increases bone marrow HSPC ROS levels, augmenting their migration and differentiation, while compromising their long-term repopulation and survival. These findings may have relevance for clinical haematopoietic stem cell transplantation and mobilization protocols.

Automatic segmentation of blood vessels from retinal fundus images ...

Indian Academy of Sciences (India)

The retinal blood vessels were segmented through color space conversion and color channel .... Retinal blood vessel segmentation was also attempted through multi-scale operators. A few works in this ... fundus camera at 35 degrees field of view. The image ... vessel segmentation is available from two human observers.

Principles of the complex therapy of gliomas in Latvia (1993-1998)

International Nuclear Information System (INIS)

Apskalne, D.; Ozolins, J.; Krumina, R.; Razuks, R.; Dzelzitis, J.

1998-01-01

60-70 malignant gliomas of 3rd and 4th degree of anaplasia are diagnosed in Latvia every year. The basic method of treatment of malignant gliomas is their surgical evacuation using CUSA, coagulation loops, binocular operation loupes and in several stages of surgery - microscope. Detailed morphological analysis of operation material according to 7 qualitative and 1 quantitative (Ki-67 antibody detection) signs. This analysis determines in general the choice of further method of complex therapy. Most often in the cases of malignant gliomas complex fractionated radiotherapy (55-60 Gy per course, 2 Gy per procedure) and systemic chemotherapy were used. In the cases when radiotherapy is not possible because of various side reasons and PI of gliomas is less than 5% and the structure is rich in blood vessels, only chemotherapy is used. Main agent are ACNU and CeeNU. Chemotherapy is carried in 2-3 stages, 6-courses in every stage. Interval between the courses - 6 weeks, between the stages - 6 month. When the schedule is accomplished CT and MR are done. At the present time 71% of the patients after complex therapy are in the phase of remission and in 29% of cases recurrent gliomas were diagnosed. (Full text)

Recovery of testicular blood flow following ligation of testicular vessels

International Nuclear Information System (INIS)

Pascual, J.A.; Villanueva-Meyer, J.; Salido, E.; Ehrlich, R.M.; Mena, I.; Rajfer, J.

1989-01-01

To determine whether initial ligation of the testicular vessels of the high undescended testis followed by a delayed secondary orchiopexy is a viable alternative to the classical Fowler-Stephens procedure, a series of preliminary experiments were conducted in the rat in which testicular blood flow was measured by the 133-xenon washout technique before, and 1 hour and 30 days after ligation of the vessels. In addition, testicular histology, and testis and sex-accessory tissue weights were measured in 6 control, 6 sham operated and 6 testicular vessel ligated rats 54 days after vessel ligation. The data demonstrate that ligation and division of the testicular blood vessels produce an 80 per cent decrease in testicular blood flow 1 hour after ligation of the vessels. However, 30 days later testis blood flow returns to the control and pre-treatment value. There were no significant changes in testis or sex-accessory tissue weights 54 days after vessel ligation. Histologically, 4 of the surgically operated testes demonstrated necrosis of less than 25 per cent of the seminiferous tubules while 1 testis demonstrated more than 75 per cent necrosis. The rest of the tubules in all 6 testes demonstrated normal spermatogenesis. From this study we conclude that initial testicular vessel ligation produces an immediate decrease in testicular blood flow but with time the collateral vessels are able to compensate and return the testis blood flow to its normal pre-treatment value. These preliminary observations lend support for the concept that initial ligation of the testicular vessels followed by a delayed secondary orchiopexy in patients with a high undescended testis may be a possible alternative to the classical Fowler-Stephens approach

Application of morphological bit planes in retinal blood vessel extraction.

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Fraz, M M; Basit, A; Barman, S A

2013-04-01

The appearance of the retinal blood vessels is an important diagnostic indicator of various clinical disorders of the eye and the body. Retinal blood vessels have been shown to provide evidence in terms of change in diameter, branching angles, or tortuosity, as a result of ophthalmic disease. This paper reports the development for an automated method for segmentation of blood vessels in retinal images. A unique combination of methods for retinal blood vessel skeleton detection and multidirectional morphological bit plane slicing is presented to extract the blood vessels from the color retinal images. The skeleton of main vessels is extracted by the application of directional differential operators and then evaluation of combination of derivative signs and average derivative values. Mathematical morphology has been materialized as a proficient technique for quantifying the retinal vasculature in ocular fundus images. A multidirectional top-hat operator with rotating structuring elements is used to emphasize the vessels in a particular direction, and information is extracted using bit plane slicing. An iterative region growing method is applied to integrate the main skeleton and the images resulting from bit plane slicing of vessel direction-dependent morphological filters. The approach is tested on two publicly available databases DRIVE and STARE. Average accuracy achieved by the proposed method is 0.9423 for both the databases with significant values of sensitivity and specificity also; the algorithm outperforms the second human observer in terms of precision of segmented vessel tree.

Fluid and mass transport in a single lymphatic blood vessel

International Nuclear Information System (INIS)

Bestman, A.R.

1987-08-01

The problem considers the single blood vessel model in pulmonary circulation in the presence of gravitation and mass transfer. The tissue surrounding the blood vessel is modelled as a permeable medium distinct from the blood vessel which is a normal free space. On the assumption that the mass concentration varies slowly at the interface between the blood vessel and the tissue, the problem is tackled by asymptotic approximation. A crucial point of the analysis is the dependence of the flow variables on the permeability K of the tissue in a completely arbitrary manner. A primary conjecture of the study is the intimacy of the pathological pulmonary edema and the parameter K. (author). 4 refs

Margination of Stiffened Red Blood Cells Regulated By Vessel Geometry.

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Chen, Yuanyuan; Li, Donghai; Li, Yongjian; Wan, Jiandi; Li, Jiang; Chen, Haosheng

2017-11-10

Margination of stiffened red blood cells has been implicated in many vascular diseases. Here, we report the margination of stiffened RBCs in vivo, and reveal the crucial role of the vessel geometry in the margination by calculations when the blood is seen as viscoelastic fluid. The vessel-geometry-regulated margination is then confirmed by in vitro experiments in microfluidic devices, and it establishes new insights to cell sorting technology and artificial blood vessel fabrication.

Immersive volume rendering of blood vessels

Science.gov (United States)

Long, Gregory; Kim, Han Suk; Marsden, Alison; Bazilevs, Yuri; Schulze, Jürgen P.

2012-03-01

In this paper, we present a novel method of visualizing flow in blood vessels. Our approach reads unstructured tetrahedral data, resamples it, and uses slice based 3D texture volume rendering. Due to the sparse structure of blood vessels, we utilize an octree to efficiently store the resampled data by discarding empty regions of the volume. We use animation to convey time series data, wireframe surface to give structure, and utilize the StarCAVE, a 3D virtual reality environment, to add a fully immersive element to the visualization. Our tool has great value in interdisciplinary work, helping scientists collaborate with clinicians, by improving the understanding of blood flow simulations. Full immersion in the flow field allows for a more intuitive understanding of the flow phenomena, and can be a great help to medical experts for treatment planning.

Interstitial Cells of Blood Vessels

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Vladimír Pucovský

2010-01-01

Full Text Available Blood vessels are made up of several distinct cell types. Although it was originally thought that the tunica media of blood vessels was composed of a homogeneous population of fully differentiated smooth muscle cells, more recent data suggest the existence of multiple smooth muscle cell subpopulations in the vascular wall. One of the cell types contributing to this heterogeneity is the novel, irregularly shaped, noncontractile cell with thin processes, termed interstitial cell, found in the tunica media of both veins and arteries. While the principal role of interstitial cells in veins seems to be pacemaking, the role of arterial interstitial cells is less clear. This review summarises the knowledge of the functional and structural properties of vascular interstitial cells accumulated so far, offers hypotheses on their physiological role, and proposes directions for future research.

Depiction of blood vessels by x-ray phase contrast

Energy Technology Data Exchange (ETDEWEB)

Momose, Atsushi [School of Engineering, University of Tokyo, Tokyo (Japan); Takeda, Tohoru; Itai, Yuji [Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki (Japan)

2001-04-01

Blood vessels in livers of a mouse and a rat were depicted by phase-contrast x-ray imaging with an x-ray interferometer without using contrast agents. X-ray interference patterns were converted to image mapping x-ray phase shift caused by the livers using the technique of phase-shifting x-ray interferometry. The arteries and veins to and from the livers were tied before excision in order to prevent blood from flowing out of the liver. The x-ray phase shift caused by blood was substantially different from that caused by other soft sues, and consequently trees of blood vessels were revealed in the images. Vessels of diameter smaller than 0.1 mm were detected. This result suggests new possibilities for investigating vascular systems. (author)

Transmigration of neural stem cells across the blood brain barrier induced by glioma cells.

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Mónica Díaz-Coránguez

Full Text Available Transit of human neural stem cells, ReNcell CX, through the blood brain barrier (BBB was evaluated in an in vitro model of BBB and in nude mice. The BBB model was based on rat brain microvascular endothelial cells (RBMECs cultured on Millicell inserts bathed from the basolateral side with conditioned media (CM from astrocytes or glioma C6 cells. Glioma C6 CM induced a significant transendothelial migration of ReNcells CX in comparison to astrocyte CM. The presence in glioma C6 CM of high amounts of HGF, VEGF, zonulin and PGE2, together with the low abundance of EGF, promoted ReNcells CX transmigration. In contrast cytokines IFN-α, TNF-α, IL-12p70, IL-1β, IL-6, IL-8 and IL-10, as well as metalloproteinases -2 and -9 were present in equal amounts in glioma C6 and astrocyte CMs. ReNcells expressed the tight junction proteins occludin and claudins 1, 3 and 4, and the cell adhesion molecule CRTAM, while RBMECs expressed occludin, claudins 1 and 5 and CRTAM. Competing CRTAM mediated adhesion with soluble CRTAM, inhibited ReNcells CX transmigration, and at the sites of transmigration, the expression of occludin and claudin-5 diminished in RBMECs. In nude mice we found that ReNcells CX injected into systemic circulation passed the BBB and reached intracranial gliomas, which overexpressed HGF, VEGF and zonulin/prehaptoglobin 2.

Transmigration of neural stem cells across the blood brain barrier induced by glioma cells.

Science.gov (United States)

Díaz-Coránguez, Mónica; Segovia, José; López-Ornelas, Adolfo; Puerta-Guardo, Henry; Ludert, Juan; Chávez, Bibiana; Meraz-Cruz, Noemi; González-Mariscal, Lorenza

2013-01-01

Transit of human neural stem cells, ReNcell CX, through the blood brain barrier (BBB) was evaluated in an in vitro model of BBB and in nude mice. The BBB model was based on rat brain microvascular endothelial cells (RBMECs) cultured on Millicell inserts bathed from the basolateral side with conditioned media (CM) from astrocytes or glioma C6 cells. Glioma C6 CM induced a significant transendothelial migration of ReNcells CX in comparison to astrocyte CM. The presence in glioma C6 CM of high amounts of HGF, VEGF, zonulin and PGE2, together with the low abundance of EGF, promoted ReNcells CX transmigration. In contrast cytokines IFN-α, TNF-α, IL-12p70, IL-1β, IL-6, IL-8 and IL-10, as well as metalloproteinases -2 and -9 were present in equal amounts in glioma C6 and astrocyte CMs. ReNcells expressed the tight junction proteins occludin and claudins 1, 3 and 4, and the cell adhesion molecule CRTAM, while RBMECs expressed occludin, claudins 1 and 5 and CRTAM. Competing CRTAM mediated adhesion with soluble CRTAM, inhibited ReNcells CX transmigration, and at the sites of transmigration, the expression of occludin and claudin-5 diminished in RBMECs. In nude mice we found that ReNcells CX injected into systemic circulation passed the BBB and reached intracranial gliomas, which overexpressed HGF, VEGF and zonulin/prehaptoglobin 2.

Induction of selective blood-tumor barrier permeability and macromolecular transport by a biostable kinin B1 receptor agonist in a glioma rat model.

Science.gov (United States)

Côté, Jérôme; Bovenzi, Veronica; Savard, Martin; Dubuc, Céléna; Fortier, Audrey; Neugebauer, Witold; Tremblay, Luc; Müller-Esterl, Werner; Tsanaclis, Ana-Maria; Lepage, Martin; Fortin, David; Gobeil, Fernand

2012-01-01

Treatment of malignant glioma with chemotherapy is limited mostly because of delivery impediment related to the blood-brain tumor barrier (BTB). B1 receptors (B1R), inducible prototypical G-protein coupled receptors (GPCR) can regulate permeability of vessels including possibly that of brain tumors. Here, we determine the extent of BTB permeability induced by the natural and synthetic peptide B1R agonists, LysdesArg(9)BK (LDBK) and SarLys[dPhe(8)]desArg(9)BK (NG29), in syngeneic F98 glioma-implanted Fischer rats. Ten days after tumor inoculation, we detected the presence of B1R on tumor cells and associated vasculature. NG29 infusion increased brain distribution volume and uptake profiles of paramagnetic probes (Magnevist and Gadomer) at tumoral sites (T(1)-weighted imaging). These effects were blocked by B1R antagonist and non-selective cyclooxygenase inhibitors, but not by B2R antagonist and non-selective nitric oxide synthase inhibitors. Consistent with MRI data, systemic co-administration of NG29 improved brain tumor delivery of Carboplatin chemotherapy (ICP-Mass spectrometry). We also detected elevated B1R expression in clinical samples of high-grade glioma. Our results documented a novel GPCR-signaling mechanism for promoting transient BTB disruption, involving activation of B1R and ensuing production of COX metabolites. They also underlined the potential value of synthetic biostable B1R agonists as selective BTB modulators for local delivery of different sized-therapeutics at (peri)tumoral sites.

Application of optical coherence tomography for in vivo monitoring of the meningeal lymphatic vessels during opening of blood-brain barrier: mechanisms of brain clearing

Science.gov (United States)

Semyachkina-Glushkovskaya, Oxana; Abdurashitov, Arkady; Dubrovsky, Alexander; Bragin, Denis; Bragina, Olga; Shushunova, Nataliya; Maslyakova, Galina; Navolokin, Nikita; Bucharskaya, Alla; Tuchin, Valery; Kurths, Juergen; Shirokov, Alexander

2017-12-01

The meningeal lymphatic vessels were discovered 2 years ago as the drainage system involved in the mechanisms underlying the clearance of waste products from the brain. The blood-brain barrier (BBB) is a gatekeeper that strongly controls the movement of different molecules from the blood into the brain. We know the scenarios during the opening of the BBB, but there is extremely limited information on how the brain clears the substances that cross the BBB. Here, using the model of sound-induced opening of the BBB, we clearly show how the brain clears dextran after it crosses the BBB via the meningeal lymphatic vessels. We first demonstrate successful application of optical coherence tomography (OCT) for imaging of the lymphatic vessels in the meninges after opening of the BBB, which might be a new useful strategy for noninvasive analysis of lymphatic drainage in daily clinical practice. Also, we give information about the depth and size of the meningeal lymphatic vessels in mice. These new fundamental data with the applied focus on the OCT shed light on the mechanisms of brain clearance and the role of lymphatic drainage in these processes that could serve as an informative platform for a development of therapy and diagnostics of diseases associated with injuries of the BBB such as stroke, brain trauma, glioma, depression, or Alzheimer disease.

“Data characterizing microfabricated human blood vessels created via hydrodynamic focusing”

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Kyle A. DiVito

2017-10-01

Full Text Available This data article provides further detailed information related to our research article titled “Microfabricated Blood Vessels Undergo Neovascularization” (DiVito et al., 2017 [1], in which we report fabrication of human blood vessels using hydrodynamic focusing (HDF. Hydrodynamic focusing with advection inducing chevrons were used in concert to encase one fluid stream within another, shaping the inner core fluid into ‘bullseye-like” cross-sections that were preserved through click photochemistry producing streams of cellularized hollow 3-dimensional assemblies, such as human blood vessels (Daniele et al., 2015a, 2015b, 2014, 2016; Roberts et al., 2016 [2–6]. Applications for fabricated blood vessels span general tissue engineering to organ-on-chip technologies, with specific utility in in vitro drug delivery and pharmacodynamics studies. Here, we report data regarding the construction of blood vessels including cellular composition and cell positioning within the engineered vascular construct as well as functional aspects of the tissues.

Expression of Zonulin, c-kit, and Glial Fibrillary Acidic Protein in Human Gliomas.

Science.gov (United States)

Skardelly, Marco; Armbruster, Franz Paul; Meixensberger, Jürgen; Hilbig, Heidegard

2009-08-18

The hallmarks of human malignant gliomas are their marked invasiveness and vascularity. Because angiogenesis and tumor invasion have been associated with extracellular matrix degradation and intercellular tight junctions, the involvement of zonulin in glioma biology is in the focus. We selected for histological examination five cases of glioblastoma WHO IV (nomenclature of the World Health Organization) and one case each from astrocytoma WHO III, meningioma WHO III, and meningioma WHO I as control samples. The meningioma WHO I is regarded as benign, whereas the meningioma WHO III is recognized as the transition form of malignant tumors in humans. The visualization of a newly designed antibody against human zonulin was studied in triple-labeling studies using fluorescence immunocytochemistry and compared with the expression of c-kit and glial fibrillary acidic protein in differently developed human gliomas. We found that increasing the expression of c-kit is accompanied by an increase of zonulin expression. Both are correlated to the degree of malignancy of human brain tumors. The expression of zonulin is correlated to the degradation of the blood-brain barrier as revealed by Griffonia simplicifolia lectin. In differently graded tumors, we found differently graded involvement of blood vessels in the tumor development, explaining patients' survival.

Acrolein generation stimulates hypercontraction in isolated human blood vessels

International Nuclear Information System (INIS)

Conklin, D.J.; Bhatnagar, A.; Cowley, H.R.; Johnson, G.H.; Wiechmann, R.J.; Sayre, L.M.; Trent, M.B.; Boor, P.J.

2006-01-01

Increased risk of vasospasm, a spontaneous hyperconstriction, is associated with atherosclerosis, cigarette smoking, and hypertension-all conditions involving oxidative stress, lipid peroxidation, and inflammation. To test the role of the lipid peroxidation- and inflammation-derived aldehyde, acrolein, in human vasospasm, we developed an ex vivo model using human coronary artery bypass graft (CABG) blood vessels and a demonstrated acrolein precursor, allylamine. Allylamine induces hypercontraction in isolated rat coronary artery in a semicarbazide-sensitive amine oxidase activity (SSAO) dependent manner. Isolated human CABG blood vessels (internal mammary artery, radial artery, saphenous vein) were used to determine: (1) vessel responses and sensitivity to acrolein, allylamine, and H 2 O 2 exposure (1 μM-1 mM), (2) SSAO dependence of allylamine-induced effects using SSAO inhibitors (semicarbazide, 1 mM; MDL 72274-E, active isomer; MDL 72274-Z, inactive isomer; 100 μM), (3) the vasoactive effects of two other SSAO amine substrates, benzylamine and methylamine, and (4) the contribution of extracellular Ca 2+ to hypercontraction. Acrolein or allylamine but not H 2 O 2 , benzylamine, or methylamine stimulated spontaneous and pharmacologically intractable hypercontraction in CABG blood vessels that was similar to clinical vasospasm. Allylamine-induced hypercontraction and blood vessel SSAO activity were abolished by pretreatment with semicarbazide or MDL 72274-E but not by MDL 72274-Z. Allylamine-induced hypercontraction also was significantly attenuated in Ca 2+ -free buffer. In isolated aorta of spontaneously hypertensive rat, allylamine-induced an SSAO-dependent contraction and enhanced norepinephrine sensitivity but not in Sprague-Dawley rat aorta. We conclude that acrolein generation in the blood vessel wall increases human susceptibility to vasospasm, an event that is enhanced in hypertension

Angiogenesis in gliomas.

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Elzbieta Czykier

2008-02-01

Full Text Available Brain gliomas are characterized by invasive growth and neovascularisation potential. Angiogenesis plays a major role in the progression of gliomas and its determination has a great prognostic value. The aim of the study was to assess the vascularisation of chosen brain gliomas and to estimate how it is correlated with tumour histological type, malignancy grade, location and size, and with age and sex of patients. Tumour vascularisation analysis was based on the determination of microvascular proliferation (MVP and microvessel density (MVD. Microvascular proliferation was measured with immunohistochemical methods using mouse monoclonal antibodies to detect cell proliferation antigens. The following antibodies were used Ki-67 and PCNA (DAKO. Identification of vessels was performed by CD31 antibody and anti-human von Willebrand factor (DAKO. The highest microvascular proliferation and microvascular density were observed in multiform glioblastomas and the lowest in oligodendrogliomas. Significant correlation was observed between the vascularisation and malignancy grade.

Cord blood stem cell-mediated induction of apoptosis in glioma downregulates X-linked inhibitor of apoptosis protein (XIAP.

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Venkata Ramesh Dasari

2010-07-01

Full Text Available XIAP (X-linked inhibitor of apoptosis protein is one of the most important members of the apoptosis inhibitor family. XIAP is upregulated in various malignancies, including human glioblastoma. It promotes invasion, metastasis, growth and survival of malignant cells. We hypothesized that downregulation of XIAP by human umbilical cord blood mesenchymal stem cells (hUCBSC in glioma cells would cause them to undergo apoptotic death.We observed the effect of hUCBSC on two malignant glioma cell lines (SNB19 and U251 and two glioma xenograft cell lines (4910 and 5310. In co-cultures of glioma cells with hUCBSC, proliferation of glioma cells was significantly inhibited. This is associated with increased cytotoxicity of glioma cells, which led to glioma cell death. Stem cells induced apoptosis in glioma cells, which was evaluated by TUNEL assay, FACS analyses and immunoblotting. The induction of apoptosis is associated with inhibition of XIAP in co-cultures of hUCBSC. Similar results were obtained by the treatment of glioma cells with shRNA to downregulate XIAP (siXIAP. Downregulation of XIAP resulted in activation of caspase-3 and caspase-9 to trigger apoptosis in glioma cells. Apoptosis is characterized by the loss of mitochondrial membrane potential and upregulation of mitochondrial apoptotic proteins Bax and Bad. Cell death of glioma cells was marked by downregulation of Akt and phospho-Akt molecules. We observed similar results under in vivo conditions in U251- and 5310-injected nude mice brains, which were treated with hUCBSC. Under in vivo conditions, Smac/DIABLO was found to be colocalized in the nucleus, showing that hUCBSC induced apoptosis is mediated by inhibition of XIAP and activation of Smac/DIABLO.Our results indicate that downregulation of XIAP by hUCBSC treatment induces apoptosis, which led to the death of the glioma cells and xenograft cells. This study demonstrates the therapeutic potential of XIAP and hUCBSC to treat malignant

Captopril improves tumor nanomedicine delivery by increasing tumor blood perfusion and enlarging endothelial gaps in tumor blood vessels.

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Zhang, Bo; Jiang, Ting; Tuo, Yanyan; Jin, Kai; Luo, Zimiao; Shi, Wei; Mei, Heng; Hu, Yu; Pang, Zhiqing; Jiang, Xinguo

2017-12-01

Poor tumor perfusion and unfavorable vessel permeability compromise nanomedicine drug delivery to tumors. Captopril dilates blood vessels, reducing blood pressure clinically and bradykinin, as the downstream signaling moiety of captopril, is capable of dilating blood vessels and effectively increasing vessel permeability. The hypothesis behind this study was that captopril can dilate tumor blood vessels, improving tumor perfusion and simultaneously enlarge the endothelial gaps of tumor vessels, therefore enhancing nanomedicine drug delivery for tumor therapy. Using the U87 tumor xenograft with abundant blood vessels as the tumor model, tumor perfusion experiments were carried out using laser Doppler imaging and lectin-labeling experiments. A single treatment of captopril at a dose of 100 mg/kg significantly increased the percentage of functional vessels in tumor tissues and improved tumor blood perfusion. Scanning electron microscopy of tumor vessels also indicated that the endothelial gaps of tumor vessels were enlarged after captopril treatment. Immunofluorescence-staining of tumor slices demonstrated that captopril significantly increased bradykinin expression, possibly explaining tumor perfusion improvements and endothelial gap enlargement. Additionally, imaging in vivo, imaging ex vivo and nanoparticle distribution in tumor slices indicated that after a single treatment with captopril, the accumulation of 115-nm nanoparticles in tumors had increased 2.81-fold with a more homogeneous distribution pattern in comparison to non-captopril treated controls. Finally, pharmacodynamics experiments demonstrated that captopril combined with paclitaxel-loaded nanoparticles resulted in the greatest tumor shrinkage and the most extensive necrosis in tumor tissues among all treatment groups. Taken together, the data from the present study suggest a novel strategy for improving tumor perfusion and enlarging blood vessel permeability simultaneously in order to improve

Blood Vessels in Allotransplantation.

Science.gov (United States)

Abrahimi, P; Liu, R; Pober, J S

2015-07-01

Human vascularized allografts are perfused through blood vessels composed of cells (endothelium, pericytes, and smooth muscle cells) that remain largely of graft origin and are thus subject to host alloimmune responses. Graft vessels must be healthy to maintain homeostatic functions including control of perfusion, maintenance of permselectivity, prevention of thrombosis, and participation in immune surveillance. Vascular cell injury can cause dysfunction that interferes with these processes. Graft vascular cells can be activated by mediators of innate and adaptive immunity to participate in graft inflammation contributing to both ischemia/reperfusion injury and allograft rejection. Different forms of rejection may affect graft vessels in different ways, ranging from thrombosis and neutrophilic inflammation in hyperacute rejection, to endothelialitis/intimal arteritis and fibrinoid necrosis in acute cell-mediated or antibody-mediated rejection, respectively, and to diffuse luminal stenosis in chronic rejection. While some current therapies targeting the host immune system do affect graft vascular cells, direct targeting of the graft vasculature may create new opportunities for preventing allograft injury and loss. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Predictive simulation of bidirectional Glenn shunt using a hybrid blood vessel model.

Science.gov (United States)

Li, Hao; Leow, Wee Kheng; Chiu, Ing-Sh

2009-01-01

This paper proposes a method for performing predictive simulation of cardiac surgery. It applies a hybrid approach to model the deformation of blood vessels. The hybrid blood vessel model consists of a reference Cosserat rod and a surface mesh. The reference Cosserat rod models the blood vessel's global bending, stretching, twisting and shearing in a physically correct manner, and the surface mesh models the surface details of the blood vessel. In this way, the deformation of blood vessels can be computed efficiently and accurately. Our predictive simulation system can produce complex surgical results given a small amount of user inputs. It allows the surgeon to easily explore various surgical options and evaluate them. Tests of the system using bidirectional Glenn shunt (BDG) as an application example show that the results produc by the system are similar to real surgical results.

Three-dimensional imaging of absolute blood flow velocity and blood vessel position under low blood flow velocity based on Doppler signal information included in scattered light from red blood cells

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Kyoden, Tomoaki; Akiguchi, Shunsuke; Tajiri, Tomoki; Andoh, Tsugunobu; Hachiga, Tadashi

2017-11-01

The development of a system for in vivo visualization of occluded distal blood vessels for diabetic patients is the main target of our research. We herein describe two-beam multipoint laser Doppler velocimetry (MLDV), which measures the instantaneous multipoint flow velocity and can be used to observe the blood flow velocity in peripheral blood vessels. By including a motorized stage to shift the measurement points horizontally and in the depth direction while measuring the velocity, the path of the blood vessel in the skin could be observed using blood flow velocity in three-dimensional space. The relationship of the signal power density between the blood vessel and the surrounding tissues was shown and helped us identify the position of the blood vessel. Two-beam MLDV can be used to simultaneously determine the absolute blood flow velocity distribution and identify the blood vessel position in skin.

Gene expression analysis in human breast cancer associated blood vessels.

Directory of Open Access Journals (Sweden)

Dylan T Jones

Full Text Available Angiogenesis is essential for solid tumour growth, whilst the molecular profiles of tumour blood vessels have been reported to be different between cancer types. Although presently available anti-angiogenic strategies are providing some promise for the treatment of some cancers it is perhaps not surprisingly that, none of the anti-angiogenic agents available work on all tumours. Thus, the discovery of novel anti-angiogenic targets, relevant to individual cancer types, is required. Using Affymetrix microarray analysis of laser-captured, CD31-positive blood vessels we have identified 63 genes that are upregulated significantly (5-72 fold in angiogenic blood vessels associated with human invasive ductal carcinoma (IDC of the breast as compared with blood vessels in normal human breast. We tested the angiogenic capacity of a subset of these genes. Genes were selected based on either their known cellular functions, their enriched expression in endothelial cells and/or their sensitivity to anti-VEGF treatment; all features implicating their involvement in angiogenesis. For example, RRM2, a ribonucleotide reductase involved in DNA synthesis, was upregulated 32-fold in IDC-associated blood vessels; ATF1, a nuclear activating transcription factor involved in cellular growth and survival was upregulated 23-fold in IDC-associated blood vessels and HEX-B, a hexosaminidase involved in the breakdown of GM2 gangliosides, was upregulated 8-fold in IDC-associated blood vessels. Furthermore, in silico analysis confirmed that AFT1 and HEX-B also were enriched in endothelial cells when compared with non-endothelial cells. None of these genes have been reported previously to be involved in neovascularisation. However, our data establish that siRNA depletion of Rrm2, Atf1 or Hex-B had significant anti-angiogenic effects in VEGF-stimulated ex vivo mouse aortic ring assays. Overall, our results provide proof-of-principle that our approach can identify a cohort of

Laparoscopic prototype for optical sealing of renal blood vessels

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Hardy, Luke A.; Hutchens, Thomas C.; Larson, Eric R.; Gonzalez, David A.; Chang, Chun-Hung; Nau, William H.; Fried, Nathaniel M.

2017-02-01

Energy-based, radiofrequency and ultrasonic devices provide rapid sealing of blood vessels during laparoscopic procedures. We are exploring infrared lasers as an alternative for vessel sealing with less collateral thermal damage. Previous studies demonstrated vessel sealing in an in vivo porcine model using a 1470-nm laser. However, the initial prototype was designed for open surgery and featured tissue clasping and light delivery mechanisms incompatible with laparoscopic surgery. In this study, a laparoscopic prototype similar to devices in surgical use was developed, and tests were conducted on porcine renal blood vessels. The 5-mm-OD prototype featured a traditional Maryland jaw configuration. Laser energy was delivered through a 550-μm-core fiber and side-delivery from the lower jaw, with beam dimensions of 18-mm-length x 1.2-mm-width. The 1470-nm diode laser delivered 68 W with 3 s activation time. A total of 69 porcine renal vessels with mean diameter of 3.3 +/- 1.7 mm were tested, ex vivo. Vessels smaller than 5 mm were consistently sealed (48/51) with burst pressures greater than malignant hypertension blood pressure (180 mmHg), averaging 1038 +/- 474 mmHg. Vessels larger than 5 mm were not consistently sealed (6/18), yielding burst pressures of only 174 +/- 221 mmHg. Seal width, thermal damage zone, and thermal spread averaged 1.7 +/- 0.8, 3.4 +/- 0.7, and 1.0 +/- 0.4 mm. A novel optical laparoscopic prototype with 5-mm- OD shaft integrated within a standard Maryland jaw design consistently sealed vessels less than 5 mm with minimal thermal spread. Further in vivo studies are planned to test performance across a variety of vessels and tissues.

Vessel Sampling and Blood Flow Velocity Distribution With Vessel Diameter for Characterizing the Human Bulbar Conjunctival Microvasculature.

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Wang, Liang; Yuan, Jin; Jiang, Hong; Yan, Wentao; Cintrón-Colón, Hector R; Perez, Victor L; DeBuc, Delia C; Feuer, William J; Wang, Jianhua

2016-03-01

This study determined (1) how many vessels (i.e., the vessel sampling) are needed to reliably characterize the bulbar conjunctival microvasculature and (2) if characteristic information can be obtained from the distribution histogram of the blood flow velocity and vessel diameter. Functional slitlamp biomicroscope was used to image hundreds of venules per subject. The bulbar conjunctiva in five healthy human subjects was imaged on six different locations in the temporal bulbar conjunctiva. The histograms of the diameter and velocity were plotted to examine whether the distribution was normal. Standard errors were calculated from the standard deviation and vessel sample size. The ratio of the standard error of the mean over the population mean was used to determine the sample size cutoff. The velocity was plotted as a function of the vessel diameter to display the distribution of the diameter and velocity. The results showed that the sampling size was approximately 15 vessels, which generated a standard error equivalent to 15% of the population mean from the total vessel population. The distributions of the diameter and velocity were not only unimodal, but also somewhat positively skewed and not normal. The blood flow velocity was related to the vessel diameter (r=0.23, Psampling size of the vessels and the distribution histogram of the blood flow velocity and vessel diameter, which may lead to a better understanding of the human microvascular system of the bulbar conjunctiva.

Heritability of retinal vessel diameters and blood pressure

DEFF Research Database (Denmark)

Taarnhøj, Nina C B B; Larsen, Michael; Sander, Birgit

2006-01-01

PURPOSE: To assess the relative influence of genetic and environmental effects on retinal vessel diameters and blood pressure in healthy adults, as well as the possible genetic connection between these two characteristics. METHODS: In 55 monozygotic and 50 dizygotic same-sex healthy twin pairs......%-80%) for CRAE, 83% (95% CI: 73%-89%) for CRVE, and 61% (95% CI: 44%-73%) for mean arterial blood pressure (MABP). Retinal artery diameter decreased with increasing age and increasing arterial blood pressure. Mean vessel diameters in the population were 165.8 +/- 14.9 microm for CRAE, 246.2 +/- 17.7 microm...... for CRVE, and 0.67 +/- 0.05 microm for AVR. No significant influence on artery or vein diameters was found for gender, smoking, body mass index (BMI), total cholesterol, fasting blood glucose, or 2-hour oral glucose tolerance test values. CONCLUSIONS: In healthy young adults with normal blood pressure...

Induction of selective blood-tumor barrier permeability and macromolecular transport by a biostable kinin B1 receptor agonist in a glioma rat model.

Directory of Open Access Journals (Sweden)

Jérôme Côté

Full Text Available Treatment of malignant glioma with chemotherapy is limited mostly because of delivery impediment related to the blood-brain tumor barrier (BTB. B1 receptors (B1R, inducible prototypical G-protein coupled receptors (GPCR can regulate permeability of vessels including possibly that of brain tumors. Here, we determine the extent of BTB permeability induced by the natural and synthetic peptide B1R agonists, LysdesArg(9BK (LDBK and SarLys[dPhe(8]desArg(9BK (NG29, in syngeneic F98 glioma-implanted Fischer rats. Ten days after tumor inoculation, we detected the presence of B1R on tumor cells and associated vasculature. NG29 infusion increased brain distribution volume and uptake profiles of paramagnetic probes (Magnevist and Gadomer at tumoral sites (T(1-weighted imaging. These effects were blocked by B1R antagonist and non-selective cyclooxygenase inhibitors, but not by B2R antagonist and non-selective nitric oxide synthase inhibitors. Consistent with MRI data, systemic co-administration of NG29 improved brain tumor delivery of Carboplatin chemotherapy (ICP-Mass spectrometry. We also detected elevated B1R expression in clinical samples of high-grade glioma. Our results documented a novel GPCR-signaling mechanism for promoting transient BTB disruption, involving activation of B1R and ensuing production of COX metabolites. They also underlined the potential value of synthetic biostable B1R agonists as selective BTB modulators for local delivery of different sized-therapeutics at (peritumoral sites.

Improvement of retinal blood vessel detection by spur removal and Gaussian matched filtering compensation

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Xiao, Di; Vignarajan, Janardhan; An, Dong; Tay-Kearney, Mei-Ling; Kanagasingam, Yogi

2016-03-01

Retinal photography is a non-invasive and well-accepted clinical diagnosis of ocular diseases. Qualitative and quantitative assessment of retinal images is crucial in ocular diseases related clinical application. In this paper, we proposed approaches for improving the quality of blood vessel detection based on our initial blood vessel detection methods. A blood vessel spur pruning method has been developed for removing the blood vessel spurs both on vessel medial lines and binary vessel masks, which are caused by artifacts and side-effect of Gaussian matched vessel enhancement. A Gaussian matched filtering compensation method has been developed for removing incorrect vessel branches in the areas of low illumination. The proposed approaches were applied and tested on the color fundus images from one publicly available database and our diabetic retinopathy screening dataset. A preliminary result has demonstrated the robustness and good performance of the proposed approaches and their potential application for improving retinal blood vessel detection.

Gliomas: Application of Cumulative Histogram Analysis of Normalized Cerebral Blood Volume on 3 T MRI to Tumor Grading

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Kim, Hyungjin; Choi, Seung Hong; Kim, Ji-Hoon; Ryoo, Inseon; Kim, Soo Chin; Yeom, Jeong A.; Shin, Hwaseon; Jung, Seung Chai; Lee, A. Leum; Yun, Tae Jin; Park, Chul-Kee; Sohn, Chul-Ho; Park, Sung-Hye

2013-01-01

Background Glioma grading assumes significant importance in that low- and high-grade gliomas display different prognoses and are treated with dissimilar therapeutic strategies. The objective of our study was to retrospectively assess the usefulness of a cumulative normalized cerebral blood volume (nCBV) histogram for glioma grading based on 3 T MRI. Methods From February 2010 to April 2012, 63 patients with astrocytic tumors underwent 3 T MRI with dynamic susceptibility contrast perfusion-weighted imaging. Regions of interest containing the entire tumor volume were drawn on every section of the co-registered relative CBV (rCBV) maps and T2-weighted images. The percentile values from the cumulative nCBV histograms and the other histogram parameters were correlated with tumor grades. Cochran’s Q test and the McNemar test were used to compare the diagnostic accuracies of the histogram parameters after the receiver operating characteristic curve analysis. Using the parameter offering the highest diagnostic accuracy, a validation process was performed with an independent test set of nine patients. Results The 99th percentile of the cumulative nCBV histogram (nCBV C99), mean and peak height differed significantly between low- and high-grade gliomas (P = histogram analysis of nCBV using 3 T MRI can be a useful method for preoperative glioma grading. The nCBV C99 value is helpful in distinguishing high- from low-grade gliomas and grade IV from III gliomas. PMID:23704910

HIFU procedures at moderate intensities-effect of large blood vessels

International Nuclear Information System (INIS)

Hariharan, P; Myers, M R; Banerjee, R K

2007-01-01

A three-dimensional computational model is presented for studying the efficacy of high-intensity focused ultrasound (HIFU) procedures targeted near large blood vessels. The analysis applies to procedures performed at intensities below the threshold for cavitation, boiling and highly nonlinear propagation, but high enough to increase tissue temperature a few degrees per second. The model is based upon the linearized KZK equation and the bioheat equation in tissue. In the blood vessel the momentum and energy equations are satisfied. The model is first validated in a tissue phantom, to verify the absence of bubble formation and nonlinear effects. Temperature rise and lesion-volume calculations are then shown for different beam locations and orientations relative to a large vessel. Both single and multiple ablations are considered. Results show that when the vessel is located within about a beam width (few mm) of the ultrasound beam, significant reduction in lesion volume is observed due to blood flow. However, for gaps larger than a beam width, blood flow has no major effect on the lesion formation. Under the clinically representative conditions considered, the lesion volume is reduced about 40% (relative to the no-flow case) when the beam is parallel to the blood vessel, compared to about 20% for a perpendicular orientation. Procedures involving multiple ablation sites are affected less by blood flow than single ablations. The model also suggests that optimally focused transducers can generate lesions that are significantly larger (>2 times) than the ones produced by highly focused beams

HIFU procedures at moderate intensities-effect of large blood vessels

Energy Technology Data Exchange (ETDEWEB)

Hariharan, P [Mechanical, Industrial, and Nuclear Engineering Department, University of Cincinnati, Cincinnati, OH (United States); Myers, M R [Division of Solid and Fluid Mechanics, Center for Devices and Radiological Health, US Food and Drug Administration, 10903 New Hampshire Avenue, Building 62, Silver Spring, MD 20993-0002 (United States); Banerjee, R K [Mechanical, Industrial, and Nuclear Engineering Department, University of Cincinnati, Cincinnati, OH (United States)

2007-07-21

A three-dimensional computational model is presented for studying the efficacy of high-intensity focused ultrasound (HIFU) procedures targeted near large blood vessels. The analysis applies to procedures performed at intensities below the threshold for cavitation, boiling and highly nonlinear propagation, but high enough to increase tissue temperature a few degrees per second. The model is based upon the linearized KZK equation and the bioheat equation in tissue. In the blood vessel the momentum and energy equations are satisfied. The model is first validated in a tissue phantom, to verify the absence of bubble formation and nonlinear effects. Temperature rise and lesion-volume calculations are then shown for different beam locations and orientations relative to a large vessel. Both single and multiple ablations are considered. Results show that when the vessel is located within about a beam width (few mm) of the ultrasound beam, significant reduction in lesion volume is observed due to blood flow. However, for gaps larger than a beam width, blood flow has no major effect on the lesion formation. Under the clinically representative conditions considered, the lesion volume is reduced about 40% (relative to the no-flow case) when the beam is parallel to the blood vessel, compared to about 20% for a perpendicular orientation. Procedures involving multiple ablation sites are affected less by blood flow than single ablations. The model also suggests that optimally focused transducers can generate lesions that are significantly larger (>2 times) than the ones produced by highly focused beams.

THE ALGORITHM OF DETERMINATION OF EYE FUNDUS VESSELS BLOOD FLOW CHARACTERISTICS ON VIDEOSEQUENCE

Directory of Open Access Journals (Sweden)

O. V. Nedzvedz

2018-01-01

Full Text Available The method of determination of the dynamic characteristics like the vessel diameter change, the linear and volume blood velocities in the vessels of the eye fundus is considered. Such characteristics allow to determine blood flow changes in the microvasculature affecting the blood flow in the brain, kidneys and coronary vessels. Developed algorithm includes four stages: the video sequence stabilization, the vessels segmentation with the help of a neural network, the determination of the instantaneous velocity in the vessels based on the optical flow and the analysis of the results.

New algorithm for detecting smaller retinal blood vessels in fundus images

Science.gov (United States)

LeAnder, Robert; Bidari, Praveen I.; Mohammed, Tauseef A.; Das, Moumita; Umbaugh, Scott E.

2010-03-01

About 4.1 million Americans suffer from diabetic retinopathy. To help automatically diagnose various stages of the disease, a new blood-vessel-segmentation algorithm based on spatial high-pass filtering was developed to automatically segment blood vessels, including the smaller ones, with low noise. Methods: Image database: Forty, 584 x 565-pixel images were collected from the DRIVE image database. Preprocessing: Green-band extraction was used to obtain better contrast, which facilitated better visualization of retinal blood vessels. A spatial highpass filter of mask-size 11 was applied. A histogram stretch was performed to enhance contrast. A median filter was applied to mitigate noise. At this point, the gray-scale image was converted to a binary image using a binary thresholding operation. Then, a NOT operation was performed by gray-level value inversion between 0 and 255. Postprocessing: The resulting image was AND-ed with its corresponding ring mask to remove the outer-ring (lens-edge) artifact. At this point, the above algorithm steps had extracted most of the major and minor vessels, with some intersections and bifurcations missing. Vessel segments were reintegrated using the Hough transform. Results: After applying the Hough transform, both the average peak SNR and the RMS error improved by 10%. Pratt's Figure of Merit (PFM) was decreased by 6%. Those averages were better than [1] by 10-30%. Conclusions: The new algorithm successfully preserved the details of smaller blood vessels and should prove successful as a segmentation step for automatically identifying diseases that affect retinal blood vessels.

Improvement of retinal blood vessel detection using morphological component analysis.

Science.gov (United States)

Imani, Elaheh; Javidi, Malihe; Pourreza, Hamid-Reza

2015-03-01

Detection and quantitative measurement of variations in the retinal blood vessels can help diagnose several diseases including diabetic retinopathy. Intrinsic characteristics of abnormal retinal images make blood vessel detection difficult. The major problem with traditional vessel segmentation algorithms is producing false positive vessels in the presence of diabetic retinopathy lesions. To overcome this problem, a novel scheme for extracting retinal blood vessels based on morphological component analysis (MCA) algorithm is presented in this paper. MCA was developed based on sparse representation of signals. This algorithm assumes that each signal is a linear combination of several morphologically distinct components. In the proposed method, the MCA algorithm with appropriate transforms is adopted to separate vessels and lesions from each other. Afterwards, the Morlet Wavelet Transform is applied to enhance the retinal vessels. The final vessel map is obtained by adaptive thresholding. The performance of the proposed method is measured on the publicly available DRIVE and STARE datasets and compared with several state-of-the-art methods. An accuracy of 0.9523 and 0.9590 has been respectively achieved on the DRIVE and STARE datasets, which are not only greater than most methods, but are also superior to the second human observer's performance. The results show that the proposed method can achieve improved detection in abnormal retinal images and decrease false positive vessels in pathological regions compared to other methods. Also, the robustness of the method in the presence of noise is shown via experimental result. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Correlation between gadolinium-diethylenetriaminepentaacetic acid contrast enhancement and thallium-201 chloride uptake in pediatric brainstem glioma.

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Maria, B L; Drane, W B; Quisling, R J; Hoang, K B

1997-09-01

We previously showed that thallium-201 (201Tl) chloride is accumulated in over 75% of brain tumors, including brainstem gliomas. The imaging of 201Tl with single photon emission computed tomography (SPECT) may require an abnormal increase in permeability of tumor vessels to allow penetration of the blood-brain barrier. To test this hypothesis, we evaluated the correlation between gadolinium enhancement and the degree of 201Tl uptake on SPECT and the contributions of either gadolinium enhancement or 201Tl uptake to the prognosis in children with brainstem gliomas. Forty-two sets of paired SPECT scans and magnetic resonance imaging (MRI) scans were obtained longitudinally in 13 cases. Altogether, 31 of 42 pairs (74%) of scans showed concordance between the presence of gadolinium enhancement and 201Tl uptake. There were no cases that demonstrated 201Tl uptake but lacked gadolinium enhancement. The results indicate that 201Tl SPECT is of value primarily when brainstem tumors have vessels that are demonstrably permeable to gadolinium, prior to or as a result of radiotherapy.

Aminopeptidase A is a functional target in angiogenic blood vessels.

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Marchiò, Serena; Lahdenranta, Johanna; Schlingemann, Reinier O; Valdembri, Donatella; Wesseling, Pieter; Arap, Marco A; Hajitou, Amin; Ozawa, Michael G; Trepel, Martin; Giordano, Ricardo J; Nanus, David M; Dijkman, Henri B P M; Oosterwijk, Egbert; Sidman, Richard L; Cooper, Max D; Bussolino, Federico; Pasqualini, Renata; Arap, Wadih

2004-02-01

We show that a membrane-associated protease, aminopeptidase A (APA), is upregulated and enzymatically active in blood vessels of human tumors. To gain mechanistic insight, we evaluated angiogenesis in APA null mice. We found that, although these mice develop normally, they fail to mount the expected angiogenic response to hypoxia or growth factors. We then isolated peptide inhibitors of APA from a peptide library and show that they specifically bind to and inhibit APA, suppress migration and proliferation of endothelial cells, inhibit angiogenesis, and home to tumor blood vessels. Finally, we successfully treated tumor-bearing mice with APA binding peptides or anti-APA blocking monoclonal antibodies. These data show that APA is a regulator of blood vessel formation, and can serve as a functional vascular target.

MRI mediated, non-invasive tracking of intratumoral distribution of nanocarriers in rat glioma

Energy Technology Data Exchange (ETDEWEB)

Karathanasis, Efstathios; Park, Jaekeun; Agarwal, Abhiruchi; Patel, Vijal; Zhao Fuqiang; Hu Xiaoping; Bellamkonda, Ravi V [Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, GA 30332 (United States); Annapragada, Ananth V [School of Health Information Sciences, University of Texas Health Science Center, 7000 Fannin Street, Houston, TX 77030 (United States)], E-mail: ravi@gatech.edu

2008-08-06

Nanocarrier mediated therapy of gliomas has shown promise. The success of systemic nanocarrier-based chemotherapy is critically dependent on the so-called leaky vasculature to permit drug extravasation across the blood-brain barrier. Yet, the extent of vascular permeability in individual tumors varies widely, resulting in a correspondingly wide range of responses to the therapy. However, there exist no tools currently for rationally determining whether tumor blood vessels are amenable to nanocarrier mediated therapy in an individualized, patient specific manner today. To address this need for brain tumor therapy, we have developed a multifunctional 100 nm scale liposomal agent encapsulating a gadolinium-based contrast agent for contrast-enhanced magnetic resonance imaging with prolonged blood circulation. Using a 9.4 T MRI system, we were able to track the intratumoral distribution of the gadolinium-loaded nanocarrier in a rat glioma model for a period of three days due to improved magnetic properties of the contrast agent being packaged in a nanocarrier. Such a nanocarrier provides a tool for non-invasively assessing the suitability of tumors for nanocarrier mediated therapy and then optimizing the treatment protocol for each individual tumor. Additionally, the ability to image the tumor in high resolution can potentially constitute a surgical planning tool for tumor resection.

miR-21 Is Linked to Glioma Angiogenesis

DEFF Research Database (Denmark)

Hermansen, Simon Kjær; Nielsen, Boye Schnack; Aaberg-Jessen, Charlotte

2016-01-01

MicroRNA-21 (miR-21) is the most consistently over-expressed microRNA (miRNA) in malignant gliomas. We have previously reported that miR-21 is upregulated in glioma vessels and subsets of glioma cells. To better understand the role of miR-21 in glioma angiogenesis and to characterize miR-21......-localized with the hypoxia- and angiogenesis-associated markers HIF-1α (p=0.0020) and VEGF (p=0.0096), whereas the putative miR-21 target, PTEN, was expressed independently of miR-21. Expression of stem cell markers Oct4, Sox2 and CD133 was not associated with miR-21. In six glioblastoma cultures, miR-21 did not correlate...... with the six markers. These findings suggest that miR-21 is linked to glioma angiogenesis, that miR-21 is unlikely to regulate PTEN, and that miR-21-positive tumor cells do not possess stem cell characteristics....

Automatic detection of blood vessels in retinal images for diabetic retinopathy diagnosis.

Science.gov (United States)

Raja, D Siva Sundhara; Vasuki, S

2015-01-01

Diabetic retinopathy (DR) is a leading cause of vision loss in diabetic patients. DR is mainly caused due to the damage of retinal blood vessels in the diabetic patients. It is essential to detect and segment the retinal blood vessels for DR detection and diagnosis, which prevents earlier vision loss in diabetic patients. The computer aided automatic detection and segmentation of blood vessels through the elimination of optic disc (OD) region in retina are proposed in this paper. The OD region is segmented using anisotropic diffusion filter and subsequentially the retinal blood vessels are detected using mathematical binary morphological operations. The proposed methodology is tested on two different publicly available datasets and achieved 93.99% sensitivity, 98.37% specificity, 98.08% accuracy in DRIVE dataset and 93.6% sensitivity, 98.96% specificity, and 95.94% accuracy in STARE dataset, respectively.

Subconjunctival Hemorrhage (Broken Blood Vessel in Eye)

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Subconjunctival hemorrhage (broken blood vessel in eye) Overview A subconjunctival hemorrhage (sub-kun-JUNK-tih-vul HEM-uh-ruj) ... may not even realize you have a subconjunctival hemorrhage until you look in the mirror and notice ...

Polymer-based blood vessel models with micro-temperature sensors in EVE

Science.gov (United States)

Mizoshiri, Mizue; Ito, Yasuaki; Hayakawa, Takeshi; Maruyama, Hisataka; Sakurai, Junpei; Ikeda, Seiichi; Arai, Fumihito; Hata, Seiichi

2017-04-01

Cu-based micro-temperature sensors were directly fabricated on poly(dimethylsiloxane) (PDMS) blood vessel models in EVE using a combined process of spray coating and femtosecond laser reduction of CuO nanoparticles. CuO nanoparticle solution coated on a PDMS blood vessel model are thermally reduced and sintered by focused femtosecond laser pulses in atmosphere to write the sensors. After removing the non-irradiated CuO nanoparticles, Cu-based microtemperature sensors are formed. The sensors are thermistor-type ones whose temperature dependences of the resistance are used for measuring temperature inside the blood vessel model. This fabrication technique is useful for direct-writing of Cu-based microsensors and actuators on arbitrary nonplanar substrates.

Blood Vessel Normalization in the Hamster Oral Cancer Model for Experimental Cancer Therapy Studies

Energy Technology Data Exchange (ETDEWEB)

Ana J. Molinari; Romina F. Aromando; Maria E. Itoiz; Marcela A. Garabalino; Andrea Monti Hughes; Elisa M. Heber; Emiliano C. C. Pozzi; David W. Nigg; Veronica A. Trivillin; Amanda E. Schwint

2012-07-01

Normalization of tumor blood vessels improves drug and oxygen delivery to cancer cells. The aim of this study was to develop a technique to normalize blood vessels in the hamster cheek pouch model of oral cancer. Materials and Methods: Tumor-bearing hamsters were treated with thalidomide and were compared with controls. Results: Twenty eight hours after treatment with thalidomide, the blood vessels of premalignant tissue observable in vivo became narrower and less tortuous than those of controls; Evans Blue Dye extravasation in tumor was significantly reduced (indicating a reduction in aberrant tumor vascular hyperpermeability that compromises blood flow), and tumor blood vessel morphology in histological sections, labeled for Factor VIII, revealed a significant reduction in compressive forces. These findings indicated blood vessel normalization with a window of 48 h. Conclusion: The technique developed herein has rendered the hamster oral cancer model amenable to research, with the potential benefit of vascular normalization in head and neck cancer therapy.

Regulation of blood vessels by prolactin and vasoinhibins.

Science.gov (United States)

Clapp, Carmen; Thebault, Stéphanie; Macotela, Yazmín; Moreno-Carranza, Bibiana; Triebel, Jakob; Martínez de la Escalera, Gonzalo

2015-01-01

Prolactin (PRL) stimulates the growth of new blood vessels (angiogenesis) either directly through actions on endothelial cells or indirectly by upregulating proangiogenic factors like vascular endothelial growth factor (VEGF). Moreover, PRL acquires antiangiogenic properties after undergoing proteolytic cleavage to vasoinhibins, a family of PRL fragments (including 16 kDa PRL) with potent antiangiogenic, vasoconstrictive, and antivasopermeability effects. In view of the opposing actions of PRL and vasoinhibins, the regulation of the proteases responsible for specific PRL cleavage represents an efficient mechanism for controlling blood vessel growth and function. This review briefly describes the vascular actions of PRL and vasoinhibins, and addresses how their interplay could help drive biological effects of PRL in the context of health and disease.

Melanopsin mediates light-dependent relaxation in blood vessels.

Science.gov (United States)

Sikka, Gautam; Hussmann, G Patrick; Pandey, Deepesh; Cao, Suyi; Hori, Daijiro; Park, Jong Taek; Steppan, Jochen; Kim, Jae Hyung; Barodka, Viachaslau; Myers, Allen C; Santhanam, Lakshmi; Nyhan, Daniel; Halushka, Marc K; Koehler, Raymond C; Snyder, Solomon H; Shimoda, Larissa A; Berkowitz, Dan E

2014-12-16

Melanopsin (opsin4; Opn4), a non-image-forming opsin, has been linked to a number of behavioral responses to light, including circadian photo-entrainment, light suppression of activity in nocturnal animals, and alertness in diurnal animals. We report a physiological role for Opn4 in regulating blood vessel function, particularly in the context of photorelaxation. Using PCR, we demonstrate that Opn4 (a classic G protein-coupled receptor) is expressed in blood vessels. Force-tension myography demonstrates that vessels from Opn4(-/-) mice fail to display photorelaxation, which is also inhibited by an Opn4-specific small-molecule inhibitor. The vasorelaxation is wavelength-specific, with a maximal response at ∼430-460 nm. Photorelaxation does not involve endothelial-, nitric oxide-, carbon monoxide-, or cytochrome p450-derived vasoactive prostanoid signaling but is associated with vascular hyperpolarization, as shown by intracellular membrane potential measurements. Signaling is both soluble guanylyl cyclase- and phosphodiesterase 6-dependent but protein kinase G-independent. β-Adrenergic receptor kinase 1 (βARK 1 or GRK2) mediates desensitization of photorelaxation, which is greatly reduced by GRK2 inhibitors. Blue light (455 nM) regulates tail artery vasoreactivity ex vivo and tail blood blood flow in vivo, supporting a potential physiological role for this signaling system. This endogenous opsin-mediated, light-activated molecular switch for vasorelaxation might be harnessed for therapy in diseases in which altered vasoreactivity is a significant pathophysiologic contributor.

An approach to localize the retinal blood vessels using bit planes and centerline detection.

Science.gov (United States)

Fraz, M M; Barman, S A; Remagnino, P; Hoppe, A; Basit, A; Uyyanonvara, B; Rudnicka, A R; Owen, C G

2012-11-01

The change in morphology, diameter, branching pattern or tortuosity of retinal blood vessels is an important indicator of various clinical disorders of the eye and the body. This paper reports an automated method for segmentation of blood vessels in retinal images. A unique combination of techniques for vessel centerlines detection and morphological bit plane slicing is presented to extract the blood vessel tree from the retinal images. The centerlines are extracted by using the first order derivative of a Gaussian filter in four orientations and then evaluation of derivative signs and average derivative values is performed. Mathematical morphology has emerged as a proficient technique for quantifying the blood vessels in the retina. The shape and orientation map of blood vessels is obtained by applying a multidirectional morphological top-hat operator with a linear structuring element followed by bit plane slicing of the vessel enhanced grayscale image. The centerlines are combined with these maps to obtain the segmented vessel tree. The methodology is tested on three publicly available databases DRIVE, STARE and MESSIDOR. The results demonstrate that the performance of the proposed algorithm is comparable with state of the art techniques in terms of accuracy, sensitivity and specificity. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

A choline derivate-modified nanoprobe for glioma diagnosis using MRI

Science.gov (United States)

Li, Jianfeng; Huang, Shixian; Shao, Kun; Liu, Yang; An, Sai; Kuang, Yuyang; Guo, Yubo; Ma, Haojun; Wang, Xuxia; Jiang, Chen

2013-04-01

Gadolinium (Gd) chelate contrast-enhanced magnetic resonance imaging (MRI) is a preferred method of glioma detection and preoperative localisation because it offers high spatial resolution and non-invasive deep tissue penetration. Gd-based contrast agents, such as Gd-diethyltriaminepentaacetic acid (DTPA-Gd, Magnevist), are widely used clinically for tumor diagnosis. However, the Gd-based MRI approach is limited for patients with glioma who have an uncompromised blood-brain barrier (BBB). Moreover, the rapid renal clearance and non-specificity of such contrast agents further hinders their prevalence. We present a choline derivate (CD)-modified nanoprobe with BBB permeability, glioma specificity and a long blood half-life. Specific accumulation of the nanoprobe in gliomas and subsequent MRI contrast enhancement are demonstrated in vitro in U87 MG cells and in vivo in a xenograft nude model. BBB and glioma dual targeting by this nanoprobe may facilitate precise detection of gliomas with an uncompromised BBB and may offer better preoperative and intraoperative tumor localization.

Correlation between blood and lymphatic vessel density and results of contrast-enhanced spectral mammography.

Science.gov (United States)

Luczynska, Elzbieta; Niemiec, Joanna; Ambicka, Aleksandra; Adamczyk, Agnieszka; Walasek, Tomasz; Ryś, Janusz; Sas-Korczyńska, Beata

2015-09-01

Contrast-enhanced spectral mammography (CESM) is a novel technique used for detection of tumour vascularity by imaging the moment in which contrast, delivered to the lesion by blood vessels, leaks out of them, and flows out through lymphatic vessels. In our study, we included 174 women for whom spectral mammography was performed for diagnostic purposes. The relationship between enhancement in CESM and blood vessel density (BVD), lymphatic vessel density (LVD) or the percentage of fields with at least one lymphatic vessel (distribution of podoplanin-positive vessels - DPV) and other related parameters was assessed in 55 cases. BVD, LVD and DPV were assessed immunohistochemically, applying podoplanin and CD31/CD34 as markers of lymphatic and blood vessels, respectively. The sensitivity (in detection of malignant lesions) of CESM was 100%, while its specificity - 39%. We found a significant positive correlation between the intensity of enhancement in CESM and BVD (p = 0.007, r = 0.357) and a negative correlation between the intensity of enhancement in CESM and DPV (p = 0.003, r = -0.390). Lesions with the highest enhancement in CESM showed a high number of blood vessels and a low number of lymphatics. 1) CESM is a method characterized by high sensitivity and acceptable specificity; 2) the correlation between CESM results and blood/lymphatic vessel density confirms its utility in detection of tissue angiogenesis and/or lymphangiogenesis.

Alterations of the Blood-Brain Barrier and Regional Perfusion in Tumor Development: MRI Insights from a Rat C6 Glioma Model.

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Huhndorf, Monika; Moussavi, Amir; Kramann, Nadine; Will, Olga; Hattermann, Kirsten; Stadelmann, Christine; Jansen, Olav; Boretius, Susann

2016-01-01

Angiogenesis and anti-angiogenetic medications play an important role in progression and therapy of glioblastoma. In this context, in vivo characterization of the blood-brain-barrier and tumor vascularization may be important for individual prognosis and therapy optimization. We analyzed perfusion and capillary permeability of C6-gliomas in rats at different stages of tumor-growth by contrast enhanced MRI and dynamic susceptibility contrast (DSC) MRI at 7 Tesla. The analyses included maps of relative cerebral blood volume (CBV) and signal recovery derived from DSC data over a time period of up to 35 days after tumor cell injections. In all rats tumor progression was accompanied by temporal and spatial changes in CBV and capillary permeability. A leakage of the blood-brain barrier (slow contrast enhancement) was observed as soon as the tumor became detectable on T2-weighted images. Interestingly, areas of strong capillary permeability (fast signal enhancement) were predominantly localized in the center of the tumor. In contrast, the tumor rim was dominated by an increased CBV and showed the highest vessel density compared to the tumor center and the contralateral hemisphere as confirmed by histology. Substantial regional differences in the tumor highlight the importance of parameter maps in contrast or in addition to region-of-interest analyses. The data vividly illustrate how MRI including contrast-enhanced and DSC-MRI may contribute to a better understanding of tumor development.

Feasibility of Using the Marginal Blood Vessels as Reference Landmarks for CT Colonography

Science.gov (United States)

Wei, Zhuoshi; Yao, Jianhua; Wang, Shijun; Liu, Jiamin; Dwyer, Andrew J.; Pickhardt, Perry J.; Nowinski, Wieslaw L.; Summers, Ronald M.

2015-01-01

OBJECTIVE The purpose of this study was to show the spatial relationship of the colonic marginal blood vessels and the teniae coli on CT colonography (CTC) and the use of the marginal blood vessels for supine-prone registration of polyps and for determination of proper connectivity of collapsed colonic segments. MATERIALS AND METHODS We manually labeled the marginal blood vessels on 15 CTC examinations. Colon segmentation, centerline extraction, teniae detection, and teniae identification were automatically performed. For assessment of their spatial relationships, the distances from the marginal blood vessels to the three teniae coli and to the colon were measured. Student t tests (paired, two-tailed) were performed to evaluate the differences among these distances. To evaluate the reliability of the marginal vessels as reference points for polyp correlation, we analyzed 20 polyps from 20 additional patients who underwent supine and prone CTC. The average difference of the circumferential polyp position on the supine and prone scans was computed. Student t tests (paired, two-tailed) were performed to evaluate the supine-prone differences of the distance. We performed a study on 10 CTC studies from 10 patients with collapsed colonic segments by manually tracing the marginal blood vessels near the collapsed regions to resolve the ambiguity of the colon path. RESULTS The average distances (± SD) from the marginal blood vessels to the tenia mesocolica, tenia omentalis, and tenia libera were 20.1 ± 3.1 mm (95% CI, 18.5–21.6 mm), 39.5 ± 4.8 mm (37.1–42.0 mm), and 36.9 ± 4.2 mm (34.8–39.1 mm), respectively. Pairwise comparison showed that these distances to the tenia libera and tenia omentalis were significantly different from the distance to the tenia mesocolica (p marginal blood vessels to the colon wall was 15.3 ± 2.0 mm (14.2–16.3 mm). For polyp localization, the average difference of the circumferential polyp position on the supine and prone scans was 9

Customizable engineered blood vessels using 3D printed inserts.

Science.gov (United States)

Pinnock, Cameron B; Meier, Elizabeth M; Joshi, Neeraj N; Wu, Bin; Lam, Mai T

2016-04-15

Current techniques for tissue engineering blood vessels are not customizable for vascular size variation and vessel wall thickness. These critical parameters vary widely between the different arteries in the human body, and the ability to engineer vessels of varying sizes could increase capabilities for disease modeling and treatment options. We present an innovative method for producing customizable, tissue engineered, self-organizing vascular constructs by replicating a major structural component of blood vessels - the smooth muscle layer, or tunica media. We utilize a unique system combining 3D printed plate inserts to control construct size and shape, and cell sheets supported by a temporary fibrin hydrogel to encourage cellular self-organization into a tubular form resembling a natural artery. To form the vascular construct, 3D printed inserts are adhered to tissue culture plates, fibrin hydrogel is deposited around the inserts, and human aortic smooth muscle cells are then seeded atop the fibrin hydrogel. The gel, aided by the innate contractile properties of the smooth muscle cells, aggregates towards the center post insert, creating a tissue ring of smooth muscle cells. These rings are then stacked into the final tubular construct. Our methodology is robust, easily repeatable and allows for customization of cellular composition, vessel wall thickness, and length of the vessel construct merely by varying the size of the 3D printed inserts. This platform has potential for facilitating more accurate modeling of vascular pathology, serving as a drug discovery tool, or for vessel repair in disease treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of non-Newtonian characteristics of blood on magnetic particle capture in occluded blood vessel

Science.gov (United States)

Bose, Sayan; Banerjee, Moloy

2015-01-01

Magnetic nanoparticles drug carriers continue to attract considerable interest for drug targeting in the treatment of cancer and other pathological conditions. Magnetic carrier particles with surface-bound drug molecules are injected into the vascular system upstream from the desired target site, and are captured at the target site via a local applied magnetic field. Herein, a numerical investigation of steady magnetic drug targeting (MDT) using functionalized magnetic micro-spheres in partly occluded blood vessel having a 90° bent is presented considering the effects of non-Newtonian characteristics of blood. An Eulerian-Lagrangian technique is adopted to resolve the hemodynamic flow and the motion of the magnetic particles in the flow using ANSYS FLUENT. An implantable infinitely long cylindrical current carrying conductor is used to create the requisite magnetic field. Targeted transport of the magnetic particles in a partly occluded vessel differs distinctly from the same in a regular unblocked vessel. Parametric investigation is conducted and the influence of the insert configuration and its position from the central plane of the artery (zoffset), particle size (dp) and its magnetic property (χ) and the magnitude of current (I) on the "capture efficiency" (CE) is reported. Analysis shows that there exists an optimum regime of operating parameters for which deposition of the drug carrying magnetic particles in a target zone on the partly occluded vessel wall can be maximized. The results provide useful design bases for in vitro set up for the investigation of MDT in stenosed blood vessels.

Mass Spectrometry and Antibody-Based Characterization of Blood Vessels from Brachylophosaurus canadensis.

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Cleland, Timothy P; Schroeter, Elena R; Zamdborg, Leonid; Zheng, Wenxia; Lee, Ji Eun; Tran, John C; Bern, Marshall; Duncan, Michael B; Lebleu, Valerie S; Ahlf, Dorothy R; Thomas, Paul M; Kalluri, Raghu; Kelleher, Neil L; Schweitzer, Mary H

2015-12-04

Structures similar to blood vessels in location, morphology, flexibility, and transparency have been recovered after demineralization of multiple dinosaur cortical bone fragments from multiple specimens, some of which are as old as 80 Ma. These structures were hypothesized to be either endogenous to the bone (i.e., of vascular origin) or the result of biofilm colonizing the empty osteonal network after degradation of original organic components. Here, we test the hypothesis that these structures are endogenous and thus retain proteins in common with extant archosaur blood vessels that can be detected with high-resolution mass spectrometry and confirmed by immunofluorescence. Two lines of evidence support this hypothesis. First, peptide sequencing of Brachylophosaurus canadensis blood vessel extracts is consistent with peptides comprising extant archosaurian blood vessels and is not consistent with a bacterial, cellular slime mold, or fungal origin. Second, proteins identified by mass spectrometry can be localized to the tissues using antibodies specific to these proteins, validating their identity. Data are available via ProteomeXchange with identifier PXD001738.

Leukemic Cells "Gas Up" Leaky Bone Marrow Blood Vessels.

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Itkin, Tomer; Rafii, Shahin

2017-09-11

In this issue of Cancer Cell, Passaro et al. demonstrate how leukemia through aberrant induction of reactive oxygen species and nitric oxide production trigger marrow vessel leakiness, instigating pro-leukemic function. Disrupted tumor blood vessels promote exhaustion of non-malignant stem and progenitor cells and may facilitate leukemia relapse following chemotherapeutic treatment. Copyright © 2017. Published by Elsevier Inc.

Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy

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Han-Chung Wu

2010-01-01

Full Text Available Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.

Parametrically defined cerebral blood vessels as non-invasive blood input functions for brain PET studies

International Nuclear Information System (INIS)

Asselin, Marie-Claude; Cunningham, Vincent J; Amano, Shigeko; Gunn, Roger N; Nahmias, Claude

2004-01-01

A non-invasive alternative to arterial blood sampling for the generation of a blood input function for brain positron emission tomography (PET) studies is presented. The method aims to extract the dimensions of the blood vessel directly from PET images and to simultaneously correct the radioactivity concentration for partial volume and spillover. This involves simulation of the tomographic imaging process to generate images of different blood vessel and background geometries and selecting the one that best fits, in a least-squares sense, the acquired PET image. A phantom experiment was conducted to validate the method which was then applied to eight subjects injected with 6-[ 18 F]fluoro-L-DOPA and one subject injected with [ 11 C]CO-labelled red blood cells. In the phantom study, the diameter of syringes filled with an 11 C solution and inserted into a water-filled cylinder were estimated with an accuracy of half a pixel (1 mm). The radioactivity concentration was recovered to 100 ± 4% in the 8.7 mm diameter syringe, the one that most closely approximated the superior sagittal sinus. In the human studies, the method systematically overestimated the calibre of the superior sagittal sinus by 2-3 mm compared to measurements made in magnetic resonance venograms on the same subjects. Sources of discrepancies related to the anatomy of the blood vessel were found not to be fundamental limitations to the applicability of the method to human subjects. This method has the potential to provide accurate quantification of blood radioactivity concentration from PET images without the need for blood samples, corrections for delay and dispersion, co-registered anatomical images, or manually defined regions of interest

Towards cavitation-enhanced permeability in blood vessel on a chip

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De Luca, R.; Silvani, G.; Scognamiglio, C.; Sinibaldi, G.; Peruzzi, G.; Chinappi, M.; Kiani, M. F.; Casciola, C. M.

2017-08-01

The development of targeted delivery systems releasing pharmaceutical agents directly at the desired site of action may improve their therapeutic efficiency while minimizing damage to healthy tissues, toxicity to the patient and drug waste. In this context, we have developed a bio-inspired microdevice mimicking the tumour microvasculature which represents a valuable tool for assessing the enhancement of blood vessel permeability due to cavitation. This novel system allows us to investigate the effects of ultrasound-driven microbubbles that temporarily open the endothelial intercellular junctions allowing drug to extravasate blood vessels into tumour tissues. The blood vessel on a chip consists of a tissue chamber and two independent vascular channels (width 200 µm, height 100 µm, length 2762 µm) cultured with endothelial cells placed side-by-side and separated by a series of 3 µm pores. Its geometry and dimensions mimic the three-dimensional morphology, size and flow characteristics of microvessels in vivo. The early stage of this project had a twofold objective: 1. To define the protocol for culturing of Human Umbilical Vein Endothelial Cells (HUVECs) within the vascular channel; 2. To develop a fluorescence based microscopy technique for measuring permeability. We have developed a reliable and reproducible protocol to culture endothelial cells within the artificial vessels in a realistic manner: HUVECs show the typical elongated shape in the direction of flow, exhibit tight junction formation and form a continuous layer with a central lumen that completely covers the channels wall. As expected, the permeability of cell-free device is higher than the one cultured with HUVECs in the vascular channels. The proposed blood vessel on a chip and the permeability measurement protocol have a significant potential to allow for the study of cavitation-enhanced permeability of the endothelium and improve efficiency in screening drug delivery systems.

A thresholding based technique to extract retinal blood vessels from fundus images

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Jyotiprava Dash

2017-12-01

Full Text Available Retinal imaging has become the significant tool among all the medical imaging technology, due to its capability to extract many data which is linked to various eye diseases. So, the accurate extraction of blood vessel is necessary that helps the eye care specialists and ophthalmologist to identify the diseases at the early stages. In this paper, we have proposed a computerized technique for extraction of blood vessels from fundus images. The process is conducted in three phases: (i pre-processing where the image is enhanced using contrast limited adaptive histogram equalization and median filter, (ii segmentation using mean-C thresholding to extract retinal blood vessels, (iii post-processing where morphological cleaning operation is used to remove isolated pixels. The performance of the proposed method is tested on and experimental results show that our method achieve an accuracies of 0.955 and 0.954 on Digital retinal images for vessel extraction (DRIVE and Child heart and health study in England (CHASE_DB1 databases respectively.

Wide-field absolute transverse blood flow velocity mapping in vessel centerline

Science.gov (United States)

Wu, Nanshou; Wang, Lei; Zhu, Bifeng; Guan, Caizhong; Wang, Mingyi; Han, Dingan; Tan, Haishu; Zeng, Yaguang

2018-02-01

We propose a wide-field absolute transverse blood flow velocity measurement method in vessel centerline based on absorption intensity fluctuation modulation effect. The difference between the light absorption capacities of red blood cells and background tissue under low-coherence illumination is utilized to realize the instantaneous and average wide-field optical angiography images. The absolute fuzzy connection algorithm is used for vessel centerline extraction from the average wide-field optical angiography. The absolute transverse velocity in the vessel centerline is then measured by a cross-correlation analysis according to instantaneous modulation depth signal. The proposed method promises to contribute to the treatment of diseases, such as those related to anemia or thrombosis.

Polysaccharides from astragali radix restore chemical-induced blood vessel loss in zebrafish

Science.gov (United States)

2012-01-01

Background Astragali Radix has been used widely for the treatment of cardiovascular and cerebrovascular diseases, and to enhance endurance and stamina in traditional Chinese medicine (TCM) for over 2000 years. The polysaccharide constituents of Astragali Radix (ARP) are considered as one of the major constituents contributing to the multiple pharmacological effects of this medicinal plant. The purpose of the study is to evaluate the vascular regenerative activities of ARPs in a chemically-induced blood vessel loss model in zebrafish. Methods Blood vessel loss was induced in both Tg(fli-1a:EGFP)y1 and Tg(fli-1a:nEGFP)y7 embryos by administration of 300 nM VEGFR tyrosine kinase inhibitor II (VRI) for 3 h at 24 hpf (hour post-fertilization). Then, the blood vessel damaged zebrafish were treated with ARPs for 21 h and 45 h after VRI withdrawal. Morphological changes in intersegmental vessels (ISVs) of zebrafish larvae were observed under the fluorescence microscope and measured quantitatively. The rescue effect of ARPs in the zebrafish models was validated by measuring the relative mRNA expressions of Kdrl, Kdr and Flt-1 using real-time PCR. Results Two polysaccharide fractions, P4 (50000 D 0.1 μm), isolated from Astragali Radix by ultrafiltration, produced a significant and dose-dependent recovery in VRI-induced blood vessel loss in zebrafish. Furthermore, the down-regulation of Flk-1 and Flt-1 mRNA expression induced by VRI was reversed by treatment with P4. Conclusion The present study demonstrates that P4 isolated from Astragali Radix reduces VRI-induced blood vessel loss in zebrafish. These findings support the hypothesis that polysaccharides are one of the active constituents in Astragali Radix, contributing to its beneficial effect on treatment of diseases associated with a deficiency in angiogenesis. PMID:22357377

Fetal blood vessel count increases in compensation of hypoxia in premature placentas

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K. Kartini

2015-04-01

Full Text Available Background Prematurity refers to live births before 37 weeks of gestation, wherein the baby is born before the body and its organ systems achieve perfect maturity, and this disorder is still a global problem. The high incidence of prematurity is a problem in developing and also in developed countries. Certain conditions accompanying pregnancies like preeclampsia, infection, and placental insufficiency, may trigger uterine hypoxia, causing premature birth. The placental condition is related to the intra-uterine fetal condition. In prolonged placental hypoxia, there occurs a compensatory mechanism, i.e. an increase in placental angiogenesis. This study aimed to evaluate the effect of hypoxia on fetal blood vessel count as compensatory mechanism for tissue hypoxia. Methods An observational-analytical cross-sectional design using paraffin blocks of conserved premature placentas, comprising 31 samples of hypoxic premature placentas and 28 samples of non-hypoxic premature placentas, selected using non-random consecutive sampling. The samples were made into slides and stained with hematoxylin-eosin for assessment of histological structure, including fetal blood vessel count and integrity, villus conditions, syncytiotrophoblastic nuclear changes, and syncytiotrophoblastic nuclear aggregation. Mann-Whitney test was used to compare the difference of blood vessel count between groups. Results Assessment of histological structure showed a significant increase in fetal blood vessel count in the hypoxic group [8.00 (5-15] as compared with the non-hypoxic group [7.50 (3-15]. Conclusion The hypoxia in premature placentas caused an increase in the number of fetal blood vessels as a form of compensation for disturbed oxygen homeostasis.

Fetal blood vessel count increases in compensation of hypoxia in premature placentas

Directory of Open Access Journals (Sweden)

K Kartini

2016-02-01

Full Text Available BACKGROUND Prematurity refers to live births before 37 weeks of gestation, wherein the baby is born before the body and its organ systems achieve perfect maturity, and this disorder is still a global problem. The high incidence of prematurity is a problem in developing and also in developed countries. Certain conditions accompanying pregnancies like preeclampsia, infection, and placental insufficiency, may trigger uterine hypoxia, causing premature birth. The placental condition is related to the intra-uterine fetal condition. In prolonged placental hypoxia, there occurs a compensatory mechanism, i.e. an increase in placental angiogenesis. This study aimed to evaluate the effect of hypoxia on fetal blood vessel count as compensatory mechanism for tissue hypoxia. METHODS An observational-analytical cross-sectional design using paraffin blocks of conserved premature placentas, comprising 31 samples of hypoxic premature placentas and 28 samples of non-hypoxic premature placentas, selected using non-random consecutive sampling. The samples were made into slides and stained with hematoxylin-eosin for assessment of histological structure, including fetal blood vessel count and integrity, villus conditions, syncytiotrophoblastic nuclear changes, and syncytiotrophoblastic nuclear aggregation. Mann-Whitney test was used to compare the difference of blood vessel count between groups. RESULTS Assessment of histological structure showed a significant increase in fetal blood vessel count in the hypoxic group [8.00 (5-15] as compared with the non-hypoxic group [7.50 (3-15]. CONCLUSION The hypoxia in premature placentas caused an increase in the number of fetal blood vessels as a form of compensation for disturbed oxygen homeostasis.

Bio-Adaption between Magnesium Alloy Stent and the Blood Vessel: A Review.

Science.gov (United States)

Ma, Jun; Zhao, Nan; Betts, Lexxus; Zhu, Donghui

2016-09-01

Biodegradable magnesium (Mg) alloy stents are the most promising next generation of bio-absorbable stents. In this article, we summarized the progresses on the in vitro studies, animal testing and clinical trials of biodegradable Mg alloy stents in the past decades. These exciting findings led us to propose the importance of the concept "bio-adaption" between the Mg alloy stent and the local tissue microenvironment after implantation. The healing responses of stented blood vessel can be generally described in three overlapping phases: inflammation, granulation and remodeling. The ideal bio-adaption of the Mg alloy stent, once implanted into the blood vessel, needs to be a reasonable function of the time and the space/dimension. First, a very slow degeneration of mechanical support is expected in the initial four months in order to provide sufficient mechanical support to the injured vessels. Although it is still arguable whether full mechanical support in stented lesions is mandatory during the first four months after implantation, it would certainly be a safety design parameter and a benchmark for regulatory evaluations based on the fact that there is insufficient human in vivo data available, especially the vessel wall mechanical properties during the healing/remodeling phase. Second, once the Mg alloy stent being degraded, the void space will be filled by the regenerated blood vessel tissues. The degradation of the Mg alloy stent should be 100% completed with no residues, and the degradation products (e.g., ions and hydrogen) will be helpful for the tissue reconstruction of the blood vessel. Toward this target, some future research perspectives are also discussed.

Accuracy of geometrical modelling of heat transfer from tissue to blood vessels

NARCIS (Netherlands)

Leeuwen, van G.M.J.; Kotte, A.N.T.J.; Bree, de J.; Koijk, van der J.F.; Crezee, J.; Lagendijk, J.J.W.

1997-01-01

We have developed a thermal model in which blood vessels are described as geometrical objects, 3D curves with associated diameters. Here the behaviour of the model is examined for low resolutions compared with the vessel diameter and for strongly curved vessels. The tests include a single straight

Bone marrow blood vessel ossification and "microvascular dead space" in rat and human long bone.

Science.gov (United States)

Prisby, Rhonda D

2014-07-01

Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (4-6 month; n=8) and old (22-24 month; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldner's Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via μCT to quantify microvascular ossification. Bone marrow blood vessels from the rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and "normal" vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (pnecrosis. Progression of bone microvascular ossification may provide the common link associated with age-related changes in bone and bone marrow. The clinical implications may be evident in the difficulties treating bone disease in the elderly. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of blood vessels on light distribution in optogenetic stimulation of cortex.

Science.gov (United States)

Azimipour, Mehdi; Atry, Farid; Pashaie, Ramin

2015-05-15

In this Letter, the impact of blood vessels on light distribution during photostimulation of cortical tissue in small rodents is investigated. Brain optical properties were extracted using a double-integrating sphere setup, and optical coherence tomography was used to image cortical vessels and capillaries to generate a three-dimensional angiogram of the cortex. By combining these two datasets, a complete volumetric structure of the cortical tissue was developed and linked to a Monte Carlo code which simulates light propagation in this inhomogeneous structure and illustrates the effect of blood vessels on the penetration depth and pattern preservation in optogenetic stimulation.

Development of glia and blood vessels in the internal capsule of rats.

Science.gov (United States)

Earle, K L; Mitrofanis, J

1998-02-01

We have explored two aspects of internal capsule development that have not been described previously, namely, the development of glia and of blood vessels. To these ends, we used antibodies to glial fibrillary acidic protein (GFAP) and to vimentin (to identify astrocytes and to radial glia) and Griffonia simplicifolia (lectin; to identify microglia and blood vessels). Further, we made intracardiac injections of Evans Blue to examine the permeability of this dye in the vessels of the internal capsule during neonatal development. Our results show that large numbers of radial glia, astrocytes and microglia are not labelled with these markers in the white matter of the internal capsule until about birth; very few are labelled earlier, during the critical stages of corticofugal and corticopetal axonal ingrowth (E15-E20). The large glial labelling in the internal capsule at birth is accompanied by a dense vascular innervation of the capsule; as with the glia, very few labelled patent vessels are seen earlier. After intracardiac injections of Evans Blue, we find that the blood vessels of the internal capsule are not particularly permeable to Evans Blue. At each age examined (P0, P5, P15), blood vessels are outlined very clearly and there is no diffuse haze of fluorescence within the extracellular space, which is indicative of a leaky vessel. There are three striking differences between the glial environment of the internal capsule and that of the adjacent thalamus. First, the internal capsule is never rich with radial glial fibres (vimentin- and GFAP-immunoreactive) during development (except at P0), whereas the thalamus has many radial fibres from very early development (E15-E17). Second, astrocytes (vimentin- and GFAP-immunoreactive) first become apparent in the internal capsule (E20-P0) well before they do in the thalamus (P15). Third, the internal capsule houses a large transient population of amoeboid microglia (P0-P22), whereas the thalamus does not; only ramified

Blood Vessel-Derived Acellular Matrix for Vascular Graft Application

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Luigi Dall’Olmo

2014-01-01

Full Text Available To overcome the issues connected to the use of autologous vascular grafts and artificial materials for reconstruction of small diameter (<6 mm blood vessels, this study aimed to develop acellular matrix- (AM- based vascular grafts. Rat iliac arteries were decellularized by a detergent-enzymatic treatment, whereas endothelial cells (ECs were obtained through enzymatic digestion of rat skin followed by immunomagnetic separation of CD31-positive cells. Sixteen female Lewis rats (8 weeks old received only AM or previously in vitro reendothelialized AM as abdominal aorta interposition grafts (about 1 cm. The detergent-enzymatic treatment completely removed the cellular part of vessels and both MHC class I and class II antigens. One month after surgery, the luminal surface of implanted AMs was partially covered by ECs and several platelets adhered in the areas lacking cell coverage. Intimal hyperplasia, already detected after 1 month, increased at 3 months. On the contrary, all grafts composed by AM and ECs were completely covered at 1 month and their structure was similar to that of native vessels at 3 months. Taken together, our findings show that prostheses composed of AM preseeded with ECs could be a promising approach for the replacement of blood vessels.

Tracking blood vessels in human forearms using visual servoing

DEFF Research Database (Denmark)

Savarimuthu, Thiusius Rajeeth; Ellekilde, Lars-Peter; Hansen, Morten

compensation. By using images taken with near-infrared light to locate the blood vessels in a human forearm and using the same images to detects movements of the arm, this paper shows that it is possible make a robot arm, potentially equipped with a needle for drawing the blood, compensate for the movements......Drawing an average of more than 2 blood sample per Danish citizen per year increases the demand for an automatic blood sampling method. This paper presents a proof of concept to one of the main challenges in making a fully automated blood sampling procedure, namely: the patient movement...

Acute effect of gamma-irradiation on blood vessels of the eye

International Nuclear Information System (INIS)

Matsushima, Hideno

1977-01-01

Radiation injuries to the eye were studied by examining the alteration of fine vasculature of irradiated rabbit eyes, by referring to the usual clinical findings, fundus photography, microangiography, and histological sections. These experiments were performed by using white rabbits whose eyes were locally irradiated with a single dose of 500, 1000, 2000, 3000, and 5000 R of 60 Co-γ-ray. The eyes were observed periodically for a period up to 10 weeks after irradiation, and the following results were obtained: 1) Radiation damage to the blood vessels was maximum around 6 weeks after irradiation for doses less than 2000 R, and the damage appeared to be reversible. 2) When given more than 3000 R irradiation, alteration of the blood vessels continued increasing for 10 weeks with no evidence of recovery. Experimental evidence from these studies supports the hypothesis that the degree of radiation injury of the eye depends highly on the damage to blood vessels serving each structure of the eye. (auth.)

Benefits of adjuvant chemotherapy in high-grade gliomas.

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DeAngelis, Lisa M

2003-12-01

The current standard of care for patients with high-grade glioma is resection followed by radiotherapy. Adjuvant chemotherapy is not widely accepted because of the low sensitivity of gliomas to traditional antineoplastic agents, the poor penetration of most drugs across the blood-brain barrier, and the significant systemic toxicity associated with current agents. However, nitrosoureas and, subsequently, temozolomide (Temodar [US], Temodal [international]; Schering-Plough Corporation, Kenilworth, NJ), a novel alkylating agent, cross the blood-brain barrier and have activity against gliomas. Nitrosoureas have been studied in phase III trials in the adjuvant setting. In individual trials, chemotherapy did not increase median survival but did increase the proportion of patients surviving >/=18 months by 15%. Only with large meta-analyses did the addition of chemotherapy achieve a statistically significant improvement in median survival. Currently there is no means of identifying which patients will benefit from adjuvant chemotherapy, but nitrosoureas and temozolomide are well tolerated in most patients, justifying the administration of adjuvant chemotherapy to all newly diagnosed patients with malignant glioma.

Blood vessel damage correlated with irradiance for in vivo vascular targeted photodynamic therapy

Science.gov (United States)

Zhang, Jinde; Tan, Zou; Niu, Xiangyu; Lin, Linsheng; Lin, Huiyun; Li, Buhong

2016-10-01

Vascular targeted photodynamic therapy (V-PDT) has been widely utilized for the prevention or treatment of vascular-related diseases, including age-related macular degeneration, port-wine stains and prostate cancer. In order to quantitative assessment the blood vessel damage during V-PDT, nude mice were implanted with Titanium dorsal skin window chambers for in vivo V-PDT studies. For treatments, various irradiances including 50, 75, 100 and 200 mW/cm2 provided by a 532 nm semiconductor laser were performed with the same total light dose of 30 J/cm2 after the mice were intravenously injection of Rose Bengal for 25 mg/Kg body weight. Laser speckle imaging and microscope were used to monitor blood flow dynamics and vessel constriction during and after V-PDT, respectively. The V-PDT induced vessel damages between different groups were compared. The results show that significant difference in blood vessel damage was found between the lower irradiances (50, 75 and 100 mW/cm2) and higher irradiance (200 mW/cm2), and the blood vessel damage induced by V-PDT is positively correlated with irradiance. This study implies that the optimization of irradiance is required for enhancing V-PDT therapeutic efficiency.

Mathematical modelling for trajectories of magnetic nanoparticles in a blood vessel under magnetic field

International Nuclear Information System (INIS)

Sharma, Shashi; Katiyar, V.K.; Singh, Uaday

2015-01-01

A mathematical model is developed to describe the trajectories of a cluster of magnetic nanoparticles in a blood vessel for the application of magnetic drug targeting (MDT). The magnetic nanoparticles are injected into a blood vessel upstream from a malignant tissue and are captured at the tumour site with help of an applied magnetic field. The applied field is produced by a rare earth cylindrical magnet positioned outside the body. All forces expected to significantly affect the transport of nanoparticles were incorporated, including magnetization force, drag force and buoyancy force. The results show that particles are slow down and captured under the influence of magnetic force, which is responsible to attract the magnetic particles towards the magnet. It is optimized that all particles are captured either before or at the centre of the magnet (z≤0) when blood vessel is very close proximity to the magnet (d=2.5 cm). However, as the distance between blood vessel and magnet (d) increases (above 4.5 cm), the magnetic nanoparticles particles become free and they flow away down the blood vessel. Further, the present model results are validated by the simulations performed using the finite element based COMSOL software. - Highlights: • A mathematical model is developed to describe the trajectories of magnetic nanoparticles. • The dominant magnetic, drag and buoyancy forces are considered. • All particles are captured when distance between blood vessel and magnet (d) is up to 4.5 cm. • Further increase in d value (above 4.5 cm) results the free movement of magnetic particles

Imaging Blood Vessel Morphology in Skin

DEFF Research Database (Denmark)

Schuh, Sandra; Holmes, Jon; Ulrich, Martina

2017-01-01

Conventional optical coherence tomography (OCT) enables the visualization of morphological changes of skin cancer. The use of OCT in the diagnostic investigation and in the therapy decision of non-melanoma skin cancer and other skin changes is already established, and has found its way into routine...... practice. With the development of speckle-variance OCT, also named dynamic OCT (D-OCT), the vascular architecture and the blood flow of the skin can be displayed in vivo and in 3D. This novel angiographic variant of OCT offers the ability to visualize and measure vessel morphology providing a new insight...... into healthy, inflammatory and neoplastic skin lesions such as malignant melanoma. This review focuses on the possibilities of using D-OCT on healthy and diseased skin. We suggest and illustrate key diagnostic characteristics by analyzing the initial publications and preliminary unpublished data on vessel...

Bio-Adaption between Magnesium Alloy Stent and the Blood Vessel: A Review

Science.gov (United States)

Ma, Jun; Zhao, Nan; Betts, Lexxus; Zhu, Donghui

2016-01-01

Biodegradable magnesium (Mg) alloy stents are the most promising next generation of bio-absorbable stents. In this article, we summarized the progresses on the in vitro studies, animal testing and clinical trials of biodegradable Mg alloy stents in the past decades. These exciting findings led us to propose the importance of the concept “bio-adaption” between the Mg alloy stent and the local tissue microenvironment after implantation. The healing responses of stented blood vessel can be generally described in three overlapping phases: inflammation, granulation and remodeling. The ideal bio-adaption of the Mg alloy stent, once implanted into the blood vessel, needs to be a reasonable function of the time and the space/dimension. First, a very slow degeneration of mechanical support is expected in the initial four months in order to provide sufficient mechanical support to the injured vessels. Although it is still arguable whether full mechanical support in stented lesions is mandatory during the first four months after implantation, it would certainly be a safety design parameter and a benchmark for regulatory evaluations based on the fact that there is insufficient human in vivo data available, especially the vessel wall mechanical properties during the healing/remodeling phase. Second, once the Mg alloy stent being degraded, the void space will be filled by the regenerated blood vessel tissues. The degradation of the Mg alloy stent should be 100% completed with no residues, and the degradation products (e.g., ions and hydrogen) will be helpful for the tissue reconstruction of the blood vessel. Toward this target, some future research perspectives are also discussed. PMID:27698548

Bone Marrow Blood Vessel Ossification and “Microvascular Dead Space” in Rat and Human Long Bone

Science.gov (United States)

Prisby, Rhonda D.

2014-01-01

Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (4–6 mon; n=8) and old (22–24 mon; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldner’s Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via µCT to quantify microvascular ossification. Bone marrow blood vessels from rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and “normal” vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (p necrosis. The progression of bone microvascular ossification may provide the common link associated with age-related changes in bone and bone marrow. The clinical implications may be evident in the difficulties treating bone disease in the elderly. PMID:24680721

Tissue Engineering of Blood Vessels: Functional Requirements, Progress, and Future Challenges.

Science.gov (United States)

Kumar, Vivek A; Brewster, Luke P; Caves, Jeffrey M; Chaikof, Elliot L

2011-09-01

Vascular disease results in the decreased utility and decreased availability of autologus vascular tissue for small diameter (requires combined approaches from biomaterials science, cell biology, and translational medicine to develop feasible solutions with the requisite mechanical support, a non-fouling surface for blood flow, and tissue regeneration. Over the past two decades interest in blood vessel tissue engineering has soared on a global scale, resulting in the first clinical implants of multiple technologies, steady progress with several other systems, and critical lessons-learned. This review will highlight the current inadequacies of autologus and synthetic grafts, the engineering requirements for implantation of tissue-engineered grafts, and the current status of tissue-engineered blood vessel research.

A numerical analysis on the curved bileaflet Mechanical Heart Valve (MHV) : leaflet motion and blood flow in an elastic blood vessel

International Nuclear Information System (INIS)

Bang, Jin Seok; Kim, Chang Nyung; Choi, Choeng Ryul

2005-01-01

In blood flow passing through the Mechanical Heart Valve (MHV) and elastic blood vessel, hemolysis and platelet activation causing thrombus formation can be seen owing to the shear stress in the blood. Also, fracture and deformation of leaflets can be observed depending on the shape and material properties of the leaflets which is opened and closed in a cycle. Hence, comprehensive study is needed on the hemodynamics which is associated with the motion of leaflet and elastic blood vessel in terms of fluid-structure interaction. In this paper, a numerical analysis has been performed for a three-dimensional pulsatile blood flow associated with the elastic blood vessel and curved bileaflet for multiple cycles in light of fluid-structure interaction. From this analysis fluttering phenomenon and rebound of the leaflet have been observed and recirculation and regurgitation have been found in the flow fields of the blood. Also, the pressure distribution and the radial displacement of the elastic blood vessel have been obtained. The motion of the leaflet and flow fields of the blood have shown similar tendency compared with the previous experiments carried out in other studies. The present study can contribute to the design methodology for the curved bileaflet mechanical heart valve. Furthermore, the proposed fluid-structure interaction method will be effectively used in various fields where the interaction between fluid flow and structure are involved

Proteomic profiling of tissue-engineered blood vessel walls constructed by adipose-derived stem cells.

Science.gov (United States)

Wang, Chen; Guo, Fangfang; Zhou, Heng; Zhang, Yun; Xiao, Zhigang; Cui, Lei

2013-02-01

Adipose-derived stem cells (ASCs) can differentiate into smooth muscle cells and have been engineered into elastic small diameter blood vessel walls in vitro. However, the mechanisms involved in the development of three-dimensional (3D) vascular tissue remain poorly understood. The present study analyzed protein expression profiles of engineered blood vessel walls constructed by human ASCs using methods of two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS). These results were compared to normal arterial walls. A total of 1701±15 and 1265±26 protein spots from normal and engineered blood vessel wall extractions were detected by 2DE, respectively. A total of 20 spots with at least 2.0-fold changes in expression were identified, and 38 differently expressed proteins were identified by 2D electrophoresis and ion trap MS. These proteins were classified into seven functional categories: cellular organization, energy, signaling pathway, enzyme, anchored protein, cell apoptosis/defense, and others. These results demonstrated that 2DE, followed by ion trap MS, could be successfully utilized to characterize the proteome of vascular tissue, including tissue-engineered vessels. The method could also be employed to achieve a better understanding of differentiated smooth muscle protein expression in vitro. These results provide a basis for comparative studies of protein expression in vascular smooth muscles of different origin and could provide a better understanding of the mechanisms of action needed for constructing blood vessels that exhibit properties consistent with normal blood vessels.

Sustained Angiopoietin-2 Expression Disrupts Vessel Formation and Inhibits Glioma Growth

Directory of Open Access Journals (Sweden)

Ok-Hee Lee

2006-05-01

Full Text Available Systematic analyses of the expression of angiogenic regulators in cancer models should yield useful information for the development of novel therapies for malignant gliomas. In this study, we analyzed tumor growth, vascularization, and angiopoietin-2 (Ang2 expression during the development of U-87 MG xenografts. We found that tumoral angiogenesis in this model follows a multistage process characterized by avascular, prolific peripheral angiogenesis, and late vascular phases. On day 4, we observed an area of central necrosis, a peripheral ring of Ang2-positive glioma cells, and reactive Ang2-positive vascular structures in the tumor/brain interface. When the tumor had developed a vascular network, Ang2 was expressed only in peripheral vascular structures. Because Ang2 expression was downmodulated in the late stages of development, probably to maintain a stable tumoral vasculature, we next studied whether sustained Ang2 expression might impair vascular development and, ultimately, tumor growth. Ang2 prevented the formation of capillary-like structures and impaired angiogenesis in a chorioallantoic membrane chicken model. Finally, we tested the effect of sustained Ang2 expression on U-87 MG xenograff development. Ang2 significantly prolonged the survival of intracranial U-87 MG tumor-bearing animals. Examination of Ang2treated xenograffs revealed areas of tumor necrosis and vascular damage. We therefore conclude that deregulated Ang2 expression during gliomagenesis hindered successful angiogenesis and that therapies that sustain Ang2 expression might be effective against malignant gliomas.

Terahertz reflectometry imaging for low and high grade gliomas

Science.gov (United States)

Ji, Young Bin; Oh, Seung Jae; Kang, Seok-Gu; Heo, Jung; Kim, Sang-Hoon; Choi, Yuna; Song, Seungri; Son, Hye Young; Kim, Se Hoon; Lee, Ji Hyun; Haam, Seung Joo; Huh, Yong Min; Chang, Jong Hee; Joo, Chulmin; Suh, Jin-Suck

2016-01-01

Gross total resection (GTR) of glioma is critical for improving the survival rate of glioma patients. One of the greatest challenges for achieving GTR is the difficulty in discriminating low grade tumor or peritumor regions that have an intact blood brain barrier (BBB) from normal brain tissues and delineating glioma margins during surgery. Here we present a highly sensitive, label-free terahertz reflectometry imaging (TRI) that overcomes current key limitations for intraoperative detection of World Health Organization (WHO) grade II (low grade), and grade III and IV (high grade) gliomas. We demonstrate that TRI provides tumor discrimination and delineation of tumor margins in brain tissues with high sensitivity on the basis of Hematoxylin and eosin (H&E) stained image. TRI may help neurosurgeons to remove gliomas completely by providing visualization of tumor margins in WHO grade II, III, and IV gliomas without contrast agents, and hence, improve patient outcomes. PMID:27782153

Selective uptake of boronophenylalanine by glioma stem/progenitor cells

International Nuclear Information System (INIS)

Sun, Ting; Zhou, Youxin; Xie, Xueshun; Chen, Guilin; Li, Bin; Wei, Yongxin; Chen, Jinming; Huang, Qiang; Du, Ziwei

2012-01-01

The success of boron neutron capture therapy (BNCT) depends on the amount of boron in cells and the tumor/blood and tumor/(normal tissue) boron concentration ratios. For the first time, measurements of boron uptake in both stem/progenitor and differentiated glioma cells were performed along with measurements of boron biodistribution in suitable animal models. In glioma stem/progenitor cells, the selective accumulation of boronophenylalanine (BPA) was lower, and retention of boron after BPA removal was longer than in differentiated glioma cells in vitro. However, boron biodistribution was not statistically significantly different in mice with xenografts. - Highlights: ► Uptake of BPA was analyzed in stem/progenitor and differentiated glioma cells. ► Selective accumulation of BPA was lower in glioma stem/progenitor cells. ► Retention of boron after BPA removal was longer in glioma stem/progenitor cells. ► Boron biodistribution was not statistically different in mice with xenografts.

Dynamic glucose enhanced (DGE) MRI for combined imaging of blood-brain barrier break down and increased blood volume in brain cancer.

Science.gov (United States)

Xu, Xiang; Chan, Kannie W Y; Knutsson, Linda; Artemov, Dmitri; Xu, Jiadi; Liu, Guanshu; Kato, Yoshinori; Lal, Bachchu; Laterra, John; McMahon, Michael T; van Zijl, Peter C M

2015-12-01

Recently, natural d-glucose was suggested as a potential biodegradable contrast agent. The feasibility of using d-glucose for dynamic perfusion imaging was explored to detect malignant brain tumors based on blood brain barrier breakdown. Mice were inoculated orthotopically with human U87-EGFRvIII glioma cells. Time-resolved glucose signal changes were detected using chemical exchange saturation transfer (glucoCEST) MRI. Dynamic glucose enhanced (DGE) MRI was used to measure tissue response to an intravenous bolus of d-glucose. DGE images of mouse brains bearing human glioma showed two times higher and persistent changes in tumor compared with contralateral brain. Area-under-curve (AUC) analysis of DGE delineated blood vessels and tumor and had contrast comparable to the AUC determined using dynamic contrast enhanced (DCE) MRI with GdDTPA, both showing a significantly higher AUC in tumor than in brain (P blood volume and permeability with respect to normal brain. We expect DGE will provide a low-risk and less expensive alternative to DCE MRI for imaging cancer in vulnerable populations, such as children and patients with renal impairment. © 2015 Wiley Periodicals, Inc.

A Computational Model Predicting Disruption of Blood Vessel Development

Science.gov (United States)

Vascular development is a complex process regulated by dynamic biological networks that vary in topology and state across different tissues and developmental stages. Signals regulating de novo blood vessel formation (vasculogenesis) and remodeling (angiogenesis) come from a varie...

Classic beta-amyloid deposits cluster around large diameter blood vessels rather than capillaries in sporadic Alzheimer's disease.

Science.gov (United States)

Armstrong, Richard A

2006-11-01

Various hypotheses could explain the relationship between beta-amyloid (Abeta) deposition and the vasculature in Alzheimer's disease (AD). Amyloid deposition may reduce capillary density, affect endothelial cells of blood vessels, result in diffusion from blood vessels, or interfere with the perivascular clearance mechanism. Hence, the spatial pattern of the classic ('cored') type of Abeta deposit was studied in the upper laminae (I,II/III) of the superior frontal gyrus in nine cases of sporadic AD (SAD). Sections were immunostained with antibodies against Abeta and with collagen IV to study the relationships between the spatial distribution of the classic deposits and the blood vessel profiles. Both the classic deposits and blood vessel profiles were distributed in clusters. In all cases, there was a positive spatial correlation between the clusters of the classic deposits and the larger diameter (>10 microm) blood vessel profiles and especially the vertically penetrating arterioles. In only 1 case, was there a significant spatial correlation between the clusters of the classic deposits and the smaller diameter (upper laminae of the frontal cortex. This aggregation could result from diffusion of proteins from blood vessels or from overloading the system of perivascular clearance from the brain.

Optics based signal processing methods for intraoperative blood vessel detection and quantification in real time (Conference Presentation)

Science.gov (United States)

Chaturvedi, Amal; Shukair, Shetha A.; Le Rolland, Paul; Vijayvergia, Mayank; Subramanian, Hariharan; Gunn, Jonathan W.

2016-03-01

Minimally invasive operations require surgeons to make difficult cuts to blood vessels and other tissues with impaired tactile and visual feedback. This leads to inadvertent cuts to blood vessels hidden beneath tissue, causing serious health risks to patients and a non-reimbursable financial burden to hospitals. Intraoperative imaging technologies have been developed, but these expensive systems can be cumbersome and provide only a high-level view of blood vessel networks. In this research, we propose a lean reflectance-based system, comprised of a dual wavelength LED, photodiode, and novel signal processing algorithms for rapid vessel characterization. Since this system takes advantage of the inherent pulsatile light absorption characteristics of blood vessels, no contrast agent is required for its ability to detect the presence of a blood vessel buried deep inside any tissue type (up to a cm) in real time. Once a vessel is detected, the system is able to estimate the distance of the vessel from the probe and the diameter size of the vessel (with a resolution of ~2mm), as well as delineate the type of tissue surrounding the vessel. The system is low-cost, functions in real-time, and could be mounted on already existing surgical tools, such as Kittner dissectors or laparoscopic suction irrigation cannulae. Having been successfully validated ex vivo, this technology will next be tested in a live porcine study and eventually in clinical trials.

Estimation of vessel diameter and blood flow dynamics from laser speckle images

DEFF Research Database (Denmark)

Postnov, Dmitry D.; Tuchin, Valery V.; Sosnovtseva, Olga

2016-01-01

Laser speckle imaging is a rapidly developing method to study changes of blood velocity in the vascular networks. However, to assess blood flow and vascular responses it is crucial to measure vessel diameter in addition to blood velocity dynamics. We suggest an algorithm that allows for dynamical...

Facing Contrast-Enhancing Gliomas: Perfusion MRI in Grade III and Grade IV Gliomas according to Tumor Area

Directory of Open Access Journals (Sweden)

Anna Luisa Di Stefano

2014-01-01

Full Text Available Tumoral neoangiogenesis characterizes high grade gliomas. Relative Cerebral Blood Volume (rCBV, calculated with Dynamic Susceptibility Contrast (DSC Perfusion-Weighted Imaging (PWI, allows for the estimation of vascular density over the tumor bed. The aim of the study was to characterize putative tumoral neoangiogenesis via the study of maximal rCBV with a Region of Interest (ROI approach in three tumor areas—the contrast-enhancing area, the nonenhancing tumor, and the high perfusion area on CBV map—in patients affected by contrast-enhancing glioma (grades III and IV. Twenty-one patients were included: 15 were affected by grade IV and 6 by grade III glioma. Maximal rCBV values for each patient were averaged according to glioma grade. Although rCBV from contrast-enhancement and from nonenhancing tumor areas was higher in grade IV glioma than in grade III (5.58 and 2.68; 3.01 and 2.2, resp., the differences were not significant. Instead, rCBV recorded in the high perfusion area on CBV map, independently of tumor compartment, was significantly higher in grade IV glioma than in grade III (7.51 versus 3.78, P=0.036. In conclusion, neoangiogenesis encompasses different tumor compartments and CBV maps appear capable of best characterizing the degree of neovascularization. Facing contrast-enhancing brain tumors, areas of high perfusion on CBV maps should be considered as the reference areas to be targeted for glioma grading.

Efficacy of NGR peptide-modified PEGylated quantum dots for crossing the blood-brain barrier and targeted fluorescence imaging of glioma and tumor vasculature.

Science.gov (United States)

Huang, Ning; Cheng, Si; Zhang, Xiang; Tian, Qi; Pi, Jiangli; Tang, Jun; Huang, Qing; Wang, Feng; Chen, Jin; Xie, Zongyi; Xu, Zhongye; Chen, Weifu; Zheng, Huzhi; Cheng, Yuan

2017-01-01

Delivery of imaging agents to brain glioma is challenging because the blood-brain barrier (BBB) functions as a physiological checkpoint guarding the central nervous system from circulating large molecules. Moreover, the ability of existing probes to target glioma has been insufficient and needs to be improved. In present study, PEG-based long circulation, CdSe/ZnS quantum dots (QDs)-based nanoscale and fluorescence, asparagines-glycine-arginine peptides (NGR)-based specific CD13 recognition were integrated to design and synthesize a novel nanoprobe by conjugating biotinylated NGR peptides to avidin-PEG-coated QDs. Our data showed that the NGR-PEG-QDs were nanoscale with less than 100 nm and were stable in various pH (4.0~8.0). These nanomaterials with non-toxic concentrations could cross the BBB and target CD13-overexpressing glioma and tumor vasculature in vitro and in vivo, contributing to fluorescence imaging of this brain malignancy. These achievements allowed groundbreaking technological advances in targeted fluorescence imaging for the diagnosis and surgical removal of glioma, facilitating potential transformation toward clinical nanomedicine. Copyright © 2016 Elsevier Inc. All rights reserved.

Computational Fluid Dynamics Analysis of Pulsatile Blood Flow Behavior in Modelled Stenosed Vessels with Different Severities

Directory of Open Access Journals (Sweden)

Mohsen Mehrabi

2012-01-01

Full Text Available This study focuses on the behavior of blood flow in the stenosed vessels. Blood is modelled as an incompressible non-Newtonian fluid which is based on the power law viscosity model. A numerical technique based on the finite difference method is developed to simulate the blood flow taking into account the transient periodic behaviour of the blood flow in cardiac cycles. Also, pulsatile blood flow in the stenosed vessel is based on the Womersley model, and fluid flow in the lumen region is governed by the continuity equation and the Navier-Stokes equations. In this study, the stenosis shape is cosine by using Tu and Devil model. Comparing the results obtained from three stenosed vessels with 30%, 50%, and 75% area severity, we find that higher percent-area severity of stenosis leads to higher extrapressure jumps and higher blood speeds around the stenosis site. Also, we observe that the size of the stenosis in stenosed vessels does influence the blood flow. A little change on the cross-sectional value makes vast change on the blood flow rate. This simulation helps the people working in the field of physiological fluid dynamics as well as the medical practitioners.

An Experimental Study to Replace the Thoracic Descending Aorta for Pigs with a Self-Made Sutureless Blood Vessel

Directory of Open Access Journals (Sweden)

Fenglin Song

2014-01-01

Full Text Available To simplify the procedure of blood vessel replacement operation and shorten the vascular anastomosis time, we developed a special artificial blood vessel which can be connected to native blood vessels without suture. The self-made sutureless blood vessel (SMSBV was made from two titanium connectors and a Gore-Tex graft. To investigate blood compatibility and histocompatibility of the SMSBV, we carried thoracic descending aorta replacement using either SMSBV or Gore-Tex, respectively, in pigs. The aortic clamp time and the operative blood loss in the experimental group (using SMSBV were less than those in the control group (using Gore-Tex. The whole blood hematocrit, platelet count, plasma soluble P-selectin, plasma free hemoglobin, and interleukins 2, 6 at each time point were not different significantly between the two groups. Light microscopy and transmission electron microscopy examination showed there were layers of vascular smooth muscle cells and endothelial cells adhered in the inner wall of artificial blood vessel without any signs of thrombosis. Based on the result, we have drawn the conclusion that the application of SMSBV can significantly shorten the vascular anastomosis time, reduce operative blood loss, and show good blood and tissue compatibility.

Amide proton transfer imaging to discriminate between low- and high-grade gliomas: added value to apparent diffusion coefficient and relative cerebral blood volume

Energy Technology Data Exchange (ETDEWEB)

Choi, Yoon Seong; Ahn, Sung Soo; Lee, Seung-Koo [Yonsei University College of Medicine, Department of Radiology and Research Institute of Radiological Science, College of Medicine, Seoul (Korea, Republic of); Chang, Jong Hee; Kang, Seok-Gu [Yonsei University College of Medicine, Department of Neurosurgery, Seoul (Korea, Republic of); Kim, Se Hoon [Yonsei University College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Zhou, Jinyuan [Johns Hopkins University School of Medicine, Division of MRI Research, Department of Radiology, Baltimore, MD (United States)

2017-08-15

To evaluate the added value of amide proton transfer (APT) imaging to the apparent diffusion coefficient (ADC) from diffusion tensor imaging (DTI) and the relative cerebral blood volume (rCBV) from perfusion magnetic resonance imaging (MRI) for discriminating between high- and low-grade gliomas. Forty-six consecutive adult patients with diffuse gliomas who underwent preoperative APT imaging, DTI and perfusion MRI were enrolled. APT signals were compared according to the World Health Organization grade. The diagnostic ability and added value of the APT signal to the ADC and rCBV for discriminating between low- and high-grade gliomas were evaluated using receiver operating characteristic (ROC) analyses and integrated discrimination improvement. The APT signal increased as the glioma grade increased. The discrimination abilities of the APT, ADC and rCBV values were not significantly different. Using both the APT signal and ADC significantly improved discrimination vs. the ADC alone (area under the ROC curve [AUC], 0.888 vs. 0.910; P = 0.007), whereas using both the APT signal and rCBV did not improve discrimination vs. the rCBV alone (AUC, 0.927 vs. 0.923; P = 0.222). APT imaging may be a useful imaging biomarker that adds value to the ADC for discriminating between low- and high-grade gliomas. (orig.)

Continuum mathematical modelling of pathological growth of blood vessels

Science.gov (United States)

Stadnik, N. E.; Dats, E. P.

2018-04-01

The present study is devoted to the mathematical modelling of a human blood vessel pathological growth. The vessels are simulated as the thin-walled circular tube. The boundary value problem of the surface growth of an elastic thin-walled cylinder is solved. The analytical solution is obtained in terms of velocities of stress strain state parameters. The condition of thinness allows us to study finite displacements of cylinder surfaces by means of infinitesimal deformations. The stress-strain state characteristics, which depend on the mechanical parameters of the biological processes, are numerically computed and graphically analysed.

Waves and fluid-solid interaction in stented blood vessels

Science.gov (United States)

Frecentese, S.; Argani, L. P.; Movchan, A. B.; Movchan, N. V.; Carta, G.; Wall, M. L.

2018-01-01

This paper focuses on the modelling of fluid-structure interaction and wave propagation problems in a stented artery. Reflection of waves in blood vessels is well documented in the literature, but it has always been linked to a strong variation in geometry, such as the branching of vessels. The aim of this work is to detect the possibility of wave reflection in a stented artery due to the repetitive pattern of the stents. The investigation of wave propagation and possible blockages under time-harmonic conditions is complemented with numerical simulations in the transient regime.

Effects of the nitric oxide donor JS-K on the blood-tumor barrier and on orthotopic U87 rat gliomas assessed by MRI.

Science.gov (United States)

Weidensteiner, Claudia; Reichardt, Wilfried; Shami, Paul J; Saavedra, Joseph E; Keefer, Larry K; Baumer, Brunhilde; Werres, Anna; Jasinski, Robert; Osterberg, Nadja; Weyerbrock, Astrid

2013-04-01

Nitric oxide (NO) released from NO donors can be cytotoxic in tumor cells and can enhance the transport of drugs into brain tumors by altering blood-tumor barrier permeability. The NO donor JS-K [O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate] releases NO upon enzymatic activation selectively in cells overexpressing glutathione-S-transferases (GSTs) such as gliomas. Thus, JS-K-dependent NO effects - especially on cell viability and vascular permeability - were investigated in U87 glioma cells in vitro and in an orthotopic U87 xenograft model in vivo by magnetic resonance imaging (MRI). In vitro experiments showed dose-dependent antiproliferative and cytotoxic effects in U87 cells. In addition, treatment of U87 cells with JS-K resulted in a dose-dependent activation of soluble guanylate cyclase and intracellular accumulation of cyclic guanosine monophosphate (cGMP) which was irreversibly inhibited by the selective inhibitor of soluble guanylate cyclase ODQ (1H-[1,2,4]oxadiazolo(4,3a)quinoxaline-1-one). Using dynamic contrast enhanced MRI (DCE-MRI) as a minimally invasive technique, we demonstrated for the first time a significant increase in the DCE-MRI read-out initial area under the concentration curve (iAUC60) indicating an acute increase in blood-tumor barrier permeability after i.v. treatment with JS-K. Repeated MR imaging of animals with intracranial U87 gliomas under treatment with JS-K (3.5 μmol/kg JS-K 3×/week) and of untreated controls on day 12 and 19 after tumor inoculation revealed no significant changes in tumor growth, edema formation or tumor perfusion. Immunohistochemical workup of the brains showed a significant antiproliferative effect of JS-K in the gliomas. Taken together, in vitro and in vivo data suggest that JS-K has antiproliferative effects in U87 gliomas and opens the blood-tumor barrier by activation of the NO/cGMP signaling pathway. This might be a novel approach to facilitate entry of therapeutic

Chitosan-alginate 3D scaffolds as a mimic of the glioma tumor microenvironment.

Science.gov (United States)

Kievit, Forrest M; Florczyk, Stephen J; Leung, Matthew C; Veiseh, Omid; Park, James O; Disis, Mary L; Zhang, Miqin

2010-08-01

Despite recent advances in the understanding of its cell biology, glioma remains highly lethal. Development of effective therapies requires a cost-effective in vitro tumor model that more accurately resembles the in vivo tumor microenvironment as standard two-dimensional (2D) tissue culture conditions do so poorly. Here we report on the use of a three-dimensional (3D) chitosan-alginate (CA) scaffold to serve as an extracellular matrix that promotes the conversion of cultured cancer cells to a more malignant in vivo-like phenotype. Human U-87 MG and U-118 MG glioma cells and rat C6 glioma cells were chosen for the study. In vitro tumor cell proliferation and secretion of factors that promote tumor malignancy, including VEGF, MMP-2, fibronectin, and laminin, were assessed. The scaffolds pre-cultured with U-87 MG and C6 cells were then implanted into nude mice to evaluate tumor growth and blood vessel recruitment compared to the standard 2D cell culture and 3D Matrigel matrix xenograft controls. Our results indicate that while the behavior of C6 cells showed minimal differences due to their highly malignant and invasive nature, U-87 MG and U-118 MG cells exhibited notably higher malignancy when cultured in CA scaffolds. CA scaffolds provide a 3D microenvironment for glioma cells that is more representative of the in vivo tumor, thus can serve as a more effective platform for development and study of anticancer therapeutics. This unique CA scaffold platform may offer a valuable alternative strategy to the time-consuming and costly animal studies for a wide variety of experimental designs. Copyright 2010 Elsevier Ltd. All rights reserved.

Automatic segmentation of blood vessels from retinal fundus images ...

Indian Academy of Sciences (India)

The retinal blood vessels were segmented through color space conversion and color channel extraction, image pre-processing, Gabor filtering, image postprocessing, feature construction through application of principal component analysis, k-means clustering and first level classification using Naïve–Bayes classification ...

Fluid Dynamics of Magnetic Nanoparticles in Simulated Blood Vessels

Science.gov (United States)

Blue, Lauren; Sewell, Mary Kathryn; Brazel, Christopher S.

2008-11-01

Magnetic nanoparticles (MNPs) can be used to locally target therapies and offer the benefit of using an AC magnetic field to combine hyperthermia treatment with the triggered release of therapeutic agents. Here, we investigate localization of MNPs in a simulated environment to understand the relationship between magnetic field intensity and bulk fluid dynamics to determine MNP retention in a simulated blood vessel. As MNPs travel through blood vessels, they can be slowed or trapped in a specific area by applying a magnetic field. Magnetic cobalt ferrite nanoparticles were synthesized and labeled with a fluorescent rhodamine tag to visualize patterns in a flow cell, as monitored by a fluorescence microscope. Particle retention was determined as a function of flow rate, concentration, and magnetic field strength. Understanding the relationship between magnetic field intensity, flow behavior and nanoparticle characteristics will aid in the development of therapeutic systems specifically targeted to diseased tissue.

DLC coating of textile blood vessels using PLD

Czech Academy of Sciences Publication Activity Database

Kocourek, Tomáš; Jelínek, Miroslav; Vorlíček, Vladimír; Zemek, Josef; Janča, T.; Žížková, V.; Podlaha, J.; Popov, C.

2008-01-01

Roč. 93, č. 3 (2008), s. 627-632 ISSN 0947-8396 R&D Projects: GA MPO FI-IM2/068; GA ČR GA202/06/0216 Institutional research plan: CEZ:AV0Z10100522 Keywords : blood vessels * PLD * DLC * sp2 * sp3 Subject RIV: BH - Optics, Masers, Lasers Impact factor: 1.884, year: 2008

Application of blood-pool agents in visualization of peripheral vessels

International Nuclear Information System (INIS)

Giovagnoni, A.; Catalano, C.

2007-01-01

Effective arterial imaging is essential in patients with peripheral arterial disease (PAD) in whom a revascularization procedure is planned. Digital subtraction angiography (DSA) has traditionally been regarded as the gold standard for imaging in peripheral arterial disease, but this technique is subject to certain limitations, such as the risks of adverse reactions associated with arterial catheterization and iodinated contrast agents. Contrast-enhanced magnetic resonance angiography is now recommended as an effective and useful imaging technique in peripheral arterial disease, since it offers high enhanced contrast between blood and stationary tissue and fast acquisition times. However, extracellular gadolinium contrast agents rapidly diffuse into the interstitial spaces, and thus are suitable only for first-pass imaging. This limitation can be overcome by the use of blood-pool (intravascular) contrast agents, such as gadofosveset trisodium (Vasovist, Bayer Schering Pharma AG, Berlin, Germany), which are retained within the blood vessels and hence facilitate both first-pass and steady-state imaging with high spatial resolution. Blood-pool agents, therefore, offer improved imaging, particularly of distal vessels, compared with extracellular contrast agents. Examples of first-pass and steady-state imaging with gadofosveset are presented. (orig.)

Ring enhancement in recurrent gliomas

International Nuclear Information System (INIS)

Ogashiwa, Motohide; Takeuchi, Kazuo; Akai, Keiichiro

1981-01-01

The clinical courses,CT scans, and postmortem reports for 6 glioma patients treated by surgery, radiation, and chemotherapy were reviewed. They underwent reoperation and/or retreatment with radiation or chemotherapy for recurrent tumors. CT scans taken at the time of recurrence or about one month prior to death showed ring enhancement of varied size and form after intensive treatment. The cases were examined histologically in correlation with the CT features and divided into two groups based on the pathological findings in the centers surrounded by areas of ring enhancement. The 1st group demonstrated a large necrotic area in the center, and the 2nd group, a cystic tumor. Tumor cells were found to have spread throughout the high-density areas around the necrotic area or cyst. However, gross differentiation between tumor and necrosis was difficult. In addition to an increase in cellularity, all cases demonstrated vascular proliferation, and dilatation of vessels in the sulci or sulci adjacent to gyri invaded by the tumor. The contrast enhancement corresponded well with the vascular proliferation in these areas. It is concluded that vascular proliferation or dilatation of vessels in and around the tumor is an important factor in demonstrating high-density areas in ring enhancement, while a cyst or necrosis in the tumor center is revealed as a low-density area in the CT scan of recurrent gliomas. (author)

Ring enhancement in recurrent gliomas

Energy Technology Data Exchange (ETDEWEB)

Ogashiwa, M; Takeuchi, K; Akai, K [Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine

1981-08-01

The clinical courses,CT scans, and postmortem reports for 6 glioma patients treated by surgery, radiation, and chemotherapy were reviewed. They underwent reoperation and/or retreatment with radiation or chemotherapy for recurrent tumors. CT scans taken at the time of recurrence or about one month prior to death showed ring enhancement of varied size and form after intensive treatment. The cases were examined histologically in correlation with the CT features and divided into two groups based on the pathological findings in the centers surrounded by areas of ring enhancement. The 1st group demonstrated a large necrotic area in the center, and the 2nd group, a cystic tumor. Tumor cells were found to have spread throughout the high-density areas around the necrotic area or cyst. However, gross differentiation between tumor and necrosis was difficult. In addition to an increase in cellularity, all cases demonstrated vascular proliferation, and dilatation of vessels in the sulci or sulci adjacent to gyri invaded by the tumor. The contrast enhancement corresponded well with the vascular proliferation in these areas. It is concluded that vascular proliferation or dilatation of vessels in and around the tumor is an important factor in demonstrating high-density areas in ring enhancement, while a cyst or necrosis in the tumor center is revealed as a low-density area in the CT scan of recurrent gliomas.

Establishment of an animal model of mice with radiation- injured soft tissue blood vessels

International Nuclear Information System (INIS)

Wang Daiyou; Yu Dahai; Wu Jiaxiao; Wei Shanliang; Wen Yuming

2004-01-01

Objective: The aim of this study was to establish an animal model of mice with radiation-injured soft tissue blood vessels. Methods: Forty male mice were irradiated with 30 Gy on the right leg. After the irradiation was finished each of the 40 male mice was tested with angiography, and its muscle tissues on the bilateral legs were examined with vessel staining assay and electron microscopy. Results: The results showed that the number of vessels on the right leg was less than that on the left leg, the microvessel density, average diameter and average sectional area of the right leg were all lower than those of the left, and the configuration and ultra-structure of vessels were also different between both sides of legs. Conclusion: In the study authors successfully established an animal model of mice with radiation-injured soft tissue blood vessels

Association of preoperative levels of selected blood inflammatory markers with prognosis in gliomas

Directory of Open Access Journals (Sweden)

Auezova R

2016-10-01

Full Text Available Raushan Auezova,1 Nurzhan Ryskeldiev,1 Aidos Doskaliyev,1 Yerbol Kuanyshev,1 Berik Zhetpisbaev,1 Nurgul Aldiyarova,1 Natalia Ivanova,2 Serik Akshulakov,1 Lizette Auezova3 1Department of Pathology of the Central Nervous System, National Centre for Neurosurgery, Astana, Kazakhstan; 2Polenov Russian Scientific Research Institute of Neurosurgery (a branch of Federal Almazov North-West Medical Research Centre, Ministry of Health of the Russian Federation, Saint-Petersburg, Russia; 3Bioactive Molecules Research Group, Department of Chemistry and Biochemistry, Faculty of Sciences-II, Lebanese University, Beirut, Lebanon Background: Red cell distribution width (RDW, neutrophil–lymphocyte ratio (NLR, and platelet count (PLT routinely tested as part of the complete blood count are indicative of systemic inflammation. The prognostic significance of NLR and PLT in cancer was demonstrated in many studies while the role of RDW has been hardly investigated. The present study aimed to assess the association of RDW, NLR, and PLT with survival and tumor grade in glioma patients. Methods: Clinical data from 178 patients with primary gliomas treated in a single institution were retrospectively analyzed. Receiver operating characteristic curves for cutoff value determination, Kaplan–Meier survival analysis, various bivariate tests, and univariate and multivariate Cox regression analyses were performed. Results: Patients with high RDW (≥13.95 and NLR (≥4 levels had worse overall survival (OS (Wilcoxon test, P<0.026 and P<0.003, respectively while the effect of thrombocytosis (≥400×109/L on prognosis was not significant. Besides, a strong association between RDW and NLR was found (Spearman’s rho =0.230, P<0.02; χ2=8.887, P<0.03; Mann–Whitney U-test, P<0.017. Moreover, RDW and NLR were significantly associated with tumor grade. In univariate Cox analysis, elevated NLR (hazard ratio, HR 1.385; confidence interval, CI 1.020–1.881, P<0.037, older age

Mouse lung contains endothelial progenitors with high capacity to form blood and lymphatic vessels

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Barleon Bernhard

2010-07-01

Full Text Available Abstract Background Postnatal endothelial progenitor cells (EPCs have been successfully isolated from whole bone marrow, blood and the walls of conduit vessels. They can, therefore, be classified into circulating and resident progenitor cells. The differentiation capacity of resident lung endothelial progenitor cells from mouse has not been evaluated. Results In an attempt to isolate differentiated mature endothelial cells from mouse lung we found that the lung contains EPCs with a high vasculogenic capacity and capability of de novo vasculogenesis for blood and lymph vessels. Mouse lung microvascular endothelial cells (MLMVECs were isolated by selection of CD31+ cells. Whereas the majority of the CD31+ cells did not divide, some scattered cells started to proliferate giving rise to large colonies (> 3000 cells/colony. These highly dividing cells possess the capacity to integrate into various types of vessels including blood and lymph vessels unveiling the existence of local microvascular endothelial progenitor cells (LMEPCs in adult mouse lung. EPCs could be amplified > passage 30 and still expressed panendothelial markers as well as the progenitor cell antigens, but not antigens for immune cells and hematopoietic stem cells. A high percentage of these cells are also positive for Lyve1, Prox1, podoplanin and VEGFR-3 indicating that a considerabe fraction of the cells are committed to develop lymphatic endothelium. Clonogenic highly proliferating cells from limiting dilution assays were also bipotent. Combined in vitro and in vivo spheroid and matrigel assays revealed that these EPCs exhibit vasculogenic capacity by forming functional blood and lymph vessels. Conclusion The lung contains large numbers of EPCs that display commitment for both types of vessels, suggesting that lung blood and lymphatic endothelial cells are derived from a single progenitor cell.

Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy.

Science.gov (United States)

Maurer, Gabriele D; Brucker, Daniel P; Bähr, Oliver; Harter, Patrick N; Hattingen, Elke; Walenta, Stefan; Mueller-Klieser, Wolfgang; Steinbach, Joachim P; Rieger, Johannes

2011-07-26

Even in the presence of oxygen, malignant cells often highly depend on glycolysis for energy generation, a phenomenon known as the Warburg effect. One strategy targeting this metabolic phenotype is glucose restriction by administration of a high-fat, low-carbohydrate (ketogenic) diet. Under these conditions, ketone bodies are generated serving as an important energy source at least for non-transformed cells. To investigate whether a ketogenic diet might selectively impair energy metabolism in tumor cells, we characterized in vitro effects of the principle ketone body 3-hydroxybutyrate in rat hippocampal neurons and five glioma cell lines. In vivo, a non-calorie-restricted ketogenic diet was examined in an orthotopic xenograft glioma mouse model. The ketone body metabolizing enzymes 3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and 2), 3-oxoacid-CoA transferase 1 (OXCT1) and acetyl-CoA acetyltransferase 1 (ACAT1) were expressed at the mRNA and protein level in all glioma cell lines. However, no activation of the hypoxia-inducible factor-1α (HIF-1α) pathway was observed in glioma cells, consistent with the absence of substantial 3-hydroxybutyrate metabolism and subsequent accumulation of succinate. Further, 3-hydroxybutyrate rescued hippocampal neurons from glucose withdrawal-induced cell death but did not protect glioma cell lines. In hypoxia, mRNA expression of OXCT1, ACAT1, BDH1 and 2 was downregulated. In vivo, the ketogenic diet led to a robust increase of blood 3-hydroxybutyrate, but did not alter blood glucose levels or improve survival. In summary, glioma cells are incapable of compensating for glucose restriction by metabolizing ketone bodies in vitro, suggesting a potential disadvantage of tumor cells compared to normal cells under a carbohydrate-restricted ketogenic diet. Further investigations are necessary to identify co-treatment modalities, e.g. glycolysis inhibitors or antiangiogenic agents that efficiently target non-oxidative pathways.

Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy

International Nuclear Information System (INIS)

Maurer, Gabriele D; Brucker, Daniel P; Bähr, Oliver; Harter, Patrick N; Hattingen, Elke; Walenta, Stefan; Mueller-Klieser, Wolfgang; Steinbach, Joachim P; Rieger, Johannes

2011-01-01

Even in the presence of oxygen, malignant cells often highly depend on glycolysis for energy generation, a phenomenon known as the Warburg effect. One strategy targeting this metabolic phenotype is glucose restriction by administration of a high-fat, low-carbohydrate (ketogenic) diet. Under these conditions, ketone bodies are generated serving as an important energy source at least for non-transformed cells. To investigate whether a ketogenic diet might selectively impair energy metabolism in tumor cells, we characterized in vitro effects of the principle ketone body 3-hydroxybutyrate in rat hippocampal neurons and five glioma cell lines. In vivo, a non-calorie-restricted ketogenic diet was examined in an orthotopic xenograft glioma mouse model. The ketone body metabolizing enzymes 3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and 2), 3-oxoacid-CoA transferase 1 (OXCT1) and acetyl-CoA acetyltransferase 1 (ACAT1) were expressed at the mRNA and protein level in all glioma cell lines. However, no activation of the hypoxia-inducible factor-1α (HIF-1α) pathway was observed in glioma cells, consistent with the absence of substantial 3-hydroxybutyrate metabolism and subsequent accumulation of succinate. Further, 3-hydroxybutyrate rescued hippocampal neurons from glucose withdrawal-induced cell death but did not protect glioma cell lines. In hypoxia, mRNA expression of OXCT1, ACAT1, BDH1 and 2 was downregulated. In vivo, the ketogenic diet led to a robust increase of blood 3-hydroxybutyrate, but did not alter blood glucose levels or improve survival. In summary, glioma cells are incapable of compensating for glucose restriction by metabolizing ketone bodies in vitro, suggesting a potential disadvantage of tumor cells compared to normal cells under a carbohydrate-restricted ketogenic diet. Further investigations are necessary to identify co-treatment modalities, e.g. glycolysis inhibitors or antiangiogenic agents that efficiently target non-oxidative pathways

Sensitivity of MRI tumor biomarkers to VEGFR inhibitor therapy in an orthotopic mouse glioma model.

Directory of Open Access Journals (Sweden)

Christian T Farrar

Full Text Available MRI biomarkers of tumor edema, vascular permeability, blood volume, and average vessel caliber are increasingly being employed to assess the efficacy of tumor therapies. However, the dependence of these biomarkers on a number of physiological factors can compromise their sensitivity and complicate the assessment of therapeutic efficacy. Here we examine the response of these MRI tumor biomarkers to cediranib, a potent vascular endothelial growth factor receptor (VEGFR inhibitor, in an orthotopic mouse glioma model. A significant increase in the tumor volume and relative vessel caliber index (rVCI and a slight decrease in the water apparent diffusion coefficient (ADC were observed for both control and cediranib treated animals. This contrasts with a clinical study that observed a significant decrease in tumor rVCI, ADC and volume with cediranib therapy. While the lack of a difference between control and cediranib treated animals in these biomarker responses might suggest that cediranib has no therapeutic benefit, cediranib treated mice had a significantly increased survival. The increased survival benefit of cediranib treated animals is consistent with the significant decrease observed for cediranib treated animals in the relative cerebral blood volume (rCBV, relative microvascular blood volume (rMBV, transverse relaxation time (T2, blood vessel permeability (K(trans, and extravascular-extracellular space (ν(e. The differential response of pre-clinical and clinical tumors to cediranib therapy, along with the lack of a positive response for some biomarkers, indicates the importance of evaluating the whole spectrum of different tumor biomarkers to properly assess the therapeutic response and identify and interpret the therapy-induced changes in the tumor physiology.

The efficiency of laser radiation absorption by hemoglobin and oxyhemoglobin in the skin blood vessels

International Nuclear Information System (INIS)

Asimov, M.; Asimov, R.; Gisbrecht, A.

1999-01-01

The results of the investigation of the efficiency of light absorption by oxyhemoglobin (HbO 2 ) and deoxyhemoglobin (Hb) in cutaneous blood vessels in dependence on the radiation wavelength and the optical properties of the tissue is presented. Using the Kubelka - Munk optical model of the tissue the spectral dependence of the efficiency of laser interaction both on HbO 2 and Hb of blood vessels at different depths of the tissue layer are calculated. The obtained results show that for blood vessels located in tissue up to a depth of 2500 μm the efficiency of laser radiation absorption follows the shape of the Q -absorption bands of HbO 2 and Hb

Simulative study on dose distribution of 103Pd stent in blood-vessel

International Nuclear Information System (INIS)

Yuan Shuyu; Dai Guangfu; Xu Zhiyong; Sun Fuyin; Xu Shuhe; Ma Fengwu

2003-01-01

Objective: To evaluate the dose distribution of 103 Pd stent in the blood-vessel. Methods: Simulative study on dose distribution of endovascular 103 Pd stent was conducted with thermoluminescence dosimeter. The vessel wall was substituted by muscle equivalent material in this simulative study. Results: When radioactivity of the study 103 Pd stent was 9.8 MBq the absorbed dose from the stent surface by muscle equivalent material was 9.8 Gy at 17 d (the half-life period of 103 Pd). The radioactivity of 103 Pd stent surface rapidly attenuated over the radial distance. 80% of the radioactivity at the area that was radially 0.4 mm apart from the stent surface was absorbed by the simulative blood-vessel wall. Conclusion: Endovascular 103 Pd stent does not exert significant injury on the surrounding organs or tissues

3-D segmentation of retinal blood vessels in spectral-domain OCT volumes of the optic nerve head

Science.gov (United States)

Lee, Kyungmoo; Abràmoff, Michael D.; Niemeijer, Meindert; Garvin, Mona K.; Sonka, Milan

2010-03-01

Segmentation of retinal blood vessels can provide important information for detecting and tracking retinal vascular diseases including diabetic retinopathy, arterial hypertension, arteriosclerosis and retinopathy of prematurity (ROP). Many studies on 2-D segmentation of retinal blood vessels from a variety of medical images have been performed. However, 3-D segmentation of retinal blood vessels from spectral-domain optical coherence tomography (OCT) volumes, which is capable of providing geometrically accurate vessel models, to the best of our knowledge, has not been previously studied. The purpose of this study is to develop and evaluate a method that can automatically detect 3-D retinal blood vessels from spectral-domain OCT scans centered on the optic nerve head (ONH). The proposed method utilized a fast multiscale 3-D graph search to segment retinal surfaces as well as a triangular mesh-based 3-D graph search to detect retinal blood vessels. An experiment on 30 ONH-centered OCT scans (15 right eye scans and 15 left eye scans) from 15 subjects was performed, and the mean unsigned error in 3-D of the computer segmentations compared with the independent standard obtained from a retinal specialist was 3.4 +/- 2.5 voxels (0.10 +/- 0.07 mm).

Neutrophil-Mediated Delivery of Therapeutic Nanoparticles across Blood Vessel Barrier for Treatment of Inflammation and Infection.

Science.gov (United States)

Chu, Dafeng; Gao, Jin; Wang, Zhenjia

2015-12-22

Endothelial cells form a monolayer in lumen of blood vessels presenting a great barrier for delivery of therapeutic nanoparticles (NPs) into extravascular tissues where most diseases occur, such as inflammation disorders and infection. Here, we report a strategy for delivering therapeutic NPs across this blood vessel barrier by nanoparticle in situ hitchhiking activated neutrophils. Using intravital microscopy of TNF-α-induced inflammation of mouse cremaster venules and a mouse model of acute lung inflammation, we demonstrated that intravenously (iv) infused NPs made from denatured bovine serum albumin (BSA) were specifically internalized by activated neutrophils, and subsequently, the neutrophils containing NPs migrated across blood vessels into inflammatory tissues. When neutrophils were depleted using anti-Gr-1 in a mouse, the transport of albumin NPs across blood vessel walls was robustly abolished. Furthermore, it was found that albumin nanoparticle internalization did not affect neutrophil mobility and functions. Administration of drug-loaded albumin NPs markedly mitigated the lung inflammation induced by LPS (lipopolysaccharide) or infection by Pseudomonas aeruginosa. These results demonstrate the use of an albumin nanoparticle platform for in situ targeting of activated neutrophils for delivery of therapeutics across the blood vessel barriers into diseased sites. This study demonstrates our ability to hijack neutrophils to deliver nanoparticles to targeted diseased sites.

"Sausage-string" appearance of arteries and arterioles can be caused by an instability of the blood vessel wall

DEFF Research Database (Denmark)

Jacobsen, Jens Christian Brings; Beierholm, Ulrik; Mikkelsen, Rene

2002-01-01

Vascular damage induced by acute hypertension is preceded by a peculiar pattern where blood vessels show alternating regions of constrictions and dilations ("sausages on a string"). The pattern occurs in the smaller blood vessels, and it plays a central role in causing the vascular damage. A rela...... phenomenon. Experimental data suggest that the structural changes induced by the instability may cause secondary damage to the wall of small arteries and arterioles in the form of endothelial hyperpermeability followed by local fibrinoid necrosis of the vascular wall.......Vascular damage induced by acute hypertension is preceded by a peculiar pattern where blood vessels show alternating regions of constrictions and dilations ("sausages on a string"). The pattern occurs in the smaller blood vessels, and it plays a central role in causing the vascular damage....... A related vascular pattern has been observed in larger vessels from several organs during angiography. In the larger vessels the occurrence of the pattern does not appear to be related to acute hypertension. A unifying feature between the phenomenon in large and small vessels seems to be an increase...

MACROMICROSCOPIC AND ULTRAMICROSCOPIC CHARACTERISTICS OF THE HART AND ITS BLOOD VESSELS IN MICE EHRLICHIOSIS INFECTION

Directory of Open Access Journals (Sweden)

Pokhil S. I.

2013-12-01

Full Text Available The macromicroscopic, ultramicroscopic studying change’s in the hart and its blood vessels in unlinear immunocomprometive laboratory male and female mice with the experimental ehrlichiosis is presented in this article. The cardiac destructive and degenerative changes,cardiomyopathy, cardiosclerosis had been established inexperimental animal group’s. The blood vessels endothelial lieyr disorganization, stasis, thrombosis has been noted.

An experimental system for the study of ultrasound exposure of isolated blood vessels

NARCIS (Netherlands)

Tokarczyk, Anna; Rivens, Ian; van Bavel, E.; Symonds-Tayler, Richard; ter Haar, Gail

2013-01-01

An experimental system designed for the study of the effects of diagnostic or therapeutic ultrasound exposure on isolated blood vessels in the presence or absence of intraluminal contrast agent is described. The system comprised several components. A microscope was used to monitor vessel size (and

Theoretical evaluations of magnetic nanoparticle-enhanced heating on tumor embedded with large blood vessels during hyperthermia

International Nuclear Information System (INIS)

Wang, Q.; Deng, Z. S.; Liu, J.

2012-01-01

The large blood vessels surrounding the tumor would significantly result in heat sink, and thus seriously limit the thermal ablative area during tumor hyperthermia. Magnetic nanoparticle (MNP) was recently identified as an important heating enhancer to improve the treatment efficiency. It will not only help to absorb more energy under the irradiation of external magnetic field, but also can block the blood flow and subsequently weaken the heat sink effect of large vessels. In this study, these two critical factors, reserved to be undisclosed before in theory, were comprehensively investigated through three-dimensional numerical simulation. The results suggested that concerning the contribution to temperature increase in the tissues surrounding large vessel, the factor of blood flow blocking is more effective than that of energy absorption. Therefore, selective loading of MNPs to the target sites is expected to serve as a promising method to perform successful hyperthermia treatment for tumor tissues embedded with large blood vessels.

Theoretical evaluations of magnetic nanoparticle-enhanced heating on tumor embedded with large blood vessels during hyperthermia

Energy Technology Data Exchange (ETDEWEB)

Wang, Q. [Tsinghua University, Department of Biomedical Engineering, School of Medicine (China); Deng, Z. S. [Chinese Academy of Sciences, Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry (China); Liu, J., E-mail: jliubme@tsinghua.edu.cn [Tsinghua University, Department of Biomedical Engineering, School of Medicine (China)

2012-07-15

The large blood vessels surrounding the tumor would significantly result in heat sink, and thus seriously limit the thermal ablative area during tumor hyperthermia. Magnetic nanoparticle (MNP) was recently identified as an important heating enhancer to improve the treatment efficiency. It will not only help to absorb more energy under the irradiation of external magnetic field, but also can block the blood flow and subsequently weaken the heat sink effect of large vessels. In this study, these two critical factors, reserved to be undisclosed before in theory, were comprehensively investigated through three-dimensional numerical simulation. The results suggested that concerning the contribution to temperature increase in the tissues surrounding large vessel, the factor of blood flow blocking is more effective than that of energy absorption. Therefore, selective loading of MNPs to the target sites is expected to serve as a promising method to perform successful hyperthermia treatment for tumor tissues embedded with large blood vessels.

Modification method to reduce the impact of blood vessel on noncontact discrimination of human blood based on ;M+N; theory

Science.gov (United States)

Zhang, Linna; Ding, Hongyan; Lin, Ling; Wang, Yimin; Guo, Xin

2018-01-01

Noncontact discriminating human blood is significantly crucial for import-export ports and inspection and quarantine departments. We had already demonstrated that visible diffuse reflectance spectroscopy combining PLS-DA method can successfully realize noncontact human blood discrimination. However, the circulated blood vessels may be produced with different materials. The use of various kinds of blood tubes may have a negative effect on the discrimination, based on ;M+N; theory (Li et al., 2016). In this research, we explored the impact of different material of blood vessels, such as glass tube and plastic tube, on the prediction ability of the discrimination model. Furthermore, we searched for the modification method to reduce the influence from the blood tubes. Our work indicated that generalized diffuse reflectance method can greatly improve the discrimination accuracy. This research can greatly facilitate the application of noncontact discrimination method based on visible and near-infrared diffuse reflectance spectroscopy.

The immunohistochemical expression of calcitonin receptor-like receptor (CRLR) in human gliomas.

Science.gov (United States)

Benes, L; Kappus, C; McGregor, G P; Bertalanffy, H; Mennel, H D; Hagner, S

2004-02-01

Gliomas are the most common primary tumours of the central nervous system and exhibit rapid growth that is associated with neovascularisation. Adrenomedullin is an important tumour survival factor in human carcinogenesis. It has growth promoting effects on gliomas, and blockade of its actions has been experimentally shown to reduce the growth of glioma tissues and cell lines. There is some evidence that the calcitonin receptor-like receptor (CRLR) mediates the tumorigenic actions of adrenomedullin. To determine whether CRLR is expressed in human gliomas and the probable cellular targets of adrenomedullin. Biopsies from 95 human gliomas of varying grade were processed for immunohistochemical analysis using a previously developed and characterised antibody to CRLR. All tumour specimens were positive for CRLR. As previously found in normal peripheral tissues, CRLR immunostaining was particularly intense in the endothelial cells. This was evident in all the various vascular conformations that were observed, and which are typical of gliomas. In addition, clear immunostaining of tumour cells with astrocyte morphology was observed. These were preferentially localised around vessels. This study has shown for the first time that the CRLR protein is present in human glioma tissue. The expression of the receptor in endothelial cells and in astrocytic tumour cells is consistent with the evidence that its endogenous ligand, adrenomedullin, may influence glioma growth by means of both direct mitogenic and indirect angiogenic effects. CRLR may be a valuable target for effective therapeutic intervention in these malignant tumours.

Segmentation of retinal blood vessels using artificial neural networks for early detection of diabetic retinopathy

Science.gov (United States)

Mann, Kulwinder S.; Kaur, Sukhpreet

2017-06-01

There are various eye diseases in the patients suffering from the diabetes which includes Diabetic Retinopathy, Glaucoma, Hypertension etc. These all are the most common sight threatening eye diseases due to the changes in the blood vessel structure. The proposed method using supervised methods concluded that the segmentation of the retinal blood vessels can be performed accurately using neural networks training. It uses features which include Gray level features; Moment Invariant based features, Gabor filtering, Intensity feature, Vesselness feature for feature vector computation. Then the feature vector is calculated using only the prominent features.

Synergistic effect of cisplatin and synchrotron irradiation on F98 gliomas growing in nude mice

Energy Technology Data Exchange (ETDEWEB)

Ricard, Clement; Fernandez, Manuel [Grenoble Institut des Neurosciences, Grenoble (France); Université Joseph Fourier, Grenoble (France); Requardt, Herwig [European Synchrotron Radiation Facility, Grenoble (France); Wion, Didier [Grenoble Institut des Neurosciences, Grenoble (France); Université Joseph Fourier, Grenoble (France); Vial, Jean-Claude [Université Joseph Fourier, Grenoble (France); Laboratoire Interdisciplinaire de Physique, St Martin d’Hères (France); Segebarth, Christoph; Sanden, Boudewijn van der, E-mail: boudewijn.vandersanden@ujf-grenoble.fr [Grenoble Institut des Neurosciences, Grenoble (France); Université Joseph Fourier, Grenoble (France)

2013-09-01

Synchrotron photoactivation therapy of cisplatin relies on a synergistic effect of synchrotron X-rays and platinum and leads to tumor-cell-killing effects and reduction of the tumor blood perfusion. Among brain tumors, glioblastoma multiforme appears as one of the most aggressive forms of cancer with poor prognosis and no curative treatment available. Recently, a new kind of radio-chemotherapy has been developed using synchrotron irradiation for the photoactivation of molecules with high-Z elements such as cisplatin (PAT-Plat). This protocol showed a cure of 33% of rats bearing the F98 glioma but the efficiency of the treatment was only measured in terms of overall survival. Here, characterization of the effects of the PAT-Plat on tumor volume and tumor blood perfusion are proposed. Changes in these parameters may predict the overall survival. Firstly, changes in tumor growth of the F98 glioma implanted in the hindlimb of nude mice after the PAT-Plat treatment and its different modalities have been characterized. Secondly, the effects of the treatment on tumor blood perfusion have been observed by intravital two-photon microscopy. Cisplatin alone had no detectable effect on the tumor volume. A reduction of tumor growth was measured after a 15 Gy synchrotron irradiation, but the whole therapy (15 Gy irradiation + cisplatin) showed the largest decrease in tumor growth, indicating a synergistic effect of both synchrotron irradiation and cisplatin treatment. A high number of unperfused vessels (52%) were observed in the peritumoral area in comparison with untreated controls. In the PAT-Plat protocol the transient tumor growth reduction may be due to synergistic interactions of tumor-cell-killing effects and reduction of the tumor blood perfusion.

A three-temperature model of selective photothermolysis for laser treatment of port wine stain containing large malformed blood vessels

International Nuclear Information System (INIS)

Li, D.; Wang, G.X.; He, Y.L.; Wu, W.J.; Chen, B.

2014-01-01

As congenital vascular malformations, port wine stain (PWS) is composed of ectatic venular capillary blood vessels buried within healthy dermis. In clinic, pulsed dye laser (PDL) in visible band (e.g. 585 nm) together with cryogen spray cooling (CSC) have become the golden standard for treatment of PWS. However, due to the limited energy deposition of the PDL in blood, large blood vessels are likely to survive from the laser irradiation. As a result, complete clearance of the lesions is rarely achieved. Assuming the local thermal non-equilibrium in skin tissue during the laser surgery, a three-temperature model is proposed to treat the PWS tissue as a porous media composed of a non-absorbing dermal matrix buried with the blood as well as the large malformed blood vessels. Three energy equations are constructed and solved coupling for the temperature of the blood in average-sized PWS vessels, non-absorbing dermal tissues and large malformed blood vessels, respectively. Subsequently, the thermal responses of human skin to visible (585 nm) and near-infrared (1064 nm) laser irradiations with various pulse durations in conjunction with cryogen spray cooling are investigated by the new model, and Arrhenius integral is used to analyze the thermal damage. The simulations show that the short pulse duration of 1.5 ms results in a higher selective heating of blood over epidermis, which will lead to a desired clinic outcome than the longer pulse duration. Due to a much deeper light penetration depth, laser irradiation with 1064 nm in wavelength is superior to that with 585 nm in treating patients with cutaneous hyper-vascular malformation. Complete coagulations are predicted in large-sized and deeply extending blood vessels by 1064 nm laser. - Highlights: •A three-temperature model is proposed for the laser treatment of port wine stain (PWS). •Average sized and large malformed blood vessels in porous medium (tissue) are considered. •Thermal responses of PWS to

Retinal blood vessel extraction using tunable bandpass filter and fuzzy conditional entropy.

Science.gov (United States)

Sil Kar, Sudeshna; Maity, Santi P

2016-09-01

Extraction of blood vessels on retinal images plays a significant role for screening of different opthalmologic diseases. However, accurate extraction of the entire and individual type of vessel silhouette from the noisy images with poorly illuminated background is a complicated task. To this aim, an integrated system design platform is suggested in this work for vessel extraction using a sequential bandpass filter followed by fuzzy conditional entropy maximization on matched filter response. At first noise is eliminated from the image under consideration through curvelet based denoising. To include the fine details and the relatively less thick vessel structures, the image is passed through a bank of sequential bandpass filter structure optimized for contrast enhancement. Fuzzy conditional entropy on matched filter response is then maximized to find the set of multiple optimal thresholds to extract the different types of vessel silhouettes from the background. Differential Evolution algorithm is used to determine the optimal gain in bandpass filter and the combination of the fuzzy parameters. Using the multiple thresholds, retinal image is classified as the thick, the medium and the thin vessels including neovascularization. Performance evaluated on different publicly available retinal image databases shows that the proposed method is very efficient in identifying the diverse types of vessels. Proposed method is also efficient in extracting the abnormal and the thin blood vessels in pathological retinal images. The average values of true positive rate, false positive rate and accuracy offered by the method is 76.32%, 1.99% and 96.28%, respectively for the DRIVE database and 72.82%, 2.6% and 96.16%, respectively for the STARE database. Simulation results demonstrate that the proposed method outperforms the existing methods in detecting the various types of vessels and the neovascularization structures. The combination of curvelet transform and tunable bandpass

Dynamic Glucose Enhanced (DGE) MRI for Combined Imaging of Blood Brain Barrier Break Down and Increased Blood Volume in Brain Cancer

Science.gov (United States)

Xu, Xiang; Chan, Kannie WY; Knutsson, Linda; Artemov, Dmitri; Xu, Jiadi; Liu, Guanshu; Kato, Yoshinori; Lal, Bachchu; Laterra, John; McMahon, Michael T.; van Zijl, Peter C.M.

2015-01-01

Purpose Recently, natural d-glucose was suggested as a potential biodegradable contrast agent. The feasibility of using d-glucose for dynamic perfusion imaging was explored to detect malignant brain tumors based on blood brain barrier breakdown. Methods Mice were inoculated orthotopically with human U87-EGFRvIII glioma cells. Time-resolved glucose signal changes were detected using chemical exchange saturation transfer (glucoCEST) MRI. Dynamic glucose enhanced (DGE) MRI was used to measure tissue response to an intravenous bolus of d-glucose. Results DGE images of mouse brains bearing human glioma showed two times higher and persistent changes in tumor compared to contralateral brain. Area-under-curve (AUC) analysis of DGE delineated blood vessels and tumor and had contrast comparable to the AUC determined using dynamic contrast enhanced (DCE) MRI with GdDTPA, both showing a significantly higher AUC in tumor than in brain (pblood volume and permeability with respect to normal brain. We expect DGE will provide a low-risk and less expensive alternative to DCE MRI for imaging cancer in vulnerable populations, such as children and patients with renal impairment. PMID:26404120

Blood vessel growth blocker may treat AIDS-related Kaposi’s sarcoma

Science.gov (United States)

Patients with an AIDS-associated cancer, Kaposi's sarcoma (KS), showed improvement after receiving the combination of bevacizumab, a cancer drug that blocks the growth of new blood vessels, and highly active antiretroviral therapy (HAART).

Fine structural alterations of the blood vessels in the delayed radionecrosis of the human brain and its pathogenesis

Energy Technology Data Exchange (ETDEWEB)

Matsumura, H [Nagasaki Univ. (Japan). School of Medicine

1981-05-01

The blood vessels in the delayed radionecrosis of the human brain were studied under light and electron microscopes. Microscopically, the blood vessels demonstrated characteristic findings such as fibrinoid necrosis, hyalinized thickened vessels, perivascular fibrosis and thrombosed vessels. Electron microscopy revealed the formation of fenestrae, separation of endothelial cells, increased pinocytotic vesicles as well as the initial thrombus formation. Our results strongly verified that vascular alterations are primary in the pathogenesis of radionecrosis whereas the parenchymal changes are secondary.

Molecular imaging of tumor blood vessels in prostate cancer.

Science.gov (United States)

Tilki, Derya; Seitz, Michael; Singer, Bernhard B; Irmak, Ster; Stief, Christian G; Reich, Oliver; Ergün, Süleyman

2009-05-01

In the past three decades many efforts have been undertaken to understand the mechanisms of tumor angiogenesis. The introduction of anti-angiogenic drugs in tumor therapy during the last few years necessitates the establishment of new techniques enabling molecular imaging of tumor vascular remodelling. The determination of tumor size as commonly used is not appropriate since the extended necrosis under anti-angiogenic therapy does not necessarily result in the reduction of tumor diameter. The basis for the molecular imaging of tumor blood vessels is the remodelling of the tumor vessels under anti-angiogenic therapy which obviously occurs at an early stage and seems to be a convincing parameter. Beside the enormous progress in this field during the last few years the resolution is still not high enough to evaluate the remodelling of the micro tumor vessels. New imaging approaches combining specific molecular markers for tumor vessels with the different imaging techniques are needed to overcome this issue as exemplarily discussed for prostate cancer in this review. Molecular contrast agents targeting the vasculature will allow clinicians the visualization of vascular remodelling processes taking place under anti-angiogenic therapy and improve tumor diagnosis and follow-up.

Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy

Directory of Open Access Journals (Sweden)

Mueller-Klieser Wolfgang

2011-07-01

Full Text Available Abstract Background Even in the presence of oxygen, malignant cells often highly depend on glycolysis for energy generation, a phenomenon known as the Warburg effect. One strategy targeting this metabolic phenotype is glucose restriction by administration of a high-fat, low-carbohydrate (ketogenic diet. Under these conditions, ketone bodies are generated serving as an important energy source at least for non-transformed cells. Methods To investigate whether a ketogenic diet might selectively impair energy metabolism in tumor cells, we characterized in vitro effects of the principle ketone body 3-hydroxybutyrate in rat hippocampal neurons and five glioma cell lines. In vivo, a non-calorie-restricted ketogenic diet was examined in an orthotopic xenograft glioma mouse model. Results The ketone body metabolizing enzymes 3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and 2, 3-oxoacid-CoA transferase 1 (OXCT1 and acetyl-CoA acetyltransferase 1 (ACAT1 were expressed at the mRNA and protein level in all glioma cell lines. However, no activation of the hypoxia-inducible factor-1α (HIF-1α pathway was observed in glioma cells, consistent with the absence of substantial 3-hydroxybutyrate metabolism and subsequent accumulation of succinate. Further, 3-hydroxybutyrate rescued hippocampal neurons from glucose withdrawal-induced cell death but did not protect glioma cell lines. In hypoxia, mRNA expression of OXCT1, ACAT1, BDH1 and 2 was downregulated. In vivo, the ketogenic diet led to a robust increase of blood 3-hydroxybutyrate, but did not alter blood glucose levels or improve survival. Conclusion In summary, glioma cells are incapable of compensating for glucose restriction by metabolizing ketone bodies in vitro, suggesting a potential disadvantage of tumor cells compared to normal cells under a carbohydrate-restricted ketogenic diet. Further investigations are necessary to identify co-treatment modalities, e.g. glycolysis inhibitors or antiangiogenic

Aminopeptidase A is a functional target in angiogenic blood vessels.

NARCIS (Netherlands)

Marchio, S.; Lahdenranta, J.; Schlingemann, R.O.; Valdembri, D.; Wesseling, P.; Arap, M.A.; Hajitou, A.; Ozawa, M.G.; Trepel, M.; Giordano, R.J.; Nanus, D.M.; Dijkman, H.B.P.M.; Oosterwijk, E.; Sidman, R.L.; Cooper, M.D.; Bussolino, F.; Pasqualini, R.; Arap, W.

2004-01-01

We show that a membrane-associated protease, aminopeptidase A (APA), is upregulated and enzymatically active in blood vessels of human tumors. To gain mechanistic insight, we evaluated angiogenesis in APA null mice. We found that, although these mice develop normally, they fail to mount the expected

Aminopeptidase A is a functional target in angiogenic blood vessels

NARCIS (Netherlands)

Marchiò, Serena; Lahdenranta, Johanna; Schlingemann, Reinier O.; Valdembri, Donatella; Wesseling, Pieter; Arap, Marco A.; Hajitou, Amin; Ozawa, Michael G.; Trepel, Martin; Giordano, Ricardo J.; Nanus, David M.; Dijkman, Henri B. P. M.; Oosterwijk, Egbert; Sidman, Richard L.; Cooper, Max D.; Bussolino, Federico; Pasqualini, Renata; Arap, Wadih

2004-01-01

We show that a membrane-associated protease, aminopeptidase A (APA), is upregulated and enzymatically active in blood vessels of human tumors. To gain mechanistic insight, we evaluated angiogenesis in APA null mice. We found that, although these mice develop normally, they fail to mount the expected

In vitro drug response and efflux transporters associated with drug resistance in pediatric high grade glioma and diffuse intrinsic pontine glioma.

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Susanna J E Veringa

Full Text Available Pediatric high-grade gliomas (pHGG, including diffuse intrinsic pontine gliomas (DIPG, are the leading cause of cancer-related death in children. While it is clear that surgery (if possible, and radiotherapy are beneficial for treatment, the role of chemotherapy for these tumors is still unclear. Therefore, we performed an in vitro drug screen on primary glioma cells, including three DIPG cultures, to determine drug sensitivity of these tumours, without the possible confounding effect of insufficient drug delivery. This screen revealed a high in vitro cytotoxicity for melphalan, doxorubicine, mitoxantrone, and BCNU, and for the novel, targeted agents vandetanib and bortezomib in pHGG and DIPG cells. We subsequently determined the expression of the drug efflux transporters P-gp, BCRP1, and MRP1 in glioma cultures and their corresponding tumor tissues. Results indicate the presence of P-gp, MRP1 and BCRP1 in the tumor vasculature, and expression of MRP1 in the glioma cells themselves. Our results show that pediatric glioma and DIPG tumors per se are not resistant to chemotherapy. Treatment failure observed in clinical trials, may rather be contributed to the presence of drug efflux transporters that constitute a first line of drug resistance located at the blood-brain barrier or other resistance mechanism. As such, we suggest that alternative ways of drug delivery may offer new possibilities for the treatment of pediatric high-grade glioma patients, and DIPG in particular.

Dependence of light scattering profile in tissue on blood vessel diameter and distribution: a computer simulation study.

Science.gov (United States)

Duadi, Hamootal; Fixler, Dror; Popovtzer, Rachela

2013-11-01

Most methods for measuring light-tissue interactions focus on the volume reflectance while very few measure the transmission. We investigate both diffusion reflection and diffuse transmission at all exit angles to receive the full scattering profile. We also investigate the influence of blood vessel diameter on the scattering profile of a circular tissue. The photon propagation path at a wavelength of 850 nm is calculated from the absorption and scattering constants via Monte Carlo simulation. Several simulations are performed where a different vessel diameter and location were chosen but the blood volume was kept constant. The fraction of photons exiting the tissue at several central angles is presented for each vessel diameter. The main result is that there is a central angle that below which the photon transmission decreased for lower vessel diameters while above this angle the opposite occurred. We find this central angle to be 135 deg for a two-dimensional 10-mm diameter circular tissue cross-section containing blood vessels. These findings can be useful for monitoring blood perfusion and oxygen delivery in the ear lobe and pinched tissues. © 2013 Society of Photo-Optical Instrumentation Engineers (SPIE)

Radiation-induced vasculopathy implicated by depressed blood flow and metabolism in a pineal glioma

Energy Technology Data Exchange (ETDEWEB)

Mineura, K; Sasajima, T; Kowada, M [Akita University Hospital (Japan). Neurosurgical Service; Saitoh, H [Oodate Municipal Hospital (Japan). Dept. of Neurosurgery; Shishido, F [Research Inst. of Brain and Blood Vessels, Akita (Japan)

1993-08-01

A case of radiation-induced vasculopathy of a pineal glioma was presented with haemodynamic and metabolic changes before and after radiotherapy. After radiation of 60 Gy with conventional fractionation (1.8-2.0 Gy daily, 5 days per week), regional blood flow, oxygen extraction fraction, metabolic rate of oxygen, kinetic metabolic rate of glucose and the rate constants (K2, K3) were markedly depressed (20% or greater) compared with the pre-irradiated study. 7 months after radiotherapy, the patient developed transient episodes of both right and left upper limb convulsion, terminating in generalized convulsion. When she developed status epilepticus, computed tomography showed extensive low density areas in the territory supplied by the right middle cerebral and the right posterior cerebral arteries. (author).

Radiation-induced vasculopathy implicated by depressed blood flow and metabolism in a pineal glioma

International Nuclear Information System (INIS)

Mineura, K.; Sasajima, T.; Kowada, M.

1993-01-01

A case of radiation-induced vasculopathy of a pineal glioma was presented with haemodynamic and metabolic changes before and after radiotherapy. After radiation of 60 Gy with conventional fractionation (1.8-2.0 Gy daily, 5 days per week), regional blood flow, oxygen extraction fraction, metabolic rate of oxygen, kinetic metabolic rate of glucose and the rate constants (K2, K3) were markedly depressed (20% or greater) compared with the pre-irradiated study. 7 months after radiotherapy, the patient developed transient episodes of both right and left upper limb convulsion, terminating in generalized convulsion. When she developed status epilepticus, computed tomography showed extensive low density areas in the territory supplied by the right middle cerebral and the right posterior cerebral arteries. (author)

Ultrasonographic Examination of Some Vessels in Dogs and the Characteristics of Blood Flow in These Vessels

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Figurová M.

2017-12-01

Full Text Available The examination by Doppler ultrasonography provides haemodynamic information about blood flow velocity in a respective vessel. It specifies high- and lowresistance flow patterns. The aim of our study was to record the flow in a. carotis communis, a. femoralis and aa. renales in 16 adult clinically healthy dogs of small and medium size; characterize the types of vessels and also determine the pulsatility index (PI and the resistive index (RI of these vessels. The a. femoralis is a high-resistance vessel with a pronounced three-peak waveform. The aa. renales gives a typical picture of a low-resistance flow pattern. The characteristics of a. carotis communis involves different images of its branches a. carotis interna and a. carotis externa. In the investigated groups we observed a medium degree of pulsatility (atypical highresistance flow pattern with an absence of reverse flow. The mean measured values of indices for a. carotis communis were: left side PI 1.824 and RI 0.742; right side PI 1.891 and RI 0.746, and for aa. renales: PI 1.366 ± 0.04 and RI 0.684 ± 0.05.

Vascular patterns in the heads of crocodilians: blood vessels and sites of thermal exchange.

Science.gov (United States)

Porter, William Ruger; Sedlmayr, Jayc C; Witmer, Lawrence M

2016-12-01

Extant crocodilians are a highly apomorphic archosaur clade that is ectothermic, yet often achieve large body sizes that can be subject to higher heat loads. Therefore, the anatomical and physiological roles that blood vessels play in crocodilian thermoregulation need further investigation to better understand how crocodilians establish and maintain cephalic temperatures and regulate neurosensory tissue temperatures during basking and normal activities. The cephalic vascular anatomy of extant crocodilians, particularly American alligator (Alligator mississippiensis) was investigated using a differential-contrast, dual-vascular injection technique and high resolution X-ray micro-computed tomography (μCT). Blood vessels were digitally isolated to create representations of vascular pathways. The specimens were then dissected to confirm CT results. Sites of thermal exchange, consisting of the oral, nasal, and orbital regions, were given special attention due to their role in evaporative cooling and cephalic thermoregulation in other diapsids. Blood vessels to and from sites of thermal exchange were studied to detect conserved vascular patterns and to assess their ability to deliver cooled blood to neurosensory tissues. Within the orbital region, both the arteries and veins demonstrated consistent branching patterns, with the supraorbital, infraorbital, and ophthalmotemporal vessels supplying and draining the orbit. The venous drainage of the orbital region showed connections to the dural sinuses via the orbital veins and cavernous sinus. The palatal region demonstrated a vast plexus that comprised both arteries and veins. The most direct route of venous drainage of the palatal plexus was through the palatomaxillary veins, essentially bypassing neurosensory tissues. Anastomotic connections with the nasal region, however, may provide an alternative route for palatal venous blood to reach neurosensory tissues. The nasal region in crocodilians is probably the most

Hybrid PIV-PTV technique for measuring blood flow in rat mesenteric vessels.

Science.gov (United States)

Ha, Hojin; Nam, Kweon-Ho; Lee, Sang Joon

2012-11-01

The micro-particle tracking velocimetry (μ-PTV) technique is used to obtain the velocity fields of blood flow in the microvasculature under in vivo conditions because it can provide the blood velocity distribution in microvessels with high spatial resolution. The in vivo μ-PTV technique usually requires a few to tens of seconds to obtain a whole velocity profile across the vessel diameter because of the limited number density of tracer particles under in vivo conditions. Thus, the μ-PTV technique alone is limited in measuring unsteady blood flows that fluctuate irregularly due to the heart beating and muscle movement in surrounding tissues. In this study, a new hybrid PIV-PTV technique was established by combining PTV and particle image velocimetry (PIV) techniques to resolve the drawbacks of the μ-PTV method in measuring blood flow in microvessels under in vivo conditions. Images of red blood cells (RBCs) and fluorescent particles in rat mesenteric vessels were obtained simultaneously. Temporal variations of the centerline blood velocity were monitored using a fast Fourier transform-based cross-correlation PIV method. The fluorescence particle images were analyzed using the μ-PTV technique to extract the spatial distribution of the velocity vectors. Data from the μ-PTV and PIV methods were combined to obtain a better estimate of the velocity profile in actual blood flow. This technique will be useful in investigating hemodynamics in microcirculation by measuring unsteady irregular blood flows more accurately. Copyright © 2012 Elsevier Inc. All rights reserved.

Feasibility evaluation of 3D photoacoustic imaging of blood vessel structure using multiple wavelengths with a handheld probe

Science.gov (United States)

Uchimoto, Yo; Namita, Takeshi; Kondo, Kengo; Yamakawa, Makoto; Shiina, Tsuyoshi

2018-02-01

Photoacoustic imaging is anticipated for use in portraying blood vessel structures (e.g. neovascularization in inflamed regions). To reduce invasiveness and enhance ease handling, we developed a handheld photoacoustic imaging system using multiple wavelengths. The usefulness of the proposed system was investigated in phantom experiments and in vivo measurements. A silicon tube was embedded into chicken breast meat to simulate the blood vessel. The tube was filled with ovine blood. Then laser light was guided to the phantom surface by an optical fiber bundle close to the linear ultrasound probe. Photoacoustic images were obtained at 750-950 nm wavelengths. Strong photoacoustic signals from the boundary between blood and silicon tube are observed in these images. The shape of photoacoustic spectrum at the boundary resembles that of the HbO2 absorption spectrum at 750-920 nm. In photoacoustic images, similarity between photoacoustic spectrum and HbO2 absorption spectrum was evaluated by calculating the normalized correlation coefficient. Results show high correlation in regions of strong photoacoustic signals in photoacoustic images. These analyses demonstrate the feasibility of portraying blood vessel structures under practical conditions. To evaluate the feasibility of three-dimensional vascular imaging, in vivo experiments were conducted using three wavelengths. A right hand and ultrasound probe were set in degassed water. By scanning a probe, cross-sectional ultrasound and photoacoustic images were obtained at each location. Then, all ultrasound or photoacoustic images were piled up respectively. Then three-dimensional images were constructed. Resultant images portrayed blood vessel-like structures three-dimensionally. Furthermore, to distinguish blood vessels from other tissues (e.g. skin), distinguishing images of them were constructed by comparing photoacoustic signal intensity among three wavelengths. The resultant image portrayed blood vessels as

Analysis of trends and prospects regarding stents for human blood vessels.

Science.gov (United States)

Lee, Jeong Hee; Kim, Eung Do; Jun, Eun Jung; Yoo, Hyoung Sun; Lee, Joon Woo

2018-01-01

The purpose of this paper is to provide technology trends and information regarding market and prospects in stents used for human blood vessels in Korea and the world.A stent is a medical device in the form of a cylindrical metal net used to normalize flow when blood or other bodily fluids such as biliary fluids are obstructed in blood vessels, gastrointestinal tracts, etc. by inserting the stent into a narrowed or clogged area. Stents are classified into vascular and non-vascular stents. The coronary artery stent is avascular stent that is used for coronary atherosclerosis.The demand is increasing for stents to treat diseases such as those affecting the heart and blood vessels of elderly and middle-aged patients. Due to the current shift in the demographic structure caused by an aging society, the prospect for stents seems to be very bright.The use of a stent designed to prevent acute vascular occlusion and restenosis, which is a side effect of conventional balloon angioplasty, has rapidly become popular because it can prevent acute complications and improve clinical outcomes. Since the initial release of this stent, there have been significant developments in its design, the most notable of which has been the introduction of drug-eluting stents (DES). Bioresorbable scaffolds (BRS) have the potential to introduce a paradigm shift in interventional cardiology, a true anatomical and functional "vascular restoration" instead of an artificial stiff tube encased by a persistent metallic foreign body. Data for this research were gathered from primary and secondary sources as well as the databases of the Korea Institute of Science Technology Information (KISTI) located in Seoul, Korea like KISTI Market Report. The sources used for primary research included the databases available from the Korea Institute of Science Technology Information, past industry research services/studies, economic and demographic data, and trade and industry journals. Secondary research was used

An experimental system for the study of ultrasound exposure of isolated blood vessels

International Nuclear Information System (INIS)

Tokarczyk, Anna; Rivens, Ian; Symonds-Tayler, Richard; Ter Haar, Gail; Van Bavel, E

2013-01-01

An experimental system designed for the study of the effects of diagnostic or therapeutic ultrasound exposure on isolated blood vessels in the presence or absence of intraluminal contrast agent is described. The system comprised several components. A microscope was used to monitor vessel size (and thus vessel functionality), and potential leakage of intraluminal 70 kDa FITC-dextran fluorescence marker. A vessel chamber allowed the mounting of an isolated vessel whilst maintaining its viability, with pressure regulation for the control of intraluminal pressure and induction of flow for the infusion of contrast microbubbles. A fibre-optic hydrophone sensor mounted on the vessel chamber using a micromanipulator allowed pre-exposure targeting of the vessel to within 150 µm, and monitoring of acoustic cavitation emissions during exposures. Acoustic cavitation was also detected using changes in the ultrasound drive voltage and by detection of audible emissions using a submerged microphone. The suitability of this system for studying effects in the isolated vessel model has been demonstrated using a pilot study of 6 sham exposed and 18 high intensity focused ultrasound exposed vessels, with or without intraluminal contrast agent (SonoVue) within the vessels. (paper)

Angiogenesis and blood vessel stability in inflammatory arthritis.

LENUS (Irish Health Repository)

Kennedy, Aisling

2012-02-01

OBJECTIVE: To assess blood vessel stability in inflammatory synovial tissue (ST) and to examine neural cell adhesion molecule (NCAM), oxidative DNA damage, and hypoxia in vivo. METHODS: Macroscopic vascularity and ST oxygen levels were determined in vivo in patients with inflammatory arthritis who were undergoing arthroscopy. Vessel maturity\\/stability was quantified in matched ST samples by dual immunofluorescence staining for factor VIII (FVIII)\\/alpha-smooth muscle actin (alpha-SMA). NCAM and 8-oxo-7,8-dihydro-2\\'-deoxyguanosine (8-oxodG) were examined by immunohistochemistry. Angiogenesis was assessed in vitro, using human dermal endothelial cells (HDECs) in a Matrigel tube formation assay. RESULTS: A significant number of immature vessels (showing no pericyte recruitment) was observed in tissue from patients with inflammatory arthritis (P < 0.001), in contrast to osteoarthritic and normal tissue, which showed complete recruitment of pericytes. Low in vivo PO(2) levels in the inflamed joint (median [range] 22.8 [3.2-54.1] mm Hg) were inversely related to increased macroscopic vascularity (P < 0.04) and increased microscopic expression of FVIII and alpha-SMA (P < 0.04 and P < 0.03, respectively). A significant proportion of vessels showed focal expression of NCAM and strong nuclear 8-oxodG expression, implicating a loss of EC-pericyte contact and increased DNA damage, levels of which were inversely associated with low in vivo PO(2) (P = 0.04 for each comparison). Circulating cells were completely negative for 8-oxodG. Exposure of HDEC to 3% O(2) (reflecting mean ST in vivo measurements) significantly increased EC tube formation (P < 0.05). CONCLUSION: Our findings indicate the presence of unstable vessels in inflamed joints associated with hypoxia, incomplete EC-pericyte interactions, and increased DNA damage. These changes may further contribute to persistent hypoxia in the inflamed joint to further drive this unstable microenvironment.

Why are tumour blood vessels abnormal and why is it important to know?

Science.gov (United States)

Nagy, J A; Chang, S-H; Dvorak, A M; Dvorak, H F

2009-01-01

Tumour blood vessels differ from their normal counterparts for reasons that have received little attention. We report here that they are of at least six distinct types, we describe how each forms, and, looking forward, encourage the targeting of tumour vessel subsets that have lost their vascular endothelial growth factor-A (VEGF-A) dependency and so are likely unresponsive to anti-VEGF-A therapies. PMID:19240721

Tight junction between endothelial cells: the interaction between nanoparticles and blood vessels

Directory of Open Access Journals (Sweden)

Yue Zhang

2016-05-01

Full Text Available Since nanoparticles are now widely applied as food additives, in cosmetics and other industries, especially in medical therapy and diagnosis, we ask here whether nanoparticles can cause several adverse effects to human health. In this review, based on research on nanotoxicity, we mainly discuss the negative influence of nanoparticles on blood vessels in several aspects and the potential mechanism for nanoparticles to penetrate endothelial layers of blood vessels, which are the sites of phosphorylation of tight junction proteins (claudins, occludins, and ZO (Zonula occludens proteins, oxidative stress and shear stress. We propose a connection between the presence of nanoparticles and the regulation of the tight junction, which might be the key approach for nanoparticles to penetrate endothelial layers and then have an impact on other tissues and organs.

Multi-detector spiral CT study of the relationships between pulmonary ground-glass nodules and blood vessels

International Nuclear Information System (INIS)

Gao, Feng; Li, Ming; Ge, Xiaojun; Ren, Qingguo; Hua, Yanqing; Zheng, Xiangpeng; Chen, Yan; Lv, Fangzhen

2013-01-01

To investigate the relationships between pulmonary ground-glass nodules (GGN) and blood vessels and their diagnostic values in differentiating GGNs. Multi-detector spiral CT imaging of 108 GGNs was retrospectively reviewed. The spatial relationships between GGNs and supplying blood vessels were categorized into four types: I, vessels passing by GGNs; II, intact vessels passing through GGNs; III, distorted, dilated or tortuous vessels seen within GGNs; IV, more complicated vasculature other than described above. Relationship types were correlated to pathologic and/or clinical findings of GGNs. Of 108 GGNs, 10 were benign, 24 preinvasive nodules and 74 adenocarcinomas that were pathologically proven. Types I, II, III and IV vascular relationships were observed in 9, 58, 21 and 20 GGNs, respectively. Type II relationship was the dominating relationship for each GGN group, but significant differences were shown among them. Correlation analysis showed strong correlation between invasive adenocarcinoma and type III and IV relationships. Subgroup analysis indicated that type III was more commonly seen in IAC with comparison to type IV more likely seen in MIA. Different GGNs have different relationships with vessels. Understanding and recognising characteristic GGN-vessel relationships may help identify which GGNs are more likely to be malignant. (orig.)

Utility of multiparametric 3-T MRI for glioma characterization

International Nuclear Information System (INIS)

Roy, Bhaswati; Gupta, Rakesh K.; Maudsley, Andrew A.; Sheriff, Sulaiman; Awasthi, Rishi; Mohakud, Sudipta; Gu, Meng; Spielman, Daniel M.; Husain, Nuzhat; Behari, Sanjay; Pandey, Chandra M.; Rathore, Ram K.S.; Alger, Jeffry R.

2013-01-01

Accurate grading of cerebral glioma using conventional structural imaging techniques remains challenging due to the relatively poor sensitivity and specificity of these methods. The purpose of this study was to evaluate the relative sensitivity and specificity of structural magnetic resonance imaging and MR measurements of perfusion, diffusion, and whole-brain spectroscopic parameters for glioma grading. Fifty-six patients with radiologically suspected untreated glioma were studied with T1- and T2-weighted MR imaging, dynamic contrast-enhanced MR imaging, diffusion tensor imaging, and volumetric whole-brain MR spectroscopic imaging. Receiver-operating characteristic analysis was performed using the relative cerebral blood volume (rCBV), apparent diffusion coefficient, fractional anisotropy, and multiple spectroscopic parameters to determine optimum thresholds for tumor grading and to obtain the sensitivity, specificity, and positive and negative predictive values for identifying high-grade gliomas. Logistic regression was performed to analyze all the parameters together. The rCBV individually classified glioma as low and high grade with a sensitivity and specificity of 100 and 88 %, respectively, based on a threshold value of 3.34. On combining all parameters under consideration, the classification was achieved with 2 % error and sensitivity and specificity of 100 and 96 %, respectively. Individually, CBV measurement provides the greatest diagnostic performance for predicting glioma grade; however, the most accurate classification can be achieved by combining all of the imaging parameters. (orig.)

Neutrophil-Mediated Delivery of Therapeutic Nanoparticles across Blood Vessel Barrier for Treatment of Inflammation and Infection

OpenAIRE

Chu, Dafeng; Gao, Jin; Wang, Zhenjia

2015-01-01

Endothelial cells form a monolayer in lumen of blood vessels presenting a great barrier for delivery of therapeutic nanoparticles (NPs) into extravascular tissues where most diseases occur, such as inflammation disorders and infection. Here, we report a strategy for delivering therapeutic NPs across this blood vessel barrier by nanoparticle in situ hitchhiking activated neutrophils. Using intravital microscopy of TNF-α-induced inflammation of mouse cremaster venules and a mouse model of acute...

In vivo measurement of hemodynamic information in stenosed rat blood vessels using X-ray PIV.

Science.gov (United States)

Park, Hanwook; Park, Jun Hong; Lee, Sang Joon

2016-11-28

Measurements of the hemodynamic information of blood flows, especially wall shear stress (WSS), in animal models with circulatory vascular diseases (CVDs) are important to understand the pathological mechanism of CVDs. In this study, X-ray particle image velocimetry (PIV) with high spatial resolution was applied to obtain velocity field information in stenosed blood vessels with high WSS. 3D clips fabricated with a 3D printer were applied to the abdominal aorta of a rat cadaver to induce artificial stenosis in the real blood vessel of an animal model. The velocity and WSS information of blood flows in the stenosed vessel were obtained and compared at various stenosis severities. In vivo measurement was also conducted by fastening a stenotic clip on a live rat model through surgical intervention to reduce the flow rate to match the limited temporal resolution of the present X-ray PIV system. Further improvement of the temporal resolution of the system might be able to provide in vivo measurements of hemodynamic information from animal disease models under physiological conditions. The present results would be helpful for understanding the relation between hemodynamic characteristics and the pathological mechanism in animal CVD models.

Delayed astrocytic contact with cerebral blood vessels in FGF-2 deficient mice does not compromise permeability properties at the developing blood-brain barrier.

Science.gov (United States)

Saunders, Norman R; Dziegielewska, Katarzyna M; Unsicker, Klaus; Ek, C Joakim

2016-11-01

The brain functions within a specialized environment tightly controlled by brain barrier mechanisms. Understanding the regulation of barrier formation is important for understanding brain development and may also lead to finding new ways to deliver pharmacotherapies to the brain; access of many potentially promising drugs is severely hindered by these barrier mechanisms. The cellular composition of the neurovascular unit of the blood-brain barrier proper and their effects on regulation of its function are beginning to be understood. One hallmark of the neurovascular unit in the adult is the astroglial foot processes that tightly surround cerebral blood vessels. However their role in barrier formation is still unclear. In this study we examined barrier function in newborn, juvenile and adult mice lacking fibroblast growth factor-2 (FGF-2), which has been shown to result in altered astroglial differentiation during development. We show that during development of FGF-2 deficient mice the astroglial contacts with cerebral blood vessels are delayed compared with wild-type animals. However, this delay did not result in changes to the permeability properties of the blood brain barrier as assessed by exclusion of either small or larger sized molecules at this interface. In addition cerebral vessels were positive for tight-junction proteins and we observed no difference in the ultrastructure of the tight-junctions. The results indicate that the direct contact of astroglia processes to cerebral blood vessels is not necessary for either the formation of the tight-junctions or for basic permeability properties and function of the blood-brain barrier. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1201-1212, 2016. © 2016 Wiley Periodicals, Inc.

Monocyte galactose/N-acetylgalactosamine-specific C-type lectin receptor stimulant immunotherapy of an experimental glioma. Part 1: stimulatory effects on blood monocytes and monocyte-derived cells of the brain

Directory of Open Access Journals (Sweden)

Kushchayev SV

2012-09-01

Full Text Available Sergiy V Kushchayev,1 Tejas Sankar,1 Laura L Eggink,4,5 Yevgeniya S Kushchayeva,5 Philip C Wiener,1,5 J Kenneth Hoober,5,6 Jennifer Eschbacher,3 Ruolan Liu,2 Fu-Dong Shi,2 Mohammed G Abdelwahab,4 Adrienne C Scheck,4 Mark C Preul11Neurosurgery Research Laboratory, 2Neuroimmunology Laboratory, 3Department of Pathology, 4Neurooncology Research, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, 5School of Life Sciences, Arizona State University, Tempe, 6Susavion Biosciences, Inc, Tempe, AZ, USAObjectives: Immunotherapy with immunostimulants is an attractive therapy against gliomas. C-type lectin receptors specific for galactose/N-acetylgalactosamine (GCLR regulate cellular differentiation, recognition, and trafficking of monocyte-derived cells. A peptide mimetic of GCLR ligands (GCLRP was used to activate blood monocytes and populations of myeloid-derived cells against a murine glioblastoma.Methods: The ability of GCLRP to stimulate phagocytosis by human microglia and monocyte-derived cells of the brain (MDCB isolated from a human glioblastoma was initially assessed in vitro. Induction of activation markers on blood monocytes was assayed by flow cytometry after administration of GCLRP to naive mice. C57BL/6 mice underwent stereotactic intracranial implantation of GL261 glioma cells and were randomized for tumor size by magnetic resonance imaging, which was also used to assess increase in tumor size. Brain tumor tissues were analyzed using flow cytometry, histology, and enzyme-linked immunosorbent assay with respect to tumor, peritumoral area, and contralateral hemisphere regions.Results: GCLRP exhibited strong stimulatory effect on MDCBs and blood monocytes in vitro and in vivo. GCLRP was associated with an increased percentage of precursors of dendritic cells in the blood (P = 0.003, which differentiated into patrolling macrophages in tumoral (P = 0.001 and peritumoral areas (P = 0.04, rather than into dendritic cells

Beyond Alkylating Agents for Gliomas: Quo Vadimus?

Science.gov (United States)

Puduvalli, Vinay K; Chaudhary, Rekha; McClugage, Samuel G; Markert, James

2017-01-01

Recent advances in therapies have yielded notable success in terms of improved survival in several cancers. However, such treatments have failed to improve outcome in patients with gliomas for whom surgery followed by radiation therapy and chemotherapy with alkylating agents remain the standard of care. Genetic and epigenetic studies have helped identify several alterations specific to gliomas. Attempts to target these altered pathways have been unsuccessful due to various factors, including tumor heterogeneity, adaptive resistance of tumor cells, and limitations of access across the blood-brain barrier. Novel therapies that circumvent such limitations have been the focus of intense study and include approaches such as immunotherapy, targeting of signaling hubs and metabolic pathways, and use of biologic agents. Immunotherapeutic approaches including tumor-targeted vaccines, immune checkpoint blockade, antibody-drug conjugates, and chimeric antigen receptor-expressing cell therapies are in various stages of clinical trials. Similarly, identification of key metabolic pathways or converging hubs of signaling pathways that are tumor specific have yielded novel targets for therapy of gliomas. In addition, the failure of conventional therapies against gliomas has led to a growing interest among patients in the use of alternative therapies, which in turn has necessitated developing evidence-based approaches to the application of such therapies in clinical studies. The development of these novel approaches bears potential for providing breakthroughs in treatment of more meaningful and improved outcomes for patients with gliomas.

Vascular Patterns in Iguanas and Other Squamates: Blood Vessels and Sites of Thermal Exchange.

Directory of Open Access Journals (Sweden)

William Ruger Porter

Full Text Available Squamates use the circulatory system to regulate body and head temperatures during both heating and cooling. The flexibility of this system, which possibly exceeds that of endotherms, offers a number of physiological mechanisms to gain or retain heat (e.g., increase peripheral blood flow and heart rate, cooling the head to prolong basking time for the body as well as to shed heat (modulate peripheral blood flow, expose sites of thermal exchange. Squamates also have the ability to establish and maintain the same head-to-body temperature differential that birds, crocodilians, and mammals demonstrate, but without a discrete rete or other vascular physiological device. Squamates offer important anatomical and phylogenetic evidence for the inference of the blood vessels of dinosaurs and other extinct archosaurs in that they shed light on the basal diapsid condition. Given this basal positioning, squamates likewise inform and constrain the range of physiological thermoregulatory mechanisms that may have been found in Dinosauria. Unfortunately, the literature on squamate vascular anatomy is limited. Cephalic vascular anatomy of green iguanas (Iguana iguana was investigated using a differential-contrast, dual-vascular injection (DCDVI technique and high-resolution X-ray microcomputed tomography (μCT. Blood vessels were digitally segmented to create a surface representation of vascular pathways. Known sites of thermal exchange, consisting of the oral, nasal, and orbital regions, were given special attention due to their role in brain and cephalic thermoregulation. Blood vessels to and from sites of thermal exchange were investigated to detect conserved vascular patterns and to assess their ability to deliver cooled blood to the dural venous sinuses. Arteries within sites of thermal exchange were found to deliver blood directly and through collateral pathways. The venous drainage was found to have multiple pathways that could influence neurosensory

Vascular Patterns in Iguanas and Other Squamates: Blood Vessels and Sites of Thermal Exchange.

Science.gov (United States)

Porter, William Ruger; Witmer, Lawrence M

2015-01-01

Squamates use the circulatory system to regulate body and head temperatures during both heating and cooling. The flexibility of this system, which possibly exceeds that of endotherms, offers a number of physiological mechanisms to gain or retain heat (e.g., increase peripheral blood flow and heart rate, cooling the head to prolong basking time for the body) as well as to shed heat (modulate peripheral blood flow, expose sites of thermal exchange). Squamates also have the ability to establish and maintain the same head-to-body temperature differential that birds, crocodilians, and mammals demonstrate, but without a discrete rete or other vascular physiological device. Squamates offer important anatomical and phylogenetic evidence for the inference of the blood vessels of dinosaurs and other extinct archosaurs in that they shed light on the basal diapsid condition. Given this basal positioning, squamates likewise inform and constrain the range of physiological thermoregulatory mechanisms that may have been found in Dinosauria. Unfortunately, the literature on squamate vascular anatomy is limited. Cephalic vascular anatomy of green iguanas (Iguana iguana) was investigated using a differential-contrast, dual-vascular injection (DCDVI) technique and high-resolution X-ray microcomputed tomography (μCT). Blood vessels were digitally segmented to create a surface representation of vascular pathways. Known sites of thermal exchange, consisting of the oral, nasal, and orbital regions, were given special attention due to their role in brain and cephalic thermoregulation. Blood vessels to and from sites of thermal exchange were investigated to detect conserved vascular patterns and to assess their ability to deliver cooled blood to the dural venous sinuses. Arteries within sites of thermal exchange were found to deliver blood directly and through collateral pathways. The venous drainage was found to have multiple pathways that could influence neurosensory tissue temperature

Phase I Pharmacokinetic Study of the VEGFR Tyrosine Kinase Inhibitor Vatalanib (PTK787) plus Imatinib and Hydroxyurea for Malignant Glioma

Science.gov (United States)

Reardon, David A.; Egorin, Merrill J.; Desjardins, Annick; Vredenburgh, James J.; Beumer, Jan H.; Lagattuta, Theodore F.; Gururangan, Sridharan; Herndon, James E.; Salvado, August J.; Friedman, Henry S.

2009-01-01

Background We determined the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of the oral vascular endothelial growth factor receptor (VEGFR) inhibitor, vatalanib, when administered with imatinib and hydroxyurea on a continuous daily schedule among recurrent malignant glioma patients. Methods All patients received 500 mg of hydroxyurea twice daily. Imatinib was dosed at 400 mg per day for patients not taking enzyme-inducing antiepileptic drugs (EIAEDs; stratum A) and at 500 mg twice-a-day for patients taking EIAEDs (stratum B). Vatalanib was escalated from 500 mg to 1250 mg twice daily in successive cohorts, independently for each stratum. Pharmacokinetics of each drug were assessed. Results Thirty-seven recurrent patients, including 34 (92%) with glioblastoma and 3 (8%) with grade 3 malignant glioma, were enrolled. Nineteen patients (51%) were taking EIAEDs. The MTD of vatalanib for all patients was 1000 mg twice-a-day. DLTs were hematologic, gastrointestinal, renal and hepatic. No patients developed intracranial hemorrhage. Concurrent administration of imatinib and hydroxyurea did not affect vatalanib exposure, but EIAEDs decreased vatalanib and imatinib plasma exposures. Conclusion Vatalanib doses up to 1000 mg twice-a-day combined with imatinib and hydroxyurea are well tolerated. Strategies to target tumor blood vessel endothelial cells and pericytes by inhibiting VEGFR and PDGFR, respectively, are safe among recurrent malignant glioma patients and may enhance anti-angiogenesis activity. PMID:19248046

Regulation of cellular communication by signaling microdomains in the blood vessel wall.

Science.gov (United States)

Billaud, Marie; Lohman, Alexander W; Johnstone, Scott R; Biwer, Lauren A; Mutchler, Stephanie; Isakson, Brant E

2014-01-01

It has become increasingly clear that the accumulation of proteins in specific regions of the plasma membrane can facilitate cellular communication. These regions, termed signaling microdomains, are found throughout the blood vessel wall where cellular communication, both within and between cell types, must be tightly regulated to maintain proper vascular function. We will define a cellular signaling microdomain and apply this definition to the plethora of means by which cellular communication has been hypothesized to occur in the blood vessel wall. To that end, we make a case for three broad areas of cellular communication where signaling microdomains could play an important role: 1) paracrine release of free radicals and gaseous molecules such as nitric oxide and reactive oxygen species; 2) role of ion channels including gap junctions and potassium channels, especially those associated with the endothelium-derived hyperpolarization mediated signaling, and lastly, 3) mechanism of exocytosis that has considerable oversight by signaling microdomains, especially those associated with the release of von Willebrand factor. When summed, we believe that it is clear that the organization and regulation of signaling microdomains is an essential component to vessel wall function.

Adaptable three-dimensional Monte Carlo modeling of imaged blood vessels in skin

Science.gov (United States)

Pfefer, T. Joshua; Barton, Jennifer K.; Chan, Eric K.; Ducros, Mathieu G.; Sorg, Brian S.; Milner, Thomas E.; Nelson, J. Stuart; Welch, Ashley J.

1997-06-01

In order to reach a higher level of accuracy in simulation of port wine stain treatment, we propose to discard the typical layered geometry and cylindrical blood vessel assumptions made in optical models and use imaging techniques to define actual tissue geometry. Two main additions to the typical 3D, weighted photon, variable step size Monte Carlo routine were necessary to achieve this goal. First, optical low coherence reflectometry (OLCR) images of rat skin were used to specify a 3D material array, with each entry assigned a label to represent the type of tissue in that particular voxel. Second, the Monte Carlo algorithm was altered so that when a photon crosses into a new voxel, the remaining path length is recalculated using the new optical properties, as specified by the material array. The model has shown good agreement with data from the literature. Monte Carlo simulations using OLCR images of asymmetrically curved blood vessels show various effects such as shading, scattering-induced peaks at vessel surfaces, and directionality-induced gradients in energy deposition. In conclusion, this augmentation of the Monte Carlo method can accurately simulate light transport for a wide variety of nonhomogeneous tissue geometries.

Regulation of Cellular Communication by Signaling Microdomains in the Blood Vessel Wall

Science.gov (United States)

Billaud, Marie; Lohman, Alexander W.; Johnstone, Scott R.; Biwer, Lauren A.; Mutchler, Stephanie; Isakson, Brant E.

2014-01-01

It has become increasingly clear that the accumulation of proteins in specific regions of the plasma membrane can facilitate cellular communication. These regions, termed signaling microdomains, are found throughout the blood vessel wall where cellular communication, both within and between cell types, must be tightly regulated to maintain proper vascular function. We will define a cellular signaling microdomain and apply this definition to the plethora of means by which cellular communication has been hypothesized to occur in the blood vessel wall. To that end, we make a case for three broad areas of cellular communication where signaling microdomains could play an important role: 1) paracrine release of free radicals and gaseous molecules such as nitric oxide and reactive oxygen species; 2) role of ion channels including gap junctions and potassium channels, especially those associated with the endothelium-derived hyperpolarization mediated signaling, and lastly, 3) mechanism of exocytosis that has considerable oversight by signaling microdomains, especially those associated with the release of von Willebrand factor. When summed, we believe that it is clear that the organization and regulation of signaling microdomains is an essential component to vessel wall function. PMID:24671377

Magnetic navigation system for the precise helical and translational motions of a microrobot in human blood vessels

Science.gov (United States)

Jeon, S. M.; Jang, G. H.; Choi, H. C.; Park, S. H.; Park, J. O.

2012-04-01

Different magnetic navigation systems (MNSs) have been investigated for the wireless manipulation of microrobots in human blood vessels. Here we propose a MNS and methodology for generation of both the precise helical and translational motions of a microrobot to improve its maneuverability in complex human blood vessel. We then present experiments demonstrating the helical and translational motions of a spiral-type microrobot to verify the proposed MNS.

Antibody guided irradiation of brain glioma by arterial infusion of radioactive monoclonal antibody against epidermal growth factor receptor and blood group A antigen

Energy Technology Data Exchange (ETDEWEB)

Epenetos, A.A.; Courtenay-Luck, N.; Pickering, D.; Hooker, G.; Lavender, J.P.; McKenzie, C.G. (Hammersmith Hospital, London (UK)); Durbin, H. (Imperial Cancer Research Fund, London (UK). Labs.)

1985-05-18

In a patient with recurrent grade IV glioma of the brain resistant to conventional treatment an antibody guided isotopic scan showed uptake by the tumour of a monoclonal antibody (9A) that was developed against epidermal growth factor receptor but cross reacted with blood group A antigen. As a therapeutic attempt antibody labelled with 1665 MBq (45.0 mCi) iodine-131 was delivered to the tumour area by infusion into the internal carotid artery. Computed tomography showed regression of the tumour after treatment, and an appreciable and sustained clinical improvement was noted without any toxicity. Delivery of irradiation guided by monoclonal antibody delivered by arterial infusion of the tumour area may be of clinical value in the treatment of brain gliomas resistant to conventional forms of treatment.

In vivo detection of inducible nitric oxide synthase in rodent gliomas.

Science.gov (United States)

Towner, Rheal A; Smith, Nataliya; Doblas, Sabrina; Garteiser, Philippe; Watanabe, Yasuko; He, Ting; Saunders, Debra; Herlea, Oana; Silasi-Mansat, Robert; Lupu, Florea

2010-03-01

Increased iNOS expression is often found in brain tumors, such as gliomas. The goal of this study was to develop and assess a novel molecular MRI (mMRI) probe for in vivo detection of iNOS in rodent models for gliomas (intracerebral implantation of rat C6 or RG2 cells or ethyl nitrosourea-induced glioma). The probe we used incorporated a Gd-DTPA (gadolinium(III) complex of diethylenetriamine-N,N,N',N'',N''-pentaacetate) backbone with albumin and biotin moieties and covalent binding of an anti-iNOS antibody (Ab) to albumin (anti-iNOS probe). We used mMRI with the anti-iNOS probe to detect in vivo iNOS levels in gliomas. Nonimmune normal rat IgG coupled to albumin-Gd-DTPA-biotin was used as a control nonspecific contrast agent. By targeting the biotin component of the anti-iNOS probe with streptavidin Cy3, fluorescence imaging confirmed the specificity of the probe for iNOS in glioma tissue. iNOS levels in glioma tumors were also confirmed via Western blots and immunohistochemistry. The presence of plasma membrane-associated iNOS in glioma cells was established by transmission electron microscopy and gold-labeled anti-iNOS Ab. The more aggressive RG2 glioma was not found to have higher levels of iNOS compared to C6. Differences in glioma vascularization and blood-brain barrier permeability between the C6 and the RG2 gliomas are discussed. In vivo assessment of iNOS levels associated with tumor development is quite feasible in heterogeneous tissues with mMRI. (c) 2009 Elsevier Inc. All rights reserved.

The effect of transluminal stent-graft placement on blood flow of abdominal branch vessels in type B aortic dissection

International Nuclear Information System (INIS)

Huang Lianjun; Yang Jian; Yu Feicheng; Sun Lizhong; Zhu Junming; Zhang Yan; Jiang Shiliang

2005-01-01

Objective: To evaluate the effect of TSGP on blood flow of abdominal branch vessels of Type B dissection. Methods: Thirty-five patients with type B aortic dissection underwent TSGP. The blood flow of abdominal branch vessels was analyzed via EBCT, MRI, and DSA before and after procedure. Results: A total of 140 important vessels from abdominal aorta in 35 patients, including celiac artery, SMA, right and left renal arteries were analyzed via EBCT, MRI, and DSA. 58 branches were affected by dissection, of which 14 (10% ) were dynamic impairment; and 44 (31.4%) were static impairment. After TSGP, the blood flow of impaired branches all showed improvement at different degrees, no post-operative ischemic complications occurred. Conclusion: TSGP could improve the blood flow immediately not only the dynamic but also the static ischemia of abdominal aorta branch vessels caused by type B aortic dissection. Further study is still need to observe the mid-term and long-term effect of TSGP. (authors)

[Conjunct changes in the resistance and engorgement of the cerebral vessels in shifts in the blood gas composition].

Science.gov (United States)

Krasil'nikov, V G; Artem'eva, A I

1982-08-01

In anesthetized cats, under perfusion and with constant volume of the hemodynamically isolated brain, hypercapnia and hypoxia led to a decrease of cerebral vessels resistance and to a reduction of the brain blood flow, whereas a decrease in the PCO2 and an increase in the PO2 in the blood exerted on opposite effect. The different responses of the vessels had some similar features in respect to threshold changes of the PCO2 and PO2, to potentiation of effects of both parts of the brain vascular system on increased shifts of the blood gas tension, to greater sensitivity of both parts to PCO2 changes, to effect of the blood gas tension on reactivity of both parts to noradrenaline. The authors suggest a possibility of alterations of the filter-absorption interrelationships in the brain due to different responses of arterial and venous vessels to changes of the blood gas tension.

Boronophenylalanine uptake in C6 glioma model is dramatically increased by L-DOPA preloading

Energy Technology Data Exchange (ETDEWEB)

Capuani, S. [CNR-INFM SOFT, Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Enrico Fermi Center, Compendio Viminale, Rome (Italy)], E-mail: silvia.capuani@roma1.infn.it; Gili, T. [CNR-INFM SOFT, Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Enrico Fermi Center, Compendio Viminale, Rome (Italy); Bozzali, M. [Neuroimaging Laboratory, Santa Lucia Foundation, Via Ardeatina 306, Rome (Italy); Russo, S. [Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Queen Square, London (United Kingdom); Porcari, P. [CNR-INFM SOFT, Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Cametti, C. [CNR-INFM SOFT, Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 2, Rome (Italy); Muolo, M. [Department of Biological Science, University ' Rome III' , Viale G. Marconi 446, Rome (Italy); D' Amore, E. [Serv. Qual./Sicurezza Sperim. Anim., Istituto Superiore di Sanita, Rome (Italy); Maraviglia, B. [Enrico Fermi Center, Compendio Viminale, Rome (Italy); Neuroimaging Laboratory, Santa Lucia Foundation, Via Ardeatina 306, Rome (Italy); Lazzarino, G. [Laboratory of Biochemistry, Department of Chemical Sciences, University of Catania, Viale A. Doria 6, Catania (Italy); Pastore, F.S. [Department of Neuroscience, Institute of Neurosurgery, University ' Tor Vergata' , Via Montpellier 1, Rome (Italy)

2009-07-15

One of the main limitations for BNCT effectiveness is the insufficient intake of {sup 10}B nuclei within tumour cells. This work was aimed at investigating the use of L-DOPA as enhancer for boronophenylalanine (BPA) uptake in the C6 glioma model. The investigation was first performed in vitro, and then extended in vivo to the animal model. BPA accumulation in C6 glioma cells was assessed, using radiowave dielectric spectroscopy (RDS), with and without L-DOPA preloading. C6 glioma cells were also implanted in the brain of 25 rats, randomly assigned to two experimental branches: (1) intra-carotid BPA infusion; (2) intra-carotid BPA infusion after pre-treatment with L-DOPA, administrated 24 h before BPA infusion. All animals were sacrificed, and assessment of BPA concentrations in tumour tissue, normal brain, and blood samples was performed using high performance liquid chromatography (HPLC). L-DOPA preloading induced a massive increase of BPA concentration either in vitro on C6 glioma cells or in vivo in the animal model tumour. Moreover, no significant difference was found in the normal brain and blood samples between the two animal groups. This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT.

Boronophenylalanine uptake in C6 glioma model is dramatically increased by L-DOPA preloading

International Nuclear Information System (INIS)

Capuani, S.; Gili, T.; Bozzali, M.; Russo, S.; Porcari, P.; Cametti, C.; Muolo, M.; D'Amore, E.; Maraviglia, B.; Lazzarino, G.; Pastore, F.S.

2009-01-01

One of the main limitations for BNCT effectiveness is the insufficient intake of 10 B nuclei within tumour cells. This work was aimed at investigating the use of L-DOPA as enhancer for boronophenylalanine (BPA) uptake in the C6 glioma model. The investigation was first performed in vitro, and then extended in vivo to the animal model. BPA accumulation in C6 glioma cells was assessed, using radiowave dielectric spectroscopy (RDS), with and without L-DOPA preloading. C6 glioma cells were also implanted in the brain of 25 rats, randomly assigned to two experimental branches: (1) intra-carotid BPA infusion; (2) intra-carotid BPA infusion after pre-treatment with L-DOPA, administrated 24 h before BPA infusion. All animals were sacrificed, and assessment of BPA concentrations in tumour tissue, normal brain, and blood samples was performed using high performance liquid chromatography (HPLC). L-DOPA preloading induced a massive increase of BPA concentration either in vitro on C6 glioma cells or in vivo in the animal model tumour. Moreover, no significant difference was found in the normal brain and blood samples between the two animal groups. This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT.

High-grade and low-grade gliomas: differentiation by using perfusion MR imaging

International Nuclear Information System (INIS)

Hakyemez, B.; Erdogan, C.; Ercan, I.; Ergin, N.; Uysal, S.; Atahan, S.

2005-01-01

AIM: Relative cerebral blood volume (rCBV) is a commonly used perfusion magnetic resonance imaging (MRI) technique for the evaluation of tumour grade. Relative cerebral blood flow (rCBF) has been less studied. The goal of our study was to determine the usefulness of these parameters in evaluating the histopathological grade of the cerebral gliomas. METHODS: This study involved 33 patients (22 high-grade and 11 low-grade glioma cases). MRI was performed for all tumours by using a first-passage gadopentetate dimeglumine T2*-weighted gradient-echo single-shot echo-planar sequence followed by conventional MRI. The rCBV and rCBF were calculated by deconvolution of an arterial input function. The rCBV and rCBF ratios of the lesions were obtained by dividing the values obtained from the normal white matter of the contralateral hemisphere. For statistical analysis Mann-Whitney testing was carried out. A p value of less than 0.05 indicated a statistically significant difference. Receiver operating characteristic curve (ROC) analysis was performed to assess the relationship between the rCBV and rCBF ratios and grade of gliomas. Their cut-off value permitting discrimination was calculated. The correlation between rCBV and CBF ratios and glioma grade was assessed using Pearson correlation analysis. RESULTS: In high-grade gliomas, rCBV and rCBF ratios were measured as 6.50±4.29 and 3.32±1.87 (mean±SD), respectively. In low-grade gliomas, rCBV and rCBF ratios were 1.69±0.51 and 1.16±0.38, respectively. The rCBV and rCBF ratios for high-grade gliomas were statistically different from those of low-grade gliomas (p 0.05). The cut-off value was taken as 1.98 in the rCBV ratio and 1.25 in the rCBF ratio. There was a strong correlation between the rCBV and CBF ratios (Pearson correlation = 0.830, p<0.05). CONCLUSION: Perfusion MRI is useful in the preoperative assessment of the histopathologicalal grade of gliomas; the rCBF ratio in addition to the rCBV ratio can be incorporated

Extraction of liver volumetry based on blood vessel from the portal phase CT dataset

Science.gov (United States)

Maklad, Ahmed S.; Matsuhiro, Mikio; Suzuki, Hidenobu; Kawata, Yoshiki; Niki, Noboru; Utsunomiya, Tohru; Shimada, Mitsuo

2012-02-01

At liver surgery planning stage, the liver volumetry would be essential for surgeons. Main problem at liver extraction is the wide variability of livers in shapes and sizes. Since, hepatic blood vessels structure varies from a person to another and covers liver region, the present method uses that information for extraction of liver in two stages. The first stage is to extract abdominal blood vessels in the form of hepatic and nonhepatic blood vessels. At the second stage, extracted vessels are used to control extraction of liver region automatically. Contrast enhanced CT datasets at only the portal phase of 50 cases is used. Those data include 30 abnormal livers. A reference for all cases is done through a comparison of two experts labeling results and correction of their inter-reader variability. Results of the proposed method agree with the reference at an average rate of 97.8%. Through application of different metrics mentioned at MICCAI workshop for liver segmentation, it is found that: volume overlap error is 4.4%, volume difference is 0.3%, average symmetric distance is 0.7 mm, Root mean square symmetric distance is 0.8 mm, and maximum distance is 15.8 mm. These results represent the average of overall data and show an improved accuracy compared to current liver segmentation methods. It seems to be a promising method for extraction of liver volumetry of various shapes and sizes.

Primo vessel inside a lymph vessel emerging from a cancer tissue.

Science.gov (United States)

Lee, Sungwoo; Ryu, Yeonhee; Cha, Jinmyung; Lee, Jin-Kyu; Soh, Kwang-Sup; Kim, Sungchul; Lim, Jaekwan

2012-10-01

Primo vessels were observed inside the lymph vessels near the caudal vena cava of a rabbit and a rat and in the thoracic lymph duct of a mouse. In the current work we found a primo vessel inside the lymph vessel that came out from the tumor tissue of a mouse. A cancer model of a nude mouse was made with human lung cancer cell line NCI-H460. We injected fluorescent nanoparticles into the xenografted tumor tissue and studied their flow in blood, lymph, and primo vessels. Fluorescent nanoparticles flowed through the blood vessels quickly in few minutes, and but slowly in the lymph vessels. The bright fluorescent signals of nanoparticles disappeared within one hour in the blood vessels but remained much longer up to several hours in the case of lymph vessels. We found an exceptional case of lymph vessels that remained bright with fluorescence up to 24 hours. After detailed examination we found that the bright fluorescence was due to a putative primo vessel inside the lymph vessel. This rare observation is consistent with Bong-Han Kim's claim on the presence of a primo vascular system in lymph vessels. It provides a significant suggestion on the cancer metastasis through primo vessels and lymph vessels. Copyright © 2012. Published by Elsevier B.V.

[Do double gloves protect against contamination during cannulation of blood vessels? A prospective randomized study].

Science.gov (United States)

Szarpak, Łukasz; Kurowski, Andrzej

2014-01-01

Undamaged medical gloves protect medical personnel from contact with physiological fluids of the patient. Thus they protect the assistance provider from hand skin contamination with potentially infectious biological materials. The aim of the study was to evaluate the occurrence of pierce, perforations or damage of medical gloves during cannulation of blood vessels. In the prospective randomized study 303 pairs of gloves, used during cannulation of blood vessels under simulated resuscitation, were analyzed. Gloves were tested by the water leak test. The water test revealed 44 cases of damage to the gloves used during cannulation of blood vessels. Significant differences were noted in the frequency of damage to both the outer and single pairs of gloves and the inner pair of gloves. The study showed that the use of double gloves provides a higher level of security for a paramedic than the use of a single pair of gloves, however, double gloves reduce the manual dexterity of a paramedic. A large number of damages to gloves are not noticed by medical personnel during surgery.

Epidemiology of glioma

DEFF Research Database (Denmark)

Rasmussen, Birthe Krogh; Hansen, Steinbjorn; Laursen, Rene J.

2017-01-01

in 15%. The overall male:female ratio was 3:2 and the mean age at onset was 60 years. Data for WHO grade I, II, III and IV glioma showed several important differences regarding age and sex distribution and symptomatology at presentation. The mean age increased with the grade of glioma and males...... duration, and headache rates for glioma grade I-IV showed decreasing survival with increasing grade. Glioma grade I-IV showed...

[Stem and progenitor cells in biostructure of blood vessel walls].

Science.gov (United States)

Korta, Krzysztof; Kupczyk, Piotr; Skóra, Jan; Pupka, Artur; Zejler, Paweł; Hołysz, Marcin; Gajda, Mariusz; Nowakowska, Beata; Barć, Piotr; Dorobisz, Andrzej T; Dawiskiba, Tomasz; Szyber, Piotr; Bar, Julia

2013-09-18

Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, "anchored" in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC). Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as "subendothelial or vasculogenic zones". Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

Stem and progenitor cells in biostructure of blood vessel walls

Directory of Open Access Journals (Sweden)

Krzysztof Korta

2013-09-01

Full Text Available Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, “anchored” in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC. Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as “subendothelial or vasculogenic zones”. Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

Histogram analysis reveals a better delineation of tumor volume from background in 18F-FET PET compared to CBV maps in a hybrid PET–MR studie in gliomas

International Nuclear Information System (INIS)

Filss, Christian P.; Stoffels, Gabriele; Galldiks, Norbert; Sabel, Michael; Wittsack, Hans J.; Coenen, Heinz H.; Shah, Nadim J.; Herzog, Hans

2014-01-01

Anatomical imaging with magnetic resonance imaging (MRI) is currently the method of first choice for diagnostic investigation of glial tumors. However, different MR sequences may over- or underestimate tumor size and thus it may not be possible to delineate tumor from adjacent brain. In order to compensate this confinement additonal MR sequences like perfusion weighted MRI (PWI) with regional cerebral blood volume (rCBV) or positron emission tomography (PET) with aminoacids are used to gain further information. Recent studies suggest that both of theses image modalities provide similar diagnostic information. For comparison tumor to brain ratios (TBR) with mean and maximum values are frequently used but results from different studies can often not be checked against each other. Furthermore, especially the maximum TBR in rCBV is at risk to be falsified by artifacts (e.g. blood vessels). These confinements are reduced by the use of histograms since all information of the VOIs are equally displayed. In this study we measured and compared the intersection of tumor and reference tissue histograms in 18 F-FET PET and rCBV maps in glioma patients. Methods: Twenty-seven glioma patients with contrast enhancing lesion on T1-weighted MR images were investigated using static 18 F-FET PET and rCBV in MRI using a PET–MR hybrid scanner. In all patients diagnosis was confirmed histologically (7 grade II gliomas, 6 grade III gliomas and 14 grade IV gliomas). We generated a set of tumor and reference tissue Volumes-of-Interest (VOIs) based on T1 weighted images in MRI with the tumor VOI defined by contrast enhancement and transferred these VOIs to the corresponding 18 F-FET PET scans and rCBV maps. From these VOIs we generated tumor and reference tissue histograms with a unity of one for each curve integral and measured the proportion of the area under the tumor curve that falls into the reference curve for 18 F-FET PET and rCBV maps for each patient. Results: The mean proportion

Histogram analysis of T2*-based pharmacokinetic imaging in cerebral glioma grading.

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Liu, Hua-Shan; Chiang, Shih-Wei; Chung, Hsiao-Wen; Tsai, Ping-Huei; Hsu, Fei-Ting; Cho, Nai-Yu; Wang, Chao-Ying; Chou, Ming-Chung; Chen, Cheng-Yu

2018-03-01

To investigate the feasibility of histogram analysis of the T2*-based permeability parameter volume transfer constant (K trans ) for glioma grading and to explore the diagnostic performance of the histogram analysis of K trans and blood plasma volume (v p ). We recruited 31 and 11 patients with high- and low-grade gliomas, respectively. The histogram parameters of K trans and v p , derived from the first-pass pharmacokinetic modeling based on the T2* dynamic susceptibility-weighted contrast-enhanced perfusion-weighted magnetic resonance imaging (T2* DSC-PW-MRI) from the entire tumor volume, were evaluated for differentiating glioma grades. Histogram parameters of K trans and v p showed significant differences between high- and low-grade gliomas and exhibited significant correlations with tumor grades. The mean K trans derived from the T2* DSC-PW-MRI had the highest sensitivity and specificity for differentiating high-grade gliomas from low-grade gliomas compared with other histogram parameters of K trans and v p . Histogram analysis of T2*-based pharmacokinetic imaging is useful for cerebral glioma grading. The histogram parameters of the entire tumor K trans measurement can provide increased accuracy with additional information regarding microvascular permeability changes for identifying high-grade brain tumors. Copyright © 2017 Elsevier B.V. All rights reserved.

The Behaviors of Ferro-Magnetic Nano-Particles In and Around Blood Vessels under Applied Magnetic Fields

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Nacev, A.; Beni, C.; Bruno, O.; Shapiro, B.

2010-01-01

In magnetic drug delivery, therapeutic magnetizable particles are typically injected into the blood stream and magnets are then used to concentrate them to disease locations. The behavior of such particles in-vivo is complex and is governed by blood convection, diffusion (in blood and in tissue), extravasation, and the applied magnetic fields. Using physical first-principles and a sophisticated vessel-membrane-tissue (VMT) numerical solver, we comprehensively analyze in detail the behavior of magnetic particles in blood vessels and surrounding tissue. For any blood vessel (of any size, depth, and blood velocity) and tissue properties, particle size and applied magnetic fields, we consider a Krogh tissue cylinder geometry and solve for the resulting spatial distribution of particles. We find that there are three prototypical behaviors (blood velocity dominated, magnetic force dominated, and boundary-layer formation) and that the type of behavior observed is uniquely determined by three non-dimensional numbers (the magnetic-Richardson number, mass Péclet number, and Renkin reduced diffusion coefficient). Plots and equations are provided to easily read out which behavior is found under which circumstances (Figures 5, 6, 7, and 8). We compare our results to previously published in-vitro and in-vivo magnetic drug delivery experiments. Not only do we find excellent agreement between our predictions and prior experimental observations, but we are also able to qualitatively and quantitatively explain behavior that was previously not understood. PMID:21278859

Migraine aura pathophysiology: the role of blood vessels and microembolisation

OpenAIRE

Dalkara, Turgay; Nozari, Ala; Moskowitz, Michael A

2010-01-01

Migraine attacks with auras are sometimes associated with underlying hereditary or acquired cerebrovascular disorders. A unifying pathophysiological explanation linking migraine to these conditions has been diffcult to identify. On the basis of genetic and epidemiological evidence, we suggest that changes in blood vessels, hypoperfusion disorders, and microembolisation can cause neurovascular dysfunction and evoke cortical spreading depression, an event that is widely thought to underlie aura...

A Morphological Hessian Based Approach for Retinal Blood Vessels Segmentation and Denoising Using Region Based Otsu Thresholding.

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Khan BahadarKhan

Full Text Available Diabetic Retinopathy (DR harm retinal blood vessels in the eye causing visual deficiency. The appearance and structure of blood vessels in retinal images play an essential part in the diagnoses of an eye sicknesses. We proposed a less computational unsupervised automated technique with promising results for detection of retinal vasculature by using morphological hessian based approach and region based Otsu thresholding. Contrast Limited Adaptive Histogram Equalization (CLAHE and morphological filters have been used for enhancement and to remove low frequency noise or geometrical objects, respectively. The hessian matrix and eigenvalues approach used has been in a modified form at two different scales to extract wide and thin vessel enhanced images separately. Otsu thresholding has been further applied in a novel way to classify vessel and non-vessel pixels from both enhanced images. Finally, postprocessing steps has been used to eliminate the unwanted region/segment, non-vessel pixels, disease abnormalities and noise, to obtain a final segmented image. The proposed technique has been analyzed on the openly accessible DRIVE (Digital Retinal Images for Vessel Extraction and STARE (STructured Analysis of the REtina databases along with the ground truth data that has been precisely marked by the experts.

Von Willebrand factor regulation of blood vessel formation.

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Randi, Anna M; Smith, Koval E; Castaman, Giancarlo

2018-06-04

Several important physiological processes, from permeability to inflammation to haemostasis, take place at the vessel wall and are regulated by endothelial cells (EC). Thus, proteins that have been identified as regulators of one process are increasingly found to be involved in other vascular functions. Such is the case for Von Willebrand Factor (VWF), a large glycoprotein best known for its critical role in haemostasis. In vitro and in vivo studies have shown that lack of VWF causes enhanced vascularisation, both constitutively and following ischemia. This evidence is supported by studies on blood outgrowth endothelial cells (BOEC) from patients with lack of VWF synthesis (type 3 von Willebrand disease [VWD]). The molecular pathways are likely to involve VWF binding partners, such as integrin αvβ3, and components of Weibel Palade bodies (WPB), such as Angiopoietin-2 and Galectin-3, whose storage is regulated by VWF; these converge on the master regulator of angiogenesis and endothelial homeostasis, vascular endothelial growth factor (VEGF) signalling. Recent studies suggest that the roles of VWF may be tissue-specific. The ability of VWF to regulate angiogenesis has clinical implications for a subset of VWD patients with severe, intractable gastrointestinal bleeding due to vascular malformations. In this article, we review the evidence showing that VWF is involved in blood vessel formation, discuss the role of VWF high molecular weight multimers in regulating angiogenesis, and the value of studies on BOEC in developing a precision medicine approach to validate novel treatments for angiodysplasia in congenital VWD and acquired von Willebrand syndrome. Copyright © 2018 American Society of Hematology.

Monstrous cell in malignant gliomas. In relation to radiation and chemotherapy

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Ogashiwa, M; Takeuchi, K; Akai, K [Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine

1981-06-01

The pathological effects of irradiation and chemotherapy have been studied in 9 autopsy cases of malignant and low grade gliomas. The brains have been examined by means of the complete study technique. Many histological features have been related to surgery, grading of histological classification of gliomas, irradiation and chemotherapy. Following irradiation and chemotherapy, in addition to increased necrosis and vascular response, a variety of characteristic changes were observed in cell and nuclear morphology with prominent formation of monstrous cells in all of 5 malignant gliomas treated with nitrosourea. These monstrous cells had irregular and hyperchromatic multinuclei and showed cytoplasmic degeneration. These cells which had no direct relationship to vessels distributed both in the periphery of tumor or necrosis and in the white matter remote from the main tumor. These changes were more pronounced in autopsy than in biopsy. The features showed here indicate that the monstrous cells may appear due to the result of inhibition of tumor cell division at the late mitotic phase after irradiation and chemotherapy.

Glutamate/glutamine metabolism coupling between astrocytes and glioma cells: neuroprotection and inhibition of glioma growth.

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Yao, Pei-Sen; Kang, De-Zhi; Lin, Ru-Ying; Ye, Bing; Wang, Wei; Ye, Zu-Cheng

2014-07-18

Glioma glutamate release has been shown to promote the growth of glioma cells and induce neuronal injuries from epilepsy to neuronal death. However, potential counteractions from normal astrocytes against glioma glutamate release have not been fully evaluated. In this study, we investigated the glutamate/glutamine cycling between glioma cells and astrocytes and their impact on neuronal function. Co-cultures of glioma cells with astrocytes (CGA) in direct contact were established under different mix ratio of astrocyte/glioma. Culture medium conditioned in these CGAs were sampled for HPLC measurement, for neuronal ratiometric calcium imaging, and for neuronal survival assay. We found: (1) High levels of glutaminase expression in glioma cells, but not in astrocytes, glutaminase enables glioma cells to release large amount of glutamate in the presence of glutamine. (2) Glutamate levels in CGAs were directly determined by the astrocyte/glioma ratios, indicating a balance between glioma glutamate release and astrocyte glutamate uptake. (3) Culture media from CGAs of higher glioma/astrocyte ratios induced stronger neuronal Ca(2+) response and more severe neuronal death. (4) Co-culturing with astrocytes significantly reduced the growth rate of glioma cells. These results indicate that normal astrocytes in the brain play pivotal roles in glioma growth inhibition and in reducing neuronal injuries from glioma glutamate release. However, as tumor growth, the protective role of astrocytes gradually succumb to glioma cells. Copyright © 2014 Elsevier Inc. All rights reserved.

Fibre optic confocal imaging (FOCI) of keratinocytes, blood vessels and nerves in hairless mouse skin in vivo

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BUSSAU, L. J.; VO, L. T.; DELANEY, P. M.; PAPWORTH, G. D.; BARKLA, D. H.; KING, R. G.

1998-01-01

Fibre optic confocal imaging (FOCI) enabled subsurface fluorescence microscopy of the skin of hairless mice in vivo. Application of acridine orange enabled imaging of the layers of the epidermis. The corneocytes of the stratum corneum, the keratinocytes in the basal layers and redundant hair follicles were visualised at depths greater than 100 μm. Cellular and nuclear membranes of keratinocytes of the skin were visualised by the use of acridine orange and DIOC5(3). Imaging of the skin after injection of FITC-dextran revealed an extensive network of blood vessels with a size range up to 20 μm. Blood cells could be seen moving through dermal vessels and the blood circulation through the dermal vascular bed was video-taped. The fluorescent dye 4-di-2-ASP showed the presence of nerves fibres around the hair follicles and subsurface blood vessels. Comparison was made between images obtained in vivo using FOCI and in vitro scanning electron microscopy and conventional histology. FOCI offers the potential to study dynamic events in vivo, such as blood flow, skin growth, nerve regeneration and many pathological processes, in ways which have not previously been possible. PMID:9643419

Monochromatic Minibeams Radiotherapy: From Healthy Tissue-Sparing Effect Studies Toward First Experimental Glioma Bearing Rats Therapy

International Nuclear Information System (INIS)

Deman, Pierre; Vautrin, Mathias; Edouard, Magali; Stupar, Vasile; Bobyk, Laure; Farion, Régine; Elleaume, Hélène; Rémy, Chantal; Barbier, Emmanuel L.; Estève, François; Adam, Jean-François

2012-01-01

Purpose: The purpose of this study was to evaluate high-dose single fraction delivered with monochromatic X-rays minibeams for the radiotherapy of primary brain tumors in rats. Methods and Materials: Two groups of healthy rats were irradiated with one anteroposterior minibeam incidence (four minibeams, 123 Gy prescribed dose at 1 cm depth in the brain) or two interleaved incidences (54 Gy prescribed dose in a 5 × 5 × 4.8 mm 3 volume centered in the right hemisphere), respectively. Magnetic resonance imaging (MRI) follow-up was performed over 1 year. T2-weighted (T2w) images, apparent diffusion coefficient (ADC), and blood vessel permeability maps were acquired. F98 tumor bearing rats were also irradiated with interleaved minibeams to achieve a homogeneous dose of 54 Gy delivered to an 8 × 8 × 7.8 mm 3 volume centered on the tumor. Anatomic and functional MRI follow-up was performed every 10 days after irradiation. T2w images, ADC, and perfusion maps were acquired. Results: All healthy rats were euthanized 1 year after irradiation without any clinical alteration visible by simple examination. T2w and ADC measurements remain stable for the single incidence irradiation group. Localized Gd-DOTA permeability, however, was observed 9 months after irradiation for the interleaved incidences group. The survival time of irradiated glioma bearing rats was significantly longer than that of untreated animals (49 ± 12.5 days versus 23.3 ± 2 days, p < 0.001). The tumoral cerebral blood flow and blood volume tend to decrease after irradiation. Conclusions: This study demonstrates the sparing effect of minibeams on healthy tissue. The increased life span achieved for irradiated glioma bearing rats was similar to the one obtained with other radiotherapy techniques. This experimental tumor therapy study shows the feasibility of using X-ray minibeams with high doses in brain tumor radiotherapy.

Introduction of a standardized multimodality image protocol for navigation-guided surgery of suspected low-grade gliomas.

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Mert, Aygül; Kiesel, Barbara; Wöhrer, Adelheid; Martínez-Moreno, Mauricio; Minchev, Georgi; Furtner, Julia; Knosp, Engelbert; Wolfsberger, Stefan; Widhalm, Georg

2015-01-01

OBJECT Surgery of suspected low-grade gliomas (LGGs) poses a special challenge for neurosurgeons due to their diffusely infiltrative growth and histopathological heterogeneity. Consequently, neuronavigation with multimodality imaging data, such as structural and metabolic data, fiber tracking, and 3D brain visualization, has been proposed to optimize surgery. However, currently no standardized protocol has been established for multimodality imaging data in modern glioma surgery. The aim of this study was therefore to define a specific protocol for multimodality imaging and navigation for suspected LGG. METHODS Fifty-one patients who underwent surgery for a diffusely infiltrating glioma with nonsignificant contrast enhancement on MRI and available multimodality imaging data were included. In the first 40 patients with glioma, the authors retrospectively reviewed the imaging data, including structural MRI (contrast-enhanced T1-weighted, T2-weighted, and FLAIR sequences), metabolic images derived from PET, or MR spectroscopy chemical shift imaging, fiber tracking, and 3D brain surface/vessel visualization, to define standardized image settings and specific indications for each imaging modality. The feasibility and surgical relevance of this new protocol was subsequently prospectively investigated during surgery with the assistance of an advanced electromagnetic navigation system in the remaining 11 patients. Furthermore, specific surgical outcome parameters, including the extent of resection, histological analysis of the metabolic hotspot, presence of a new postoperative neurological deficit, and intraoperative accuracy of 3D brain visualization models, were assessed in each of these patients. RESULTS After reviewing these first 40 cases of glioma, the authors defined a specific protocol with standardized image settings and specific indications that allows for optimal and simultaneous visualization of structural and metabolic data, fiber tracking, and 3D brain

Mathematical Modeling of Bingham Plastic Model of Blood Flow Through Stenotic Vessel

OpenAIRE

S.R. Verma

2014-01-01

The aim of the present paper is to study the axially symmetric, laminar, steady, one-dimensional flow of blood through narrow stenotic vessel. Blood is considered as Bingham plastic fluid. The analytical results such as pressure drop, resistance to flow and wall shear stress have been obtained. Effect of yield stress and shape of stenosis on resistance to flow and wall shear stress have been discussed through tables and graphically. It has been shown that resistance to flow and th...

Segmentation of retinal blood vessels for detection of diabetic retinopathy: A review

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Rezty Amalia Aras

2016-05-01

Full Text Available Diabetic detinopathy (DR is effect of diabetes mellitus to the human vision that is the major cause of blindness. Early diagnosis of DR is an important requirement in diabetes treatment. Retinal fundus image is commonly used to observe the diabetic retinopathy symptoms. It can present retinal features such as blood vessel and also capture the pathologies which may lead to DR. Blood vessel is one of retinal features which can show the retina pathologies. It can be extracted from retinal image by image processing with following stages: pre-processing, segmentation, and post-processing. This paper contains a review of public retinal image dataset and several methods from various conducted researches. All discussed methods are applicable to each researcher cases. There is no further analysis to conclude the best method which can be used for general cases. However, we suggest morphological and multiscale method that gives the best accuracy in segmentation.

Automated artery-venous classification of retinal blood vessels based on structural mapping method

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Joshi, Vinayak S.; Garvin, Mona K.; Reinhardt, Joseph M.; Abramoff, Michael D.

2012-03-01

Retinal blood vessels show morphologic modifications in response to various retinopathies. However, the specific responses exhibited by arteries and veins may provide a precise diagnostic information, i.e., a diabetic retinopathy may be detected more accurately with the venous dilatation instead of average vessel dilatation. In order to analyze the vessel type specific morphologic modifications, the classification of a vessel network into arteries and veins is required. We previously described a method for identification and separation of retinal vessel trees; i.e. structural mapping. Therefore, we propose the artery-venous classification based on structural mapping and identification of color properties prominent to the vessel types. The mean and standard deviation of each of green channel intensity and hue channel intensity are analyzed in a region of interest around each centerline pixel of a vessel. Using the vector of color properties extracted from each centerline pixel, it is classified into one of the two clusters (artery and vein), obtained by the fuzzy-C-means clustering. According to the proportion of clustered centerline pixels in a particular vessel, and utilizing the artery-venous crossing property of retinal vessels, each vessel is assigned a label of an artery or a vein. The classification results are compared with the manually annotated ground truth (gold standard). We applied the proposed method to a dataset of 15 retinal color fundus images resulting in an accuracy of 88.28% correctly classified vessel pixels. The automated classification results match well with the gold standard suggesting its potential in artery-venous classification and the respective morphology analysis.

Detection of Blood Vessels in Color Fundus Images using a Local Radon Transform

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Reza Pourreza

2010-09-01

Full Text Available Introduction: This paper addresses a method for automatic detection of blood vessels in color fundus images which utilizes two main tools: image partitioning and local Radon transform. Material and Methods: The input images are firstly divided into overlapping windows and then the Radon transform is applied to each. The maximum of the Radon transform in each window corresponds to the probable available sub-vessel. To verify the detected sub-vessel, the maximum is compared with a predefined threshold. The verified sub-vessels are reconstructed using the Radon transform information. All detected and reconstructed sub-vessels are finally combined to make the final vessel tree. Results: The algorithm’s performance was evaluated numerically by applying it to 40 images of DRIVE database, a standard retinal image database. The vessels were extracted manually by two physicians. This database was used to test and compare the available and proposed algorithms for vessel detection in color fundus images. By comparing the output of the algorithm with the manual results, the two parameters TPR and FPR were calculated for each image and the average of TPRs and FPRs were used to plot the ROC curve. Discussion and Conclusion: Comparison of the ROC curve of this algorithm with other algorithms demonstrated the high achieved accuracy. Beside the high accuracy, the Radon transform which is integral-based makes the algorithm robust against noise.

Does Physical Fitness Buffer the Relationship between Psychosocial Stress, Retinal Vessel Diameters, and Blood Pressure among Primary Schoolchildren?

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Endes, Katharina; Herrmann, Christian; Colledge, Flora; Brand, Serge; Donath, Lars; Faude, Oliver; Pühse, Uwe; Hanssen, Henner; Zahner, Lukas

2016-01-01

Background. Strong evidence exists showing that psychosocial stress plays an important part in the development of cardiovascular diseases. Because physical inactivity is associated with less favourable retinal vessel diameter and blood pressure profiles, this study explores whether physical fitness is able to buffer the negative effects of psychosocial stress on retinal vessel diameters and blood pressure in young children. Methods. 325 primary schoolchildren (51% girls, Mage = 7.28 years) took part in this cross-sectional research project. Retinal arteriolar diameters, retinal venular diameters, arteriolar to venular ratio, and systolic and diastolic blood pressure were assessed in all children. Interactions terms between physical fitness (performance in the 20 m shuttle run test) and four indicators of psychosocial stress (parental reports of critical life events, family, peer and school stress) were tested in a series of hierarchical regression analyses. Results. Critical life events and family, peer, and school-related stress were only weakly associated with retinal vessel diameters and blood pressure. No support was found for a stress-buffering effect of physical fitness. Conclusion. More research is needed with different age groups to find out if and from what age physical fitness can protect against arteriolar vessel narrowing and the occurrence of other cardiovascular disease risk factors. PMID:27795958

Blood Vessel Extraction in Color Retinal Fundus Images with Enhancement Filtering and Unsupervised Classification

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Zafer Yavuz

2017-01-01

Full Text Available Retinal blood vessels have a significant role in the diagnosis and treatment of various retinal diseases such as diabetic retinopathy, glaucoma, arteriosclerosis, and hypertension. For this reason, retinal vasculature extraction is important in order to help specialists for the diagnosis and treatment of systematic diseases. In this paper, a novel approach is developed to extract retinal blood vessel network. Our method comprises four stages: (1 preprocessing stage in order to prepare dataset for segmentation; (2 an enhancement procedure including Gabor, Frangi, and Gauss filters obtained separately before a top-hat transform; (3 a hard and soft clustering stage which includes K-means and Fuzzy C-means (FCM in order to get binary vessel map; and (4 a postprocessing step which removes falsely segmented isolated regions. The method is tested on color retinal images obtained from STARE and DRIVE databases which are available online. As a result, Gabor filter followed by K-means clustering method achieves 95.94% and 95.71% of accuracy for STARE and DRIVE databases, respectively, which are acceptable for diagnosis systems.

A multi-parametric imaging investigation of the response of C6 glioma xenografts to MLN0518 (tandutinib treatment.

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Jessica K R Boult

Full Text Available Angiogenesis, the development of new blood vessels, is essential for tumour growth; this process is stimulated by the secretion of numerous growth factors including platelet derived growth factor (PDGF. PDGF signalling, through its receptor platelet derived growth factor receptor (PDGFR, is involved in vessel maturation, stimulation of angiogenesis and upregulation of other angiogenic factors, including vascular endothelial growth factor (VEGF. PDGFR is a promising target for anti-cancer therapy because it is expressed on both tumour cells and stromal cells associated with the vasculature. MLN0518 (tandutinib is a potent inhibitor of type III receptor tyrosine kinases that demonstrates activity against PDGFRα/β, FLT3 and c-KIT. In this study a multi-parametric MRI and histopathological approach was used to interrogate changes in vascular haemodynamics, structural response and hypoxia in C6 glioma xenografts in response to treatment with MLN0518. The doubling time of tumours in mice treated with MLN0518 was significantly longer than tumours in vehicle treated mice. The perfused vessel area, number of alpha smooth muscle actin positive vessels and hypoxic area in MLN0518 treated tumours were also significantly lower after 10 days treatment. These changes were not accompanied by alterations in vessel calibre or fractional blood volume as assessed using susceptibility contrast MRI. Histological assessment of vessel size and total perfused area did not demonstrate any change with treatment. Intrinsic susceptibility MRI did not reveal any difference in baseline R2* or carbogen-induced change in R2*. Dynamic contrast-enhanced MRI revealed anti-vascular effects of MLN0518 following 3 days treatment. Hypoxia confers chemo- and radio-resistance, and alongside PDGF, is implicated in evasive resistance to agents targeted against VEGF signalling. PDGFR antagonists may improve potency and efficacy of other therapeutics in combination. This study highlights

A multi-parametric imaging investigation of the response of C6 glioma xenografts to MLN0518 (tandutinib) treatment.

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Boult, Jessica K R; Terkelsen, Jennifer; Walker-Samuel, Simon; Bradley, Daniel P; Robinson, Simon P

2013-01-01

Angiogenesis, the development of new blood vessels, is essential for tumour growth; this process is stimulated by the secretion of numerous growth factors including platelet derived growth factor (PDGF). PDGF signalling, through its receptor platelet derived growth factor receptor (PDGFR), is involved in vessel maturation, stimulation of angiogenesis and upregulation of other angiogenic factors, including vascular endothelial growth factor (VEGF). PDGFR is a promising target for anti-cancer therapy because it is expressed on both tumour cells and stromal cells associated with the vasculature. MLN0518 (tandutinib) is a potent inhibitor of type III receptor tyrosine kinases that demonstrates activity against PDGFRα/β, FLT3 and c-KIT. In this study a multi-parametric MRI and histopathological approach was used to interrogate changes in vascular haemodynamics, structural response and hypoxia in C6 glioma xenografts in response to treatment with MLN0518. The doubling time of tumours in mice treated with MLN0518 was significantly longer than tumours in vehicle treated mice. The perfused vessel area, number of alpha smooth muscle actin positive vessels and hypoxic area in MLN0518 treated tumours were also significantly lower after 10 days treatment. These changes were not accompanied by alterations in vessel calibre or fractional blood volume as assessed using susceptibility contrast MRI. Histological assessment of vessel size and total perfused area did not demonstrate any change with treatment. Intrinsic susceptibility MRI did not reveal any difference in baseline R2* or carbogen-induced change in R2*. Dynamic contrast-enhanced MRI revealed anti-vascular effects of MLN0518 following 3 days treatment. Hypoxia confers chemo- and radio-resistance, and alongside PDGF, is implicated in evasive resistance to agents targeted against VEGF signalling. PDGFR antagonists may improve potency and efficacy of other therapeutics in combination. This study highlights the challenges

A computational study for investigating acoustic streaming and tissue heating during high intensity focused ultrasound through blood vessel with an obstacle

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Parvin, Salma; Sultana, Aysha

2017-06-01

The influence of High Intensity Focused Ultrasound (HIFU) on the obstacle through blood vessel is studied numerically. A three-dimensional acoustics-thermal-fluid coupling model is employed to compute the temperature field around the obstacle through blood vessel. The model construction is based on the linear Westervelt and conjugate heat transfer equations for the obstacle through blood vessel. The system of equations is solved using Finite Element Method (FEM). We found from this three-dimensional numerical study that the rate of heat transfer is increasing from the obstacle and both the convective cooling and acoustic streaming can considerably change the temperature field.

Different Effects of Implanting Sensory Nerve or Blood Vessel on the Vascularization, Neurotization, and Osteogenesis of Tissue-Engineered Bone In Vivo

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Fan, Jun-jun; Mu, Tian-wang; Qin, Jun-jun; Bi, Long; Pei, Guo-xian

2014-01-01

To compare the different effects of implanting sensory nerve tracts or blood vessel on the osteogenesis, vascularization, and neurotization of the tissue-engineered bone in vivo, we constructed the tissue engineered bone and implanted the sensory nerve tracts (group SN), blood vessel (group VB), or nothing (group Blank) to the side channel of the bone graft to repair the femur defect in the rabbit. Better osteogenesis was observed in groups SN and VB than in group Blank, and no significant difference was found between groups SN and VB at 4, 8, and 12 weeks postoperatively. The neuropeptides expression and the number of new blood vessels in the bone tissues were increased at 8 weeks and then decreased at 12 weeks in all groups and were highest in group VB and lowest in group Blank at all three time points. We conclude that implanting either blood vessel or sensory nerve tract into the tissue-engineered bone can significantly enhance both the vascularization and neurotization simultaneously to get a better osteogenesis effect than TEB alone, and the method of implanting blood vessel has a little better effect of vascularization and neurotization but almost the same osteogenesis effect as implanting sensory nerve. PMID:25101279

TLR9 expression in glioma tissues correlated to glioma progression and the prognosis of GBM patients

International Nuclear Information System (INIS)

Wang, Chao; Cao, Shouqiang; Yan, Ying; Ying, Qiao; Jiang, Tao; Xu, Ke; Wu, Anhua

2010-01-01

Our study aims to evaluate the expression of TLR9 in glioma tissues, examine the association between TLR9 expression, clinicopathological variables, and glioma patient outcome, we further characterized the direct effects of TLR9 agonist CpG ODN upon the proliferation and invasion of glioma cells in vitro. RT-PCR and immunofluorescence were used to determine the expression of TLR9 in glioma cell lines and clinical glioma samples. Tissue microarry and immunohistochemistry were applied to evaluated TLR9 expression in 292 newly diagnosed glioma and 13 non-neoplastic brain tissues. We further investigated the effect of CpG ODN on the proliferation and invasion of glioma cells in vitro with MTT assays and matrigel transwell assay respectively. RT-PCR showed that TLR9 expressed in all the glioma samples and glioma cell lines we examined. The tissue array analysis indicated that TLR9 expression is correlated with malignancy of glioma (p < 0.01). Multivariate Cox regression analysis revealed that TLR9 expression is an independent prognostic factor for PFS of GBM patients(P = 0.026). TLR9 agonist CpG ODN has no significant effect on glioma proliferation, but matrigel transwell analysis showed that TLR9 agonist CpG ODN can significantly enhance glioma invasion in vitro. Our data indicated that TLR9 expression increases according to the histopathological grade of glioma, and the TLR9 expression level is related to the PFS of GBM patients. In addition, our findings warrant caution in the directly injection of TLR9 agonist CpG ODN into glioma tissues for the glioma immunotherapy

Histomorphometric comparative study of blood vessels and their pattern in follicular cyst, odontogenic keratocyst, and ameloblastoma.

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Seifi, Safora; Feizi, Farideh; Khafri, Thoraya; Aram, Mehrdad

2013-03-01

The present study aimed at assessment and histomorphometric analysis of intratumoral and peritumoral (cystic) blood vessels in odontogenic lesions and their pattern on their clinical behavior by immunohistochemistry and morphometry. In a descriptive and analytical cross-sectional study, 45 paraffin blocks of ameloblastoma, odontogenic keratocyst, and follicular cyst were selected and stained immunohistochemically for CD34. In each slide, images of 3 microscopic fields with the highest microvessel density in intratumoral and peritumoral (cystic) areas were captured at 40× magnification with attached camera system. Inner vascular diameter (IVD) and outer vascular diameter (OVD), cross-sectional area (CSA), and the wall thickness (WT) of the vessels were measured with Motic Plus 2 software. The vascular pattern in odontogenic lesions was analyzed. Outer vascular diameter, IVD, and CSA of the vessels in peritumoral (cystic) areas were greater in ameloblastoma than keratocyst (P = 0.001) and follicular cyst (P keratocyst and follicular cyst. Morphometric specifications of blood vessels (IVD, OVD, CSA) and their pattern in peritumoral (cystic) areas may influence the aggressive clinical behavior of ameloblastoma in comparison with keratocyst and follicular cyst.

Did antepartum hypoxic insult caused by fetal vessel thrombosis influence the procalcitonin level in umbilical blood? A case report.

Science.gov (United States)

Kaneko, Masatoki; Yamauchi, Aya; Yamashita, Rie; Sato, Yuichiro; Kodama, Yuki; Sameshima, Hiroshi

2015-11-01

We report a case of marked elevation of the procalcitonin level in umbilical blood and neonatal blood at birth. The mother did not perceive fetal motion. Antepartum fetal heart rate monitoring showed a loss of variability and absence of acceleration. No fetal breathing movement, fetal movement, or fetal tone were observed by ultrasonography. The female neonate was delivered by cesarean section at 25 weeks of gestation, with birthweight 774 g. The umbilical arterial pH value at birth was 7.29. Mild elevation in interleukin-6 and tumor necrosis factor-α in umbilical blood were observed. Cytochrome c showed a high level in umbilical and neonatal blood at birth. Placental histopathology revealed multiple fetal vessel thrombosis in the large stem villi and chorionic vessels. The neonate showed no infectious signs throughout the neonatal period. Computed tomography at 3 months of age revealed atrophy in the cerebrum and cerebellum. At 1 year after birth, the infant showed spastic quadriplegia. In this case, antepartum asphyxia due to fetal vessel thrombosis may have influenced the elevation of procalcitonin level in umbilical blood and neonatal blood at birth. © 2015 Japan Society of Obstetrics and Gynecology.

111Indium (DTPA-octreotide) scintigraphy in patients with cerebral gliomas

International Nuclear Information System (INIS)

Luyken, C.; Hildebrandt, G.; Klug, N.; Scheidhauer, K.; Schicha, H.; Krisch, B.

1994-01-01

Somatostatin receptors (SR) have been identified in vitro in normal brain tissue, in neuro-endocrine tumours and in cerebral gliomas WHO grade 1 or 2 by autoradiography or using somatostatin-gold conjugates. In vivo, SR detection has become possible by scintigraphy applying the somatostatin analogue octreotide, radio-labelled with 111 indium. It was supposed that expression of SR in cerebral gliomas corresponds to low grade tumour malignancy and that, in vivo, somatostatin receptor scintigraphy (SRS) could refine and improve the WHO grading system for cerebral gliomas. Nineteen patients with cerebral gliomas (grade 2: n=8, grade 3: n=3, grade 4: n=8) were examined with 111 In (DTPA-octreotide) to evaluate, whether SRS could improve the pre-operative estimation of tumour biology and the postoperative management. The results of SRS were related with the histological findings and with the in vitro demonstration of somatostatin-binding sites on cultured tumour cells incubated with a somatostatin-gold conjugate. In vivo, none of the patients with glioma grade 2 showed enhanced tracer uptake in the SRS, whereas in vitro SR were detected in cultured tumour tissue in 5 out of 5 cases. Every patient with glioma grade 3 or 4 demonstrated a high focal uptake of 111 In (DTPA-octreotide), as shown by SRS. Three patients with glioma grade 4, additionally examined with 99mTc-DTPA, showed an increased tracer uptake within the tumour area when compared with results of SRS. In vitro, SR were detected on tumour cell surface in 5 out of 6 tissue samples from patients with gliomas grade 3 or 4. One patient harbouring a cerebral abscess with a high focal tracer uptake in the SRS but with absence of somatostatin-binding sites in vitro. We conclude, that in glioma patients enhanced tracer uptake in receptor scintigraphy with 111 In (DTPA-octreotide) does not depend on the presence of SR in tumour but on the dysfunction of the blood-brain barrier. Thus, SRS dose not improve the

Dynamic CT perfusion imaging of intra-axial brain tumours: differentiation of high-grade gliomas from primary CNS lymphomas

International Nuclear Information System (INIS)

Schramm, Peter; Xyda, Argyro; Knauth, Michael; Klotz, Ernst; Tronnier, Volker; Hartmann, Marius

2010-01-01

Perfusion computed tomography (PCT) allows to quantitatively assess haemodynamic characteristics of brain tissue. We investigated if different brain tumor types can be distinguished from each other using Patlak analysis of PCT data. PCT data from 43 patients with brain tumours were analysed with a commercial implementation of the Patlak method. Four patients had low-grade glioma (WHO II), 31 patients had glioblastoma (WHO IV) and eight patients had intracerebral lymphoma. Tumour regions of interest (ROIs) were drawn in a morphological image and automatically transferred to maps of cerebral blood flow (CBF), cerebral blood volume (CBV) and permeability (K Trans ). Mean values were calculated, group differences were tested using Wilcoxon and Mann Whitney U-tests. In comparison with normal parenchyma, low-grade gliomas showed no significant difference of perfusion parameters (p > 0.05), whereas high-grade gliomas demonstrated significantly higher values (p Trans , p Trans values compared with unaffected cerebral parenchyma (p = 0.0078) but no elevation of CBV. High-grade gliomas show significant higher CBV values than lymphomas (p = 0.0078). PCT allows to reliably classify gliomas and lymphomas based on quantitative measurements of CBV and K Trans . (orig.)

Vascular targeting of LIGHT normalizes blood vessels in primary brain cancer and induces intratumoural high endothelial venules.

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He, Bo; Jabouille, Arnaud; Steri, Veronica; Johansson-Percival, Anna; Michael, Iacovos P; Kotamraju, Venkata Ramana; Junckerstorff, Reimar; Nowak, Anna K; Hamzah, Juliana; Lee, Gabriel; Bergers, Gabriele; Ganss, Ruth

2018-06-01

High-grade brain cancer such as glioblastoma (GBM) remains an incurable disease. A common feature of GBM is the angiogenic vasculature, which can be targeted with selected peptides for payload delivery. We assessed the ability of micelle-tagged, vascular homing peptides RGR, CGKRK and NGR to specifically bind to blood vessels in syngeneic orthotopic GBM models. By using the peptide CGKRK to deliver the tumour necrosis factor (TNF) superfamily member LIGHT (also known as TNF superfamily member 14; TNFSF14) to angiogenic tumour vessels, we have generated a reagent that normalizes the brain cancer vasculature by inducing pericyte contractility and re-establishing endothelial barrier integrity. LIGHT-mediated vascular remodelling also activates endothelia and induces intratumoural high endothelial venules (HEVs), which are specialized blood vessels for lymphocyte infiltration. Combining CGKRK-LIGHT with anti-vascular endothelial growth factor and checkpoint blockade amplified HEV frequency and T-cell accumulation in GBM, which is often sparsely infiltrated by immune effector cells, and reduced tumour burden. Furthermore, CGKRK and RGR peptides strongly bound to blood vessels in freshly resected human GBM, demonstrating shared peptide-binding activities in mouse and human primary brain tumour vessels. Thus, peptide-mediated LIGHT targeting is a highly translatable approach in primary brain cancer to reduce vascular leakiness and enhance immunotherapy. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Blood vessel classification into arteries and veins in retinal images

Science.gov (United States)

Kondermann, Claudia; Kondermann, Daniel; Yan, Michelle

2007-03-01

The prevalence of diabetes is expected to increase dramatically in coming years; already today it accounts for a major proportion of the health care budget in many countries. Diabetic Retinopathy (DR), a micro vascular complication very often seen in diabetes patients, is the most common cause of visual loss in working age population of developed countries today. Since the possibility of slowing or even stopping the progress of this disease depends on the early detection of DR, an automatic analysis of fundus images would be of great help to the ophthalmologist due to the small size of the symptoms and the large number of patients. An important symptom for DR are abnormally wide veins leading to an unusually low ratio of the average diameter of arteries to veins (AVR). There are also other diseases like high blood pressure or diseases of the pancreas with one symptom being an abnormal AVR value. To determine it, a classification of vessels as arteries or veins is indispensable. As to our knowledge despite the importance there have only been two approaches to vessel classification yet. Therefore we propose an improved method. We compare two feature extraction methods and two classification methods based on support vector machines and neural networks. Given a hand-segmentation of vessels our approach achieves 95.32% correctly classified vessel pixels. This value decreases by 10% on average, if the result of a segmentation algorithm is used as basis for the classification.

Retinal hemodynamic oxygen reactivity assessed by perfusion velocity, blood oximetry and vessel diameter measurements

DEFF Research Database (Denmark)

Klefter, Oliver Niels; Lauritsen, Anne Øberg; Larsen, Michael

2015-01-01

PURPOSE: To test the oxygen reactivity of a fundus photographic method of measuring macular perfusion velocity and to integrate macular perfusion velocities with measurements of retinal vessel diameters and blood oxygen saturation. METHODS: Sixteen eyes in 16 healthy volunteers were studied at two...... is a valid method for assessing macular perfusion. Results were consistent with previous observations of hyperoxic blood flow reduction using blue field entoptic and laser Doppler velocimetry. Retinal perfusion seemed to be regulated around individual set points according to blood glucose levels. Multimodal...

Perfusion MRI derived indices of microvascular shunting and flow control correlate with tumor grade and outcome in patients with cerebral glioma

DEFF Research Database (Denmark)

Tietze, Anna; Mouridsen, Kim; Lassen-Ramshad, Yasmin

2015-01-01

Objectives: Deficient microvascular blood flow control is thought to cause tumor hypoxia and increase resistance to therapy. In glioma patients, we tested whether perfusion-weighted MRI (PWI) based indices of microvascular flow control provide more information on tumor grade and patient outcome...... than does the established PWI angiogenesis marker, cerebral blood volume (CBV). Material and Methods: Seventy-two glioma patients (sixty high-grade, twelve low-grade gliomas) were included. Capillary transit time heterogeneity (CTH) and COV, its ratio to blood mean transit time, provide indices...... of microvascular flow control and the extent to which oxygen can be extracted by tumor tissue. The ability of these parameters and CBV to differentiate tumor grade were assessed by receiver operating characteristic curves and logistic regression. Their ability to predict time to progression and overall survival...

[Topography of the blood vessels in the hilum of the kidney of Myrmecophaga tridactyla].

Science.gov (United States)

Souza, W M; Miglino, M A; Arantes, I G; Nascimento, A A

1991-01-01

The study was undertaken in 10 formol-imbibed kidneys of great anteater (Myrmecophaga tridactyla). After the dissection the following characteristics were showed: kidney blood vessels are distributed in 2 different sites, namely hilar and extrahilar, amounting 3 to 6 in the right side 3 to 7 in the left side. Arterial branches in extrahilar region range from 1 to 2 in both sides and in hilar region they present from 1 to 4 in the right and 1 to 2 in the left. Venous roots occur in 1 to 2 vessels in the right and 1 to 3 vessels in the left, occupying only the hilar region, except one case where it was present in the right side.

Heterogeneity of muscarinic receptor subtypes in cerebral blood vessels

International Nuclear Information System (INIS)

Garcia-Villalon, A.L.; Krause, D.N.; Ehlert, F.J.; Duckles, S.P.

1991-01-01

The identity and distribution of muscarinic cholinergic receptor subtypes and associated signal transduction mechanisms was characterized for the cerebral circulation using correlated functional and biochemical investigations. Subtypes were distinguished by the relative affinities of a panel of muscarinic antagonists, pirenzepine, AF-DX 116 [11-2-[[2-[diethylaminomethyl]- 1-piperidinyl]acetyl]-5,11-dihydro-6H- pyrido[2,3-b][1,4]benzodiazepine-6-one], hexahydrosiladifenidol, methoctramine, 4-diphenylacetoxy-N-methylpiperidine methobromide, dicyclomine, para-fluoro-hexahydrosiladifenidol and atropine. Muscarinic receptors characterized by inhibition of [3H]quinuclidinylbenzilate binding in membranes of bovine pial arteries were of the M2 subtype. In contrast pharmacological analysis of [3H]-quinuclidinylbenzilate binding in bovine intracerebral microvessels suggests the presence of an M4 subtype. Receptors mediating endothelium-dependent vasodilation in rabbit pial arteries were of the M3 subtype, whereas muscarinic receptors stimulating endothelium-independent phosphoinositide hydrolysis in bovine pial arteries were of the M1 subtype. These findings suggest that characteristics of muscarinic receptors in cerebral blood vessels vary depending on the type of vessel, cellular location and function mediated

Imaging transient blood vessel fusion events in zebrafish by correlative volume electron microscopy.

Directory of Open Access Journals (Sweden)

Hannah E J Armer

Full Text Available The study of biological processes has become increasingly reliant on obtaining high-resolution spatial and temporal data through imaging techniques. As researchers demand molecular resolution of cellular events in the context of whole organisms, correlation of non-invasive live-organism imaging with electron microscopy in complex three-dimensional samples becomes critical. The developing blood vessels of vertebrates form a highly complex network which cannot be imaged at high resolution using traditional methods. Here we show that the point of fusion between growing blood vessels of transgenic zebrafish, identified in live confocal microscopy, can subsequently be traced through the structure of the organism using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM and Serial Block Face/Scanning Electron Microscopy (SBF/SEM. The resulting data give unprecedented microanatomical detail of the zebrafish and, for the first time, allow visualization of the ultrastructure of a time-limited biological event within the context of a whole organism.

Genetic Alterations in Glioma

International Nuclear Information System (INIS)

Bralten, Linda B. C.; French, Pim J.

2011-01-01

Gliomas are the most common type of primary brain tumor and have a dismal prognosis. Understanding the genetic alterations that drive glioma formation and progression may help improve patient prognosis by identification of novel treatment targets. Recently, two major studies have performed in-depth mutation analysis of glioblastomas (the most common and aggressive subtype of glioma). This systematic approach revealed three major pathways that are affected in glioblastomas: The receptor tyrosine kinase signaling pathway, the TP53 pathway and the pRB pathway. Apart from frequent mutations in the IDH1/2 gene, much less is known about the causal genetic changes of grade II and III (anaplastic) gliomas. Exceptions include TP53 mutations and fusion genes involving the BRAF gene in astrocytic and pilocytic glioma subtypes, respectively. In this review, we provide an update on all common events involved in the initiation and/or progression across the different subtypes of glioma and provide future directions for research into the genetic changes

A Strategy for Rapid Construction of Blood Vessel-Like Structures with Complex Cell Alignments.

Science.gov (United States)

Wang, Nuoxin; Peng, Yunhu; Zheng, Wenfu; Tang, Lixue; Cheng, Shiyu; Yang, Junchuan; Liu, Shaoqin; Zhang, Wei; Jiang, Xingyu

2018-04-17

A method is developed that can rapidly produce blood vessel-like structures by bonding cell-laden electrospinning (ES) films layer by layer using fibrin glue within 90 min. This strategy allows control of cell type, cell orientation, and material composition in separate layers. Furthermore, ES films with thicker fibers (polylactic-co-glycolic acid, fiber diameter: ≈3.7 µm) are used as cell-seeding layers to facilitate the cell in-growth; those with thinner fibers (polylactic acid, fiber diameter: ≈1.8 µm) are used as outer reinforcing layers to improve the mechanical strength and reduce the liquid leakage of the scaffold. Cells grow, proliferate, and migrate well in the multilayered structure. This design aims at a new type of blood vessel substitute with flexible control of parameters and implementation of functions. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cigarette smoking, alcohol intake, and risk of glioma in the NIH-AARP Diet and Health Study.

Science.gov (United States)

Braganza, M Z; Rajaraman, P; Park, Y; Inskip, P D; Freedman, N D; Hollenbeck, A R; de González, A Berrington; Kitahara, C M

2014-01-07

Although cigarette smoking and alcohol drinking increase the risk of several cancers and certain components of cigarette smoke and alcohol can penetrate the blood-brain barrier, it remains unclear whether these exposures influence the risk of glioma. We examined the associations between cigarette smoking, alcohol intake, and risk of glioma in the National Institutes of Health-AARP Diet and Health Study, a prospective study of 477,095 US men and women ages 50-71 years at baseline. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using models with age as the time metric and adjusted for sex, race/ethnicity, education, and marital status. During a median 10.5 person-years of follow-up, 492 men and 212 women were diagnosed with first primary glioma. Among men, current, heavier smoking was associated with a reduced risk of glioma compared with never smoking, but this was based on only nine cases. No associations were observed between smoking behaviours and glioma risk in women. Greater alcohol consumption was associated with a decreased risk of glioma, particularly among men (>2 drinks per day vs Smoking and alcohol drinking do not appear to increase the risk of glioma.

Molecular Diagnostics of Gliomas Using Next Generation Sequencing of a Glioma-Tailored Gene Panel.

Science.gov (United States)

Zacher, Angela; Kaulich, Kerstin; Stepanow, Stefanie; Wolter, Marietta; Köhrer, Karl; Felsberg, Jörg; Malzkorn, Bastian; Reifenberger, Guido

2017-03-01

Current classification of gliomas is based on histological criteria according to the World Health Organization (WHO) classification of tumors of the central nervous system. Over the past years, characteristic genetic profiles have been identified in various glioma types. These can refine tumor diagnostics and provide important prognostic and predictive information. We report on the establishment and validation of gene panel next generation sequencing (NGS) for the molecular diagnostics of gliomas. We designed a glioma-tailored gene panel covering 660 amplicons derived from 20 genes frequently aberrant in different glioma types. Sensitivity and specificity of glioma gene panel NGS for detection of DNA sequence variants and copy number changes were validated by single gene analyses. NGS-based mutation detection was optimized for application on formalin-fixed paraffin-embedded tissue specimens including small stereotactic biopsy samples. NGS data obtained in a retrospective analysis of 121 gliomas allowed for their molecular classification into distinct biological groups, including (i) isocitrate dehydrogenase gene (IDH) 1 or 2 mutant astrocytic gliomas with frequent α-thalassemia/mental retardation syndrome X-linked (ATRX) and tumor protein p53 (TP53) gene mutations, (ii) IDH mutant oligodendroglial tumors with 1p/19q codeletion, telomerase reverse transcriptase (TERT) promoter mutation and frequent Drosophila homolog of capicua (CIC) gene mutation, as well as (iii) IDH wildtype glioblastomas with frequent TERT promoter mutation, phosphatase and tensin homolog (PTEN) mutation and/or epidermal growth factor receptor (EGFR) amplification. Oligoastrocytic gliomas were genetically assigned to either of these groups. Our findings implicate gene panel NGS as a promising diagnostic technique that may facilitate integrated histological and molecular glioma classification. © 2016 International Society of Neuropathology.

Rapid sealing of porcine renal blood vessels, ex vivo, using a high power, 1470-nm laser, and laparoscopic prototype

Science.gov (United States)

Hardy, Luke A.; Hutchens, Thomas C.; Larson, Eric R.; Gonzalez, David A.; Chang, Chun-Hung; Nau, William H.; Fried, Nathaniel M.

2017-05-01

Energy-based, radiofrequency (RF) and ultrasonic (US) devices currently provide rapid sealing of blood vessels during laparoscopic procedures. We are exploring infrared lasers as an alternate energy modality for vessel sealing, capable of generating less collateral thermal damage. Previous studies demonstrated feasibility of sealing vessels in an in vivo porcine model using a 1470-nm laser. However, the initial prototype was designed for testing in open surgery and featured tissue clasping and light delivery mechanisms incompatible with laparoscopic surgery. In this study, a laparoscopic prototype similar to devices currently in surgical use was developed, and performance tests were conducted on porcine renal blood vessels, ex vivo. The 5-mm outer-diameter laparoscopic prototype featured a traditional Maryland jaw configuration that enables tissue manipulation and blunt dissection. Laser energy was delivered through a 550-μm-core-diameter optical fiber with side-delivery from the lower jaw and beam dimensions of 18-mm length×1.2-mm width. The 1470-nm diode laser delivered 68 W with 3-s activation time, consistent with vessel seal times associated with RF and US-based devices. A total of 69 fresh porcine renal vessels with mean diameter of 3.3±1.7 mm were tested, ex vivo. Vessels smaller than 5-mm diameter were consistently sealed (48/51) with burst pressures greater than malignant hypertension blood pressure (180 mmHg), averaging 1038±474 mmHg. Vessels larger than 5 mm were not consistently sealed (6/18), yielding burst pressures of only 174±221 mmHg. Seal width, thermal damage zone, and thermal spread averaged 1.7±0.8, 3.4±0.7, and 1.0±0.4 mm, respectively. Results demonstrated that the 5-mm optical laparoscopic prototype consistently sealed vessels less than 5-mm diameter with low thermal spread. Further in vivo studies are planned to test the performance across a variety of vessels and tissues.

Products of cells from gliomas: VIII. Multiple-well immunoperoxidase assay of immunoreactivity of primary hybridoma supernatants with human glioma and brain tissue and cultured glioma cells.

Science.gov (United States)

McKeever, P E; Wahl, R L; Shakui, P; Jackson, G A; Letica, L H; Liebert, M; Taren, J A; Beierwaltes, W H; Hoff, J T

1990-06-01

To test the feasibility of primary screening of hybridoma supernatants against human glioma tissue, over 5000 combinations of hybridoma supernatants with glioma tissue, cultured glioma cells, and normal central neural tissue were screened with a new multiple-well (M-well) screening system. This is an immunoperoxidase assay system with visual endpoints for screening 20-30 hybridoma supernatants per single microscope slide. There were extensive differences between specificities to tissue and to cultured glioma cells when both were screened with M-wells and when cultured cells were screened with standard semi-automated fluorescence. Primary M-well screening with glioma tissue detected seven hybridoma supernatants that specifically identified parenchymal cells of glioma tissue and that were not detected with cultured cells. Immunoreactivities of individual supernatants for vascular components (nine supernatants), necrosis (five supernatants), and nuclei (three supernatants) were detected. Other supernatants bound multiple sites on glioma tissue and/or subpopulations of neurons and glia of normal tissue. The results show that primary screening with glioma tissue detects a number of different specificities of hybridoma supernatants to gliomas not detected by conventional screening with cultured cells. These are potentially applicable to diagnosis and therapy.

Limitations of quantitative photoacoustic measurements of blood oxygenation in small vessels

International Nuclear Information System (INIS)

Sivaramakrishnan, Mathangi; Maslov, Konstantin; Zhang, Hao F; Stoica, George; Wang, Lihong V

2007-01-01

We investigate the feasibility of obtaining accurate quantitative information, such as local blood oxygenation level (sO 2 ), with a spatial resolution of about 50 μm from spectral photoacoustic (PA) measurements. The optical wavelength dependence of the peak values of the PA signals is utilized to obtain the local blood oxygenation level. In our in vitro experimental models, the PA signal amplitude is found to be linearly proportional to the blood optical absorption coefficient when using ultrasonic transducers with central frequencies high enough such that the ultrasonic wavelengths are shorter than the light penetration depth into the blood vessels. For an optical wavelength in the 578-596 nm region, with a transducer central frequency that is above 25 MHz, the sensitivity and accuracy of sO 2 inversion is shown to be better than 4%. The effect of the transducer focal position on the accuracy of quantifying blood oxygenation is found to be negligible. In vivo oxygenation measurements of rat skin microvasculature yield results consistent with those from in vitro studies, although factors specific to in vivo measurements, such as the spectral dependence of tissue optical attenuation, dramatically affect the accuracy of sO 2 quantification in vivo

Radioimmunoimaging of experimental gliomas using radiolabelled monoclonal antibodies

International Nuclear Information System (INIS)

Glaessner, H.

1986-01-01

The biodistribution and tumour uptake of radiolabelled (131 I) glioma-seeking monoclonal antibodies (14 AC1) and their F(ab') 2 fragments were investigated in nude mice having received glioma transplants. Radioimmunoimaging by external scintigraphy at 48 and 96 hours pointed to a superior tumour localisation by the fragments that was clearly related to the dose. Wholebody determinations of the biokinetic behaviour led to the following results: Faster clearance anc more ready elimination from the blood pool for the fragments, preferential uptake in the tumour; intact antibodies; binding in the liver, spleen and lungs. The study confirmed the value of fragments of monoclonal antibodies in the diagnosis of tumours and pointed to the possibility of using intact monoclonal antibodies as carriers of radioisotopes and cytotoxic drugs within the scope of therapeutic programmes. (TRV) [de

Modeling the Role of the Glymphatic Pathway and Cerebral Blood Vessel Properties in Alzheimer's Disease Pathogenesis.

Science.gov (United States)

Kyrtsos, Christina Rose; Baras, John S

2015-01-01

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, affecting over 10% population over the age of 65 years. Clinically, AD is described by the symptom set of short term memory loss and cognitive decline, changes in mentation and behavior, and eventually long-term memory deficit as the disease progresses. On imaging studies, significant atrophy with subsequent increase in ventricular volume have been observed. Pathology on post-mortem brain specimens demonstrates the classic findings of increased beta amyloid (Aβ) deposition and the presence of neurofibrillary tangles (NFTs) within affected neurons. Neuroinflammation, dysregulation of blood-brain barrier transport and clearance, deposition of Aβ in cerebral blood vessels, vascular risk factors such as atherosclerosis and diabetes, and the presence of the apolipoprotein E4 allele have all been identified as playing possible roles in AD pathogenesis. Recent research has demonstrated the importance of the glymphatic system in the clearance of Aβ from the brain via the perivascular space surrounding cerebral blood vessels. Given the variety of hypotheses that have been proposed for AD pathogenesis, an interconnected, multilayer model offers a unique opportunity to combine these ideas into a single unifying model. Results of this model demonstrate the importance of vessel stiffness and heart rate in maintaining adequate clearance of Aβ from the brain.

MicroRNA in Human Glioma

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Li, Mengfeng, E-mail: limf@mail.sysu.edu.cn [Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou 510080 (China); Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Li, Jun [Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou 510080 (China); Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Liu, Lei; Li, Wei [Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou 510080 (China); Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Yang, Yi [Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou 510080 (China); Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Yuan, Jie [Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou 510080 (China); Key Laboratory of Functional Molecules from Oceanic Microorganisms (Sun Yat-sen University), Department of Education of Guangdong Province, Guangzhou 510080 (China)

2013-10-23

Glioma represents a serious health problem worldwide. Despite advances in surgery, radiotherapy, chemotherapy, and targeting therapy, the disease remains one of the most lethal malignancies in humans, and new approaches to improvement of the efficacy of anti-glioma treatments are urgently needed. Thus, new therapeutic targets and tools should be developed based on a better understanding of the molecular pathogenesis of glioma. In this context, microRNAs (miRNAs), a class of small, non-coding RNAs, play a pivotal role in the development of the malignant phenotype of glioma cells, including cell survival, proliferation, differentiation, tumor angiogenesis, and stem cell generation. This review will discuss the biological functions of miRNAs in human glioma and their implications in improving clinical diagnosis, prediction of prognosis, and anti-glioma therapy.

MicroRNA in Human Glioma

International Nuclear Information System (INIS)

Li, Mengfeng; Li, Jun; Liu, Lei; Li, Wei; Yang, Yi; Yuan, Jie

2013-01-01

Glioma represents a serious health problem worldwide. Despite advances in surgery, radiotherapy, chemotherapy, and targeting therapy, the disease remains one of the most lethal malignancies in humans, and new approaches to improvement of the efficacy of anti-glioma treatments are urgently needed. Thus, new therapeutic targets and tools should be developed based on a better understanding of the molecular pathogenesis of glioma. In this context, microRNAs (miRNAs), a class of small, non-coding RNAs, play a pivotal role in the development of the malignant phenotype of glioma cells, including cell survival, proliferation, differentiation, tumor angiogenesis, and stem cell generation. This review will discuss the biological functions of miRNAs in human glioma and their implications in improving clinical diagnosis, prediction of prognosis, and anti-glioma therapy

Comparison of the number of gingival blood vessels between type 2 diabetes mellitus and chronic periodontitis patients: An immunohistological study

Directory of Open Access Journals (Sweden)

Gautami Subhadra Penmetsa

2015-01-01

Full Text Available Background: The relationship between diabetes and periodontitis has been studied for more than 50 years and is generally agreed that the periodontal disease is more prevalent in diabetic patients compared to nondiabetics. Vascular changes like increased thickness of basement membrane in small vessels has been reported in diabetic patients, but the quantity of blood vessels in gingiva of diabetic patients has not been discussed much. The aim of this study was to compare the number of blood vessels in gingiva between chronic periodontitis (CP patients, CP with diabetes (type 2, and normal healthy gingiva. Materials and Methods: The study included 75 patients, divided into three groups of 25 patients each-Group I with healthy periodontium (HP, Group II with CP, and Group III with CP with diabetes mellitus (CPDM.Gingival biopsies were obtained from the subjects undergoing crown lengthening procedure for Group I, and in patients with CP and in CPDM biopsies were collected from teeth undergoing extraction. Sections were prepared for immune histochemical staining with CD34. Results: Difference was observed in the average number of blood vessels when compared between HP, CP, and CPDM groups. Statistical significant difference was observed when the HP and CP groups and HP and CPDM groups were compared. Conclusion: The results of the study indicated that the number of blood vessels in gingival connective tissue is significantly higher in CP and CPDM patients.

X-ray PIV measurement of blood flow in deep vessels of a rat: An in vivo feasibility study.

Science.gov (United States)

Park, Hanwook; Yeom, Eunseop; Lee, Sang Joon

2016-01-18

X-ray PIV measurement is a noninvasive approach to measure opaque blood flows. However, it is not easy to measure real pulsatile blood flows in the blood vessels located at deep position of the body, because the surrounding tissues significantly attenuate the contrast of X-ray images. This study investigated the effect of surrounding tissues on X-ray beam attenuation by measuring the velocity fields of blood flows in deep vessels of a live rat. The decrease in image contrast was minimized by employing biocompatible CO2 microbubbles as tracer particles. The maximum measurable velocity of blood flows in the abdominal aorta of a rat model was found through comparative examination between the PIV measurement accuracy and the level of image contrast according to the input flow rate. Furthermore, the feasibility of using X-ray PIV to accurately measure in vivo blood flows was demonstrated by determining the velocity field of blood flows in the inferior vena cava of a rat. This study may serve as a reference in conducting in vivo X-ray PIV measurements of pulsatile blood flows in animal disease models and investigating hemodynamic characteristics and circulatory vascular diseases.

Spatial distribution of diffuse, primitive, and classic amyloid-beta deposits and blood vessels in the upper laminae of the frontal cortex in Alzheimer disease.

Science.gov (United States)

Armstrong, R A; Cairns, N J; Lantos, P L

1998-12-01

The spatial distribution of the diffuse, primitive, and classic amyloid-beta deposits was studied in the upper laminae of the superior frontal gyrus in cases of sporadic Alzheimer disease (AD). Amyloid-beta-stained tissue was counterstained with collagen IV to determine whether the spatial distribution of the amyloid-beta deposits along the cortex was related to blood vessels. In all patients, amyloid-beta deposits and blood vessels were aggregated into distinct clusters and in many patients, the clusters were distributed with a regular periodicity along the cortex. The clusters of diffuse and primitive deposits did not coincide with the clusters of blood vessels in most patients. However, the clusters of classic amyloid-beta deposits coincided with those of the large diameter (>10 microm) blood vessels in all patients and with clusters of small-diameter (upper cortical laminae.

Whole-tumor histogram analysis of the cerebral blood volume map: tumor volume defined by 11C-methionine positron emission tomography image improves the diagnostic accuracy of cerebral glioma grading.

Science.gov (United States)

Wu, Rongli; Watanabe, Yoshiyuki; Arisawa, Atsuko; Takahashi, Hiroto; Tanaka, Hisashi; Fujimoto, Yasunori; Watabe, Tadashi; Isohashi, Kayako; Hatazawa, Jun; Tomiyama, Noriyuki

2017-10-01

This study aimed to compare the tumor volume definition using conventional magnetic resonance (MR) and 11C-methionine positron emission tomography (MET/PET) images in the differentiation of the pre-operative glioma grade by using whole-tumor histogram analysis of normalized cerebral blood volume (nCBV) maps. Thirty-four patients with histopathologically proven primary brain low-grade gliomas (n = 15) and high-grade gliomas (n = 19) underwent pre-operative or pre-biopsy MET/PET, fluid-attenuated inversion recovery, dynamic susceptibility contrast perfusion-weighted magnetic resonance imaging, and contrast-enhanced T1-weighted at 3.0 T. The histogram distribution derived from the nCBV maps was obtained by co-registering the whole tumor volume delineated on conventional MR or MET/PET images, and eight histogram parameters were assessed. The mean nCBV value had the highest AUC value (0.906) based on MET/PET images. Diagnostic accuracy significantly improved when the tumor volume was measured from MET/PET images compared with conventional MR images for the parameters of mean, 50th, and 75th percentile nCBV value (p = 0.0246, 0.0223, and 0.0150, respectively). Whole-tumor histogram analysis of CBV map provides more valuable histogram parameters and increases diagnostic accuracy in the differentiation of pre-operative cerebral gliomas when the tumor volume is derived from MET/PET images.

Intra-lesional spatial correlation of static and dynamic FET-PET parameters with MRI-based cerebral blood volume in patients with untreated glioma.

Science.gov (United States)

Göttler, Jens; Lukas, Mathias; Kluge, Anne; Kaczmarz, Stephan; Gempt, Jens; Ringel, Florian; Mustafa, Mona; Meyer, Bernhard; Zimmer, Claus; Schwaiger, Markus; Förster, Stefan; Preibisch, Christine; Pyka, Thomas

2017-03-01

18 F-fluorethyltyrosine-(FET)-PET and MRI-based relative cerebral blood volume (rCBV) have both been used to characterize gliomas. Recently, inter-individual correlations between peak static FET-uptake and rCBV have been reported. Herein, we assess the local intra-lesional relation between FET-PET parameters and rCBV. Thirty untreated glioma patients (27 high-grade) underwent simultaneous PET/MRI on a 3 T hybrid scanner obtaining structural and dynamic susceptibility contrast sequences. Static FET-uptake and dynamic FET-slope were correlated with rCBV within tumour hotspots across patients and intra-lesionally using a mixed-effects model to account for inter-individual variation. Furthermore, maximal congruency of tumour volumes defined by FET-uptake and rCBV was determined. While the inter-individual relationship between peak static FET-uptake and rCBV could be confirmed, our intra-lesional, voxel-wise analysis revealed significant positive correlations (median r = 0.374, p dynamic FET-PET variance and maximal overlap of respective tumour volumes was 37% on average. Our results show that the relation between peak values of MR-based rCBV and static FET-uptake can also be observed intra-individually on a voxel basis and also applies to a dynamic FET parameter, possibly determining hotspots of higher biological malignancy. However, just a small part of the FET-PET signal variance is explained by rCBV and tumour volumes determined by the two modalities showed only moderate overlap. These findings indicate that FET-PET and MR-based rCBV provide both congruent and complimentary information on glioma biology.

Numerical modeling of the pulse wave propagation in large blood vessels based on liquid and wall interaction

International Nuclear Information System (INIS)

Rup, K; Dróżdż, A

2014-01-01

The purpose of this article is to develop a non-linear, one-dimensional model of pulse wave propagation in the arterial cardiovascular system. The model includes partial differential equations resulting from the balance of mass and momentum for the fluid-filled area and the balance equation for the area of the wall and vessels. The considered mathematical model of pulse wave propagation in the thoracic aorta section takes into account the viscous dissipation of fluid energy, realistic values of parameters describing the physicochemical properties of blood and vessel wall. Boundary and initial conditions contain the appropriate information obtained from in vivo measurements. As a result of the numerical solution of the mass and momentum balance equations for the blood and the equilibrium equation for the arterial wall area, time- dependent deformation, respective velocity profiles and blood pressure were determined.

Monochromatic Minibeams Radiotherapy: From Healthy Tissue-Sparing Effect Studies Toward First Experimental Glioma Bearing Rats Therapy

Energy Technology Data Exchange (ETDEWEB)

Deman, Pierre [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Vautrin, Mathias [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); DOSIsoft, Cachan (France); Edouard, Magali [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Stupar, Vasile [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); Bobyk, Laure; Farion, Regine [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Elleaume, Helene [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Grenoble University Hospital, Grenoble (France); Remy, Chantal; Barbier, Emmanuel L. [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); Esteve, Francois [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Grenoble University Hospital, Grenoble (France); Adam, Jean-Francois, E-mail: adam@esrf.fr [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Grenoble University Hospital, Grenoble (France)

2012-03-15

Purpose: The purpose of this study was to evaluate high-dose single fraction delivered with monochromatic X-rays minibeams for the radiotherapy of primary brain tumors in rats. Methods and Materials: Two groups of healthy rats were irradiated with one anteroposterior minibeam incidence (four minibeams, 123 Gy prescribed dose at 1 cm depth in the brain) or two interleaved incidences (54 Gy prescribed dose in a 5 Multiplication-Sign 5 Multiplication-Sign 4.8 mm{sup 3} volume centered in the right hemisphere), respectively. Magnetic resonance imaging (MRI) follow-up was performed over 1 year. T2-weighted (T2w) images, apparent diffusion coefficient (ADC), and blood vessel permeability maps were acquired. F98 tumor bearing rats were also irradiated with interleaved minibeams to achieve a homogeneous dose of 54 Gy delivered to an 8 Multiplication-Sign 8 Multiplication-Sign 7.8 mm{sup 3} volume centered on the tumor. Anatomic and functional MRI follow-up was performed every 10 days after irradiation. T2w images, ADC, and perfusion maps were acquired. Results: All healthy rats were euthanized 1 year after irradiation without any clinical alteration visible by simple examination. T2w and ADC measurements remain stable for the single incidence irradiation group. Localized Gd-DOTA permeability, however, was observed 9 months after irradiation for the interleaved incidences group. The survival time of irradiated glioma bearing rats was significantly longer than that of untreated animals (49 {+-} 12.5 days versus 23.3 {+-} 2 days, p < 0.001). The tumoral cerebral blood flow and blood volume tend to decrease after irradiation. Conclusions: This study demonstrates the sparing effect of minibeams on healthy tissue. The increased life span achieved for irradiated glioma bearing rats was similar to the one obtained with other radiotherapy techniques. This experimental tumor therapy study shows the feasibility of using X-ray minibeams with high doses in brain tumor radiotherapy.

An Automatic Cognitive Graph-Based Segmentation for Detection of Blood Vessels in Retinal Images

Directory of Open Access Journals (Sweden)

Rasha Al Shehhi

2016-01-01

Full Text Available This paper presents a hierarchical graph-based segmentation for blood vessel detection in digital retinal images. This segmentation employs some of perceptual Gestalt principles: similarity, closure, continuity, and proximity to merge segments into coherent connected vessel-like patterns. The integration of Gestalt principles is based on object-based features (e.g., color and black top-hat (BTH morphology and context and graph-analysis algorithms (e.g., Dijkstra path. The segmentation framework consists of two main steps: preprocessing and multiscale graph-based segmentation. Preprocessing is to enhance lighting condition, due to low illumination contrast, and to construct necessary features to enhance vessel structure due to sensitivity of vessel patterns to multiscale/multiorientation structure. Graph-based segmentation is to decrease computational processing required for region of interest into most semantic objects. The segmentation was evaluated on three publicly available datasets. Experimental results show that preprocessing stage achieves better results compared to state-of-the-art enhancement methods. The performance of the proposed graph-based segmentation is found to be consistent and comparable to other existing methods, with improved capability of detecting small/thin vessels.

Astroblastoma: beside being a tumor entity, an occasional phenotype of astrocytic gliomas?

Directory of Open Access Journals (Sweden)

Mellai M

2015-02-01

Full Text Available Marta Mellai,1 Angela Piazzi,1 Cristina Casalone,2 Silvia Grifoni,2 Antonio Melcarne,3 Laura Annovazzi,1 Paola Cassoni,4 Tetyana Denysenko,1 Maria Consuelo Valentini,5 Angelina Cistaro,6,7 Davide Schiffer1 1Neuro-Bio-Oncology Center, Policlinico di Monza Foundation/Consorzio di Neuroscienze, University of Pavia, Vercelli, Italy; 2Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, Turin, Italy; 3Department of Neurosurgery, CTO Hospital/Città della Salute e della Scienza, Turin, Italy; 4Department of Medical Sciences, University of Turin, Turin, Italy; 5Department of Neuroradiology, CTO Hospital/Città della Salute e della Scienza, Turin, Italy; 6Positron Emission Tomography Center IRMET S.p.A, Euromedic Inc., Turin, Italy; 7Institute of Cognitive Sciences and Technologies, National Research Council, Rome, Italy Abstract: The diagnosis of astroblastoma is based on a typical histological aspect with perivascular distribution of cells sending cytoplasmic extensions to the vessels and vascular hyalinization. These criteria are useful for standardizing the identification of the tumor, but, in spite of this, there are discrepancies in the literature concerning the age distribution and the benign or malignant nature of the tumor. Three cases are discussed in this study: Case 1 was a typical high-grade astroblastoma; Case 2 was an oligodendroglioma at the first intervention and an oligoastrocytoma at the second intervention with typical perivascular arrangements in the astrocytic component; Case 3 was a gemistocytic glioma with malignant features and typical perivascular arrangements. Genetic analysis showed genetic alterations that are typical of gliomas of all malignancy grades. Using the neurosphere assay, neurospheres and adherent cells were found to have developed in Case 1, while adherent cells only developed in Case 2, in line with the stemness potential of the tumors. The cases are discussed in relation to their

Decreased circulation time offsets increased efficacy of PEGylated nanocarriers targeting folate receptors of glioma

International Nuclear Information System (INIS)

McNeeley, Kathleen M; Annapragada, Ananth; Bellamkonda, Ravi V

2007-01-01

Liposomal and other nanocarrier based drug delivery vehicles can localize to tumours through passive and/or active targeting. Passively targeted liposomal nanocarriers accumulate in tumours via 'leaky' vasculature through the enhanced permeability and retention (EPR) effect. Passive accumulation depends upon the circulation time and the degree of tumour vessel 'leakiness'. After extravasation, actively targeted liposomal nanocarriers efficiently deliver their payload by receptor-mediated uptake. However, incorporation of targeting moieties can compromise circulation time in the blood due to recognition and clearance by the reticuloendothelial system, decreasing passive accumulation. Here, we compare the efficacy of passively targeted doxorubicin-loaded PEGylated liposomal nanocarriers to that of actively targeted liposomal nanocarriers in a rat 9L brain tumour model. Although folate receptor (FR)-targeted liposomal nanocarriers had significantly reduced blood circulation time compared to PEGylated liposomal nanocarriers; intratumoural drug concentrations both at 20 and 50 h after administration were equal for both treatments. Both treatments significantly increased tumour inoculated animal survival by 60-80% compared to non-treated controls, but no difference in survival was observed between FR-targeted and passively targeted nanocarriers. Therefore, alternate approaches allowing for active targeting without compromising circulation time may be important for fully realizing the benefits of receptor-mediated active targeting of gliomas

Known glioma risk loci are associated with glioma with a family history of brain tumours

DEFF Research Database (Denmark)

Melin, Beatrice; Dahlin, Anna M; Andersson, Ulrika

2013-01-01

significantly associated with glioma risk, rs6010620 (ORtrend for the minor (A) allele, 0.39; 95% CI: 0.25-0.61; Bonferroni adjusted ptrend , 1.7 × 10(-4) ). In conclusion, as previously shown for glioma regardless of family history of brain tumours, rs6010620 (RTEL1) was associated with an increased risk...... family history of brain tumours, defined as having at least one first- or second-degree relative with a history of brain tumour, are associated with known glioma risk loci. One thousand four hundred and thirty-one glioma cases and 2,868 cancer-free controls were identified from four case-control studies...... and two prospective cohorts from USA, Sweden and Denmark and genotyped for seven SNPs previously reported to be associated with glioma risk in case-control designed studies. Odds ratios were calculated by unconditional logistic regression. In analyses including glioma cases with a family history of brain...

A SURVEY OF RETINA BASED DISEASE IDENTIFICATION USING BLOOD VESSEL SEGMENTATION

Directory of Open Access Journals (Sweden)

P Kuppusamy

2016-11-01

Full Text Available The colour retinal photography is one of the most essential features to identify the confirmation of various eye diseases. The iris is primary attribute to authenticate the human. This research work presents the survey and comparison of various blood vessel related feature identification, segmentation, extraction and enhancement methods. Additionally, this study is observed the various databases performance for storing the images and testing in minimal time. This paper is also provides the better performance techniques based on the survey.

Modeling the Role of the Glymphatic Pathway and Cerebral Blood Vessel Properties in Alzheimer's Disease Pathogenesis.

Directory of Open Access Journals (Sweden)

Christina Rose Kyrtsos

Full Text Available Alzheimer's disease (AD is the most common cause of dementia in the elderly, affecting over 10% population over the age of 65 years. Clinically, AD is described by the symptom set of short term memory loss and cognitive decline, changes in mentation and behavior, and eventually long-term memory deficit as the disease progresses. On imaging studies, significant atrophy with subsequent increase in ventricular volume have been observed. Pathology on post-mortem brain specimens demonstrates the classic findings of increased beta amyloid (Aβ deposition and the presence of neurofibrillary tangles (NFTs within affected neurons. Neuroinflammation, dysregulation of blood-brain barrier transport and clearance, deposition of Aβ in cerebral blood vessels, vascular risk factors such as atherosclerosis and diabetes, and the presence of the apolipoprotein E4 allele have all been identified as playing possible roles in AD pathogenesis. Recent research has demonstrated the importance of the glymphatic system in the clearance of Aβ from the brain via the perivascular space surrounding cerebral blood vessels. Given the variety of hypotheses that have been proposed for AD pathogenesis, an interconnected, multilayer model offers a unique opportunity to combine these ideas into a single unifying model. Results of this model demonstrate the importance of vessel stiffness and heart rate in maintaining adequate clearance of Aβ from the brain.

Semiautomated segmentation of blood vessels using ellipse-overlap criteria: Method and comparison to manual editing

International Nuclear Information System (INIS)

Shiffman, Smadar; Rubin, Geoffrey D.; Schraedley-Desmond, Pamela; Napel, Sandy

2003-01-01

Two-dimensional intensity-based methods for the segmentation of blood vessels from computed-tomography-angiography data often result in spurious segments that originate from other objects whose intensity distributions overlap with those of the vessels. When segmented images include spurious segments, additional methods are required to select segments that belong to the target vessels. We describe a method that allows experts to select vessel segments from sequences of segmented images with little effort. Our method uses ellipse-overlap criteria to differentiate between segments that belong to different objects and are separated in plane but are connected in the through-plane direction. To validate our method, we used it to extract vessel regions from volumes that were segmented via analysis of isolabel-contour maps, and showed that the difference between the results of our method and manually-edited results was within inter-expert variability. Although the total editing duration for our method, which included user-interaction and computer processing, exceeded that of manual editing, the extent of user interaction required for our method was about a fifth of that required for manual editing

Chronic mild hypoxia promotes profound vascular remodeling in spinal cord blood vessels, preferentially in white matter, via an α5β1 integrin-mediated mechanism.

Science.gov (United States)

Halder, Sebok K; Kant, Ravi; Milner, Richard

2018-05-01

Spinal cord injury (SCI) leads to rapid destruction of neuronal tissue, resulting in devastating motor and sensory deficits. This is exacerbated by damage to spinal cord blood vessels and loss of vascular integrity. Thus, approaches that protect existing blood vessels or stimulate the growth of new blood vessels might present a novel approach to minimize loss or promote regeneration of spinal cord tissue following SCI. In light of the remarkable power of chronic mild hypoxia (CMH) to stimulate vascular remodeling in the brain, the goal of this study was to examine how CMH (8% O 2 for up to 7 days) affects blood vessel remodeling in the spinal cord. We found that CMH promoted the following: (1) endothelial proliferation and increased vascularity as a result of angiogenesis and arteriogenesis, (2) increased vascular expression of the angiogenic extracellular matrix protein fibronectin as well as concomitant increases in endothelial expression of the fibronectin receptor α5β1 integrin, (3) strongly upregulated endothelial expression of the tight junction proteins claudin-5, ZO-1 and occludin and (4) astrocyte activation. Of note, the vascular remodeling changes induced by CMH were more extensive in white matter. Interestingly, hypoxic-induced vascular remodeling in spinal cord blood vessels was markedly attenuated in mice lacking endothelial α5 integrin expression (α5-EC-KO mice). Taken together, these studies demonstrate the considerable remodeling potential of spinal cord blood vessels and highlight an important angiogenic role for the α5β1 integrin in promoting endothelial proliferation. They also imply that stimulation of the α5β1 integrin or controlled use of mild hypoxia might provide new approaches for promoting angiogenesis and improving vascular integrity in spinal cord blood vessels.

Effects of X-irradiation on artificial blood vessel wall degradation by invasive tumor cells

International Nuclear Information System (INIS)

Heisel, M.A.; Laug, W.E.; Stowe, S.M.; Jones, P.A.

1984-01-01

Artificial vessel wall cultures, constructed by growing arterial endothelial cells on preformed layers of rat smooth muscle cells, were used to evaluate the effects of X-irradiation on tumor cell-induced tissue degradation. Bovine endothelial cells had radiation sensitivities similar to those of rat smooth muscle cells. Preirradiation of smooth muscle cells, before the addition of human fibrosarcoma (HT 1080) cells, did not increase the rate of degradation and destruction by the invasive cells. However, the degradation rate was decreased if the cultures were irradiated after the addition of HT 1080 cells. The presence of bovine endothelial cells markedly inhibited the destructive abilities of fibrosarcoma cells, but preirradiation of artificial vessel walls substantially decreased their capabilities to resist HT 1080-induced lysis. These findings suggest that the abilities of blood vessels to limit extravasation may be compromised by ionizing radiation

High Endothelial Venules and Other Blood Vessels: Critical Regulators of Lymphoid Organ Development and Function

Science.gov (United States)

Ager, Ann

2017-01-01

The blood vasculature regulates both the development and function of secondary lymphoid organs by providing a portal for entry of hemopoietic cells. During the development of lymphoid organs in the embryo, blood vessels deliver lymphoid tissue inducer cells that initiate and sustain the development of lymphoid tissues. In adults, the blood vessels are structurally distinct from those in other organs due to the requirement for high levels of lymphocyte recruitment under non-inflammatory conditions. In lymph nodes (LNs) and Peyer’s patches, high endothelial venules (HEVs) especially adapted for lymphocyte trafficking form a spatially organized network of blood vessels, which controls both the type of lymphocyte and the site of entry into lymphoid tissues. Uniquely, HEVs express vascular addressins that regulate lymphocyte entry into lymphoid organs and are, therefore, critical to the function of lymphoid organs. Recent studies have demonstrated important roles for CD11c+ dendritic cells in the induction, as well as the maintenance, of vascular addressin expression and, therefore, the function of HEVs. Tertiary lymphoid organs (TLOs) are HEV containing LN-like structures that develop inside organized tissues undergoing chronic immune-mediated inflammation. In autoimmune lesions, the development of TLOs is thought to exacerbate disease. In cancerous tissues, the development of HEVs and TLOs is associated with improved patient outcomes in several cancers. Therefore, it is important to understand what drives the development of HEVs and TLOs and how these structures contribute to pathology. In several human diseases and experimental animal models of chronic inflammation, there are some similarities between the development and function of HEVs within LN and TLOs. This review will summarize current knowledge of how hemopoietic cells with lymphoid tissue-inducing, HEV-inducing, and HEV-maintaining properties are recruited from the bloodstream to induce the development and

High-resolution ultrasound imaging and noninvasive optoacoustic monitoring of blood variables in peripheral blood vessels

Science.gov (United States)

Petrov, Irene Y.; Petrov, Yuriy; Prough, Donald S.; Esenaliev, Rinat O.

2011-03-01

Ultrasound imaging is being widely used in clinics to obtain diagnostic information non-invasively and in real time. A high-resolution ultrasound imaging platform, Vevo (VisualSonics, Inc.) provides in vivo, real-time images with exceptional resolution (up to 30 microns) using high-frequency transducers (up to 80 MHz). Recently, we built optoacoustic systems for probing radial artery and peripheral veins that can be used for noninvasive monitoring of total hemoglobin concentration, oxyhemoglobin saturation, and concentration of important endogenous and exogenous chromophores (such as ICG). In this work we used the high-resolution ultrasound imaging system Vevo 770 for visualization of the radial artery and peripheral veins and acquired corresponding optoacoustic signals from them using the optoacoustic systems. Analysis of the optoacoustic data with a specially developed algorithm allowed for measurement of blood oxygenation in the blood vessels as well as for continuous, real-time monitoring of arterial and venous blood oxygenation. Our results indicate that: 1) the optoacoustic technique (unlike pure optical approaches and other noninvasive techniques) is capable of accurate peripheral venous oxygenation measurement; and 2) peripheral venous oxygenation is dependent on skin temperature and local hemodynamics. Moreover, we performed for the first time (to the best of our knowledge) a comparative study of optoacoustic arterial oximetry and a standard pulse oximeter in humans and demonstrated superior performance of the optoacoustic arterial oximeter, in particular at low blood flow.

Nanotechnology Applications for Diffuse Intrinsic Pontine Glioma.

Science.gov (United States)

Bredlau, Amy Lee; Dixit, Suraj; Chen, Chao; Broome, Ann-Marie

2017-01-01

Diffuse intrinsic pontine gliomas (DIPGs) are invariably fatal tumors found in the pons of elementary school aged children. These tumors are grade II-IV gliomas, with a median survival of less than 1 year from diagnosis when treated with standard of care (SOC) therapy. Nanotechnology may offer therapeutic options for the treatment of DIPGs. Multiple nanoparticle formulations are currently being investigated for the treatment of DIPGs. Nanoparticles based upon stable elements, polymer nanoparticles, and organic nanoparticles are under development for the treatment of brain tumors, including DIPGs. Targeting of nanoparticles is now possible as delivery techniques that address the difficulty in crossing the blood brain barrier (BBB) are developed. Theranostic nanoparticles, a combination of therapeutics and diagnostic nanoparticles, improve imaging of the cancerous tissue while delivering therapy to the local region. However, additional time and attention should be directed to developing a nanoparticle delivery system for treatment of the uniformly fatal pediatric disease of DIPG.

Photoacoustic imaging of blood vessels with a double-ring sensor featuring a narrow angular aperture

NARCIS (Netherlands)

Kolkman, R.G.M.; Hondebrink, Erwin; Steenbergen, Wiendelt; van Leeuwen, Ton; de Mul, F.F.M.

2004-01-01

A photoacoustic double-ring sensor, featuring a narrow angular aperture, is developed for laser-induced photoacoustic imaging of blood vessels. An integrated optical fiber enables reflection-mode detection of ultrasonic waves. By using the cross-correlation between the signals detected by the two

Fotemustine: A Third-Generation Nitrosourea for the Treatment of Recurrent Malignant Gliomas

International Nuclear Information System (INIS)

Beauchesne, Patrick

2012-01-01

Malignant gliomas account for approximately 60% of all primary brain tumors in adults. The prognosis for patients with malignant glioma has not changed significantly in recent years. Despite debulking surgery, radiotherapy and cytotoxic chemotherapy, the median survival time is nine to 12 months, and very few, if any, patients are cured from this illness. Fotemustine is an alkylating agent characterized by the grafting of a phosphonoalanine group onto the nitrosourea radical with consequent high lipophilicity and improved diffusion through the cell membrane and the blood-brain barrier. Fotemustine has been registered for use in two indications: disseminated malignant melanoma, including cerebral metastases, and primary brain tumors. Fotemustine is currently used in Europe, particularly in France and Italy, as a salvage therapy for recurrent malignant gliomas. Myelosuppression, leucopenia and thrombocytopenia are the most frequent side effects of treatment with fotemustine. The objective response to this treatment is between 26% and 70%, and the reported median survival time is 10 months. New drug combinations containing fotemustine and angiogenesis inhibitors, such as bevacizumab, are currently under development. In this review, we describe all the combinations of fotemustine currently used in clinical practice for recurrent malignant gliomas

Fotemustine: A Third-Generation Nitrosourea for the Treatment of Recurrent Malignant Gliomas

Directory of Open Access Journals (Sweden)

Patrick Beauchesne

2012-02-01

Full Text Available Malignant gliomas account for approximately 60% of all primary brain tumors in adults. The prognosis for patients with malignant glioma has not changed significantly in recent years. Despite debulking surgery, radiotherapy and cytotoxic chemotherapy, the median survival time is nine to 12 months, and very few, if any, patients are cured from this illness. Fotemustine is an alkylating agent characterized by the grafting of a phosphonoalanine group onto the nitrosourea radical with consequent high lipophilicity and improved diffusion through the cell membrane and the blood-brain barrier. Fotemustine has been registered for use in two indications: disseminated malignant melanoma, including cerebral metastases, and primary brain tumors. Fotemustine is currently used in Europe, particularly in France and Italy, as a salvage therapy for recurrent malignant gliomas. Myelosuppression, leucopenia and thrombocytopenia are the most frequent side effects of treatment with fotemustine. The objective response to this treatment is between 26% and 70%, and the reported median survival time is 10 months. New drug combinations containing fotemustine and angiogenesis inhibitors, such as bevacizumab, are currently under development. In this review, we describe all the combinations of fotemustine currently used in clinical practice for recurrent malignant gliomas.

Fotemustine: A Third-Generation Nitrosourea for the Treatment of Recurrent Malignant Gliomas

Energy Technology Data Exchange (ETDEWEB)

Beauchesne, Patrick [Neuro-oncology/Neurology, University Hospital of Nancy, Hôpital CENTRAL, CO N 34,54035 Nancy cedex (France)

2012-02-01

Malignant gliomas account for approximately 60% of all primary brain tumors in adults. The prognosis for patients with malignant glioma has not changed significantly in recent years. Despite debulking surgery, radiotherapy and cytotoxic chemotherapy, the median survival time is nine to 12 months, and very few, if any, patients are cured from this illness. Fotemustine is an alkylating agent characterized by the grafting of a phosphonoalanine group onto the nitrosourea radical with consequent high lipophilicity and improved diffusion through the cell membrane and the blood-brain barrier. Fotemustine has been registered for use in two indications: disseminated malignant melanoma, including cerebral metastases, and primary brain tumors. Fotemustine is currently used in Europe, particularly in France and Italy, as a salvage therapy for recurrent malignant gliomas. Myelosuppression, leucopenia and thrombocytopenia are the most frequent side effects of treatment with fotemustine. The objective response to this treatment is between 26% and 70%, and the reported median survival time is 10 months. New drug combinations containing fotemustine and angiogenesis inhibitors, such as bevacizumab, are currently under development. In this review, we describe all the combinations of fotemustine currently used in clinical practice for recurrent malignant gliomas.

TCGA_LowerGradeGliomas

Science.gov (United States)

TCGA researchers analyzed nearly 300 cases of diffuse low- and intermediate-grade gliomas, which together comprise lower-grade gliomas. LGGs occur mainly in adults and include astrocytomas, oligodendrogliomas and oligoastrocytomas.

Tumor blood vessel "normalization" improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

Energy Technology Data Exchange (ETDEWEB)

D. W. Nigg

2012-01-01

We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer.

Tumor blood vessel 'normalization' improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

International Nuclear Information System (INIS)

Nigg, D.W.

2012-01-01

We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer.

Quantitative phase imaging characterization of tumor-associated blood vessel formation on a chip

Science.gov (United States)

Guo, Peng; Huang, Jing; Moses, Marsha A.

2018-02-01

Angiogenesis, the formation of new blood vessels from existing ones, is a biological process that has an essential role in solid tumor growth, development, and progression. Recent advances in Lab-on-a-Chip technology has created an opportunity for scientists to observe endothelial cell (EC) behaviors during the dynamic process of angiogenesis using a simple and economical in vitro platform that recapitulates in vivo blood vessel formation. Here, we use quantitative phase imaging (QPI) microscopy to continuously and non-invasively characterize the dynamic process of tumor cell-induced angiogenic sprout formation on a microfluidic chip. The live tumor cell-induced angiogenic sprouts are generated by multicellular endothelial sprouting into 3 dimensional (3D) Matrigel using human umbilical vein endothelial cells (HUVECs). By using QPI, we quantitatively measure a panel of cellular morphological and behavioral parameters of each individual EC participating in this sprouting. In this proof-of-principle study, we demonstrate that QPI is a powerful tool that can provide real-time quantitative analysis of biological processes in in vitro 3D biomimetic devices, which, in turn, can improve our understanding of the biology underlying functional tissue engineering.

Subsurface thermal behaviour of tissue mimics embedded with large blood vessels during plasmonic photo-thermal therapy.

Science.gov (United States)

Paul, Anup; Narasimhan, Arunn; Das, Sarit K; Sengupta, Soujit; Pradeep, Thalappil

2016-11-01

The purpose of this study was to understand the subsurface thermal behaviour of a tissue phantom embedded with large blood vessels (LBVs) when exposed to near-infrared (NIR) radiation. The effect of the addition of nanoparticles to irradiated tissue on the thermal sink behaviour of LBVs was also studied. Experiments were performed on a tissue phantom embedded with a simulated blood vessel of 2.2 mm outer diameter (OD)/1.6 mm inner diameter (ID) with a blood flow rate of 10 mL/min. Type I collagen from bovine tendon and agar gel were used as tissue. Two different nanoparticles, gold mesoflowers (AuMS) and graphene nanostructures, were synthesised and characterised. Energy equations incorporating a laser source term based on multiple scattering theories were solved using finite element-based commercial software. The rise in temperature upon NIR irradiation was seen to vary according to the position of the blood vessel and presence of nanoparticles. While the maximum rise in temperature was about 10 °C for bare tissue, it was 19 °C for tissue embedded with gold nanostructures and 38 °C for graphene-embedded tissues. The axial temperature distribution predicted by computational simulation matched the experimental observations. A different subsurface temperature distribution has been obtained for different tissue vascular network models. The position of LBVs must be known in order to achieve optimal tissue necrosis. The simulation described here helps in predicting subsurface temperature distributions within tissues during plasmonic photo-thermal therapy so that the risks of damage and complications associated with in vivo experiments and therapy may be avoided.

Gamma-secretase inhibitor treatment promotes VEGF-A-driven blood vessel growth and vascular leakage but disrupts neovascular perfusion.

Directory of Open Access Journals (Sweden)

Mattias Kalén

Full Text Available The Notch signaling pathway is essential for normal development due to its role in control of cell differentiation, proliferation and survival. It is also critically involved in tumorigenesis and cancer progression. A key enzyme in the activation of Notch signaling is the gamma-secretase protein complex and therefore, gamma-secretase inhibitors (GSIs--originally developed for Alzheimer's disease--are now being evaluated in clinical trials for human malignancies. It is also clear that Notch plays an important role in angiogenesis driven by Vascular Endothelial Growth Factor A (VEGF-A--a process instrumental for tumor growth and metastasis. The effect of GSIs on tumor vasculature has not been conclusively determined. Here we report that Compound X (CX, a GSI previously reported to potently inhibit Notch signaling in vitro and in vivo, promotes angiogenic sprouting in vitro and during developmental angiogenesis in mice. Furthermore, CX treatment suppresses tumor growth in a mouse model of renal carcinoma, leads to the formation of abnormal vessels and an increased tumor vascular density. Using a rabbit model of VEGF-A-driven angiogenesis in skeletal muscle, we demonstrate that CX treatment promotes abnormal blood vessel growth characterized by vessel occlusion, disrupted blood flow, and increased vascular leakage. Based on these findings, we propose a model for how GSIs and other Notch inhibitors disrupt tumor blood vessel perfusion, which might be useful for understanding this new class of anti-cancer agents.

Glioma-related seizures in relation to histopathological subtypes: a report from the glioma international case-control study.

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Berntsson, Shala G; Merrell, Ryan T; Amirian, E Susan; Armstrong, Georgina N; Lachance, Daniel; Smits, Anja; Zhou, Renke; Jacobs, Daniel I; Wrensch, Margaret R; Olson, Sara H; Il'yasova, Dora; Claus, Elizabeth B; Barnholtz-Sloan, Jill S; Schildkraut, Joellen; Sadetzki, Siegal; Johansen, Christoffer; Houlston, Richard S; Jenkins, Robert B; Bernstein, Jonine L; Lai, Rose; Shete, Sanjay; Amos, Christopher I; Bondy, Melissa L; Melin, Beatrice S

2018-04-23

The purpose of this study was to evaluate the distribution of glioma-related seizures and seizure control at the time of tumor diagnosis with respect to tumor histologic subtypes, tumor treatment and patient characteristics, and to compare seizure history preceding tumor diagnosis (or study enrollment) between glioma patients and healthy controls. The Glioma International Case Control study (GICC) risk factor questionnaire collected information on demographics, past medical/medication history, and occupational history. Cases from eight centers were also asked detailed questions on seizures in relation to glioma diagnosis; cases (n = 4533) and controls (n = 4171) were also asked about seizures less than 2 years from diagnosis and previous seizure history more than 2 years prior to tumor diagnosis, including childhood seizures. Low-grade gliomas (LGGs), particularly oligodendrogliomas/oligoastrocytomas, had the highest proportion of glioma-related seizures. Patients with low-grade astrocytoma demonstrated the most medically refractory seizures. A total of 83% of patients were using only one antiepileptic drug (AED), which was levetiracetam in 71% of cases. Gross total resection was strongly associated with reduced seizure frequency (p related seizures were most common in low-grade gliomas. Gross total resection was associated with lower seizure frequency. Additionally, having a history of childhood seizures is not a risk factor ***for developing glioma-related seizures or glioma.

Glioma cells on the run – the migratory transcriptome of 10 human glioma cell lines

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Holz David

2008-01-01

Full Text Available Abstract Background Glioblastoma multiforme (GBM is the most common primary intracranial tumor and despite recent advances in treatment regimens, prognosis for affected patients remains poor. Active cell migration and invasion of GBM cells ultimately lead to ubiquitous tumor recurrence and patient death. To further understand the genetic mechanisms underlying the ability of glioma cells to migrate, we compared the matched transcriptional profiles of migratory and stationary populations of human glioma cells. Using a monolayer radial migration assay, motile and stationary cell populations from seven human long term glioma cell lines and three primary GBM cultures were isolated and prepared for expression analysis. Results Gene expression signatures of stationary and migratory populations across all cell lines were identified using a pattern recognition approach that integrates a priori knowledge with expression data. Principal component analysis (PCA revealed two discriminating patterns between migrating and stationary glioma cells: i global down-regulation and ii global up-regulation profiles that were used in a proband-based rule function implemented in GABRIEL to find subsets of genes having similar expression patterns. Genes with up-regulation pattern in migrating glioma cells were found to be overexpressed in 75% of human GBM biopsy specimens compared to normal brain. A 22 gene signature capable of classifying glioma cultures based on their migration rate was developed. Fidelity of this discovery algorithm was assessed by validation of the invasion candidate gene, connective tissue growth factor (CTGF. siRNA mediated knockdown yielded reduced in vitro migration and ex vivo invasion; immunohistochemistry on glioma invasion tissue microarray confirmed up-regulation of CTGF in invasive glioma cells. Conclusion Gene expression profiling of migratory glioma cells induced to disperse in vitro affords discovery of genomic signatures; selected

ICG-assisted blood vessel detection during stereotactic neurosurgery: simulation study on excitation power limitations due to thermal effects in human brain tissue.

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Rühm, Adrian; Göbel, Werner; Sroka, Ronald; Stepp, Herbert

2014-09-01

Intraoperative blood vessel detection based on intraluminal indocyanin-green (ICG) would allow to minimize the risk of blood vessel perforation during stereotactic brain tumor biopsy. For a fiber-based approach compatible with clinical conditions, the maximum tolerable excitation light power was derived from simulations of the thermal heat load on the tissue. Using the simulation software LITCIT, the temperature distribution in human brain tissue was calculated as a function of time for realistic single-fiber probes (0.72mm active diameter, numerical aperture 0.35, optional focusing to 0.29mm diameter) and for the optimum ICG excitation wavelength of 785nm. The asymptotic maximum temperature in the simulated tissue region was derived for different radiant fluxes at the distal fiber end. Worst case values were assumed for all other parameters. In addition to homogeneous (normal and tumor) brain tissue with homogeneous blood perfusion, models with localized extra blood vessels incorporated ahead of the distal fiber end were investigated. If one demands that destruction of normal brain tissue must be excluded by limiting the tissue heating to 42°C, then the radiant flux at the distal fiber end must be limited to 33mW with and 43mW without focusing. When considering extra blood vessels of 0.1mm diameter incorporated into homogeneously perfused brain tissue, the tolerable radiant flux is reduced to 22mW with and 32mW without focusing. The threshold value according to legal laser safety regulations for human skin tissue is 28.5mW. For the envisaged modality of blood vessel detection, light power limits for an application-relevant fiber configuration were determined and found to be roughly consistent with present legal regulations for skin tissue. Copyright © 2014 Elsevier B.V. All rights reserved.

A composite chitosan-gelatin bi-layered, biomimetic macroporous scaffold for blood vessel tissue engineering.

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Badhe, Ravindra V; Bijukumar, Divya; Chejara, Dharmesh R; Mabrouk, Mostafa; Choonara, Yahya E; Kumar, Pradeep; du Toit, Lisa C; Kondiah, Pierre P D; Pillay, Viness

2017-02-10

A composite chitosan-gelatin macroporous hydrogel-based scaffold with bi-layered tubular architecture was engineered by solvent casting-co-particulate leaching. The scaffold constituted an inner macroporous layer concealed by a non-porous outer layer mimicking the 3D matrix of blood vessels with cellular adhesion and proliferation. The scaffold was evaluated for its morphological, physicochemical, physicomechanical and biodurability properties employing SEM, FTIR, DSC, XRD, porositometry, rheology and texture analysis. The fluid uptake and biodegradation in the presence of lysozymes was also investigated. Cellular attachment and proliferation was analysed using human dermal fibroblasts (HDF-a) seeded onto the scaffold and evaluated by MTT assay, SEM, and confocal microscopy. Results demonstrated that the scaffold had a desirable tensile strength=95.81±11kPa, elongation at break 112.5±13%, porosity 82% and pores between 100 and 230μm, 50% in vitro biodegradation at day 16 and proliferated fibroblasts over 20 days. These results demonstrate that scaffold may be an excellent tubular archetype for blood vessel tissue engineering. Copyright © 2016 Elsevier Ltd. All rights reserved.

Frequent Nek1 overexpression in human gliomas

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Zhu, Jun [School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai (China); Neurosurgery Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Cai, Yu, E-mail: aihaozuqiu22@163.com [School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai (China); Neurosurgery Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Liu, Pin [Med-X Research Institute, Shanghai Jiao Tong University, Shanghai (China); Zhao, Weiguo [Neurosurgery Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China)

2016-08-05

Never in mitosis A (NIMA)-related kinase 1 (Nek1) regulates cell cycle progression to mitosis. Its expression and potential functions in human gliomas have not been studied. Here, our immunohistochemistry (IHC) assay and Western blot assay results showed that Nek1 expression was significantly upregulated in fresh and paraffin-embedded human glioma tissues. Its level in normal brain tissues was low. Nek1 overexpression in human gliomas was correlated with the proliferation marker (Ki-67), tumor grade, Karnofsky performance scale (KPS) and more importantly, patients’ poor survival. Further studies showed that Nek1 expression level was also increased in multiple human glioma cell lines (U251-MG, U87-MG, U118, H4 and U373). Significantly, siRNA-mediated knockdown of Nek1 inhibited glioma cell (U87-MG/U251-MG) growth. Nek1 siRNA also sensitized U87-MG/U251-MG cells to temozolomide (TMZ), causing a profound apoptosis induction and growth inhibition. The current study indicates Nek1 might be a novel and valuable oncotarget of glioma, it is important for glioma cell growth and TMZ-resistance. - Highlights: • Nek1 is upregulated in multiple human glioma tissues and cell lines. • Nek1 overexpression correlates with glioma grades and patients’ KPS score. • Nek1 overexpression correlates with patients’ poor overall survival. • siRNA knockdown of Nek1 inhibits glioma cell growth. • siRNA knockdown of Nek1 sensitizes human glioma cells to temozolomide.

Frequent Nek1 overexpression in human gliomas

International Nuclear Information System (INIS)

Zhu, Jun; Cai, Yu; Liu, Pin; Zhao, Weiguo

2016-01-01

Never in mitosis A (NIMA)-related kinase 1 (Nek1) regulates cell cycle progression to mitosis. Its expression and potential functions in human gliomas have not been studied. Here, our immunohistochemistry (IHC) assay and Western blot assay results showed that Nek1 expression was significantly upregulated in fresh and paraffin-embedded human glioma tissues. Its level in normal brain tissues was low. Nek1 overexpression in human gliomas was correlated with the proliferation marker (Ki-67), tumor grade, Karnofsky performance scale (KPS) and more importantly, patients’ poor survival. Further studies showed that Nek1 expression level was also increased in multiple human glioma cell lines (U251-MG, U87-MG, U118, H4 and U373). Significantly, siRNA-mediated knockdown of Nek1 inhibited glioma cell (U87-MG/U251-MG) growth. Nek1 siRNA also sensitized U87-MG/U251-MG cells to temozolomide (TMZ), causing a profound apoptosis induction and growth inhibition. The current study indicates Nek1 might be a novel and valuable oncotarget of glioma, it is important for glioma cell growth and TMZ-resistance. - Highlights: • Nek1 is upregulated in multiple human glioma tissues and cell lines. • Nek1 overexpression correlates with glioma grades and patients’ KPS score. • Nek1 overexpression correlates with patients’ poor overall survival. • siRNA knockdown of Nek1 inhibits glioma cell growth. • siRNA knockdown of Nek1 sensitizes human glioma cells to temozolomide.

Synergistic actions of blocking angiopoietin-2 and tumor necrosis factor-α in suppressing remodeling of blood vessels and lymphatics in airway inflammation.

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Le, Catherine T K; Laidlaw, Grace; Morehouse, Christopher A; Naiman, Brian; Brohawn, Philip; Mustelin, Tomas; Connor, Jane R; McDonald, Donald M

2015-11-01

Remodeling of blood vessels and lymphatics are prominent features of sustained inflammation. Angiopoietin-2 (Ang2)/Tie2 receptor signaling and tumor necrosis factor-α (TNF)/TNF receptor signaling are known to contribute to these changes in airway inflammation after Mycoplasma pulmonis infection in mice. We determined whether Ang2 and TNF are both essential for the remodeling on blood vessels and lymphatics, and thereby influence the actions of one another. Their respective contributions to the initial stage of vascular remodeling and sprouting lymphangiogenesis were examined by comparing the effects of function-blocking antibodies to Ang2 or TNF, given individually or together during the first week after infection. As indices of efficacy, vascular enlargement, endothelial leakiness, venular marker expression, pericyte changes, and lymphatic vessel sprouting were assessed. Inhibition of Ang2 or TNF alone reduced the remodeling of blood vessels and lymphatics, but inhibition of both together completely prevented these changes. Genome-wide analysis of changes in gene expression revealed synergistic actions of the antibody combination over a broad range of genes and signaling pathways involved in inflammatory responses. These findings demonstrate that Ang2 and TNF are essential and synergistic drivers of remodeling of blood vessels and lymphatics during the initial stage of inflammation after infection. Inhibition of Ang2 and TNF together results in widespread suppression of the inflammatory response. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Modeling the Role of the Glymphatic Pathway and Cerebral Blood Vessel Properties in Alzheimer’s Disease Pathogenesis

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Kyrtsos, Christina Rose; Baras, John S.

2015-01-01

Alzheimer’s disease (AD) is the most common cause of dementia in the elderly, affecting over 10% population over the age of 65 years. Clinically, AD is described by the symptom set of short term memory loss and cognitive decline, changes in mentation and behavior, and eventually long-term memory deficit as the disease progresses. On imaging studies, significant atrophy with subsequent increase in ventricular volume have been observed. Pathology on post-mortem brain specimens demonstrates the classic findings of increased beta amyloid (Aβ) deposition and the presence of neurofibrillary tangles (NFTs) within affected neurons. Neuroinflammation, dysregulation of blood-brain barrier transport and clearance, deposition of Aβ in cerebral blood vessels, vascular risk factors such as atherosclerosis and diabetes, and the presence of the apolipoprotein E4 allele have all been identified as playing possible roles in AD pathogenesis. Recent research has demonstrated the importance of the glymphatic system in the clearance of Aβ from the brain via the perivascular space surrounding cerebral blood vessels. Given the variety of hypotheses that have been proposed for AD pathogenesis, an interconnected, multilayer model offers a unique opportunity to combine these ideas into a single unifying model. Results of this model demonstrate the importance of vessel stiffness and heart rate in maintaining adequate clearance of Aβ from the brain. PMID:26448331

Altered intraoperative cerebrovascular reactivity in brain areas of high-grade glioma recurrence.

Science.gov (United States)

Fierstra, Jorn; van Niftrik, Bas; Piccirelli, Marco; Burkhardt, Jan Karl; Pangalu, Athina; Kocian, Roman; Valavanis, Antonios; Weller, Michael; Regli, Luca; Bozinov, Oliver

2016-07-01

Current MRI sequences are limited in identifying brain areas at risk for high grade glioma recurrence. We employed intraoperative 3-Tesla functional MRI to assess cerebrovascular reactivity (CVR) after high-grade glioma resection and analyzed regional CVR responses in areas of tumor recurrence on clinical follow-up imaging. Five subjects with high-grade glioma that underwent an intraoperative Blood Oxygen-Level Dependent (BOLD) MRI CVR examination and had a clinical follow-up of at least 18months were selected from a prospective database. For this study, location of tumor recurrence was spatially matched to the intraoperative imaging to assess CVR response in that particular area. CVR is defined as the percent BOLD signal change during repeated cycles of apnea. Of the 5 subjects (mean age 44, 2 females), 4 were diagnosed with a WHO grade III and 1 subject with a WHO grade IV glioma. Three subjects exhibited a tumor recurrence on clinical follow-up MRI (mean: 15months). BOLD CVR measured in the spatially matched area of tumor recurrence was on average 94% increased (range-32% to 183%) as compared to contralateral hemisphere CVR response, 1.50±0.81 versus 1.03±0.46 respectively (p=0.31). For this first analysis in a small cohort, we found altered intraoperative CVR in brain areas exhibiting high grade glioma recurrence on clinical follow-up imaging. Copyright © 2016 Elsevier Inc. All rights reserved.

Aptamer-conjugated PEGylated quantum dots targeting epidermal growth factor receptor variant III for fluorescence imaging of glioma.

Science.gov (United States)

Tang, Jiaze; Huang, Ning; Zhang, Xiang; Zhou, Tao; Tan, Ying; Pi, Jiangli; Pi, Li; Cheng, Si; Zheng, Huzhi; Cheng, Yuan

2017-01-01

The extent of resection is a significant prognostic factor in glioma patients. However, the maximum safe resection level is difficult to determine due to the inherent infiltrative character of tumors. Recently, fluorescence-guided surgery has emerged as a new technique that allows safe resection of glioma. In this study, we constructed a new kind of quantum dot (QD)-labeled aptamer (QD-Apt) nanoprobe by conjugating aptamer 32 (A32) to the QDs surface, which can specially bind to the tumors. A32 is a single-stranded DNA capable of binding to the epidermal growth factor receptor variant III (EGFRvIII) specially distributed on the surface of glioma cells. To detect the expression of EGFRvIII in human brain tissues, 120 specimens, including 110 glioma tissues and 10 normal brain tissues, were examined by immunohistochemistry, and the results showed that the rate of positive expression of EGFRvIII in the glioma tissues was 41.82%, and 0.00% in normal brain tissues. Besides, the physiochemical properties of QD-Apt nanoparticles (NPs) were thoroughly characterized. Biocompatibility of the NPs was evaluated, and the results suggested that the QD-Apt was nontoxic in vivo and vitro. Furthermore, the use of the QD-Apt in labeling glioma cell lines and human brain glioma tissues, and target gliomas in situ was also investigated. We found that not only could QD-Apt specially bind to the U87-EGFRvIII glioma cells but also bind to human glioma tissues in vitro. Fluorescence imaging in vivo with orthotopic glioma model mice bearing U87-EGFRvIII showed that QD-Apt could penetrate the blood-brain barrier and then selectively accumulate in the tumors through binding to EGFRvIII, and consequently, generate a strong fluorescence, which contributed to the margins of gliomas that were visualized clearly, and thus, help the surgeons realize the maximum safe resection of glioma. In addition, QD-Apt can also be applied in preoperative diagnosis and postoperative examination of glioma

Automatic blood vessel based-liver segmentation using the portal phase abdominal CT

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Maklad, Ahmed S.; Matsuhiro, Mikio; Suzuki, Hidenobu; Kawata, Yoshiki; Niki, Noboru; Shimada, Mitsuo; Iinuma, Gen

2018-02-01

Liver segmentation is the basis for computer-based planning of hepatic surgical interventions. In diagnosis and analysis of hepatic diseases and surgery planning, automatic segmentation of liver has high importance. Blood vessel (BV) has showed high performance at liver segmentation. In our previous work, we developed a semi-automatic method that segments the liver through the portal phase abdominal CT images in two stages. First stage was interactive segmentation of abdominal blood vessels (ABVs) and subsequent classification into hepatic (HBVs) and non-hepatic (non-HBVs). This stage had 5 interactions that include selective threshold for bone segmentation, selecting two seed points for kidneys segmentation, selection of inferior vena cava (IVC) entrance for starting ABVs segmentation, identification of the portal vein (PV) entrance to the liver and the IVC-exit for classifying HBVs from other ABVs (non-HBVs). Second stage is automatic segmentation of the liver based on segmented ABVs as described in [4]. For full automation of our method we developed a method [5] that segments ABVs automatically tackling the first three interactions. In this paper, we propose full automation of classifying ABVs into HBVs and non- HBVs and consequently full automation of liver segmentation that we proposed in [4]. Results illustrate that the method is effective at segmentation of the liver through the portal abdominal CT images.

Glucose metabolism in diabetic blood vessels

International Nuclear Information System (INIS)

Brown, B.J.; Crass, M.F. III

1986-01-01

Since glycolysis appears to be coupled to active ion transport in vascular smooth muscle, alterations in glucose metabolism may contribute to cellular dysfunction and angiopathy in diabetes. Uptake and utilization of glucose were studied in perfused blood vessels in which pulsatile flow and perfusion pressure were similar to those measured directly in vivo. Thoracic aortae isolated from 8-wk alloxan diabetic (D) and nondiabetic control rabbits were cannulated, tethered, and perfused with oxygenated buffer containing 7 or 25 mM glucose and tracer amounts of glucose-U -14 C. Norepinephrine (NE) (10 -6 M) and/or insulin (I) (150 μU/ml) and albumin (0.2%) were added. NE-induced tension development increased glucose uptake 39% and 14 CO 2 and lactate production 2.3-fold. With 7 mM glucose, marked decreases in glucose uptake (74%), 14 CO 2 (68%), lactate (30%), total tissue glycogen (75%), and tissue phospholipids (70%) were observed in D. Addition of I or elevation of exogenous glucose to 25 mM normalized glucose uptake, but had differential effects on the pattern of substrate utilization. Thus, in D, there was a marked depression of vascular glucose metabolism that was partially reversed by addition of low concentrations of insulin or D levels of glucose

Rapid sealing and cutting of porcine blood vessels, ex vivo, using a high-power, 1470-nm diode laser.

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Giglio, Nicholas C; Hutchens, Thomas C; Perkins, William C; Latimer, Cassandra; Ward, Arlen; Nau, William H; Fried, Nathaniel M

2014-03-01

Suture ligation with subsequent cutting of blood vessels to maintain hemostasis during surgery is time consuming and skill intensive. Energy-based electrosurgical and ultrasonic devices are often used to replace sutures and mechanical clips to provide rapid hemostasis and decrease surgery time. Some of these devices may create undesirably large collateral zones of thermal damage and tissue necrosis, or require separate mechanical blades for cutting. Infrared lasers are currently being explored as alternative energy sources for vessel sealing applications. In a previous study, a 1470-nm laser was used to seal vessels 1 to 6 mm in diameter in 5 s, yielding burst pressures of ∼500  mmHg. The purpose of this study was to provide vessel sealing times comparable with current energy-based devices, incorporate transection of sealed vessels, and demonstrate high vessel burst pressures to provide a safety margin for future clinical use. A 110-W, 1470-nm laser beam was transmitted through a fiber and beam shaping optics, producing a 90-W linear beam 3.0 by 9.5 mm for sealing (400  W/cm2), and 1.1 by 9.6 mm for cutting (1080  W/cm2). A two-step process sealed and then transected ex vivo porcine renal vessels (1.5 to 8.5 mm diameter) in a bench top setup. Seal and cut times were 1.0 s each. A burst pressure system measured seal strength, and histologic measurements of lateral thermal spread were also recorded. All blood vessels tested (n=55 seal samples) were sealed and cut, with total irradiation times of 2.0 s and mean burst pressures of 1305±783  mmHg. Additional unburst vessels were processed for histological analysis, showing a lateral thermal spread of 0.94±0.48  mm (n=14 seal samples). This study demonstrated that an optical-based system is capable of precisely sealing and cutting a wide range of porcine renal vessel sizes and, with further development, may provide an alternative to radiofrequency- and ultrasonic-based vessel sealing devices.

Comparison between PVHIS on the MRI and the permeability of brain blood vessels in elderly patients

International Nuclear Information System (INIS)

Yamaguchi, Katsuhiko; Tanaka, Yuriko; Kubo, Hideki; Takagi, Yasushi; Tachikawa, Shinzo; Katsunuma, Hideyo.

1989-01-01

The degree of PVHIS (periventricular high intensity signal) on the MRI was composed with the permeability of brain blood vessels using the cerebrospinal fluid (CSF)/serum ratio for albumin, and the CSF/serum ratio for IgG in elderly patients. The 47 elderly patients (mean age=79.9) were divided into three groups: (1) Mild group (20 cases, M:6, F:14, mean age=75.8), (2) Moderate group (18 cases, M:7, F:11, mean age=82.6), (3) Severe group (9 cases, M:2, F:7, mean age=82.9), in accordance with the degree of PVHIS on the MRI. The MRI was operated at a field strength of 0.22 tesla. The pulse sequence (used on all patients) had a repetition times (TR) of 2,000 msec and a time to echo (TE) of 40 msec. The levels of albumin and IgG in the serum and CSF were measured. The CSF/serum ratio for albumin was used of analyze the permeability of the brain blood vessels in each group. There was no significant difference in the level of the serum albumin, the CSF albumin, the serum IgG, the CSF IgG and the CSF/serum ratio for IgG among the three groups. The same was found to be true for the IgG index which indicates the synthesis of immunoglobulin in the central nervous system. However, there was a statistically significant difference (p<0.05) in the CSF/serum ratio for albumin between groups (1) and (3). The increased CSF/serum ratio for albumin in the severe group indicated there were confluent lesions involving the entire extent of the periventriular white matter on the MRI. This suggested an increased permeability of brain blood vessels which revealed the dysfunction of the blood brain barrier due to affected cerebral endothelial cells in capillaries. (author)

The Glioma International Case-Control Study

DEFF Research Database (Denmark)

Amirian, E. Susan; Armstrong, Georgina N; Zhou, Renke

2016-01-01

Decades of research have established only a few etiological factors for glioma, which is a rare and highly fatal brain cancer. Common methodological challenges among glioma studies include small sample sizes, heterogeneity of tumor subtypes, and retrospective exposure assessment. Here, we briefly...... describe the Glioma International Case-Control (GICC) Study (recruitment, 2010-2013), a study being conducted by the Genetic Epidemiology of Glioma International Consortium that integrates data from multiple data collection sites, uses a common protocol and questionnaire, and includes biospecimen...

Hemodynamics in stenotic vessels of small diameter under steady state conditions: Effect of viscoelasticity and migration of red blood cells.

Science.gov (United States)

Dimakopoulos, Yannis; Kelesidis, George; Tsouka, Sophia; Georgiou, Georgios C; Tsamopoulos, John

2015-01-01

In microcirculation, the non-Newtonian behavior of blood and the complexity of the microvessel network are responsible for the high flow resistance and the large reduction of the blood pressure. Red blood cell aggregation along with inward radial migration are two significant mechanisms determining the former. Yet, their impact on hemodynamics in non-straight vessels is not well understood. In this study, the steady state blood flow in stenotic rigid vessels is examined, employing a sophisticated non-homogeneous constitutive law. The effect of red blood cells migration on the hydrodynamics is quantified and the constitutive model's accuracy is evaluated. A numerical algorithm based on the two-dimensional mixed finite element method and the EVSS/SUPG technique for a stable discretization of the mass and momentum conservation equations in addition to the constitutive model is employed. The numerical simulations show that a cell-depleted layer develops along the vessel wall with an almost constant thickness for slow flow conditions. This causes the reduction of the drag force and the increase of the pressure gradient as the constriction ratio decreases. Viscoelastic effects in blood flow were found to be responsible for steeper decreases of tube and discharge hematocrits as decreasing function of constriction ratio.

Intra-lesional spatial correlation of static and dynamic FET-PET parameters with MRI-based cerebral blood volume in patients with untreated glioma

Energy Technology Data Exchange (ETDEWEB)

Goettler, Jens; Preibisch, Christine [TU Muenchen, Department of Neuroradiology, Klinikum rechts der Isar, Munich (Germany); TU Muenchen, TUM Neuroimaging Center (TUM-NIC), Klinikum rechts der Isar, Munich (Germany); Lukas, Mathias; Mustafa, Mona; Schwaiger, Markus; Pyka, Thomas [TU Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Kluge, Anne; Kaczmarz, Stephan; Zimmer, Claus [TU Muenchen, Department of Neuroradiology, Klinikum rechts der Isar, Munich (Germany); Gempt, Jens; Ringel, Florian; Meyer, Bernhard [TU Muenchen, Department of Neurosurgery, Klinikum rechts der Isar, Munich (Germany); Foerster, Stefan [TU Muenchen, TUM Neuroimaging Center (TUM-NIC), Klinikum rechts der Isar, Munich (Germany); TU Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Klinikum Bayreuth, Department of Nuclear Medicine, Bayreuth (Germany)

2017-03-15

{sup 18}F-fluorethyltyrosine-(FET)-PET and MRI-based relative cerebral blood volume (rCBV) have both been used to characterize gliomas. Recently, inter-individual correlations between peak static FET-uptake and rCBV have been reported. Herein, we assess the local intra-lesional relation between FET-PET parameters and rCBV. Thirty untreated glioma patients (27 high-grade) underwent simultaneous PET/MRI on a 3 T hybrid scanner obtaining structural and dynamic susceptibility contrast sequences. Static FET-uptake and dynamic FET-slope were correlated with rCBV within tumour hotspots across patients and intra-lesionally using a mixed-effects model to account for inter-individual variation. Furthermore, maximal congruency of tumour volumes defined by FET-uptake and rCBV was determined. While the inter-individual relationship between peak static FET-uptake and rCBV could be confirmed, our intra-lesional, voxel-wise analysis revealed significant positive correlations (median r = 0.374, p < 0.0001). Similarly, significant inter- and intra-individual correlations were observed between FET-slope and rCBV. However, rCBV explained only 12% of the static and 5% of the dynamic FET-PET variance and maximal overlap of respective tumour volumes was 37% on average. Our results show that the relation between peak values of MR-based rCBV and static FET-uptake can also be observed intra-individually on a voxel basis and also applies to a dynamic FET parameter, possibly determining hotspots of higher biological malignancy. However, just a small part of the FET-PET signal variance is explained by rCBV and tumour volumes determined by the two modalities showed only moderate overlap. These findings indicate that FET-PET and MR-based rCBV provide both congruent and complimentary information on glioma biology. (orig.)

The effects of Anadara granosa shell-Stichopus hermanni on bFGF expressions and blood vessel counts in the bone defect healing process of Wistar rats

Directory of Open Access Journals (Sweden)

Rima Parwati Sari

2017-12-01

Full Text Available Background: Bone damage can be caused by various factors with treatment usually involving graft materials being applied to the defective area. Moreover, in the bone defect healing process, blood vessels are also considered to be an important energy source for cell proliferation. One of the angiogenic factors playing an important role in blood vessel formation is basic fibroblast growth factor (bFGF. Furthermore, synthesized hydroxyapatite derived from Anadara granosa (AG shells constitutes one of the potential materials for use in bone graft. The gold sea cucumber genus Stichopus hermanni (SH possesses the ability to stimulate endothelial progenitor cells inducing bFGF. Purpose: This study aims to investigate the effects of AG shells and SH on bFGF expressions and blood vessel counts within the bone healing process. Methods: Twenty four male Wistar rats were divided into three groups, namely: a control group (C, a treatment group was administered with blood cockle shell (AG, and a treatment group with blood cockle shell and golden sea cucumber (AG+SH. Defects were made on their femurs measuring half the diameter of a circular, no. 018. bur These rats were subsequently sacrificed on day 7 after surgery. The expressions of bFGF were measured by means of IHC technique, while the number of blood vessels was quantified using HE technique. The resulting data was subjected to statistical analysis using an Anova test followed by an LSD test (p < 0.05. Results: The one-way Anova test results combined with those of an LSD test showed there to be significant differences in bFGF expressions and blood vessel counts between the control group (K and the treatment group (AG as well as between the treatment group (AG and the treatment group (AG+SH. Conclusions: A combination of Anadara granosa shell and Stichopus hermanni can increase the expression of bFGF and the number of blood vessels on day 7 during the bone healing process in Wistar rats.

C-reactive protein and chitinase 3-like protein 1 as biomarkers of spatial redistribution of retinal blood vessels on digital retinal photography in patients with diabetic retinopathy.

Science.gov (United States)

Cekić, Sonja; Cvetković, Tatjana; Jovanović, Ivan; Jovanović, Predrag; Pesić, Milica; Stanković Babić, Gordana; Milenković, Svetislav; Risimić, Dijana

2014-08-20

The aim of the study was to investigate the correlation between the levels of C-reactive protein (CRP) and chitinase 3-like protein 1 (YKL-40) in blood samples with morpohometric parameters of retinal blood vessels in patients with diabetic retinopathy. Blood laboratory examination of 90 patients included the measurement of glycemia, HbA1C, total cholesterol, LDL-C, HDL-C, triglycerides and CRP. Levels of YKL-40 were detected and measured in serum by ELISA (Micro VueYKL-40 EIA Kit, Quidel Corporation, San Diego, USA). YKL-40 correlated positively with diameter and negatively with number of retinal blood vessels. The average number of the blood vessels per retinal zone was significantly higher in the group of patients with mild non-proliferative diabetic retinopathy than in the group with severe form in the optic disc and all five retinal zones. The average outer diameter of the evaluated retinal zones and optic disc vessels was significantly higher in the group with severe compared to the group with mild diabetic retinopathy. Morphological analysis of the retinal vessels on digital fundus photography and correlation with YKL-40 may be valuable for the follow-up of diabetic retinopathy.

Spinal metastases of malignant gliomas

International Nuclear Information System (INIS)

Materlik, B.; Steidle-Katic, U.; Feyerabend, T.; Richter, E.; Wauschkuhn, B.

1998-01-01

Purpose: Extracranial metastases of malignant gliomas are rare. We report 2 cases with spinal metastases in patients suffering from glioma. Patients and Method: Two patients (33 and 57 years old) developed spinal canal metastases of a glioblastoma multiforme and anaplastic astrocytoma Grade III respectively 25 and 9 months after surgical resection and radiotherapy. Both metastases were confirmed pathohistologically. Results: Intraspinal metastases were irradiated with a total dose of 12.6 Gy and 50 Gy. Treatment withdrawal was necessary in one patient due to reduced clinical condition. Regression of neurological symptoms was observed in the second patient. Conclusions: Spinal spread of malignant glioma should be considered during care and follow-up in glioma patients with spinal symptoms. (orig.) [de

Molecular markers in glioma.

Science.gov (United States)

Ludwig, Kirsten; Kornblum, Harley I

2017-09-01

Gliomas are the most malignant and aggressive form of brain tumors, and account for the majority of brain cancer related deaths. Malignant gliomas, including glioblastoma are treated with radiation and temozolomide, with only a minor benefit in survival time. A number of advances have been made in understanding glioma biology, including the discovery of cancer stem cells, termed glioma stem cells (GSC). Some of these advances include the delineation of molecular heterogeneity both between tumors from different patients as well as within tumors from the same patient. Such research highlights the importance of identifying and validating molecular markers in glioma. This review, intended as a practical resource for both clinical and basic investigators, summarizes some of the more well-known molecular markers (MGMT, 1p/19q, IDH, EGFR, p53, PI3K, Rb, and RAF), discusses how they are identified, and what, if any, clinical relevance they may have, in addition to discussing some of the specific biology for these markers. Additionally, we discuss identification methods for studying putative GSC's (CD133, CD15, A2B5, nestin, ALDH1, proteasome activity, ABC transporters, and label-retention). While much research has been done on these markers, there is still a significant amount that we do not yet understand, which may account for some conflicting reports in the literature. Furthermore, it is unlikely that the investigator will be able to utilize one single marker to prospectively identify and isolate GSC from all, or possibly, any gliomas.

Neuronavigator-guided glioma surgery.

Science.gov (United States)

Du, Guhong; Zhou, Liangfu; Mao, Ying

2003-10-01

To evaluate the effectiveness of neuronavigator-guided surgery for the resection of gliomas. A total of 80 patients with gliomas underwent surgical treatment under the StealthStation neuronavigator to estimate the extent of the tumors. In 27 cases, the measurements of brain shifts at the dura, cortical surface and lesion margin were recorded during the operations. A technique termed "micro-catheter fence post" was used in superficial gliomas to compensate for brain shift. Mean fiducial error and predicted accuracy in the 80 cases were 2.03 mm +/- 0.89 mm and 2.43 mm +/- 0.99 mm, respectively. The shifts at the dura, cortical surface and lesion margin were 3.44 mm +/- 2.39 mm, 7.58 mm +/- 3.75 mm, and 6.55 mm +/- 3.19 mm, respectively. Although neuronavigation revealed residual tumors, operations were discontinued in 5 cases of deep-seated gliomas. In the other 75 cases, total tumor removals were achieved in 62 (82.7%), and subtotal removals were achieved in 13 (17.3%). Post-operation, neurological symptoms were improved or unchanged in 68 cases (85.0%), and worsened in 12 (15.0%). No deaths occurred during the operations and post-operations. Intraoperative brain shifts mainly contribute to the fail of spatial accuracy during neuronavigator-guided glioma surgery. The "micro-catheter fence post" technique used for glioma surgery is shown to be useful for compensating for intraoperative brain shifts. This technique, thus, contributes to an increase in total tumor removal and a decrease in surgical complications.

Overexpressed KDM5B is associated with the progression of glioma and promotes glioma cell growth via downregulating p21

Energy Technology Data Exchange (ETDEWEB)

Dai, Bin [Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038 (China); Hu, Zhiqiang, E-mail: zhiqhutg@126.com [Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038 (China); Huang, Hui; Zhu, Guangtong; Xiao, Zhiyong [Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038 (China); Wan, Weiqing; Zhang, Peng; Jia, Wang; Zhang, Liwei [Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050 (China)

2014-11-07

Highlights: • KDM5B is overexpressed in glioma samples. • KDM5B stimulated proliferation of glioma cells. • Inhibition of p21contributes to KDM5B-induced proliferation. - Abstract: Epigenetic alterations such as aberrant expression of histone-modifying enzymes have been implicated in tumorigenesis. Upregulation of lysine (K)-specific demethylase 5B (KDM5B) has been reported in a variety of malignant tumors. However, the impact of KDM5B in glioma remains unclear. The objective of this study was to investigate the expression and prognostic value of KDM5B in glioma. In clinical glioma samples, we found that KDM5B expression was significantly upregulated in cancer lesions compared with normal brain tissues. Kaplan–Meier analysis showed that patients with glioma and higher KDM5B expression tend to have shorter overall survival time. By silencing or overexpressing KDM5B in glioma cells, we found that KDM5B could promote cell growth both in vitro and in vivo. Moreover, we demonstrated that KDM5B promoted glioma proliferation partly via regulation of the expression of p21. Our study provided evidence that KDM5B functions as a novel tumor oncogene in glioma and may be a potential therapeutic target for glioma management.

Characterization of PD-1 upregulation on tumor-infiltrating lymphocytes in human and murine gliomas and preclinical therapeutic blockade.

Science.gov (United States)

Dejaegher, Joost; Verschuere, Tina; Vercalsteren, Ellen; Boon, Louis; Cremer, Jonathan; Sciot, Raf; Van Gool, Stefaan W; De Vleeschouwer, Steven

2017-11-01

Blockade of the immune checkpoint molecule programmed-cell-death-protein-1 (PD-1) yielded promising results in several cancers. To understand the therapeutic potential in human gliomas, quantitative data describing the expression of PD-1 are essential. Moreover, due the immune-specialized region of the brain in which gliomas arise, differences between tumor-infiltrating and circulating lymphocytes should be acknowledged. In this study we have used flow cytometry to quantify PD-1 expression on tumor-infiltrating T cells of 25 freshly resected glioma cell suspensions (10 newly and 5 relapsed glioblastoma, 10 lower grade gliomas) and simultaneously isolated circulating T cells. A strong upregulation of PD-1 expression in the tumor microenvironment compared to the blood circulation was seen in all glioma patients. Additionally, circulating T cells were isolated from 15 age-matched healthy volunteers, but no differences in PD-1 expression were found compared to glioma patients. In the murine GL261 malignant glioma model, there was a similar upregulation of PD-1 on brain-infiltrating lymphocytes. Using a monoclonal PD-1 blocking antibody, we found a marked prolonged survival with 55% of mice reaching long-term survival. Analysis of brain-infiltrating cells 21 days after GL261 tumor implantation showed a shift in infiltrating lymphocyte subgroups with increased CD8+ T cells and decreased regulatory T cells. Together, our results suggest an important role of PD-1 in glioma-induced immune escape, and provide translational evidence for the use of PD-1 blocking antibodies in human malignant gliomas. © 2017 UICC.

Targeting ανβ3 and ανβ5 inhibits photon-induced hypermigration of malignant glioma cells

International Nuclear Information System (INIS)

Rieken, Stefan; Habermehl, Daniel; Mohr, Angela; Wuerth, Lena; Lindel, Katja; Weber, Klaus; Debus, Jürgen; Combs, Stephanie E

2011-01-01

Sublethal photon irradiation was recently suspected to increase tumor cell motility and promote locoregional recurrence of disease. This study was set up to describe mechanisms underlying increased glioma cell migration through photon irradiation and to analyse the modifiability of photon-altered glioma cell motility by integrin inhibition. Eight μm pore size membranes were coated with vitronectin (VN), collagen I and collagen IV. U87 and Ln229 glioma cells were analysed in migration experiments with and without radiotherapy (RT), serum stimulation and addition of monoclonal antibodies directed to human integrins α ν β 3 and α ν β 5 . Quantitative FACS analysis of integrins was performed in U87 and Ln229 glioma cells following RT. Statistical analysis was performed using Student's t-test. Glioma cell migration is serum-dependent and can be increased by photon RT which leads to enhanced expression of Vn receptor integrins. Blocking of either α ν β 3 or α ν β 5 integrins by antibodies inhibits Vn-based migration of both untreated and photon-irradiated glioma cells. Peripheral glioma cells are at risk of attraction into the adjacent healthy brain by serum components leaking through the blood brain barrier (BBB). Radiation therapy is associated with upregulation of Vn receptor integrins and enhanced glioma cell migration at sublethal doses. This effect can be inhibited by specific integrin blockade. Future therapeutical benefit may be derived from pharmacological integrin inhibition in combination with photon irradiation

C - reactive protein and chitinase 3-like protein 1 as biomarkers of spatial redistribution of retinal blood vessels on digital retinal photography in patients with diabetic retinopathy

Directory of Open Access Journals (Sweden)

Sonja Predrag Cekic

2014-08-01

Full Text Available The aim of the study was to investegate the correlation between the levels of CRP and YKL-40 in blood samples with morphometric parameters of retinal blood vessels in patients with diabetic retinopathy.Blood laboratory examination of 90 patients included the measurement of glycemia, HbA1C, total cholesterol, LDL-C, HDL-C, triglycerides and CRP. Levels of YKL-40 were detected and measured in serum by ELISA (Micro VueYKL-40 EIA Kit, Quidel Corporation, San Diego, USA.Morphmetric analysis was performed with ImageJ software (http://rsbweb.nih.gov/ij/ for digital retinal photography. We measured the number, diameter of retinal blood vessels in five different parts concentric to the optic disc. Differences between the morphometric parameters and the blood test analysis results were evaluated using the Student’s t – test. One Way ANOVA was used to establish the significance of differences.CRP and YKL-40 levels were moderately higher in the group of patients with severe diabetic retinopathy. Levels of YKL-40 correlated positively with diameter and negatively with number of retinal blood vessels. The average number of the blood vessels per retinal zone was significantly higher in the group of patients with mild non-proliferative diabetic retinopathy than in the group with severe form in the optic disc and all five retinal zones. The average outer diameter of the evaluated retinal zones and optic disc vessels was significantly higher in the group with severe compared to the group with mild diabetic retinopathy.Morphological analysis of the retinal vessels on digital fundus photography and correlation with YKL-40 may be valuable for the follow-up of diabetic retinopathy.

Cognitive impairments in patients with low grade gliomas and high grade gliomas

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Eliane C. Miotto

2011-08-01

Full Text Available OBJECTIVE: The relationship between brain tumors and cognitive deficits is well established in the literature. However, studies investigating the cognitive status in low and high-grade gliomas patients are scarce, particularly in patients with average or lower educational level. This study aimed at investigating the cognitive functioning in a sample of patients with low and high-grade gliomas before surgical intervention. METHOD: The low-grade (G1, n=19 and high-grade glioma (G2, n=8 patients underwent a detailed neuropsychological assessment of memory, executive functions, visuo-perceptive and visuo-spatial abilities, intellectual level and language. RESULTS: There was a significant impairment on verbal and visual episodic memory, executive functions including mental flexibility, nominal and categorical verbal fluency and speed of information processing in G2. G1 showed only specific deficits on verbal and visual memory recall, mental flexibility and processing speed. CONCLUSION: These findings demonstrated different levels of impairments in the executive and memory domains in patients with low and high grade gliomas.

Effect of heat transfer on unsteady MHD flow of blood in a permeable vessel in the presence of non-uniform heat source

OpenAIRE

A. Sinha; J.C. Misra; G.C. Shit

2016-01-01

This paper presents a theoretical analysis of blood flow and heat transfer in a permeable vessel in the presence of an external magnetic field. The unsteadiness in the coupled flow and temperature fields is considered to be caused due to the time-dependent stretching velocity and the surface temperature of the vessel. The non-uniform heat source/sink effect on blood flow and heat transfer is taken into account. This study is of potential value in the clinical treatment of cardiovascular disor...

Unique identification code for medical fundus images using blood vessel pattern for tele-ophthalmology applications.

Science.gov (United States)

Singh, Anushikha; Dutta, Malay Kishore; Sharma, Dilip Kumar

2016-10-01

Identification of fundus images during transmission and storage in database for tele-ophthalmology applications is an important issue in modern era. The proposed work presents a novel accurate method for generation of unique identification code for identification of fundus images for tele-ophthalmology applications and storage in databases. Unlike existing methods of steganography and watermarking, this method does not tamper the medical image as nothing is embedded in this approach and there is no loss of medical information. Strategic combination of unique blood vessel pattern and patient ID is considered for generation of unique identification code for the digital fundus images. Segmented blood vessel pattern near the optic disc is strategically combined with patient ID for generation of a unique identification code for the image. The proposed method of medical image identification is tested on the publically available DRIVE and MESSIDOR database of fundus image and results are encouraging. Experimental results indicate the uniqueness of identification code and lossless recovery of patient identity from unique identification code for integrity verification of fundus images. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Improving Seroreactivity-Based Detection of Glioma

Directory of Open Access Journals (Sweden)

Nicole Ludwig

2009-12-01

Full Text Available Seroreactivity profiling emerges as valuable technique for minimal invasive cancer detection. Recently, we provided first evidence for the applicability of serum profiling of glioma using a limited number of immunogenic antigens. Here, we screened 57 glioma and 60 healthy sera for autoantibodies against 1827 Escherichia coli expressed clones, including 509 in-frame peptide sequences. By a linear support vector machine approach, we calculated mean specificity, sensitivity, and accuracy of 100 repetitive classifications. We were able to differentiate glioma sera from sera of the healthy controls with a specificity of 90.28%, a sensitivity of 87.31% and an accuracy of 88.84%. We were also able to differentiate World Health Organization grade IV glioma sera from healthy sera with a specificity of 98.45%, a sensitivity of 80.93%, and an accuracy of 92.88%. To rank the antigens according to their information content, we computed the area under the receiver operator characteristic curve value for each clone. Altogether, we found 46 immunogenic clones including 16 in-frame clones that were informative for the classification of glioma sera versus healthy sera. For the separation of glioblastoma versus healthy sera, we found 91 informative clones including 26 in-frame clones. The best-suited in-frame clone for the classification glioma sera versus healthy sera corresponded to the vimentin gene (VIM that was previously associated with glioma. In the future, autoantibody signatures in glioma not only may prove useful for diagnosis but also offer the prospect for a personalized immune-based therapy.

Imaging of adult brainstem gliomas

Energy Technology Data Exchange (ETDEWEB)

Purohit, Bela, E-mail: purohitbela@yahoo.co.in; Kamli, Ali A.; Kollias, Spyros S.

2015-04-15

Highlights: •BSG are classified on MRI into diffuse low-grade, malignant, focal tectal and exophytic subtypes. •Their prognosis and treatment is variable and is almost similar to adult supratentorial gliomas. •This article illustrates the imaging of adult BSGs on MRI and FET-PET. •We also describe prognostic factors and the treatment options of these tumours. -- Abstract: Brainstem gliomas (BSGs) are uncommon in adults accounting for about 2% of all intracranial neoplasms. They are often phenotypically low-grade as compared to their more common paediatric counterparts. Since brainstem biopsies are rarely performed, these tumours are commonly classified according to their MR imaging characteristics into 4 subgroups: (a) diffuse intrinsic low-grade gliomas, (b) enhancing malignant gliomas, (c) focal tectal gliomas and (d) exophytic gliomas/other subtypes. The prognosis and treatment is variable for the different types and is almost similar to adult supratentorial gliomas. Radiotherapy (RT) with adjuvant chemotherapy is the standard treatment of diffuse low-grade and malignant BSGs, whereas, surgical resection is limited to the exophytic subtypes. Review of previous literature shows that the detailed imaging of adult BSGs has not received significant attention. This review illustrates in detail the imaging features of adult BSGs using conventional and advanced MR techniques like diffusion weighted imaging (DWI), diffusion tensor imaging (DTI), MR perfusion weighted imaging (PWI), MR spectroscopy (MRS), as well as {sup 18}F-fluoro-ethyl-tyrosine positron emission tomography ({sup 18}F-FET/PET). We have discussed the pertinent differences between childhood and adult BSGs, imaging mimics, prognostic factors and briefly reviewed the treatment options of these tumours.

In vivo phage display screening for tumor vascular targets in glioblastoma identifies a llama nanobody against dynactin-1-p150Glued.

Science.gov (United States)

van Lith, Sanne A M; Roodink, Ilse; Verhoeff, Joost J C; Mäkinen, Petri I; Lappalainen, Jari P; Ylä-Herttuala, Seppo; Raats, Jos; van Wijk, Erwin; Roepman, Ronald; Letteboer, Stef J; Verrijp, Kiek; Leenders, William P J

2016-11-01

Diffuse gliomas are primary brain cancers that are characterised by infiltrative growth. Whereas high-grade glioma characteristically presents with perinecrotic neovascularisation, large tumor areas thrive on pre-existent vasculature as well. Clinical studies have revealed that pharmacological inhibition of the angiogenic process does not improve survival of glioblastoma patients. Direct targeting of tumor vessels may however still be an interesting therapeutic approach as it allows pinching off the blood supply to tumor cells. Such tumor vessel targeting requires the identification of tumor-specific vascular targeting agents (TVTAs).Here we describe a novel TVTA, C-C7, which we identified via in vivo biopanning of a llama nanobody phage display library in an orthotopic mouse model of diffuse glioma. We show that C-C7 recognizes a subpopulation of tumor blood vessels in glioma xenografts and clinical glioma samples. Additionally, C-C7 recognizes macrophages and activated endothelial cells in atherosclerotic lesions. By using C-C7 as bait in yeast-2-hybrid (Y2H) screens we identified dynactin-1-p150Glued as its binding partner. The interaction was confirmed by co-immunostainings with C-C7 and a commercial anti-dynactin-1-p150Glued antibody, and via co-immunoprecipitation/western blot studies. Normal brain vessels do not express dynactin-1-p150Glued and its expression is reduced under anti-VEGF therapy, suggesting that dynactin-1-p150Glued is a marker for activated endothelial cells.In conclusion, we show that in vivo phage display combined with Y2H screenings provides a powerful approach to identify tumor-targeting nanobodies and their binding partners. Using this combination of methods we identify dynactin-1-p150Glued as a novel targetable protein on activated endothelial cells and macrophages.

Molecular analysis of ex-vivo CD133+ GBM cells revealed a common invasive and angiogenic profile but different proliferative signatures among high grade gliomas

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Garcia Juan L

2010-08-01

Full Text Available Abstract Background Gliomas are the most common type of primary brain tumours, and in this group glioblastomas (GBMs are the higher-grade gliomas with fast progression and unfortunate prognosis. Two major aspects of glioma biology that contributes to its awful prognosis are the formation of new blood vessels through the process of angiogenesis and the invasion of glioma cells. Despite of advances, two-year survival for GBM patients with optimal therapy is less than 30%. Even in those patients with low-grade gliomas, that imply a moderately good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells with characteristics of neural stem cells which are able to grow in vitro forming neurospheres and that can be isolated in vivo using surface markers such as CD133. The aim of this study was to define the molecular signature of GBM cells expressing CD133 in comparison with non expressing CD133 cells. This molecular classification could lead to the finding of new potential therapeutic targets for the rationale treatment of high grade GBM. Methods Eight fresh, primary and non cultured GBMs were used in order to study the gene expression signatures from its CD133 positive and negative populations isolated by FACS-sorting. Dataset was generated with Affymetrix U133 Plus 2 arrays and analysed using the software of the Affymetrix Expression Console. In addition, genomic analysis of these tumours was carried out by CGH arrays, FISH studies and MLPA; Results Gene expression analysis of CD133+ vs. CD133- cell population from each tumour showed that CD133+ cells presented common characteristics in all glioblastoma samples (up-regulation of genes involved in angiogenesis, permeability and down-regulation of genes implicated in cell assembly, neural cell organization and neurological disorders. Furthermore, unsupervised clustering of gene expression led us to distinguish between two groups

Safety and maximum tolerated dose of superselective intraarterial cerebral infusion of bevacizumab after osmotic blood-brain barrier disruption for recurrent malignant glioma. Clinical article.

Science.gov (United States)

Boockvar, John A; Tsiouris, Apostolos J; Hofstetter, Christoph P; Kovanlikaya, Ilhami; Fralin, Sherese; Kesavabhotla, Kartik; Seedial, Stephen M; Pannullo, Susan C; Schwartz, Theodore H; Stieg, Philip; Zimmerman, Robert D; Knopman, Jared; Scheff, Ronald J; Christos, Paul; Vallabhajosula, Shankar; Riina, Howard A

2011-03-01

The authors assessed the safety and maximum tolerated dose of superselective intraarterial cerebral infusion (SIACI) of bevacizumab after osmotic disruption of the blood-brain barrier (BBB) with mannitol in patients with recurrent malignant glioma. A total of 30 patients with recurrent malignant glioma were included in the current study. The authors report no dose-limiting toxicity from a single dose of SIACI of bevacizumab up to 15 mg/kg after osmotic BBB disruption with mannitol. Two groups of patients were studied; those without prior bevacizumab exposure (naïve patients; Group I) and those who had received previous intravenous bevacizumab (exposed patients; Group II). Radiographic changes demonstrated on MR imaging were assessed at 1 month postprocedure. In Group I patients, MR imaging at 1 month showed a median reduction in the area of tumor enhancement of 34.7%, a median reduction in the volume of tumor enhancement of 46.9%, a median MR perfusion (MRP) reduction of 32.14%, and a T2-weighted/FLAIR signal decrease in 9 (47.4%) of 19 patients. In Group II patients, MR imaging at 1 month showed a median reduction in the area of tumor enhancement of 15.2%, a median volume reduction of 8.3%, a median MRP reduction of 25.5%, and a T2-weighted FLAIR decrease in 0 (0%) of 11 patients. The authors conclude that SIACI of mannitol followed by bevacizumab (up to 15 mg/kg) for recurrent malignant glioma is safe and well tolerated. Magnetic resonance imaging shows that SIACI treatment with bevacizumab can lead to reduction in tumor area, volume, perfusion, and T2-weighted/FLAIR signal.

Tests of the geometrical description of blood vessels in a thermal model using counter-current geometries

NARCIS (Netherlands)

van Leeuwen, G. M.; Kotte, A. N.; Crezee, J.; Lagendijk, J. J.

1997-01-01

We have developed a thermal model, for use in hyperthermia treatment planning, in which blood vessels are described as geometrical objects; 3D curves with associated diameters. For the calculation of the heat exchange with the tissue an analytic result is used. To arrive at this result some

An agent-based model of the response to angioplasty and bare-metal stent deployment in an atherosclerotic blood vessel.

Directory of Open Access Journals (Sweden)

Antonia E Curtin

Full Text Available PURPOSE: While animal models are widely used to investigate the development of restenosis in blood vessels following an intervention, computational models offer another means for investigating this phenomenon. A computational model of the response of a treated vessel would allow investigators to assess the effects of altering certain vessel- and stent-related variables. The authors aimed to develop a novel computational model of restenosis development following an angioplasty and bare-metal stent implantation in an atherosclerotic vessel using agent-based modeling techniques. The presented model is intended to demonstrate the body's response to the intervention and to explore how different vessel geometries or stent arrangements may affect restenosis development. METHODS: The model was created on a two-dimensional grid space. It utilizes the post-procedural vessel lumen diameter and stent information as its input parameters. The simulation starting point of the model is an atherosclerotic vessel after an angioplasty and stent implantation procedure. The model subsequently generates the final lumen diameter, percent change in lumen cross-sectional area, time to lumen diameter stabilization, and local concentrations of inflammatory cytokines upon simulation completion. Simulation results were directly compared with the results from serial imaging studies and cytokine levels studies in atherosclerotic patients from the relevant literature. RESULTS: The final lumen diameter results were all within one standard deviation of the mean lumen diameters reported in the comparison studies. The overlapping-stent simulations yielded results that matched published trends. The cytokine levels remained within the range of physiological levels throughout the simulations. CONCLUSION: We developed a novel computational model that successfully simulated the development of restenosis in a blood vessel following an angioplasty and bare-metal stent deployment based on

Diagnostic Values of DCE-MRI and DSC-MRI for Differentiation Between High-grade and Low-grade Gliomas: A Comprehensive Meta-analysis.

Science.gov (United States)

Liang, Jianye; Liu, Dexiang; Gao, Peng; Zhang, Dong; Chen, Hanwei; Shi, Changzheng; Luo, Liangping

2018-03-01

This study aimed to collect the studies on the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and dynamic susceptibility contrast MRI (DSC-MRI) in differentiating the grades of gliomas, and evaluate the diagnostic performances of relevant quantitative parameters in glioma grading. We systematically searched studies on the diagnosis of gliomas with DCE-MRI or DSC-MRI in Medline, PubMed, China National Knowledge Infrastructure database, Cochrane Library, and Embase published between January 2005 and December 2016. Standardized mean differences and 95% confidence intervals were calculated for volume transfer coefficient (K trans ), volume fraction of extravascular extracellular space (V e ), rate constant of backflux (K ep ), relative cerebral blood volume (rCBV), and relative cerebral blood flow (rCBF) using Review Manager 5.2 software. Sensitivity, specificity, area under the curve (AUC), and Begg test were calculated by Stata 12.0. Twenty-two studies with available outcome data were included in the analysis. The standardized mean difference of K trans values between high-grade glioma and low-grade glioma were 1.18 (0.91, 1.45); V e values were 1.43 (1.06, 1.80); K ep values were 0.65 (-0.05, 1.36); rCBV values were 1.44 (1.08, 1.81); and rCBF values were 1.17 (0.68, 1.67), respectively. The results were all significant statistically (P values (P = .07), and high-grade glioma had higher K trans , V e , rCBV, and rCBF values than low-grade glioma. AUC values of K trans , V e , rCBV, and rCBF were 0.90, 0.88, 0.93, and 0.73, respectively; rCBV had the largest AUC among the four parameters (P < .05). Both DCE-MRI and DSC-MRI are reliable techniques in differentiating the grades of gliomas, and rCBV was found to be the most sensitive one. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

The relationship between Cho/NAA and glioma metabolism: implementation for margin delineation of cerebral gliomas.

Science.gov (United States)

Guo, Jun; Yao, Chengjun; Chen, Hong; Zhuang, Dongxiao; Tang, Weijun; Ren, Guang; Wang, Yin; Wu, Jinsong; Huang, Fengping; Zhou, Liangfu

2012-08-01

The marginal delineation of gliomas cannot be defined by conventional imaging due to their infiltrative growth pattern. Here we investigate the relationship between changes in glioma metabolism by proton magnetic resonance spectroscopic imaging ((1)H-MRSI) and histopathological findings in order to determine an optimal threshold value of choline/N-acetyl-aspartate (Cho/NAA) that can be used to define the extent of glioma spread. Eighteen patients with different grades of glioma were examined using (1)H-MRSI. Needle biopsies were performed under the guidance of neuronavigation prior to craniotomy. Intraoperative magnetic resonance imaging (MRI) was performed to evaluate the accuracy of sampling. Haematoxylin and eosin, and immunohistochemical staining with IDH1, MIB-1, p53, CD34 and glial fibrillary acidic protein (GFAP) antibodies were performed on all samples. Logistic regression analysis was used to determine the relationship between Cho/NAA and MIB-1, p53, CD34, and the degree of tumour infiltration. The clinical threshold ratio distinguishing tumour tissue in high-grade (grades III and IV) glioma (HGG) and low-grade (grade II) glioma (LGG) was calculated. In HGG, higher Cho/NAA ratios were associated with a greater probability of higher MIB-1 counts, stronger CD34 expression, and tumour infiltration. Ratio threshold values of 0.5, 1.0, 1.5 and 2.0 appeared to predict the specimens containing the tumour with respective probabilities of 0.38, 0.60, 0.79, 0.90 in HGG and 0.16, 0.39, 0.67, 0.87 in LGG. HGG and LGG exhibit different spectroscopic patterns. Using (1)H-MRSI to guide the extent of resection has the potential to improve the clinical outcome of glioma surgery.

Nonparenchymal cells cultivated from explants of fibrotic liver resemble endothelial and smooth muscle cells from blood vessel walls

International Nuclear Information System (INIS)

Voss, B.; Rauterberg, J.; Pott, G.; Brehmer, U.; Allam, S.; Lehmann, R.; von Bassewitz, D.B.

1982-01-01

Tissue specimens from human fibrotic liver obtained by needle biopsy were cultured. Two cell types emerged from the tissue explants. From their morphology and biosynthetic products they resembled smooth muscle cells and endothelial cells from blood vessel walls. In the endothelial cells, factor VIII-associated protein was demonstrated by indirect immunofluorescence. Synthesis of collagen types I and III, basement membrane collagen types IV and V, and fibronectin by both cell types was observed by immunofluorescence microscopy. Homogeneous cultures of smooth muscle cells were observed in subcultures. After incubation with [ 14 C]glycine, collagen was isolated and characterized by CM cellulose chromatography, and consisted mainly of types I and III. These data suggest involvement of mesenchymal cells in hepatic fibrosis; they presumably originate from blood vessel or sinusoidal walls

Hypothalamic glioma masquerading as craniopharyngioma

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Sameer Vyas

2013-01-01

Full Text Available Hypothalamic glioma account for 10-15% of supratentorial tumors in children. They usually present earlier (first 5 years of age than craniopharyngioma. Hypothalamic glioma poses a diagnostic dilemma with craniopharyngioma and other hypothalamic region tumors, when they present with atypical clinical or imaging patterns. Neuroimaging modalities especially MRI plays a very important role in scrutinizing the lesions in the hypothalamic region. We report a case of a hypothalamic glioma masquerading as a craniopharyngioma on imaging along with brief review of both the tumors.

Lactoferrin modified graphene oxide iron oxide nanocomposite for glioma-targeted drug delivery.

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Song, Meng-Meng; Xu, Huai-Liang; Liang, Jun-Xing; Xiang, Hui-Hui; Liu, Rui; Shen, Yu-Xian

2017-08-01

Targeting delivery of drugs in a specific manner represents a potential powerful technology in gliomas. Herein, we prepared a multifunctional targeted delivery system based on graphene oxide (GO) that contains a molecular bio-targeting ligand and superparamagnetic iron oxide nanoparticles on the surface of GO for magnetic targeting. Superparamagnetic Fe 3 O 4 nanoparticles was loaded on the surface of GO via chemical precipitation method to form GO@Fe 3 O 4 nanocomposites. Lactoferrin (Lf), an iron-transporting serum glycoprotein that binds to receptors overexpressed at the surface of glioma cells and vascular endothelial cell of the blood brain barrier, was chosen as the targeted ligand to construct the targeted delivery system Lf@GO@Fe 3 O 4 through EDC/NHS chemistry. With the confirmation of TEM, DLS and VSM, the resulting Lf@GO@Fe 3 O 4 had a size distribution of 200-1000nm and exhibited a superparamagnetic behavior. The nano delivery system had a high loading capacity and exhibited a pH-dependent release behavior. Compared with free DOX and DOX@GO@Fe 3 O 4 , Lf@GO@Fe 3 O 4 @DOX displayed greater intracellular delivery efficiency and stronger cytotoxicity against C6 glioma cells. The results demonstrated the potential utility of Lf conjugated GO@Fe 3 O 4 nanocomposites for therapeutic application in the treatment of gliomas. Copyright © 2017. Published by Elsevier B.V.

Use of statins and risk of glioma

DEFF Research Database (Denmark)

Gaist, David; Andersen, L; Hallas, Jesper

2013-01-01

Laboratory studies and a single case-control study have suggested a protective effect of statins on the risk of glioma. We wished to investigate the influence of statin use on the risk of glioma in a population-based setting.......Laboratory studies and a single case-control study have suggested a protective effect of statins on the risk of glioma. We wished to investigate the influence of statin use on the risk of glioma in a population-based setting....

Effects of x rays on the morphology and physiology of the CNS blood vessels of mice

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Gladysz, J [Akademia Medyczna, Poznan (Poland)

1974-01-01

Irradiation of the CNS of mice with 4000 to 7600 R produces transitional disorder of the permeability of vascular walls, followed by a permanent (irreversible) degenerative lesion of blood capillaries and the surrounding astrogial cells. Intensity of this alterations may however not be the same in different terminal blood vessels. It is very likely that the above described lesion appearing in the acute phase can be the main cause of further alterations in the CNS which are observed in late phase of postradiation disease.

Blood Vessel Enhancement and Segmentation for Screening of Diabetic Retinopathy

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Ibaa Jamal

2012-06-01

Full Text Available Diabetic retinopathy is an eye disease caused by the increase of insulin in blood and it is one of the main cuases of blindness in idusterlized countries. It is a progressive disease and needs an early detection and treatment. Vascular pattern of human retina helps the ophthalmologists in automated screening and diagnosis of diabetic retinopathy. In this article, we present a method for vascular pattern ehnacement and segmentation. We present an automated system which uses wavelets to enhance the vascular pattern and then it applies a piecewise threshold probing and adaptive thresholding for vessel localization and segmentation respectively. The method is evaluated and tested using publicly available retinal databases and we further compare our method with already proposed techniques.

Blood vessels segmentation of hatching eggs based on fully convolutional networks

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Geng, Lei; Qiu, Ling; Wu, Jun; Xiao, Zhitao

2018-04-01

FCN, trained end-to-end, pixels-to-pixels, predict result of each pixel. It has been widely used for semantic segmentation. In order to realize the blood vessels segmentation of hatching eggs, a method based on FCN is proposed in this paper. The training datasets are composed of patches extracted from very few images to augment data. The network combines with lower layer and deconvolution to enables precise segmentation. The proposed method frees from the problem that training deep networks need large scale samples. Experimental results on hatching eggs demonstrate that this method can yield more accurate segmentation outputs than previous researches. It provides a convenient reference for fertility detection subsequently.

The effects of gene polymorphisms on glioma prognosis.

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Cui, Ying; Li, Guolin; Yan, Mengdan; Li, Jing; Jin, Tianbo; Li, Shanqu; Mu, Shijie

2017-11-01

Malignant gliomas are the most common primary brain tumors. Various genetic factors play important roles in the development and prognosis of glioma. The present study focuses on the impact of MPHOSPH6, TNIP1 and several other genes (ACYP2, NAF1, TERC, TERT, OBFC1, ZNF208 and RTEL1) on telomere length and how this affects the prognosis of glioma. Forty-three polymorphisms in nine genes from 605 glioma patients were selected. The association between genotype and survival outcome was analyzed using the Kaplan-Meier method, Cox regression analysis and the log-rank test. The 1-year overall survival (OS) rates of patients younger than 40 years of age was higher compared to those in patients older than 40 years of age. The 1-year OS rate of patients who underwent total resection was higher than that of patients whose gliomas were not completely resected. The 1-year OS rates of patients undergoing chemotherapy and of patients who did not undergo chemotherapy were 39.90% and 26.80%, respectively. Univariate analyses showed that ACYP2 rs12615793 and TERT rs2853676 loci affected progression-free survival in glioma patients; both ZNF208 rs8105767 and ACYP2 rs843720 affected the OS of patients with low-grade gliomas. Multivariate analyses suggested that MPHOSPH6 rs1056629 and rs1056654, and TERT rs2853676 loci were associated with good prognoses of patients with glioma or high-grade gliomas, whereas ZNF208 rs8105767 was associated with good prognosis of patients with low-grade glioma. Age, surgical resection and chemotherapy influenced the survival rates of glioma patients. TERT, MPHOSPH6, ACYP2 and ZNF208 genes were found to affect glioma prognosis. Copyright © 2017 John Wiley & Sons, Ltd.

An Original Approach for Quantification of Blood Vessels on the Whole Tumour Section

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Nga Tran Kim

2003-01-01

Full Text Available Relative abundance of tumour angiogenesis has been shown to be of clinical relevance in cancers of various locations such as the ovary. Nevertheless, several problems are encountered when quantifying tumour microvessels: (i as many other tumour markers, vascularity pattern is often heterogeneous within the tumour mass and even within the same histological section. As a consequence, an adequate acquisition method must be developed for accurate field sampling. (ii Manual microvessel counting is long, tedious and subject to poor reproducibility. Introduction in routine practice requires a fast, reproducible and reliable automatic image processing. In this study we present an original procedure combining a slide scanner image acquisition and a fully automatic image analysis sequence. The slide scanner offers the advantage of recording an image of the whole histological section for subsequent automatic blood vessel detection and hot spot area location. Microvessel density and surface fraction were measured for the whole section as well as within hot spots. Different immunostaining methods were tested in order to optimise the procedure. Moreover, the method proposed was submitted to a quality control procedure, with reference to interactive identification of microvessels at scanner level. This experiment showed that 93 to 97% of blood vessels were detected, according to the staining protocol used. Colour figures can be viewed on http://www.esacp.org/acp/2003/25‐2/kim.htm.

Approaching a Scientific Consensus on the Association between Allergies and Glioma Risk: A Report from the Glioma International Case-Control Study.

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Amirian, E Susan; Zhou, Renke; Wrensch, Margaret R; Olson, Sara H; Scheurer, Michael E; Il'yasova, Dora; Lachance, Daniel; Armstrong, Georgina N; McCoy, Lucie S; Lau, Ching C; Claus, Elizabeth B; Barnholtz-Sloan, Jill S; Schildkraut, Joellen; Ali-Osman, Francis; Sadetzki, Siegal; Johansen, Christoffer; Houlston, Richard S; Jenkins, Robert B; Bernstein, Jonine L; Merrell, Ryan T; Davis, Faith G; Lai, Rose; Shete, Sanjay; Amos, Christopher I; Melin, Beatrice S; Bondy, Melissa L

2016-02-01

Several previous studies have found inverse associations between glioma susceptibility and a history of allergies or other atopic conditions. Some evidence indicates that respiratory allergies are likely to be particularly relevant with regard to glioma risk. Using data from the Glioma International Case-Control Study (GICC), we examined the effects of respiratory allergies and other atopic conditions on glioma risk. The GICC contains detailed information on history of atopic conditions for 4,533 cases and 4,171 controls, recruited from 14 study sites across five countries. Using two-stage random-effects restricted maximum likelihood modeling to calculate meta-analysis ORs, we examined the associations between glioma and allergy status, respiratory allergy status, asthma, and eczema. Having a history of respiratory allergies was associated with an approximately 30% lower glioma risk, compared with not having respiratory allergies (mOR, 0.72; 95% confidence interval, 0.58-0.90). This association was similar when restricting to high-grade glioma cases. Asthma and eczema were also significantly protective against glioma. A substantial amount of data on the inverse association between atopic conditions and glioma has accumulated, and findings from the GICC study further strengthen the existing evidence that the relationship between atopy and glioma is unlikely to be coincidental. As the literature approaches a consensus on the impact of allergies in glioma risk, future research can begin to shift focus to what the underlying biologic mechanism behind this association may be, which could, in turn, yield new opportunities for immunotherapy or cancer prevention. ©2016 American Association for Cancer Research.

SVM-based glioma grading. Optimization by feature reduction analysis

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Zoellner, Frank G.; Schad, Lothar R.; Emblem, Kyrre E.; Harvard Medical School, Boston, MA; Oslo Univ. Hospital

2012-01-01

We investigated the predictive power of feature reduction analysis approaches in support vector machine (SVM)-based classification of glioma grade. In 101 untreated glioma patients, three analytic approaches were evaluated to derive an optimal reduction in features; (i) Pearson's correlation coefficients (PCC), (ii) principal component analysis (PCA) and (iii) independent component analysis (ICA). Tumor grading was performed using a previously reported SVM approach including whole-tumor cerebral blood volume (CBV) histograms and patient age. Best classification accuracy was found using PCA at 85% (sensitivity = 89%, specificity = 84%) when reducing the feature vector from 101 (100-bins rCBV histogram + age) to 3 principal components. In comparison, classification accuracy by PCC was 82% (89%, 77%, 2 dimensions) and 79% by ICA (87%, 75%, 9 dimensions). For improved speed (up to 30%) and simplicity, feature reduction by all three methods provided similar classification accuracy to literature values (∝87%) while reducing the number of features by up to 98%. (orig.)

SVM-based glioma grading. Optimization by feature reduction analysis

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Zoellner, Frank G.; Schad, Lothar R. [University Medical Center Mannheim, Heidelberg Univ., Mannheim (Germany). Computer Assisted Clinical Medicine; Emblem, Kyrre E. [Massachusetts General Hospital, Charlestown, A.A. Martinos Center for Biomedical Imaging, Boston MA (United States). Dept. of Radiology; Harvard Medical School, Boston, MA (United States); Oslo Univ. Hospital (Norway). The Intervention Center

2012-11-01

We investigated the predictive power of feature reduction analysis approaches in support vector machine (SVM)-based classification of glioma grade. In 101 untreated glioma patients, three analytic approaches were evaluated to derive an optimal reduction in features; (i) Pearson's correlation coefficients (PCC), (ii) principal component analysis (PCA) and (iii) independent component analysis (ICA). Tumor grading was performed using a previously reported SVM approach including whole-tumor cerebral blood volume (CBV) histograms and patient age. Best classification accuracy was found using PCA at 85% (sensitivity = 89%, specificity = 84%) when reducing the feature vector from 101 (100-bins rCBV histogram + age) to 3 principal components. In comparison, classification accuracy by PCC was 82% (89%, 77%, 2 dimensions) and 79% by ICA (87%, 75%, 9 dimensions). For improved speed (up to 30%) and simplicity, feature reduction by all three methods provided similar classification accuracy to literature values ({proportional_to}87%) while reducing the number of features by up to 98%. (orig.)

PEGylated Polyamidoamine dendrimer conjugated with tumor homing peptide as a potential targeted delivery system for glioma.

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Jiang, Yan; Lv, Lingyan; Shi, Huihui; Hua, Yabing; Lv, Wei; Wang, Xiuzhen; Xin, Hongliang; Xu, Qunwei

2016-11-01

Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system (CNS) tumor with a short survival time. The failure of chemotherapy is ascribed to the low transport of chemotherapeutics across the Blood Brain Tumor Barrier (BBTB) and poor penetration into tumor tissue. In order to overcome the two barriers, small nanoparticles with active targeted capability are urgently needed for GBM drug delivery. In this study, we proposed PEGylated Polyamidoamine (PAMAM) dendrimer nanoparticles conjugated with glioma homing peptides (Pep-1) as potential glioma targeting delivery system (Pep-PEG-PAMAM), where PEGylated PAMAM dendrimer nanoparticle was utilized as carrier due to its small size and perfect penetration into tumor and Pep-1 was used to overcome BBTB via interleukin 13 receptor α2 (IL-13Rα2) mediated endocytosis. The preliminary availability and safety of Pep-PEG-PAMAM as a nanocarrier for glioma was evaluated. In vitro results indicated that a significantly higher amount of Pep-PEG-PAMAM was endocytosed by U87 MG cells. In vivo fluorescence imaging of U87MG tumor-bearing mice confirmed that the fluorescence intensity at glioma site of targeted group was 2.02 folds higher than that of untargeted group (**p<0.01), and glioma distribution experiment further revealed that Pep-PEG-PAMAM exhibited a significantly enhanced accumulation and improved penetration at tumor site. In conclusion, Pep-1 modified PAMAM was a promising nanocarrier for targeted delivery of brain glioma. Copyright © 2016 Elsevier B.V. All rights reserved.

Known glioma risk loci are associated with glioma with a family history of brain tumours -- a case-control gene association study.

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Melin, Beatrice; Dahlin, Anna M; Andersson, Ulrika; Wang, Zhaoming; Henriksson, Roger; Hallmans, Göran; Bondy, Melissa L; Johansen, Christoffer; Feychting, Maria; Ahlbom, Anders; Kitahara, Cari M; Wang, Sophia S; Ruder, Avima M; Carreón, Tania; Butler, Mary Ann; Inskip, Peter D; Purdue, Mark; Hsing, Ann W; Mechanic, Leah; Gillanders, Elizabeth; Yeager, Meredith; Linet, Martha; Chanock, Stephen J; Hartge, Patricia; Rajaraman, Preetha

2013-05-15

Familial cancer can be used to leverage genetic association studies. Recent genome-wide association studies have reported independent associations between seven single nucleotide polymorphisms (SNPs) and risk of glioma. The aim of this study was to investigate whether glioma cases with a positive family history of brain tumours, defined as having at least one first- or second-degree relative with a history of brain tumour, are associated with known glioma risk loci. One thousand four hundred and thirty-one glioma cases and 2,868 cancer-free controls were identified from four case-control studies and two prospective cohorts from USA, Sweden and Denmark and genotyped for seven SNPs previously reported to be associated with glioma risk in case-control designed studies. Odds ratios were calculated by unconditional logistic regression. In analyses including glioma cases with a family history of brain tumours (n = 104) and control subjects free of glioma at baseline, three of seven SNPs were associated with glioma risk: rs2736100 (5p15.33, TERT), rs4977756 (9p21.3, CDKN2A-CDKN2B) and rs6010620 (20q13.33, RTEL1). After Bonferroni correction for multiple comparisons, only one marker was statistically significantly associated with glioma risk, rs6010620 (ORtrend for the minor (A) allele, 0.39; 95% CI: 0.25-0.61; Bonferroni adjusted ptrend , 1.7 × 10(-4) ). In conclusion, as previously shown for glioma regardless of family history of brain tumours, rs6010620 (RTEL1) was associated with an increased risk of glioma when restricting to cases with family history of brain tumours. These findings require confirmation in further studies with a larger number of glioma cases with a family history of brain tumours. Copyright © 2012 UICC.

Morphological evaluation of the cerebral blood vessels in the late gestation fetal sheep following hypoxia in utero.

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Baburamani, Ana A; Lo, Camden; Castillo-Melendez, Margie; Walker, David W

2013-01-01

Hypoxia can significantly contribute to the development of permanent brain injury in the term neonate; however the response of cerebral blood vessels is not well understood. This study aimed to quantitatively measure vascular density and morphology using laminin immunohistochemistry as a marker of blood vessels, and determine the effects of a single, severe bout of hypoxia (umbilical cord occlusion, UCO) late in gestation on the developing cerebrovasculature in fetal sheep. At 124-126 days gestation singleton fetal sheep underwent surgery for implantation of catheters and placement of an inflatable cuff around the umbilical cord. A 10 min UCO or sham UCO (n=5) occurred at 132 days gestation. Fetal brains were collected at 24 h (n=5) or 48 h (n=4) after UCO for vascular density and morphology analysis of laminin immunohistochemistry. 48 h following a single, brief bout of severe hypoxia late in gestation decreased vascular density was seen in the caudate nucleus and no changes in vascular morphology occurred. However closer analysis revealed a significant shift in the frequency of smaller (≤10 μm) to larger (≤100 μm) perimeter blood vessels in periventricular and subcortical white matter. Close examination of the frequency distribution of vascular perimeter highlights that alterations in vascular morphology persist in the near term fetal brain for up to 48 h following a brief (10 min) hypoxia in white but not gray matter. These findings suggest that the near term brain may still be vulnerable to white matter injury following in utero hypoxia. Copyright © 2012 Elsevier Inc. All rights reserved.

L-DOPA Preloading Increases the Uptake of Borophenylalanine in C6 Glioma Rat Model: A New Strategy to Improve BNCT Efficacy

International Nuclear Information System (INIS)

Capuani, Silvia; Gili, Tommaso; Bozzali, Marco; Russo, Salvatore; Porcari, Paola; Cametti, Cesare; D'Amore, Emanuela; Colasanti, Marco; Venturini, Giorgio; Maraviglia, Bruno; Lazzarino, Giuseppe; Pastore, Francesco S.

2008-01-01

Purpose: Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on 10 B(n,α) 7 Li reaction, for the treatment of malignant gliomas. One of the main limitations for BNCT effectiveness is the insufficient intake of 10 B nuclei in the tumor cells. This work was aimed at investigating the use of L-DOPA as a putative enhancer for 10 B-drug 4-dihydroxy-borylphenylalanine (BPA) uptake in the C6-glioma model. The investigation was first performed in vitro and then extended to the animal model. Methods and Materials: BPA accumulation in C6-glioma cells was assessed using radiowave dielectric spectroscopy, with and without L-DOPA preloading. Two L-DOPA incubation times (2 and 4 hours) were investigated, and the corresponding effects on BPA accumulation were quantified. C6-glioma cells were also implanted in the brain of 32 rats, and tumor growth was monitored by magnetic resonance imaging. Rats were assigned to two experimental branches: (1) BPA administration; (2) BPA administration after pretreatment with L-DOPA. All animals were sacrificed, and assessments of BPA concentrations in tumor tissue, normal brain, and blood samples were performed using high-performance liquid chromatography. Results: L-DOPA preloading induced a massive increase of BPA concentration in C6-glioma cells only after a 4-hour incubation. In the animal model, L-DOPA pretreatment produced a significantly higher accumulation of BPA in tumor tissue but not in normal brain and blood samples. Conclusions: This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT. L-DOPA preloading effect is discussed in terms of membrane transport mechanisms

Disrupting established tumor blood vessels: an emerging therapeutic strategy for cancer.

Science.gov (United States)

McKeage, Mark J; Baguley, Bruce C

2010-04-15

The unique characteristics of tumor vasculature represent an attractive target that may be exploited by vascular-targeting anticancer agents. A promising strategy involves the selective disruption of established tumor blood vessels by tumor-vascular disrupting agents (tumor-VDAs), which exhibit antivascular activity, resulting in inhibition of tumor blood flow and extensive necrosis within the tumor core. The tumor-VDA class can be subdivided into flavonoid compounds, which are related to flavone acetic acid, and tubulin-binding compounds. ASA404, of the flavonoid class, is the most advanced tumor-VDA in clinical development and has been evaluated preclinically and in several phase 1 and phase 2 studies. Preclinical studies have demonstrated the selective apoptosis of tumor endothelial cells and the inhibition of tumor blood flow. Synergistic activity was observed with ASA404 and with several chemotherapeutic agents, particularly taxanes. In clinical trials, compared with chemotherapy alone, ASA404 was tolerated well and produced improved activity in patients with nonsmall cell lung cancer when combined with paclitaxel and carboplatin. Phase 3 clinical trials are ongoing. Selectively targeting established tumor vasculature with tumor-VDAs represents a promising and innovative approach to improving the efficacy of standard anticancer therapies. (c) 2010 American Cancer Society.

Local delivery of cancer-cell glycolytic inhibitors in high-grade glioma

Science.gov (United States)

Wicks, Robert T.; Azadi, Javad; Mangraviti, Antonella; Zhang, Irma; Hwang, Lee; Joshi, Avadhut; Bow, Hansen; Hutt-Cabezas, Marianne; Martin, Kristin L.; Rudek, Michelle A.; Zhao, Ming; Brem, Henry; Tyler, Betty M.

2015-01-01

Background 3-bromopyruvate (3-BrPA) and dichloroacetate (DCA) are inhibitors of cancer-cell specific aerobic glycolysis. Their application in glioma is limited by 3-BrPA's inability to cross the blood-brain-barrier and DCA's dose-limiting toxicity. The safety and efficacy of intracranial delivery of these compounds were assessed. Methods Cytotoxicity of 3-BrPA and DCA were analyzed in U87, 9L, and F98 glioma cell lines. 3-BrPA and DCA were incorporated into biodegradable pCPP:SA wafers, and the maximally tolerated dose was determined in F344 rats. Efficacies of the intracranial 3-BrPA wafer and DCA wafer were assessed in a rodent allograft model of high-grade glioma, both as a monotherapy and in combination with temozolomide (TMZ) and radiation therapy (XRT). Results 3-BrPA and DCA were found to have similar IC50 values across the 3 glioma cell lines. 5% 3-BrPA wafer-treated animals had significantly increased survival compared with controls (P = .0027). The median survival of rats with the 50% DCA wafer increased significantly compared with both the oral DCA group (P = .050) and the controls (P = .02). Rats implanted on day 0 with a 5% 3-BrPA wafer in combination with TMZ had significantly increased survival over either therapy alone. No statistical difference in survival was noted when the wafers were added to the combination therapy of TMZ and XRT, but the 5% 3-BrPA wafer given on day 0 in combination with TMZ and XRT resulted in long-term survivorship of 30%. Conclusion Intracranial delivery of 3-BrPA and DCA polymer was safe and significantly increased survival in an animal model of glioma, a potential novel therapeutic approach. The combination of intracranial 3-BrPA and TMZ provided a synergistic effect. PMID:25053853

Study of blood flow inside the stenosis vessel under the effect of solenoid magnetic field using ferrohydrodynamics principles

Science.gov (United States)

Badfar, Homayoun; Motlagh, Saber Yekani; Sharifi, Abbas

2017-10-01

In this paper, biomagnetic blood flow in the stenosis vessel under the effect of the solenoid magnetic field is studied using the ferrohydrodynamics (FHD) model. The parabolic profile is considered at an inlet of the axisymmetric stenosis vessel. Blood is modeled as electrically non-conducting, Newtonian and homogeneous fluid. Finite volume and the SIMPLE (Semi-Implicit Method for Pressure Linked Equations) algorithm are utilized to discretize governing equations. The investigation is studied at different magnetic numbers ( MnF=164, 328, 1640 and 3280) and the number of the coil loops (three, five and nine loops). Results indicate an increase in heat transfer, wall shear stress and energy loss (pressure drop) with an increment in the magnetic number (ratio of Kelvin force to dynamic pressure force), arising from the FHD, and the number of solenoid loops. Furthermore, the flow pattern is affected by the magnetic field, and the temperature of blood can be decreased up to 1.48 {}°C under the effect of the solenoid magnetic field with nine loops and reference magnetic field ( B0) of 2 tesla.

Amino acid study of cerebral gliomas using positron emission tomography; Analysis of ( sup 11 C-methyl)-L-methionine uptake index

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Mineura, Katsuyoshi; Sasajima, Toshio; Suda, Yoshitaka; Kowada, Masayoshi [Akita Univ. (Japan). School of Medicine; Shishido, Fumio; Uemura, Kazuo

1990-12-01

Sixteen patients with gliomas (7 low grade, 9 high grade) were examined using positron emission tomography (PET) with intravenous administration of 22.2 MBq/kg (0.6 mCi/Kg) of ({sup 11}C-methyl)-L-methionine (C-11 Met). The tracer uptake in regions of interest was calculated on PET images taken 45 minutes after injection; the uptake index was represented as a percentage of the total count in the arterial blood summed over 45 minutes. C-11 Met uptake indices in the tumors ranged from 0.020 to 0.041% with a mean of 0.032% for the low-grade gliomas and from 0.013 to 0.044% with a mean of 0.036% for the high-grade gliomas. These indices significantly increased as compared with those in the contralateral gray matter (0.008-0.032% with a mean of 0.023%; p<0.01 vs low-grade gliomas, p<0.001 vs high-grade gliomas). In the low-grade gliomas, C-11 Met PET images clearly depicted the existence and even the extent of the tumors, although x-ray computed tomography (CT) did not always distinguish tumoral lesions. In the high-grade gliomas, the areas of tracer accumulation regionally extended to peritumoral low density on CT scans, where malignant tumor cell infiltration was proved by operative and follow-up CT findings. C-11 Met may be a useful radiopharmaceutical for differential diagnosis of gliomas, and the accuracy of tumor localization will give us a better rationale in therapeutic strategies for surgery and radiation therapy of gliomas. (author).

Grading of Cerebral Glioma with Multiparametric MR Imaging and {sup 18}F-FDG-PET: Concordance and Accuracy

Energy Technology Data Exchange (ETDEWEB)

Yoon, Jeong Hee; Kim, Ji-hoon; Sohn, Chul-Ho; Choi, Seung Hong; Yun, Tae Jin; Song, Yong Sub [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Kang, Won Jun [Seoul National University Hospital, Department of Nuclear Medicine, Seoul (Korea, Republic of); Yonsei University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Eun, Yong [Seoul National University, College of Medicine, Seoul (Korea, Republic of); Chang, Kee-Hyun [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Soonchunhyang University Bucheon Hospital, Department of Radiology, Bucheon (Korea, Republic of)

2014-02-15

To retrospectively evaluate concordance rates and predictive values in concordant cases among multiparametric MR techniques and FDG-PET to grade cerebral gliomas. Multiparametric MR imaging and FDG-PET were performed in 60 consecutive patients with cerebral gliomas (12 low-grade and 48 high-grade gliomas). As the dichotomic variables, conventional MRI, minimum apparent diffusion coefficient in diffusion-weighted imaging, maximum relative cerebral blood volume ratio in perfusion-weighted imaging, choline/creatine ratio and (lipid and lactate)/creatine ratio in MR spectroscopy, and maximum standardised uptake value ratio in FDG-PET in low- and high-grade gliomas were compared. Their concordance rates and positive/negative predictive values (PPV/NPV) in concordant cases were obtained for the various combinations of multiparametric MR techniques and FDG-PET. There were significant differences between low- and high-grade gliomas in all techniques. Combinations of two, three, four, and five out of the five techniques showed concordance rates of 77.0 ± 4.8 %, 65.5 ± 4.0 %, 58.3 ± 2.6 % and 53.3 %, PPV in high-grade concordant cases of 97.3 ± 1.7 %, 99.1 ± 1.4 %, 100.0 ± 0 % and 100.0 % and NPV in low-grade concordant cases of 70.2 ± 7.5 %, 78.0 ± 6.0 %, 80.3 ± 3.4 % and 80.0 %, respectively. Multiparametric MR techniques and FDG-PET have a concordant tendency in a two-tiered classification for the grading of cerebral glioma. If at least two examinations concordantly indicated high-grade gliomas, the PPV was about 95 %. (orig.)

Evidence of Flicker-Induced Functional Hyperaemia in the Smallest Vessels of the Human Retinal Blood Supply.

Directory of Open Access Journals (Sweden)

Angelina Duan

Full Text Available Regional changes in blood flow are initiated within neural tissue to help fuel local differences in neural activity. Classically, this response was thought to arise only in larger arterioles and venules. However, recently, it has been proposed that a the smallest vessels of the circulation make a comparable contribution, and b the response should be localised intermittently along such vessels, due to the known distribution of contractile mural cells. To assess these hypotheses in human neural tissue in vivo, we imaged the retinal microvasculature (diameters 3-28 μm non-invasively, using adaptive optics, before and after delivery of focal (360 μm patches of flickering visible light. Our results demonstrated a definite average response in 35% of all vessel segments analysed. In these responding vessels, the magnitude of proportional dilation (mean ± SEM for pre-capillary arterioles 13 ± 5%, capillaries 31 ± 8%, and post-capillary venules 10 ± 3% is generally far greater than the magnitudes we and others have measured in the larger retinal vessels, supporting proposition a above. The dilations observed in venules were unexpected based on previous animal work, and may be attributed either to differences in stimulus or species. Response heterogeneity across the network was high; responses were also heterogeneous along individual vessels (45% of vessel segments showed demonstrable locality in their response. These observations support proposition b above. We also observed a definite average constriction across 7% of vessel segments (mean ± SEM constriction for capillaries -16 ± 3.2%, and post-capillary venules -18 ± 12%, which paints a picture of dynamic redistribution of flow throughout the smallest vessel networks in the retina in response to local, stimulus-driven metabolic demand.

Perfusion magnetic resonance imaging and magnetic resonance spectroscopy of cerebral gliomas showing imperceptible contrast enhancement on conventional magnetic resonance imaging

International Nuclear Information System (INIS)

Batra, A.; Tripathi, R.P.; Singh, A.K.

2004-01-01

The purpose of the present paper was to evaluate the utility of perfusion MRI in cerebral gliomas showing imperceptible contrast enhancement on conventional MRI, and to evaluate the relationships of perfusion MRI and magnetic resonance (MR) spectroscopic results in these tumours. Twenty-two patients with histopathologically proven cerebral gliomas and showing insignificant contrast enhancement on conventional MR were included in the present study. All patients underwent perfusion MRI and MR spectroscopy on a 1.5-T MR system. Significant differences of the relative cerebral blood volume (rCBV) values and the choline : creatine ratios were noted between low-grade and anaplastic gliomas (P < 0.01). Good correlation was found between the rCBV values and the choline : creatine values (y = 0. 532x + 1.5643; r = 0.67). Perfusion MRI can be a useful tool in assessing the histopathological grade of non-contrast-enhancing cerebral gliomas. Along with MR spectroscopic imaging it can serve as an important technique for preoperative characterization of such gliomas, so that accurate targeting by stereotactic biopsies is possible. Copyright (2004) Blackwell Science Pty Ltd

Nasal Glioma: Case report

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Ozgur Surmelioglu

2011-02-01

Full Text Available Nasal gliomas are rare, benign, congenital tumors that are thought to be result of abnormality in embryonic development. Three types of clinical presentations have been recognized; extranasal, intranasal and combined. Clinically, these masses are non-pulsatile, gray or purple lesions that obstruct the nasal cavity and cause deformity extranasaly. Histologically, they are made up of astrocytic cells, fibrous and vascular connective tissue that is covered with nasal respiratory mucosa. Treatment of the nasal glioma requires a multidisciplinary approach including an radiologist, neurosurgeon and otorhinolaryngologist. Radiological investigation should be performed to describe intracranial extension. In this case, a 2 years old boy with nasal mass that was diagnosed as nasal glioma is reported. . [Cukurova Med J 2011; 36(1.000: 34-36

Nasal Glioma: Case report

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Ozgur Surmelioglu

2011-03-01

Full Text Available Nasal gliomas are rare, benign, congenital tumors that are thought to be result of abnormality in embryonic development. Three types of clinical presentations have been recognized; extranasal, intranasal and combined. Clinically, these masses are non-pulsatile, gray or purple lesions that obstruct the nasal cavity and cause deformity extranasaly. Histologically, they are made up of astrocytic cells, fibrous and vascular connective tissue that is covered with nasal respiratory mucosa. Treatment of the nasal glioma requires a multidisciplinary approach including an radiologist, neurosurgeon and otorhinolaryngologist. Radiological investigation should be performed to describe intracranial extension. In this case, a 2 years old boy with nasal mass that was diagnosed as nasal glioma is reported. . [Cukurova Med J 2011; 36(1: 34-36

Human gliomas contain morphine

DEFF Research Database (Denmark)

Olsen, Peter; Rasmussen, Mads; Zhu, Wei

2005-01-01

BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogeno...... of the solutions used in the study nor was it present as a residual material in blank HPLC runs. CONCLUSIONS: Morphine is present in human gliomas, suggesting that it may exert an action that effects tumour physiology/pathology.......BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogenous...

An automated vessel segmentation of retinal images using multiscale vesselness

International Nuclear Information System (INIS)

Ben Abdallah, M.; Malek, J.; Tourki, R.; Krissian, K.

2011-01-01

The ocular fundus image can provide information on pathological changes caused by local ocular diseases and early signs of certain systemic diseases, such as diabetes and hypertension. Automated analysis and interpretation of fundus images has become a necessary and important diagnostic procedure in ophthalmology. The extraction of blood vessels from retinal images is an important and challenging task in medical analysis and diagnosis. In this paper, we introduce an implementation of the anisotropic diffusion which allows reducing the noise and better preserving small structures like vessels in 2D images. A vessel detection filter, based on a multi-scale vesselness function, is then applied to enhance vascular structures.

Distribution of Vascular Patterns in Different Subtypes of Renal Cell Carcinoma. A Morphometric Study in Two Distinct Types of Blood Vessels.

Science.gov (United States)

Ruiz-Saurí, Amparo; García-Bustos, V; Granero, E; Cuesta, S; Sales, M A; Marcos, V; Llombart-Bosch, A

2017-07-01

To analyze the presence of mature and immature vessels as a prognostic factor in patients with renal cell carcinoma and propose a classification of renal cancer tumor blood vessels according to morphometric parameters. Tissue samples were obtained from 121 renal cell carcinoma patients who underwent radical nephrectomy. Staining with CD31 and CD34 was used to differentiate between immature (CD31+) and mature (CD34+) blood vessels. We quantified the microvascular density, microvascular area and different morphometric parameters: maximum diameter, minimum diameter, major axis, minor axis, perimeter, radius ratio and roundness. We found that the microvascular density was higher in CD31+ than CD34+ vessels, but CD34+ vessels were larger than CD31+ vessels, as well as being strongly correlated with the ISUP tumor grade. We also identified four vascular patterns: pseudoacinar, fascicular, reticular and diffuse. Pseudoacinar and fascicular patterns were more frequent in clear cell renal cell carcinoma (37.62 and 35.64% respectively), followed by reticular pattern (21.78%), while in chromophobe tumors the reticular pattern predominated (90%). The isolated pattern was present in all papillary tumors (100%). In healthy renal tissue, the pseudoacinar and isolated patterns were differentially found in the renal cortex and medulla respectively. We defined four distinct vascular patterns significantly related with the ISUP tumor grade in renal cell carcinomas. Further studies in larger series are needed in order to validate these results. Analysis of both mature and immature vessels (CD34+ and CD31+) provides additional information when evaluating microvascular density.

Blood Pressure Control in Aging Predicts Cerebral Atrophy Related to Small-Vessel White Matter Lesions

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Kyle C. Kern

2017-05-01

Full Text Available Cerebral small-vessel damage manifests as white matter hyperintensities and cerebral atrophy on brain MRI and is associated with aging, cognitive decline and dementia. We sought to examine the interrelationship of these imaging biomarkers and the influence of hypertension in older individuals. We used a multivariate spatial covariance neuroimaging technique to localize the effects of white matter lesion load on regional gray matter volume and assessed the role of blood pressure control, age and education on this relationship. Using a case-control design matching for age, gender, and educational attainment we selected 64 participants with normal blood pressure, controlled hypertension or uncontrolled hypertension from the Northern Manhattan Study cohort. We applied gray matter voxel-based morphometry with the scaled subprofile model to (1 identify regional covariance patterns of gray matter volume differences associated with white matter lesion load, (2 compare this relationship across blood pressure groups, and (3 relate it to cognitive performance. In this group of participants aged 60–86 years, we identified a pattern of reduced gray matter volume associated with white matter lesion load in bilateral temporal-parietal regions with relative preservation of volume in the basal forebrain, thalami and cingulate cortex. This pattern was expressed most in the uncontrolled hypertension group and least in the normotensives, but was also more evident in older and more educated individuals. Expression of this pattern was associated with worse performance in executive function and memory. In summary, white matter lesions from small-vessel disease are associated with a regional pattern of gray matter atrophy that is mitigated by blood pressure control, exacerbated by aging, and associated with cognitive performance.

Changes in peripapillary blood vessel density in Graves' orbitopathy after orbital decompression surgery as measured by optical coherence tomography angiography.

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Lewis, Kyle T; Bullock, John R; Drumright, Ryan T; Olsen, Matthew J; Penman, Alan D

2018-03-08

The purpose is to evaluate the utility of optical coherence tomography (OCT) angiography in the evaluation of Graves' orbitopathy (GO) and response to orbital decompression in patients with and without dysthyroid optic neuropathy (DON). This was a single-center, prospective case series in a cohort of 12 patients (24 orbits) with GO and ±DON, (6 orbits) who underwent bilateral orbital decompression. All patients underwent pre- and postoperative OCT angiography of the peripapillary area. Vessel density indices were calculated in a 4.5 mm × 4.5 mm ellipsoid centered on the optic disk using split-spectrum amplitude decorrelation angiography algorithm, producing the vessel density measurements. Mean change in vessel density indices was compared between pre- and postoperative sessions and between patients with and without DON. Patient 1, a 34-year-old male with GO and unilateral DON OD, showed a significant reduction in blood vessel density indices oculus dexter (OD) (DON eye) after decompression while a more modest reduction was found oculus sinister (OS) with the greatest change noted intrapapillary. Patient 2, a 50-year-old male with DON OU, showed worsening neuropathy following decompression OD that was confirmed by angiographic density indices. Patient 3, a 55-year-female with DON, showed a reduction in blood vessel density OD and increased density OS. Patients without DON showed overall less impressive changes in indices as compared to those with DON. Using OCT angiography, response to surgical treatment in GO orbits, more so in orbits with DON, can be demonstrated and quantified using vessel density indices with reproducibility.

Ultrastructural analysis of small blood vessels in skin biopsies in CADASIL

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Lačković Vesna

2008-01-01

Full Text Available Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL is an inherited small- and medium-artery disease of the brain caused by mutation of the Notch3 gene. Very often, this disease is misdiagnosed. We examined skin biopsies in two members of the first discovered Serbian family affected by CADASIL. Electron microscopy showed that skin blood vessels of both patients contain numerous deposits of granular osmiophilic material (GOM around vascular smooth muscle cells (VSMCs. We observed degeneration of VSMCs, reorganization of their cytoskeleton and dense bodies, disruption of myoendothelial contacts, and apoptosis. Our results suggest that the presence of GOM in small skin arteries represents a specific marker in diagnosis of CADASIL.

Cortical and Subcortical Structural Plasticity Associated with the Glioma Volumes in Patients with Cerebral Gliomas Revealed by Surface-Based Morphometry

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Jinping Xu

2017-06-01

Full Text Available Postlesional plasticity has been identified in patients with cerebral gliomas by inducing a large functional reshaping of brain networks. Although numerous non-invasive functional neuroimaging methods have extensively investigated the mechanisms of this functional redistribution in patients with cerebral gliomas, little effort has been made to investigate the structural plasticity of cortical and subcortical structures associated with the glioma volume. In this study, we aimed to investigate whether the contralateral cortical and subcortical structures are able to actively reorganize by themselves in these patients. The compensation mechanism following contralateral cortical and subcortical structural plasticity is considered. We adopted the surface-based morphometry to investigate the difference of cortical and subcortical gray matter (GM volumes in a cohort of 14 healthy controls and 13 patients with left-hemisphere cerebral gliomas [including 1 patients with World Health Organization (WHO I, 8 WHO II, and 4 WHO III]. The glioma volume ranges from 5.1633 to 208.165 cm2. Compared to healthy controls, we found significantly increased GM volume of the right cuneus and the left thalamus, as well as a trend toward enlargement in the right globus pallidus in patients with cerebral gliomas. Moreover, the GM volumes of these regions were positively correlated with the glioma volumes of the patients. These results provide evidence of cortical and subcortical enlargement, suggesting the usefulness of surface-based morphometry to investigate the structural plasticity. Moreover, the structural plasticity might be acted as the compensation mechanism to better fulfill its functions in patients with cerebral gliomas as the gliomas get larger.

Distinct mechanisms of relaxation to bioactive components from chamomile species in porcine isolated blood vessels

International Nuclear Information System (INIS)

Roberts, R.E.; Allen, S.; Chang, A.P.Y.; Henderson, H.; Hobson, G.C.; Karania, B.; Morgan, K.N.; Pek, A.S.Y.; Raghvani, K.; Shee, C.Y.; Shikotra, J.; Street, E.; Abbas, Z.; Ellis, K.; Heer, J.K.; Alexander, S.P.H.

2013-01-01

German chamomile (Matricaria recutita L.), a widely-used herbal medicine, has been reported to have a wide range of biological effects, including smooth muscle relaxation. The aim of this study was to compare the effects of representative compounds from chamomile (apigenin, luteolin, (−)-α-bisabolol, farnesene, umbelliferone; 3–30 μM) on vascular tone using porcine coronary and splenic arteries mounted for isometric tension recording in isolated tissue baths and precontracted with the thromboxane-mimetic U46619. Apigenin, luteolin, and (−)-α-bisabolol produced slow, concentration-dependent relaxations in both the coronary and splenic arteries that were not blocked by inhibition of nitric oxide synthase or potassium channels. Removal of extracellular calcium inhibited the relaxations to all three compounds, and these compounds also inhibited calcium re-addition-evoked contractions, indicating that the relaxation response may be mediated through inhibition of calcium influx. Apigenin and luteolin, but not (−)-α-bisabolol, enhanced the relaxation to the nitric oxide donor sodium nitroprusside, indicating that apigenin and luteolin may act to regulate cyclic GMP levels. Umbelliferone produced a rapid, transient relaxation in the splenic artery, but not the coronary artery, that was inhibited by L-NAME and removal of the endothelium, suggesting an influence on nitric oxide production. Farnesene, at concentrations up to 30 μM, was without effect in either blood vessel. In conclusion, hydroxylated compounds (apigenin, luteolin and (−)-α-bisabolol) found in chamomile all caused a slow relaxation of isolated blood vessels through an effect on calcium influx. Umbelliferone, on the other hand, produced a rapid, transient relaxation dependent upon release of nitric oxide from the endothelium. - Highlights: • Apigenin, luteolin, and (-)-α-bisabolol are present in chamomile. • They produced slow, concentration-dependent relaxations in arteries. • These

Chronic hydrocephalus-induced hypoxia: increased expression of VEGFR-2+ and blood vessel density in hippocampus.

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Dombrowski, S M; Deshpande, A; Dingwall, C; Leichliter, A; Leibson, Z; Luciano, M G

2008-03-18

Chronic hydrocephalus (CH) is a neurological disease characterized by increased cerebrospinal fluid volume and pressure that is often associated with impaired cognitive function. By and large, CH is a complex and heterogeneous cerebrospinal fluid (CSF) disorder where the exact site of brain insult is uncertain. Several mechanisms including neural compression, fiber stretch, and local or global hypoxia have been implicated in the underlying pathophysiology of CH. Specifically, the hippocampus, which plays a significant role in memory processing and is in direct contact with expanding CSF ventricles, may be involved. Using our model of chronic hydrocephalus, we quantified the density of vascular endothelial growth factor receptor 2 (VEGFR-2(+)) neurons, glial, endothelial cells, and blood vessels in hippocampal regions CA1, CA2-3, dentate gyrus and hilus using immunohistochemical and stereological methods. Density and %VEGFR-2(+) cell populations were estimated for CH animals (2-3 weeks vs. 12-16 weeks) and surgical controls (SC). Overall, we found approximately six- to eightfold increase in the cellular density of VEGFR-2(+) and more than double blood vessel density (BVd) in the hippocampus of CH compared with SC. There were no significant regional differences in VEGFR-2(+) cellular and BVd expression in the CH group. VEGFR-2(+) and BVds were significantly related to changes in CSF volume (Pblood vessel expression was related to focal compression alone or in combination with global ischemia/hypoxia conditions as previously described. These findings suggest that VEGFR-2 may play an adaptive role in angiogenesis after CH

Distinct mechanisms of relaxation to bioactive components from chamomile species in porcine isolated blood vessels

Energy Technology Data Exchange (ETDEWEB)

Roberts, R.E., E-mail: Richard.roberts@nottingham.ac.uk; Allen, S.; Chang, A.P.Y.; Henderson, H.; Hobson, G.C.; Karania, B.; Morgan, K.N.; Pek, A.S.Y.; Raghvani, K.; Shee, C.Y.; Shikotra, J.; Street, E.; Abbas, Z.; Ellis, K.; Heer, J.K.; Alexander, S.P.H., E-mail: steve.alexander@nottingham.ac.uk

2013-11-01

German chamomile (Matricaria recutita L.), a widely-used herbal medicine, has been reported to have a wide range of biological effects, including smooth muscle relaxation. The aim of this study was to compare the effects of representative compounds from chamomile (apigenin, luteolin, (−)-α-bisabolol, farnesene, umbelliferone; 3–30 μM) on vascular tone using porcine coronary and splenic arteries mounted for isometric tension recording in isolated tissue baths and precontracted with the thromboxane-mimetic U46619. Apigenin, luteolin, and (−)-α-bisabolol produced slow, concentration-dependent relaxations in both the coronary and splenic arteries that were not blocked by inhibition of nitric oxide synthase or potassium channels. Removal of extracellular calcium inhibited the relaxations to all three compounds, and these compounds also inhibited calcium re-addition-evoked contractions, indicating that the relaxation response may be mediated through inhibition of calcium influx. Apigenin and luteolin, but not (−)-α-bisabolol, enhanced the relaxation to the nitric oxide donor sodium nitroprusside, indicating that apigenin and luteolin may act to regulate cyclic GMP levels. Umbelliferone produced a rapid, transient relaxation in the splenic artery, but not the coronary artery, that was inhibited by L-NAME and removal of the endothelium, suggesting an influence on nitric oxide production. Farnesene, at concentrations up to 30 μM, was without effect in either blood vessel. In conclusion, hydroxylated compounds (apigenin, luteolin and (−)-α-bisabolol) found in chamomile all caused a slow relaxation of isolated blood vessels through an effect on calcium influx. Umbelliferone, on the other hand, produced a rapid, transient relaxation dependent upon release of nitric oxide from the endothelium. - Highlights: • Apigenin, luteolin, and (-)-α-bisabolol are present in chamomile. • They produced slow, concentration-dependent relaxations in arteries. • These

IDH-mutant glioma specific association of rs55705857 located at 8q24.21 involves MYC deregulation

Science.gov (United States)

Oktay, Yavuz; Ülgen, Ege; Can, Özge; Akyerli, Cemaliye B.; Yüksel, Şirin; Erdemgil, Yiğit; Durası, İ. Melis; Henegariu, Octavian Ioan; Nanni, E. Paolo; Selevsek, Nathalie; Grossmann, Jonas; Erson-Omay, E. Zeynep; Bai, Hanwen; Gupta, Manu; Lee, William; Turcan, Şevin; Özpınar, Aysel; Huse, Jason T.; Sav, M. Aydın; Flanagan, Adrienne; Günel, Murat; Sezerman, O. Uğur; Yakıcıer, M. Cengiz; Pamir, M. Necmettin; Özduman, Koray

2016-01-01

The single nucleotide polymorphism rs55705857, located in a non-coding but evolutionarily conserved region at 8q24.21, is strongly associated with IDH-mutant glioma development and was suggested to be a causal variant. However, the molecular mechanism underlying this association has remained unknown. With a case control study in 285 gliomas, 316 healthy controls, 380 systemic cancers, 31 other CNS-tumors, and 120 IDH-mutant cartilaginous tumors, we identified that the association was specific to IDH-mutant gliomas. Odds-ratios were 9.25 (5.17–16.52; 95% CI) for IDH-mutated gliomas and 12.85 (5.94–27.83; 95% CI) for IDH-mutated, 1p/19q co-deleted gliomas. Decreasing strength with increasing anaplasia implied a modulatory effect. No somatic mutations were noted at this locus in 114 blood-tumor pairs, nor was there a copy number difference between risk-allele and only-ancestral allele carriers. CCDC26 RNA-expression was rare and not different between the two groups. There were only minor subtype-specific differences in common glioma driver genes. RNA sequencing and LC-MS/MS comparisons pointed to significantly altered MYC-signaling. Baseline enhancer activity of the conserved region specifically on the MYC promoter and its further positive modulation by the SNP risk-allele was shown in vitro. Our findings implicate MYC deregulation as the underlying cause of the observed association. PMID:27282637

Molecular Therapeutic Targets for Glioma Angiogenesis

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Shingo Takano

2010-01-01

Full Text Available Due to the prominent angiogenesis that occurs in malignant glioma, antiangiogenic therapy has been attempted. There have been several molecular targets that are specific to malignant gliomas, as well as more broadly in systemic cancers. In this review, I will focus on some topics related to molecular therapeutic targets for glioma angiogenesis. First, important angiogenic factors that could be considered molecular targets are VEGF, VEGF-induced proteins on endothelial cells, tissue factor, osteopontin, v3 integrin, and thymidine phosphorylase as well as endogenous inhibitors, soluble Flt1, and thrombospondin 1. Second, hypoxic areas are also decreased by metronomic CPT11 treatment as well as temozolomide. Third, glioma-derived endothelial cells that are genetically and functionally distinct from normal endothelial cells should be targeted, for example, with SDF-1 and CXCR7 chemokine. Fourth, endothelial progenitor cells (EPCs likely contribute towards glioma angiogenesis in the brain and could be useful as a drug delivery tool. Finally, blockade of delta-like 4 (Dll4 results in a nonfunctioning vasculature and could be another important target distinct from VEGF.

Use of tricyclic antidepressants and risk of glioma

DEFF Research Database (Denmark)

Pottegård, Anton; García Rodríguez, Luis Alberto; Rasmussen, Lotte

2016-01-01

glioma (cases) in Denmark between 2000 and 2012 and matched these 1 : 20 to population controls. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) for glioma associated with long-term (⩾3 years) use of TCAs. Similar analyses were performed for selective serotonin reuptake...... inhibitors (SSRIs). RESULTS: We identified 3767 glioma cases and 75 340 population controls. Long-term use of TCAs was inversely associated with risk of glioma (OR 0.72, 95% CI: 0.41-1.25). Long-term SSRI use was not associated with glioma risk (OR 0.93, 95% CI: 0.75-1.16). CONCLUSIONS: Our study indicated...

Dimethyl phenyl piperazine iodide (DMPP) induces glioma regression by inhibiting angiogenesis

International Nuclear Information System (INIS)

He, Yan-qing; Li, Yan; Wang, Xiao-yu; He, Xiao-dong; Jun, Li; Chuai, Manli; Lee, Kenneth Ka Ho; Wang, Ju; Wang, Li-jing; Yang, Xuesong

2014-01-01

1,1-Dimethyl-4-phenyl piperazine iodide (DMPP) is a synthetic nicotinic acetylcholine receptor (nAChR) agonist that could reduce airway inflammation. In this study, we demonstrated that DMPP could dramatically inhibit glioma size maintained on the chick embryonic chorioallantoic membrane (CAM). We first performed MTT and BrdU incorporation experiments on U87 glioma cells in vitro to understand the mechanism involved. We established that DMPP did not significantly affect U87 cell proliferation and survival. We speculated that DMPP directly caused the tumor to regress by affecting the vasculature in and around the implanted tumor on our chick CAM model. Hence, we conducted detailed analysis of DMPP's inhibitory effects on angiogenesis. Three vasculogenesis and angiogenesis in vivo models were used in the study which included (1) early chick blood islands formation, (2) chick yolk-sac membrane (YSW) and (3) CAM models. The results revealed that DMPP directly suppressed all developmental stages involved in vasculogenesis and angiogenesis – possibly by acting through Ang-1 and HIF-2α signaling. In sum, our results show that DMPP could induce glioma regression grown on CAM by inhibiting vasculogenesis and angiogenesis. - Highlights: ●We demonstrated that DMPP inhibited the growth of glioma cells on chick CAM. ●DMPP did not significantly affect the proliferation and survival of U87 cells. ●We revealed that DMPP suppressed vasculogenesis and angiogenesis in chick embryo. ●Angiogenesis in chick CAM was inhibited by DMPP via most probably Ang-1 and HIF-2α. ●DMPP could be potentially developed as an anti-tumor drug in the future

Long-term culture of organotypic multicellular glioma spheroids: a good culture model for studying gliomas

NARCIS (Netherlands)

Kaaijk, P.; Troost, D.; Das, P. K.; Leenstra, S.; Bosch, D. A.

1995-01-01

Gliomas, as well as other solid tumours, contain tumour stroma composed of connective tissue, macrophages, capillaries and other non-cellular constituents. Therefore, a homogeneous culture of tumour cells alone, as is often used as a culture model for gliomas, is not ideal to study all aspects of

A report on radiation-induced gliomas

International Nuclear Information System (INIS)

Salvati, M.; Artico, M.; Caruso, R.; Rocchi, G.; Orlando, E.R.; Nucci, F.

1991-01-01

Radiation-induced gliomas are uncommon, with only 73 cases on record to date. The disease that most frequently occasioned radiation therapy has been acute lymphoblastic leukemia (ALL). Three more cases are added here, two after irradiation for ALL and one after irradiation for tinea capitis. In a review of the relevant literature, the authors stress the possibility that the ALL-glioma and the retinoblastoma-glioma links point to syndromes in their own right that may occur without radiation therapy.56 references

The Art of Intraoperative Glioma Identification

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Zoe Z Zhang

2015-07-01

Full Text Available A major dilemma in brain tumor surgery is the identification of tumor boundaries to maximize tumor excision and minimize postoperative neurological damage. Gliomas, especially low-grade tumors, and normal brain have a similar color and texture which poses a challenge to the neurosurgeon. Advances in glioma resection techniques combine the experience of the neurosurgeon and various advanced technologies. Intraoperative methods to delineate gliomas from normal tissue consist of 1 image-based navigation, 2 intraoperative sampling, 3 electrophysiological monitoring, and 4 enhanced visual tumor demarcation. The advantages and disadvantages of each technique are discussed. A combination of these methods is becoming widely accepted in routine glioma surgery. Gross total resection in conjunction with radiation, chemotherapy, or immune/gene therapy may increase the rates of cure in this devastating disease.

Micropatterned coculture of vascular endothelial and smooth muscle cells on layered electrospun fibrous mats toward blood vessel engineering.

Science.gov (United States)

Li, Huinan; Liu, Yaowen; Lu, Jinfu; Wei, Jiaojun; Li, Xiaohong

2015-06-01

A major challenge in vascular engineering is the establishment of proper microenvironment to guide the spatial organization, growth, and extracellular matrix (ECM) productions of cells found in blood vessels. In the current study, micropatterned fibrous mats with distinct ridges and grooves of different width were created to load smooth muscle cells (SMCs), which were assembled by stacking on vascular endothelial cell (EC)-loaded flat fibrous mats to mimic the in vivo-like organized structure of blood vessels. SMCs were mainly distributed in the ridges, and aligned fibers in the patterned regions led to the formation of elongated cell bodies, intense actin filaments, and expressions of collagen I and α-smooth muscle actin in a parallel direction with fibers. ECs spread over the flat fibrous mats and expressed collagen IV and laminin with a cobblestone-like feature. A z-stack scanning of fluorescently stained fibrous mats indicated that SMCs effectively infiltrated into fibrous scaffolds at the depth of around 200 μm. Compared with SMCs cultured alone, the coculture with ECs enhanced the proliferation, infiltration, and cytoskeleton elongation of SMCs on patterned fibrous mats. Although the coculture of SMCs made no significant difference in the EC growth, the coculture system on patterned fibrous scaffolds promoted ECM productions of both ECs and SMCs. Thus, this patterned fibrous configuration not only offers a promising technology in the design of tissue engineering scaffolds to construct blood vessels with durable mechanical properties, but also provides a platform for patterned coculture to investigate cell-matrix and cell-cell interactions in highly organized tissues. © 2014 Wiley Periodicals, Inc.

Glioma Association and Balancing Selection of ZFPM2.

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Shui-Ying Tsang

Full Text Available ZFPM2, encoding a zinc finger protein and abundantly expressed in the brain, uterus and smooth muscles, plays important roles in cardiac and gonadal development. Abnormal expression of ZFPM2 in ovarian tumors and neuroblastoma has been reported but hitherto its genetic association with cancer and effects on gliomas have not been studied. In the present study, the hexamer insertion-deletion polymorphism rs71305152, located within a large haplotype block spanning intron 1 to intron 3 of ZFPM2, was genotyped in Chinese cohorts of glioma (n = 350, non-glioma cancer (n = 354 and healthy control (n = 463 by direct sequencing and length polymorphism in gel electrophoresis, and ZFPM2 expression in glioma tissues (n = 69 of different grades was quantified by real-time RT-PCR. Moreover, potential natural selection pressure acting on the gene was investigated. Disease-association analysis showed that the overall genotype of rs71305152 was significantly associated with gliomas (P = 0.016, and the heterozygous genotype compared to the combined homozygous genotypes was less frequent in gliomas than in controls (P = 0.005 or non-glioma cancers (P = 0.020. ZFPM2 mRNA expression was negatively correlated with the grades of gliomas (P = 0.002, with higher expression levels in the low-grade gliomas. In the astrocytoma subtype, higher ZFPM2 expression was also correlated with the rs71305152 heterozygous genotype (P = 0.028. In addition, summary statistics tests gave highly positive values, demonstrating that the gene is under the influence of balancing selection. These findings suggest that ZFPM2 is a glioma susceptibility gene, its genotype and expression showing associations with incidence and severity, respectively. Moreover, the balancing selection acting on ZFPM2 may be related to the important roles it has to play in multiple organ development or associated disease etiology.

Current status of cerebral glioma surgery in China.

Science.gov (United States)

Wu, Jin-song; Zhang, Jie; Zhuang, Dong-xiao; Yao, Cheng-jun; Qiu, Tian-ming; Lu, Jun-feng; Zhu, Feng-ping; Mao, Ying; Zhou, Liang-fu

2011-09-01

The treatment of gliomas is highly individualized. Surgery for gliomas is essentially for histological diagnosis, to alleviate mass effect, and most importantly, to favor longer survival expectancy. During the past two decades, many surgical techniques and adjuvants have been applied to glioma surgery in China, which lead to a rapid development in the field of cerebral glioma surgery. This article broadly and critically reviewed the existing studies on cerebral glioma surgery and to portrait the current status of glioma surgery in China. A literature search was conducted covering major innovative surgical techniques and adjuvants for glioma surgery in China. The following databases were searched: the Pubmed (January 1995 to date); China Knowledge Resource Integrated Database (January 1995 to date) and VIP Database for Chinese Technical Periodicals (January 1995 to date). A selection criterion was established to exclude duplicates and irrelevant studies. The outcome measures were extracted from included studies. A total of 3307 articles were initially searched. After excluded by abstracts and full texts, 69 studies conducted in the mainland of China were included and went through further analysis. The philosophy of surgical strategies for cerebral gliomas in China is undergoing tremendous change. Nowadays Chinese neurosurgeons pay more attention to the postoperative neurofunctional status of the patients. The aim of the glioma surgery is not only the more extensive tumor resection but also the maximal safety of intervention. The well balance of longer overall survival and higher quality of life should be judged with respect to each individual patient.

Human autologous in vitro models of glioma immunogene therapy using B7-2, GM-CSF, and IL12

International Nuclear Information System (INIS)

Parney, I.F.; Farr-Jones, M.A.; Kane, K.; Chang, L.-J.; Petruk, K.C.

2002-01-01

Cancer immunogene therapy is based on vaccination with radiated, autologous tumor cells transduced with immunostimulatory genes. To help determine an optimal glioma immunogene therapy strategy, we stimulated lymphocytes with autologous human glioma cells transduced with B7-2 (CD86), granulocyte-macrophage colony-stimulating factor (GM-CSF), and/or interleukin-12 (IL12). A human glioma-derived cell culture (Ed147.BT) was transduced with B7-2, GM-CSF, and/or IL12 using retroviral vectors. Autologous peripheral blood mononuclear cells (PBMC) were co-cultured with irradiated gene-transduced tumor alone or a combination of radiated wild type and gene-transduced cells. Peripheral blood mononuclear cells proliferation was determined by serial cell counts. Peripheral blood mononuclear cells phenotype was assessed by flow cytometry for CD4, CD8, and CD16. Anti-tumor cytotoxicity was determined by chromium-51 ( 51 Cr) release assay. Peripheral blood mononuclear cells cell numbers all decreased during primary stimulation but tumor cells expressing B7-2 or GM-CSF consistently caused secondary proliferation. Tumors expressing B7-2 and GM-CSF or B7-2,GM-CSF,and IL12 consistently increased PBMC CD8+ (cytotoxic T) and CD16+ (natural killer) percentages. Interestingly, anti-tumor cytotoxicity only exceeded that of PBMC stimulated with wild type tumor alone when peripheral blood mononuclear cells were stimulated with both wild type tumor and B7-2/GM-CSF- (but not IL12) transduced cells. PBMC proliferation and phenotype is altered as expected by exposure to immunostimulatory gene-transduced tumor. However, transduced tumor cells alone do not stimulate greater anti-tumor cytotoxicity than wild type tumor. Only B7-2/GM-CSF-transduced cells combined with wild type produced increased cytotoxicity. This may reflect selection of turnor subclones with limited antigenic spectra during retrovirus-mediated gene transfer. (author)

Tricyclic Neovibsanin Scaffold Inhibits Glioma by Targeting Glioma ...

African Journals Online (AJOL)

Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. ... median survival time of mice bearing glioma to 34 days compared to 22 days in untreated mice. .... CX22 microscope (Olympus Corp, Inc, Tokyo,.

Treatment of hepatocellular carcinoma adjacent to large blood vessels using 1.5T MRI-guided percutaneous radiofrequency ablation combined with iodine-125 radioactive seed implantation

Energy Technology Data Exchange (ETDEWEB)

Lin, Zheng-Yu, E-mail: linsinlan@yahoo.com.cn [The Department of Radiology, First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou 350005 (China); Chen, Jin, E-mail: snow8968851@163.com [The Department of Radiology, First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou 350005 (China); Deng, Xiu-Fen, E-mail: dxf197286@yahoo.com.cn [The Department of Radiology, First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou 350005 (China)

2012-11-15

Objective: The objective is to study the technology associated with and feasibility of the treatment of hepatocellular carcinoma (HCC) adjacent to large blood vessels using 1.5T MRI-guided radiofrequency ablation combined with iodine-125 (I-125) radioactive seed implantation. Methods: Sixteen patients with a total of 24 HCC lesions (average maximum diameter: 2.35 {+-} 1.03 cm) were pathologically confirmed by biopsy or clinically diagnosed received 1.5T MRI-guided percutaneous radiofrequency ablation (RFA) treatment. Each patient had one lesion adjacent to large blood vessels ({>=}3 mm); after the ablation, I-125 radioactive seeds were implanted in the portions of the lesions that were adjacent to the blood vessels. Results: All the ablations and I-125 radioactive seed implantations were successful; a total of 118 seeds were implanted. The ablated lesions exhibited hypointense signals on the T2WI sequence with a thin rim of hyperintense signals; they also exhibited significant hyperintense signals on the T1WI sequence with clear boundaries. The average follow-up period was 11.1 {+-} 6.2 months. There were 23 complete responses and one partial response in the 24 lesions. The alpha-fetoprotein (AFP) levels of the patients significantly decreased. Conclusion: The 1.5T MRI-guided RFA combined with I-125 radioactive seed implantation for the treatment of HCC adjacent to large blood vessels is an effective technology.

Effect of antiprogesterone RU486 on VEGF expression and blood vessel remodeling on ovarian follicles before ovulation.

Directory of Open Access Journals (Sweden)

Annunziata Mauro

Full Text Available BACKGROUND: The success of ovarian follicle growth and ovulation is strictly related to the development of an adequate blood vessel network required to sustain the proliferative and endocrine functions of the follicular cells. Even if the Vascular Endothelial Growth Factor (VEGF drives angiogenesis before ovulation, the local role exerted by Progesterone (P₄ remains to be clarified, in particular when its concentration rapidly increases before ovulation. AIM: This in vivo study was designed to clarify the effect promoted by a P₄ receptor antagonist, RU486, on VEGF expression and follicular angiogenesis before ovulation, in particular, during the transition from pre to periovulatory follicles induced by human Chorionic Gonadotropins (hCG administration. MATERIAL AND METHODS: Preovulatory follicle growth and ovulation were pharmacologically induced in prepubertal gilts by combining equine Chorionic Gonadotropins (eCG and hCG used in the presence or absence of RU486. The effects on VEGF expression were analyzed using biochemical and immunohistochemical studies, either on granulosa or on theca layers of follicles isolated few hours before ovulation. This angiogenic factor was also correlated to follicular morphology and to blood vessels architecture. RESULTS AND CONCLUSIONS: VEGF production, blood vessel network and follicle remodeling were impaired by RU486 treatment, even if the cause-effect correlation remains to be clarified. The P₄ antagonist strongly down-regulated theca VEGF expression, thus, preventing most of the angiogenic follicle response induced by hCG. RU486-treated follicles displayed a reduced vascular area, a lower rate of endothelial cell proliferation and a reduced recruitment of perivascular mural cells. These data provide important insights on the biological role of RU486 and, indirectly, on steroid hormones during periovulatory follicular phase. In addition, an in vivo model is proposed to evaluate how periovulatory

Blood vessel endothelium-directed tumor cell streaming in breast tumors requires the HGF/C-Met signaling pathway.

Science.gov (United States)

Leung, E; Xue, A; Wang, Y; Rougerie, P; Sharma, V P; Eddy, R; Cox, D; Condeelis, J

2017-05-11

During metastasis to distant sites, tumor cells migrate to blood vessels. In vivo, breast tumor cells utilize a specialized mode of migration known as streaming, where a linear assembly of tumor cells migrate directionally towards blood vessels on fibronectin-collagen I-containing extracellular matrix (ECM) fibers in response to chemotactic signals. We have successfully reconstructed tumor cell streaming in vitro by co-plating tumors cells, macrophages and endothelial cells on 2.5 μm thick ECM-coated micro-patterned substrates. We found that tumor cells and macrophages, when plated together on the micro-patterned substrates, do not demonstrate sustained directional migration in only one direction (sustained directionality) but show random bi-directional walking. Sustained directionality of tumor cells as seen in vivo was established in vitro when beads coated with human umbilical vein endothelial cells were placed at one end of the micro-patterned 'ECM fibers' within the assay. We demonstrated that these endothelial cells supply the hepatocyte growth factor (HGF) required for the chemotactic gradient responsible for sustained directionality. Using this in vitro reconstituted streaming system, we found that directional streaming is dependent on, and most effectively blocked, by inhibiting the HGF/C-Met signaling pathway between endothelial cells and tumor cells. Key observations made with the in vitro reconstituted system implicating C-Met signaling were confirmed in vivo in mammary tumors using the in vivo invasion assay and intravital multiphoton imaging of tumor cell streaming. These results establish HGF/C-Met as a central organizing signal in blood vessel-directed tumor cell migration in vivo and highlight a promising role for C-Met inhibitors in blocking tumor cell streaming and metastasis in vivo, and for use in human trials.

Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas.

Science.gov (United States)

Brat, Daniel J; Verhaak, Roel G W; Aldape, Kenneth D; Yung, W K Alfred; Salama, Sofie R; Cooper, Lee A D; Rheinbay, Esther; Miller, C Ryan; Vitucci, Mark; Morozova, Olena; Robertson, A Gordon; Noushmehr, Houtan; Laird, Peter W; Cherniack, Andrew D; Akbani, Rehan; Huse, Jason T; Ciriello, Giovanni; Poisson, Laila M; Barnholtz-Sloan, Jill S; Berger, Mitchel S; Brennan, Cameron; Colen, Rivka R; Colman, Howard; Flanders, Adam E; Giannini, Caterina; Grifford, Mia; Iavarone, Antonio; Jain, Rajan; Joseph, Isaac; Kim, Jaegil; Kasaian, Katayoon; Mikkelsen, Tom; Murray, Bradley A; O'Neill, Brian Patrick; Pachter, Lior; Parsons, Donald W; Sougnez, Carrie; Sulman, Erik P; Vandenberg, Scott R; Van Meir, Erwin G; von Deimling, Andreas; Zhang, Hailei; Crain, Daniel; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Penny, Robert; Shelton, Troy; Sherman, Mark; Yena, Peggy; Black, Aaron; Bowen, Jay; Dicostanzo, Katie; Gastier-Foster, Julie; Leraas, Kristen M; Lichtenberg, Tara M; Pierson, Christopher R; Ramirez, Nilsa C; Taylor, Cynthia; Weaver, Stephanie; Wise, Lisa; Zmuda, Erik; Davidsen, Tanja; Demchok, John A; Eley, Greg; Ferguson, Martin L; Hutter, Carolyn M; Mills Shaw, Kenna R; Ozenberger, Bradley A; Sheth, Margi; Sofia, Heidi J; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean Claude; Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Jensen, Mark A; Liu, Jia; Pihl, Todd; Raman, Rohini; Wan, Yunhu; Wu, Ye; Ally, Adrian; Auman, J Todd; Balasundaram, Miruna; Balu, Saianand; Baylin, Stephen B; Beroukhim, Rameen; Bootwalla, Moiz S; Bowlby, Reanne; Bristow, Christopher A; Brooks, Denise; Butterfield, Yaron; Carlsen, Rebecca; Carter, Scott; Chin, Lynda; Chu, Andy; Chuah, Eric; Cibulskis, Kristian; Clarke, Amanda; Coetzee, Simon G; Dhalla, Noreen; Fennell, Tim; Fisher, Sheila; Gabriel, Stacey; Getz, Gad; Gibbs, Richard; Guin, Ranabir; Hadjipanayis, Angela; Hayes, D Neil; Hinoue, Toshinori; Hoadley, Katherine; Holt, Robert A; Hoyle, Alan P; Jefferys, Stuart R; Jones, Steven; Jones, Corbin D; Kucherlapati, Raju; Lai, Phillip H; Lander, Eric; Lee, Semin; Lichtenstein, Lee; Ma, Yussanne; Maglinte, Dennis T; Mahadeshwar, Harshad S; Marra, Marco A; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew L; Mieczkowski, Piotr A; Moore, Richard A; Mose, Lisle E; Mungall, Andrew J; Pantazi, Angeliki; Parfenov, Michael; Park, Peter J; Parker, Joel S; Perou, Charles M; Protopopov, Alexei; Ren, Xiaojia; Roach, Jeffrey; Sabedot, Thaís S; Schein, Jacqueline; Schumacher, Steven E; Seidman, Jonathan G; Seth, Sahil; Shen, Hui; Simons, Janae V; Sipahimalani, Payal; Soloway, Matthew G; Song, Xingzhi; Sun, Huandong; Tabak, Barbara; Tam, Angela; Tan, Donghui; Tang, Jiabin; Thiessen, Nina; Triche, Timothy; Van Den Berg, David J; Veluvolu, Umadevi; Waring, Scot; Weisenberger, Daniel J; Wilkerson, Matthew D; Wong, Tina; Wu, Junyuan; Xi, Liu; Xu, Andrew W; Yang, Lixing; Zack, Travis I; Zhang, Jianhua; Aksoy, B Arman; Arachchi, Harindra; Benz, Chris; Bernard, Brady; Carlin, Daniel; Cho, Juok; DiCara, Daniel; Frazer, Scott; Fuller, Gregory N; Gao, JianJiong; Gehlenborg, Nils; Haussler, David; Heiman, David I; Iype, Lisa; Jacobsen, Anders; Ju, Zhenlin; Katzman, Sol; Kim, Hoon; Knijnenburg, Theo; Kreisberg, Richard Bailey; Lawrence, Michael S; Lee, William; Leinonen, Kalle; Lin, Pei; Ling, Shiyun; Liu, Wenbin; Liu, Yingchun; Liu, Yuexin; Lu, Yiling; Mills, Gordon; Ng, Sam; Noble, Michael S; Paull, Evan; Rao, Arvind; Reynolds, Sheila; Saksena, Gordon; Sanborn, Zack; Sander, Chris; Schultz, Nikolaus; Senbabaoglu, Yasin; Shen, Ronglai; Shmulevich, Ilya; Sinha, Rileen; Stuart, Josh; Sumer, S Onur; Sun, Yichao; Tasman, Natalie; Taylor, Barry S; Voet, Doug; Weinhold, Nils; Weinstein, John N; Yang, Da; Yoshihara, Kosuke; Zheng, Siyuan; Zhang, Wei; Zou, Lihua; Abel, Ty; Sadeghi, Sara; Cohen, Mark L; Eschbacher, Jenny; Hattab, Eyas M; Raghunathan, Aditya; Schniederjan, Matthew J; Aziz, Dina; Barnett, Gene; Barrett, Wendi; Bigner, Darell D; Boice, Lori; Brewer, Cathy; Calatozzolo, Chiara; Campos, Benito; Carlotti, Carlos Gilberto; Chan, Timothy A; Cuppini, Lucia; Curley, Erin; Cuzzubbo, Stefania; Devine, Karen; DiMeco, Francesco; Duell, Rebecca; Elder, J Bradley; Fehrenbach, Ashley; Finocchiaro, Gaetano; Friedman, William; Fulop, Jordonna; Gardner, Johanna; Hermes, Beth; Herold-Mende, Christel; Jungk, Christine; Kendler, Ady; Lehman, Norman L; Lipp, Eric; Liu, Ouida; Mandt, Randy; McGraw, Mary; Mclendon, Roger; McPherson, Christopher; Neder, Luciano; Nguyen, Phuong; Noss, Ardene; Nunziata, Raffaele; Ostrom, Quinn T; Palmer, Cheryl; Perin, Alessandro; Pollo, Bianca; Potapov, Alexander; Potapova, Olga; Rathmell, W Kimryn; Rotin, Daniil; Scarpace, Lisa; Schilero, Cathy; Senecal, Kelly; Shimmel, Kristen; Shurkhay, Vsevolod; Sifri, Suzanne; Singh, Rosy; Sloan, Andrew E; Smolenski, Kathy; Staugaitis, Susan M; Steele, Ruth; Thorne, Leigh; Tirapelli, Daniela P C; Unterberg, Andreas; Vallurupalli, Mahitha; Wang, Yun; Warnick, Ronald; Williams, Felicia; Wolinsky, Yingli; Bell, Sue; Rosenberg, Mara; Stewart, Chip; Huang, Franklin; Grimsby, Jonna L; Radenbaugh, Amie J; Zhang, Jianan

2015-06-25

Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty is compounded by interobserver variability in histologic diagnosis. Mutations in IDH, TP53, and ATRX and codeletion of chromosome arms 1p and 19q (1p/19q codeletion) have been implicated as clinically relevant markers of lower-grade gliomas. We performed genomewide analyses of 293 lower-grade gliomas from adults, incorporating exome sequence, DNA copy number, DNA methylation, messenger RNA expression, microRNA expression, and targeted protein expression. These data were integrated and tested for correlation with clinical outcomes. Unsupervised clustering of mutations and data from RNA, DNA-copy-number, and DNA-methylation platforms uncovered concordant classification of three robust, nonoverlapping, prognostically significant subtypes of lower-grade glioma that were captured more accurately by IDH, 1p/19q, and TP53 status than by histologic class. Patients who had lower-grade gliomas with an IDH mutation and 1p/19q codeletion had the most favorable clinical outcomes. Their gliomas harbored mutations in CIC, FUBP1, NOTCH1, and the TERT promoter. Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%). The large majority of lower-grade gliomas without an IDH mutation had genomic aberrations and clinical behavior strikingly similar to those found in primary glioblastoma. The integration of genomewide data from multiple platforms delineated three molecular classes of lower-grade gliomas that were more concordant with IDH, 1p/19q, and TP53 status than with histologic class. Lower-grade gliomas with an IDH mutation either had 1p/19q codeletion or carried a TP53 mutation. Most

Microglia immunophenotyping in gliomas

Science.gov (United States)

Annovazzi, Laura; Mellai, Marta; Bovio, Enrica; Mazzetti, Samanta; Pollo, Bianca; Schiffer, Davide

2018-01-01

Microglia, once assimilated to peripheral macrophages, in gliomas has long been discussed and currently it is hypothesized to play a pro-tumor role in tumor progression. Uncertain between M1 and M2 polarization, it exchanges signals with glioma cells to create an immunosuppressive microenvironment and stimulates cell proliferation and migration. Four antibodies are currently used for microglia/macrophage identification in tissues that exhibit different cell forms and cell localization. The aim of the present work was to describe the distribution of the different cell forms and to deduce their significance on the basis of what is known on their function from the literature. Normal resting microglia, reactive microglia, intermediate and bumpy forms and macrophage-like cells can be distinguished by Iba1, CD68, CD16 and CD163 and further categorized by CD11b, CD45, c-MAF and CD98. The number of microglia/macrophages strongly increased from normal cortex and white matter to infiltrating and solid tumors. The ramified microglia accumulated in infiltration areas of both high- and low-grade gliomas, when hypertrophy and hyperplasia occur. In solid tumors, intermediate and bumpy forms prevailed and there is a large increase of macrophage-like cells in glioblastoma. The total number of microglia cells did not vary among the three grades of malignancy, but macrophage-like cells definitely prevailed in high-grade gliomas and frequently expressed CD45 and c-MAF. CD98+ cells were present. Microglia favors tumor progression, but many aspects suggest that the phagocytosing function is maintained. CD98+ cells can be the product of fusion, but also of phagocytosis. Microglia correlated with poorer survival in glioblastoma, when considering CD163+ cells, whereas it did not change prognosis in isocitrate dehydrogenase-mutant low grade gliomas. PMID:29399160

Correlation between {sup 18}F-fluoromisonidazole PET and expression of HIF-1α and VEGF in newly diagnosed and recurrent malignant gliomas

Energy Technology Data Exchange (ETDEWEB)

Kawai, Nobuyuki; Ogawa, Daisuke; Miyake, Keisuke; Tamiya, Takashi [Kagawa University, Department of Neurological Surgery, Faculty of Medicine, Kagawa (Japan); Lin, Wei [Kagawa University, Department of Neurological Surgery, Faculty of Medicine, Kagawa (Japan); Fourth Military Medical University, Department of Neurosurgery, Xijing Hospital, Xi' an (China); Cao, Wei-Dong [Fourth Military Medical University, Department of Neurosurgery, Xijing Hospital, Xi' an (China); Haba, Reiji [Kagawa University, Department of Diagnostic Pathology, Faculty of Medicine, Kagawa (Japan); Maeda, Yukito; Yamamoto, Yuka; Nishiyama, Yoshihiro [Kagawa University, Department of Radiology, Faculty of Medicine, Kagawa (Japan)

2014-10-15

Hypoxia and its consequences at the molecular level promote tumour progression and affect patient prognosis. One of the main early cellular events evoked by hypoxia is induction of hypoxia-inducible factor 1 (HIF-1) and subsequent upregulation of vascular endothelial growth factor (VEGF). In this study we sought to determine whether hypoxia detected by {sup 18}F-fluoromisonidazole (FMISO) PET accurately reflects the expression of HIF-1α and VEGF in the tumour and can be used as a biomarker of antiangiogenic treatment and as a prognostic factor in newly diagnosed and recurrent malignant gliomas. Enrolled in this study were 32 patients with newly diagnosed glioma and 16 with recurrent glioma of grade III or grade IV. All the patients had undergone FMISO PET preoperatively. The maximum tumour-to-blood FMISO activity ratio (T/B{sub max}) was used to evaluate the degree of tumour hypoxia and the hypoxic volume (HV) was calculated using a tumour-to-blood FMISO uptake ratio of ≥1.2. Immunohistochemical expressions of HIF-1α and VEGF were evaluated semiquantitatively using the immunoreactivity score (IRS, scores 0 to 12) and the correlation was examined between IRS of HIF-1α or VEGF and FMISO uptake of the tumour (SUV{sub tumour}) using navigation-based sampling. Survival was estimated using the Kaplan-Meier method in relation to the T/B{sub max} and the HV. The T/B{sub max} and the HV in grade IV gliomas were significantly higher than in grade III gliomas (P < 0.01 and P < 0.01, respectively). Moderate to strong HIF-1α and VEGF expression was observed in the majority of malignant gliomas. The IRS of HIF-1α and VEGF in the tumour were not significantly different between grade III and grade IV gliomas. The IRS of HIF-1α in the tumour did not correlate with the SUV{sub tumour} of FMISO in either newly diagnosed or recurrent glioma. There was a significant but weak correlation between the IRS of VEGF and the SUV{sub tumour} of FMISO in newly diagnosed glioma, but not

Blood vessel-based liver segmentation through the portal phase of a CT dataset

Science.gov (United States)

Maklad, Ahmed S.; Matsuhiro, Mikio; Suzuki, Hidenobu; Kawata, Yoshiki; Niki, Noboru; Moriyama, Noriyuki; Utsunomiya, Toru; Shimada, Mitsuo

2013-02-01

Blood vessels are dispersed throughout the human body organs and carry unique information for each person. This information can be used to delineate organ boundaries. The proposed method relies on abdominal blood vessels (ABV) to segment the liver considering the potential presence of tumors through the portal phase of a CT dataset. ABV are extracted and classified into hepatic (HBV) and nonhepatic (non-HBV) with a small number of interactions. HBV and non-HBV are used to guide an automatic segmentation of the liver. HBV are used to individually segment the core region of the liver. This region and non-HBV are used to construct a boundary surface between the liver and other organs to separate them. The core region is classified based on extracted posterior distributions of its histogram into low intensity tumor (LIT) and non-LIT core regions. Non-LIT case includes normal part of liver, HBV, and high intensity tumors if exist. Each core region is extended based on its corresponding posterior distribution. Extension is completed when it reaches either a variation in intensity or the constructed boundary surface. The method was applied to 80 datasets (30 Medical Image Computing and Computer Assisted Intervention (MICCAI) and 50 non-MICCAI data) including 60 datasets with tumors. Our results for the MICCAI-test data were evaluated by sliver07 [1] with an overall score of 79.7, which ranks seventh best on the site (December 2013). This approach seems a promising method for extraction of liver volumetry of various shapes and sizes and low intensity hepatic tumors.

C-MET overexpression and amplification in gliomas.

Science.gov (United States)

Kwak, Yoonjin; Kim, Seong-Ik; Park, Chul-Kee; Paek, Sun Ha; Lee, Soon-Tae; Park, Sung-Hye

2015-01-01

We investigated c-Met overexpression and MET gene amplification in gliomas to determine their incidence and prognostic significance. c-Met immunohistochemistry and MET gene fluorescence in situ hybridization were carried out on tissue microarrays from 250 patients with gliomas (137 grade IV GBMs and 113 grade II and III diffuse gliomas). Clinicopathological features of these cases were reviewed. c-Met overexpression and MET gene amplification were detected in 13.1% and 5.1% of the GBMs, respectively. All the MET-amplified cases showed c-Met overexpression, but MET amplification was not always concordant with c-Met overexpression. None of grade II and III gliomas demonstrated c-Met overexpression or MET gene amplification. Mean survival of the GBM patients with MET amplification was not significantly different from patients without MET amplification (P=0.155). However, GBM patients with c-Met overexpression survived longer than patients without c-Met overexpression (P=0.035). Although MET amplification was not related to poor GBM prognosis, it is partially associated with the aggressiveness of gliomas, as MET amplification was found only in grade IV, not in grade II and III gliomas. We suggest that MET inhibitor therapy may be beneficial in about 5% GBMs, which was the incidence of MET gene amplification found in the patients included in this study.

CD147 and glioma: a meta-analysis.

Science.gov (United States)

Li, Hui; Xi, Zhouhuan; Dai, Xuejiao; Wu, Wenyue; Li, Yanwen; Liu, Yanting; Zhang, Hanwen

2017-08-01

Gliomas are the most common primary brain tumors. This meta-analysis aimed to systematically evaluate the relationship between CD147 expression in tissues and the clinicopathological features of patients with glioma. We searched PubMed (1966-2016), EMBASE (1980-2016), Cochrane Library (1996-2016), Web of Science (1945-2016), China National Knowledge Infrastructure (1982-2016), and Wan Fang databases (1988-2016). Quality assessment of the literature was performed using the Newcastle-Ottawa Scale, with Revman 5.3 and Stata 14.0 for analysis. In total, 1806 glioma patients from 19 studies were included, and patients with CD147 overexpression had poorer overall survival [hazard ratio (HR) = 2.211, P CD147 expression when comparing glioma tissues versus non-cancerous brain tissues (OR 20.42; 95% CI 13.94-29.91; P CD147 expression did not differ based on patient's age (young vs. old, P = 0.89) or gender (female vs. male, P = 0.57). CD147 expression may be a potential prognostic biomarker for poorer overall and relapse-free survival, and may affect the 5-year survival rate in glioma patients. CD147 expression is also closely correlated with poor clinical characteristics in glioma patients.

Dimethyl phenyl piperazine iodide (DMPP) induces glioma regression by inhibiting angiogenesis

Energy Technology Data Exchange (ETDEWEB)

He, Yan-qing; Li, Yan; Wang, Xiao-yu [Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology and Embryology, Medical College, Jinan University, Guangzhou 510632 (China); He, Xiao-dong [Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510006 (China); Jun, Li [Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Centre of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China); Chuai, Manli [Division of Cell and Developmental Biology, University of Dundee, Dundee, DD1 5EH (United Kingdom); Lee, Kenneth Ka Ho [Key Laboratory for Regenerative Medicine of the Ministry of Education, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin (Hong Kong); Wang, Ju [Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Centre of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China); Wang, Li-jing, E-mail: wanglijing62@163.com [Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510006 (China); Yang, Xuesong, E-mail: yang_xuesong@126.com [Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology and Embryology, Medical College, Jinan University, Guangzhou 510632 (China)

2014-01-15

1,1-Dimethyl-4-phenyl piperazine iodide (DMPP) is a synthetic nicotinic acetylcholine receptor (nAChR) agonist that could reduce airway inflammation. In this study, we demonstrated that DMPP could dramatically inhibit glioma size maintained on the chick embryonic chorioallantoic membrane (CAM). We first performed MTT and BrdU incorporation experiments on U87 glioma cells in vitro to understand the mechanism involved. We established that DMPP did not significantly affect U87 cell proliferation and survival. We speculated that DMPP directly caused the tumor to regress by affecting the vasculature in and around the implanted tumor on our chick CAM model. Hence, we conducted detailed analysis of DMPP's inhibitory effects on angiogenesis. Three vasculogenesis and angiogenesis in vivo models were used in the study which included (1) early chick blood islands formation, (2) chick yolk-sac membrane (YSW) and (3) CAM models. The results revealed that DMPP directly suppressed all developmental stages involved in vasculogenesis and angiogenesis – possibly by acting through Ang-1 and HIF-2α signaling. In sum, our results show that DMPP could induce glioma regression grown on CAM by inhibiting vasculogenesis and angiogenesis. - Highlights: ●We demonstrated that DMPP inhibited the growth of glioma cells on chick CAM. ●DMPP did not significantly affect the proliferation and survival of U87 cells. ●We revealed that DMPP suppressed vasculogenesis and angiogenesis in chick embryo. ●Angiogenesis in chick CAM was inhibited by DMPP via most probably Ang-1 and HIF-2α. ●DMPP could be potentially developed as an anti-tumor drug in the future.

A novel synergetic targeting strategy for glioma therapy employing borneol combination with angiopep-2-modified, DOX-loaded PAMAM dendrimer.

Science.gov (United States)

Han, Shunping; Zheng, Hongyue; Lu, Yanping; Sun, Yue; Huang, Anhao; Fei, Weidong; Shi, Xiaowei; Xu, Xiuling; Li, Jingjing; Li, Fanzhu

2018-01-01

Glioma is the most common primary malignant brain tumour and the effect of chemotherapy is hampered by low permeability across the blood-brain-barrier (BBB). Borneol is a time-honoured 'Guide' drug in traditional Chinese medicine and has been proved to be capable of promoting free drugs into the brain efficiently, but there are still risks that free drugs, especially anti-glioma drugs, may be disassembled and metabolised before penetrating the BBB and caused the whole brain distribution. The purpose of this paper was to investigate whether borneol intervention could facilitate the BBB penetration and assist glioma treatment by combining with doxorubicin (DOX) loaded PAMAM dendrimers drug delivery system modified with Angiopep-2 (a ligand of the low-density lipoprotein receptor-related protein, which overexpress both in the BBB and gliomas). The results demonstrated that Angiopep-2 modification could actually enhance the affinity between the dendrimers and the targeting cells and finally increase the cell uptake and boost the anti-tumour ability. Borneol physical combination could further enhance the anti-tumour efficiency of this targeting drug delivery system (TDDS) after penetrating BBB. Compared with free DOX solution, this TDDS illustrated obviously sustained and pH-dependent drug release. This suggested that this synergetic strategy provided a promising way for glioma therapy.

Design and development of a blood vessel localization system using a Nir viewer

International Nuclear Information System (INIS)

Hernandez R, A.; Plascencia C, L. E.; Cordova F, T.; Padilla R, N.

2017-10-01

In addition to the multiple applications of ionizing radiation in clinical diagnosis there is the possibility of using another part of the electromagnetic spectrum such as near infrared (Nir). This paper presents the design and construction of a Nir Biosensor in a range between 800 and 900 nm, which allows the visualization of blood vessels for the venepuncture procedure with the aim of reducing the trauma of venous access to patients of all ages. The possibility that the device is used in the location of venous ulcers as an alternative to veno grams obtained by X-rays is also explored. (Author)

Remote non-invasive stereoscopic imaging of blood vessels: first in-vivo results of a new multispectral contrast enhancement technology

NARCIS (Netherlands)

Wieringa, F.P.; Mastik, F.; Cate, F.J. ten; Neumann, H.A.M.; Steen, A.F.W. van der

2006-01-01

We describe a contactless optical technique selectively enhancing superficial blood vessels below variously pigmented intact human skin by combining images in different spectral bands. Two CMOS-cameras, with apochromatic lenses and dual-band LED-arrays, simultaneously streamed Left (L) and Right (R)

3-D MDT with spherical targets by bilinear interpolation for determining blood velocity profiles including the vessel wall effect

Science.gov (United States)

Choomphon-anomakhun, Natthaphon; Natenapit, Mayuree

2018-02-01

A numerical simulation of three-dimensional (3-D) implant assisted-magnetic drug targeting (IA-MDT) using ferromagnetic spherical targets, including the effect from the vessel wall on the blood flow, is presented. The targets were implanted within arterioles and subjected to an externally uniform applied magnetic field in order to increase the effectiveness of targeting magnetic drug carrier particles (MDCPs). The capture area (As) of the MDCPs was determined by inspection of the particle trajectories simulated from the particle equations of motion. The blood flow velocities at any particle position around the target were obtained by applying bilinear interpolation to the numerical blood velocity data. The effects on As of the type of ferromagnetic materials in the targets and MDCPs, average blood flow rates, mass fraction of the ferromagnetic material in the MDCPs, average radii of MDCPs (Rp) and the externally applied magnetic field strength (μ0H0) were evaluated. Furthermore, the appropriate μ0H0 and Rp for the IA-MDT design is suggested. In the case of the SS409 target and magnetite MDCPs, dimensionless capture areas ranging from 4.1- to 12.4 and corresponding to particle capture efficiencies of 31-94% were obtained with Rp ranging from 100- to 500 nm, weight fraction of 80%, μ0H0 of 0.6 T and an average blood flow rate of 0.01 ms-1. In addition, the more general 3-D modelling of IA-MDT in this work is applicable to IA-MDT using spherical targets implanted within blood vessels for both laminar and potential blood flows including the wall effect.

Paediatric and adult malignant glioma

DEFF Research Database (Denmark)

Jones, Chris; Perryman, Lara; Hargrave, Darren

2012-01-01

Gliomas in children differ from their adult counterparts by their distribution of histological grade, site of presentation and rate of malignant transformation. Although rare in the paediatric population, patients with high-grade gliomas have, for the most part, a comparably dismal clinical outcome...... to older patients with morphologically similar lesions. Molecular profiling data have begun to reveal the major genetic alterations underpinning these malignant tumours in children. Indeed, the accumulation of large datasets on adult high-grade glioma has revealed key biological differences between...... the adult and paediatric disease. Furthermore, subclassifications within the childhood age group can be made depending on age at diagnosis and tumour site. However, challenges remain on how to reconcile clinical data from adult patients to tailor novel treatment strategies specifically for paediatric...

Diffuse brain calcification after radiation therapy in infantile cerebral malignant glioma

International Nuclear Information System (INIS)

Hondo, Hiroaki; Tanaka, Ryuichi; Yamada, Nobuhisa; Takeda, Norio

1987-01-01

We reported a case of infantile cerebral malignant glioma, which showed extensive intracranial calcification following radiation therapy, and reviewed the literature. A 4-month-old female infant was admitted to our hospital because of vomiting, enlargement of the head and convulsive seizures. Computerized tomography (CT) scans demonstrated a heterogeneously contrast-enhanced mass in the right temporo-parieto-occipital region and marked obstructive hydrocephalus. Subsequent to ventriculo-peritoneal shunt, biopsy was performed. The surgical specimen revealed anaplastic glioma. She then underwent whole brain irradiation with 1800 rads before subtotal removal and 3000 rads postoperatively. Calcification was first identified in the right frontal region and left basal ganglia 2.5 months after radiation therapy. At the age of 14 months, CT scans demonstrated extensive intracranial calcification in the cerebral hemispheres, basal ganglias, thalami, pons and cerebellum. A biopsy specimen of the frontal lobe revealed calcospherites of various sizes within and beside the walls of small vessels, but no tumor cells were observed. Cranial radiation therapy is a standard modality for treatment of children with neoplasm in the central nervous system. Since, however this therapy possibly causes long-term complications on the developing brain, it is important to plan radiation therapy for the brain tumor carefully. (author)

Inherited neurovascular diseases affecting cerebral blood vessels and smooth muscle.

Science.gov (United States)

Sam, Christine; Li, Fei-Feng; Liu, Shu-Lin

2015-10-01

Neurovascular diseases are among the leading causes of mortality and permanent disability due to stroke, aneurysm, and other cardiovascular complications. Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and Marfan syndrome are two neurovascular disorders that affect smooth muscle cells through accumulation of granule and osmiophilic materials and defective elastic fiber formations respectively. Moyamoya disease, hereditary hemorrhagic telangiectasia (HHT), microcephalic osteodysplastic primordial dwarfism type II (MOPD II), and Fabry's disease are disorders that affect the endothelium cells of blood vessels through occlusion or abnormal development. While much research has been done on mapping out mutations in these diseases, the exact mechanisms are still largely unknown. This paper briefly introduces the pathogenesis, genetics, clinical symptoms, and current methods of treatment of the diseases in the hope that it can help us better understand the mechanism of these diseases and work on ways to develop better diagnosis and treatment.

Pembrolizumab in Treating Younger Patients With Recurrent, Progressive, or Refractory High-Grade Gliomas, Diffuse Intrinsic Pontine Gliomas, Hypermutated Brain Tumors, Ependymoma or Medulloblastoma

Science.gov (United States)

2018-06-18

Constitutional Mismatch Repair Deficiency Syndrome; Lynch Syndrome; Malignant Glioma; Progressive Ependymoma; Progressive Medulloblastoma; Recurrent Brain Neoplasm; Recurrent Childhood Ependymoma; Recurrent Diffuse Intrinsic Pontine Glioma; Recurrent Medulloblastoma; Refractory Brain Neoplasm; Refractory Diffuse Intrinsic Pontine Glioma; Refractory Ependymoma; Refractory Medulloblastoma

Effects of High-sugar and High-fat Diet on Fat Deposition and Blood Vessel Wall on Sprague Dawley Rats Liver

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Vera Citra Setiawan Hoei

2013-11-01

Full Text Available People nowadays tend to consume more fast food and sweetened beverages. These foods usually contain high amount sugar and fat that have effects on the body including liver.This study was conducted to explore the effects of extensive intake of sugar and fat on blood glucose and  cholesterol level as well as changes in liver. Research was conducted with experimental method using 20 Sprague Dawley rats which were divided into 4 groups; 2 controls and 2 treatments. Rats were given 5 ml sugar or lard alternatively every 2 consecutive days for 1-month and 2-month respectively. Data was retrieved include blood glucose and cholesterol level, fatty liver percentage and blood vessel thickening after intervention through HE staining. The results showed that both 1-month and 2-month intervention group has significant increase in blood glucose and cholesterol level. However, the enhancement of fatty liver percentage and number of thickened blood vessels (p<0.05 were only foundsignificant (p<0.05 in 1-month intervention group.  We concluded that high intake of sugar and fat within 1-monthintervention have significant effects on the rat body including liver. Nevertheless, it was not found significant in 2-months intervention. Further studies are still needed to analyze this incongruent result.Key words: high-sugar diet, high-fat diet, fatty liver, atherosclerosis 

A new anti-glioma therapy, AG119: pre-clinical assessment in a mouse GL261 glioma model.

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Towner, Rheal A; Ihnat, Michael; Saunders, Debra; Bastian, Anja; Smith, Nataliya; Pavana, Roheeth Kumar; Gangjee, Aleem

2015-07-17

High grade gliomas (HGGs; grades III and IV) are the most common primary brain tumors in adults, and their malignant nature ranks them fourth in incidence of cancer death. Standard treatment for glioblastomas (GBM), involving surgical resection followed by radiation and chemotherapy with temozolomide (TMZ) and the anti-angiogenic therapy bevacizumab, have not substantially improved overall survival. New therapeutic agents are desperately needed for this devastating disease. Here we study the potential therapeutic agent AG119 in a pre-clinical model for gliomas. AG119 possesses both anti-angiogenic (RTK inhibition) and antimicrotubule cytotoxic activity in a single molecule. GL261 glioma-bearing mice were either treated with AG119, anti-VEGF (vascular endothelial growth factor) antibody, anti c-Met antibody or TMZ, and compared to untreated tumor-bearing mice. Animal survival was assessed, and tumor volumes and vascular alterations were monitored with morphological magnetic resonance imaging (MRI) and perfusion-weighted imaging, respectively. Percent survival of GL261 HGG-bearing mice treated with AG119 was significantly higher (p mouse GL261 glioma model, and that AG119 is also not subject to methyl guanine transferase (MGMT) mediated resistance, as is the case with TMZ, indicating that AG119 may be potentially useful in treating resistant gliomas.

The progress of radiosensitive genes of human brain glioma

International Nuclear Information System (INIS)

Wang Xi; Liu Qiang

2008-01-01

Human gliomas are one of the most aggressive tumors in brain which grow infiltrativly. Surgery is the mainstay of treatment. But as the tumor could not be entirely cut off, it is easy to relapse. Radiotherapy plays an important role for patients with gliomas after surgery. The efficacy of radiotherapy is associated with radio sensitivity of human gliomas. This paper makes a summary of current situation and progress for radiosensitive genes of human brain gliomas. (authors)

Epstein–Barr Virus in Gliomas: Cause, Association, or Artifact?

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Saghir Akhtar

2018-04-01

Full Text Available Gliomas are the most common malignant brain tumors and account for around 60% of all primary central nervous system cancers. Glioblastoma multiforme (GBM is a grade IV glioma associated with a poor outcome despite recent advances in chemotherapy. The etiology of gliomas is unknown, but neurotropic viruses including the Epstein–Barr virus (EBV that is transmitted via salivary and genital fluids have been implicated recently. EBV is a member of the gamma herpes simplex family of DNA viruses that is known to cause infectious mononucleosis (glandular fever and is strongly linked with the oncogenesis of several cancers, including B-cell lymphomas, nasopharyngeal, and gastric carcinomas. The fact that EBV is thought to be the causative agent for primary central nervous system (CNS lymphomas in immune-deficient patients has led to its investigations in other brain tumors including gliomas. Here, we provide a review of the clinical literature pertaining to EBV in gliomas and discuss the possibilities of this virus being simply associative, causative, or even an experimental artifact. We searched the PubMed/MEDLINE databases using the following key words such as: glioma(s, glioblastoma multiforme, brain tumors/cancers, EBV, and neurotropic viruses. Our literature analysis indicates conflicting results on the presence and role of EBV in gliomas. Further comprehensive studies are needed to fully implicate EBV in gliomagenesis and oncomodulation. Understanding the role of EBV and other oncoviruses in the etiology of gliomas, would likely open up new avenues for the treatment and management of these, often fatal, CNS tumors.

Activation of glioma cells generates immune tolerant NKT cells.

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Tang, Bo; Wu, Wei; Wei, Xiaowei; Li, Yang; Ren, Gang; Fan, Wenhai

2014-12-12

Therapeutic outcomes of glioma are currently not encouraging. Tumor tolerance plays an important role in the pathogenesis of glioma. It is reported that micro RNAs (miR) are associated with tumor development. This study aims to investigate the role of miR-92a in the development of tolerant natural killer T (NKT) cells. In this study, U87 cells (a human glioma cell line) and primary glioma cells were prepared. The assessment of miR-92a was performed by real time RT-PCR. The expression of interleukin (IL)-10 and IL-6 in NKT cells was evaluated by flow cytometry. Results showed that abundant IL-6(+) IL-10(+) NKT cells were detected in glioma tissue. Cultures of glioma cells and NKT cells induced the expression of IL-6 and IL-10 in NKT cells. Glioma cells expressed miR-92a; the latter played a critical role in the induction of IL-6 and IL-10 expression in NKT cells. The expression of the antitumor molecules, including perforin, Fas ligand, and interferon-γ, was significantly attenuated compared with control NKT cells. The IL-6(+) IL-10(+) NKT cells showed less capability in the induction of apoptosis in glioma cells, but showed the immune suppressor functions on CD8(+) T cell activities. We conclude that glioma-derived miR-92a induces IL-6(+) IL-10(+) NKT cells; this fraction of NKT cells can suppress cytotoxic CD8(+) T cells. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Autophagy involved in resveratrol increased radiosensitivity in glioma stem cells

International Nuclear Information System (INIS)

Long Linmei; Zhang Qingqing; Yang Neng; Ji Wenjun; Song Yunzhen; Zhao Jianghu; Liang Zhongqin

2012-01-01

Objective: To investigate the effect of Resveratrol combined with X-ray on radiosensitivity in glioma stem cells. Methods: The proliferation inhibition of glioma stem cells induced by X-rays and Resveratrol was assessed with MTT assay. The activation of proapoptotic effect was characterized by Hoechst 33258 stain. MDC stain and Western blot analysis were used to analyze the autophagy mechanism in X-rays-induced death of glioma stem cells. Results: MTT assay indicated that X-rays and Resveratrol decreased the viability of glioma stem cells (P<0.05); we found the proliferative inhibition of glioma stem cells was declined when we used 3-MA to inhibit autophagy(P<0.05). When the cells were treated by the Resveratrol and x-rays, their spherical shape were changed. Apoptosis was induced in glioma stem cells by combined X-rays and Resveratrol as detected by Hoechst 33258 staining. In addition, autophagy was induced in glioma stem cells in the combined treatment group as detected by MDC staining. Western blotting showed that Bcl-2 expression was decreased. in the combined treatment group (P<0.01), and the LC3-Ⅱ expression was increased in the combined treatment group (P<0.01). Conclusion: Resveratrol can increased the radiation sensitivity of glioma stem cells, the apoptosis and autophagy was induced in the glioma stem cells in the combined treatment X-rays and Resveratrol. Our results suggest that autophagy plays an essential role in the regulation of radiosensitization of glioma stem cells. (authors)

Phase I study of low-dose metronomic temozolomide for recurrent malignant gliomas

International Nuclear Information System (INIS)

Wong, Eric T.; Timmons, Joshua; Callahan, Amy; O’Loughlin, Lauren; Giarusso, Bridget; Alsop, David C.

2016-01-01

The treatment goal for recurrent malignant gliomas centers on disease stabilization while minimizing therapy-related side effects. Metronomic dosing of cytotoxic chemotherapy has emerged as a promising option to achieve this objective. This phase I study was performed using metronomic temozolomide (mTMZ) at 25 or 50 mg/m 2 /day continuously in 42-day cycles. Correlative studies were incorporated using arterial spin labeling MRI to assess tumor blood flow, analysis of matrix metalloproteinase-2 (MMP-2) and MMP-9 activities in the cerebrospinal fluid (CSF) as surrogates for tumor angiogenesis and invasion, as well as determination of CSF soluble interleukin-2 receptor alpha (sIL-2Rα) levels as a marker of immune modulation. Nine subjects were enrolled and toxicity consisted of primarily grade 1 or 2 hematological and gastrointestinal side effects; only one patient had a grade 3 elevated liver enzyme level that was reversible. Tumor blood flow was variable across subjects and time, with two experiencing a transient increase before a decrease to below baseline level while one exhibited a gradual drop in blood flow over time. MMP-2 activity correlated with overall survival but not with progression free survival, while MMP-9 activity did not correlate with either outcome parameters. Baseline CSF sIL-2Rα level was inversely correlated with time from initial diagnosis to first progression, suggesting that subjects with higher sIL-2Rα may have more aggressive disease. But they lived longer when treated with mTMZ, probably due to drug-related changes in T-cell constituency. mTMZ possesses efficacy against recurrent malignant gliomas by altering blood flow, slowing invasion and modulating antitumor immune function

Childhood Brain Stem Glioma Treatment (PDQ®)—Health Professional Version

Science.gov (United States)

Childhood brain stem glioma presents as a diffuse intrinsic pontine glioma (DIPG; a fast-growing tumor that is difficult to treat and has a poor prognosis) or a focal glioma (grows more slowly, is easier to treat, and has a better prognosis). Learn about the diagnosis, cellular classification, staging, treatment, and clinical trials for pediatric brain stem glioma in this expert-reviewed summary.

MRI Evaluation of Non-Necrotic T2-Hyperintense Foci in Pediatric Diffuse Intrinsic Pontine Glioma.

Science.gov (United States)

Clerk-Lamalice, O; Reddick, W E; Li, X; Li, Y; Edwards, A; Glass, J O; Patay, Z

2016-05-19

The conventional MR imaging appearance of diffuse intrinsic pontine glioma suggests intralesional histopathologic heterogeneity, and various distinct lesion components, including T2-hypointense foci, have been described. Here we report the prevalence, conventional MR imaging semiology, and advanced MR imaging features of non-necrotic T2-hyperintense foci in diffuse intrinsic pontine glioma. Twenty-five patients with diffuse intrinsic pontine gliomas were included in this study. MR imaging was performed at 3T by using conventional and advanced MR imaging sequences. Perfusion (CBV), vascular permeability (v e , K trans ), and diffusion (ADC) metrics were calculated and used to characterize non-necrotic T2-hyperintense foci in comparison with other lesion components, namely necrotic T2-hyperintense foci, T2-hypointense foci, peritumoral edema, and normal brain stem. Statistical analysis was performed by using Kruskal-Wallis and Wilcoxon rank sum tests. Sixteen non-necrotic T2-hyperintense foci were found in 12 tumors. In these foci, ADC values were significantly higher than those in either T2-hypointense foci (P = .002) or normal parenchyma (P = .0002), and relative CBV values were significantly lower than those in either T2-hypointense (P = .0002) or necrotic T2-hyperintense (P = .006) foci. Volume transfer coefficient values in T2-hyperintense foci were lower than those in T2-hypointense (P = .0005) or necrotic T2-hyperintense (P = .0348) foci. Non-necrotic T2-hyperintense foci are common, distinct lesion components within diffuse intrinsic pontine gliomas. Advanced MR imaging data suggest low cellularity and an early stage of angioneogenesis with leaky vessels resulting in expansion of the extracellular space. Because of the lack of biopsy validation, the underlying histoarchitectural and pathophysiologic changes remain unclear; therefore, these foci may correspond to a poorly understood biologic event in tumor evolution. © 2016 American Society of Neuroradiology.

Antiangiogenic Therapy and Mechanisms of Tumor Resistance in Malignant Glioma

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Ruman Rahman

2010-01-01

Full Text Available Despite advances in surgery, radiation therapy, and chemotherapeutics, patients with malignant glioma have a dismal prognosis. The formations of aberrant tumour vasculature and glioma cell invasion are major obstacles for effective treatment. Angiogenesis is a key event in the progression of malignant gliomas, a process involving endothelial cell proliferation, migration, reorganization of extracellular matrix and tube formation. Such processes are regulated by the homeostatic balance between proangiogenic and antiangiogenic factors, most notably vascular endothelial growth factors (VEGFs produced by glioma cells. Current strategies targeting VEGF-VEGF receptor signal transduction pathways, though effective in normalizing abnormal tumor vasculature, eventually result in tumor resistance whereby a highly infiltrative and invasive phenotype may be adopted. Here we review recent anti-angiogenic therapy for malignant glioma and highlight implantable devices and nano/microparticles as next-generation methods for chemotherapeutic delivery. Intrinsic and adaptive modes of glioma resistance to anti-angiogenic therapy will be discussed with particular focus on the glioma stem cell paradigm.

Zero-valent Fe confined mesoporous silica nanocarriers (Fe(0) @ MCM-41) for targeting experimental orthotopic glioma in rats

Science.gov (United States)

Shevtsov, M. A.; Parr, M. A.; Ryzhov, V. A.; Zemtsova, E. G.; Arbenin, A. Yu; Ponomareva, A. N.; Smirnov, V. M.; Multhoff, G.

2016-01-01

Mesoporous silica nanoparticles (MSNs) impregnated with zero-valent Fe (Fe(0) @ MCM-41) represent an attractive nanocarrier system for drug delivery into tumor cells. The major goal of this work was to assess whether MSNs can penetrate the blood-brain barrier in a glioblastoma rat model. Synthesized MSNs nanomaterials were characterized by energy dispersive X-ray spectroscopy, measurements of X-ray diffraction, scanning electron microscopy and Mössbauer spectroscopy. For the detection of the MSNs by MR and for biodistribution studies MSNs were labeled with zero-valent Fe. Subsequent magnetometry and nonlinear-longitudinal-response-M2 (NLR-M2) measurements confirmed the MR negative contrast enhancement properties of the nanoparticles. After incubation of different tumor (C6 glioma, U87 glioma, K562 erythroleukemia, HeLa cervix carcinoma) and normal cells such as fibroblasts and peripheral blood mononuclear cells (PBMCs) MSNs rapidly get internalized into the cytosol. Intracellular residing MSNs result in an enhanced cytotoxicity as Fe(0) @ MCM-41 promote the reactive oxygen species production. MRI and histological studies indicated an accumulation of intravenously injected Fe(0) @ MCM-41 MSNs in orthotopic C6 glioma model. Biodistribution studies with measurements of second harmonic of magnetization demonstrated an increased and dose-dependent retention of MSNs in tumor tissues. Taken together, this study demonstrates that MSNs can enter the blood-brain barrier and accumulate in tumorous tissues. PMID:27386761

The absorbed dose to blood from blood-borne activity

International Nuclear Information System (INIS)

Hänscheid, H; Fernández, M; Lassmann, M

2015-01-01

The radiation absorbed dose to blood and organs from activity in the blood is relevant for nuclear medicine dosimetry and for research in biodosimetry. The present study provides coefficients for the average absorbed dose rates to the blood from blood-borne activity for radionuclides frequently used in targeted radiotherapy and in PET diagnostics. The results were deduced from published data for vessel radius-dependent dose rate coefficients and reasonable assumptions on the blood-volume distribution as a function of the vessel radius. Different parts of the circulatory system were analyzed separately. Vessel size information for heart chambers, aorta, vena cava, pulmonary artery, and capillaries was taken from published results of morphometric measurements. The remaining blood not contained in the mentioned vessels was assumed to reside in fractal-like vascular trees, the smallest branches of which are the arterioles or venules. The applied vessel size distribution is consistent with recommendations of the ICRP on the blood-volume distribution in the human. The resulting average absorbed dose rates to the blood per nuclear disintegration per milliliter (ml) of blood are (in 10 −11  Gy·s −1 ·Bq −1 ·ml) Y-90: 5.58, I-131: 2.49, Lu-177: 1.72, Sm-153: 2.97, Tc-99m: 0.366, C-11: 4.56, F-18: 3.61, Ga-68: 5.94, I-124: 2.55. Photon radiation contributes 1.1–1.2·10 −11  Gy·s −1 ·Bq −1 ·ml to the total dose rate for positron emitters but significantly less for the other nuclides. Blood self-absorption of the energy emitted by ß-particles in the whole blood ranges from 37% for Y-90 to 80% for Tc-99m. The correspondent values in vascular trees, which are important for the absorbed dose to organs, range from 30% for Y-90 to 82% for Tc-99m. (paper)

Profound tumor-specific Th2 bias in patients with malignant glioma

International Nuclear Information System (INIS)

Shimato, Shinji; Maier, Lisa M; Maier, Richard; Bruce, Jeffrey N; Anderson, Richard CE; Anderson, David E

2012-01-01

Vaccination against tumor-associated antigens is one promising approach to immunotherapy against malignant gliomas. While previous vaccine efforts have focused exclusively on HLA class I-restricted peptides, class II-restricted peptides are necessary to induce CD4 + helper T cells and sustain effective anti-tumor immunity. In this report we investigated the ability of five candidate peptide epitopes derived from glioma-associated antigens MAGE and IL-13 receptor α2 to detect and characterize CD4 + helper T cell responses in the peripheral blood of patients with malignant gliomas. Primary T cell responses were determined by stimulating freshly isolated PBMCs from patients with primary glioblastoma (GBM) (n = 8), recurrent GBM (n = 5), meningioma (n = 7), and healthy controls (n = 6) with each candidate peptide, as well as anti-CD3 monoclonal antibody (mAb) and an immunodominant peptide epitope derived from myelin basic protein (MBP) serving as positive and negative controls, respectively. ELISA was used to measure IFN-γ and IL-5 levels, and the ratio of IFN-γ/IL-5 was used to determine whether the response had a predominant Th1 or Th2 bias. We demonstrate that novel HLA Class-II restricted MAGE-A3 and IL-13Rα2 peptides can detect T cell responses in patients with GBMs as well as in healthy subjects. Stimulation with a variety of peptide antigens over-expressed by gliomas is associated with a profound reduction in the IFN-γ/IL-5 ratio in GBM patients relative to healthy subjects. This bias is more pronounced in patients with recurrent GBMs. Therapeutic vaccine strategies to shift tumor antigen-specific T cell response to a more immunostimulatory Th1 bias may be needed for immunotherapeutic trials to be more successful clinically

Growth inhibition and chemosensitization of exogenous nitric oxide released from NONOates in glioma cells in vitro.

Science.gov (United States)

Weyerbrock, Astrid; Baumer, Brunhilde; Papazoglou, Anna

2009-01-01

Exogenous nitric oxide (NO) from NO donors has cytotoxic, chemosensitizing, and radiosensitizing effects, and increases vascular permeability and blood flow in tumors. Yet little is known about whether these cytotoxic and chemosensitizing effects can be observed in glioma cells at doses that alter tumor physiological characteristics in vivo and whether these effects are tumor selective. The effect of NO released from proline NONOate, diethylamine NONOate, spermine NONOate, and sodium nitrite on cell proliferation, apoptosis, and chemosensitivity to carboplatin of cultured glioma cells was studied in C6, U87 glioma cells, human glioblastoma cells, and human astrocytes and fibroblasts. Although proline NONOate failed to induce cell death, the other NO donors induced growth arrest when present in high concentrations (10(-2) M) in all cell lines. Chemosensitization was observed after concomitant incubation with spermine NONOate and carboplatin in C6 and human glioblastoma cells. There is strong evidence that cell death occurs primarily by necrosis and to a lesser degree by apoptosis. The NO doses, which altered tumor physiology in vivo, were not cytotoxic, indicating that NO alters vascular permeability and cell viability in vivo by different mechanisms. The authors found that NO-generating agents at high concentrations are potent growth inhibitors and might also be useful as chemosensitizers in glioma cells. These data corroborate the theory that the use of NOgenerating agents may play a role in the multimodal treatment of malignant gliomas but that the NO release must be targeted more specifically to tumor cells to improve selectivity and efficacy.

Dilated thin-walled blood and lymphatic vessels in human endometrium: a potential role for VEGF-D in progestin-induced break-through bleeding.

Directory of Open Access Journals (Sweden)

Jacqueline F Donoghue

Full Text Available Progestins provide safe, effective and cheap options for contraception as well as the treatment of a variety of gynaecological disorders. Episodes of irregular endometrial bleeding or breakthrough bleeding (BTB are a major unwanted side effect of progestin treatment, such that BTB is the leading cause for discontinued use of an otherwise effective and popular medication. The cellular mechanisms leading to BTB are poorly understood. In this study, we make the novel finding that the large, dilated, thin walled vessels characteristic of human progestin-treated endometrium include both blood and lymphatic vessels. Increased blood and lymphatic vessel diameter are features of VEGF-D action in other tissues and we show by immunolocalisation and Western blotting that stromal cell decidualisation results in a significant increase in VEGF-D protein production, particularly of the proteolytically processed 21 kD form. Using a NOD/scid mouse model with xenografted human endometrium we were able to show that progestin treatment causes decidualisation, VEGF-D production and endometrial vessel dilation. Our results lead to a novel hypothesis to explain BTB, with stromal cell decidualisation rather than progestin treatment per se being the proposed causative event, and VEGF-D being the proposed effector agent.

Development of a system for measuring wall shear stress in blood vessels using magnetic resonance imaging and computational fluid dynamics

International Nuclear Information System (INIS)

Yoshida, Keita; Nagao, Taisuke; Okada, Kouji; Miyazaki, Shohei; Yang, Xiaomei; Yamazaki, Youichi; Murase, Kenya

2008-01-01

We developed a system for measuring the wall shear stress (WSS) in blood vessels using magnetic resonance imaging (MRI) and computational fluid dynamics (CFD). The time-dependent velocity at the center of the blood vessel was measured by phase-contrast MRI and was approximated by finite Fourier series, which was used for generating the velocity profile at the inlet for the boundary condition to the CFD method. To validate the CFD method, we compared the WSS obtained by the CFD method with the theoretical value in a straight cylinder with various radii for both steady and pulsatile flows. We also investigated the dependence of the WSS on the inlet velocity profile incorporated into the CFD method. For steady flow, there was a good agreement between the WSS obtained by the CFD method and the theoretical value. For pulsatile flow, there was a relatively good agreement between them when the radius of the cylinder was 2.5 mm and the inlet velocity profile was given by the Womersley solution for fully developed pulsatile flow in a straight circular cylinder. When the radius of the cylinder was 5 mm and/or the inlet velocity profile was assumed to be parabolic, large differences were observed between them, suggesting that the assumption of fully developed flow does not hold true in these cases. In human studies, the vortex due to the secondary blood flow in the carotid arterial sinus was clearly observed. The WSS in the bifurcation was the highest, while that in the carotid arterial sinus was the smallest. In conclusion, the system presented here appears to be useful for measuring the WSS in blood vessels and for analyzing the cause and/or extent of atherosclerosis, and our results suggest that the inlet velocity profile should be carefully considered. (author)

Evaluation de l'IRM multiparamétrique comme indicateur de l'effet de thérapies anti-angiogéniques sur des modèles de gliomes implantés chez le rat

OpenAIRE

Lemasson, Benjamin

2010-01-01

In the context of glioma, MRI plays an extremely important role in the evaluation of new anti-tumor therapies in preclinical research for their development and in clinical routine to monitor patients under therapy. The aim of this thesis was to determine if one or several MRI parameters can be used as biomarker of therapy effects on glioma models in rats. We evaluated different MRI parameters (ADC: apparent diffusion coefficient of water, BVf: blood volume fraction and VSI: vessel size index)...

Blood vessel formation during tail regeneration in the leopard gecko (Eublepharis macularius): The blastema is not avascular.

Science.gov (United States)

Payne, Samantha L; Peacock, Hanna M; Vickaryous, Matthew K

2017-03-01

Unique among amniotes, many lizards are able to self-detach (autotomize) their tail and then regenerate a replacement. Tail regeneration involves the formation of a blastema, an accumulation of proliferating cells at the site of autotomy. Over time, cells of the blastema give rise to most of the tissues in the replacement tail. In non-amniotes capable of regenerating (such as urodeles and some teleost fish), the blastema is reported to be essentially avascular until tissue differentiation takes place. For tail regenerating lizards less is known. Here, we investigate neovascularization during tail regeneration in the leopard gecko (Eublepharis macularius). We demonstrate that the gecko tail blastema is not an avascular structure. Beginning with the onset of regenerative outgrowth, structurally mature (mural cell supported) blood vessels are found within the blastema. Although the pattern of blood vessel distribution in the regenerate tail differs from that of the original, a hierarchical network is established, with vessels of varying luminal diameters and wall thicknesses. Using immunostaining, we determine that blastema outgrowth and tissue differentiation is characterized by a dynamic interplay between the pro-angiogenic protein vascular endothelial growth factor (VEGF) and the anti-angiogenic protein thrombospondin-1 (TSP-1). VEGF-expression is initially widespread, but diminishes as tissues differentiate. In contrast, TSP-1 expression is initially restricted but becomes more abundant as VEGF-expression wanes. We predict that variation in the neovascular response observed between different regeneration-competent species likely relates to the volume of the blastema. J. Morphol. 278:380-389, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Molecular and Genetic Determinants of Glioma Cell Invasion

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Kenta Masui

2017-12-01

Full Text Available A diffusely invasive nature is a major obstacle in treating a malignant brain tumor, “diffuse glioma”, which prevents neurooncologists from surgically removing the tumor cells even in combination with chemotherapy and radiation. Recently updated classification of diffuse gliomas based on distinct genetic and epigenetic features has culminated in a multilayered diagnostic approach to combine histologic phenotypes and molecular genotypes in an integrated diagnosis. However, it is still a work in progress to decipher how the genetic aberrations contribute to the aggressive nature of gliomas including their highly invasive capacity. Here we depict a set of recent discoveries involving molecular genetic determinants of the infiltrating nature of glioma cells, especially focusing on genetic mutations in receptor tyrosine kinase pathways and metabolic reprogramming downstream of common cancer mutations. The specific biology of glioma cell invasion provides an opportunity to explore the genotype-phenotype correlation in cancer and develop novel glioma-specific therapeutic strategies for this devastating disease.

Regional cerebral blood flow measurement in brain tumors

International Nuclear Information System (INIS)

Izunaga, Hiroshi; Hirota, Yoshihisa; Takahashi, Mutsumasa; Fuwa, Isao; Kodama, Takafumi; Matsukado, Yasuhiko

1986-01-01

The regional cerebral blood flow (CBF) was determined on seventeen patients with brain tumors. Ring type single photon emission CT (SPECT) was used following intravenous injection of 133 Xe. Case materials included eleven meningiomas and six malignant gliomas. Evaluation was performed with emphasis on the following points; 1. Correlation of the flow data within tumors to the angiographic tumor stains, 2. Influence of tumors on the cerebral blood flow of the normal brain tissue, 3. Correlation between degree of peripheral edema and the flow data of the affected hemispheres. There was significant correlation between flow data within tumors and angiographic tumor stains in meningiomas. Influence of tumors on cerebral blood flow of the normal tissue was greater in meningiomas than in gliomas. There was negative correlation between the degree of peripheral edema and the flow data of the affected hemisphere. It has been concluded that the measurement of CBF in brain tumors is a valuable method in evaluation of brain tumors. (author)

Regional cerebral blood flow measurement in brain tumors

Energy Technology Data Exchange (ETDEWEB)

Izunaga, Hiroshi; Hirota, Yoshihisa; Takahashi, Mutsumasa; Fuwa, Isao; Kodama, Takafumi; Matsukado, Yasuhiko

1986-10-01

The regional cerebral blood flow (CBF) was determined on seventeen patients with brain tumors. Ring type single photon emission CT (SPECT) was used following intravenous injection of /sup 133/Xe. Case materials included eleven meningiomas and six malignant gliomas. Evaluation was performed with emphasis on the following points; 1. Correlation of the flow data within tumors to the angiographic tumor stains, 2. Influence of tumors on the cerebral blood flow of the normal brain tissue, 3. Correlation between degree of peripheral edema and the flow data of the affected hemispheres. There was significant correlation between flow data within tumors and angiographic tumor stains in meningiomas. Influence of tumors on cerebral blood flow of the normal tissue was greater in meningiomas than in gliomas. There was negative correlation between the degree of peripheral edema and the flow data of the affected hemisphere. It has been concluded that the measurement of CBF in brain tumors is a valuable method in evaluation of brain tumors.

Novel drugs in pediatric gliomas

OpenAIRE

Zhang, Dongli; Liu, Xiaoming; Fan, Conghai; Chen, Jiao

2017-01-01

Astrocytomas (gliomas) are the most common primary brain tumors among adults and second most frequent neoplasm among children. New ideas and novel approaches are being explored world over with aim to devise better management strategeies for this deadly pathological state. We searched the electronic database PubMed for pre-clinical as well as clinical controlled trials reporting importance of various therapeutic drugs against gliomas. It was observed clearly that this approach of using therape...

Glioma epidemiology in the central Tunisian population: 1993-2012.

Science.gov (United States)

Trabelsi, Saoussen; Brahim, Dorra H'mida-Ben; Ladib, Mohamed; Mama, Nadia; Harrabi, Imed; Tlili, Kalthoum; Yacoubi, Mohamed Tahar; Krifa, Hedi; Hmissa, Sihem; Saad, Ali; Mokni, Moncef

2014-01-01

Glioma is a heterogeneous central nervous system (CNS) tumor group that encompasses different histological subtypes with high variability in prognosis. The lesions account for almost 80% of primary malignant brain tumors. The aim of this study is to extend our understanding of the glioma epidemiology in the central Tunisian region. We analyzed 393 gliomas recorded in cancer registry of central Tunisia from 1993 to 2012. Crude incidence rates (CR) and world age-standardized rates (ASR) were estimated using annual population data size and age structure. Statistic correlations were established using Chi-square and Kaplan-Meier test. Tunisian glioma patients were identified with a mean age at diagnosis of 48 years and 1.5 sex ratio (male/female). During the 19 years period of study the highest incidence value was observed in male group between 1998 and 2002 (CR: 0.28, ASR: 0.3). Incidence results underline increasing high grade glioma occurring in the adulthood in the last period (2007-2012). Median survival was 27 months, with 1-, 2- and 5-year survival rates of 42%, 30% and 26%, respectively. Survival was greater in patients with younger age, lower tumor grade, infratentrial tumor location and undergoing a palliative treatment. This central Tunisia gliomas registry study provides important information that could improve glioma management and healthcare practice.

NY-ESO-1- and survivin-specific T-cell responses in the peripheral blood from patients with glioma

DEFF Research Database (Denmark)

Liu, Zhenjiang; Poiret, Thomas; Persson, Oscar

2018-01-01

The prognosis for patients with glioblastoma is grim. Ex vivo expanded tumor-associated antigen (TAA)-reactive T-cells from patients with glioma may represent a viable source for anticancer-directed cellular therapies. Immunohistochemistry was used to test the survivin (n = 40 samples) and NY-ESO...

Intraoperative Cerebral Glioma Characterization with Contrast Enhanced Ultrasound

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Francesco Prada

2014-01-01

Full Text Available Background. Contrast enhanced ultrasound (CEUS is a dynamic and continuous modality providing real-time view of vascularization and flow distribution patterns of different organs and tumors. Nevertheless its intraoperative use for brain tumors visualization has been performed few times, and a thorough characterization of cerebral glioma had never been performed before. Aim. To perform the first characterization of cerebral glioma using CEUS and to possibly achieve an intraoperative differentiation of different gliomas. Methods. We performed CEUS in an off-label setting in 69 patients undergoing surgery for cerebral glioma. An intraoperative qualitative analysis was performed comparing iCEUS with B-mode imaging. A postprocedural semiquantitative analysis was then performed for each case, according to EFSUMB criteria. Results were related to histopathology. Results. We observed different CE patterns: LGG show a mild, dotted CE with diffuse appearance and slower, delayed arterial and venous phase. HGG have a high CE with a more nodular, nonhomogeneous appearance and fast perfusion patterns. Conclusion. Our study characterizes for the first time human brain glioma with CEUS, providing further insight regarding these tumors’ biology. CEUS is a fast, safe, dynamic, real-time, and economic tool that might be helpful during surgery in differentiating malignant and benign gliomas and refining surgical strategy.

Methylation of the miR-126 gene associated with glioma progression.

Science.gov (United States)

Cui, Hongwei; Mu, Yongping; Yu, Lei; Xi, Ya-guang; Matthiesen, Rune; Su, Xiulan; Sun, Wenjie

2016-04-01

Gliomas are the most common and the most malignant brain tumors, accouting for 45-55% of all intracranial tumors. The incidence of glioma worldwide is about 6-12 per 100,000. Recently, several studies showed that the activation of the oncogenes and the inactivation and/or loss of the tumor suppressor genes, especially for miRNA-21, let-7 and so on, are the most primary molecule event in gliomas. MicroRNAs (miRNAs) are a class of endogenously expressed small noncoding RNAs which are usually 21-23 nucleotides long. miRNAs regulate gene expression and play important roles in a variety of physiological and pathological processes, such as cell proliferation, differentiation and apoptosis. To date, Growing evidence has shown that mi RNAs are frequently dysregulated in human cancers and can act as both tumor suppressors and oncogenes. Along with the discovery of micro RNA, more and more research focusing on its relationship with glioma was carried out to investigate the biological features of glioma and to provide experimental evidence for glioma mechanism. In the present study, we aimed to verify the miRNA-126 down-regulation which showed in the results of glioma tissue miRNAs chip and discuss the miRNA-126 methylation in patients with glioma. A total of 50 samples from patients with glioma and 20 control samples from patients with cerebral trauma were included in this study. The expression levels of the miR-126 gene were detected using quantitative polymerase chain reaction (PCR), and the methylation status of miR-126 was examined using methylation-specific PCR-denaturing high-performance liquid chromatography (MSP-DHPLC). The expression level of miRNA-126 was found to be significantly higher in the control group (0.6134 ± 0.1214) than in the glioma group (0.2771 ± 0.1529; P < 0.05). The expression was also significantly elevated in low-grade gliomas (0.3117 ± 0.1474) compared with high-grade gliomas (0.1582 ± 0.1345; P < 0.05). In addition, increased methylation of

A Novel Candidate Molecule in Pathological Grading Of Gliomas: ELABELA.

Science.gov (United States)

Artas, Gokhan; Ozturk, Sait; Kuloglu, Tuncay; Dagli, Adile Ferda; Gonen, Murat; Artas, Hakan; Aydin, Suleyman; Erol, Fatih Serhat

2018-04-06

This study aimed to investigate the possible role of ELABELA (ELA) in the histopathological grading of gliomas. We retrospectively assessed pathological specimens of patients who underwent surgery for intracranial space-occupying lesions. Only primary glioma specimens were included in this study. We enrolled 11 patients histologically diagnosed with low-grade glioma and 22 patients with high-grade glioma. The ELA antibody was applied to 4-6-µm-thick sections obtained from paraffin blocks. Histoscores were calculated using the distribution and intensity of staining immunoreactivity. An independent sample t-test was used for two-point inter-group assessments, whereas one-way analysis of variance was used for the other assessments. P 0.05 was considered statistically significant. The histoscores of the control brain, low-grade glioma, and high-grade glioma tissues were found to be 0.08, 0.37, and 0.92, respectively. The difference in ELA immunoreactivity between the control brain tissue and glioma tissue was statistically significant (p 0.05). In addition, a statistically significant increase was observed in ELA immunoreactivity in high-grade glioma tissues compared with that in low-grade glioma tissues (p 0.05). ELA has an angiogenetic role in the progression of glial tumors. ELA, which is an endogenous ligand of the apelin receptor, activates the apelinergic system and causes the progression of glial tumors. Further studies with a large number of patients are necessary to investigate the angiogenetic role of ELA in glial tumors.

Porous hybrid structures based on P(DLLA-co-TMC) and collagen for tissue engineering of small-diameter blood vessels

NARCIS (Netherlands)

Buttafoco, L.; Boks, Niels P.; Engbers-Buijtenhuijs, P.; Grijpma, Dirk W.; Poot, Andreas A.; Dijkstra, Pieter J.; Vermes, I.; Feijen, Jan

2006-01-01

Poly (D,L-lactide)-7co-(1,3-trimethylene carbonate) [P(DLLA-co-TMC)] (83 mol % DLLA) was used to produce matrices suitable for tissue engineering of small-diameter blood vessels. The copolymer was processed into tubular structures with a porosity of 98% by melt spinning and fiber winding, thus

Targeting Potassium Channels for Increasing Delivery of Imaging Agents and Therapeutics to Brain Tumors

Directory of Open Access Journals (Sweden)

Nagendra Sanyasihally Ningaraj

2013-05-01

Full Text Available Every year in the US, 20,000 new primary and nearly 200,000 metastatic brain tumor cases are reported. The cerebral microvessels/ capillaries that form the blood–brain barrier (BBB not only protect the brain from toxic agents in the blood but also pose a significant hindrance to the delivery of small and large therapeutic molecules. Different strategies have been employed to circumvent the physiological barrier posed by blood-brain tumor barrier (BTB. Studies in our laboratory have identified significant differences in the expression levels of certain genes and proteins between normal and brain tumor capillary endothelial cells. In this study, we validated the non-invasive and clinically relevant Dynamic Contrast Enhancing-Magnetic Resonance Imaging (DCE-MRI method with invasive, clinically irrelevant but highly accurate Quantitative Autoradiography (QAR method using rat glioma model. We also showed that DCE-MRI metric of tissue vessel perfusion-permeability is sensitive to changes in blood vessel permeability following administration of calcium-activated potassium (BKCa channel activator NS-1619. Our results show that human gliomas and brain tumor endothelial cells that overexpress BKCa channels can be targeted for increased BTB permeability for MRI enhancing agents to brain tumors. We conclude that monitoring the outcome of increased MRI enhancing agents’ delivery to microsatellites and leading tumor edges in glioma patients would lead to beneficial clinical outcome.

3-D trajectory model for MDT using micro-spheres implanted within large blood vessels

Science.gov (United States)

Choomphon-anomakhun, Natthaphon; Natenapit, Mayuree

2016-09-01

Implant assisted magnetic drug targeting (IA-MDT) using ferromagnetic spherical targets implanted within large blood vessels and subjected to a uniform externally applied magnetic field (H0) has been investigated and reported for the first time. The capture areas (As) of magnetic drug carrier particles (MDCPs) were determined from the analysis of particle trajectories simulated from equations of motion. Then, the effects of various parameters, such as types of ferromagnetic materials in the targets and MDCPs, blood flow rates, mass fraction of the ferromagnetic material in the MDCPs, average radii of MDCPs (Rp) and the strength of H0 on the As were obtained. Furthermore, the effects of saturation magnetization of the ferromagnetic materials in the MDCPs and within the targets on the As were analyzed. After this, the suitable strengths of H0 and Rp for IA-MDT designs were reported. Dimensionless As, ranging from 2 to 7, was obtained with Rp ranging from 500 to 2500 nm, μ0H0 less than 0.8 T and a blood flow rate of 0.1 m s-1. The target-MDCP materials considered are iron-iron, iron-magnetite and SS409-magnetite, respectively.

Isthmin inhibits glioma growth through antiangiogenesis in vivo.

Science.gov (United States)

Yuan, Bangqing; Xian, Ronghua; Ma, Jianfang; Chen, Yujian; Lin, Chuangan; Song, Yaoming

2012-09-01

Among glioma treatment strategies, antiangiogenesis emerges as a meaningful and feasible treatment approach for inducing long-term survival. Isthmin is a gene highly expressed in the isthmus of the midbrain-hindbrain organizer in Xenopus, and has recently been identified as a novel angiogenesis inhibitor. However, the potential of isthmin on the glioma angiogenesis has not been well studied. In the present study, we demonstrated that the recombinant adenovirus isthmin (Ad-isthmin) could inhibit VEGF-stimulated endothelial cell proliferation and induce apoptosis through a caspase-dependent pathway. In addition, Ad-isthmin significantly suppressed glioma growth through antiangiogenesis without apparent side effects. Taken together, our results demonstrated that isthmin could act as a novel angiogenesis inhibitor and might be utilized in the glioma antiangiogenesis therapy.

Therapy of Patients with Malignant Glioma with Targeted A-Radionuclide Therapy Using 213Bi-DOTA-[Thi8, Met (Oo)11]-Substanz P

International Nuclear Information System (INIS)

Forrer, F.; Mueller-Brand, J.; Cordier, D.; Merlo, A.; Morgenstern, A.; Bruchertseifer, F.; Maecke, H.R.

2009-01-01

The prognosis of patients with malignant glioma is very poor. New therapy options are mandatory. Substance P is the main ligand of neurokinin type 1 (NK-1) receptors, which are consistently over-expressed in malignant gliomas and surrounding tumor vessels. Administration of 90 Y-DOTA-[Thi 8 , Met (O o ) 11 ]-Substanz P was shown to be feasible and safe. However, in critically located tumors, the mean tissue range of 5 mm of 90 Y may lead to unacceptable damage of adjacent, functional critical areas of the brain. We report a phase I study with locally administered 213 Bi labeled DOTA-[Thi 8 , Met (O o ) 11 ]-Substanz P in patients with malignant glioma. By using a direct, intratumoral injection, the problem of the short physical half life of Bismuth-213 can be circumvent. To date, 5 patients with malignant glioma (2 Grade IV, 1 Grade III and 2 grade II) without previous treatment were included. One to three catheter systems were placed stereotactically into the tumor. After a diagnostic injection with 111 In-DOTA-[Thi 8 , Met (O o ) 11 ]-Substanz P and subsequent dosimetry, totally 30 to 138 mCi of 213 Bi-DOTA-[Thi8, Met (O o ) 11 ]-Substanz P was injected intratumorally performing 3 to 4 applications over 2 days. SPECT/CT was used to assess the biodistribution. Follow up was performed clinically and with morphological imaging. Targeted radiopeptide therapy using 213 Bi-DOTA-[Thi 8 , Met (O o ) 11 ]-Substanz P was very well tolerated by all patients. No additional neurological deficit was observed. Repetitive imaging is suggestive of progressive radiation-induced necrosis, which was validated by subsequent resection of the tumors. Time to progression was found to be 11 and 14 months respectively in patients with grade IV glioma. No progression is found after 18 to 23 months in patients with grade II or III glioma. We conclude that targeted loco-regional radiotherapy using 213 Bi-DOTA-[Thi 8 , Met (O o ) 11 ]-Substanz P represents an innovative and effective

Assessment of glioma response to radiotherapy using 3D pulsed-continuous arterial spin labeling and 3D segmented volume

Energy Technology Data Exchange (ETDEWEB)

Wang, Peng; Li, Jianrui; Diao, Qiang; Lin, YuanKai; Zhang, Jun; Li, Lin; Yang, Gang; Fang, Xiaokun; Li, Xie; Chen, YingQi; Zheng, Ling, E-mail: lingzheng1989@yeah.net; Lu, Guangming, E-mail: guangminglu1905@163.com

2016-11-15

Background: Gliomas are the most common primary brain tumors in adults, in some cases, radiotherapy may be the preferred treatment option especially for elderly people who cannot endure surgery. Therefore, it is necessary to evaluate the effects of radiotherapy on glioma. Arterial spin labeling (ASL) is an MR imaging technique that allows for a quantitative determination of cerebral blood flow (CBF) noninvasively. Tumor volume is still an important determinant for evaluating treatment response. The purpose of this study was to investigate the relationship between the tumor perfusion parameters and tumor volume and assess the effects of radiotherapy on glioma using pulsed-continuous arterial spin labeling (pcASL) technique. Methods: 35 patients with gliomas, histologically classified as low-grade group (n = 16) and high-grade group (n = 19), treated with radiotherapy only or before using other therapies were included in this study. MR examinations, including T1 weighted image and pcASL, were performed before and 4, 8, 12, 16 weeks after radiotherapy. Regional CBF of normal tissue, mean tumor blood flow (TBF{sub mean}), maximum tumor blood flow (TBF{sub max}), and tumor volume were evaluated at each time point. Both the percentage change in CBF (CBF ratio), TBF{sub mean} (TBF{sub mean} ratio), TBF{sub max} (TBF{sub max} ratio) and the percentage change in tumor volume (volume ratio) were calculated using values obtained before and after radiotherapy. The correlation between the volume ratio and CBF ratio, TBF{sub mean} ratio, TBF{sub max} ratio was assessed using linear regression analysis and Pearson’s correlation. Results: The TBF{sub mean} and TBF{sub max} of high-grade gliomas were significantly higher than that of low-grade group. In high-grade group, a strong correlation was demonstrated between the tumor volume and the TBF{sub max} before radiotherapy (R{sup 2} = 0.35, r{sub s} = 0.59, p < 0.05). There was also a significant correlation between the TBF

Capacity of ultraviolet-induced DNA repair in human glioma cells

Energy Technology Data Exchange (ETDEWEB)

Itoh, Hiroji

1987-04-01

A DNA repair abnormality is likely related to an increased incidence of neoplasms in several autosomal recessive diseases such as xeroderma pigmentosum, Fanconi's anemia, Bloom's syndrome and ataxia telangiectasia. In human glioma cells, however, there are only a few reports on DNA repair. In this study, an ultraviolet (UV)-induced DNA repair was examined systematically in many human glioma cells. Two human malignant glioma cell lines (MMG-851, U-251-MG) and 7 human glioma cell strains (4, benign; 3, malignant) of short term culture, in which glial fibrillary acidic protein (GFAP) staining were positive, were used. To investigate the capacity of DNA repair, UV sensitivity was determined by colony formation; excision repair by autoradiography and Cytosine Arabinoside (Ara-C) assay; and post-replication repair by the joining rate of newly synthesized DNA. As a result, the colony-forming abilities of malignant glioma cell lines were lower than those of normal human fibroblasts, but no difference was found between two malignant glioma cell lines. The excision repair of the malignant group (2 cell lines and 3 cell strains) was apparently lower than that of the benign group (4 cell strains). In two malignant glioma cell lines, the excision repair of MMG-851 was lower than that of U-251-MG, and the post-replication repair of MMG-851 was higher than that of U-251-MG. These results were considered to correspond well with colony-forming ability. The results indicate that there are some differences in each human malignant glioma cell in its UV-induced DNA repair mechanism, and that the excision repair of the malignant glioma cells is apparently lower than that of the benign glioma cells. These findings may be useful for diagnosis and treatment.

Tipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma

Science.gov (United States)

2013-10-07

Childhood High-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Differential expression of centrosomal proteins at different stages of human glioma