WorldWideScience

Sample records for tissue model studies

  1. Adaptive Breast Radiation Therapy Using Modeling of Tissue Mechanics: A Breast Tissue Segmentation Study

    International Nuclear Information System (INIS)

    Juneja, Prabhjot; Harris, Emma J.; Kirby, Anna M.; Evans, Philip M.

    2012-01-01

    Purpose: To validate and compare the accuracy of breast tissue segmentation methods applied to computed tomography (CT) scans used for radiation therapy planning and to study the effect of tissue distribution on the segmentation accuracy for the purpose of developing models for use in adaptive breast radiation therapy. Methods and Materials: Twenty-four patients receiving postlumpectomy radiation therapy for breast cancer underwent CT imaging in prone and supine positions. The whole-breast clinical target volume was outlined. Clinical target volumes were segmented into fibroglandular and fatty tissue using the following algorithms: physical density thresholding; interactive thresholding; fuzzy c-means with 3 classes (FCM3) and 4 classes (FCM4); and k-means. The segmentation algorithms were evaluated in 2 stages: first, an approach based on the assumption that the breast composition should be the same in both prone and supine position; and second, comparison of segmentation with tissue outlines from 3 experts using the Dice similarity coefficient (DSC). Breast datasets were grouped into nonsparse and sparse fibroglandular tissue distributions according to expert assessment and used to assess the accuracy of the segmentation methods and the agreement between experts. Results: Prone and supine breast composition analysis showed differences between the methods. Validation against expert outlines found significant differences (P<.001) between FCM3 and FCM4. Fuzzy c-means with 3 classes generated segmentation results (mean DSC = 0.70) closest to the experts' outlines. There was good agreement (mean DSC = 0.85) among experts for breast tissue outlining. Segmentation accuracy and expert agreement was significantly higher (P<.005) in the nonsparse group than in the sparse group. Conclusions: The FCM3 gave the most accurate segmentation of breast tissues on CT data and could therefore be used in adaptive radiation therapy-based on tissue modeling. Breast tissue segmentation

  2. Adaptive Breast Radiation Therapy Using Modeling of Tissue Mechanics: A Breast Tissue Segmentation Study

    Energy Technology Data Exchange (ETDEWEB)

    Juneja, Prabhjot, E-mail: Prabhjot.Juneja@icr.ac.uk [Joint Department of Physics, Institute of Cancer Research, Sutton (United Kingdom); Harris, Emma J. [Joint Department of Physics, Institute of Cancer Research, Sutton (United Kingdom); Kirby, Anna M. [Department of Academic Radiotherapy, Royal Marsden National Health Service Foundation Trust, Sutton (United Kingdom); Evans, Philip M. [Joint Department of Physics, Institute of Cancer Research, Sutton (United Kingdom)

    2012-11-01

    Purpose: To validate and compare the accuracy of breast tissue segmentation methods applied to computed tomography (CT) scans used for radiation therapy planning and to study the effect of tissue distribution on the segmentation accuracy for the purpose of developing models for use in adaptive breast radiation therapy. Methods and Materials: Twenty-four patients receiving postlumpectomy radiation therapy for breast cancer underwent CT imaging in prone and supine positions. The whole-breast clinical target volume was outlined. Clinical target volumes were segmented into fibroglandular and fatty tissue using the following algorithms: physical density thresholding; interactive thresholding; fuzzy c-means with 3 classes (FCM3) and 4 classes (FCM4); and k-means. The segmentation algorithms were evaluated in 2 stages: first, an approach based on the assumption that the breast composition should be the same in both prone and supine position; and second, comparison of segmentation with tissue outlines from 3 experts using the Dice similarity coefficient (DSC). Breast datasets were grouped into nonsparse and sparse fibroglandular tissue distributions according to expert assessment and used to assess the accuracy of the segmentation methods and the agreement between experts. Results: Prone and supine breast composition analysis showed differences between the methods. Validation against expert outlines found significant differences (P<.001) between FCM3 and FCM4. Fuzzy c-means with 3 classes generated segmentation results (mean DSC = 0.70) closest to the experts' outlines. There was good agreement (mean DSC = 0.85) among experts for breast tissue outlining. Segmentation accuracy and expert agreement was significantly higher (P<.005) in the nonsparse group than in the sparse group. Conclusions: The FCM3 gave the most accurate segmentation of breast tissues on CT data and could therefore be used in adaptive radiation therapy-based on tissue modeling. Breast tissue

  3. Comparison of plasma input and reference tissue models for analysing [(11)C]flumazenil studies

    NARCIS (Netherlands)

    Klumpers, Ursula M. H.; Veltman, Dick J.; Boellaard, Ronald; Comans, Emile F.; Zuketto, Cassandra; Yaqub, Maqsood; Mourik, Jurgen E. M.; Lubberink, Mark; Hoogendijk, Witte J. G.; Lammertsma, Adriaan A.

    2008-01-01

    A single-tissue compartment model with plasma input is the established method for analysing [(11)C]flumazenil ([(11)C]FMZ) studies. However, arterial cannulation and measurement of metabolites are time-consuming. Therefore, a reference tissue approach is appealing, but this approach has not been

  4. A 3D Human Lung Tissue Model for Functional Studies on Mycobacterium tuberculosis Infection.

    Science.gov (United States)

    Braian, Clara; Svensson, Mattias; Brighenti, Susanna; Lerm, Maria; Parasa, Venkata R

    2015-10-05

    Tuberculosis (TB) still holds a major threat to the health of people worldwide, and there is a need for cost-efficient but reliable models to help us understand the disease mechanisms and advance the discoveries of new treatment options. In vitro cell cultures of monolayers or co-cultures lack the three-dimensional (3D) environment and tissue responses. Herein, we describe an innovative in vitro model of a human lung tissue, which holds promise to be an effective tool for studying the complex events that occur during infection with Mycobacterium tuberculosis (M. tuberculosis). The 3D tissue model consists of tissue-specific epithelial cells and fibroblasts, which are cultured in a matrix of collagen on top of a porous membrane. Upon air exposure, the epithelial cells stratify and secrete mucus at the apical side. By introducing human primary macrophages infected with M. tuberculosis to the tissue model, we have shown that immune cells migrate into the infected-tissue and form early stages of TB granuloma. These structures recapitulate the distinct feature of human TB, the granuloma, which is fundamentally different or not commonly observed in widely used experimental animal models. This organotypic culture method enables the 3D visualization and robust quantitative analysis that provides pivotal information on spatial and temporal features of host cell-pathogen interactions. Taken together, the lung tissue model provides a physiologically relevant tissue micro-environment for studies on TB. Thus, the lung tissue model has potential implications for both basic mechanistic and applied studies. Importantly, the model allows addition or manipulation of individual cell types, which thereby widens its use for modelling a variety of infectious diseases that affect the lungs.

  5. Finite element model to study temperature distribution in skin and deep tissues of human limbs.

    Science.gov (United States)

    Agrawal, Mamta; Pardasani, K R

    2016-12-01

    The temperature of body tissues is viewed as an indicator of tissue response in clinical applications since ancient times. The tissue temperature depends on various physical and physiological parameters like blood flow, metabolic heat generation, thermal conductivity of tissues, shape and size of organs etc. In this paper a finite element model has been proposed to study temperature distribution in skin and deep tissues of human limbs. The geometry of human limb is taken as elliptical tapered shape. It is assumed that outer surface of the limb is exposed to the environment. The appropriate boundary conditions have been framed based on physical conditions of the problem. The model has been developed for a three dimensional steady state case. Hexahedral circular sectoral elements are used to discretize the region. The results have been computed to obtain temperature profiles and study the relation of tissue temperature with the parameters like atmospheric temperature, rate of evaporation, thickness of tissues layers and shape of the limb. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Modeling an Excitable Biosynthetic Tissue with Inherent Variability for Paired Computational-Experimental Studies.

    Directory of Open Access Journals (Sweden)

    Tanmay A Gokhale

    2017-01-01

    Full Text Available To understand how excitable tissues give rise to arrhythmias, it is crucially necessary to understand the electrical dynamics of cells in the context of their environment. Multicellular monolayer cultures have proven useful for investigating arrhythmias and other conduction anomalies, and because of their relatively simple structure, these constructs lend themselves to paired computational studies that often help elucidate mechanisms of the observed behavior. However, tissue cultures of cardiomyocyte monolayers currently require the use of neonatal cells with ionic properties that change rapidly during development and have thus been poorly characterized and modeled to date. Recently, Kirkton and Bursac demonstrated the ability to create biosynthetic excitable tissues from genetically engineered and immortalized HEK293 cells with well-characterized electrical properties and the ability to propagate action potentials. In this study, we developed and validated a computational model of these excitable HEK293 cells (called "Ex293" cells using existing electrophysiological data and a genetic search algorithm. In order to reproduce not only the mean but also the variability of experimental observations, we examined what sources of variation were required in the computational model. Random cell-to-cell and inter-monolayer variation in both ionic conductances and tissue conductivity was necessary to explain the experimentally observed variability in action potential shape and macroscopic conduction, and the spatial organization of cell-to-cell conductance variation was found to not impact macroscopic behavior; the resulting model accurately reproduces both normal and drug-modified conduction behavior. The development of a computational Ex293 cell and tissue model provides a novel framework to perform paired computational-experimental studies to study normal and abnormal conduction in multidimensional excitable tissue, and the methodology of modeling

  7. Tissue engineered tumor models.

    Science.gov (United States)

    Ingram, M; Techy, G B; Ward, B R; Imam, S A; Atkinson, R; Ho, H; Taylor, C R

    2010-08-01

    Many research programs use well-characterized tumor cell lines as tumor models for in vitro studies. Because tumor cells grown as three-dimensional (3-D) structures have been shown to behave more like tumors in vivo than do cells growing in monolayer culture, a growing number of investigators now use tumor cell spheroids as models. Single cell type spheroids, however, do not model the stromal-epithelial interactions that have an important role in controlling tumor growth and development in vivo. We describe here a method for generating, reproducibly, more realistic 3-D tumor models that contain both stromal and malignant epithelial cells with an architecture that closely resembles that of tumor microlesions in vivo. Because they are so tissue-like we refer to them as tumor histoids. They can be generated reproducibly in substantial quantities. The bioreactor developed to generate histoid constructs is described and illustrated. It accommodates disposable culture chambers that have filled volumes of either 10 or 64 ml, each culture yielding on the order of 100 or 600 histoid particles, respectively. Each particle is a few tenths of a millimeter in diameter. Examples of histological sections of tumor histoids representing cancers of breast, prostate, colon, pancreas and urinary bladder are presented. Potential applications of tumor histoids include, but are not limited to, use as surrogate tumors for pre-screening anti-solid tumor pharmaceutical agents, as reference specimens for immunostaining in the surgical pathology laboratory and use in studies of invasive properties of cells or other aspects of tumor development and progression. Histoids containing nonmalignant cells also may have potential as "seeds" in tissue engineering. For drug testing, histoids probably will have to meet certain criteria of size and tumor cell content. Using a COPAS Plus flow cytometer, histoids containing fluorescent tumor cells were analyzed successfully and sorted using such criteria.

  8. Simulation studies of optimum energies for DXA: dependence on tissue type, patient size and dose model

    International Nuclear Information System (INIS)

    Michael, G. J.; Henderson, C. J.

    1999-01-01

    Dual-energy x-ray absorptiometry (DXA) is a well established technique for measuring bone mineral density (BMD). However, in recent years DXA is increasingly being used to measure body composition in terms of fat and fat-free mass. DXA scanners must also determine the soft tissue baseline value from soft-tissue-only regions adjacent to bone. The aim of this work is to determine, using computer simulations, the optimum x- ray energies for a number of dose models, different tissues, i.e. bone mineral, average soft tissue, lean soft tissue and fat; and a range of anatomical sites and patient sizes. Three models for patient dose were evaluated total beam energy, entrance exposure and absorbed dose calculated by Monte Carlo modelling. A range of tissue compositions and thicknesses were chosen to cover typical patient variations for the three sites femoral neck, PA spine and lateral spine. In this work, the optimisation of the energies is based on (1) the uncertainty that arises from the quantum statistical nature of the number of x-rays recorded by the detector, and (2) the radiation dose received by the patient. This study has deliberately not considered other parameters such as detector response, electronic noise, x-ray tube heat load etc, because these are technology dependent parameters, not ones that are inherent to the measuring technique. Optimisation of the energies is achieved by minimisation of the product of variance of density measurement and dose which is independent of the absolute intensities of the x-ray beams. The results obtained indicate that if solving for bone density, then E-low in the range 34 to 42 keV, E-high in the range 100 to 200 keV and incident intensity ratio (low energy/high energy) in the range 3 to 10 is a reasonable compromise for the normal range of patient sizes. The choice of energies is complicated by the fact that the DXA unit must also solve for fat and lean soft tissue in soft- tissue-only regions adjacent to the bone. In this

  9. Computational Modeling in Tissue Engineering

    CERN Document Server

    2013-01-01

    One of the major challenges in tissue engineering is the translation of biological knowledge on complex cell and tissue behavior into a predictive and robust engineering process. Mastering this complexity is an essential step towards clinical applications of tissue engineering. This volume discusses computational modeling tools that allow studying the biological complexity in a more quantitative way. More specifically, computational tools can help in:  (i) quantifying and optimizing the tissue engineering product, e.g. by adapting scaffold design to optimize micro-environmental signals or by adapting selection criteria to improve homogeneity of the selected cell population; (ii) quantifying and optimizing the tissue engineering process, e.g. by adapting bioreactor design to improve quality and quantity of the final product; and (iii) assessing the influence of the in vivo environment on the behavior of the tissue engineering product, e.g. by investigating vascular ingrowth. The book presents examples of each...

  10. Experimental study and constitutive modeling of the viscoelastic mechanical properties of the human prolapsed vaginal tissue.

    Science.gov (United States)

    Peña, Estefania; Calvo, B; Martínez, M A; Martins, P; Mascarenhas, T; Jorge, R M N; Ferreira, A; Doblaré, M

    2010-02-01

    In this paper, the viscoelastic mechanical properties of vaginal tissue are investigated. Using previous results of the authors on the mechanical properties of biological soft tissues and newly experimental data from uniaxial tension tests, a new model for the viscoelastic mechanical properties of the human vaginal tissue is proposed. The structural model seems to be sufficiently accurate to guarantee its application to prediction of reliable stress distributions, and is suitable for finite element computations. The obtained results may be helpful in the design of surgical procedures with autologous tissue or prostheses.

  11. Reducing the number of laboratory animals used in tissue engineering research by restricting the variety of animal models. Articular cartilage tissue engineering as a case study.

    Science.gov (United States)

    de Vries, Rob B M; Buma, Pieter; Leenaars, Marlies; Ritskes-Hoitinga, Merel; Gordijn, Bert

    2012-12-01

    The use of laboratory animals in tissue engineering research is an important underexposed ethical issue. Several ethical questions may be raised about this use of animals. This article focuses on the possibilities of reducing the number of animals used. Given that there is considerable debate about the adequacy of the current animal models in tissue engineering research, we investigate whether it is possible to reduce the number of laboratory animals by selecting and using only those models that have greatest predictive value for future clinical application of the tissue engineered product. The field of articular cartilage tissue engineering is used as a case study. Based on a study of the scientific literature and interviews with leading experts in the field, an overview is provided of the animal models used and the advantages and disadvantages of each model, particularly in terms of extrapolation to the human situation. Starting from this overview, it is shown that, by skipping the small models and using only one large preclinical model, it is indeed possible to restrict the number of animal models, thereby reducing the number of laboratory animals used. Moreover, it is argued that the selection of animal models should become more evidence based and that researchers should seize more opportunities to choose or create characteristics in the animal models that increase their predictive value.

  12. Reference tissue modeling with parameter coupling: application to a study of SERT binding in HIV

    Energy Technology Data Exchange (ETDEWEB)

    Endres, Christopher J; Pomper, Martin G [Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD 21231 (United States); Hammoud, Dima A, E-mail: endres@jhmi.edu [Radiology and Imaging Sciences, National Institutes of Health/Clinical Center, Bethesda, MD (United States)

    2011-04-21

    When applicable, it is generally preferred to evaluate positron emission tomography (PET) studies using a reference tissue-based approach as that avoids the need for invasive arterial blood sampling. However, most reference tissue methods have been shown to have a bias that is dependent on the level of tracer binding, and the variability of parameter estimates may be substantially affected by noise level. In a study of serotonin transporter (SERT) binding in HIV dementia, it was determined that applying parameter coupling to the simplified reference tissue model (SRTM) reduced the variability of parameter estimates and yielded the strongest between-group significant differences in SERT binding. The use of parameter coupling makes the application of SRTM more consistent with conventional blood input models and reduces the total number of fitted parameters, thus should yield more robust parameter estimates. Here, we provide a detailed evaluation of the application of parameter constraint and parameter coupling to [{sup 11}C]DASB PET studies. Five quantitative methods, including three methods that constrain the reference tissue clearance (k{sup r}{sub 2}) to a common value across regions were applied to the clinical and simulated data to compare measurement of the tracer binding potential (BP{sub ND}). Compared with standard SRTM, either coupling of k{sup r}{sub 2} across regions or constraining k{sup r}{sub 2} to a first-pass estimate improved the sensitivity of SRTM to measuring a significant difference in BP{sub ND} between patients and controls. Parameter coupling was particularly effective in reducing the variance of parameter estimates, which was less than 50% of the variance obtained with standard SRTM. A linear approach was also improved when constraining k{sup r}{sub 2} to a first-pass estimate, although the SRTM-based methods yielded stronger significant differences when applied to the clinical study. This work shows that parameter coupling reduces the

  13. Diode laser-induced tissue effects: in vitro tissue model study and in vivo evaluation of wound healing following non-contact application.

    Science.gov (United States)

    Havel, Miriam; Betz, Christian S; Leunig, Andreas; Sroka, Ronald

    2014-08-01

    The basic difference between the various common medical laser systems is the wavelength of the emitted light, leading to altered light-tissue interactions due to the optical parameters of the tissue. This study examines laser induced tissue effects in an in vitro tissue model using 1,470 nm diode laser compared to our standard practice for endonasal applications (940 nm diode laser) under standardised and reproducible conditions. Additionally, in vivo induced tissue effects following non-contact application with focus on mucosal healing were investigated in a controlled intra-individual design in patients treated for hypertrophy of nasal turbinate. A certified diode laser system emitting the light of λ = 1470 nm was evaluated with regards to its tissue effects (ablation, coagulation) in an in vitro setup on porcine liver and turkey muscle tissue model. To achieve comparable macroscopic tissue effects the laser fibres (600 µm core diameter) were fixed to a computer controlled stepper motor and the laser light was applied in a reproducible procedure under constant conditions. For the in vivo evaluation, 20 patients with nasal obstruction due to hyperplasia of inferior nasal turbinates were included in this prospective randomised double-blinded comparative trial. The endoscopic controlled endonasal application of λ = 1470 nm on the one and λ = 940 nm on the other side, both in 'non-contact' mode, was carried out as an outpatient procedure under local anaesthesia. The postoperative wound healing process (mucosal swelling, scab formation, bleeding, infection) was endoscopically documented and assessed by an independent physician. In the experimental setup, the 1,470 nm laser diode system proved to be efficient in inducing tissue effects in non-contact mode with a reduced energy factor of 5-10 for highly perfused liver tissue to 10-20 for muscle tissue as compared to the 940 nm diode laser system. In the in vivo evaluation scab formation

  14. Black-box modeling to estimate tissue temperature during radiofrequency catheter cardiac ablation: feasibility study on an agar phantom model

    International Nuclear Information System (INIS)

    Blasco-Gimenez, Ramón; Lequerica, Juan L; Herrero, Maria; Hornero, Fernando; Berjano, Enrique J

    2010-01-01

    The aim of this work was to study linear deterministic models to predict tissue temperature during radiofrequency cardiac ablation (RFCA) by measuring magnitudes such as electrode temperature, power and impedance between active and dispersive electrodes. The concept involves autoregressive models with exogenous input (ARX), which is a particular case of the autoregressive moving average model with exogenous input (ARMAX). The values of the mode parameters were determined from a least-squares fit of experimental data. The data were obtained from radiofrequency ablations conducted on agar models with different contact pressure conditions between electrode and agar (0 and 20 g) and different flow rates around the electrode (1, 1.5 and 2 L min −1 ). Half of all the ablations were chosen randomly to be used for identification (i.e. determination of model parameters) and the other half were used for model validation. The results suggest that (1) a linear model can be developed to predict tissue temperature at a depth of 4.5 mm during RF cardiac ablation by using the variables applied power, impedance and electrode temperature; (2) the best model provides a reasonably accurate estimate of tissue temperature with a 60% probability of achieving average errors better than 5 °C; (3) substantial errors (larger than 15 °C) were found only in 6.6% of cases and were associated with abnormal experiments (e.g. those involving the displacement of the ablation electrode) and (4) the impact of measuring impedance on the overall estimate is negligible (around 1 °C)

  15. Bone tissue ultrastructural defects in a mouse model for osteogenesis imperfecta: a Raman spectroscopy study

    Science.gov (United States)

    Chen, Tsoching; Kozloff, Kenneth M.; Goldstein, Steven A.; Morris, Michael D.

    2004-07-01

    Osteogenesis imperfecta (OI) is genetic defect in which the genes that code for the α1(I) or α2(I) chains of type I collagen are defective. The defects often result in substitution of a bulky amino acid for glycine, causing formation of collagen that can not form the normal triple helix. Depending on the details of the defects, the outcomes range from controllable to lethal. This study focuses on OI type IV, a more common and moderately severe form of the disease. People with the disease have a substantial increase in the risk and rate of fracture. We examine the spectroscopic consequences of these defects, using a mouse model (BRTL) that mimics OI type IV. We compare Raman images from tibial cortical tissue of wild-type mice and BRTL mice with single copy of mutation and show that both mineral to matrix ratios and collagen inter-fibril cross-links are different in wild-type and mutant mice.

  16. Modelling of Cortical Bone Tissue as a Fluid Saturated Double-Porous Material - Parametric Study

    Directory of Open Access Journals (Sweden)

    Jana TURJANICOVÁ

    2013-06-01

    Full Text Available In this paper, the cortical bone tissue is considered as a poroelastic material with periodic structure represented at microscopic and mesoscopic levels. The pores of microscopic scale are connected with the pores of mesoscopic scale creating one system of connected network filled with compressible fluid. The method of asymptotic homogenization is applied to upscale the microscopic model of the fluid-solid interaction under a static loading. Obtained homogenized coefficients describe material properties of the poroelastic matrix fractured by fluid-filled pores whose geometry is described at the mesoscopic level. The second-level upscaling provides homogenized poroelastic coefficients relevant on the macroscopic scale. Furthermore, we study the dependence of these coefficients on geometrical parameters on related microscopic and macroscopic scales.

  17. Full experimental modelling of a liver tissue mimicking phantom for medical ultrasound studies employing different hydrogels.

    Science.gov (United States)

    Casciaro, Sergio; Conversano, Francesco; Musio, Stefano; Casciaro, Ernesto; Demitri, Christian; Sannino, Alessandro

    2009-04-01

    Tissue mimicking phantoms have been widely reported to be an important tool for development, optimisation and performance testing of ultrasound-based diagnostic techniques. In particular, modern applications of tissue mimicking phantoms often include characterisation of the nonlinear behaviour of experimental ultrasound contrast agents. In such cases, the tissue-mimicking materials should be chosen not only based on the values of their density, speed of sound and attenuation coefficient, but also considering their effect on the appearance of "native harmonics" due to nonlinear distortion of ultrasound signal during propagation. In a previous paper it was demonstrated that a cellulose-based hydrogel is suitable to simulate nonlinear acoustical behaviour of liver tissue for thicknesses up to 8 cm. In this paper we present the experimental characterisation of the nonlinear acoustical behaviour of a different polyethylene glycol diacrylate (PEGDA)-based hydrogel, in order to assess whether and how it can improve the performances and overcome some limitations of the cellulose-based hydrogel as liver tissue-mimicking material. Samples of pig liver tissue, cellulose-based hydrogel and PEGDA-based hydrogel were insonified in a through-transmission set-up, employing 2.25-MHz pulses with different mechanical index (MI) values. Second harmonic and first harmonic amplitudes were extracted from the spectra of received signals and their difference was then used to compare sample behaviours. Obtained results show how a new more accurate and combined experimental model of linear and nonlinear acoustical behaviour of liver tissue is feasible. In fact, a further confirmation of the cellulose-based hydrogel effectiveness to precisely simulate the liver tissue for penetration depths up to 8 cm was provided, and it was also shown that the employment of the PEGDA-based hydrogel can extend the range of useful tissue-mimicking material thicknesses up to 11 cm, moreover allowing a

  18. An ex vivo spinal cord injury model to study ependymal cells in adult mouse tissue.

    Science.gov (United States)

    Fernandez-Zafra, Teresa; Codeluppi, Simone; Uhlén, Per

    2017-08-15

    Traumatic spinal cord injury is characterized by an initial cell loss that is followed by a concerted cellular response in an attempt to restore the damaged tissue. Nevertheless, little is known about the signaling mechanisms governing the cellular response to injury. Here, we have established an adult ex vivo system that exhibits multiple hallmarks of spinal cord injury and allows the study of complex processes that are difficult to address using animal models. We have characterized the ependymal cell response to injury in this model system and found that ependymal cells can become activated, proliferate, migrate out of the central canal lining and differentiate in a manner resembling the in vivo situation. Moreover, we show that these cells respond to external adenosine triphosphate and exhibit spontaneous Ca 2+ activity, processes that may play a significant role in the regulation of their response to spinal cord injury. This model provides an attractive tool to deepen our understanding of the ependymal cell response after spinal cord injury, which may contribute to the development of new treatment options for spinal cord injury. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. A facile in vitro model to study rapid mineralization in bone tissues.

    Science.gov (United States)

    Deegan, Anthony J; Aydin, Halil M; Hu, Bin; Konduru, Sandeep; Kuiper, Jan Herman; Yang, Ying

    2014-09-16

    Mineralization in bone tissue involves stepwise cell-cell and cell-ECM interaction. Regulation of osteoblast culture microenvironments can tailor osteoblast proliferation and mineralization rate, and the quality and/or quantity of the final calcified tissue. An in vitro model to investigate the influencing factors is highly required. We developed a facile in vitro model in which an osteoblast cell line and aggregate culture (through the modification of culture well surfaces) were used to mimic intramembranous bone mineralization. The effect of culture environments including culture duration (up to 72 hours for rapid mineralization study) and aggregates size (monolayer culture as control) on mineralization rate and mineral quantity/quality were examined by osteogenic gene expression (PCR) and mineral markers (histological staining, SEM-EDX and micro-CT). Two size aggregates (on average, large aggregates were 745 μm and small 79 μm) were obtained by the facile technique with high yield. Cells in aggregate culture generated visible and quantifiable mineralized matrix within 24 hours, whereas cells in monolayer failed to do so by 72 hours. The gene expression of important ECM molecules for bone formation including collagen type I, alkaline phosphatase, osteopontin and osteocalcin, varied temporally, differed between monolayer and aggregate cultures, and depended on aggregate size. Monolayer specimens stayed in a proliferation phase for the first 24 hours, and remained in matrix synthesis up to 72 hours; whereas the small aggregates were in the maturation phase for the first 24 and 48 hour cultures and then jumped to a mineralization phase at 72 hours. Large aggregates were in a mineralization phase at all these three time points and produced 36% larger bone nodules with a higher calcium content than those in the small aggregates after just 72 hours in culture. This study confirms that aggregate culture is sufficient to induce rapid mineralization and that aggregate

  20. A 3D human tissue-engineered lung model to study influenza A infection.

    Science.gov (United States)

    Bhowmick, Rudra; Derakhshan, Mina; Liang, Yurong; Ritchey, Jerry; Liu, Lin; Gappa-Fahlenkamp, Heather

    2018-05-05

    Influenza A virus (IAV) claims approximately 250,000-500,000 lives annually worldwide. Currently, there are a few in vitro models available to study IAV immunopathology. Monolayer cultures of cell lines and primary lung cells (2D cell culture) is the most commonly used tool, however, this system does not have the in vivo-like structure of the lung and immune responses to IAV as it lacks the three-dimensional (3D) tissue structure. To recapitulate the lung physiology in vitro, a system that contains multiple cell types within a 3D environment that allows cell movement and interaction, would provide a critical tool. In this study, as a first step in designing a 3D-Human Tissue-Engineering Lung Model (3D-HTLM), we described the 3D culture of primary human small airway epithelial cells (HSAEpCs), and determined the immunophenotype of this system in response to IAV infections. We constructed a 3D chitosan-collagen scaffold and cultured HSAEpCs on these scaffolds at air-liquid interface (ALI). These 3D cultures were compared with 2D-cultured HSAEpCs for viability, morphology, marker protein expression, and cell differentiation. Results showed that the 3D-cultured HSAEpCs at ALI yielded maximum viable cells and morphologically resembled the in vivo lower airway epithelium. There were also significant increases in aquaporin-5 and cytokeratin-14 expression for HSAEpCs cultured in 3D compared to 2D. The 3D culture system was used to study the infection of HSAEpCs with two major IAV strains, H1N1 and H3N2.The HSAEpCs showed distinct changes in marker protein expression, both at mRNA and protein levels, and the release of proinflammatory cytokines. This study is the first step in the development of the 3D-HTLM, which will have wide applicability in studying pulmonary pathophysiology and therapeutics development.

  1. Dextrose-induced subsynovial connective tissue fibrosis in the rabbit carpal tunnel: A potential model to study carpal tunnel syndrome?

    NARCIS (Netherlands)

    Oh, S.; Ettema, A.M.; Zhao, C.; Zobitz, M.E.; Wold, L.E.; An, K.N.; Amadio, P.C.

    2008-01-01

    In this pilot study, hypertonic dextrose solution was used to induce fibrosis of the subsynovial connective tissue (SSCT) and create an animal model of potential use in the study of carpal tunnel syndrome (CTS). The SSCT of the carpal tunnel in 15 New Zealand white rabbits were injected with 0.05 ml

  2. Dynamics of soft tissue healing at implants and teeth: a study in a dog model.

    Science.gov (United States)

    Sukekava, Flávia; Pannuti, Claudio M; Lima, Luiz A; Tormena, Mariana; Araújo, Mauricio G

    2016-05-01

    The aim of this study was to describe and to compare some characteristics of the soft tissue healing process around teeth and implants after flap surgery. Five adult beagle dogs had their third and fourth lower premolars extracted. After 3 months, four implants per dog were placed on the healed alveolar ridge and allowed to heal non-submerged during 3 months. After 3 months, four regions characterized by one implant and one adjacent tooth were identified in each dog. One region was randomly selected and soft tissue ressective flap surgery was performed at its buccal aspect. The remaining three regions were randomly treated in an identical manner, and the dogs were sacrificed to provide biopsies representing healing intervals of 1, 2, 4, and 12 weeks. The biopsies were prepared for histological and morphological analyses. Morphometric and histometric analyses have shown that the gingival tissues surrounding teeth were completely healed after a 4-week interval. However, it took from 4 to 12 weeks for the peri-implant mucosa to heal completely. The healing process around teeth and implants follows a similar sequence of events. Nevertheless, the complete process of healing and maturation of the peri-implant tissues takes longer than around teeth. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Piezosurgery prevents brain tissue damage: an experimental study on a new rat model.

    Science.gov (United States)

    Pavlíková, G; Foltán, R; Burian, M; Horká, E; Adámek, S; Hejčl, A; Hanzelka, T; Sedý, J

    2011-08-01

    Piezosurgery is a promising meticulous system for bone cutting, based on ultrasound microvibrations. It is thought that the impact of piezosurgery on the integrity of soft tissue is generally low, but it has not been examined critically. The authors undertook an experimental study to evaluate the brain tissue response to skull bone removal using piezosurgery compared with a conventional drilling method. In Wistar male rats, a circular bone window was drilled to the parietal bone using piezosurgery on one side and a conventional bone drill on the other side. The behavioural performance of animals was evaluated using the motor BBB test and sensory plantar test. The brains of animals were evaluated by magnetic resonance imaging (MRI) and histology. The results of MRI showed significantly increased depth and width of the brain lesion in the region of conventional drilling compared with the region where piezosurgery was used. Cresylviolet and NF 160 staining confirmed these findings. There was no significant difference in any of the behavioural tests between the two groups. In conclusion, piezosurgery is a safe method for the performance of osteotomy in close relation to soft tissue, including an extremely injury-sensitive tissue such as brain. Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  4. Wound healing in a fetal, adult, and scar tissue model: a comparative study

    NARCIS (Netherlands)

    Coolen, N.A.; Schouten, K.C.; Boekema, B.K.; Middelkoop, E.; Ulrich, M.

    2010-01-01

    Early gestation fetal wounds heal without scar formation. Understanding the mechanism of this scarless healing may lead to new therapeutic strategies for improving adult wound healing. The aims of this study were to develop a human fetal wound model in which fetal healing can be studied and to

  5. A tissue-engineered gastric cancer model for mechanistic study of anti-tumor drugs

    International Nuclear Information System (INIS)

    Gao, Ming; Cai, Yiting; Wu, Wei; Shi, Yazhou; Fei, Zhewei

    2013-01-01

    The use of the traditional xenograft subcutaneous tumor model has been contested because of its limitations, such as a slow tumorigenesis, inconsistent chemotherapeutic results, etc. In light of these challenges, we aim to revamp the traditional model by employing an electrospun scaffold composed of polydioxanone, gelatin and elastin to boost the tumorigenesis. The scaffold featured a highly porous microstructure and successfully supported the growth of tumor cells in vitro without provoking apoptosis. In vivo studies showed that in the scaffold model the tumor volume increased by 43.27% and the weight by 75.58%, respectively, within a 12-week period. In addition, the scaffold model saw an increase of CD24 + and CD44 + cells in the tumor mass by 42% and 313%, respectively. The scaffolding materials did not lead to phenotypic changes during the tumorigenesis. Thereafter, in the scaffold model, we found that the chemotherapeutic regimen of docetaxel, cisplatin and fluorouracil unleashed a stronger capability than the regimen comprising cisplatin and fluorouracil to deplete the CD44 + subpopulation. This discovery sheds mechanistic lights on the role of docetaxel for its future chemotherapeutic applications. This revamped model affords cancer scientists a convenient and reliable platform to mechanistically investigate the chemotherapeutic drugs on gastric cancer stem cells. (paper)

  6. Implications of human tissue studies

    International Nuclear Information System (INIS)

    Kathren, R.L.

    1986-10-01

    Through radiochemical analysis of voluntary tissue donations, the United States Transuranium and Uranium Registries are gaining improved understanding of the distribution and biokinetics of actinide elements in occupationally exposed persons. Evaluation of the first two whole body contributions to the Transuranium Registry revealed an inverse proportionality between actinide concentration and bone ash fraction. The analysis of a whole body with a documented 241 Am deposition indicated a significantly shorter half-time in liver and a greater fraction resident in the skeleton than predicted by existing models. Other studies of the Registries are designed to evaluate in vivo estimates of actinide deposition with those derived from postmortem tissue analysis, compare results of animal experiments with human data, and reviw histopathologic slides for tissue toxicity that might be attributable to exposure to uranium and the transuranic elements. The implications of these recent findings and other work of the Registries are discussed from the standpoint of their potential impact on biokinetic modeling, internal dose assessment, safety standards, and operational health physics practices

  7. Impact of anesthesia and euthanasia on metabolomics of mammalian tissues: studies in a C57BL/6J mouse model.

    Science.gov (United States)

    Overmyer, Katherine A; Thonusin, Chanisa; Qi, Nathan R; Burant, Charles F; Evans, Charles R

    2015-01-01

    A critical application of metabolomics is the evaluation of tissues, which are often the primary sites of metabolic dysregulation in disease. Laboratory rodents have been widely used for metabolomics studies involving tissues due to their facile handing, genetic manipulability and similarity to most aspects of human metabolism. However, the necessary step of administration of anesthesia in preparation for tissue sampling is not often given careful consideration, in spite of its potential for causing alterations in the metabolome. We examined, for the first time using untargeted and targeted metabolomics, the effect of several commonly used methods of anesthesia and euthanasia for collection of skeletal muscle, liver, heart, adipose and serum of C57BL/6J mice. The data revealed dramatic, tissue-specific impacts of tissue collection strategy. Among many differences observed, post-euthanasia samples showed elevated levels of glucose 6-phosphate and other glycolytic intermediates in skeletal muscle. In heart and liver, multiple nucleotide and purine degradation metabolites accumulated in tissues of euthanized compared to anesthetized animals. Adipose tissue was comparatively less affected by collection strategy, although accumulation of lactate and succinate in euthanized animals was observed in all tissues. Among methods of tissue collection performed pre-euthanasia, ketamine showed more variability compared to isoflurane and pentobarbital. Isoflurane induced elevated liver aspartate but allowed more rapid initiation of tissue collection. Based on these findings, we present a more optimal collection strategy mammalian tissues and recommend that rodent tissues intended for metabolomics studies be collected under anesthesia rather than post-euthanasia.

  8. Impact of Anesthesia and Euthanasia on Metabolomics of Mammalian Tissues: Studies in a C57BL/6J Mouse Model

    Science.gov (United States)

    Overmyer, Katherine A.; Thonusin, Chanisa; Qi, Nathan R.; Burant, Charles F.; Evans, Charles R.

    2015-01-01

    A critical application of metabolomics is the evaluation of tissues, which are often the primary sites of metabolic dysregulation in disease. Laboratory rodents have been widely used for metabolomics studies involving tissues due to their facile handing, genetic manipulability and similarity to most aspects of human metabolism. However, the necessary step of administration of anesthesia in preparation for tissue sampling is not often given careful consideration, in spite of its potential for causing alterations in the metabolome. We examined, for the first time using untargeted and targeted metabolomics, the effect of several commonly used methods of anesthesia and euthanasia for collection of skeletal muscle, liver, heart, adipose and serum of C57BL/6J mice. The data revealed dramatic, tissue-specific impacts of tissue collection strategy. Among many differences observed, post-euthanasia samples showed elevated levels of glucose 6-phosphate and other glycolytic intermediates in skeletal muscle. In heart and liver, multiple nucleotide and purine degradation metabolites accumulated in tissues of euthanized compared to anesthetized animals. Adipose tissue was comparatively less affected by collection strategy, although accumulation of lactate and succinate in euthanized animals was observed in all tissues. Among methods of tissue collection performed pre-euthanasia, ketamine showed more variability compared to isoflurane and pentobarbital. Isoflurane induced elevated liver aspartate but allowed more rapid initiation of tissue collection. Based on these findings, we present a more optimal collection strategy mammalian tissues and recommend that rodent tissues intended for metabolomics studies be collected under anesthesia rather than post-euthanasia. PMID:25658945

  9. Piezosurgery prevents brain tissue damage: an experimental study on a new rat model

    Czech Academy of Sciences Publication Activity Database

    Pavlíková, G.; Foltán, R.; Burian, M.; Horká, E.; Adámek, S.; Hejčl, Aleš; Hanzelka, T.; Šedý, Jiří

    2011-01-01

    Roč. 40, č. 8 (2011), s. 840-844 ISSN 0901-5027 R&D Projects: GA MŠk(CZ) LC554; GA ČR GAP304/10/0320 Grant - others:GA MŠk(CZ) 1M0538 Program:1M Institutional research plan: CEZ:AV0Z50390703 Keywords : piezosurgery * brain * tissue damage Subject RIV: FJ - Surgery incl. Transplants; FH - Neurology (UEM-P) Impact factor: 1.506, year: 2011

  10. Soft tissue modelling with conical springs.

    Science.gov (United States)

    Omar, Nadzeri; Zhong, Yongmin; Jazar, Reza N; Subic, Aleksandar; Smith, Julian; Shirinzadeh, Bijan

    2015-01-01

    This paper presents a new method for real-time modelling soft tissue deformation. It improves the traditional mass-spring model with conical springs to deal with nonlinear mechanical behaviours of soft tissues. A conical spring model is developed to predict soft tissue deformation with reference to deformation patterns. The model parameters are formulated according to tissue deformation patterns and the nonlinear behaviours of soft tissues are modelled with the stiffness variation of conical spring. Experimental results show that the proposed method can describe different tissue deformation patterns using one single equation and also exhibit the typical mechanical behaviours of soft tissues.

  11. 3D-printed soft-tissue physical models of renal malignancies for individualized surgical simulation: a feasibility study.

    Science.gov (United States)

    Maddox, Michael M; Feibus, Allison; Liu, James; Wang, Julie; Thomas, Raju; Silberstein, Jonathan L

    2018-03-01

    To construct patient-specific physical three-dimensional (3D) models of renal units with materials that approximates the properties of renal tissue to allow pre-operative and robotic training surgical simulation, 3D physical kidney models were created (3DSystems, Rock Hill, SC) using computerized tomography to segment structures of interest (parenchyma, vasculature, collection system, and tumor). Images were converted to a 3D surface mesh file for fabrication using a multi-jet 3D printer. A novel construction technique was employed to approximate normal renal tissue texture, printers selectively deposited photopolymer material forming the outer shell of the kidney, and subsequently, an agarose gel solution was injected into the inner cavity recreating the spongier renal parenchyma. We constructed seven models of renal units with suspected malignancies. Partial nephrectomy and renorrhaphy were performed on each of the replicas. Subsequently all patients successfully underwent robotic partial nephrectomy. Average tumor diameter was 4.4 cm, warm ischemia time was 25 min, RENAL nephrometry score was 7.4, and surgical margins were negative. A comparison was made between the seven cases and the Tulane Urology prospectively maintained robotic partial nephrectomy database. Patients with surgical models had larger tumors, higher nephrometry score, longer warm ischemic time, fewer positive surgical margins, shorter hospitalization, and fewer post-operative complications; however, the only significant finding was lower estimated blood loss (186 cc vs 236; p = 0.01). In this feasibility study, pre-operative resectable physical 3D models can be constructed and used as patient-specific surgical simulation tools; further study will need to demonstrate if this results in improvement of surgical outcomes and robotic simulation education.

  12. Influence of a dexamethasone-eluting covered stent on tissue reaction: an experimental study in a canine bronchial model

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Ji Hoon; Song, Ho-Young; Choi, Gi Bok; Kim, Tae-Hyung; Suh, Ji-Yeon [University of Ulsan College of Medicine, Department of Radiology, Asan Medical Center, Seoul (Korea); Seo, Tae-Seok [Gachon Medical School, Department of Radiology, Gil Medical Center, Inchon (Korea); Yuk, Soon Hong [Hannam University, Department of Polymer Science and Engineering, College of Engineering, Daejeon (Korea); Kim, Young-Hwa [Soonchunhyang University Chonan Hospital, Department of Radiology, Chonan (Korea); Cho, Yong-Mee [University of Ulsan College of Medicine, Department of Pathology, Asan Medical Center, Seoul (Korea)

    2005-06-01

    This study was designed to evaluate the feasibility and efficacy of a dexamethasone (DXM)-eluting, covered, self-expanding metallic stent to reduce tissue reaction following stent placement in a canine bronchial model. We placed a DXM-eluting, polyurethane-covered, self-expanding metallic stent (drug stent, DS) and a polyurethane-covered, self-expanding metallic stent (control stent, CS) alternately in each left main bronchus and left lower lobe bronchus in 12 dogs. The stents were 20 mm in diameter and length when fully expanded. The dose of DXM was approximately 36.7 mg in each DS, but was absent in the CS. The dogs were euthanased 1 week (n=4), 2 weeks (n=4) or 4 weeks (n=4) after stent placement. Histologic findings, such as epithelial erosion/ulcer or granulation tissue thickness, were obtained from the mid-portion of the bronchus, where the stent had been placed, and evaluated between DS and CS. There were no procedure-related complications or malpositioning of any of the bronchial stents. Stent migration was detected in one dog just before euthanasia 1 week following stent placement. Stent patency was maintained until euthanasia in all dogs. Epithelial erosion/ulcer (%) was significantly less in the DS (mean{+-}standard deviation, 46.88{+-}23.75) than in the CS (73.75{+-}14.08) (P=0.026) for all time-points. There was a decrease in epithelial erosion/ulcer as the follow-up period increased in both DS and CS. The granulation tissue thickness (mm) was less in DS (2.63{+-}2.05) than in CS (3.49{+-}2.95), although the difference was not significant (P=0.751) for all time-points. There was a tendency toward an increase in granulation tissue thickness and chronic lymphocytic infiltration as the follow-up period increased in both DS and CS. In conclusion, DXM-eluting, covered, self-expanding metallic stent seems to be effective in reducing tissue reaction secondary to stent placement in a canine bronchial model. (orig.)

  13. Influence of a dexamethasone-eluting covered stent on tissue reaction: an experimental study in a canine bronchial model

    International Nuclear Information System (INIS)

    Shin, Ji Hoon; Song, Ho-Young; Choi, Gi Bok; Kim, Tae-Hyung; Suh, Ji-Yeon; Seo, Tae-Seok; Yuk, Soon Hong; Kim, Young-Hwa; Cho, Yong-Mee

    2005-01-01

    This study was designed to evaluate the feasibility and efficacy of a dexamethasone (DXM)-eluting, covered, self-expanding metallic stent to reduce tissue reaction following stent placement in a canine bronchial model. We placed a DXM-eluting, polyurethane-covered, self-expanding metallic stent (drug stent, DS) and a polyurethane-covered, self-expanding metallic stent (control stent, CS) alternately in each left main bronchus and left lower lobe bronchus in 12 dogs. The stents were 20 mm in diameter and length when fully expanded. The dose of DXM was approximately 36.7 mg in each DS, but was absent in the CS. The dogs were euthanased 1 week (n=4), 2 weeks (n=4) or 4 weeks (n=4) after stent placement. Histologic findings, such as epithelial erosion/ulcer or granulation tissue thickness, were obtained from the mid-portion of the bronchus, where the stent had been placed, and evaluated between DS and CS. There were no procedure-related complications or malpositioning of any of the bronchial stents. Stent migration was detected in one dog just before euthanasia 1 week following stent placement. Stent patency was maintained until euthanasia in all dogs. Epithelial erosion/ulcer (%) was significantly less in the DS (mean±standard deviation, 46.88±23.75) than in the CS (73.75±14.08) (P=0.026) for all time-points. There was a decrease in epithelial erosion/ulcer as the follow-up period increased in both DS and CS. The granulation tissue thickness (mm) was less in DS (2.63±2.05) than in CS (3.49±2.95), although the difference was not significant (P=0.751) for all time-points. There was a tendency toward an increase in granulation tissue thickness and chronic lymphocytic infiltration as the follow-up period increased in both DS and CS. In conclusion, DXM-eluting, covered, self-expanding metallic stent seems to be effective in reducing tissue reaction secondary to stent placement in a canine bronchial model. (orig.)

  14. Impact of anesthesia and euthanasia on metabolomics of mammalian tissues: studies in a C57BL/6J mouse model.

    Directory of Open Access Journals (Sweden)

    Katherine A Overmyer

    Full Text Available A critical application of metabolomics is the evaluation of tissues, which are often the primary sites of metabolic dysregulation in disease. Laboratory rodents have been widely used for metabolomics studies involving tissues due to their facile handing, genetic manipulability and similarity to most aspects of human metabolism. However, the necessary step of administration of anesthesia in preparation for tissue sampling is not often given careful consideration, in spite of its potential for causing alterations in the metabolome. We examined, for the first time using untargeted and targeted metabolomics, the effect of several commonly used methods of anesthesia and euthanasia for collection of skeletal muscle, liver, heart, adipose and serum of C57BL/6J mice. The data revealed dramatic, tissue-specific impacts of tissue collection strategy. Among many differences observed, post-euthanasia samples showed elevated levels of glucose 6-phosphate and other glycolytic intermediates in skeletal muscle. In heart and liver, multiple nucleotide and purine degradation metabolites accumulated in tissues of euthanized compared to anesthetized animals. Adipose tissue was comparatively less affected by collection strategy, although accumulation of lactate and succinate in euthanized animals was observed in all tissues. Among methods of tissue collection performed pre-euthanasia, ketamine showed more variability compared to isoflurane and pentobarbital. Isoflurane induced elevated liver aspartate but allowed more rapid initiation of tissue collection. Based on these findings, we present a more optimal collection strategy mammalian tissues and recommend that rodent tissues intended for metabolomics studies be collected under anesthesia rather than post-euthanasia.

  15. Three-dimensional immersive virtual reality for studying cellular compartments in 3D models from EM preparations of neural tissues

    KAUST Repository

    Cali, Corrado

    2015-07-14

    Advances for application of electron microscopy to serial imaging are opening doors to new ways of analyzing cellular structure. New and improved algorithms and workflows for manual and semiautomated segmentation allow to observe the spatial arrangement of the smallest cellular features with unprecedented detail in full three-dimensions (3D). From larger samples, higher complexity models can be generated; however, they pose new challenges to data management and analysis. Here, we review some currently available solutions and present our approach in detail. We use the fully immersive virtual reality (VR) environment CAVE (cave automatic virtual environment), a room where we are able to project a cellular reconstruction and visualize in 3D, to step into a world created with Blender, a free, fully customizable 3D modeling software with NeuroMorph plug-ins for visualization and analysis of electron microscopy (EM) preparations of brain tissue. Our workflow allows for full and fast reconstructions of volumes of brain neuropil using ilastik, a software tool for semiautomated segmentation of EM stacks. With this visualization environment, we can walk into the model containing neuronal and astrocytic processes to study the spatial distribution of glycogen granules, a major energy source that is selectively stored in astrocytes. The use of CAVE was key to observe a nonrandom distribution of glycogen, and led us to develop tools to quantitatively analyze glycogen clustering and proximity to other subcellular features. This article is protected by copyright. All rights reserved.

  16. Experimental study of mechanical response of artificial tissue models irradiated with Nd:YAG nanosecond laser pulses

    Science.gov (United States)

    Pérez-Gutiérrez, Francisco G.; Camacho-López, Santiago; Aguilar, Guillermo

    2011-07-01

    Nanosecond long laser pulses are used in medical applications where precise tissue ablation with minimal thermal and mechanical collateral damage is required. When a laser pulse is incident on a material, optical energy will be absorbed by a combination of linear and nonlinear absorption according to both: laser light irradiance and material properties. In the case of water or gels, the first results in heat generation and thermoelastic expansion; while the second results in an expanding plasma formation that launches a shock wave and a cavitation/boiling bubble. Plasma formation due to nonlinear absorption of nanosecond laser pulses is originated by a combination of multiphoton ionization and thermionic emission of free electrons, which is enhanced when the material has high linear absorption coefficient. In this work, we present three experimental approaches to study pressure transients originated when 6 ns laser pulses are incident on agar gels and water with varying linear absorption coefficient, using laser radiant exposures above and below threshold for bubble formation: (a) PVDF sensors, (b) Time-resolved shadowgraphy and (c) Time-resolved interferometry. The underlying hypothesis is that pressure transients are composed of the superposition of both: shock wave originated by hot expanding plasma resulting from nonlinear absorption of optical energy and, thermoelastic expansion originated by heat generation due to linear absorption of optical energy. The objective of this study is to carry out a comprehensive experimental analysis of the mechanical effects that result when tissue models are irradiated with nanosecond laser pulses to elucidate the relative contribution of linear and nonlinear absorption to bubble formation. Furthermore, we investigate cavitation bubble formation with temperature increments as low as 3 °C.

  17. Deep-tissue temperature mapping by multi-illumination photoacoustic tomography aided by a diffusion optical model: a numerical study

    Science.gov (United States)

    Zhou, Yuan; Tang, Eric; Luo, Jianwen; Yao, Junjie

    2018-01-01

    Temperature mapping during thermotherapy can help precisely control the heating process, both temporally and spatially, to efficiently kill the tumor cells and prevent the healthy tissues from heating damage. Photoacoustic tomography (PAT) has been used for noninvasive temperature mapping with high sensitivity, based on the linear correlation between the tissue's Grüneisen parameter and temperature. However, limited by the tissue's unknown optical properties and thus the optical fluence at depths beyond the optical diffusion limit, the reported PAT thermometry usually takes a ratiometric measurement at different temperatures and thus cannot provide absolute measurements. Moreover, ratiometric measurement over time at different temperatures has to assume that the tissue's optical properties do not change with temperatures, which is usually not valid due to the temperature-induced hemodynamic changes. We propose an optical-diffusion-model-enhanced PAT temperature mapping that can obtain the absolute temperature distribution in deep tissue, without the need of multiple measurements at different temperatures. Based on the initial acoustic pressure reconstructed from multi-illumination photoacoustic signals, both the local optical fluence and the optical parameters including absorption and scattering coefficients are first estimated by the optical-diffusion model, then the temperature distribution is obtained from the reconstructed Grüneisen parameters. We have developed a mathematic model for the multi-illumination PAT of absolute temperatures, and our two-dimensional numerical simulations have shown the feasibility of this new method. The proposed absolute temperature mapping method may set the technical foundation for better temperature control in deep tissue in thermotherapy.

  18. Pilot study of Alteplase (tissue plasminogen activator) for treatment of urinary clot retention in an in vitro model.

    Science.gov (United States)

    Ritch, Chad R; Ordonez, Maria A; Okhunov, Zhamshid; Araujo, Juan; Walsh, Rhonda; Baudin, Vania; Lee, Daniel; Badani, Ketan K; Gupta, Mantu; Landman, Jaime

    2009-08-01

    The management of urinary clot retention and hematuria involves manual irrigation with sterile water or normal saline via a Foley catheter followed by continuous bladder irrigation. Irrigation may become difficult because of the formation of dense blood clots. Tissue plasminogen activator (t-PA/Alteplase) may be a useful pharmacological agent to improve the efficacy of manual irrigation of large, dense clots. The goal of the current study was to compare t-PA to sterile water for clot irrigation in an in vitro model. In vitro models of clot retention were created using 500-cc urinary leg bags each filled with 80 cc of unpreserved whole blood from a healthy volunteer. Each model was incubated at 25 degrees C for 24 hours to allow clot formation. Four models each with 25 mL solution of t-PA at concentrations of 2, 1, 0.5, and 0.25 mg/mL were evaluated and compared to a control (25 mL sterile water). Models were instilled with solution (t-PA or control) and incubated for 30 minutes at 37 degrees C, and then irrigated with sterile water via 18F Foley by a blinded investigator. Three separate experiments were conducted, and statistical analysis was performed comparing various irrigation parameters. Clot evacuation with 25 mL of t-PA at a concentration of 2 mg/mL (50 mg) was significantly easier (p = 0.05) and faster (p < 0.05) than the sterile water control. The mean time for clot evacuation in this model was 2.7 minutes for t-PA solution 2 mg/mL versus 7.3 minutes for the control (p < 0.05). Compared to the control, irrigation with t-PA solution 2 mg/mL also required less irrigant (180 mL vs. 500 mL) (p < 0.05) for complete evacuation. There was a similar trend in efficacy for the lower doses of t-PA, but this was not statistically significant. In this in vitro study, a single 25 mL instillation of t-PA solution 2 mg/mL is significantly better than sterile water alone for clot evacuation. In vivo animal studies are pending.

  19. Tissue Sampling Guides for Porcine Biomedical Models.

    Science.gov (United States)

    Albl, Barbara; Haesner, Serena; Braun-Reichhart, Christina; Streckel, Elisabeth; Renner, Simone; Seeliger, Frank; Wolf, Eckhard; Wanke, Rüdiger; Blutke, Andreas

    2016-04-01

    This article provides guidelines for organ and tissue sampling adapted to porcine animal models in translational medical research. Detailed protocols for the determination of sampling locations and numbers as well as recommendations on the orientation, size, and trimming direction of samples from ∼50 different porcine organs and tissues are provided in the Supplementary Material. The proposed sampling protocols include the generation of samples suitable for subsequent qualitative and quantitative analyses, including cryohistology, paraffin, and plastic histology; immunohistochemistry;in situhybridization; electron microscopy; and quantitative stereology as well as molecular analyses of DNA, RNA, proteins, metabolites, and electrolytes. With regard to the planned extent of sampling efforts, time, and personnel expenses, and dependent upon the scheduled analyses, different protocols are provided. These protocols are adjusted for (I) routine screenings, as used in general toxicity studies or in analyses of gene expression patterns or histopathological organ alterations, (II) advanced analyses of single organs/tissues, and (III) large-scale sampling procedures to be applied in biobank projects. Providing a robust reference for studies of porcine models, the described protocols will ensure the efficiency of sampling, the systematic recovery of high-quality samples representing the entire organ or tissue as well as the intra-/interstudy comparability and reproducibility of results. © The Author(s) 2016.

  20. Non-invasive pulsed cavitational ultrasound for fetal tissue ablation: feasibility study in a fetal sheep model.

    Science.gov (United States)

    Kim, Y; Gelehrter, S K; Fifer, C G; Lu, J C; Owens, G E; Berman, D R; Williams, J; Wilkinson, J E; Ives, K A; Xu, Z

    2011-04-01

    Currently available fetal intervention techniques rely on invasive procedures that carry inherent risks. A non-invasive technique for fetal intervention could potentially reduce the risk of fetal and obstetric complications. Pulsed cavitational ultrasound therapy (histotripsy) is an ablation technique that mechanically fractionates tissue at the focal region using extracorporeal ultrasound. In this study, we investigated the feasibility of using histotripsy as a non-invasive approach to fetal intervention in a sheep model. The experiments involved 11 gravid sheep at 102-129 days of gestation. Fetal kidney, liver, lung and heart were exposed to ultrasound pulses (bones. Histological assessment confirmed lesion locations and sizes corresponding to regions where cavitation was monitored, with no lesions found when cavitation was absent. Inability to generate cavitation was primarily associated with increased depth to target and obstructing structures such as fetal limbs. Extracorporeal histotripsy therapy successfully created targeted lesions in fetal sheep organs without significant damage to overlying structures. With further improvements, histotripsy may evolve into a viable technique for non-invasive fetal intervention procedures. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

  1. Tookad-mediated photodynamic effects on the prostate and its adjacent tissues: in vivo study in canine models

    Science.gov (United States)

    Huang, Zheng; Chen, Qun; Luck, David; Beckers, Jill; Blanc, Dominique; Hetzel, Fred W.

    2005-04-01

    Photodynamic therapy (PDT) mediated with a vascular acting photosensitizer Tookad (pd-bacteriopheophorbide), was investigated as an alternative treatment modality for prostate cancer. Tookad photodynamic effects on the prostate and its adjacent tissues were evaluated in canine models. Interstitial prostate PDT was performed by irradiating individual lobes with a diode laser (763 nm) and 1-cm cylindrical diffuser fibers at various light doses to activate the IV administered photosensitizer Tookad (1 - 2 mg/kg). The sensitivity of the adjacent tissues to Tookad-PDT was determined by superficially irradiating the surfaces of the bladder, colon, abdominal muscle and pelvic plexus with a microlens fiber at various drug/light doses. PDT effect on the prostatic urethra was evaluated by transurethral irradiation. The prostate and adjacent tissues were harvested one-week after the treatment and subjected to histopathologic examination. At one-week post interstitial prostate PDT, the animals recovered well with little or no urethral complications. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis. The bladder, colon, abdominal muscle and pelvic plexus, appeared to also be sensitive to Tookad-PDT at light dose levels greater than 40 Jcm2. Urethral mucosa appeared less sensitive to Tookad-PDT. In conclusion, Tookad-mediated PDT demonstrates very strong vascular effects and can provide an effective alternative for the treatment of localized prostate cancer. Protection of the adjacent tissues should be taken into consideration in the total prostate ablation process due to their sensitivity to the Tookad-mediated PDT.

  2. Study of Different Tissue Density Effects on the Dose Distribution of a 103Pd Brachytherapy Source Model MED3633

    Directory of Open Access Journals (Sweden)

    Ali Asghar Mowlavi

    2010-09-01

    Full Text Available Introduction: Clinical application of encapsulated radioactive brachytherapy sources has a major role in cancer treatment. In the present research, the effects of different tissue densities on the dose distribution of a 103Pd brachytherapy source in a spherical phantom of 50 cm radius have been studied. Material and Methods: As is well known, absorbed dose in tissue depends to its density, but this difference is not clear in measurements. Therefore, we applied the MCNP code to evaluate the effect of density on the dose distribution. 103Pd brachytherapy sources are used to treat prostate, breast and other cancers. Results: Absorbed dose has been calculated and presented around a source placed in the center of the phantom for different tissue densities. Also, we derived anisotropy and radial dose functions and compared our Monte Carlo results with experimental results of Rivard and Li et al. for F(1, θ and g(r in 1.040 g/cm3 tissue. Conclusion: The results of this study show that relative dose variations around the source center are very considerable at different densities, because of the presence of a photoabsorber (Au-Cu alloy in the source core. Dose variation exceeds 80% at the point (Z = 2.4 mm, Y = 0 mm. Computed values of anisotropy and radial dose functions are in good agreement with the experimental results of Rivard and Li et al.

  3. Pseudofracture: an acute peripheral tissue trauma model.

    Science.gov (United States)

    Darwiche, Sophie S; Kobbe, Philipp; Pfeifer, Roman; Kohut, Lauryn; Pape, Hans-Christoph; Billiar, Timothy

    2011-04-18

    Following trauma there is an early hyper-reactive inflammatory response that can lead to multiple organ dysfunction and high mortality in trauma patients; this response is often accompanied by a delayed immunosuppression that adds the clinical complications of infection and can also increase mortality. Many studies have begun to assess these changes in the reactivity of the immune system following trauma. Immunologic studies are greatly supported through the wide variety of transgenic and knockout mice available for in vivo modeling; these strains aid in detailed investigations to assess the molecular pathways involved in the immunologic responses. The challenge in experimental murine trauma modeling is long term investigation, as fracture fixation techniques in mice, can be complex and not easily reproducible. This pseudofracture model, an easily reproduced trauma model, overcomes these difficulties by immunologically mimicking an extremity fracture environment, while allowing freedom of movement in the animals and long term survival without the continual, prolonged use of anaesthesia. The intent is to recreate the features of long bone fracture; injured muscle and soft tissue are exposed to damaged bone and bone marrow without breaking the native bone. The pseudofracture model consists of two parts: a bilateral muscle crush injury to the hindlimbs, followed by injection of a bone solution into these injured muscles. The bone solution is prepared by harvesting the long bones from both hindlimbs of an age- and weight-matched syngeneic donor. These bones are then crushed and resuspended in phosphate buffered saline to create the bone solution. Bilateral femur fracture is a commonly used and well-established model of extremity trauma, and was the comparative model during the development of the pseudofracture model. Among the variety of available fracture models, we chose to use a closed method of fracture with soft tissue injury as our comparison to the

  4. Influence of paclitaxel-eluting expandable metallic stent on tissue hyperplasia: an experimental study in a canine tracheal model

    International Nuclear Information System (INIS)

    Shin, Ji Hoon; Kim, Jung Sun; Kim, Tae Hyung; Kim, Eun Young; Choi, Won Chan; Woo, Chul Woong; Di, Zhenhai; Song, Ho Young; Yuk, Soon Hong; Lee, Yong Seok

    2005-01-01

    To evaluate the efficacy of a paclitaxel-eluting expandable metallic stent in reducing tissue hyperplasia following stent placement in a canine tracheal model. Nine paclitaxel-eluting stents (drug stent, DS) consisting of a proximal bare part and a distal polyurethane-covered part were placed in the trachea of nine dogs and nine control stents (control stent, CS) were placed in the other nine dogs. The dogs were scheduled to be sacrificed 12 weeks after stent placement. Gross and histological factors, such as epithelial erosion/ulcer, granulation tissue thickness and inflammatory cell infiltration were evaluated after each dog was sacrificed. There were no procedure-related complications or malpositioning of any of the stents. One CS migrated less than eight weeks following stent placement. Four dogs (one DS and three CS dogs) died between three and five weeks following stent placement. Therefore, pathologic specimens were obtained from eight DS and five CS dogs. Epithelial erosion/ulcer or inflammatory cell infiltration was slightly more prominent in the DS cases than in the CS cases, in both the bare part and the covered part. However, the data was not statistically significant. Granulation tissue thickness was lower in the DS cases than in the CS cases in both the bare part (mean, 3.63-mm vs. 4.37-mm) and the covered part (mean, 1.75-mm vs. 2,78 mm), but the data was also statistically insignificant. Although the data was not statistically significant, placement of paclitaxel-eluting expandable metallic stent demonstrates a tendency toward a decrease in granulation tissue thickness in canine tracheal models

  5. Influence of paclitaxel-eluting expandable metallic stent on tissue hyperplasia: an experimental study in a canine tracheal model

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Ji Hoon; Kim, Jung Sun; Kim, Tae Hyung; Kim, Eun Young; Choi, Won Chan; Woo, Chul Woong; Di, Zhenhai; Song, Ho Young [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Yuk, Soon Hong [Hannam University, College of Engineering, Daejeon (Korea, Republic of); Lee, Yong Seok [Wonkwang University College of Medicine, Iksan (Korea, Republic of)

    2005-07-15

    To evaluate the efficacy of a paclitaxel-eluting expandable metallic stent in reducing tissue hyperplasia following stent placement in a canine tracheal model. Nine paclitaxel-eluting stents (drug stent, DS) consisting of a proximal bare part and a distal polyurethane-covered part were placed in the trachea of nine dogs and nine control stents (control stent, CS) were placed in the other nine dogs. The dogs were scheduled to be sacrificed 12 weeks after stent placement. Gross and histological factors, such as epithelial erosion/ulcer, granulation tissue thickness and inflammatory cell infiltration were evaluated after each dog was sacrificed. There were no procedure-related complications or malpositioning of any of the stents. One CS migrated less than eight weeks following stent placement. Four dogs (one DS and three CS dogs) died between three and five weeks following stent placement. Therefore, pathologic specimens were obtained from eight DS and five CS dogs. Epithelial erosion/ulcer or inflammatory cell infiltration was slightly more prominent in the DS cases than in the CS cases, in both the bare part and the covered part. However, the data was not statistically significant. Granulation tissue thickness was lower in the DS cases than in the CS cases in both the bare part (mean, 3.63-mm vs. 4.37-mm) and the covered part (mean, 1.75-mm vs. 2,78 mm), but the data was also statistically insignificant. Although the data was not statistically significant, placement of paclitaxel-eluting expandable metallic stent demonstrates a tendency toward a decrease in granulation tissue thickness in canine tracheal models.

  6. A measurement and modeling study of temperature in living and fixed tissue during and after radiofrequency exposure.

    Science.gov (United States)

    Bermingham, Jacqueline F; Chen, Yuen Y; McIntosh, Robert L; Wood, Andrew W

    2014-04-01

    Fluorescent intensity of the dye Rhodamine-B (Rho-B) decreases with increasing temperature. We show that in fresh rat brain tissue samples in a custom-made radiofrequency (RF) tissue exposure device, temperature rise due to RF radiation as measured by absorbed dye correlates well with temperature measured nearby by fiber optic probes. Estimates of rate of initial temperature rise (using both probe measurement and the dye method) accord well with estimates of local specific energy absorption rate (SAR). We also modeled the temperature characteristics of the exposure device using combined electromagnetic and finite-difference thermal modeling. Although there are some differences in the rate of cooling following cessation of RF exposure, there is reasonable agreement between modeling and both probe measurement and dye estimation of temperature. The dye method also permits measurement of regional temperature rise (due to RF). There is no clear evidence of local differential RF absorption, but further refinement of the method may be needed to fully clarify this issue. © 2014 Wiley Periodicals, Inc.

  7. Nonlinear Rheology in a Model Biological Tissue

    Science.gov (United States)

    Matoz-Fernandez, D. A.; Agoritsas, Elisabeth; Barrat, Jean-Louis; Bertin, Eric; Martens, Kirsten

    2017-04-01

    The rheological response of dense active matter is a topic of fundamental importance for many processes in nature such as the mechanics of biological tissues. One prominent way to probe mechanical properties of tissues is to study their response to externally applied forces. Using a particle-based model featuring random apoptosis and environment-dependent division rates, we evidence a crossover from linear flow to a shear-thinning regime with an increasing shear rate. To rationalize this nonlinear flow we derive a theoretical mean-field scenario that accounts for the interplay of mechanical and active noise in local stresses. These noises are, respectively, generated by the elastic response of the cell matrix to cell rearrangements and by the internal activity.

  8. Reducing the number of laboratory animals used in tissue engineering research by restricting the variety of animal models. Articular cartilage tissue engineering as a case study

    NARCIS (Netherlands)

    Vries, R.B.M. de; Buma, P.; Leenaars, M.; Ritskes-Hoitinga, M.; Gordijn, B.

    2012-01-01

    The use of laboratory animals in tissue engineering research is an important underexposed ethical issue. Several ethical questions may be raised about this use of animals. This article focuses on the possibilities of reducing the number of animals used. Given that there is considerable debate about

  9. The tissue-engineered human cornea as a model to study expression of matrix metalloproteinases during corneal wound healing.

    Science.gov (United States)

    Couture, Camille; Zaniolo, Karine; Carrier, Patrick; Lake, Jennifer; Patenaude, Julien; Germain, Lucie; Guérin, Sylvain L

    2016-02-01

    Corneal injuries remain a major cause of consultation in the ophthalmology clinics worldwide. Repair of corneal wounds is a complex mechanism that involves cell death, migration, proliferation, differentiation, and extracellular matrix (ECM) remodeling. In the present study, we used a tissue-engineered, two-layers (epithelium and stroma) human cornea as a biomaterial to study both the cellular and molecular mechanisms of wound healing. Gene profiling on microarrays revealed important alterations in the pattern of genes expressed by tissue-engineered corneas in response to wound healing. Expression of many MMPs-encoding genes was shown by microarray and qPCR analyses to increase in the migrating epithelium of wounded corneas. Many of these enzymes were converted into their enzymatically active form as wound closure proceeded. In addition, expression of MMPs by human corneal epithelial cells (HCECs) was affected both by the stromal fibroblasts and the collagen-enriched ECM they produce. Most of all, results from mass spectrometry analyses provided evidence that a fully stratified epithelium is required for proper synthesis and organization of the ECM on which the epithelial cells adhere. In conclusion, and because of the many characteristics it shares with the native cornea, this human two layers corneal substitute may prove particularly useful to decipher the mechanistic details of corneal wound healing. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Damage Models for Soft Tissues: A Survey.

    Science.gov (United States)

    Li, Wenguang

    Damage to soft tissues in the human body has been investigated for applications in healthcare, sports, and biomedical engineering. This paper reviews and classifies damage models for soft tissues to summarize achievements, identify new directions, and facilitate finite element analysis. The main ideas of damage modeling methods are illustrated and interpreted. A few key issues related to damage models, such as experimental data curve-fitting, computational effort, connection between damage and fractures/cracks, damage model applications, and fracture/crack extension simulation, are discussed. Several new challenges in the field are identified and outlined. This review can be useful for developing more advanced damage models and extending damage modeling methods to a variety of soft tissues.

  11. From cells to tissue: A continuum model of epithelial mechanics

    Science.gov (United States)

    Ishihara, Shuji; Marcq, Philippe; Sugimura, Kaoru

    2017-08-01

    A two-dimensional continuum model of epithelial tissue mechanics was formulated using cellular-level mechanical ingredients and cell morphogenetic processes, including cellular shape changes and cellular rearrangements. This model incorporates stress and deformation tensors, which can be compared with experimental data. Focusing on the interplay between cell shape changes and cell rearrangements, we elucidated dynamical behavior underlying passive relaxation, active contraction-elongation, and tissue shear flow, including a mechanism for contraction-elongation, whereby tissue flows perpendicularly to the axis of cell elongation. This study provides an integrated scheme for the understanding of the orchestration of morphogenetic processes in individual cells to achieve epithelial tissue morphogenesis.

  12. Marginal bone and soft tissue behavior following platform switching abutment connection/disconnection--a dog model study.

    Science.gov (United States)

    Alves, Célia C; Muñoz, Fernando; Cantalapiedra, António; Ramos, Isabel; Neves, Manuel; Blanco, Juan

    2015-09-01

    The effect on the marginal peri-implant tissues following repeated platform switching abutment removal and subsequent reconnection was studied. Six adult female Beagle dogs were selected, and Pm3 and Pm4 teeth, both left and right sides, were extracted and the sites healed for 3 months. At this time, 24 bone level (BL) (Straumann, Basel, Switzerland) Ø 3.3/8 mm implants were placed, 2 in each side on Pm3 and Pm4 regions. In one side (control group), 12 bone level conical Ø 3.6 mm healing abutments and, on the other side (test group), 12 Narrow CrossFit (NC) multibase abutments (Straumann) , Basel, Switzerland) were connected at time of implant surgery. On test group, all prosthetic procedures were carried out direct to multibase abutment without disconnecting it, where in the control group, the multibase abutment was connected/disconnected five times (at 6/8/10/12/14 weeks) during prosthetic procedures. Twelve fixed metal bridges were delivered 14 weeks after implant placement. A cleaning/control appointment was scheduled 6 months after implant placement. The animals were sacrificed at 9 months of the study. Clinical parameters and peri-apical x-rays were registered in every visit. Histomorphometric analysis was carried out for the 24 implants. The distance from multibase abutment shoulder to the first bone implant contact (S-BIC) was defined as the primary histomorphometric parameter. Wilcoxon comparison paired test (n = 6) found no statistically significant differences (buccal P = 0.917; Lingual P = 0.463) between test and control groups both lingually and buccally for S-BIC distance. Only Pm3 buccal aBE-BC (distance from the apical end of the barrier epithelium to the first bone implant contact) (P = 0.046) parameter presented statistically significant differences between test and control groups. Control group presented 0.57 mm more recession than test group, being this difference statistically significant between the two groups (P < 0.001). It can be conclude

  13. Mechanical characterization of bioprinted in vitro soft tissue models

    International Nuclear Information System (INIS)

    Zhang, Ting; Ouyang, Liliang; Sun, Wei; Yan, Karen Chang

    2013-01-01

    Recent development in bioprinting technology enables the fabrication of complex, precisely controlled cell-encapsulated tissue constructs. Bioprinted tissue constructs have potential in both therapeutic applications and nontherapeutic applications such as drug discovery and screening, disease modelling and basic biological studies such as in vitro tissue modelling. The mechanical properties of bioprinted in vitro tissue models play an important role in mimicking in vivo the mechanochemical microenvironment. In this study, we have constructed three-dimensional in vitro soft tissue models with varying structure and porosity based on the 3D cell-assembly technique. Gelatin/alginate hybrid materials were used as the matrix material and cells were embedded. The mechanical properties of these models were assessed via compression tests at various culture times, and applicability of three material constitutive models was examined for fitting the experimental data. An assessment of cell bioactivity in these models was also carried out. The results show that the mechanical properties can be improved through structure design, and the compression modulus and strength decrease with respect to time during the first week of culture. In addition, the experimental data fit well with the Ogden model and experiential function. These results provide a foundation to further study the mechanical properties, structural and combined effects in the design and the fabrication of in vitro soft tissue models. (paper)

  14. Spaceflight bioreactor studies of cells and tissues.

    Science.gov (United States)

    Freed, Lisa E; Vunjak-Novakovic, Gordana

    2002-01-01

    Studies of the fundamental role of gravity in the development and function of biological organisms are a central component of the human exploration of space. Microgravity affects numerous physical phenomena relevant to biological research, including the hydrostatic pressure in fluid filled vesicles, sedimentation of organelles, and buoyancy-driven convection of flow and heat. These physical phenomena can in turn directly and indirectly affect cellular morphology, metabolism, locomotion, secretion of extracellular matrix and soluble signals, and assembly into functional tissues. Studies aimed at distinguishing specific effects of gravity on biological systems require the ability to: (i) control and systematically vary gravity, e.g. by utilizing the microgravity environment of space in conjunction with an in-flight centrifuge; and (ii) maintain constant all other factors in the immediate environment, including in particular concentrations and exchange rates of biochemical species and hydrodynamic shear. The latter criteria imply the need for gravity-independent mechanisms to provide for mass transport between the cells and their environment. Available flight hardware has largely determined the experimental design and scientific objectives of spaceflight cell and tissue culture studies carried out to date. Simple culture vessels have yielded important quantitative data, and helped establish in vitro models of cell locomotion, growth and differentiation in various mammalian cell types including embryonic lung cells [6], lymphocytes [2,8], and renal cells [7,31]. Studies done using bacterial cells established the first correlations between gravity-dependent factors such as cell settling velocity and diffusional distance and the respective cell responses [12]. The development of advanced bioreactors for microgravity cell and tissue culture and for tissue engineering has benefited both research areas and provided relevant in vitro model systems for studies of astronaut

  15. A constitutive model of soft tissue: From nanoscale collagen to tissue continuum

    KAUST Repository

    Tang, Huang

    2009-04-08

    Soft collagenous tissue features many hierarchies of structure, starting from tropocollagen molecules that form fibrils, and proceeding to a bundle of fibrils that form fibers. Here we report the development of an atomistically informed continuum model of collagenous tissue. Results from full atomistic and molecular modeling are linked with a continuum theory of a fiber-reinforced composite, handshaking the fibril scale to the fiber and continuum scale in a hierarchical multi-scale simulation approach. Our model enables us to study the continuum-level response of the tissue as a function of cross-link density, making a link between nanoscale collagen features and material properties at larger tissue scales. The results illustrate a strong dependence of the continuum response as a function of nanoscopic structural features, providing evidence for the notion that the molecular basis for protein materials is important in defining their larger-scale mechanical properties. © 2009 Biomedical Engineering Society.

  16. Modelling the electrical properties of tissue as a porous medium

    International Nuclear Information System (INIS)

    Smye, S W; Evans, C J; Robinson, M P; Sleeman, B D

    2007-01-01

    Models of the electrical properties of biological tissue have been the subject of many studies. These models have sought to explain aspects of the dielectric dispersion of tissue. This paper develops a mathematical model of the complex permittivity of tissue as a function of frequency f, in the range 10 4 7 Hz, which is derived from a formulation used to describe the complex permittivity of porous media. The model introduces two parameters, porosity and percolation probability, to the description of the electrical properties of any tissue which comprises a random arrangement of cells. The complex permittivity for a plausible porosity and percolation probability distribution is calculated and compared with the published measured electrical properties of liver tissue. Broad agreement with the experimental data is noted. It is suggested that future detailed experimental measurements should be undertaken to validate the model. The model may be a more convenient method of parameterizing the electrical properties of biological tissue and subsequent measurement of these parameters in a range of tissues may yield information of biological and clinical significance

  17. Particle size modeling and morphology study of chitosan/gelatin/nanohydroxyapatite nanocomposite microspheres for bone tissue engineering.

    Science.gov (United States)

    Bagheri-Khoulenjani, Shadab; Mirzadeh, Hamid; Etrati-Khosroshahi, Mohammad; Shokrgozar, Mohammad Ali

    2013-06-01

    In this study, nanocomposite microspheres based on chitosan/gelatin/nanohydroxyapatite were fabricated, and effects of the nanohydroxyapatite/biopolymer (chitosan/gelatin) weight ratio (nHA/P), stirring rate, chitosan concentration and biopolymer concentration on the particle size, and morphology of nanocomposite microspheres were investigated. Particle size of microspheres was modeled by design of experiments using the surface response method. Particle size, morphology of microspheres, and distribution of nanoparticles within the composite microspheres were evaluated using an optical microscope, scanning electron microscopy (SEM) and transmission electron microscopy (TEM), respectively. X-ray diffraction and Fourier transform infrared spectroscopy were applied to study the physical and chemical characteristics of microspheres. Results showed that by modulating the nHA/P ratio, chitosan concentration, polymer concentration, and stirring rate, it is possible to fabricate microspheres in wide rages of particle size (5-150 μm). Analysis of variance confirmed that the modified quadratic model can be used to predict the particle size of nanocomposite microspheres within the design space. SEM studies showed that microspheres with different compositions had totally different morphologies from dense morphologies to porous ones. TEM images demonstrated that nanoparticles were distributed uniformly within the polymeric matrix. MTT assay and cell culture studies showed that microspheres with different compositions possessed good biocompatibility. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013. Copyright © 2012 Wiley Periodicals, Inc.

  18. A family of hyperelastic models for human brain tissue

    Science.gov (United States)

    Mihai, L. Angela; Budday, Silvia; Holzapfel, Gerhard A.; Kuhl, Ellen; Goriely, Alain

    2017-09-01

    Experiments on brain samples under multiaxial loading have shown that human brain tissue is both extremely soft when compared to other biological tissues and characterized by a peculiar elastic response under combined shear and compression/tension: there is a significant increase in shear stress with increasing axial compression compared to a moderate increase with increasing axial tension. Recent studies have revealed that many widely used constitutive models for soft biological tissues fail to capture this characteristic response. Here, guided by experiments of human brain tissue, we develop a family of modeling approaches that capture the elasticity of brain tissue under varying simple shear superposed on varying axial stretch by exploiting key observations about the behavior of the nonlinear shear modulus, which can be obtained directly from the experimental data.

  19. Modeling collagen remodeling in tissue engineered cardiovascular tissues

    NARCIS (Netherlands)

    Soares, A.L.F.

    2012-01-01

    Commonly, heart valve replacements consist of non-living materials lacking the ability to grow, repair and remodel. Tissue engineering (TE) offers a promising alternative to these replacement strategies since it can overcome its disadvantages. The technique aims to create an autologous living tissue

  20. Rabbit tissue model (RTM) harvesting technique.

    Science.gov (United States)

    Medina, Marelyn

    2002-01-01

    A method for creating a tissue model using a female rabbit for laparoscopic simulation exercises is described. The specimen is called a Rabbit Tissue Model (RTM). Dissection techniques are described for transforming the rabbit carcass into a small, compact unit that can be used for multiple training sessions. Preservation is accomplished by using saline and refrigeration. Only the animal trunk is used, with the rest of the animal carcass being discarded. Practice exercises are provided for using the preserved organs. Basic surgical skills, such as dissection, suturing, and knot tying, can be practiced on this model. In addition, the RTM can be used with any pelvic trainer that permits placement of larger practice specimens within its confines.

  1. Human tissue models in cancer research: looking beyond the mouse.

    Science.gov (United States)

    Jackson, Samuel J; Thomas, Gareth J

    2017-08-01

    Mouse models, including patient-derived xenograft mice, are widely used to address questions in cancer research. However, there are documented flaws in these models that can result in the misrepresentation of human tumour biology and limit the suitability of the model for translational research. A coordinated effort to promote the more widespread development and use of 'non-animal human tissue' models could provide a clinically relevant platform for many cancer studies, maximising the opportunities presented by human tissue resources such as biobanks. A number of key factors limit the wide adoption of non-animal human tissue models in cancer research, including deficiencies in the infrastructure and the technical tools required to collect, transport, store and maintain human tissue for lab use. Another obstacle is the long-standing cultural reliance on animal models, which can make researchers resistant to change, often because of concerns about historical data compatibility and losing ground in a competitive environment while new approaches are embedded in lab practice. There are a wide range of initiatives that aim to address these issues by facilitating data sharing and promoting collaborations between organisations and researchers who work with human tissue. The importance of coordinating biobanks and introducing quality standards is gaining momentum. There is an exciting opportunity to transform cancer drug discovery by optimising the use of human tissue and reducing the reliance on potentially less predictive animal models. © 2017. Published by The Company of Biologists Ltd.

  2. A Humanized Mouse Model Generated Using Surplus Neonatal Tissue

    Directory of Open Access Journals (Sweden)

    Matthew E. Brown

    2018-04-01

    Full Text Available Summary: Here, we describe the NeoThy humanized mouse model created using non-fetal human tissue sources, cryopreserved neonatal thymus and umbilical cord blood hematopoietic stem cells (HSCs. Conventional humanized mouse models are made by engrafting human fetal thymus and HSCs into immunocompromised mice. These mice harbor functional human T cells that have matured in the presence of human self-peptides and human leukocyte antigen molecules. Neonatal thymus tissue is more abundant and developmentally mature and allows for creation of up to ∼50-fold more mice per donor compared with fetal tissue models. The NeoThy has equivalent frequencies of engrafted human immune cells compared with fetal tissue humanized mice and exhibits T cell function in assays of ex vivo cell proliferation, interferon γ secretion, and in vivo graft infiltration. The NeoThy model may provide significant advantages for induced pluripotent stem cell immunogenicity studies, while bypassing the requirement for fetal tissue. : Corresponding author William Burlingham and colleagues created a humanized mouse model called the NeoThy. The NeoThy uses human neonatal, rather than fetal, tissue sources for generating a human immune system within immunocompromised mouse hosts. NeoThy mice are an attractive alternative to conventional humanized mouse models, as they enable robust and reproducible iPSC immunogenicity experiments in vivo. Keywords: NeoThy, humanized mouse, iPSC, PSC, immunogenicity, transplantation, immunology, hematopoietic stem cells, induced pluripotent stem cells, thymus

  3. Dopaminergic Immunofluorescence Studies in Kidney Tissue.

    Science.gov (United States)

    Gildea, J J; Van Sciver, R E; McGrath, H E; Kemp, B A; Jose, P A; Carey, R M; Felder, R A

    2017-01-01

    The kidney is a highly integrated system of specialized differentiated cells that are responsible for fluid and electrolyte balance in the body. While much of today's research focuses on isolated nephron segments or cells from nephron segments grown in tissue culture, an often overlooked technique that can provide a unique view of many cell types in the kidney is slice culture. Here, we describe techniques that use freshly excised kidney tissue from rats to perform a variety of experiments shortly after isolating the tissue. By slicing the rat kidney in a "bread loaf" format, multiple studies can be performed on slices from the same tissue in parallel. Cryosectioning and staining of the tissue allow for the evaluation of physiological or biochemical responses in a wide variety of specific nephron segments. The procedures described within this chapter can also be extended to human or mouse kidney tissue.

  4. Human tissue models in cancer research: looking beyond the mouse

    Directory of Open Access Journals (Sweden)

    Samuel J. Jackson

    2017-08-01

    Full Text Available Mouse models, including patient-derived xenograft mice, are widely used to address questions in cancer research. However, there are documented flaws in these models that can result in the misrepresentation of human tumour biology and limit the suitability of the model for translational research. A coordinated effort to promote the more widespread development and use of ‘non-animal human tissue’ models could provide a clinically relevant platform for many cancer studies, maximising the opportunities presented by human tissue resources such as biobanks. A number of key factors limit the wide adoption of non-animal human tissue models in cancer research, including deficiencies in the infrastructure and the technical tools required to collect, transport, store and maintain human tissue for lab use. Another obstacle is the long-standing cultural reliance on animal models, which can make researchers resistant to change, often because of concerns about historical data compatibility and losing ground in a competitive environment while new approaches are embedded in lab practice. There are a wide range of initiatives that aim to address these issues by facilitating data sharing and promoting collaborations between organisations and researchers who work with human tissue. The importance of coordinating biobanks and introducing quality standards is gaining momentum. There is an exciting opportunity to transform cancer drug discovery by optimising the use of human tissue and reducing the reliance on potentially less predictive animal models.

  5. Metabolomics studies in brain tissue: A review.

    Science.gov (United States)

    Gonzalez-Riano, Carolina; Garcia, Antonia; Barbas, Coral

    2016-10-25

    Brain is still an organ with a composition to be discovered but beyond that, mental disorders and especially all diseases that curse with dementia are devastating for the patient, the family and the society. Metabolomics can offer an alternative tool for unveiling new insights in the discovery of new treatments and biomarkers of mental disorders. Until now, most of metabolomic studies have been based on biofluids: serum/plasma or urine, because brain tissue accessibility is limited to animal models or post mortem studies, but even so it is crucial for understanding the pathological processes. Metabolomics studies of brain tissue imply several challenges due to sample extraction, along with brain heterogeneity, sample storage, and sample treatment for a wide coverage of metabolites with a wide range of concentrations of many lipophilic and some polar compounds. In this review, the current analytical practices for target and non-targeted metabolomics are described and discussed with emphasis on critical aspects: sample treatment (quenching, homogenization, filtration, centrifugation and extraction), analytical methods, as well as findings considering the used strategies. Besides that, the altered analytes in the different brain regions have been associated with their corresponding pathways to obtain a global overview of their dysregulation, trying to establish the link between altered biological pathways and pathophysiological conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Reference gene selection for quantitative gene expression studies during biological invasions: A test on multiple genes and tissues in a model ascidian Ciona savignyi.

    Science.gov (United States)

    Huang, Xuena; Gao, Yangchun; Jiang, Bei; Zhou, Zunchun; Zhan, Aibin

    2016-01-15

    As invasive species have successfully colonized a wide range of dramatically different local environments, they offer a good opportunity to study interactions between species and rapidly changing environments. Gene expression represents one of the primary and crucial mechanisms for rapid adaptation to local environments. Here, we aim to select reference genes for quantitative gene expression analysis based on quantitative Real-Time PCR (qRT-PCR) for a model invasive ascidian, Ciona savignyi. We analyzed the stability of ten candidate reference genes in three tissues (siphon, pharynx and intestine) under two key environmental stresses (temperature and salinity) in the marine realm based on three programs (geNorm, NormFinder and delta Ct method). Our results demonstrated only minor difference for stability rankings among the three methods. The use of different single reference gene might influence the data interpretation, while multiple reference genes could minimize possible errors. Therefore, reference gene combinations were recommended for different tissues - the optimal reference gene combination for siphon was RPS15 and RPL17 under temperature stress, and RPL17, UBQ and TubA under salinity treatment; for pharynx, TubB, TubA and RPL17 were the most stable genes under temperature stress, while TubB, TubA and UBQ were the best under salinity stress; for intestine, UBQ, RPS15 and RPL17 were the most reliable reference genes under both treatments. Our results suggest that the necessity of selection and test of reference genes for different tissues under varying environmental stresses. The results obtained here are expected to reveal mechanisms of gene expression-mediated invasion success using C. savignyi as a model species. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. The Use of a Fresh-Tissue Cadaver Model for the Instruction of Dermatological Procedures: A Laboratory Study for Training Medical Students.

    Science.gov (United States)

    Cervantes, Jose A; Costello, Collin M; Maarouf, Melody; McCrary, Hilary C; Zeitouni, Nathalie C

    2017-09-01

    A realistic model for the instruction of basic dermatologic procedural skills was developed, while simultaneously increasing medical student exposure to the field of dermatology. The primary purpose of the authors' study was to evaluate the utilization of a fresh-tissue cadaver model (FTCM) as a method for the instruction of common dermatologic procedures. The authors' secondary aim was to assess students' perceived clinical skills and overall perception of the field of dermatology after the lab. Nineteen first- and second-year medical students were pre- and post-tested on their ability to perform punch and excisional biopsies on a fresh-tissue cadaver. Students were then surveyed on their experience. Assessment of the cognitive knowledge gain and technical skills revealed a statistically significant improvement in all categories (p < .001). An analysis of the survey demonstrated that 78.9% were more interested in selecting dermatology as a career and 63.2% of participants were more likely to refer their future patients to a Mohs surgeon. An FTCM is a viable method for the instruction and training of dermatologic procedures. In addition, the authors conclude that an FTCM provides realistic instruction for common dermatologic procedures and enhances medical students' early exposure and interest in the field of dermatology.

  8. Development of a 3D bone marrow adipose tissue model.

    Science.gov (United States)

    Fairfield, Heather; Falank, Carolyne; Farrell, Mariah; Vary, Calvin; Boucher, Joshua M; Driscoll, Heather; Liaw, Lucy; Rosen, Clifford J; Reagan, Michaela R

    2018-01-26

    Over the past twenty years, evidence has accumulated that biochemically and spatially defined networks of extracellular matrix, cellular components, and interactions dictate cellular differentiation, proliferation, and function in a variety of tissue and diseases. Modeling in vivo systems in vitro has been undeniably necessary, but when simplified 2D conditions rather than 3D in vitro models are used, the reliability and usefulness of the data derived from these models decreases. Thus, there is a pressing need to develop and validate reliable in vitro models to reproduce specific tissue-like structures and mimic functions and responses of cells in a more realistic manner for both drug screening/disease modeling and tissue regeneration applications. In adipose biology and cancer research, these models serve as physiologically relevant 3D platforms to bridge the divide between 2D cultures and in vivo models, bringing about more reliable and translationally useful data to accelerate benchtop to bedside research. Currently, no model has been developed for bone marrow adipose tissue (BMAT), a novel adipose depot that has previously been overlooked as "filler tissue" but has more recently been recognized as endocrine-signaling and systemically relevant. Herein we describe the development of the first 3D, BMAT model derived from either human or mouse bone marrow (BM) mesenchymal stromal cells (MSCs). We found that BMAT models can be stably cultured for at least 3 months in vitro, and that myeloma cells (5TGM1, OPM2 and MM1S cells) can be cultured on these for at least 2 weeks. Upon tumor cell co-culture, delipidation occurred in BMAT adipocytes, suggesting a bidirectional relationship between these two important cell types in the malignant BM niche. Overall, our studies suggest that 3D BMAT represents a "healthier," more realistic tissue model that may be useful for elucidating the effects of MAT on tumor cells, and tumor cells on MAT, to identify novel therapeutic

  9. Mathematical modelling of tissue formation in chondrocyte filter cultures.

    Science.gov (United States)

    Catt, C J; Schuurman, W; Sengers, B G; van Weeren, P R; Dhert, W J A; Please, C P; Malda, J

    2011-12-17

    In the field of cartilage tissue engineering, filter cultures are a frequently used three-dimensional differentiation model. However, understanding of the governing processes of in vitro growth and development of tissue in these models is limited. Therefore, this study aimed to further characterise these processes by means of an approach combining both experimental and applied mathematical methods. A mathematical model was constructed, consisting of partial differential equations predicting the distribution of cells and glycosaminoglycans (GAGs), as well as the overall thickness of the tissue. Experimental data was collected to allow comparison with the predictions of the simulation and refinement of the initial models. Healthy mature equine chondrocytes were expanded and subsequently seeded on collagen-coated filters and cultured for up to 7 weeks. Resulting samples were characterised biochemically, as well as histologically. The simulations showed a good representation of the experimentally obtained cell and matrix distribution within the cultures. The mathematical results indicate that the experimental GAG and cell distribution is critically dependent on the rate at which the cell differentiation process takes place, which has important implications for interpreting experimental results. This study demonstrates that large regions of the tissue are inactive in terms of proliferation and growth of the layer. In particular, this would imply that higher seeding densities will not significantly affect the growth rate. A simple mathematical model was developed to predict the observed experimental data and enable interpretation of the principal underlying mechanisms controlling growth-related changes in tissue composition.

  10. Computer modeling the boron compound factor in normal brain tissue

    International Nuclear Information System (INIS)

    Gavin, P.R.; Huiskamp, R.; Wheeler, F.J.; Griebenow, M.L.

    1993-01-01

    The macroscopic distribution of borocaptate sodium (Na 2 B 12 H 11 SH or BSH) in normal tissues has been determined and can be accurately predicted from the blood concentration. The compound para-borono-phenylalanine (p-BPA) has also been studied in dogs and normal tissue distribution has been determined. The total physical dose required to reach a biological isoeffect appears to increase directly as the proportion of boron capture dose increases. This effect, together with knowledge of the macrodistribution, led to estimates of the influence of the microdistribution of the BSH compound. This paper reports a computer model that was used to predict the compound factor for BSH and p-BPA and, hence, the equivalent radiation in normal tissues. The compound factor would need to be calculated for other compounds with different distributions. This information is needed to design appropriate normal tissue tolerance studies for different organ systems and/or different boron compounds

  11. Multiphase poroelastic finite element models for soft tissue structures

    International Nuclear Information System (INIS)

    Simon, B.R.

    1992-01-01

    During the last two decades, biological structures with soft tissue components have been modeled using poroelastic or mixture-based constitutive laws, i.e., the material is viewed as a deformable (porous) solid matrix that is saturated by mobile tissue fluid. These structures exhibit a highly nonlinear, history-dependent material behavior; undergo finite strains; and may swell or shrink when tissue ionic concentrations are altered. Give the geometric and material complexity of soft tissue structures and that they are subjected to complicated initial and boundary conditions, finite element models (FEMs) have been very useful for quantitative structural analyses. This paper surveys recent applications of poroelastic and mixture-based theories and the associated FEMs for the study of the biomechanics of soft tissues, and indicates future directions for research in this area. Equivalent finite-strain poroelastic and mixture continuum biomechanical models are presented. Special attention is given to the identification of material properties using a porohyperelastic constitutive law ans a total Lagrangian view for the formulation. The associated FEMs are then formulated to include this porohyperelastic material response and finite strains. Extensions of the theory are suggested in order to include inherent viscoelasticity, transport phenomena, and swelling in soft tissue structures. A number of biomechanical research areas are identified, and possible applications of the porohyperelastic and mixture-based FEMs are suggested. 62 refs., 11 figs., 3 tabs

  12. Computational model of soft tissues in the human upper airway.

    Science.gov (United States)

    Pelteret, J-P V; Reddy, B D

    2012-01-01

    This paper presents a three-dimensional finite element model of the tongue and surrounding soft tissues with potential application to the study of sleep apnoea and of linguistics and speech therapy. The anatomical data was obtained from the Visible Human Project, and the underlying histological data was also extracted and incorporated into the model. Hyperelastic constitutive models were used to describe the material behaviour, and material incompressibility was accounted for. An active Hill three-element muscle model was used to represent the muscular tissue of the tongue. The neural stimulus for each muscle group was determined through the use of a genetic algorithm-based neural control model. The fundamental behaviour of the tongue under gravitational and breathing-induced loading is investigated. It is demonstrated that, when a time-dependent loading is applied to the tongue, the neural model is able to control the position of the tongue and produce a physiologically realistic response for the genioglossus.

  13. Animal models for bone tissue engineering and modelling disease

    Science.gov (United States)

    Griffin, Michelle

    2018-01-01

    ABSTRACT Tissue engineering and its clinical application, regenerative medicine, are instructing multiple approaches to aid in replacing bone loss after defects caused by trauma or cancer. In such cases, bone formation can be guided by engineered biodegradable and nonbiodegradable scaffolds with clearly defined architectural and mechanical properties informed by evidence-based research. With the ever-increasing expansion of bone tissue engineering and the pioneering research conducted to date, preclinical models are becoming a necessity to allow the engineered products to be translated to the clinic. In addition to creating smart bone scaffolds to mitigate bone loss, the field of tissue engineering and regenerative medicine is exploring methods to treat primary and secondary bone malignancies by creating models that mimic the clinical disease manifestation. This Review gives an overview of the preclinical testing in animal models used to evaluate bone regeneration concepts. Immunosuppressed rodent models have shown to be successful in mimicking bone malignancy via the implantation of human-derived cancer cells, whereas large animal models, including pigs, sheep and goats, are being used to provide an insight into bone formation and the effectiveness of scaffolds in induced tibial or femoral defects, providing clinically relevant similarity to human cases. Despite the recent progress, the successful translation of bone regeneration concepts from the bench to the bedside is rooted in the efforts of different research groups to standardise and validate the preclinical models for bone tissue engineering approaches. PMID:29685995

  14. 3D Bioprinting of Tissue/Organ Models.

    Science.gov (United States)

    Pati, Falguni; Gantelius, Jesper; Svahn, Helene Andersson

    2016-04-04

    In vitro tissue/organ models are useful platforms that can facilitate systematic, repetitive, and quantitative investigations of drugs/chemicals. The primary objective when developing tissue/organ models is to reproduce physiologically relevant functions that typically require complex culture systems. Bioprinting offers exciting prospects for constructing 3D tissue/organ models, as it enables the reproducible, automated production of complex living tissues. Bioprinted tissues/organs may prove useful for screening novel compounds or predicting toxicity, as the spatial and chemical complexity inherent to native tissues/organs can be recreated. In this Review, we highlight the importance of developing 3D in vitro tissue/organ models by 3D bioprinting techniques, characterization of these models for evaluating their resemblance to native tissue, and their application in the prioritization of lead candidates, toxicity testing, and as disease/tumor models. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Modelling Brain Tissue using Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Dyrby, Tim Bjørn

    2008-01-01

    Diffusion MRI, or diffusion weighted imaging (DWI), is a technique that measures the restricted diffusion of water molecules within brain tissue. Different reconstruction methods quantify water-diffusion anisotropy in the intra- and extra-cellular spaces of the neural environment. Fibre tracking...... models then use the directions of greatest diffusion as estimates of white matter fibre orientation. Several fibre tracking algorithms have emerged in the last few years that provide reproducible visualizations of three-dimensional fibre bundles. One class of these algorithms is probabilistic...... the possibility of using high-field experimental MR scanners and long scanning times, thereby significantly improving the signal-to-noise ratio (SNR) and anatomical resolution. Moreover, many of the degrading effects observed in vivo, such as physiological noise, are no longer present. However, the post mortem...

  16. A biphasic model for bleeding in soft tissue

    Science.gov (United States)

    Chang, Yi-Jui; Chong, Kwitae; Eldredge, Jeff D.; Teran, Joseph; Benharash, Peyman; Dutson, Erik

    2017-11-01

    The modeling of blood passing through soft tissues in the body is important for medical applications. The current study aims to capture the effect of tissue swelling and the transport of blood under bleeding or hemorrhaging conditions. The soft tissue is considered as a non-static poro-hyperelastic material with liquid-filled voids. A biphasic formulation effectively, a generalization of Darcy's law-is utilized, treating the phases as occupying fractions of the same volume. The interaction between phases is captured through a Stokes-like friction force on their relative velocities and a pressure that penalizes deviations from volume fractions summing to unity. The soft tissue is modeled as a hyperelastic material with a typical J-shaped stress-strain curve, while blood is considered as a Newtonian fluid. The method of Smoothed Particle Hydrodynamics is used to discretize the conservation equations based on the ease of treating free surfaces in the liquid. Simulations of swelling under acute hemorrhage and of draining under gravity and compression will be demonstrated. Ongoing progress in modeling of organ tissues under injuries and surgical conditions will be discussed.

  17. A tissue in the tissue: models of microvascular plasticity

    DEFF Research Database (Denmark)

    Jacobsen, Jens Christian Brings; Hornbech, Morten Sonne; Holstein-Rathlou, Niels-Henrik

    2009-01-01

    network. The pronounced plasticity and the inherently complex nature of vascular networks have spurred an enduring interest in mathematical modeling of the microcirculation. This has been advanced by the continuous increase in computing power over recent decades enabling simulation of increasingly...

  18. A dynamic cellular vertex model of growing epithelial tissues

    Science.gov (United States)

    Lin, Shao-Zhen; Li, Bo; Feng, Xi-Qiao

    2017-04-01

    Intercellular interactions play a significant role in a wide range of biological functions and processes at both the cellular and tissue scales, for example, embryogenesis, organogenesis, and cancer invasion. In this paper, a dynamic cellular vertex model is presented to study the morphomechanics of a growing epithelial monolayer. The regulating role of stresses in soft tissue growth is revealed. It is found that the cells originating from the same parent cell in the monolayer can orchestrate into clustering patterns as the tissue grows. Collective cell migration exhibits a feature of spatial correlation across multiple cells. Dynamic intercellular interactions can engender a variety of distinct tissue behaviors in a social context. Uniform cell proliferation may render high and heterogeneous residual compressive stresses, while stress-regulated proliferation can effectively release the stresses, reducing the stress heterogeneity in the tissue. The results highlight the critical role of mechanical factors in the growth and morphogenesis of epithelial tissues and help understand the development and invasion of epithelial tumors.

  19. A Wearable Goggle Navigation System for Dual-Mode Optical and Ultrasound Localization of Suspicious Lesions: Validation Studies Using Tissue-Simulating Phantoms and an Ex Vivo Human Breast Tissue Model.

    Directory of Open Access Journals (Sweden)

    Zeshu Zhang

    Full Text Available Surgical resection remains the primary curative treatment for many early-stage cancers, including breast cancer. The development of intraoperative guidance systems for identifying all sites of disease and improving the likelihood of complete surgical resection is an area of active ongoing research, as this can lead to a decrease in the need of subsequent additional surgical procedures. We develop a wearable goggle navigation system for dual-mode optical and ultrasound imaging of suspicious lesions. The system consists of a light source module, a monochromatic CCD camera, an ultrasound system, a Google Glass, and a host computer. It is tested in tissue-simulating phantoms and an ex vivo human breast tissue model. Our experiments demonstrate that the surgical navigation system provides useful guidance for localization and core needle biopsy of simulated tumor within the tissue-simulating phantom, as well as a core needle biopsy and subsequent excision of Indocyanine Green (ICG-fluorescing sentinel lymph nodes. Our experiments support the contention that this wearable goggle navigation system can be potentially very useful and fully integrated by the surgeon for optimizing many aspects of oncologic surgery. Further engineering optimization and additional in vivo clinical validation work is necessary before such a surgical navigation system can be fully realized in the everyday clinical setting.

  20. An electromechanical based deformable model for soft tissue simulation.

    Science.gov (United States)

    Zhong, Yongmin; Shirinzadeh, Bijan; Smith, Julian; Gu, Chengfan

    2009-11-01

    Soft tissue deformation is of great importance to surgery simulation. Although a significant amount of research efforts have been dedicated to simulating the behaviours of soft tissues, modelling of soft tissue deformation is still a challenging problem. This paper presents a new deformable model for simulation of soft tissue deformation from the electromechanical viewpoint of soft tissues. Soft tissue deformation is formulated as a reaction-diffusion process coupled with a mechanical load. The mechanical load applied to a soft tissue to cause a deformation is incorporated into the reaction-diffusion system, and consequently distributed among mass points of the soft tissue. Reaction-diffusion of mechanical load and non-rigid mechanics of motion are combined to govern the simulation dynamics of soft tissue deformation. An improved reaction-diffusion model is developed to describe the distribution of the mechanical load in soft tissues. A three-layer artificial cellular neural network is constructed to solve the reaction-diffusion model for real-time simulation of soft tissue deformation. A gradient based method is established to derive internal forces from the distribution of the mechanical load. Integration with a haptic device has also been achieved to simulate soft tissue deformation with haptic feedback. The proposed methodology does not only predict the typical behaviours of living tissues, but it also accepts both local and large-range deformations. It also accommodates isotropic, anisotropic and inhomogeneous deformations by simple modification of diffusion coefficients.

  1. Y-90 SPECT ML image reconstruction with a new model for tissue-dependent bremsstrahlung production using CT information: a proof-of-concept study

    Science.gov (United States)

    Lim, Hongki; Fessler, Jeffrey A.; Wilderman, Scott J.; Brooks, Allen F.; Dewaraja, Yuni K.

    2018-06-01

    While the yield of positrons used in Y-90 PET is independent of tissue media, Y-90 SPECT imaging is complicated by the tissue dependence of bremsstrahlung photon generation. The probability of bremsstrahlung production is proportional to the square of the atomic number of the medium. Hence, the same amount of activity in different tissue regions of the body will produce different numbers of bremsstrahlung photons. Existing reconstruction methods disregard this tissue-dependency, potentially impacting both qualitative and quantitative imaging of heterogeneous regions of the body such as bone with marrow cavities. In this proof-of-concept study, we propose a new maximum-likelihood method that incorporates bremsstrahlung generation probabilities into the system matrix, enabling images of the desired Y-90 distribution to be reconstructed instead of the ‘bremsstrahlung distribution’ that is obtained with existing methods. The tissue-dependent probabilities are generated by Monte Carlo simulation while bone volume fractions for each SPECT voxel are obtained from co-registered CT. First, we demonstrate the tissue dependency in a SPECT/CT imaging experiment with Y-90 in bone equivalent solution and water. Visually, the proposed reconstruction approach better matched the true image and the Y-90 PET image than the standard bremsstrahlung reconstruction approach. An XCAT phantom simulation including bone and marrow regions also demonstrated better agreement with the true image using the proposed reconstruction method. Quantitatively, compared with the standard reconstruction, the new method improved estimation of the liquid bone:water activity concentration ratio by 40% in the SPECT measurement and the cortical bone:marrow activity concentration ratio by 58% in the XCAT simulation.

  2. Tissue

    Directory of Open Access Journals (Sweden)

    David Morrissey

    2012-01-01

    Full Text Available Purpose. In vivo gene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expression in vivo in mice and ex vivo in human tissues. Methods. Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadriceps in vivo was examined. Temporal control was assessed using a doxycycline-inducible system. An ex vivo model was developed and optimised using murine tissue, and applied in ex vivo human tissue. Results. In vivo plasmid-based transgene expression did not silence in murine muscle, unlike in liver. Although maximum luciferase expression was higher in muscle with adenoviral delivery compared with plasmid, expression reduced over time. The inducible promoter cassette successfully regulated gene expression with maximum levels a factor of 11 greater than baseline. Expression was re-induced to a similar level on a temporal basis. Luciferase expression was readily detected ex vivo in human muscle and tendon. Conclusions. Plasmid constructs resulted in long-term in vivo gene expression in skeletal muscle, in a controllable fashion utilising an inducible promoter in combination with oral agents. Successful plasmid gene transfection in human ex vivo mesenchymal tissue was demonstrated for the first time.

  3. Tissue Acoustoelectric Effect Modeling From Solid Mechanics Theory.

    Science.gov (United States)

    Song, Xizi; Qin, Yexian; Xu, Yanbin; Ingram, Pier; Witte, Russell S; Dong, Feng

    2017-10-01

    The acoustoelectric (AE) effect is a basic physical phenomenon, which underlies the changes made in the conductivity of a medium by the application of focused ultrasound. Recently, based on the AE effect, several biomedical imaging techniques have been widely studied, such as ultrasound-modulated electrical impedance tomography and ultrasound current source density imaging. To further investigate the mechanism of the AE effect in tissue and to provide guidance for such techniques, we have modeled the tissue AE effect using the theory of solid mechanics. Both bulk compression and thermal expansion of tissue are considered and discussed. Computation simulation shows that the muscle AE effect result, conductivity change rate, is 3.26×10 -3 with 4.3-MPa peak pressure, satisfying the theoretical value. Bulk compression plays the main role for muscle AE effect, while thermal expansion makes almost no contribution to it. In addition, the AE signals of porcine muscle are measured at different focal positions. With the same magnitude order and the same change trend, the experiment result confirms that the simulation result is effective. Both simulation and experimental results validate that tissue AE effect modeling using solid mechanics theory is feasible, which is of significance for the further development of related biomedical imaging techniques.

  4. Theoretical model of intravascular paramagnetic tracers effect on tissue relaxation

    DEFF Research Database (Denmark)

    Kjølby, Birgitte Fuglsang; Østergaard, Leif; Kiselev, Valerij G

    2006-01-01

    The concentration of MRI tracers cannot be measured directly by MRI and is commonly evaluated indirectly using their relaxation effect. This study develops a comprehensive theoretical model to describe the transverse relaxation in perfused tissue caused by intravascular tracers. The model takes...... into account a number of individual compartments. The signal dephasing is simulated in a semianalytical way by embedding Monte Carlo simulations in the framework of analytical theory. This approach yields a tool for fast, realistic simulation of the change in the transverse relaxation. The results indicate...... with bulk blood. The enhancement of relaxation in tissue is due to the contrast in magnetic susceptibility between blood vessels and parenchyma induced by the presence of paramagnetic tracer. Beyond the perfusion measurements, the results can be applied to quantitation of functional MRI and to vessel size...

  5. Study on tissue culture for Gelidium seedling

    Science.gov (United States)

    Pei, Lu-Qing; Luo, Qi-Jun; Fei, Zhi-Qing; Ma, Bin

    1996-06-01

    As seedling culture is a crucial factor for successful cultivation of Gelidium, the authors researched tissue culture technology for producing seedlings. The morphogeny and experimental ecology were observed and studied fully in 2 5 mm isolated tissue fragments. Regeneration, appearance of branching creepers and attaching structure and new erect seedlings production and development were studied. Fragments were sown on bamboo slice and vinylon rope. The seedlings were cultured 20 30 days indoor, then cultured in the sea, where the density of erect seedlings was 3 19 seedlings/cm2, growth rate was 3.84% day. The frond arising from seedlings directly was up to 10 cm per year. The ecological conditions for regenerated seedlings are similar to the natural ones. The regenerated seedlings are suitable for raft culture in various sea areas.

  6. Micromechanics and constitutive modeling of connective soft tissues.

    Science.gov (United States)

    Fallah, A; Ahmadian, M T; Firozbakhsh, K; Aghdam, M M

    2016-07-01

    In this paper, a micromechanical model for connective soft tissues based on the available histological evidences is developed. The proposed model constituents i.e. collagen fibers and ground matrix are considered as hyperelastic materials. The matrix material is assumed to be isotropic Neo-Hookean while the collagen fibers are considered to be transversely isotropic hyperelastic. In order to take into account the effects of tissue structure in lower scales on the macroscopic behavior of tissue, a strain energy density function (SEDF) is developed for collagen fibers based on tissue hierarchical structure. Macroscopic response and properties of tissue are obtained using the numerical homogenization method with the help of ABAQUS software. The periodic boundary conditions and the proposed constitutive models are implemented into ABAQUS using the DISP and the UMAT subroutines, respectively. The existence of the solution and stable material behavior of proposed constitutive model for collagen fibers are investigated based on the poly-convexity condition. Results of the presented micromechanics model for connective tissues are compared and validated with available experimental data. Effects of geometrical and material parameters variation at microscale on macroscopic mechanical behavior of tissues are investigated. The results show that decrease in collagen content of the connective tissues like the tendon due to diseases leads 20% more stretch than healthy tissue under the same load which can results in connective tissue malfunction and hypermobility in joints. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. A longitudinal study of whole body, tissue, and cellular physiology in a mouse model of fibrosing NASH with high fidelity to the human condition.

    Science.gov (United States)

    Krishnan, Anuradha; Abdullah, Tasduq Sheikh; Mounajjed, Taofic; Hartono, Stella; McConico, Andrea; White, Thomas; LeBrasseur, Nathan; Lanza, Ian; Nair, Sreekumaran; Gores, Gregory; Charlton, Michael

    2017-06-01

    The sequence of events that lead to inflammation and fibrosing nonalcoholic steatohepatitis (NASH) is incompletely understood. Hence, we investigated the chronology of whole body, tissue, and cellular events that occur during the evolution of diet-induced NASH. Male C57Bl/6 mice were assigned to a fast-food (FF; high calorie, high cholesterol, high fructose) or standard-chow (SC) diet over a period of 36 wk. Liver histology, body composition, mitochondrial respiration, metabolic rate, gene expression, and hepatic lipid content were analyzed. Insulin resistance [homeostasis model assessment-insulin resistance (HOMA-IR)] increased 10-fold after 4 wk. Fibrosing NASH was fully established by 16 wk. Total hepatic lipids increased by 4 wk and remained two- to threefold increased throughout. Hepatic triglycerides declined from sixfold increase at 8 wk to threefold increase by 36 wk. In contrast, hepatic cholesterol levels steadily increased from baseline at 8 wk to twofold by 36 wk. The hepatic immune cell population altered over time with macrophages persisting beyond 16 wk. Mitochondrial oxygen flux rates of FF mice diet were uniformly lower with all the tested substrates (13-276 pmol·s -1 ·ml -1 per unit citrate synthase) than SC mice (17-394 pmol·s -1 ·ml -1 per unit citrate synthase) and was accompanied by decreased mitochondrial:nuclear gene copy number ratios after 4 wk. Metabolic rate was lower in FF mice. Mitochondrial glutathione was significantly decreased at 24 wk in FF mice. Expression of dismutases and catalase was also decreased in FF mice. The evolution of NASH in the FF diet-induced model is multiphasic, particularly in terms of hepatic lipid composition. Insulin resistance precedes hepatic inflammation and fibrosis. Mitochondrial dysfunction and depletion occur after the histological features of NASH are apparent. Collectively, these observations provide a unique overview of the sequence of changes that coevolve with the histological evolution of

  8. Soft Tissue Biomechanical Modeling for Computer Assisted Surgery

    CERN Document Server

    2012-01-01

      This volume focuses on the biomechanical modeling of biological tissues in the context of Computer Assisted Surgery (CAS). More specifically, deformable soft tissues are addressed since they are the subject of the most recent developments in this field. The pioneering works on this CAS topic date from the 1980's, with applications in orthopaedics and biomechanical models of bones. More recently, however, biomechanical models of soft tissues have been proposed since most of the human body is made of soft organs that can be deformed by the surgical gesture. Such models are much more complicated to handle since the tissues can be subject to large deformations (non-linear geometrical framework) as well as complex stress/strain relationships (non-linear mechanical framework). Part 1 of the volume presents biomechanical models that have been developed in a CAS context and used during surgery. This is particularly new since most of the soft tissues models already proposed concern Computer Assisted Planning, with ...

  9. The involvement of oxidative stress in the mechanisms of damaging cadmium action in bone tissue: A study in a rat model of moderate and relatively high human exposure

    International Nuclear Information System (INIS)

    Brzoska, Malgorzata M.; Rogalska, Joanna; Kupraszewicz, Elzbieta

    2011-01-01

    It was investigated whether cadmium (Cd) may induce oxidative stress in the bone tissue in vivo and in this way contribute to skeleton damage. Total antioxidative status (TAS), antioxidative enzymes (glutathione peroxidase, superoxide dismutase, catalase), total oxidative status (TOS), hydrogen peroxide (H 2 O 2 ), lipid peroxides (LPO), total thiol groups (TSH) and protein carbonyl groups (PC) as well as Cd in the bone tissue at the distal femoral epiphysis and femoral diaphysis of the male rats that received drinking water containing 0, 5, or 50 mg Cd/l for 6 months were measured. Cd, depending on the level of exposure and bone location, decreased the bone antioxidative capacity and enhanced its oxidative status resulting in oxidative stress and oxidative protein and/or lipid modification. The treatment with 5 and 50 mg Cd/l decreased TAS and activities of antioxidative enzymes as well as increased TOS and concentrations of H 2 O 2 and PC at the distal femur. Moreover, at the higher exposure, the concentration of LPO increased and that of TSH decreased. The Cd-induced changes in the oxidative/antioxidative balance of the femoral diaphysis, abundant in cortical bone, were less advanced than at the distal femur, where trabecular bone predominates. The results provide evidence that, even moderate, exposure to Cd induces oxidative stress and oxidative modifications in the bone tissue. Numerous correlations noted between the indices of oxidative/antioxidative bone status, and Cd accumulation in the bone tissue as well as indices of bone turnover and bone mineral status, recently reported by us (Toxicology 2007, 237, 89-103) in these rats, allow for the hypothesis that oxidative stress is involved in the mechanisms of damaging Cd action in the skeleton. The paper is the first report from an in vivo study indicating that Cd may affect bone tissue through disorders in its oxidative/antioxidative balance resulting in oxidative stress.

  10. The assessment of cold atmospheric plasma treatment of DNA in synthetic models of tissue fluid, tissue and cells

    Science.gov (United States)

    Szili, Endre J.; Gaur, Nishtha; Hong, Sung-Ha; Kurita, Hirofumi; Oh, Jun-Seok; Ito, Masafumi; Mizuno, Akira; Hatta, Akimitsu; Cowin, Allison J.; Graves, David B.; Short, Robert D.

    2017-07-01

    There is a growing literature database that demonstrates the therapeutic potential of cold atmospheric plasma (herein referred to as plasma). Given the breadth of proposed applications (e.g. from teeth whitening to cancer therapy) and vast gamut of plasma devices being researched, it is timely to consider plasma interactions with specific components of the cell in more detail. Plasma can produce highly reactive oxygen and nitrogen species (RONS) such as the hydroxyl radical (OH•), peroxynitrite (ONOO-) and superoxide (\\text{O}2- ) that would readily modify essential biomolecules such as DNA. These modifications could in principle drive a wide range of biological processes. Against this possibility, the reported therapeutic action of plasmas are not underpinned by a particularly deep knowledge of the potential plasma-tissue, -cell or -biomolecule interactions. In this study, we aim to partly address this issue by developing simple models to study plasma interactions with DNA, in the form of DNA-strand breaks. This is carried out using synthetic models of tissue fluid, tissue and cells. We argue that this approach makes experimentation simpler, more cost-effective and faster than compared to working with real biological materials and cells. Herein, a helium plasma jet source was utilised for these experiments. We show that the plasma jet readily induced DNA-strand breaks in the tissue fluid model and in the cell model, surprisingly without any significant poration or rupture of the phospholipid membrane. In the plasma jet treatment of the tissue model, DNA-strand breaks were detected in the tissue mass after pro-longed treatment (on the time-scale of minutes) with no DNA-strand breaks being detected in the tissue fluid model underneath the tissue model. These data are discussed in the context of the therapeutic potential of plasma.

  11. Implications of human tissue studies for radiation protection

    International Nuclear Information System (INIS)

    Kathren, R.L.

    1988-01-01

    Through radiochemical analysis of voluntary tissue donations, the U.S. Transuranium and Uranium Registries (USTR) are gaining improved understanding of the distribution and biokinetics of actinide elements in occupationally exposed persons. Evaluation of the first two whole-body contributions to the USTR revealed an inverse proportionality between actinide concentration and bone ash. The analysis of a whole body with significant 241 Am deposition indicated a significantly shorter half-time in liver and a greater fraction resident in the skeleton than predicted by existing models. Other studies with tissues obtained at autopsy suggest that existing biokinetic models for 238 Pu and 241 Am and the currently accepted models and limits on intake, which use these models as their basis, may be inaccurately implying that revisions of existing safety standards may be necessary. Other studies of the registries are designed to evaluate in-vivo estimates of actinide deposition with those derived from postmortem tissue analysis, to compare results of animal experiments with human data, and to review histopathologic slides for tissue changes that might be attributable to exposure to transuranic elements. The implications of these recent findings and other work of the registries is discussed from the standpoint of this potential effect on biokinetic modeling, internal dose assessment, and safety standards and operational health physics practices

  12. Implications of human tissue studies for radiation protection.

    Science.gov (United States)

    Kathren, R L

    1988-08-01

    Through radiochemical analysis of voluntary tissue donations, the U.S. Transuranium and Uranium Registries (USTR) are gaining improved understanding of the distribution and biokinetics of actinide elements in occupationally exposed persons. Evaluation of the first two whole-body contributions to the USTR revealed an inverse proportionality between actinide concentration and bone ash. The analysis of a whole body with significant 241Am deposition indicated a significantly shorter half-time in liver and a greater fraction resident in the skeleton than predicted by existing models. Other studies with tissues obtained at autopsy suggest that existing biokinetic models for 238Pu and 241Am and the currently accepted models and limits on intake, which use these models as their basis, may be inaccurately implying that revisions of existing safety standards may be necessary. Other studies of the registries are designed to evaluate in-vivo estimates of actinide deposition with those derived from postmortem tissue analysis, to compare results of animal experiments with human data, and to review histopathologic slides for tissue changes that might be attributable to exposure to transuranic elements. The implications of these recent findings and other work of the registries is discussed from the standpoint of this potential effect on biokinetic modeling, internal dose assessment, and safety standards and operational health physics practices.

  13. Modeling the development of tissue engineered cartilage

    NARCIS (Netherlands)

    Sengers, B.G.

    2005-01-01

    The limited healing capacity of articular cartilage forms a major clinical problem. In general, current treatments of cartilage damage temporarily reliefs symptoms, but fail in the long term. Tissue engineering (TE) has been proposed as a more permanent repair strategy. Cartilage TE aims at

  14. Training for laparoscopic Nissen fundoplication with a newly designed model: a replacement for animal tissue models?

    Science.gov (United States)

    Christie, Lorna; Goossens, Richard; Jakimowicz, Jack J.

    2010-01-01

    Background To bridge the early learning curve for laparoscopic Nissen fundoplication from the clinical setting to a safe environment, training models can be used. This study aimed to develop a reusable, low-cost model to be used for training in laparoscopic Nissen fundoplication procedure as an alternative to the use of animal tissue models. Methods From artificial organs and tissue, an anatomic model of the human upper abdomen was developed for training in performing laparoscopic Nissen fundoplication. The 20 participants and tutors in the European Association for Endoscopic Surgery (EAES) upper gastrointestinal surgery course completed four complementary tasks of laparoscopic Nissen fundoplication with the artificial model, then compared the realism, haptic feedback, and training properties of the model with those of animal tissue models. Results The main difference between the two training models was seen in the properties of the stomach. The wrapping of the stomach in the artificial model was rated significantly lower than that in the animal tissue model (mean, 3.6 vs. 4.2; p = 0.010). The main criticism of the stomach of the artificial model was that it was too rigid for making a proper wrap. The suturing of the stomach wall, however, was regarded as fairly realistic (mean, 3.6). The crura on the artificial model were rated better (mean, 4.3) than those on the animal tissue (mean, 4.0), although the difference was not significant. The participants regarded the model as a good to excellent (mean, 4.3) training tool. Conclusion The newly developed model is regarded as a good tool for training in laparoscopic Nissen fundoplication procedure. It is cheaper, more durable, and more readily available for training and can therefore be used in every training center. The stomach of this model, however, still needs improvement because it is too rigid for making the wrap. PMID:20526629

  15. 2010 Great Lakes Human Health Fish Tissue Study Fish Tissue Data Dictionary

    Science.gov (United States)

    The Office of Science and Technology (OST) is providing the fish tissue results from the 2010 Great Lakes Human Health Fish Tissue Study (GLHHFTS). This document includes the “data dictionary” for Mercury, PFC, PBDE and PCBs.

  16. Modeling biological tissue growth: discrete to continuum representations.

    Science.gov (United States)

    Hywood, Jack D; Hackett-Jones, Emily J; Landman, Kerry A

    2013-09-01

    There is much interest in building deterministic continuum models from discrete agent-based models governed by local stochastic rules where an agent represents a biological cell. In developmental biology, cells are able to move and undergo cell division on and within growing tissues. A growing tissue is itself made up of cells which undergo cell division, thereby providing a significant transport mechanism for other cells within it. We develop a discrete agent-based model where domain agents represent tissue cells. Each agent has the ability to undergo a proliferation event whereby an additional domain agent is incorporated into the lattice. If a probability distribution describes the waiting times between proliferation events for an individual agent, then the total length of the domain is a random variable. The average behavior of these stochastically proliferating agents defining the growing lattice is determined in terms of a Fokker-Planck equation, with an advection and diffusion term. The diffusion term differs from the one obtained Landman and Binder [J. Theor. Biol. 259, 541 (2009)] when the rate of growth of the domain is specified, but the choice of agents is random. This discrepancy is reconciled by determining a discrete-time master equation for this process and an associated asymmetric nonexclusion random walk, together with consideration of synchronous and asynchronous updating schemes. All theoretical results are confirmed with numerical simulations. This study furthers our understanding of the relationship between agent-based rules, their implementation, and their associated partial differential equations. Since tissue growth is a significant cellular transport mechanism during embryonic growth, it is important to use the correct partial differential equation description when combining with other cellular functions.

  17. Mathematical models of tumour and normal tissue response

    International Nuclear Information System (INIS)

    Jones, B.; Dale, R.G.; Charing Cross Group of Hospitals, London

    1999-01-01

    The historical application of mathematics in the natural sciences and in radiotherapy is compared. The various forms of mathematical models and their limitations are discussed. The Linear Quadratic (LQ) model can be modified to include (i) radiobiological parameter changes that occur during fractionated radiotherapy, (ii) situations such as focal forms of radiotherapy, (iii) normal tissue responses, and (iv) to allow for the process of optimization. The inclusion of a variable cell loss factor in the LQ model repopulation term produces a more flexible clonogenic doubling time, which can simulate the phenomenon of 'accelerated repopulation'. Differential calculus can be applied to the LQ model after elimination of the fraction number integers. The optimum dose per fraction (maximum cell kill relative to a given normal tissue fractionation sensitivity) is then estimated from the clonogen doubling times and the radiosensitivity parameters (or α/β ratios). Economic treatment optimization is described. Tumour volume studies during or following teletherapy are used to optimize brachytherapy. The radiation responses of both individual tumours and tumour populations (by random sampling 'Monte-Carlo' techniques from statistical ranges of radiobiological and physical parameters) can be estimated. Computerized preclinical trials can be used to guide choice of dose fractionation scheduling in clinical trials. The potential impact of gene and other biological therapies on the results of radical radiotherapy are testable. New and experimentally testable hypotheses are generated from limited clinical data by exploratory modelling exercises. (orig.)

  18. High-dose mode of mortality in Tribolium: A model system for study of radiation injury and repair in non-proliferative tissues

    International Nuclear Information System (INIS)

    Cheng, Chihing Christina.

    1989-01-01

    With appropriate doses of ionizing radiation, both the acute, or lethal-midlethal, dose-independent pattern of mortality, and the hyperacute, dose-dependent pattern, were demonstrated within a single insect genus (Tribolium). This demonstration provides resolution of apparently contradictory reports of insect radiation responses in terms of doses required to cause lethality and those based on survival time as a function of dose. A dose-dependent mortality pattern was elicited in adult Tribolium receiving high doses, viz., 300 Gy or greater; its time course was complete in 10 days, before the dose-independent pattern of mortality began. Visual observations of heavily-irradiated Tribolium suggested neural and/or neuromuscular damage, as had been previously proposed by others for lethally-irradiated wasps, flies, and mosquitoes. Results of experiments using fractionated high doses supported the suggestion that the hyperacute or high-dose mode of death is the result of damage to nonproliferative tissues. Relative resistance of a strain to the hyperacute or high-dose mode of death was not correlated with resistance to the midlethal mode, which is believed to be the result of damage to the proliferative cells of the midgut. Using the high-dose mode of death as a model of radiation damage to nonproliferative tissues, the effects of age, and of a moderate priming dose were assessed. Beetles showed age-related increase in sensitivity to the high-dose mode of death, suggesting a decline in capacity to repair radiation damage to postmitotic tissue. This correlated with a decrease (50%) in the amount of repair reflected in the sparing effect of dose-fractionation (SDF) between the age of 1 to 3 months. The age related increase in radiosensitivity was reduced by a moderate priming dose (40 or 65 Gy) given at a young age

  19. Microstructure based hygromechanical modelling of deformation of fruit tissue

    Science.gov (United States)

    Abera, M. K.; Wang, Z.; Verboven, P.; Nicolai, B.

    2017-10-01

    Quality parameters such as firmness and susceptibility to mechanical damage are affected by the mechanical properties of fruit tissue. Fruit tissue is composed of turgid cells that keep cell walls under tension, and intercellular gas spaces where cell walls of neighboring cells have separated. How the structure and properties of these complex microstructures are affecting tissue mechanics is difficult to unravel experimentally. In this contribution, a modelling methodology is presented to calculate the deformation of apple fruit tissue affected by differences in structure and properties of cells and cell walls. The model can be used to perform compression experiments in silico using a hygromechanical model that computes the stress development and water loss during tissue deformation, much like in an actual compression test. The advantage of the model is that properties and structure can be changed to test the influence on the mechanical deformation process. The effect of microstructure, turgor pressure, cell membrane permeability, wall thickness and damping) on the compressibility of the tissue was simulated. Increasing the turgor pressure and thickness of the cell walls results in increased compression resistance of apple tissue increases, as do decreasing cell size and porosity. Geometric variability of the microstructure of tissues plays a major role, affecting results more than other model parameters. Different fruit cultivars were compared, and it was demonstrated, that microstructure variations within a cultivar are so large that interpretation of cultivar-specific effects is difficult.

  20. Reference Models for Multi-Layer Tissue Structures

    Science.gov (United States)

    2016-09-01

    function of multi-layer tissues (etiology and management of pressure ulcers ). What was the impact on other disciplines? As part of the project, a data...simplification to develop cost -effective models of surface manipulation of multi-layer tissues. Deliverables. Specimen- (or subject) and region-specific...simplification to develop cost -effective models of surgical manipulation. Deliverables. Specimen-specific surrogate models of upper legs confirmed against data

  1. Heat transfer modelling of pulsed laser-tissue interaction

    Science.gov (United States)

    Urzova, J.; Jelinek, M.

    2018-03-01

    Due to their attributes, the application of medical lasers is on the rise in numerous medical fields. From a biomedical point of view, the most interesting applications are the thermal interactions and the photoablative interactions, which effectively remove tissue without excessive heat damage to the remaining tissue. The objective of this work is to create a theoretical model for heat transfer in the tissue following its interaction with the laser beam to predict heat transfer during medical laser surgery procedures. The dimensions of the ablated crater (shape and ablation depth) were determined by computed tomography imaging. COMSOL Multiphysics software was used for temperature modelling. The parameters of tissue and blood, such as density, specific heat capacity, thermal conductivity and diffusivity, were calculated from the chemical ratio. The parameters of laser-tissue interaction, such as absorption and reflection coefficients, were experimentally determined. The parameters of the laser beam were power density, repetition frequency, pulse length and spot dimensions. Heat spreading after laser interaction with tissue was captured using a Fluke thermal camera. The model was verified for adipose tissue, skeletal muscle tissue and heart muscle tissue.

  2. Models for radiation-induced tissue degeneration and conceptualization of rehabilitation of irradiated tissue by cell therapy

    International Nuclear Information System (INIS)

    Phulpin, Berengere

    2011-01-01

    Radiation therapy induced acute and late sequelae within healthy tissue included in the irradiated area. In general, lesions are characterized by ischemia, cell apoptosis and fibrosis. In this context, cell therapy using bone marrow mesenchymal stem cells (BMSC) might represent an attractive new therapeutic approach, based partly on their angiogenic ability and their involvement in the natural processes of tissue repair. The first part of this work consisted in the development of experimental mouse model of radio-induced tissue degeneration similar to that occurring after radiotherapy. The aim was to better understand the physiopathological mechanisms of radiation-induced tissue damage and to determine the best treatment strategy. The second part of this work investigated the feasibility of autologous BMSC therapy on the murine model of radiation previously established with emphasis on two pre-requisites: the retention of the injected cells within the target tissue and the evaluation of the graft on bone metabolism. This preclinical investigation in a mouse model constitutes an essential step allowing an evaluation of the benefit of cell therapy for the treatment of radiation-induced tissue injury. Data from these studies could allow the proposal of clinical studies [fr

  3. Geometry Modeling Program Implementation of Human Hip Tissue

    Directory of Open Access Journals (Sweden)

    WANG Mo-nan

    2017-10-01

    Full Text Available Abstract:Aiming to design a simulate software of human tissue modeling and analysis,Visual Studio 2010 is selected as a development tool to develop a 3 D reconstruction software of human tissue with language C++.It can be used alone. It also can be a module of the virtual surgery systems. The system includes medical image segmentation modules and 3 D reconstruction modules,and can realize the model visualization. This software system has been used to reconstruct hip muscles,femur and hip bone accurately. The results show these geometry models can simulate the structure of hip tissues.

  4. Geometry Modeling Program Implementation of Human Hip Tissue

    Directory of Open Access Journals (Sweden)

    WANG Monan

    2017-04-01

    Full Text Available Aiming to design a simulate software of human tissue modeling and analysis,Visual Studio 2010 is selected as a development tool to develop a 3 D reconstruction software of human tissue with language C++.It can be used alone. It also can be a module of the virtual surgery systems. The system includes medical image segmentation modules and 3 D reconstruction modules,and can realize the model visualization. This software system has been used to reconstruct hip muscles,femur and hip bone accurately. The results show these geometry models can simulate the structure of hip tissues.

  5. A simple tissue model for practicing ultrasound guided vascular ...

    African Journals Online (AJOL)

    Introduction: The use of ultrasound in anaesthetic practice continues to be more established and the use of ultrasound guidance in establishing vascular access is recommended by various groups. We have developed a tissue model for the practice and skills development in ultrasound vascular access. Method: The tissue ...

  6. Modeling light–tissue interaction in optical coherence tomography systems

    DEFF Research Database (Denmark)

    Andersen, Peter E.; Jørgensen, Thomas Martini; Thrane, Lars

    2015-01-01

    Optical coherence tomography (OCT) performs high-resolution, cross-sectional tomographic imaging of the internal tissue microstructure by measuring backscattered or backreflected light. The scope of this chapter is to present analytical and numerical models that are able to describe light-tissue ...

  7. Micromechanical modeling of rate-dependent behavior of Connective tissues.

    Science.gov (United States)

    Fallah, A; Ahmadian, M T; Firozbakhsh, K; Aghdam, M M

    2017-03-07

    In this paper, a constitutive and micromechanical model for prediction of rate-dependent behavior of connective tissues (CTs) is presented. Connective tissues are considered as nonlinear viscoelastic material. The rate-dependent behavior of CTs is incorporated into model using the well-known quasi-linear viscoelasticity (QLV) theory. A planar wavy representative volume element (RVE) is considered based on the tissue microstructure histological evidences. The presented model parameters are identified based on the available experiments in the literature. The presented constitutive model introduced to ABAQUS by means of UMAT subroutine. Results show that, monotonic uniaxial test predictions of the presented model at different strain rates for rat tail tendon (RTT) and human patellar tendon (HPT) are in good agreement with experimental data. Results of incremental stress-relaxation test are also presented to investigate both instantaneous and viscoelastic behavior of connective tissues. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. The dielectric properties of biological tissues: III. Parametric models for the dielectric spectrum of tissues

    International Nuclear Information System (INIS)

    Gabriel, S.; Lau, R.W.; Gabriel, C.

    1996-01-01

    A parametric model was developed to describe the variation of dielectric properties of tissues as a function of frequency. The experimental spectrum from 10 Hz to 100 GHz was modelled with four dispersion regions. The development of the model was based on recently acquired data, complemented by data surveyed from the literature. The purpose is to enable the prediction of dielectric data that are in line with those contained in the vast body of literature on the subject. The analysis was carried out on a Microsoft Excel spreadsheet. Parameters are given for 17 tissue types. (author)

  9. Roentgenographic studies on the soft tissue profile

    International Nuclear Information System (INIS)

    Park, Tae Won; Ahn, Hyung Kyu

    1971-01-01

    Modern orthodontics implies not only occlusal excellence, but also the positioning of teeth to produce optimal facial harmony for the individual patients. Several methods have been used in the study of facial height, width and depth were made from living subjects. These methods, however, complicate to control the subjects, therefore many investigators have used profile cephalometric technics. Practically, cephalometric technics were used in orthodontic treatment, maxillo-facial surgery and anthropometric studies. Author was studied to investigate the normal standards of soft tissue profile in Korean adolescences. The subjects consisted of 53 males and 54 females from 17 to 22 years of age and with normal occlusion and acceptable profile. Aluminum filter was designed to obtain both hard and soft tissue structures on a single film. Eight profile landmarks were plotted and drawn on the tracings of all cephalograms and eighteen depth, height an d angles were measured from each landmarks of the cephalograms. The following conclusions were obtained from this studies; 1. Total facial convexity was 170.75 in males and females samples and lower facial and labiomandibular convexity were each of 141.44, 171.05. 2. Maxillary and mandibular sulcus angulations were 137.61, 129.52 and upper and lower lip inclinations were each of 12 3.26 and 49.56 in male and females. 3. Soft tissue depth of several points were as follows; Subnasale 18.74 mm in males and 16.65 mm in females Pogonion 13.40 mm in males and 13.07 mm in females upper lip 14.06 mm in males and 11.91 mm in females lower lip 15.46 mm, 13.63 in males and females 4. The protrusion of nose were 16.28 mm in males and 15.56 mm in females 5. The vertical length of upper and lower lips were 25.67 mm, 52.96 mm and the lip posture was indicated 93.43 per cent (closed state) in centric occlusions.

  10. Statistical validation of normal tissue complication probability models

    NARCIS (Netherlands)

    Xu, Cheng-Jian; van der Schaaf, Arjen; van t Veld, Aart; Langendijk, Johannes A.; Schilstra, Cornelis

    2012-01-01

    PURPOSE: To investigate the applicability and value of double cross-validation and permutation tests as established statistical approaches in the validation of normal tissue complication probability (NTCP) models. METHODS AND MATERIALS: A penalized regression method, LASSO (least absolute shrinkage

  11. Bioprinting towards Physiologically Relevant Tissue Models for Pharmaceutics.

    Science.gov (United States)

    Peng, Weijie; Unutmaz, Derya; Ozbolat, Ibrahim T

    2016-09-01

    Improving the ability to predict the efficacy and toxicity of drug candidates earlier in the drug discovery process will speed up the introduction of new drugs into clinics. 3D in vitro systems have significantly advanced the drug screening process as 3D tissue models can closely mimic native tissues and, in some cases, the physiological response to drugs. Among various in vitro systems, bioprinting is a highly promising technology possessing several advantages such as tailored microarchitecture, high-throughput capability, coculture ability, and low risk of cross-contamination. In this opinion article, we discuss the currently available tissue models in pharmaceutics along with their limitations and highlight the possibilities of bioprinting physiologically relevant tissue models, which hold great potential in drug testing, high-throughput screening, and disease modeling. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. A Pharmacokinetic Model of a Tissue Implantable Cortisol Sensor.

    Science.gov (United States)

    Lee, Michael A; Bakh, Naveed; Bisker, Gili; Brown, Emery N; Strano, Michael S

    2016-12-01

    Cortisol is an important glucocorticoid hormone whose biochemistry influences numerous physiological and pathological processes. Moreover, it is a biomarker of interest for a number of conditions, including posttraumatic stress disorder, Cushing's syndrome, Addison's disease, and others. An implantable biosensor capable of real time monitoring of cortisol concentrations in adipose tissue may revolutionize the diagnosis and treatment of these disorders, as well as provide an invaluable research tool. Toward this end, a mathematical model, informed by the physiological literature, is developed to predict dynamic cortisol concentrations in adipose, muscle, and brain tissues, where a significant number of important processes with cortisol occur. The pharmacokinetic model is applied to both a prototypical, healthy male patient and a previously studied Cushing's disease patient. The model can also be used to inform the design of an implantable sensor by optimizing the sensor dissociation constant, apparent delay time, and magnitude of the sensor output versus system dynamics. Measurements from such a sensor would help to determine systemic cortisol levels, providing much needed insight for proper medical treatment for various cortisol-related conditions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Mathematical modeling in wound healing, bone regeneration and tissue engineering.

    Science.gov (United States)

    Geris, Liesbet; Gerisch, Alf; Schugart, Richard C

    2010-12-01

    The processes of wound healing and bone regeneration and problems in tissue engineering have been an active area for mathematical modeling in the last decade. Here we review a selection of recent models which aim at deriving strategies for improved healing. In wound healing, the models have particularly focused on the inflammatory response in order to improve the healing of chronic wound. For bone regeneration, the mathematical models have been applied to design optimal and new treatment strategies for normal and specific cases of impaired fracture healing. For the field of tissue engineering, we focus on mathematical models that analyze the interplay between cells and their biochemical cues within the scaffold to ensure optimal nutrient transport and maximal tissue production. Finally, we briefly comment on numerical issues arising from simulations of these mathematical models.

  14. Association between Gene Polymorphisms and Pain Sensitivity Assessed in a Multi-Modal Multi-Tissue Human Experimental Model - An Explorative Study

    DEFF Research Database (Denmark)

    Nielsen, Lecia Møller; Olesen, Anne Estrup; Sato, Hiroe

    2016-01-01

    The genetic influence on sensitivity to noxious stimuli (pain sensitivity) remains controversial and needs further investigation. In the present study, the possible influence of polymorphisms in three opioid receptor (OPRM, OPRD and OPRK) genes and the catechol-O-methyltransferase (COMT) gene...... on pain sensitivity in healthy participants was investigated. Catechol-O-methyltransferase has an indirect effect on the mu opioid receptor by changing its activity through an altered endogenous ligand effect. Blood samples for genetic analysis were withdrawn in a multi-modal and multi-tissue experimental......, electrical and thermal visceral stimulations. A cold pressor test was also conducted. DNA was available from 38 of 40 participants. Compared to non-carriers of the COMT rs4680A allele, carriers reported higher bone pressure pain tolerance threshold (i.e. less pain) by up to 23.8% (p

  15. Impact of statistical learning methods on the predictive power of multivariate normal tissue complication probability models

    NARCIS (Netherlands)

    Xu, Cheng-Jian; van der Schaaf, Arjen; Schilstra, Cornelis; Langendijk, Johannes A.; van t Veld, Aart A.

    2012-01-01

    PURPOSE: To study the impact of different statistical learning methods on the prediction performance of multivariate normal tissue complication probability (NTCP) models. METHODS AND MATERIALS: In this study, three learning methods, stepwise selection, least absolute shrinkage and selection operator

  16. Evaluation of computer-based computer tomography stratification against outcome models in connective tissue disease-related interstitial lung disease: a patient outcome study.

    Science.gov (United States)

    Jacob, Joseph; Bartholmai, Brian J; Rajagopalan, Srinivasan; Brun, Anne Laure; Egashira, Ryoko; Karwoski, Ronald; Kokosi, Maria; Wells, Athol U; Hansell, David M

    2016-11-23

    To evaluate computer-based computer tomography (CT) analysis (CALIPER) against visual CT scoring and pulmonary function tests (PFTs) when predicting mortality in patients with connective tissue disease-related interstitial lung disease (CTD-ILD). To identify outcome differences between distinct CTD-ILD groups derived following automated stratification of CALIPER variables. A total of 203 consecutive patients with assorted CTD-ILDs had CT parenchymal patterns evaluated by CALIPER and visual CT scoring: honeycombing, reticular pattern, ground glass opacities, pulmonary vessel volume, emphysema, and traction bronchiectasis. CT scores were evaluated against pulmonary function tests: forced vital capacity, diffusing capacity for carbon monoxide, carbon monoxide transfer coefficient, and composite physiologic index for mortality analysis. Automated stratification of CALIPER-CT variables was evaluated in place of and alongside forced vital capacity and diffusing capacity for carbon monoxide in the ILD gender, age physiology (ILD-GAP) model using receiver operating characteristic curve analysis. Cox regression analyses identified four independent predictors of mortality: patient age (P < 0.0001), smoking history (P = 0.0003), carbon monoxide transfer coefficient (P = 0.003), and pulmonary vessel volume (P < 0.0001). Automated stratification of CALIPER variables identified three morphologically distinct groups which were stronger predictors of mortality than all CT and functional indices. The Stratified-CT model substituted automated stratified groups for functional indices in the ILD-GAP model and maintained model strength (area under curve (AUC) = 0.74, P < 0.0001), ILD-GAP (AUC = 0.72, P < 0.0001). Combining automated stratified groups with the ILD-GAP model (stratified CT-GAP model) strengthened predictions of 1- and 2-year mortality: ILD-GAP (AUC = 0.87 and 0.86, respectively); stratified CT-GAP (AUC = 0.89 and 0.88, respectively

  17. Tissue engineering rib with the incorporation of biodegradable polymer cage and BMSCs/decalcified bone: an experimental study in a canine model.

    Science.gov (United States)

    Tang, Hua; Wu, Bin; Qin, Xiong; Zhang, Lu; Kretlow, Jim; Xu, Zhifei

    2013-05-20

    The reconstruction of large bone defects, including rib defects, remains a challenge for surgeons. In this study, we used biodegradable polydioxanone (PDO) cages to tissue engineer ribs for the reconstruction of 4cm-long costal defects. PDO sutures were used to weave 6cm long and 1cm diameter cages. Demineralized bone matrix (DBM) which is a xenograft was molded into cuboids and seeded with second passage bone marrow mesenchymal stem cells (BMSCs) that had been osteogenically induced. Two DBM cuboids seeded with BMSCs were put into the PDO cage and used to reconstruct the costal defects. Radiographic examination including 3D reconstruction, histologic examination and mechanical test was performed after 24 postoperative weeks. All the experimental subjects survived. In all groups, the PDO cage had completely degraded after 24 weeks and been replaced by fibrous tissue. Better shape and radian were achieved in PDO cages filled with DBM and BMSCs than in the other two groups (cages alone, or cages filled with acellular DBM cuboids). When the repaired ribs were subjected to an outer force, the ribs in the PDO cage/DBMs/BMSCs group kept their original shape while ribs in the other two groups deformed. In the PDO cage/DBMs/BMSCs groups, we also observed bony union at all the construct interfaces while there was no bony union observed in the other two groups. This result was also confirmed by radiographic and histologic examination. This study demonstrates that biodegradable PDO cage in combination with two short BMSCs/DBM cuboids can repair large rib defects. The satisfactory repair rate suggests that this might be a feasible approach for large bone repair.

  18. POLARIZATION IMAGING AND SCATTERING MODEL OF CANCEROUS LIVER TISSUES

    Directory of Open Access Journals (Sweden)

    DONGZHI LI

    2013-07-01

    Full Text Available We apply different polarization imaging techniques for cancerous liver tissues, and compare the relative contrasts for difference polarization imaging (DPI, degree of polarization imaging (DOPI and rotating linear polarization imaging (RLPI. Experimental results show that a number of polarization imaging parameters are capable of differentiating cancerous cells in isotropic liver tissues. To analyze the contrast mechanism of the cancer-sensitive polarization imaging parameters, we propose a scattering model containing two types of spherical scatterers and carry on Monte Carlo simulations based on this bi-component model. Both the experimental and Monte Carlo simulated results show that the RLPI technique can provide a good imaging contrast of cancerous tissues. The bi-component scattering model provides a useful tool to analyze the contrast mechanism of polarization imaging of cancerous tissues.

  19. Studying cytokinesis in Drosophila epithelial tissues.

    Science.gov (United States)

    Pinheiro, D; Bellaïche, Y

    2017-01-01

    Epithelial tissue cohesiveness is ensured through cell-cell junctions that maintain both adhesion and mechanical coupling between neighboring cells. During development, epithelial tissues undergo intensive cell proliferation. Cell division, and particularly cytokinesis, is coupled to the formation of new adhesive contacts, thereby preserving tissue integrity and propagating cell polarity. Remarkably, the geometry of the new interfaces is determined by the combined action of the dividing cell and its neighbors. To further understand the interplay between the dividing cell and its neighbors, as well as the role of cell division for tissue morphogenesis, it is important to analyze cytokinesis in vivo. Here we present methods to perform live imaging of cell division in Drosophila epithelial tissues and discuss some aspects of image processing and analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Experimental Human Cell and Tissue Models of Pemphigus

    Science.gov (United States)

    van der Wier, Gerda; Pas, Hendri H.; Jonkman, Marcel F.

    2010-01-01

    Pemphigus is a chronic mucocutaneous autoimmune bullous disease that is characterized by loss of cell-cell contact in skin and/or mucous membranes. Past research has successfully identified desmosomes as immunological targets and has demonstrated that acantholysis is initiated through direct binding of IgG. The exact mechanisms of acantholysis, however, are still missing. Experimental model systems have contributed considerably to today's knowledge and are still a favourite tool of research. In this paper we will describe to what extent human cell and tissue models represent the in vivo situation, for example, organ cultures of human skin, keratinocyte cultures, and human skin grafted on mice and, furthermore, how suitable they are to study the pathogenesis of pemphigus. Organ cultures closely mimic the architecture of the epidermis but are less suitable to answer posed biochemical questions. Cultured keratinocyte monolayers are convenient in this respect, but their desmosomal make-up in terms of adhesion molecules does not exactly reflect the in vivo situation. Reconstituted skin is a relatively new model that approaches organ culture. In models of human skin grafted on mice, acantholysis can be studied in actual human skin but now with all the advantages of an animal model. PMID:20585596

  1. A 3D intestinal tissue model supports Clostridioides difficile germination, colonization, toxin production and epithelial damage.

    Science.gov (United States)

    Shaban, Lamyaa; Chen, Ying; Fasciano, Alyssa C; Lin, Yinan; Kaplan, David L; Kumamoto, Carol A; Mecsas, Joan

    2018-04-01

    Endospore-forming Clostridioides difficile is a causative agent of antibiotic-induced diarrhea, a major nosocomial infection. Studies of its interactions with mammalian tissues have been hampered by the fact that C. difficile requires anaerobic conditions to survive after spore germination. We recently developed a bioengineered 3D human intestinal tissue model and found that low O 2 conditions are produced in the lumen of these tissues. Here, we compared the ability of C. difficile spores to germinate, produce toxin and cause tissue damage in our bioengineered 3D tissue model versus in a 2D transwell model in which human cells form a polarized monolayer. 3D tissue models or 2D polarized monolayers on transwell filters were challenged with the non-toxin producing C. difficile CCUG 37787 serotype X (ATCC 43603) and the toxin producing UK1 C. difficile spores in the presence of the germinant, taurocholate. Spores germinated in both the 3D tissue model as well as the 2D transwell system, however toxin activity was significantly higher in the 3D tissue models compared to the 2D transwells. Moreover, the epithelium damage in the 3D tissue model was significantly more severe than in 2D transwells and damage correlated significantly with the level of toxin activity detected but not with the amount of germinated spores. Combined, these results show that the bioengineered 3D tissue model provides a powerful system with which to study early events leading to toxin production and tissue damage of C. difficile with mammalian cells under anaerobic conditions. Furthermore, these systems may be useful for examining the effects of microbiota, novel drugs and other potential therapeutics directed towards C. difficile infections. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Finite-element modeling of soft tissue rolling indentation.

    Science.gov (United States)

    Sangpradit, Kiattisak; Liu, Hongbin; Dasgupta, Prokar; Althoefer, Kaspar; Seneviratne, Lakmal D

    2011-12-01

    We describe a finite-element (FE) model for simulating wheel-rolling tissue deformations using a rolling FE model (RFEM). A wheeled probe performing rolling tissue indentation has proven to be a promising approach for compensating for the loss of haptic and tactile feedback experienced during robotic-assisted minimally invasive surgery (H. Liu, D. P. Noonan, B. J. Challacombe, P. Dasgupta, L. D. Seneviratne, and K. Althoefer, "Rolling mechanical imaging for tissue abnormality localization during minimally invasive surgery, " IEEE Trans. Biomed. Eng., vol. 57, no. 2, pp. 404-414, Feb. 2010; K. Sangpradit, H. Liu, L. Seneviratne, and K. Althoefer, "Tissue identification using inverse finite element analysis of rolling indentation," in Proc. IEEE Int. Conf. Robot. Autom. , Kobe, Japan, 2009, pp. 1250-1255; H. Liu, D. Noonan, K. Althoefer, and L. Seneviratne, "The rolling approach for soft tissue modeling and mechanical imaging during robot-assisted minimally invasive surgery," in Proc. IEEE Int. Conf. Robot. Autom., May 2008, pp. 845-850; H. Liu, P. Puangmali, D. Zbyszewski, O. Elhage, P. Dasgupta, J. S. Dai, L. Seneviratne, and K. Althoefer, "An indentation depth-force sensing wheeled probe for abnormality identification during minimally invasive surgery," Proc. Inst. Mech. Eng., H, vol. 224, no. 6, pp. 751-63, 2010; D. Noonan, H. Liu, Y. Zweiri, K. Althoefer, and L. Seneviratne, "A dual-function wheeled probe for tissue viscoelastic property identification during minimally invasive surgery," in Proc. IEEE Int. Conf. Robot. Autom. , 2008, pp. 2629-2634; H. Liu, J. Li, Q. I. Poon, L. D. Seneviratne, and K. Althoefer, "Miniaturized force indentation-depth sensor for tissue abnormality identification," IEEE Int. Conf. Robot. Autom., May 2010, pp. 3654-3659). A sound understanding of wheel-tissue rolling interaction dynamics will facilitate the evaluation of signals from rolling indentation. In this paper, we model the dynamic interactions between a wheeled probe and a

  3. A Combined Tissue Kinetics and Dosimetric Model of Respiratory Tissue Exposed to Radiation. Final Technical Report

    International Nuclear Information System (INIS)

    John R. Ford

    2005-01-01

    Existing dosimetric models of the radiation response of tissues are essentially static. Consideration of changes in the cell populations over time has not been addressed realistically. For a single acute dose this is not a concern, but for modeling chronic exposures or fractionated acute exposures, the natural turnover and progression of cells could have a significant impact on a variety of endpoints. This proposal addresses the shortcomings of current methods by combining current dose-based calculation techniques with information on the cell turnover for a model tissue. The proposed model will examine effects at the single-cell level for an exposure of a section of human bronchiole. The cell model will be combined with Monte Carlo calculations of doses to cells and cell nuclei due to varying dose-rates of different radiation qualities. Predictions from the model of effects on survival, apoptosis rates, and changes in the number of cycling and differentiating cells will be tested experimentally. The availability of dynamic dosimetric models of tissues at the single-cell level will be useful for analysis of low-level radiation exposures and in the development of new radiotherapy protocols

  4. A Combined Tissue Kinetics and Dosimetric Model of Respiratory Tissue Exposed to Radiation

    Energy Technology Data Exchange (ETDEWEB)

    John R. Ford

    2005-11-01

    Existing dosimetric models of the radiation response of tissues are essentially static. Consideration of changes in the cell populations over time has not been addressed realistically. For a single acute dose this is not a concern, but for modeling chronic exposures or fractionated acute exposures, the natural turnover and progression of cells could have a significant impact on a variety of endpoints. This proposal addresses the shortcomings of current methods by combining current dose-based calculation techniques with information on the cell turnover for a model tissue. The proposed model will examine effects at the single-cell level for an exposure of a section of human bronchiole. The cell model will be combined with Monte Carlo calculations of doses to cells and cell nuclei due to varying dose-rates of different radiation qualities. Predictions from the model of effects on survival, apoptosis rates, and changes in the number of cycling and differentiating cells will be tested experimentally. The availability of dynamic dosimetric models of tissues at the single-cell level will be useful for analysis of low-level radiation exposures and in the development of new radiotherapy protocols.

  5. Ex Vivo Model of Human Penile Transplantation and Rejection: Implications for Erectile Tissue Physiology.

    Science.gov (United States)

    Sopko, Nikolai A; Matsui, Hotaka; Lough, Denver M; Miller, Devin; Harris, Kelly; Kates, Max; Liu, Xiaopu; Billups, Kevin; Redett, Richard; Burnett, Arthur L; Brandacher, Gerald; Bivalacqua, Trinity J

    2017-04-01

    Penile transplantation is a potential treatment option for severe penile tissue loss. Models of human penile rejection are lacking. Evaluate effects of rejection and immunosuppression on cavernous tissue using a novel ex vivo mixed lymphocyte reaction (MLR) model. Cavernous tissue and peripheral blood mononuclear cells (PBMCs) from 10 patients undergoing penile prosthesis operations and PBMCs from a healthy volunteer were obtained. Ex vivo MLRs were prepared by culturing cavernous tissue for 48h in media alone, in media with autologous PBMCs, or in media with allogenic PBMCs to simulate control, autotransplant, and allogenic transplant conditions with or without 1μM cyclosporine A (CsA) or 20nM tacrolimus (FK506) treatment. Rejection was characterized by PBMC flow cytometry and gene expression transplant array. Cavernous tissues were evaluated by histomorphology and myography to assess contraction and relaxation. Data were analyzed using two-way analysis of variance and unpaired Student t test. Flow cytometry and tissue array demonstrated allogenic PBMC activation consistent with rejection. Rejection impaired cavernous tissue physiology and was associated with cellular infiltration and apoptosis. CsA prevented rejection but did not improve tissue relaxation. CsA treatment impaired relaxation in tissues cultured without PBMCs compared with media and FK506. Study limitations included the use of penile tissue with erectile dysfunction and lack of cross-matching data. This model could be used to investigate the effects of penile rejection and immunosuppression. Additional studies are needed to optimize immunosuppression to prevent rejection and maximize corporal tissue physiology. This report describes a novel ex vivo model of human penile transplantation rejection. Tissue rejection impaired erectile tissue physiology. This report suggests that cyclosporin A might hinder corporal physiology and that other immunosuppressant agents, such as FK506, might be better suited

  6. Average intensity and spreading of partially coherent model beams propagating in a turbulent biological tissue

    International Nuclear Information System (INIS)

    Wu, Yuqian; Zhang, Yixin; Wang, Qiu; Hu, Zhengda

    2016-01-01

    For Gaussian beams with three different partially coherent models, including Gaussian-Schell model (GSM), Laguerre-Gaussian Schell-model (LGSM) and Bessel-Gaussian Schell-model (BGSM) beams propagating through a biological turbulent tissue, the expression of the spatial coherence radius of a spherical wave propagating in a turbulent biological tissue, and the average intensity and beam spreading for GSM, LGSM and BGSM beams are derived based on the fractal model of power spectrum of refractive-index variations in biological tissue. Effects of partially coherent model and parameters of biological turbulence on such beams are studied in numerical simulations. Our results reveal that the spreading of GSM beams is smaller than LGSM and BGSM beams on the same conditions, and the beam with larger source coherence width has smaller beam spreading than that with smaller coherence width. The results are useful for any applications involved light beam propagation through tissues, especially the cases where the average intensity and spreading properties of the light should be taken into account to evaluate the system performance and investigations in the structures of biological tissue. - Highlights: • Spatial coherence radius of a spherical wave propagating in a turbulent biological tissue is developed. • Expressions of average intensity and beam spreading for GSM, LGSM and BGSM beams in a turbulent biological tissue are derived. • The contrast for the three partially coherent model beams is shown in numerical simulations. • The results are useful for any applications involved light beam propagation through tissues.

  7. Skin Diseases Modeling using Combined Tissue Engineering and Microfluidic Technologies.

    Science.gov (United States)

    Mohammadi, Mohammad Hossein; Heidary Araghi, Behnaz; Beydaghi, Vahid; Geraili, Armin; Moradi, Farshid; Jafari, Parya; Janmaleki, Mohsen; Valente, Karolina Papera; Akbari, Mohsen; Sanati-Nezhad, Amir

    2016-10-01

    In recent years, both tissue engineering and microfluidics have significantly contributed in engineering of in vitro skin substitutes to test the penetration of chemicals or to replace damaged skins. Organ-on-chip platforms have been recently inspired by the integration of microfluidics and biomaterials in order to develop physiologically relevant disease models. However, the application of organ-on-chip on the development of skin disease models is still limited and needs to be further developed. The impact of tissue engineering, biomaterials and microfluidic platforms on the development of skin grafts and biomimetic in vitro skin models is reviewed. The integration of tissue engineering and microfluidics for the development of biomimetic skin-on-chip platforms is further discussed, not only to improve the performance of present skin models, but also for the development of novel skin disease platforms for drug screening processes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Normal tissue dose-effect models in biological dose optimisation

    International Nuclear Information System (INIS)

    Alber, M.

    2008-01-01

    Sophisticated radiotherapy techniques like intensity modulated radiotherapy with photons and protons rely on numerical dose optimisation. The evaluation of normal tissue dose distributions that deviate significantly from the common clinical routine and also the mathematical expression of desirable properties of a dose distribution is difficult. In essence, a dose evaluation model for normal tissues has to express the tissue specific volume effect. A formalism of local dose effect measures is presented, which can be applied to serial and parallel responding tissues as well as target volumes and physical dose penalties. These models allow a transparent description of the volume effect and an efficient control over the optimum dose distribution. They can be linked to normal tissue complication probability models and the equivalent uniform dose concept. In clinical applications, they provide a means to standardize normal tissue doses in the face of inevitable anatomical differences between patients and a vastly increased freedom to shape the dose, without being overly limiting like sets of dose-volume constraints. (orig.)

  9. A minimal spatial cell lineage model of epithelium: tissue stratification and multi-stability

    Science.gov (United States)

    Yeh, Wei-Ting; Chen, Hsuan-Yi

    2018-05-01

    A minimal model which includes spatial and cell lineage dynamics for stratified epithelia is presented. The dependence of tissue steady state on cell differentiation models, cell proliferation rate, cell differentiation rate, and other parameters are studied numerically and analytically. Our minimal model shows some important features. First, we find that morphogen or mechanical stress mediated interaction is necessary to maintain a healthy stratified epithelium. Furthermore, comparing with tissues in which cell differentiation can take place only during cell division, tissues in which cell division and cell differentiation are decoupled can achieve relatively higher degree of stratification. Finally, our model also shows that in the presence of short-range interactions, it is possible for a tissue to have multiple steady states. The relation between our results and tissue morphogenesis or lesion is discussed.

  10. Finite difference time domain (FDTD) modeling of implanted deep brain stimulation electrodes and brain tissue.

    Science.gov (United States)

    Gabran, S R I; Saad, J H; Salama, M M A; Mansour, R R

    2009-01-01

    This paper demonstrates the electromagnetic modeling and simulation of an implanted Medtronic deep brain stimulation (DBS) electrode using finite difference time domain (FDTD). The model is developed using Empire XCcel and represents the electrode surrounded with brain tissue assuming homogenous and isotropic medium. The model is created to study the parameters influencing the electric field distribution within the tissue in order to provide reference and benchmarking data for DBS and intra-cortical electrode development.

  11. A Dirichlet process mixture model for brain MRI tissue classification.

    Science.gov (United States)

    Ferreira da Silva, Adelino R

    2007-04-01

    Accurate classification of magnetic resonance images according to tissue type or region of interest has become a critical requirement in diagnosis, treatment planning, and cognitive neuroscience. Several authors have shown that finite mixture models give excellent results in the automated segmentation of MR images of the human normal brain. However, performance and robustness of finite mixture models deteriorate when the models have to deal with a variety of anatomical structures. In this paper, we propose a nonparametric Bayesian model for tissue classification of MR images of the brain. The model, known as Dirichlet process mixture model, uses Dirichlet process priors to overcome the limitations of current parametric finite mixture models. To validate the accuracy and robustness of our method we present the results of experiments carried out on simulated MR brain scans, as well as on real MR image data. The results are compared with similar results from other well-known MRI segmentation methods.

  12. Radiofrequency tissue ablation with cooled-tip electrodes:an experimental study in a bovine liver model on variables influencing lesion size

    International Nuclear Information System (INIS)

    Han, Hyun Young; Lee, Jeong Min; Kim, Chong Soo

    2001-01-01

    The purpose of this study was to determine the influence of various factors on the extent of thermal coagulation necrosis after radiofrequency (RF) tissue ablation using a cooled-tip electrode in bovine liver. RF ablation was induced by a monopolar 500 KHz-RF generator (CC-1; Radionics, Burlington, Mass., U.S.A.) and an 18-G cooled-tip with single or clustered electrodes. The ablation protocol involved a combination of varying current, ablation time, power output, gradual or abrupt increase of this out-put, and pulsed radiofrequency techniques. The maximum diameter of all thermal lesions which showed a color change was measured perpendicular to the electrode axis by two observers who reached their decisions by consensus. Twenty representative lesions were pathologically examined. With increasing current lesion diameter also increased, but above 1500 mA no further increase was induced. Extending the ablation time to 9 minutes for a single electrode and 15 minutes for a clustered electrode increased lesion diameter until a steady state was reached. Higher power levels caused larger lesions, but above 100 W no increase was observed. Ample exposure time coupled with a stepwise increase in power level induced a lesion larger than that resulting from an abrupt increase. Continuous pulsed RF with a high current led to increased coagulation necrosis diameter. These experimental findings may be useful thermotherapy. The data suggest that all involved factors significantly affect lesion size:if the factors are better understood, cancer thermotherapy can be better controlled

  13. A Framework for Modelling Connective Tissue Changes in VIIP Syndrome

    Science.gov (United States)

    Ethier, C. R.; Best, L.; Gleason, R.; Mulugeta, L.; Myers, J. G.; Nelson, E. S.; Samuels, B. C.

    2014-01-01

    Insertion of astronauts into microgravity induces a cascade of physiological adaptations, notably including a cephalad fluid shift. Longer-duration flights carry an increased risk of developing Visual Impairment and Intracranial Pressure (VIIP) syndrome, a spectrum of ophthalmic changes including posterior globe flattening, choroidal folds, distension of the optic nerve sheath, kinking of the optic nerve and potentially permanent degradation of visual function. The slow onset of changes in VIIP, their chronic nature, and the similarity of certain clinical features of VIIP to ophthalmic findings in patients with raised intracranial pressure strongly suggest that: (i) biomechanical factors play a role in VIIP, and (ii) connective tissue remodeling must be accounted for if we wish to understand the pathology of VIIP. Our goal is to elucidate the pathophysiology of VIIP and suggest countermeasures based on biomechanical modeling of ocular tissues, suitably informed by experimental data, and followed by validation and verification. We specifically seek to understand the quasi-homeostatic state that evolves over weeks to months in space, during which ocular tissue remodeling occurs. This effort is informed by three bodies of work: (i) modeling of cephalad fluid shifts; (ii) modeling of ophthalmic tissue biomechanics in glaucoma; and (iii) modeling of connective tissue changes in response to biomechanical loading.

  14. Artery Soft-Tissue Modelling for Stent Implant Training System

    Directory of Open Access Journals (Sweden)

    Giovanni Aloisio

    2004-08-01

    Full Text Available Virtual reality technology can be utilised to provide new systematic training methods for surgical procedures. Our aim is to build a simulator that allows medical students to practice the coronary stent implant procedure and avoids exposing patients to risks. The designed simulation system consists of a virtual environment and a haptic interface, in order to provide both the visualization of the coronary arteries and the tactile and force feedback generated during the interactions of the surgical instruments in the virtual environment. Since the arteries are soft tissues, their shape may change during an operation; for this reason physical modelling of the organs is necessary to render their behaviour under the influence of surgeon's instruments. The idea is to define a model that computes the displacement of the tissue versus time; from the displacement it is possible to calculate the response of the tissue to the surgical tool external stimuli. Information about tools displacements and tissue responses are also used to graphically model the artery wall and virtual surgical instrument deformations generated as a consequence of their coming into contact. In order to obtain a realistic simulation, the Finite Element Method has been used to model the soft tissues of the artery, using linear elasticity to reduce computational time and speed up interaction rates.

  15. Human tissue optical properties measurements and light propagation modelling

    CSIR Research Space (South Africa)

    Dam, JS

    2006-07-01

    Full Text Available Biomedical Optics is the study of the optical properties of living biological material, especially its scattering and absorption characteristics, and their significance to light propagation within the material. Determination of tissue optical...

  16. Elastic properties of synthetic materials for soft tissue modeling

    International Nuclear Information System (INIS)

    Mansy, H A; Grahe, J R; Sandler, R H

    2008-01-01

    Mechanical models of soft tissue are useful for studying vibro-acoustic phenomena. They may be used for validating mathematical models and for testing new equipment and techniques. The objective of this study was to measure density and visco-elastic properties of synthetic materials that can be used to build such models. Samples of nine different materials were tested under dynamic (0.5 Hz) compressive loading conditions. The modulus of elasticity of the materials was varied, whenever possible, by adding a softener during manufacturing. The modulus was measured over a nine month period to quantify the effect of ageing and softener loss on material properties. Results showed that a wide range of the compression elasticity modulus (10 to 1400 kPa) and phase (3.5 0 -16.7 0 ) between stress and strain were possible. Some materials tended to exude softener over time, resulting in a weight loss and elastic properties change. While the weight loss under normal conditions was minimal in all materials (<3% over nine months), loss under accelerated weight-loss conditions can reach 59%. In the latter case an elasticity modulus increase of up to 500% was measured. Key advantages and limitations of candidate materials were identified and discussed

  17. Doxorubicin plus the IGF-1R antibody cixutumumab in soft tissue sarcoma: a phase I study using the TITE-CRM model.

    Science.gov (United States)

    Chugh, R; Griffith, K A; Davis, E J; Thomas, D G; Zavala, J D; Metko, G; Brockstein, B; Undevia, S D; Stadler, W M; Schuetze, S M

    2015-07-01

    Insulin-like growth factor receptor (IGF-1R) has been studied as an oncologic target in soft tissue sarcoma (STS), but its role in sarcoma biology is unclear. Anti-IGF-1R antibody cixutumumab demonstrated acceptable toxicity but limited activity as a single agent in STS. We carried out a dose-escalation study of cixutumumab with doxorubicin to evaluate safety and dosing of the combination. Eligible patients with advanced STS were treated with cixutumumab intravenously on days 1/8/15 at one of three dose levels (A: 1 mg/kg, B: 3 mg/kg, C: 6 mg/kg) with doxorubicin at 75 mg/m(2) as a 48 h infusion on day 1 of a 21 day cycle. After six cycles of the combination, patients could receive cixutumumab alone. The Time-to-Event Continual Reassessment Method was used to estimate the probability of dose-limiting toxicity (DLT) and to assign patients to the dose with an estimated probability of DLT≤20%. Between September 2008 and January 2012, 30 patients with advanced STS received a median of six cycles of therapy (range <1-22). Two DLTs were observed, grade 3 mucositis (dose level B) and grade 4 hyperglycemia (dose level C). Grade 2 and 3 reduced left ventricular ejection fraction was seen in three and two patients, respectively. Five partial responses were observed, and estimated progression-free survival was 5.3 months (95% confidence interval 3.0-6.3) in 26 response-assessable patients. Immunohistochemical staining of 11 available tumor samples for IGF-1R and phospho-IGF-1R was not significantly different among responders and non-responders, and serum analysis of select single-nucleotide polymorphisms did not predict for cardiotoxicity. The maximum tolerated dose was doxorubicin 75 mg/m(2) on day 1 and cixitumumab 6 mg/kg on days 1/8/15 of a 21 day cycle. Cardiac toxicity was observed and should be monitored in subsequent studies, which should be considered in STS only if a predictive biomarker of benefit to anti-IGF-1R therapy is identified. Clinical

  18. Tissue-engineered bone with 3-dimensionally printed β-tricalcium phosphate and polycaprolactone scaffolds and early implantation: an in vivo pilot study in a porcine mandible model.

    Science.gov (United States)

    Konopnicki, Sandra; Sharaf, Basel; Resnick, Cory; Patenaude, Adam; Pogal-Sussman, Tracy; Hwang, Kyung-Gyun; Abukawa, Harutsugi; Troulis, Maria J

    2015-05-01

    Deep bone penetration into implanted scaffolds remains a challenge in tissue engineering. The purpose of this study was to evaluate bone penetration depth within 3-dimensionally (3D) printed β-tricalcium phosphate (β-TCP) and polycaprolactone (PCL) scaffolds, seeded with porcine bone marrow progenitor cells (pBMPCs), and implanted early in vivo. Scaffolds were 3D printed with 50% β-TCP and 50% PCL. The pBMPCs were harvested, isolated, expanded, and differentiated into osteoblasts. Cells were seeded into the scaffolds and constructs were incubated in a rotational oxygen-permeable bioreactor system for 14 days. Six 2- × 2-cm defects were created in each mandible (N = 2 minipigs). In total, 6 constructs were placed within defects and 6 defects were used as controls (unseeded scaffolds, n = 3; empty defects, n = 3). Eight weeks after surgery, specimens were harvested and analyzed by hematoxylin and eosin (H&E), 4',6-diamidino-2-phenylindole (DAPI), and CD31 staining. Analysis included cell counts, bone penetration, and angiogenesis at the center of the specimens. All specimens (N = 12) showed bone formation similar to native bone at the periphery. Of 6 constructs, 4 exhibited bone formation in the center. Histomorphometric analysis of the H&E-stained sections showed an average of 22.1% of bone in the center of the constructs group compared with 1.87% in the unseeded scaffolds (P bone in the center, showed massive cell penetration depth by DAPI staining, with an average of 2,109 cells/0.57 mm(2) in the center compared with 1,114 cells/0.57 mm(2) in the controls (P printed β-TCP and PCL scaffolds seeded with pBMPCs and implanted early into porcine mandibular defects display good bone penetration depth. Further study with a larger sample and larger bone defects should be performed before human applications. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  19. High-Density Spot Seeding for Tissue Model Formation

    Science.gov (United States)

    Marquette, Michele L. (Inventor); Sognier, Marguerite A. (Inventor)

    2016-01-01

    A model of tissue is produced by steps comprising seeding cells at a selected concentration on a support to form a cell spot, incubating the cells to allow the cells to partially attach, rinsing the cells to remove any cells that have not partially attached, adding culture medium to enable the cells to proliferate at a periphery of the cell spot and to differentiate toward a center of the cell spot, and further incubating the cells to form the tissue. The cells may be C2C12 cells or other subclones of the C2 cell line, H9c2(2-1) cells, L6 cells, L8 cells, QM7 cells, Sol8 cells, G-7 cells, G-8 cells, other myoblast cells, cells from other tissues, or stem cells. The selected concentration is in a range from about 1 x 10(exp 5) cells/ml to about 1 x 10(exp 6) cells/ml. The tissue formed may be a muscle tissue or other tissue depending on the cells seeded.

  20. Study of human mesenchymal stem cells plasticity into radiation injured tissues in a N.O.D./S.C.I.D. mouse model: therapeutic approach of the multiple organ dysfunction

    International Nuclear Information System (INIS)

    Francois, S.

    2006-01-01

    The therapeutic potential of bone marrow-derived human mesenchymal stem cells (h.M.S.C.) has recently been brought into the spotlight of many fields of research. One possible application of the approach is the repair of injured tissues arising from side effects of radiation treatments and accidents. The first challenge in cell therapy is to assess the quality of the cell and the ability to retain their differentiation potential during the expansion process. Efficient delivery to the sites of intended action is also necessary. We addressed both questions using h.M.S.C. cultured and then infused to Non Obese Diabetes/Severe Combined Immunodeficiency (N.O.D./S.C.I.D.) mice submitted to total body irradiation. Further, we tested the impact of additional local irradiation superimposed to total body irradiation (T.B.I.), as a model of accidental irradiation. Our results showed that the h.M.S.C. used for transplant have been expanded without significant loss in their differentiation capacities. After transplantation into adult unconditioned mice, h.M.S.C. not only migrate in bone marrow but also into other tissues. Total body irradiation increased h.M.S.C. implantation in bone marrow and muscle and further led to engraftment in brain, heart, and liver. Local irradiation, in addition to T.B.I., increased both specific homing of injected cells to the injured tissues and to other tissues outside the local irradiation field. M.S.C. may participate to restoration of intestinal homeostasis 3 days post abdominal irradiation. This study suggests that using the potential of h.M.S.C. to home to various organs in response to tissue injuries could be a promising strategy to repair the radiation induced damages. (author)

  1. A 2D Electromechanical Model of Human Atrial Tissue Using the Discrete Element Method

    Directory of Open Access Journals (Sweden)

    Paul Brocklehurst

    2015-01-01

    Full Text Available Cardiac tissue is a syncytium of coupled cells with pronounced intrinsic discrete nature. Previous models of cardiac electromechanics often ignore such discrete properties and treat cardiac tissue as a continuous medium, which has fundamental limitations. In the present study, we introduce a 2D electromechanical model for human atrial tissue based on the discrete element method (DEM. In the model, single-cell dynamics are governed by strongly coupling the electrophysiological model of Courtemanche et al. to the myofilament model of Rice et al. with two-way feedbacks. Each cell is treated as a viscoelastic body, which is physically represented by a clump of nine particles. Cell aggregations are arranged so that the anisotropic nature of cardiac tissue due to fibre orientations can be modelled. Each cell is electrically coupled to neighbouring cells, allowing excitation waves to propagate through the tissue. Cell-to-cell mechanical interactions are modelled using a linear contact bond model in DEM. By coupling cardiac electrophysiology with mechanics via the intracellular Ca2+ concentration, the DEM model successfully simulates the conduction of cardiac electrical waves and the tissue’s corresponding mechanical contractions. The developed DEM model is numerically stable and provides a powerful method for studying the electromechanical coupling problem in the heart.

  2. Tendon tissue engineering and its role on healing of the experimentally induced large tendon defect model in rabbits: a comprehensive in vivo study.

    Science.gov (United States)

    Meimandi-Parizi, Abdolhamid; Oryan, Ahmad; Moshiri, Ali

    2013-01-01

    Healing of large tendon defects is challenging. We studied the role of collagen implant with or without polydioxanone (PDS) sheath on the healing of a large Achilles tendon defect model, in rabbits. Sixty rabbits were divided into three groups. A 2 cm gap was created in the left Achilles tendon of all rabbits. In the control lesions, no implant was used. The other two groups were reconstructed by collagen and collagen-PDS implants respectively. The animals were clinically examined at weekly intervals and their lesions were observed by ultrasonography. Blood samples were obtained from the animals and were assessed for hematological analysis and determination of serum PDGF level, at 60 days post injury (DPI). The animals were then euthanized and their lesions were assessed for gross and histopathology, scanning electron microscopy, biomechanical testing, dry matter and hydroxyproline content. Another 65 pilot animals were also studied grossly and histopathologically to define the host implant interaction and graft incorporation at serial time points. The treated animals gained significantly better clinical scoring compared to the controls. Treatment with collagen and collagen-PDS implants significantly increased the biomechanical properties of the lesions compared to the control tendons at 60DPI (Ptendon. Implantation of the bioimplants had a significant role in initiating tendon healing and the implants were biocompatible, biodegradable and safe for application in tendon reconstructive surgery. The results of the present study may be valuable in clinical practice.

  3. Technical pitfalls in a porcine brain retraction model. The impact of brain spatula on the retracted brain tissue in a porcine model: a feasibility study and its technical pitfalls

    Energy Technology Data Exchange (ETDEWEB)

    Thiex, R.; Hans, F.J.; Gilsbach, J.M. [Aachen University, Department of Neurosurgery, Aachen (Germany); Krings, T. [Aachen University, Department of Neuroradiology, Aachen (Germany); Sellhaus, B. [Aachen University, Department of Neuropathology, Aachen (Germany)

    2005-10-01

    We describe technical pitfalls of a porcine brain injury model for identifying primary and secondary pathological sequelae following brain retraction by brain spatula. In 16 anaesthetised male pigs, the right frontal brain was retracted in the interhemispheric fissure by a brain spatulum with varying pressures applied by the gravitational force of weights from 10 to 70 g for a duration of 30 min. The retracted brain tissue was monitored for changes in intracranial pressure and perfusion of the cortex using a Laser Doppler Perfusion Imager (MoorLDI). To evaluate the extent of oedema and cortical contusions, MRI was performed 30 min and 72 h after brain retraction. Following the MR scan, the retracted brain areas were histopathologically assessed using H and E and Fluoro-Jade B staining for neuronal damage. Sinus occlusion occurred in four animals, resulting in bilateral cortical contusions and extensive brain oedema. Retracting the brain with weights of 70 g (n=4) caused extensive oedema on FLAIR images that correlated clinically with a hemiparesis in three animals. Morphologically, an increased number of Fluoro-Jade B-positive neurons were found. A sequential decrease in weights prevented functional deficits in animals. A retraction pressure applied by 10-g weights (n=7) caused a mean rise in intracranial pressure to 4.0{+-}3.1 mm Hg, and a decrement in mean cortical perfusion from 740.8{+-}41.5 to 693.8{+-}72.4 PU/cm2, (P<0.24). A meticulous dissection of the interhemispheric fissure and a reduction of weights to 10 g were found to be mandatory to study the cortical impact caused by brain spatula reproducibly. (orig.)

  4. Technical pitfalls in a porcine brain retraction model. The impact of brain spatula on the retracted brain tissue in a porcine model: a feasibility study and its technical pitfalls

    International Nuclear Information System (INIS)

    Thiex, R.; Hans, F.J.; Gilsbach, J.M.; Krings, T.; Sellhaus, B.

    2005-01-01

    We describe technical pitfalls of a porcine brain injury model for identifying primary and secondary pathological sequelae following brain retraction by brain spatula. In 16 anaesthetised male pigs, the right frontal brain was retracted in the interhemispheric fissure by a brain spatulum with varying pressures applied by the gravitational force of weights from 10 to 70 g for a duration of 30 min. The retracted brain tissue was monitored for changes in intracranial pressure and perfusion of the cortex using a Laser Doppler Perfusion Imager (MoorLDI). To evaluate the extent of oedema and cortical contusions, MRI was performed 30 min and 72 h after brain retraction. Following the MR scan, the retracted brain areas were histopathologically assessed using H and E and Fluoro-Jade B staining for neuronal damage. Sinus occlusion occurred in four animals, resulting in bilateral cortical contusions and extensive brain oedema. Retracting the brain with weights of 70 g (n=4) caused extensive oedema on FLAIR images that correlated clinically with a hemiparesis in three animals. Morphologically, an increased number of Fluoro-Jade B-positive neurons were found. A sequential decrease in weights prevented functional deficits in animals. A retraction pressure applied by 10-g weights (n=7) caused a mean rise in intracranial pressure to 4.0±3.1 mm Hg, and a decrement in mean cortical perfusion from 740.8±41.5 to 693.8±72.4 PU/cm2, (P<0.24). A meticulous dissection of the interhemispheric fissure and a reduction of weights to 10 g were found to be mandatory to study the cortical impact caused by brain spatula reproducibly. (orig.)

  5. Drug perfusion enhancement in tissue model by steady streaming induced by oscillating microbubbles.

    Science.gov (United States)

    Oh, Jin Sun; Kwon, Yong Seok; Lee, Kyung Ho; Jeong, Woowon; Chung, Sang Kug; Rhee, Kyehan

    2014-01-01

    Drug delivery into neurological tissue is challenging because of the low tissue permeability. Ultrasound incorporating microbubbles has been applied to enhance drug delivery into these tissues, but the effects of a streaming flow by microbubble oscillation on drug perfusion have not been elucidated. In order to clarify the physical effects of steady streaming on drug delivery, an experimental study on dye perfusion into a tissue model was performed using microbubbles excited by acoustic waves. The surface concentration and penetration length of the drug were increased by 12% and 13%, respectively, with streaming flow. The mass of dye perfused into a tissue phantom for 30s was increased by about 20% in the phantom with oscillating bubbles. A computational model that considers fluid structure interaction for streaming flow fields induced by oscillating bubbles was developed, and mass transfer of the drug into the porous tissue model was analyzed. The computed flow fields agreed with the theoretical solutions, and the dye concentration distribution in the tissue agreed well with the experimental data. The computational results showed that steady streaming with a streaming velocity of a few millimeters per second promotes mass transfer into a tissue. © 2013 Published by Elsevier Ltd.

  6. Bioprinted three dimensional human tissues for toxicology and disease modeling.

    Science.gov (United States)

    Nguyen, Deborah G; Pentoney, Stephen L

    2017-03-01

    The high rate of attrition among clinical-stage therapies, due largely to an inability to predict human toxicity and/or efficacy, underscores the need for in vitro models that better recapitulate in vivo human biology. In much the same way that additive manufacturing has revolutionized the production of solid objects, three-dimensional (3D) bioprinting is enabling the automated production of more architecturally and functionally accurate in vitro tissue culture models. Here, we provide an overview of the most commonly used bioprinting approaches and how they are being used to generate complex in vitro tissues for use in toxicology and disease modeling research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Lagrangian speckle model and tissue-motion estimation--theory.

    Science.gov (United States)

    Maurice, R L; Bertrand, M

    1999-07-01

    It is known that when a tissue is subjected to movements such as rotation, shearing, scaling, etc., changes in speckle patterns that result act as a noise source, often responsible for most of the displacement-estimate variance. From a modeling point of view, these changes can be thought of as resulting from two mechanisms: one is the motion of the speckles and the other, the alterations of their morphology. In this paper, we propose a new tissue-motion estimator to counteract these speckle decorrelation effects. The estimator is based on a Lagrangian description of the speckle motion. This description allows us to follow local characteristics of the speckle field as if they were a material property. This method leads to an analytical description of the decorrelation in a way which enables the derivation of an appropriate inverse filter for speckle restoration. The filter is appropriate for linear geometrical transformation of the scattering function (LT), i.e., a constant-strain region of interest (ROI). As the LT itself is a parameter of the filter, a tissue-motion estimator can be formulated as a nonlinear minimization problem, seeking the best match between the pre-tissue-motion image and a restored-speckle post-motion image. The method is tested, using simulated radio-frequency (RF) images of tissue undergoing axial shear.

  8. Study of human mesenchymal stem cells plasticity into radiation injured tissues in a N.O.D./S.C.I.D. mouse model: therapeutic approach of the multiple organ dysfunction; Etude de la capacite plastique des Cellules Souches Mesenchymateuses humaines (CSM) apres irradiation du tissu receveur: approche therapeutique de l'atteinte multiorgane radio-induite

    Energy Technology Data Exchange (ETDEWEB)

    Francois, S

    2006-01-15

    The therapeutic potential of bone marrow-derived human mesenchymal stem cells (h.M.S.C.) has recently been brought into the spotlight of many fields of research. One possible application of the approach is the repair of injured tissues arising from side effects of radiation treatments and accidents. The first challenge in cell therapy is to assess the quality of the cell and the ability to retain their differentiation potential during the expansion process. Efficient delivery to the sites of intended action is also necessary. We addressed both questions using h.M.S.C. cultured and then infused to Non Obese Diabetes/Severe Combined Immunodeficiency (N.O.D./S.C.I.D.) mice submitted to total body irradiation. Further, we tested the impact of additional local irradiation superimposed to total body irradiation (T.B.I.), as a model of accidental irradiation. Our results showed that the h.M.S.C. used for transplant have been expanded without significant loss in their differentiation capacities. After transplantation into adult unconditioned mice, h.M.S.C. not only migrate in bone marrow but also into other tissues. Total body irradiation increased h.M.S.C. implantation in bone marrow and muscle and further led to engraftment in brain, heart, and liver. Local irradiation, in addition to T.B.I., increased both specific homing of injected cells to the injured tissues and to other tissues outside the local irradiation field. M.S.C. may participate to restoration of intestinal homeostasis 3 days post abdominal irradiation. This study suggests that using the potential of h.M.S.C. to home to various organs in response to tissue injuries could be a promising strategy to repair the radiation induced damages. (author)

  9. Study of human mesenchymal stem cells plasticity into radiation injured tissues in a N.O.D./S.C.I.D. mouse model: therapeutic approach of the multiple organ dysfunction; Etude de la capacite plastique des Cellules Souches Mesenchymateuses humaines (CSM) apres irradiation du tissu receveur: approche therapeutique de l'atteinte multiorgane radio-induite

    Energy Technology Data Exchange (ETDEWEB)

    Francois, S

    2006-01-15

    The therapeutic potential of bone marrow-derived human mesenchymal stem cells (h.M.S.C.) has recently been brought into the spotlight of many fields of research. One possible application of the approach is the repair of injured tissues arising from side effects of radiation treatments and accidents. The first challenge in cell therapy is to assess the quality of the cell and the ability to retain their differentiation potential during the expansion process. Efficient delivery to the sites of intended action is also necessary. We addressed both questions using h.M.S.C. cultured and then infused to Non Obese Diabetes/Severe Combined Immunodeficiency (N.O.D./S.C.I.D.) mice submitted to total body irradiation. Further, we tested the impact of additional local irradiation superimposed to total body irradiation (T.B.I.), as a model of accidental irradiation. Our results showed that the h.M.S.C. used for transplant have been expanded without significant loss in their differentiation capacities. After transplantation into adult unconditioned mice, h.M.S.C. not only migrate in bone marrow but also into other tissues. Total body irradiation increased h.M.S.C. implantation in bone marrow and muscle and further led to engraftment in brain, heart, and liver. Local irradiation, in addition to T.B.I., increased both specific homing of injected cells to the injured tissues and to other tissues outside the local irradiation field. M.S.C. may participate to restoration of intestinal homeostasis 3 days post abdominal irradiation. This study suggests that using the potential of h.M.S.C. to home to various organs in response to tissue injuries could be a promising strategy to repair the radiation induced damages. (author)

  10. Three-Dimensional Culture Model of Skeletal Muscle Tissue with Atrophy Induced by Dexamethasone.

    Science.gov (United States)

    Shimizu, Kazunori; Genma, Riho; Gotou, Yuuki; Nagasaka, Sumire; Honda, Hiroyuki

    2017-06-15

    Drug screening systems for muscle atrophy based on the contractile force of cultured skeletal muscle tissues are required for the development of preventive or therapeutic drugs for atrophy. This study aims to develop a muscle atrophy model by inducing atrophy in normal muscle tissues constructed on microdevices capable of measuring the contractile force and to verify if this model is suitable for drug screening using the contractile force as an index. Tissue engineered skeletal muscles containing striated myotubes were prepared on the microdevices for the study. The addition of 100 µM dexamethasone (Dex), which is used as a muscle atrophy inducer, for 24 h reduced the contractile force significantly. An increase in the expression of Atrogin-1 and MuRF-1 in the tissues treated with Dex was established. A decrease in the number of striated myotubes was also observed in the tissues treated with Dex. Treatment with 8 ng/mL Insulin-like Growth Factor (IGF-I) for 24 h significantly increased the contractile force of the Dex-induced atrophic tissues. The same treatment, though, had no impact on the force of the normal tissues. Thus, it is envisaged that the atrophic skeletal muscle tissues induced by Dex can be used for drug screening against atrophy.

  11. Investigation of the “true” extraction recovery of analytes from multiple types of tissues and its impact on tissue bioanalysis using two model compounds

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Long, E-mail: long.yuan@bms.com [Bioanalytical Sciences, Research & Development, Bristol-Myers Squibb, Princeton, NJ 08543 (United States); Ma, Li [Biotransformation, Research & Development, Bristol-Myers Squibb, Princeton, NJ 08543 (United States); Dillon, Lisa [Discovery Toxicology, Research & Development, Bristol-Myers Squibb, Princeton, NJ 08543 (United States); Fancher, R. Marcus; Sun, Huadong [Metabolism and Pharmacokinetics, Research & Development, Bristol-Myers Squibb, Princeton, NJ 08543 (United States); Zhu, Mingshe [Biotransformation, Research & Development, Bristol-Myers Squibb, Princeton, NJ 08543 (United States); Lehman-McKeeman, Lois [Discovery Toxicology, Research & Development, Bristol-Myers Squibb, Princeton, NJ 08543 (United States); Aubry, Anne-Françoise [Bioanalytical Sciences, Research & Development, Bristol-Myers Squibb, Princeton, NJ 08543 (United States); Ji, Qin C., E-mail: qin.ji@bms.com [Bioanalytical Sciences, Research & Development, Bristol-Myers Squibb, Princeton, NJ 08543 (United States)

    2016-11-16

    LC-MS/MS has been widely applied to the quantitative analysis of tissue samples. However, one key remaining issue is that the extraction recovery of analyte from spiked tissue calibration standard and quality control samples (QCs) may not accurately represent the “true” recovery of analyte from incurred tissue samples. This may affect the accuracy of LC-MS/MS tissue bioanalysis. Here, we investigated whether the recovery determined using tissue QCs by LC-MS/MS can accurately represent the “true” recovery from incurred tissue samples using two model compounds: BMS-986104, a S1P{sub 1} receptor modulator drug candidate, and its phosphate metabolite, BMS-986104-P. We first developed a novel acid and surfactant assisted protein precipitation method for the extraction of BMS-986104 and BMS-986104-P from rat tissues, and determined their recoveries using tissue QCs by LC-MS/MS. We then used radioactive incurred samples from rats dosed with {sup 3}H-labeled BMS-986104 to determine the absolute total radioactivity recovery in six different tissues. The recoveries determined using tissue QCs and incurred samples matched with each other very well. The results demonstrated that, in this assay, tissue QCs accurately represented the incurred tissue samples to determine the “true” recovery, and LC-MS/MS assay was accurate for tissue bioanalysis. Another aspect we investigated is how the tissue QCs should be prepared to better represent the incurred tissue samples. We compared two different QC preparation methods (analyte spiked in tissue homogenates or in intact tissues) and demonstrated that the two methods had no significant difference when a good sample preparation was in place. The developed assay showed excellent accuracy and precision, and was successfully applied to the quantitative determination of BMS-986104 and BMS-986104-P in tissues in a rat toxicology study. - Highlights: • Investigated the “true” recovery in six different tissues using incurred

  12. Investigation of the “true” extraction recovery of analytes from multiple types of tissues and its impact on tissue bioanalysis using two model compounds

    International Nuclear Information System (INIS)

    Yuan, Long; Ma, Li; Dillon, Lisa; Fancher, R. Marcus; Sun, Huadong; Zhu, Mingshe; Lehman-McKeeman, Lois; Aubry, Anne-Françoise; Ji, Qin C.

    2016-01-01

    LC-MS/MS has been widely applied to the quantitative analysis of tissue samples. However, one key remaining issue is that the extraction recovery of analyte from spiked tissue calibration standard and quality control samples (QCs) may not accurately represent the “true” recovery of analyte from incurred tissue samples. This may affect the accuracy of LC-MS/MS tissue bioanalysis. Here, we investigated whether the recovery determined using tissue QCs by LC-MS/MS can accurately represent the “true” recovery from incurred tissue samples using two model compounds: BMS-986104, a S1P 1 receptor modulator drug candidate, and its phosphate metabolite, BMS-986104-P. We first developed a novel acid and surfactant assisted protein precipitation method for the extraction of BMS-986104 and BMS-986104-P from rat tissues, and determined their recoveries using tissue QCs by LC-MS/MS. We then used radioactive incurred samples from rats dosed with 3 H-labeled BMS-986104 to determine the absolute total radioactivity recovery in six different tissues. The recoveries determined using tissue QCs and incurred samples matched with each other very well. The results demonstrated that, in this assay, tissue QCs accurately represented the incurred tissue samples to determine the “true” recovery, and LC-MS/MS assay was accurate for tissue bioanalysis. Another aspect we investigated is how the tissue QCs should be prepared to better represent the incurred tissue samples. We compared two different QC preparation methods (analyte spiked in tissue homogenates or in intact tissues) and demonstrated that the two methods had no significant difference when a good sample preparation was in place. The developed assay showed excellent accuracy and precision, and was successfully applied to the quantitative determination of BMS-986104 and BMS-986104-P in tissues in a rat toxicology study. - Highlights: • Investigated the “true” recovery in six different tissues using incurred tissue

  13. Incorporation of lysosomal sequestration in the mechanistic model for prediction of tissue distribution of basic drugs.

    Science.gov (United States)

    Assmus, Frauke; Houston, J Brian; Galetin, Aleksandra

    2017-11-15

    The prediction of tissue-to-plasma water partition coefficients (Kpu) from in vitro and in silico data using the tissue-composition based model (Rodgers & Rowland, J Pharm Sci. 2005, 94(6):1237-48.) is well established. However, distribution of basic drugs, in particular into lysosome-rich lung tissue, tends to be under-predicted by this approach. The aim of this study was to develop an extended mechanistic model for the prediction of Kpu which accounts for lysosomal sequestration and the contribution of different cell types in the tissue of interest. The extended model is based on compound-specific physicochemical properties and tissue composition data to describe drug ionization, distribution into tissue water and drug binding to neutral lipids, neutral phospholipids and acidic phospholipids in tissues, including lysosomes. Physiological data on the types of cells contributing to lung, kidney and liver, their lysosomal content and lysosomal pH were collated from the literature. The predictive power of the extended mechanistic model was evaluated using a dataset of 28 basic drugs (pK a ≥7.8, 17 β-blockers, 11 structurally diverse drugs) for which experimentally determined Kpu data in rat tissue have been reported. Accounting for the lysosomal sequestration in the extended mechanistic model improved the accuracy of Kpu predictions in lung compared to the original Rodgers model (56% drugs within 2-fold or 88% within 3-fold of observed values). Reduction in the extent of Kpu under-prediction was also evident in liver and kidney. However, consideration of lysosomal sequestration increased the occurrence of over-predictions, yielding overall comparable model performances for kidney and liver, with 68% and 54% of Kpu values within 2-fold error, respectively. High lysosomal concentration ratios relative to cytosol (>1000-fold) were predicted for the drugs investigated; the extent differed depending on the lysosomal pH and concentration of acidic phospholipids among

  14. Applying the Health Belief Model and an Integrated Behavioral Model to Promote Breast Tissue Donation Among Asian Americans.

    Science.gov (United States)

    Shafer, Autumn; Kaufhold, Kelly; Luo, Yunjuan

    2018-07-01

    An important part in the effort to prevent, treat, and cure breast cancer is research done with healthy breast tissue. The Susan G. Komen for the Cure Tissue Bank at Indiana University Simon Cancer Center (KTB) encourages women to donate a small amount of healthy breast tissue and then provides that tissue to researchers studying breast cancer. Although KTB has a large donor base, the volume of tissue samples from Asian women is low despite prior marketing efforts to encourage donation among this population. This study builds on prior work promoting breast cancer screenings among Asian women by applying constructs from the Health Belief Model (HBM) and the Integrated Behavioral Model (IBM) to investigate why Asian-American women are less inclined to donate their healthy breast tissue than non-Asian women and how this population may be motivated to donate in the future. A national online survey (N = 1,317) found Asian women had significantly lower perceived severity, some lower perceived benefits, and higher perceived barriers to tissue donation than non-Asian women under HBM and significantly lower injunctive norms supporting breast tissue donation, lower perceived behavioral control, and lower intentions to donate under IBM. This study also compares and discusses similarities and differences among East, Southeast, and South Asian women on these same constructs.

  15. In vivo studies of peritendinous tissue in exercise

    DEFF Research Database (Denmark)

    Kjaer, M; Langberg, Henning; Skovgaard, D

    2000-01-01

    Soft tissue injury of tendons represents a major problem within sports medicine. Although several animal and cell culture studies have addressed this, human experiments have been limited in their ability to follow changes in specific tissue directly in response to interventions. Recently, methods...... have allowed for in vivo determination of tissue concentrations and release rates of substances involved in metabolism, inflammation and collagen synthesis, together with the measurement of tissue blood flow and oxygenation in the peritendinous region around the Achilles tendon in humans during...... exercise. This coincides with a surprisingly marked drop in tissue pressure during contraction. With regards to both circulation, metabolism and collagen formation, peritendinous tissue represents a dynamic, responsive region that adapts markedly to acute muscular activity....

  16. Statistical Validation of Normal Tissue Complication Probability Models

    Energy Technology Data Exchange (ETDEWEB)

    Xu Chengjian, E-mail: c.j.xu@umcg.nl [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schaaf, Arjen van der; Veld, Aart A. van' t; Langendijk, Johannes A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schilstra, Cornelis [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Radiotherapy Institute Friesland, Leeuwarden (Netherlands)

    2012-09-01

    Purpose: To investigate the applicability and value of double cross-validation and permutation tests as established statistical approaches in the validation of normal tissue complication probability (NTCP) models. Methods and Materials: A penalized regression method, LASSO (least absolute shrinkage and selection operator), was used to build NTCP models for xerostomia after radiation therapy treatment of head-and-neck cancer. Model assessment was based on the likelihood function and the area under the receiver operating characteristic curve. Results: Repeated double cross-validation showed the uncertainty and instability of the NTCP models and indicated that the statistical significance of model performance can be obtained by permutation testing. Conclusion: Repeated double cross-validation and permutation tests are recommended to validate NTCP models before clinical use.

  17. Statistical validation of normal tissue complication probability models.

    Science.gov (United States)

    Xu, Cheng-Jian; van der Schaaf, Arjen; Van't Veld, Aart A; Langendijk, Johannes A; Schilstra, Cornelis

    2012-09-01

    To investigate the applicability and value of double cross-validation and permutation tests as established statistical approaches in the validation of normal tissue complication probability (NTCP) models. A penalized regression method, LASSO (least absolute shrinkage and selection operator), was used to build NTCP models for xerostomia after radiation therapy treatment of head-and-neck cancer. Model assessment was based on the likelihood function and the area under the receiver operating characteristic curve. Repeated double cross-validation showed the uncertainty and instability of the NTCP models and indicated that the statistical significance of model performance can be obtained by permutation testing. Repeated double cross-validation and permutation tests are recommended to validate NTCP models before clinical use. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. A visco-hyperelastic constitutive model and its application in bovine tongue tissue.

    Science.gov (United States)

    Yousefi, Ali-Akbar Karkhaneh; Nazari, Mohammad Ali; Perrier, Pascal; Panahi, Masoud Shariat; Payan, Yohan

    2018-04-11

    Material properties of the human tongue tissue have a significant role in understanding its function in speech, respiration, suckling, and swallowing. Tongue as a combination of various muscles is surrounded by the mucous membrane and is a complicated architecture to study. As a first step before the quantitative mechanical characterization of human tongue tissues, the passive biomechanical properties in the superior longitudinal muscle (SLM) and the mucous tissues of a bovine tongue have been measured. Since the rate of loading has a sizeable contribution to the resultant stress of soft tissues, the rate dependent behavior of tongue tissues has been investigated via uniaxial tension tests (UTTs). A method to determine the mechanical properties of transversely isotropic tissues using UTTs and inverse finite element (FE) method has been proposed. Assuming the strain energy as a general nonlinear relationship with respect to the stretch and the rate of stretch, two visco-hyperelastic constitutive laws (CLs) have been proposed for isotropic and transversely isotropic soft tissues to model their stress-stretch behavior. Both of them have been implemented in ABAQUS explicit through coding a user-defined material subroutine called VUMAT and the experimental stress-stretch points have been well tracked by the results of FE analyses. It has been demonstrated that the proposed laws make a good description of the viscous nature of tongue tissues. Reliability of the proposed models has been compared with similar nonlinear visco-hyperelastic CLs. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Local stem cell depletion model for normal tissue damage

    International Nuclear Information System (INIS)

    Yaes, R.J.; Keland, A.

    1987-01-01

    The hypothesis that radiation causes normal tissue damage by completely depleting local regions of tissue of viable stem cells leads to a simple mathematical model for such damage. In organs like skin and spinal cord where destruction of a small volume of tissue leads to a clinically apparent complication, the complication probability is expressed as a function of dose, volume and stem cell number by a simple triple negative exponential function analogous to the double exponential function of Munro and Gilbert for tumor control. The steep dose response curves for radiation myelitis that are obtained with our model are compared with the experimental data for radiation myelitis in laboratory rats. The model can be generalized to include other types or organs, high LET radiation, fractionated courses of radiation, and cases where an organ with a heterogeneous stem cell population receives an inhomogeneous dose of radiation. In principle it would thus be possible to determine the probability of tumor control and of damage to any organ within the radiation field if the dose distribution in three dimensional space within a patient is known

  20. A model of engineering materials inspired by biological tissues

    Directory of Open Access Journals (Sweden)

    Holeček M.

    2009-12-01

    Full Text Available The perfect ability of living tissues to control and adapt their mechanical properties to varying external conditions may be an inspiration for designing engineering materials. An interesting example is the smooth muscle tissue since this "material" is able to change its global mechanical properties considerably by a subtle mechanism within individual muscle cells. Multi-scale continuum models may be useful in designing essentially simpler engineering materials having similar properties. As an illustration we present the model of an incompressible material whose microscopic structure is formed by flexible, soft but incompressible balls connected mutually by linear springs. This simple model, however, shows a nontrivial nonlinear behavior caused by the incompressibility of balls and is very sensitive on some microscopic parameters. It may elucidate the way by which "small" changes in biopolymer networks within individual muscular cells may control the stiffness of the biological tissue, which outlines a way of designing similar engineering materials. The 'balls and springs' material presents also prestress-induced stiffening and allows elucidating a contribution of extracellular fluids into the tissue’s viscous properties.

  1. A computational modeling approach for the characterization of mechanical properties of 3D alginate tissue scaffolds.

    Science.gov (United States)

    Nair, K; Yan, K C; Sun, W

    2008-01-01

    Scaffold guided tissue engineering is an innovative approach wherein cells are seeded onto biocompatible and biodegradable materials to form 3-dimensional (3D) constructs that, when implanted in the body facilitate the regeneration of tissue. Tissue scaffolds act as artificial extracellular matrix providing the environment conducive for tissue growth. Characterization of scaffold properties is necessary to understand better the underlying processes involved in controlling cell behavior and formation of functional tissue. We report a computational modeling approach to characterize mechanical properties of 3D gellike biomaterial, specifically, 3D alginate scaffold encapsulated with cells. Alginate inherent nonlinearity and variations arising from minute changes in its concentration and viscosity make experimental evaluation of its mechanical properties a challenging and time consuming task. We developed an in silico model to determine the stress-strain relationship of alginate based scaffolds from experimental data. In particular, we compared the Ogden hyperelastic model to other hyperelastic material models and determined that this model was the most suitable to characterize the nonlinear behavior of alginate. We further propose a mathematical model that represents the alginate material constants in Ogden model as a function of concentrations and viscosity. This study demonstrates the model capability to predict mechanical properties of 3D alginate scaffolds.

  2. The effect of hard tissue surgical changes on soft tissue displacement: a pilot CBCT study

    Directory of Open Access Journals (Sweden)

    Leonardo Koerich

    Full Text Available ABSTRACT Introduction: This pilot study had as main objective to test the reliability of a new method to evaluate orthognathic surgery outcomes and also, to understand the effect of hard tissue changes on soft tissue displacement. Methods: The sample consisted of eight patients that underwent bimaxillary advancement and had CBCT at two time points (before surgery and 6-8 months follow-up. Voxel-based cranial base superimposition was used to register the scans. A different technique of iterative closest point (ICP was used to measure and correlate the changes. The average displacement of 15 areas (4 hard tissue and 11 soft tissue were measured twice. Results: ICC was > 0.99 for all areas. Changes in the tip of the nose did not correlate with changes in any maxillary area, whereas soft tissue A point, A point and upper lips had correlation with several areas. The highest correlation for the maxilla was between the upper lip and the left/right supra cheilion (p< 0.001, r= 0.91 and p< 0.001, r= 0.93, respectively. In the mandible, the majority of the correlations involved soft tissue pogonion, pogonion and lower incisors, with the strongest one between pogonion and lower incisors (p< 0.001, r= 0.98. Conclusion: With the proper case selection, ICP is a reliable method that can be used to assess three-dimensional changes.

  3. Study of the optical properties of solid tissue phantoms using single and double integrating sphere systems

    CSIR Research Space (South Africa)

    Monem, S

    2015-12-01

    Full Text Available light propagation mechanisms inside the tissues. In this work, two calibration models based on measurements adopting integrating sphere systems have been used to determine the optical properties of the studied solid phantoms. Integrating sphere...

  4. Phytophthora ramorum tissue colonization studied with fluorescense microscopy

    Science.gov (United States)

    M. Riedel; S. Wagner; M. Gotz; L. Belbahri; F. Lefort; S. Werres

    2009-01-01

    The proceeding worldwide spread and the expanding host spectrum of P. ramorum has become a serious threat to natural plant communities. To encounter this threat detailed knowledge about infection pathways and tissue colonization is essential. To analyze these issues, histological studies of infected tissue with epifluorescence microscopy have been...

  5. Cyclic Loading of Growing Tissue in a Bioreactor: Mathematical Model and Asymptotic Analysis

    KAUST Repository

    Pohlmeyer, J. V.; Cummings, L. J.

    2013-01-01

    A simplified 2D mathematical model for tissue growth within a cyclically-loaded tissue engineering scaffold is presented and analyzed. Such cyclic loading has the potential to improve yield and functionality of tissue such as bone and cartilage when

  6. Characterizing the lung tissue mechanical properties using a micromechanical model of alveolar sac

    Science.gov (United States)

    Karami, Elham; Seify, Behzad; Moghadas, Hadi; Sabsalinejad, Masoomeh; Lee, Ting-Yim; Samani, Abbas

    2017-03-01

    According to statistics, lung disease is among the leading causes of death worldwide. As such, many research groups are developing powerful tools for understanding, diagnosis and treatment of various lung diseases. Recently, biomechanical modeling has emerged as an effective tool for better understanding of human physiology, disease diagnosis and computer assisted medical intervention. Mechanical properties of lung tissue are important requirements for methods developed for lung disease diagnosis and medical intervention. As such, the main objective of this study is to develop an effective tool for estimating the mechanical properties of normal and pathological lung parenchyma tissue based on its microstructure. For this purpose, a micromechanical model of the lung tissue was developed using finite element (FE) method, and the model was demonstrated to have application in estimating the mechanical properties of lung alveolar wall. The proposed model was developed by assembling truncated octahedron tissue units resembling the alveoli. A compression test was simulated using finite element method on the created geometry and the hyper-elastic parameters of the alveoli wall were calculated using reported alveolar wall stress-strain data and an inverse optimization framework. Preliminary results indicate that the proposed model can be potentially used to reconstruct microstructural images of lung tissue using macro-scale tissue response for normal and different pathological conditions. Such images can be used for effective diagnosis of lung diseases such as Chronic Obstructive Pulmonary Disease (COPD).

  7. Comparison of Experimental Models for Predicting Laser Tissue Interaction from 3.8-Micron Lasers

    National Research Council Canada - National Science Library

    Williams, Charles Melville

    2004-01-01

    The purpose of this study was to compare and contrast the effects of single 3.8-micron laser pulses in an in-vitro and in-vivo model of human skin and to demonstrate the efficacy of in-vitro laser tissue interaction models...

  8. Sensitivity of microwave ablation models to tissue biophysical properties: A first step toward probabilistic modeling and treatment planning.

    Science.gov (United States)

    Sebek, Jan; Albin, Nathan; Bortel, Radoslav; Natarajan, Bala; Prakash, Punit

    2016-05-01

    Computational models of microwave ablation (MWA) are widely used during the design optimization of novel devices and are under consideration for patient-specific treatment planning. The objective of this study was to assess the sensitivity of computational models of MWA to tissue biophysical properties. The Morris method was employed to assess the global sensitivity of the coupled electromagnetic-thermal model, which was implemented with the finite element method (FEM). The FEM model incorporated temperature dependencies of tissue physical properties. The variability of the model was studied using six different outputs to characterize the size and shape of the ablation zone, as well as impedance matching of the ablation antenna. Furthermore, the sensitivity results were statistically analyzed and absolute influence of each input parameter was quantified. A framework for systematically incorporating model uncertainties for treatment planning was suggested. A total of 1221 simulations, incorporating 111 randomly sampled starting points, were performed. Tissue dielectric parameters, specifically relative permittivity, effective conductivity, and the threshold temperature at which they transitioned to lower values (i.e., signifying desiccation), were identified as the most influential parameters for the shape of the ablation zone and antenna impedance matching. Of the thermal parameters considered in this study, the nominal blood perfusion rate and the temperature interval across which the tissue changes phase were identified as the most influential. The latent heat of tissue water vaporization and the volumetric heat capacity of the vaporized tissue were recognized as the least influential parameters. Based on the evaluation of absolute changes, the most important parameter (perfusion) had approximately 40.23 times greater influence on ablation area than the least important parameter (volumetric heat capacity of vaporized tissue). Another significant input parameter

  9. Multiaxial mechanical response and constitutive modeling of esophageal tissues: Impact on esophageal tissue engineering.

    Science.gov (United States)

    Sommer, Gerhard; Schriefl, Andreas; Zeindlinger, Georg; Katzensteiner, Andreas; Ainödhofer, Herwig; Saxena, Amulya; Holzapfel, Gerhard A

    2013-12-01

    Congenital defects of the esophagus are relatively frequent, with 1 out of 2500 babies suffering from such a defect. A new method of treatment by implanting tissue engineered esophagi into newborns is currently being developed and tested using ovine esophagi. For the reconstruction of the biological function of native tissues with engineered esophagi, their cellular structure as well as their mechanical properties must be considered. Since very limited mechanical and structural data for the esophagus are available, the aim of this study was to investigate the multiaxial mechanical behavior of the ovine esophagus and the underlying microstructure. Therefore, uniaxial tensile, biaxial tensile and extension-inflation tests on esophagi were performed. The underlying microstructure was examined in stained histological sections through standard optical microscopy techniques. Moreover, the uniaxial ultimate tensile strength and residual deformations of the tissue were determined. Both the mucosa-submucosa and the muscle layers showed nonlinear and anisotropic mechanical behavior during uniaxial, biaxial and inflation testing. Cyclical inflation of the intact esophageal tube caused marked softening of the passive esophagi in the circumferential direction. The rupture strength of the mucosa-submucosa layer was much higher than that of the muscle layer. Overall, the ovine esophagus showed a heterogeneous and anisotropic behavior with different mechanical properties for the individual layers. The intact and layer-specific multiaxial properties were characterized using a well-known three-dimensional microstructurally based strain-energy function. This novel and complete set of data serves the basis for a better understanding of tissue remodeling in diseased esophagi and can be used to perform computer simulations of surgical interventions or medical-device applications. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  10. Study into penetration speed during laser cutting of brain tissues.

    Science.gov (United States)

    Yilbas, Z; Sami, M; Patiroglu, T

    1998-01-01

    The applications of CO2 continuous-wave lasers in neurosurgery have become important in recent years. Theoretical considerations of laser applicability in medicine are subsequently confirmed experimentally. To obtain precision operation in the laser cutting process, further theoretical developments and experimental studies need to be conducted. Consequently, in the present study, the heat transfer mechanism taking place during laser-tissue interaction is introduced using Fourier theory. The results obtained from the theoretical model are compared with the experimental results. In connection with this, an experiment is designed to measure the penetration speed during the laser cutting process. The measurement is carried out using an optical method. It is found that both results for the penetration speed obtained from the theory and experiment are in a good agreement.

  11. Multi-tissue computational modeling analyzes pathophysiology of type 2 diabetes in MKR mice.

    Directory of Open Access Journals (Sweden)

    Amit Kumar

    Full Text Available Computational models using metabolic reconstructions for in silico simulation of metabolic disorders such as type 2 diabetes mellitus (T2DM can provide a better understanding of disease pathophysiology and avoid high experimentation costs. There is a limited amount of computational work, using metabolic reconstructions, performed in this field for the better understanding of T2DM. In this study, a new algorithm for generating tissue-specific metabolic models is presented, along with the resulting multi-confidence level (MCL multi-tissue model. The effect of T2DM on liver, muscle, and fat in MKR mice was first studied by microarray analysis and subsequently the changes in gene expression of frank T2DM MKR mice versus healthy mice were applied to the multi-tissue model to test the effect. Using the first multi-tissue genome-scale model of all metabolic pathways in T2DM, we found out that branched-chain amino acids' degradation and fatty acids oxidation pathway is downregulated in T2DM MKR mice. Microarray data showed low expression of genes in MKR mice versus healthy mice in the degradation of branched-chain amino acids and fatty-acid oxidation pathways. In addition, the flux balance analysis using the MCL multi-tissue model showed that the degradation pathways of branched-chain amino acid and fatty acid oxidation were significantly downregulated in MKR mice versus healthy mice. Validation of the model was performed using data derived from the literature regarding T2DM. Microarray data was used in conjunction with the model to predict fluxes of various other metabolic pathways in the T2DM mouse model and alterations in a number of pathways were detected. The Type 2 Diabetes MCL multi-tissue model may explain the high level of branched-chain amino acids and free fatty acids in plasma of Type 2 Diabetic subjects from a metabolic fluxes perspective.

  12. Modeling the behavior of human body tissues on penetration

    Science.gov (United States)

    Conci, A.; Brazil, A. L.; Popovici, D.; Jiga, G.; Lebon, F.

    2018-02-01

    Several procedures in medicine (such as anesthesia, injections, biopsies and percutaneous treatments) involve a needle insertion. Such procedures operate without vision of the internal involved areas. Physicians and anesthetists rely on manual (force and tactile) feedback to guide their movements, so a number of medical practice is strongly based on manual skill. In order to be expert in the execution of such procedures the medical students must practice a number of times, but before practice in a real patient they must be trained in some place and a virtual environment, using Virtual Reality (VR) or Augmented Reality (AR) is the best possible solution for such training. In a virtual environment the success of user practices is improved by the addition of force output using haptic device to improve the manual sensations in the interactions between user and computer. Haptic devices enable simulate the physical restriction of the diverse tissues and force reactions to movements of operator hands. The trainees can effectively "feel" the reactions to theirs movements and receive immediate feedback from the actions executed by them in the implemented environment. However, in order to implement such systems, the tissue reaction to penetration and cutting must be modeled. A proper model must emulate the physical sensations of the needle action in the skin, fat, muscle, and so one, as if it really done in a patient that is as they are holding a real needle and feeling each tissue resistance when inserting it through the body. For example an average force value for human skin puncture is 6.0 N, it is 2.0 N for subcutaneous fat tissue and 4.4 N for muscles: this difference of sensations to penetration of each layers trespassed by the needle makes possible to suppose the correct position inside the body. This work presents a model for tissues before and after the cutting that with proper assumptions of proprieties can model any part of human body. It was based on experiments

  13. Biomechanics of cells and tissues experiments, models and simulations

    CERN Document Server

    2013-01-01

    The application of methodological approaches and mathematical formalisms proper to Physics and Engineering to investigate and describe biological processes and design biological structures has led to the development of many disciplines in the context of computational biology and biotechnology. The best known applicative domain is tissue engineering and its branches. Recent domains of interest are in the field of biophysics, e.g.: multiscale mechanics of biological membranes and films and filaments; multiscale mechanics of adhesion; biomolecular motors and force generation.   Modern hypotheses, models, and tools are currently emerging and resulting from the convergence of the methods and philosophical approaches of the different research areas and disciplines. All these emerging approaches share the purpose of disentangling the complexity of organisms, tissues, and cells and mimicking the function of living systems. The contributions presented in this book are current research highlights of six challenging an...

  14. Mathematical model of normal tissue injury in telegammatherapy

    International Nuclear Information System (INIS)

    Belov, S.A.; Lyass, F.M.; Mamin, R.G.; Minakova, E.I.; Raevskaya, S.A.

    1983-01-01

    A model of normal tissue injury as a result of exposure to ionizing radiation is based on an assumption that the degree of tissue injury is determined by the degree of destruction by certain critical cells. The dependence of the number of lethal injuriies on a single dose is expressed by a trinomial - linear and quadratic parts and a constant, obtained as a result of the processing of experimental data. Quantitative correlations have been obtained for the skin and brain. They have been tested using clinical and experimental material. The results of the testing point out to the absence of time dependence on a single up to 6-week irradiation cources. Correlation with an irradiation field has been obtained for the skin. A conclusion has been made that the concept of isoefficacy of irradiation cources is conditional. Spatial-time fractionation is a promising direction in the development of radiation therapy

  15. Mesenchymal stem cell cultivation in electrospun scaffolds: mechanistic modeling for tissue engineering.

    Science.gov (United States)

    Paim, Ágata; Tessaro, Isabel C; Cardozo, Nilo S M; Pranke, Patricia

    2018-03-05

    Tissue engineering is a multidisciplinary field of research in which the cells, biomaterials, and processes can be optimized to develop a tissue substitute. Three-dimensional (3D) architectural features from electrospun scaffolds, such as porosity, tortuosity, fiber diameter, pore size, and interconnectivity have a great impact on cell behavior. Regarding tissue development in vitro, culture conditions such as pH, osmolality, temperature, nutrient, and metabolite concentrations dictate cell viability inside the constructs. The effect of different electrospun scaffold properties, bioreactor designs, mesenchymal stem cell culture parameters, and seeding techniques on cell behavior can be studied individually or combined with phenomenological modeling techniques. This work reviews the main culture and scaffold factors that affect tissue development in vitro regarding the culture of cells inside 3D matrices. The mathematical modeling of the relationship between these factors and cell behavior inside 3D constructs has also been critically reviewed, focusing on mesenchymal stem cell culture in electrospun scaffolds.

  16. Imaging and modeling of collagen architecture in living tissue with polarized light transfer (Conference Presentation)

    Science.gov (United States)

    Ramella-Roman, Jessica C.; Stoff, Susan; Chue-Sang, Joseph; Bai, Yuqiang

    2016-03-01

    The extra-cellular space in connective tissue of animals and humans alike is comprised in large part of collagen. Monitoring of collagen arrangement and cross-linking has been utilized to diagnose a variety of medical conditions and guide surgical intervention. For example, collagen monitoring is useful in the assessment and treatment of cervical cancer, skin cancer, myocardial infarction, and non-arteritic anterior ischemic optic neuropathy. We have developed a suite of tools and models based on polarized light transfer for the assessment of collagen presence, cross-linking, and orientation in living tissue. Here we will present some example of such approach applied to the human cervix. We will illustrate a novel Mueller Matrix (MM) imaging system for the study of cervical tissue; furthermore we will show how our model of polarized light transfer through cervical tissue compares to the experimental findings. Finally we will show validation of the methodology through histological results and Second Harmonic imaging microscopy.

  17. Modelling the mechanics of partially mineralized collagen fibrils, fibres and tissue

    Science.gov (United States)

    Liu, Yanxin; Thomopoulos, Stavros; Chen, Changqing; Birman, Victor; Buehler, Markus J.; Genin, Guy M.

    2014-01-01

    Progressive stiffening of collagen tissue by bioapatite mineral is important physiologically, but the details of this stiffening are uncertain. Unresolved questions about the details of the accommodation of bioapatite within and upon collagen's hierarchical structure have posed a central hurdle, but recent microscopy data resolve several major questions. These data suggest how collagen accommodates bioapatite at the lowest relevant hierarchical level (collagen fibrils), and suggest several possibilities for the progressive accommodation of bioapatite at higher hierarchical length scales (fibres and tissue). We developed approximations for the stiffening of collagen across spatial hierarchies based upon these data, and connected models across hierarchies levels to estimate mineralization-dependent tissue-level mechanics. In the five possible sequences of mineralization studied, percolation of the bioapatite phase proved to be an important determinant of the degree of stiffening by bioapatite. The models were applied to study one important instance of partially mineralized tissue, which occurs at the attachment of tendon to bone. All sequences of mineralization considered reproduced experimental observations of a region of tissue between tendon and bone that is more compliant than either tendon or bone, but the size and nature of this region depended strongly upon the sequence of mineralization. These models and observations have implications for engineered tissue scaffolds at the attachment of tendon to bone, bone development and graded biomimetic attachment of dissimilar hierarchical materials in general. PMID:24352669

  18. Micro-mechanical model for the tension-stabilized enzymatic degradation of collagen tissues

    Science.gov (United States)

    Nguyen, Thao; Ruberti, Jeffery

    We present a study of how the collagen fiber structure influences the enzymatic degradation of collagen tissues. Experiments of collagen fibrils and tissues show that mechanical tension can slow and halt enzymatic degradation. Tissue-level experiments also show that degradation rate is minimum at a stretch level coincident with the onset of strain-stiffening in the stress response. To understand these phenomena, we developed a micro-mechanical model of a fibrous collagen tissue undergoing enzymatic degradation. Collagen fibers are described as sinusoidal elastica beams, and the tissue is described as a distribution of fibers. We assumed that the degradation reaction is inhibited by the axial strain energy of the crimped collagen fibers. The degradation rate law was calibrated to experiments on isolated single fibrils from bovine sclera. The fiber crimp and properties were fit to uniaxial tension tests of tissue strips. The fibril-level kinetic and tissue-level structural parameters were used to predict tissue-level degradation-induced creep rate under a constant applied force. We showed that we could accurately predict the degradation-induce creep rate of the pericardium and cornea once we accounted for differences in the fiber crimp structure and properties.

  19. A dynamic model to calculate cadmium concentrations in bovine tissues from basic soil characteristics

    International Nuclear Information System (INIS)

    Waegeneers, Nadia; Ruttens, Ann; De Temmerman, Ludwig

    2011-01-01

    A chain model was developed to calculate the flow of cadmium from soil, drinking water and feed towards bovine tissues. The data used for model development were tissue Cd concentrations of 57 bovines and Cd concentrations in soil, feed and drinking water, sampled at the farms were the bovines were reared. Validation of the model occurred with a second set of measured tissue Cd concentrations of 93 bovines of which age and farm location were known. The exposure part of the chain model consists of two parts: (1) a soil-plant transfer model, deriving cadmium concentrations in feed from basic soil characteristics (pH and organic matter content) and soil Cd concentrations, and (2) bovine intake calculations, based on typical feed and water consumption patterns for cattle and Cd concentrations in feed and drinking water. The output of the exposure model is an animal-specific average daily Cd intake, which is then taken forward to a kinetic uptake model in which time-dependent Cd concentrations in bovine tissues are calculated. The chain model was able to account for 65%, 42% and 32% of the variation in observed kidney, liver and meat Cd concentrations in the validation study. - Research highlights: → Cadmium transfer from soil, drinking water and feed to bovine tissues was modeled. → The model was based on 57 bovines and corresponding feed and soil Cd concentrations. → The model was validated with an independent data set of 93 bovines. → The model explained 65% of variation in kidney Cd in the validation study.

  20. A Tissue Propagation Model for Validating Close-Proximity Biomedical Radiometer Measurements

    Science.gov (United States)

    Bonds, Q.; Herzig, P.; Weller, T.

    2016-01-01

    The propagation of thermally-generated electromagnetic emissions through stratified human tissue is studied herein using a non-coherent mathematical model. The model is developed to complement subsurface body temperature measurements performed using a close proximity microwave radiometer. The model takes into account losses and reflections as thermal emissions propagate through the body, before being emitted at the skin surface. The derivation is presented in four stages and applied to the human core phantom, a physical representation of a stomach volume of skin, muscle, and blood-fatty tissue. A drop in core body temperature is simulated via the human core phantom and the response of the propagation model is correlated to the radiometric measurement. The results are comparable, with differences on the order of 1.5 - 3%. Hence the plausibility of core body temperature extraction via close proximity radiometry is demonstrated, given that the electromagnetic characteristics of the stratified tissue layers are known.

  1. Prefabrication of axial vascularized tissue engineering coral bone by an arteriovenous loop: A better model

    International Nuclear Information System (INIS)

    Dong Qingshan; Shang Hongtao; Wu Wei; Chen Fulin; Zhang Junrui; Guo Jiaping; Mao Tianqiu

    2012-01-01

    The most important problem for the survival of thick 3-dimensional tissues is the lack of vascularization in the context of bone tissue engineering. In this study, a modified arteriovenous loop (AVL) was developed to prefabricate an axial vascularized tissue engineering coral bone in rabbit, with comparison of the arteriovenous bundle (AVB) model. An arteriovenous fistula between rabbit femoral artery and vein was anastomosed to form an AVL. It was placed in a circular side groove of the coral block. The complex was wrapped with an expanded-polytetrafluoroethylene membrane and implanted beneath inguinal skin. After 2, 4, 6 and 8 weeks, the degree of vascularization was evaluated by India ink perfusion, histological examination, vascular casts, and scanning electron microscopy images of vascular endangium. Newly formed fibrous tissues and vasculature extended over the surfaces and invaded the interspaces of entire coral block. The new blood vessels robustly sprouted from the AVL. Those invaginated cavities in the vascular endangium from scanning electron microscopy indicated vessel's sprouted pores. Above indexes in AVL model are all superior to that in AVB model, indicating that the modified AVL model could more effectively develop vascularization in larger tissue engineering bone. - Highlights: ► A modified arteriovenous loop (AVL) model in rabbit was developed in this study. ► Axial prevascularization was induced in a larger coral block by using the AVL. ► The prefabrication of axial vascularized coral bone is superior as vascular carrier.

  2. Comparative study of the iron cores in human liver ferritin, its pharmaceutical models and ferritin in chicken liver and spleen tissues using Moessbauer spectroscopy with a high velocity resolution

    Energy Technology Data Exchange (ETDEWEB)

    Alenkina, I.V.; Semionkin, V.A. [Faculty of Physical Techniques and Devices for Quality Control, Ural Federal University, Ekaterinburg (Russian Federation); Faculty of Experimental Physics, Ural Federal University, Ekaterinburg (Russian Federation); Oshtrakh, M.I. [Faculty of Physical Techniques and Devices for Quality Control, Ural Federal University, Ekaterinburg (Russian Federation); Klepova, Yu.V.; Sadovnikov, N.V. [Faculty of Physiology and Biotechnology, Ural State Agricultural Academy, Ekaterinburg, (Russian Federation); Dubiel, S.M. [Faculty of Physics and Applied Computer Science, AGH University of Science and Technology, Krakow (Poland)

    2011-07-01

    Full text: Application of the Moessbauer spectroscopy with a high velocity resolution (4096 channels) for a study of iron-containing biological species is of great interest. Improving the velocity resolution allows to reveal small variations in the electronic structure of iron, and to obtain hyperfine parameters with smaller instrumental (systematic) errors in comparison with measurements performed in 512 channels or less. It also allows a more reliable fitting of complex Moessbauer spectra. In the present study the Moessbauer spectroscopy with the high velocity resolution was used for a comparative analysis of ferritin and its pharmaceutically important models as well as iron storage proteins in a chicken liver and a spleen. The ferritin, an iron storage protein, consists of a nanosized polynuclear iron core formed by a ferrihydrite surrounded by a protein shell. Iron-polysaccharide complexes contain {beta}-FeOOH iron cores coated with various polysaccharides. The Moessbauer spectra of the ferritin and commercial products Imferon, MaltoferR and Ferrum Lek as well as those of the chicken liver and spleen tissues were measured with the high velocity resolution at 295 and 90 K. They were fitted using two models: (1) with a homogeneous iron core (an approximation using one quadrupole doublet), and (2) with a heterogeneous iron core (an approximation using several quadrupole doublets). The model (1) can be used as the first approximation fit to visualize small variations in the hyperfine parameters. Using this model, differences in the Moessbauer hyperfine parameters were obtained in both 295 and 90 K Moessbauer spectra. However, this model was considered as a rough approximation because the measured Moessbauer spectra had non-Lorentzian line shapes. Therefore, the spectra of the ferritin, Imferon, MaltoferR and Ferrum Lek as well as those of the liver and spleen tissues were fitted again using the model (2) in which a different number of the quadrupole doublets was

  3. Electrode-tissues interface: modeling and experimental validation

    International Nuclear Information System (INIS)

    Sawan, M; Laaziri, Y; Mounaim, F; Elzayat, E; Corcos, J; Elhilali, M M

    2007-01-01

    The electrode-tissues interface (ETI) is one of the key issues in implantable devices such as stimulators and sensors. Once the stimulator is implanted, safety and reliability become more and more critical. In this case, modeling and monitoring of the ETI are required. We propose an empirical model for the ETI and a dedicated integrated circuit to measure its corresponding complex impedance. These measurements in the frequency range of 1 Hz to 100 kHz were achieved in acute dog experiments. The model demonstrates a closer fitting with experimental measurements. In addition, a custom monitoring device based on a stimuli current generator has been completed to evaluate the phase shift and voltage across the electrodes and to transmit wirelessly the values to an external controller. This integrated circuit has been fabricated in a CMOS 0.18 μm process, which consumes 4 mW only during measurements and occupies an area of 1 mm 2 . (review article)

  4. Ethical tissue: a not-for-profit model for human tissue supply.

    Science.gov (United States)

    Adams, Kevin; Martin, Sandie

    2011-02-01

    Following legislative changes in 2004 and the establishment of the Human Tissue Authority, access to human tissues for biomedical research became a more onerous and tightly regulated process. Ethical Tissue was established to meet the growing demand for human tissues, using a process that provided ease of access by researchers whilst maintaining the highest ethical and regulatory standards. The establishment of a licensed research tissue bank entailed several key criteria covering ethical, legal, financial and logistical issues being met. A wide range of stakeholders, including the HTA, University of Bradford, flagged LREC, hospital trusts and clinical groups were also integral to the process.

  5. Coalescent models for developmental biology and the spatio-temporal dynamics of growing tissues.

    Science.gov (United States)

    Smadbeck, Patrick; Stumpf, Michael P H

    2016-04-01

    Development is a process that needs to be tightly coordinated in both space and time. Cell tracking and lineage tracing have become important experimental techniques in developmental biology and allow us to map the fate of cells and their progeny. A generic feature of developing and homeostatic tissues that these analyses have revealed is that relatively few cells give rise to the bulk of the cells in a tissue; the lineages of most cells come to an end quickly. Computational and theoretical biologists/physicists have, in response, developed a range of modelling approaches, most notably agent-based modelling. These models seem to capture features observed in experiments, but can also become computationally expensive. Here, we develop complementary genealogical models of tissue development that trace the ancestry of cells in a tissue back to their most recent common ancestors. We show that with both bounded and unbounded growth simple, but universal scaling relationships allow us to connect coalescent theory with the fractal growth models extensively used in developmental biology. Using our genealogical perspective, it is possible to study bulk statistical properties of the processes that give rise to tissues of cells, without the need for large-scale simulations. © 2016 The Authors.

  6. Differential superiority of heavy charged-particle irradiation to x-rays: Studies on biological effectivenes and side effect mechanisms in multicellular tumor and normal tissue models

    Directory of Open Access Journals (Sweden)

    Stefan eWalenta

    2016-02-01

    Full Text Available This review is focused on the radiobiology of carbon ions compared to x-rays using multicellular models of tumors and normal mucosa. The first part summarizes basic radiobiological effects, as observed in cancer cells. The second, more clinically oriented part of the review deals with radiation-induced cell migration and mucositis.Multicellular spheroids (MCS from V79 hamster cells were irradiated with x-rays or carbon ions under ambient or restricted oxygen supply conditions. Oxygen enhancement ratios (OER were 2.9, 2.8, and 1.4 for irradiation with photons, 12C+6 in the plateau region, and 12C+6 in the Bragg peak, respectively. A relative biological effectiveness (RBE of 4.3 and 2.1 for ambient pO2 and hypoxia was obtained, respectively. The high effectiveness of carbon ions was reflected by an enhanced accumulation of cells in G2/M, and a dose-dependent massive induction of apoptosis. Clinically relevant doses (3 Gy of x-rays induced an increase in migratory activity of U87 but not of LN229 or HCT116 tumor cells. Such an increase in cell motility following irradiation in situ could be the source of recurrence. In contrast, carbon ion treatment was associated with a dose-dependent decrease in migration with all cell lines and under all conditions investigated. The radiation-induced loss of cell motility was correlated, in most cases, with corresponding changes in 1 integrin expression. Unlike with particles, the photon-induced increase in cell migration was paralleled by an elevated phosphorylation status of the epidermal growth factor receptor (EGFR and AKT-ERK1/2 pathway. Comparing the gene toxicity of x-rays with that of particles using the gamma-H2AX technique in organotypic cultures of the oral mucosa, the superior effectiveness of heavy ions was confirmed by a two-fold higher number of foci per nucleus. Pro-inflammatory signs, however, were similar for both treatment modalities, e. g., the activation of NFkappaB, and the release of IL

  7. Active Vertex Model for cell-resolution description of epithelial tissue mechanics.

    Science.gov (United States)

    Barton, Daniel L; Henkes, Silke; Weijer, Cornelis J; Sknepnek, Rastko

    2017-06-01

    We introduce an Active Vertex Model (AVM) for cell-resolution studies of the mechanics of confluent epithelial tissues consisting of tens of thousands of cells, with a level of detail inaccessible to similar methods. The AVM combines the Vertex Model for confluent epithelial tissues with active matter dynamics. This introduces a natural description of the cell motion and accounts for motion patterns observed on multiple scales. Furthermore, cell contacts are generated dynamically from positions of cell centres. This not only enables efficient numerical implementation, but provides a natural description of the T1 transition events responsible for local tissue rearrangements. The AVM also includes cell alignment, cell-specific mechanical properties, cell growth, division and apoptosis. In addition, the AVM introduces a flexible, dynamically changing boundary of the epithelial sheet allowing for studies of phenomena such as the fingering instability or wound healing. We illustrate these capabilities with a number of case studies.

  8. A scalable platform for biomechanical studies of tissue cutting forces

    International Nuclear Information System (INIS)

    Valdastri, P; Tognarelli, S; Menciassi, A; Dario, P

    2009-01-01

    This paper presents a novel and scalable experimental platform for biomechanical analysis of tissue cutting that exploits a triaxial force-sensitive scalpel and a high resolution vision system. Real-time measurements of cutting forces can be used simultaneously with accurate visual information in order to extract important biomechanical clues in real time that would aid the surgeon during minimally invasive intervention in preserving healthy tissues. Furthermore, the in vivo data gathered can be used for modeling the viscoelastic behavior of soft tissues, which is an important issue in surgical simulator development. Thanks to a modular approach, this platform can be scaled down, thus enabling in vivo real-time robotic applications. Several cutting experiments were conducted with soft porcine tissues (lung, liver and kidney) chosen as ideal candidates for biopsy procedures. The cutting force curves show repeated self-similar units of localized loading followed by unloading. With regards to tissue properties, the depth of cut plays a significant role in the magnitude of the cutting force acting on the blade. Image processing techniques and dedicated algorithms were used to outline the surface of the tissues and estimate the time variation of the depth of cut. The depth of cut was finally used to obtain the normalized cutting force, thus allowing comparative biomechanical analysis

  9. Options and pitfalls of normal tissues complication probability models

    International Nuclear Information System (INIS)

    Dorr, Wolfgang

    2011-01-01

    Full text: Technological improvements in the physical administration of radiotherapy have led to increasing conformation of the treatment volume (TV) with the planning target volume (PTV) and of the irradiated volume (IV) with the TV. In this process of improvement of the physical quality of radiotherapy, the total volumes of organs at risk exposed to significant doses have significantly decreased, resulting in increased inhomogeneities in the dose distributions within these organs. This has resulted in a need to identify and quantify volume effects in different normal tissues. Today, irradiated volume today must be considered a 6t h 'R' of radiotherapy, in addition to the 5 'Rs' defined by Withers and Steel in the mid/end 1980 s. The current status of knowledge of these volume effects has recently been summarized for many organs and tissues by the QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) initiative [Int. J. Radiat. Oncol. BioI. Phys. 76 (3) Suppl., 2010]. However, the concept of using dose-volume histogram parameters as a basis for dose constraints, even without applying any models for normal tissue complication probabilities (NTCP), is based on (some) assumptions that are not met in clinical routine treatment planning. First, and most important, dose-volume histogram (DVH) parameters are usually derived from a single, 'snap-shot' CT-scan, without considering physiological (urinary bladder, intestine) or radiation induced (edema, patient weight loss) changes during radiotherapy. Also, individual variations, or different institutional strategies of delineating organs at risk are rarely considered. Moreover, the reduction of the 3-dimentional dose distribution into a '2dimensl' DVH parameter implies that the localization of the dose within an organ is irrelevant-there are ample examples that this assumption is not justified. Routinely used dose constraints also do not take into account that the residual function of an organ may be

  10. Advanced cell culture technology for generation of in vivo-like tissue models

    Directory of Open Access Journals (Sweden)

    Stefan Przyborski

    2017-06-01

    Full Text Available Human tissues are mostly composed of different cell types, that are often highly organised in relation to each other. Often cells are arranged in distinct layers that enable signalling and cell-to-cell interactions. Here we describe the application of scaffold-based technology, that can be used to create advanced organotypic 3D models of various tissue types that more closely resemble in vivo-like conditions (Knight et al., 2011. The scaffold comprises a highly porous polystyrene material, engineered into a 200 micron thick membrane that is presented in various ways including multi-welled plates and well inserts, for use with conventional culture plasticware and medium perfusion systems. This technology has been applied to generate numerous unique types of co-culture model. For example: 1 a full thickness human skin construct comprising dermal fibroblasts and keratinocytes, raised to the air-liquid interface to induce cornification of the upper layers (Fig.1 (Hill et al., 2015; 2 a neuron-glial co-culture to enable the study of neurite outgrowth interacting with astroglial cells to model and investigate the glial scar found in spinal cord injury (Clarke et al., 2016; 3 formation of a sub-mucosa consisting of a polarised simple epithelium, layer of ECM proteins simulating the basement membrane, and underlying stromal tissues (e.g. intestinal mucosa. These organotypic models demonstrate the versatility of scaffold membranes and the creation of advanced in vivo-like tissue models. Creating a layered arrangement more closely simulates the true anatomy and organisation of cells within many tissue types. The addition of different cell types in a temporal and spatial fashion can be used to study inter-cellular relationships and create more physiologically relevant in vivo-like cell-based assays. Methods that are relatively straightforward to use and that recreate the organised structure of real tissues will become valuable research tools for use in

  11. Differential Superiority of Heavy Charged-Particle Irradiation to X-Rays: Studies on Biological Effectiveness and Side Effect Mechanisms in Multicellular Tumor and Normal Tissue Models

    Science.gov (United States)

    Walenta, Stefan; Mueller-Klieser, Wolfgang

    2016-01-01

    This review is focused on the radiobiology of carbon ions compared to X-rays using multicellular models of tumors and normal mucosa. The first part summarizes basic radiobiological effects, as observed in cancer cells. The second, more clinically oriented part of the review, deals with radiation-induced cell migration and mucositis. Multicellular spheroids from V79 hamster cells were irradiated with X-rays or carbon ions under ambient or restricted oxygen supply conditions. Reliable oxygen enhancement ratios could be derived to be 2.9, 2.8, and 1.4 for irradiation with photons, 12C+6 in the plateau region, and 12C+6 in the Bragg peak, respectively. Similarly, a relative biological effectiveness of 4.3 and 2.1 for ambient pO2 and hypoxia was obtained, respectively. The high effectiveness of carbon ions was reflected by an enhanced accumulation of cells in G2/M and a dose-dependent massive induction of apoptosis. These data clearly show that heavy charged particles are more efficient in sterilizing tumor cells than conventional irradiation even under hypoxic conditions. Clinically relevant doses (3 Gy) of X-rays induced an increase in migratory activity of U87 but not of LN229 or HCT116 tumor cells. Such an increase in cell motility following irradiation in situ could be the source of recurrence. In contrast, carbon ion treatment was associated with a dose-dependent decrease in migration with all cell lines and under all conditions investigated. The radiation-induced loss of cell motility was correlated, in most cases, with corresponding changes in β1 integrin expression. The photon-induced increase in cell migration was paralleled by an elevated phosphorylation status of the epidermal growth factor receptor and AKT-ERK1/2 pathway. Such a hyperphosphorylation did not occur during 12C+6 irradiation under all conditions registered. Comparing the gene toxicity of X-rays with that of particles using the γH2AX technique in organotypic cultures of the oral mucosa, the

  12. Differential Superiority of Heavy Charged-Particle Irradiation to X-Rays: Studies on Biological Effectiveness and Side Effect Mechanisms in Multicellular Tumor and Normal Tissue Models.

    Science.gov (United States)

    Walenta, Stefan; Mueller-Klieser, Wolfgang

    2016-01-01

    This review is focused on the radiobiology of carbon ions compared to X-rays using multicellular models of tumors and normal mucosa. The first part summarizes basic radiobiological effects, as observed in cancer cells. The second, more clinically oriented part of the review, deals with radiation-induced cell migration and mucositis. Multicellular spheroids from V79 hamster cells were irradiated with X-rays or carbon ions under ambient or restricted oxygen supply conditions. Reliable oxygen enhancement ratios could be derived to be 2.9, 2.8, and 1.4 for irradiation with photons, (12)C(+6) in the plateau region, and (12)C(+6) in the Bragg peak, respectively. Similarly, a relative biological effectiveness of 4.3 and 2.1 for ambient pO2 and hypoxia was obtained, respectively. The high effectiveness of carbon ions was reflected by an enhanced accumulation of cells in G2/M and a dose-dependent massive induction of apoptosis. These data clearly show that heavy charged particles are more efficient in sterilizing tumor cells than conventional irradiation even under hypoxic conditions. Clinically relevant doses (3 Gy) of X-rays induced an increase in migratory activity of U87 but not of LN229 or HCT116 tumor cells. Such an increase in cell motility following irradiation in situ could be the source of recurrence. In contrast, carbon ion treatment was associated with a dose-dependent decrease in migration with all cell lines and under all conditions investigated. The radiation-induced loss of cell motility was correlated, in most cases, with corresponding changes in β1 integrin expression. The photon-induced increase in cell migration was paralleled by an elevated phosphorylation status of the epidermal growth factor receptor and AKT-ERK1/2 pathway. Such a hyperphosphorylation did not occur during (12)C(+6) irradiation under all conditions registered. Comparing the gene toxicity of X-rays with that of particles using the γH2AX technique in organotypic cultures of the oral

  13. Comparative study of radiosensitivity of normal and regenerating tissues

    International Nuclear Information System (INIS)

    Samokhvalova, H.S.; Popova, M.F.

    1983-01-01

    A comparative study of radiosensitivity of cells of normal and regenerating tissues of bone marrow and spleen has demonstrated that single exposure to X-rays produces a lesser damaging effect on regenerating tissues than on normal ones. The data obtained indicate that the increase in radioresistance of the organism during active regeneration of the haemopoietic organs is due not merely to the increase in the dividing cell pool of these organs but also to qualitative changes in their functional state

  14. Modeling of light absorption in tissue during infrared neural stimulation

    Science.gov (United States)

    Thompson, Alexander C.; Wade, Scott A.; Brown, William G. A.; Stoddart, Paul R.

    2012-07-01

    A Monte Carlo model has been developed to simulate light transport and absorption in neural tissue during infrared neural stimulation (INS). A range of fiber core sizes and numerical apertures are compared illustrating the advantages of using simulations when designing a light delivery system. A range of wavelengths, commonly used for INS, are also compared for stimulation of nerves in the cochlea, in terms of both the energy absorbed and the change in temperature due to a laser pulse. Modeling suggests that a fiber with core diameter of 200 μm and NA=0.22 is optimal for optical stimulation in the geometry used and that temperature rises in the spiral ganglion neurons are as low as 0.1°C. The results show a need for more careful experimentation to allow different proposed mechanisms of INS to be distinguished.

  15. Force modeling for incisions into various tissues with MRF haptic master

    Science.gov (United States)

    Kim, Pyunghwa; Kim, Soomin; Park, Young-Dai; Choi, Seung-Bok

    2016-03-01

    This study proposes a new model to predict the reaction force that occurs in incisions during robot-assisted minimally invasive surgery. The reaction force is fed back to the manipulator by a magneto-rheological fluid (MRF) haptic master, which is featured by a bi-directional clutch actuator. The reaction force feedback provides similar sensations to laparotomy that cannot be provided by a conventional master for surgery. This advantage shortens the training period for robot-assisted minimally invasive surgery and can improve the accuracy of operations. The reaction force modeling of incisions can be utilized in a surgical simulator that provides a virtual reaction force. In this work, in order to model the reaction force during incisions, the energy aspect of the incision process is adopted and analyzed. Each mode of the incision process is classified by the tendency of the energy change, and modeled for realistic real-time application. The reaction force model uses actual reaction force information with three types of actual tissues: hard tissue, medium tissue, and soft tissue. This modeled force is realized by the MRF haptic master through an algorithm based on the position and velocity of a scalpel using two different control methods: an open-loop algorithm and a closed-loop algorithm. The reaction forces obtained from the proposed model are compared with a desired force in time domain.

  16. Force modeling for incisions into various tissues with MRF haptic master

    International Nuclear Information System (INIS)

    Kim, Pyunghwa; Kim, Soomin; Park, Young-Dai; Choi, Seung-Bok

    2016-01-01

    This study proposes a new model to predict the reaction force that occurs in incisions during robot-assisted minimally invasive surgery. The reaction force is fed back to the manipulator by a magneto-rheological fluid (MRF) haptic master, which is featured by a bi-directional clutch actuator. The reaction force feedback provides similar sensations to laparotomy that cannot be provided by a conventional master for surgery. This advantage shortens the training period for robot-assisted minimally invasive surgery and can improve the accuracy of operations. The reaction force modeling of incisions can be utilized in a surgical simulator that provides a virtual reaction force. In this work, in order to model the reaction force during incisions, the energy aspect of the incision process is adopted and analyzed. Each mode of the incision process is classified by the tendency of the energy change, and modeled for realistic real-time application. The reaction force model uses actual reaction force information with three types of actual tissues: hard tissue, medium tissue, and soft tissue. This modeled force is realized by the MRF haptic master through an algorithm based on the position and velocity of a scalpel using two different control methods: an open-loop algorithm and a closed-loop algorithm. The reaction forces obtained from the proposed model are compared with a desired force in time domain. (paper)

  17. Imaging of oxygenation in 3D tissue models with multi-modal phosphorescent probes

    Science.gov (United States)

    Papkovsky, Dmitri B.; Dmitriev, Ruslan I.; Borisov, Sergei

    2015-03-01

    Cell-penetrating phosphorescence based probes allow real-time, high-resolution imaging of O2 concentration in respiring cells and 3D tissue models. We have developed a panel of such probes, small molecule and nanoparticle structures, which have different spectral characteristics, cell penetrating and tissue staining behavior. The probes are compatible with conventional live cell imaging platforms and can be used in different detection modalities, including ratiometric intensity and PLIM (Phosphorescence Lifetime IMaging) under one- or two-photon excitation. Analytical performance of these probes and utility of the O2 imaging method have been demonstrated with different types of samples: 2D cell cultures, multi-cellular spheroids from cancer cell lines and primary neurons, excised slices from mouse brain, colon and bladder tissue, and live animals. They are particularly useful for hypoxia research, ex-vivo studies of tissue physiology, cell metabolism, cancer, inflammation, and multiplexing with many conventional fluorophors and markers of cellular function.

  18. Parvovirus infection: an immunohistochemical study using fetal and placental tissue.

    Science.gov (United States)

    Li, Jing Jing; Henwood, Tony; Van Hal, Sebastian; Charlton, Amanda

    2015-01-01

    Parvovirus B19 infection causes 5% to 15% of cases of nonimmune hydrops fetalis. The aim of our study was to evaluate the use of immunohistochemistry in diagnosing parvovirus infection in fetal and placental tissue during routine fetal and perinatal autopsies. Histology slides of 20 cases of confirmed parvovirus infection were reviewed, and immunohistochemistry was applied to selected blocks of fetal and placental tissue. Immunohistochemistry was positive in all 20 cases, and histologic viral inclusions were seen in 19 cases. Immunohistochemical staining was closely correlated with histology and was more sensitive than histology in detecting virally infected cells, especially in autolyzed tissue. All cases also had confirmatory evidence of parvovirus infection by polymerase chain reaction of fetal liver and positive maternal serology, where it was available. We conclude that parvovirus immunohistochemistry is a reliable method for diagnosing parvovirus infection, especially in autolyzed tissue where histologic assessment may be suboptimal.

  19. An analytical model for nanoparticles concentration resulting from infusion into poroelastic brain tissue.

    Science.gov (United States)

    Pizzichelli, G; Di Michele, F; Sinibaldi, E

    2016-02-01

    We consider the infusion of a diluted suspension of nanoparticles (NPs) into poroelastic brain tissue, in view of relevant biomedical applications such as intratumoral thermotherapy. Indeed, the high impact of the related pathologies motivates the development of advanced therapeutic approaches, whose design also benefits from theoretical models. This study provides an analytical expression for the time-dependent NPs concentration during the infusion into poroelastic brain tissue, which also accounts for particle binding onto cells (by recalling relevant results from the colloid filtration theory). Our model is computationally inexpensive and, compared to fully numerical approaches, permits to explicitly elucidate the role of the involved physical aspects (tissue poroelasticity, infusion parameters, NPs physico-chemical properties, NP-tissue interactions underlying binding). We also present illustrative results based on parameters taken from the literature, by considering clinically relevant ranges for the infusion parameters. Moreover, we thoroughly assess the model working assumptions besides discussing its limitations. While not laying any claims of generality, our model can be used to support the development of more ambitious numerical approaches, towards the preliminary design of novel therapies based on NPs infusion into brain tissue. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Prefabrication of axial vascularized tissue engineering coral bone by an arteriovenous loop: a better model.

    Science.gov (United States)

    Dong, Qing-shan; Shang, Hong-tao; Wu, Wei; Chen, Fu-lin; Zhang, Jun-rui; Guo, Jia-ping; Mao, Tian-qiu

    2012-08-01

    The most important problem for the survival of thick 3-dimensional tissues is the lack of vascularization in the context of bone tissue engineering. In this study, a modified arteriovenous loop (AVL) was developed to prefabricate an axial vascularized tissue engineering coral bone in rabbit, with comparison of the arteriovenous bundle (AVB) model. An arteriovenous fistula between rabbit femoral artery and vein was anastomosed to form an AVL. It was placed in a circular side groove of the coral block. The complex was wrapped with an expanded-polytetrafluoroethylene membrane and implanted beneath inguinal skin. After 2, 4, 6 and 8 weeks, the degree of vascularization was evaluated by India ink perfusion, histological examination, vascular casts, and scanning electron microscopy images of vascular endangium. Newly formed fibrous tissues and vasculature extended over the surfaces and invaded the interspaces of entire coral block. The new blood vessels robustly sprouted from the AVL. Those invaginated cavities in the vascular endangium from scanning electron microscopy indicated vessel's sprouted pores. Above indexes in AVL model are all superior to that in AVB model, indicating that the modified AVL model could more effectively develop vascularization in larger tissue engineering bone. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. 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

  2. A Computational Modeling Approach for Investigating Soft Tissue Balancing in Bicruciate Retaining Knee Arthroplasty

    Directory of Open Access Journals (Sweden)

    Shahram Amiri

    2012-01-01

    Full Text Available Bicruciate retaining knee arthroplasty, although has shown improved functions and patient satisfaction compared to other designs of total knee replacement, remains a technically demanding option for treating severe cases of arthritic knees. One of the main challenges in bicruciate retaining arthroplasty is proper balancing of the soft tissue during the surgery. In this study biomechanics of soft tissue balancing was investigated using a validated computational model of the knee joint with high fidelity definitions of the soft tissue structures along with a Taguchi method for design of experiments. The model was used to simulate intraoperative balancing of soft tissue structures following the combinations suggested by an orthogonal array design. The results were used to quantify the corresponding effects on the laxity of the joint under anterior-posterior, internal-external, and varus-valgus loads. These effects were ranked for each ligament bundle to identify the components of laxity which were most sensitive to the corresponding surgical modifications. The resulting map of sensitivity for all the ligament bundles determined the components of laxity most suitable for examination during intraoperative balancing of the soft tissue. Ultimately, a sequence for intraoperative soft tissue balancing was suggested for a bicruciate retaining knee arthroplasty.

  3. A Computational Modeling Approach for Investigating Soft Tissue Balancing in Bicruciate Retaining Knee Arthroplasty

    Science.gov (United States)

    Amiri, Shahram; Wilson, David R.

    2012-01-01

    Bicruciate retaining knee arthroplasty, although has shown improved functions and patient satisfaction compared to other designs of total knee replacement, remains a technically demanding option for treating severe cases of arthritic knees. One of the main challenges in bicruciate retaining arthroplasty is proper balancing of the soft tissue during the surgery. In this study biomechanics of soft tissue balancing was investigated using a validated computational model of the knee joint with high fidelity definitions of the soft tissue structures along with a Taguchi method for design of experiments. The model was used to simulate intraoperative balancing of soft tissue structures following the combinations suggested by an orthogonal array design. The results were used to quantify the corresponding effects on the laxity of the joint under anterior-posterior, internal-external, and varus-valgus loads. These effects were ranked for each ligament bundle to identify the components of laxity which were most sensitive to the corresponding surgical modifications. The resulting map of sensitivity for all the ligament bundles determined the components of laxity most suitable for examination during intraoperative balancing of the soft tissue. Ultimately, a sequence for intraoperative soft tissue balancing was suggested for a bicruciate retaining knee arthroplasty. PMID:23082090

  4. Studying the distribution of deep Raman spectroscopy signals using liquid tissue phantoms with varying optical properties.

    Science.gov (United States)

    Vardaki, Martha Z; Gardner, Benjamin; Stone, Nicholas; Matousek, Pavel

    2015-08-07

    In this study we employed large volume liquid tissue phantoms, consisting of a scattering agent (Intralipid), an absorption agent (Indian ink) and a synthesized calcification powder (calcium hydroxyapatite (HAP)) similar to that found in cancerous tissues (e.g. breast and prostate), to simulate human tissues. We studied experimentally the magnitude and origin of Raman signals in a transmission Raman geometry as a function of optical properties of the medium and the location of calcifications within the phantom. The goal was to inform the development of future noninvasive cancer screening applications in vivo. The results provide insight into light propagation and Raman scattering distribution in deep Raman measurements, exploring also the effect of the variation of relative absorbance of laser and Raman photons within the phantoms. Most notably when modeling breast and prostate tissues it follows that maximum signals is obtained from the front and back faces of the tissue with the central region contributing less to the measured spectrum.

  5. A model for arterial adaptation combining microstructural collagen remodeling and 3D tissue growth

    NARCIS (Netherlands)

    Machyshyn, I.; Bovendeerd, P.H.M.; Ven, van de A.A.F.; Rongen, P.M.J.; Vosse, van de F.N.

    2010-01-01

    Long-term adaptation of soft tissues is realized through growth and remodeling (G&R). Mathematical models are powerful tools in testing hypotheses on G&R and supporting the design and interpretation of experiments. Most theoretical G&R studies concentrate on description of either growth or

  6. Model of electrical conductivity of skeletal muscle based on tissue structure

    NARCIS (Netherlands)

    Gielen, F.L.H.; Cruts, H.E.P.; Alberts, B.A.; Boon, K.L.; Wallinga, W.; Boom, H.B.K.

    1986-01-01

    Recent experiments carried out in our laboratory with the four-electrode method showed that the electrical conductivity of skeletal muscle tissue depends on the frequency of the injected current and the distance between the current electrodes. A model is proposed in order to study these effects. The

  7. Biomechanical study of the bone tissue with dental implants interaction

    Directory of Open Access Journals (Sweden)

    Navrátil P.

    2011-12-01

    Full Text Available The article deals with the stress-strain analysis of human mandible in the physiological state and after the dental implant application. The evaluation is focused on assessing of the cancellous bone tissue modeling-level. Three cancellous bone model-types are assessed: Non-trabecular model with homogenous isotropic material, nontrabecular model with inhomogeneous material obtained from computer tomography data using CT Data Analysis software, and trabecular model built from mandible section image. Computational modeling was chosen as the most suitable solution method and the solution on two-dimensional level was carried out. The results show that strain is more preferable value than stress in case of evaluation of mechanical response in cancellous bone. The non-trabecular model with CT-obtained material model is not acceptable for stress-strain analysis of the cancellous bone for singularities occurring on interfaces of regions with different values of modulus of elasticity.

  8. Bayesian models and meta analysis for multiple tissue gene expression data following corticosteroid administration

    Directory of Open Access Journals (Sweden)

    Kelemen Arpad

    2008-08-01

    Full Text Available Abstract Background This paper addresses key biological problems and statistical issues in the analysis of large gene expression data sets that describe systemic temporal response cascades to therapeutic doses in multiple tissues such as liver, skeletal muscle, and kidney from the same animals. Affymetrix time course gene expression data U34A are obtained from three different tissues including kidney, liver and muscle. Our goal is not only to find the concordance of gene in different tissues, identify the common differentially expressed genes over time and also examine the reproducibility of the findings by integrating the results through meta analysis from multiple tissues in order to gain a significant increase in the power of detecting differentially expressed genes over time and to find the differential differences of three tissues responding to the drug. Results and conclusion Bayesian categorical model for estimating the proportion of the 'call' are used for pre-screening genes. Hierarchical Bayesian Mixture Model is further developed for the identifications of differentially expressed genes across time and dynamic clusters. Deviance information criterion is applied to determine the number of components for model comparisons and selections. Bayesian mixture model produces the gene-specific posterior probability of differential/non-differential expression and the 95% credible interval, which is the basis for our further Bayesian meta-inference. Meta-analysis is performed in order to identify commonly expressed genes from multiple tissues that may serve as ideal targets for novel treatment strategies and to integrate the results across separate studies. We have found the common expressed genes in the three tissues. However, the up/down/no regulations of these common genes are different at different time points. Moreover, the most differentially expressed genes were found in the liver, then in kidney, and then in muscle.

  9. WE-EF-BRA-12: Magnetic Resonance- Guided High-Intensity Focused Ultrasound for Localized Ablation of Head and Neck Tissue Structures: A Feasibility Study in An Animal Model

    International Nuclear Information System (INIS)

    Partanen, A; Ellens, N; Noureldine, S; Tufano, R; Burdette, E; Farahani, K

    2015-01-01

    Purpose: High-intensity focused ultrasound (HIFU) ablation is feasible in the head and neck [1]. This study aims to expand upon these findings to assess the feasibility of treatment planning and monitoring via magnetic resonance imaging (MRI) guidance using a clinical MR-guided HIFU platform. Methods: Two 31 kg pigs were anaesthetized, shaved, and positioned prone on the HIFU table (Sonalleve, Philips Healthcare, Vantaa, Finland). The necks were acoustically coupled to the integrated transducer using gel pads and degassed water. MR imaging verified acoustic coupling and facilitated target selection in the thyroid and thymus. Targets were thermally ablated with 130–200 W of acoustic power over a period of 16 s at a frequency of 1.2 MHz while being monitored through real-time, multi-planar MR-thermometry. Contrast-enhanced MR imaging was used to assess treatment efficacy. Post-treatment, animals were euthanized and sonicated tissues were harvested for histology assessment. Results: MR-thermometry, post-contrast-imaging, and gross pathology demonstrated that the system was capable of causing localized thermal ablation in both the thyroid and the thymus without damaging the aerodigestive tract. In one animal, superficial bruising was observed in the ultrasound beam path. Otherwise, there were no adverse events. Analysis of the tissue histology found regions of damage consistent with acute thermal injury at the targeted locations. Conclusion: It is feasible to use a clinical MR-guided HIFU platform for extracorporeal ablation of porcine head and neck tissues. MR guidance and thermometry are sufficient to target and monitor treatment in the thyroid region, despite the presence of the inhomogeneous aerodigestive tract. Further study is necessary to assess efficacy and survival using a tumor model, and to examine what modifications should be made to the transducer positioning system and associated patient positioning aids to adapt it for clinical head and neck targets

  10. Biphasic Finite Element Modeling Reconciles Mechanical Properties of Tissue-Engineered Cartilage Constructs Across Testing Platforms.

    Science.gov (United States)

    Meloni, Gregory R; Fisher, Matthew B; Stoeckl, Brendan D; Dodge, George R; Mauck, Robert L

    2017-07-01

    Cartilage tissue engineering is emerging as a promising treatment for osteoarthritis, and the field has progressed toward utilizing large animal models for proof of concept and preclinical studies. Mechanical testing of the regenerative tissue is an essential outcome for functional evaluation. However, testing modalities and constitutive frameworks used to evaluate in vitro grown samples differ substantially from those used to evaluate in vivo derived samples. To address this, we developed finite element (FE) models (using FEBio) of unconfined compression and indentation testing, modalities commonly used for such samples. We determined the model sensitivity to tissue radius and subchondral bone modulus, as well as its ability to estimate material parameters using the built-in parameter optimization tool in FEBio. We then sequentially tested agarose gels of 4%, 6%, 8%, and 10% weight/weight using a custom indentation platform, followed by unconfined compression. Similarly, we evaluated the ability of the model to generate material parameters for living constructs by evaluating engineered cartilage. Juvenile bovine mesenchymal stem cells were seeded (2 × 10 7 cells/mL) in 1% weight/volume hyaluronic acid hydrogels and cultured in a chondrogenic medium for 3, 6, and 9 weeks. Samples were planed and tested sequentially in indentation and unconfined compression. The model successfully completed parameter optimization routines for each testing modality for both acellular and cell-based constructs. Traditional outcome measures and the FE-derived outcomes showed significant changes in material properties during the maturation of engineered cartilage tissue, capturing dynamic changes in functional tissue mechanics. These outcomes were significantly correlated with one another, establishing this FE modeling approach as a singular method for the evaluation of functional engineered and native tissue regeneration, both in vitro and in vivo.

  11. A Tissue Engineered Model of Aging: Interdependence and Cooperative Effects in Failing Tissues.

    Science.gov (United States)

    Acun, A; Vural, D C; Zorlutuna, P

    2017-07-11

    Aging remains a fundamental open problem in modern biology. Although there exist a number of theories on aging on the cellular scale, nearly nothing is known about how microscopic failures cascade to macroscopic failures of tissues, organs and ultimately the organism. The goal of this work is to bridge microscopic cell failure to macroscopic manifestations of aging. We use tissue engineered constructs to control the cellular-level damage and cell-cell distance in individual tissues to establish the role of complex interdependence and interactions between cells in aging tissues. We found that while microscopic mechanisms drive aging, the interdependency between cells plays a major role in tissue death, providing evidence on how cellular aging is connected to its higher systemic consequences.

  12. Analytical model of diffuse reflectance spectrum of skin tissue

    Energy Technology Data Exchange (ETDEWEB)

    Lisenko, S A; Kugeiko, M M; Firago, V A [Belarusian State University, Minsk (Belarus); Sobchuk, A N [B.I. Stepanov Institute of Physics, National Academy of Sciences of Belarus, Minsk (Belarus)

    2014-01-31

    We have derived simple analytical expressions that enable highly accurate calculation of diffusely reflected light signals of skin in the spectral range from 450 to 800 nm at a distance from the region of delivery of exciting radiation. The expressions, taking into account the dependence of the detected signals on the refractive index, transport scattering coefficient, absorption coefficient and anisotropy factor of the medium, have been obtained in the approximation of a two-layer medium model (epidermis and dermis) for the same parameters of light scattering but different absorption coefficients of layers. Numerical experiments on the retrieval of the skin biophysical parameters from the diffuse reflectance spectra simulated by the Monte Carlo method show that commercially available fibre-optic spectrophotometers with a fixed distance between the radiation source and detector can reliably determine the concentration of bilirubin, oxy- and deoxyhaemoglobin in the dermis tissues and the tissue structure parameter characterising the size of its effective scatterers. We present the examples of quantitative analysis of the experimental data, confirming the correctness of estimates of biophysical parameters of skin using the obtained analytical expressions. (biophotonics)

  13. Development of an experimental model of brain tissue heterotopia in the lung

    Science.gov (United States)

    Quemelo, Paulo Roberto Veiga; Sbragia, Lourenço; Peres, Luiz Cesar

    2007-01-01

    Summary The presence of heterotopic brain tissue in the lung is a rare abnormality. The cases reported thus far are usually associated with neural tube defects (NTD). As there are no reports of experimental models of NTD that present this abnormality, the objective of the present study was to develop a surgical method of brain tissue heterotopia in the lung. We used 24 pregnant Swiss mice divided into two groups of 12 animals each, denoted 17GD and 18GD according to the gestational day (GD) when caesarean section was performed to collect the fetuses. Surgery was performed on the 15th GD, one fetus was removed by hysterectomy and its brain tissue was cut into small fragments and implanted in the lung of its litter mates. Thirty-four live fetuses were obtained from the 17GD group. Of these, eight (23.5%) were used as control (C), eight (23.5%) were sham operated (S) and 18 (52.9%) were used for pulmonary brain tissue implantation (PBI). Thirty live fetuses were obtained from the females of the 18GD group. Of these, eight (26.6%) were C, eight (26.6%) S and 14 (46.6%) were used for PBI. Histological examination of the fetal trunks showed implantation of GFAP-positive brain tissue in 85% of the fetuses of the 17GD group and in 100% of those of the 18GD group, with no significant difference between groups for any of the parameters analysed. The experimental model proved to be efficient and of relatively simple execution, showing complete integration of the brain tissue with pulmonary and pleural tissue and thus representing a model that will permit the study of different aspects of cell implantation and interaction. PMID:17877535

  14. Evaluation of tissue engineered models of the oral mucosa to investigate oral candidiasis.

    Science.gov (United States)

    Yadev, Nishant P; Murdoch, Craig; Saville, Stephen P; Thornhill, Martin H

    2011-06-01

    Candida albicans is a commensal organism that can be isolated from the majority of healthy individuals. However, in certain susceptible individuals C. albicans can become pathogenic leading to the mucocutaneous infection; oral candidiasis. Murine models and in vitro monolayer cultures have generated some data on the likely virulence and host factors that contribute to oral candidiasis but these models have limitations. Recently, tissue engineered oral mucosal models have been developed to mimic the normal oral mucosa but little information is available on their true representation. In this study, we assessed the histological features of three different tissue engineered oral mucosal models compared to the normal oral mucosa and analysed both cell damage and cytokine release following infection with C. albicans. Models comprised of normal oral keratinocytes and a fibroblast-containing matrix displayed more similar immunohistological and proliferation characteristics to normal mucosa, compared to models composed of an oral carcinoma cell line. Although all models were invaded and damaged by C. albicans in a similar manner, the cytokine response was much more pronounced in models containing normal keratinocytes. These data suggest that models based on normal keratinocytes atop a fibroblast-containing connective tissue will significantly aid in dissecting the molecular pathogenesis of oral candidiasis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Roentgenographic study on maxillofacial soft tissue in the mixed dentition

    International Nuclear Information System (INIS)

    Lee, Jai Hei; Ahn, Hyung Kyu

    1977-01-01

    The purpose of this study was to obtain the cephalometric maxillofacial soft tissue measurements and to define the differences that exist between male and female on the soft tissue profile who had normal occlusion in mixed dentitions. For the object of this study, cephalometric radiographs were obtained from the centric occlusion with the relaxed lip position. Copper filter was designed to obtain both hard and soft tissue structure on the same film. The subjects consist of 100 male and 100 female from 8 to 12.4 years with the normal occlusion and acceptable profiles. The author measured facial depth, vertical height from the cephalometric soft tissue profiles in the mixed dentitions. The significant test was performed to compare male with females. The following results were obtained from the study 1. In facial convexity, much more larger female than that of male. 2. Inclination of the lip posture was more larger in maxilla (male) and in female more larger in the mandible. 3. The thickness of soft tissue was thicker in male, the height of nose was more prominent in female. 4. There were no significant differences in both sexes.

  16. Strain-time cell death threshold for skeletal muscle in a tissue-engineered model system for deep tissue injury

    NARCIS (Netherlands)

    Gefen, A.; Nierop, van B.J.; Bader, D.L.; Oomens, C.W.J.

    2008-01-01

    Deep tissue injury (DTI) is a severe pressure ulcer that results from sustained deformation of muscle tissue overlying bony prominences. In order to understand the etiology of DTI, it is essential to determine the tolerance of muscle cells to large mechanical strains. In this study, a new

  17. Culture of three-dimensional tissue model and its application in bystander-effect research

    International Nuclear Information System (INIS)

    Wu Ruqun; Xu An; Wu Lijun; Hu Burong

    2012-01-01

    Compared with the cultured monolayer (2D) cells, three-dimensional (3D) tissue could be more similar to the environment in vivo including the physical support, chemical factors, cell-cell and cell-matrix interaction and so on. With the development of three-dimensional cell culture techniques (TDCC), 3D tissue is widely used in the areas of bystander effect research. This review focuses on introducing the TDCC method and its application in bystander-effect research. First, the development process of 3D tissue culture method was introduced. Secondly, the induction of radiation induced bystander effects both in 2D cell and 3D tissue and its mechanisms were reviewed. Finally, because heavy ion (carbon ion beam) has been developed as a useful tool to cure solid cancer, and the 3D tissue model is an ideal material to study the damages on body after being irradiated and to understand the underlying mechanisms, future study about heavy ion radiation inducing bystander effect in 3D tissue was discussed. (authors)

  18. Characterization of Mechanical Properties of Tissue Scaffolds by Phase Contrast Imaging and Finite Element Modeling.

    Science.gov (United States)

    Bawolin, Nahshon K; Dolovich, Allan T; Chen, Daniel X B; Zhang, Chris W J

    2015-08-01

    In tissue engineering, the cell and scaffold approach has shown promise as a treatment to regenerate diseased and/or damaged tissue. In this treatment, an artificial construct (scaffold) is seeded with cells, which organize and proliferate into new tissue. The scaffold itself biodegrades with time, leaving behind only newly formed tissue. The degradation qualities of the scaffold are critical during the treatment period, since the change in the mechanical properties of the scaffold with time can influence cell behavior. To observe in time the scaffold's mechanical properties, a straightforward method is to deform the scaffold and then characterize scaffold deflection accordingly. However, experimentally observing the scaffold deflection is challenging. This paper presents a novel study on characterization of mechanical properties of scaffolds by phase contrast imaging and finite element modeling, which specifically includes scaffold fabrication, scaffold imaging, image analysis, and finite elements (FEs) modeling of the scaffold mechanical properties. The innovation of the work rests on the use of in-line phase contrast X-ray imaging at 20 KeV to characterize tissue scaffold deformation caused by ultrasound radiation forces and the use of the Fourier transform to identify movement. Once deformation has been determined experimentally, it is then compared with the predictions given by the forward solution of a finite element model. A consideration of the number of separate loading conditions necessary to uniquely identify the material properties of transversely isotropic and fully orthotropic scaffolds is also presented, along with the use of an FE as a form of regularization.

  19. Necrotizing soft tissue infections - a multicentre, prospective observational study (INFECT)

    NARCIS (Netherlands)

    Madsen, M.B.; Skrede, S.; Bruun, T.; Arnell, P.; Rosén, A.; Nekludov, M.; Karlsson, Y.; Bergey, F.; Saccenti, E.; Martins dos Santos, V.A.P.; Perner, A.; Norrby-Teglund, A.; Hyldegaard, O.

    2018-01-01

    Background: The INFECT project aims to advance our understanding of the pathophysiological mechanisms in necrotizing soft tissue infections (NSTIs). The INFECT observational study is part of the INFECT project with the aim of studying the clinical profile of patients with NSTIs and correlating

  20. A functional model for adult stem cells in epithelial tissues.

    NARCIS (Netherlands)

    Verstappen, J.; Katsaros, C.; Torensma, R.; Hoff, J.W. Von den

    2009-01-01

    Tissue turnover, regeneration, and repair take place throughout life. Stem cells are key players in these processes. The characteristics and niches of the stem cell populations in different tissues, and even in related tissues, vary extensively. In this review, stem cell differentiation and stem

  1. Tissue Engineering in Animal Models for Urinary Diversion: A Systematic Review

    Science.gov (United States)

    Sloff, Marije; de Vries, Rob; Geutjes, Paul; IntHout, Joanna; Ritskes-Hoitinga, Merel

    2014-01-01

    Tissue engineering and regenerative medicine (TERM) approaches may provide alternatives for gastrointestinal tissue in urinary diversion. To continue to clinically translatable studies, TERM alternatives need to be evaluated in (large) controlled and standardized animal studies. Here, we investigated all evidence for the efficacy of tissue engineered constructs in animal models for urinary diversion. Studies investigating this subject were identified through a systematic search of three different databases (PubMed, Embase and Web of Science). From each study, animal characteristics, study characteristics and experimental outcomes for meta-analyses were tabulated. Furthermore, the reporting of items vital for study replication was assessed. The retrieved studies (8 in total) showed extreme heterogeneity in study design, including animal models, biomaterials and type of urinary diversion. All studies were feasibility studies, indicating the novelty of this field. None of the studies included appropriate control groups, i.e. a comparison with the classical treatment using GI tissue. The meta-analysis showed a trend towards successful experimentation in larger animals although no specific animal species could be identified as the most suitable model. Larger animals appear to allow a better translation to the human situation, with respect to anatomy and surgical approaches. It was unclear whether the use of cells benefits the formation of a neo urinary conduit. The reporting of the methodology and data according to standardized guidelines was insufficient and should be improved to increase the value of such publications. In conclusion, animal models in the field of TERM for urinary diversion have probably been chosen for reasons other than their predictive value. Controlled and comparative long term animal studies, with adequate methodological reporting are needed to proceed to clinical translatable studies. This will aid in good quality research with the reduction in

  2. Autoradiographic studies of oleilanilide-3H distribution in rat tissues

    International Nuclear Information System (INIS)

    Negro Alvarez, M.J.; Saez Angulo, R.M.

    1987-01-01

    In this work the possibility that oleilanilides are involved in the pathgenesis of ''toxic syndrome'' is studied. Oleilanilide- 3 H labelled in the anilidi aromatic ring has been used to determine the distribution, localization and incorporation of that compound in several tissues of rats. Liquid scintillation counting for quantitative evaluation of the total radioactivity accumulated in the tissues, as well as autoradiographic techniques have been employed as analytical procedures. Results obtained from measurement of total radioactivity have shown accumulation of oleilanilide or its metabolites in all the studied tissues, mainly in the liver. No specific radioactivity localization has been detected by autoradiographic techniques, being the labelled molecules distributed in cytaplasm and cell interstice. (Author)

  3. Microdosimetric characterisation of radiation fields for modelling tissue response in radiotherapy

    Directory of Open Access Journals (Sweden)

    He Wang

    2014-02-01

    Full Text Available Purpose: Our overall goal is the development of an approach to model tissue response to radiotherapy in which a tissue is viewed as a statistical ensemble of interacting cells. This involves characterisation of radiation fields on the spatial scale of subcellular structures. On this scale, the spatial distribution of radiation energy imparted to tissue is highly non-uniform and should be characterised in statistical terms. Microdosimetry provides a formalism developed for that purpose. This study addresses limitations of the standard microdosimetric approach to modelling tissue response by introducing two new characteristics that include additional information in a form convenient for this application.Methods: The standard microdosimetric approach is based on the concept of a sensitive volume (SV representing a target volume in the cell. It is considered in isolation from other SVs, implying that energy depositions in different SVs are statistically independent and that individual cells respond to radiation independent of each other. In this study, we examined the latter approximation through analysis of correlation functions. All calculations were performed with Geant4-DNA Monte Carlo code. Results: We found that for some realistic scenarios, spatial correlations of deposited energy can be significant. Two new characteristics of radiation fields are proposed. The first is the specific energy-volume histogram (zVH, which is a microscopic analogue of the dose-volume histogram. The second describes the probability distribution of deposited energies in two SVs without assuming statistical independence between the SVs. Numerical examples for protons and carbon ions of therapeutic energies are presented and discussed.Conclusion: We extended the microdosimetric approach to modelling tissue response by including additional important characteristics and presented them in a more conventional radiotherapy format

  4. Exploring the mechanical behavior of degrading swine neural tissue at low strain rates via the fractional Zener constitutive model.

    Science.gov (United States)

    Bentil, Sarah A; Dupaix, Rebecca B

    2014-02-01

    The ability of the fractional Zener constitutive model to predict the behavior of postmortem swine brain tissue was examined in this work. Understanding tissue behavior attributed to degradation is invaluable in many fields such as the forensic sciences or cases where only cadaveric tissue is available. To understand how material properties change with postmortem age, the fractional Zener model was considered as it includes parameters to describe brain stiffness and also the parameter α, which quantifies the viscoelasticity of a material. The relationship between the viscoelasticity described by α and tissue degradation was examined by fitting the model to data collected in a previous study (Bentil, 2013). This previous study subjected swine neural tissue to in vitro unconfined compression tests using four postmortem age groups (week). All samples were compressed to a strain level of 10% using two compressive rates: 1mm/min and 5mm/min. Statistical analysis was used as a tool to study the influence of the fractional Zener constants on factors such as tissue degradation and compressive rate. Application of the fractional Zener constitutive model to the experimental data showed that swine neural tissue becomes less stiff with increased postmortem age. The fractional Zener model was also able to capture the nonlinear viscoelastic features of the brain tissue at low strain rates. The results showed that the parameter α was better correlated with compressive rate than with postmortem age. © 2013 Published by Elsevier Ltd.

  5. Monte Carlo modeling of time-resolved fluorescence for depth-selective interrogation of layered tissue.

    Science.gov (United States)

    Pfefer, T Joshua; Wang, Quanzeng; Drezek, Rebekah A

    2011-11-01

    Computational approaches for simulation of light-tissue interactions have provided extensive insight into biophotonic procedures for diagnosis and therapy. However, few studies have addressed simulation of time-resolved fluorescence (TRF) in tissue and none have combined Monte Carlo simulations with standard TRF processing algorithms to elucidate approaches for cancer detection in layered biological tissue. In this study, we investigate how illumination-collection parameters (e.g., collection angle and source-detector separation) influence the ability to measure fluorophore lifetime and tissue layer thickness. Decay curves are simulated with a Monte Carlo TRF light propagation model. Multi-exponential iterative deconvolution is used to determine lifetimes and fractional signal contributions. The ability to detect changes in mucosal thickness is optimized by probes that selectively interrogate regions superficial to the mucosal-submucosal boundary. Optimal accuracy in simultaneous determination of lifetimes in both layers is achieved when each layer contributes 40-60% of the signal. These results indicate that depth-selective approaches to TRF have the potential to enhance disease detection in layered biological tissue and that modeling can play an important role in probe design optimization. Published by Elsevier Ireland Ltd.

  6. Mechanical Model of Geometric Cell and Topological Algorithm for Cell Dynamics from Single-Cell to Formation of Monolayered Tissues with Pattern

    KAUST Repository

    Kachalo, Së ma; Naveed, Hammad; Cao, Youfang; Zhao, Jieling; Liang, Jie

    2015-01-01

    development, and other emerging behavior. Here we describe a cell model and an efficient geometric algorithm for studying the dynamic process of tissue formation in 2D (e.g. epithelial tissues). Our approach improves upon previous methods by incorporating

  7. [Principles of bone tissue structures interaction with full removable dentures fixed on intraosseous implantates modelling].

    Science.gov (United States)

    Shashmurina, V R; Chumachenko, E N; Olesova, V N; Volozhin, A I

    2008-01-01

    Math modelling "removable dentures-implantate-bone" with size and density of bone tissue as variables was created. It allowed to study biomechanical bases of mandibular bone tissue structures interaction with full removable dentures of different constructions and fixed on intraosseous implantates. Analysis of the received data showed that in the majority of cases it was expedient to recommend 3 bearing (abutments) system of denture making. Rest on 4 and more implantates was appropriate for patients with reduced density of spongy bone and significant mandibular bone atrophy. 2 abutment system can be used in patients with high density of spongy bone and absence of mandibular bone atrophy.

  8. Concurrent Longitudinal EPR Monitoring of Tissue Oxygenation, Acidosis, and Reducing Capacity in Mouse Xenograft Tumor Models.

    Science.gov (United States)

    Bobko, Andrey A; Evans, Jason; Denko, Nicholas C; Khramtsov, Valery V

    2017-06-01

    Tissue oxygenation, extracellular acidity, and tissue reducing capacity are among crucial parameters of tumor microenvironment (TME) of significant importance for tumor pathophysiology. In this paper, we demonstrate the complementary application of particulate lithium octa-n-butoxy-naphthalocyanine and soluble nitroxide paramagnetic probes for monitoring of these TME parameters using electron paramagnetic resonance (EPR) technique. Two different types of therapeutic interventions were studied: hypothermia and systemic administration of metabolically active drug. In summary, the results demonstrate the utility of EPR technique for non-invasive concurrent longitudinal monitoring of physiologically relevant chemical parameters of TME in mouse xenograft tumor models, including that under therapeutic intervention.

  9. Sampling Strategies and Processing of Biobank Tissue Samples from Porcine Biomedical Models.

    Science.gov (United States)

    Blutke, Andreas; Wanke, Rüdiger

    2018-03-06

    In translational medical research, porcine models have steadily become more popular. Considering the high value of individual animals, particularly of genetically modified pig models, and the often-limited number of available animals of these models, establishment of (biobank) collections of adequately processed tissue samples suited for a broad spectrum of subsequent analyses methods, including analyses not specified at the time point of sampling, represent meaningful approaches to take full advantage of the translational value of the model. With respect to the peculiarities of porcine anatomy, comprehensive guidelines have recently been established for standardized generation of representative, high-quality samples from different porcine organs and tissues. These guidelines are essential prerequisites for the reproducibility of results and their comparability between different studies and investigators. The recording of basic data, such as organ weights and volumes, the determination of the sampling locations and of the numbers of tissue samples to be generated, as well as their orientation, size, processing and trimming directions, are relevant factors determining the generalizability and usability of the specimen for molecular, qualitative, and quantitative morphological analyses. Here, an illustrative, practical, step-by-step demonstration of the most important techniques for generation of representative, multi-purpose biobank specimen from porcine tissues is presented. The methods described here include determination of organ/tissue volumes and densities, the application of a volume-weighted systematic random sampling procedure for parenchymal organs by point-counting, determination of the extent of tissue shrinkage related to histological embedding of samples, and generation of randomly oriented samples for quantitative stereological analyses, such as isotropic uniform random (IUR) sections generated by the "Orientator" and "Isector" methods, and vertical

  10. Studies of tissue colonization in Rhododendron by Phytophthora ramorum

    Science.gov (United States)

    Marko Riedel; Stefan Wagner; Monika Götz; Lassaad Belbahri; Francois Lefort; Sabine Werres

    2008-01-01

    The knowledge on latency is of great importance to prevent the spread of Phytophthora ramorum with healthy looking plant material. To learn more about the tissue colonisation in Rhododendron, histological studies with epifluorescence microscopy have been started. Epifluorescence images showing P. ramorum structures in different...

  11. Bioprinting of Micro-Organ Tissue Analog for Drug Metabolism Study

    Science.gov (United States)

    Sun, Wei

    An evolving application of tissue engineering is to develop in vitro 3D cell/tissue models for drug screening and pharmacological study. In order to test in space, these in vitro models are mostly manufactured through micro-fabrication techniques and incorporate living cells with MEMS or microfluidic devices. These cell-integrated microfluidic devices, or referred as microorgans, are effective in furnishing reliable and inexpensive drug metabolism and toxicity studies [1-3]. This paper will present an on-going research collaborated between Drexel University and NASA JSC Radiation Physics Laboratory for applying a direct cell printing technique to freeform fabrication of 3D liver tissue analog in drug metabolism study. The paper will discuss modeling, design, and solid freeform fabrication of micro-fluidic flow patterns and bioprinting of 3D micro-liver chamber that biomimics liver physiological microenvironment for enhanced drug metabolization. Technical details to address bioprinting of 3D liver tissue analog, integration with a microfluidic device, and basic drug metabolism study for NASA's interests will presented. 1. Holtorf H. Leslie J. Chang R, Nam J, Culbertson C, Sun W, Gonda S, "Development of a Three-Dimensional Tissue-on-a-Chip Micro-Organ Device for Pharmacokinetic Analysis", the 47th Annual Meeting of the American Society for Cell Biology, Washington, DC, December 1-5, 2007. 2. Chang, R., Nam, J., Culbertson C., Holtorf, H., Jeevarajan, A., Gonda, S. and Sun, W., "Bio-printing and Modeling of Flow Patterns for Cell Encapsulated 3D Liver Chambers For Pharmacokinetic Study", TERMIS North America 2007 Conference and Exposition, Westin Harbour Castle, Toronto, Canada, June 13-16, 2007. 3.Starly, B., Chang, R., Sun, W., Culbertson, C., Holtorf, H. and Gonda, S., "Bioprinted Tissue-on-chip Application for Pharmacokinetic Studies", Proceedings of World Congress on Tissue Engineering and Regenerative Medicine, Pittsburgh, PA, USA, April 24-27, 2006.

  12. Model of adipose tissue cellularity dynamics during food restriction.

    Science.gov (United States)

    Soula, H A; Géloën, A; Soulage, C O

    2015-01-07

    Adipose tissue and adipocytes play a central role in the pathogenesis of metabolic diseases related to obesity. Size of fat cells depends on the balance of synthesis and mobilization of lipids and can undergo important variations throughout the life of the organism. These variations usually occur when storing and releasing lipids according to energy demand. In particular when confronted to severe food restriction, adipocyte releases its lipid content via a process called lipolysis. We propose a mathematical model that combines cell diameter distribution and lipolytic response to show that lipid release is a surface (radius squared) limited mechanism. Since this size-dependent rate affects the cell׳s shrinkage speed, we are able to predict the cell size distribution evolution when lipolysis is the only factor at work: such as during an important food restriction. Performing recurrent surgical biopsies on rats, we measured the evolution of adipose cell size distribution for the same individual throughout the duration of the food restriction protocol. We show that our microscopic model of size dependent lipid release can predict macroscopic size distribution evolution. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. CHARACTERISTIC FEATURES OF MUELLER MATRIX PATTERNS FOR POLARIZATION SCATTERING MODEL OF BIOLOGICAL TISSUES

    Directory of Open Access Journals (Sweden)

    E DU

    2014-01-01

    Full Text Available We developed a model to describe polarized photon scattering in biological tissues. In this model, tissues are simplified to a mixture of scatterers and surrounding medium. There are two types of scatterers in the model: solid spheres and infinitely long solid cylinders. Variables related to the scatterers include: the densities and sizes of the spheres and cylinders, the orientation and angular distribution of cylinders. Variables related to the surrounding medium include: the refractive index, absorption coefficient and birefringence. In this paper, as a development we introduce an optical activity effect to the model. By comparing experiments and Monte Carlo simulations, we analyze the backscattering Mueller matrix patterns of several tissue-like media, and summarize the different effects coming from anisotropic scattering and optical properties. In addition, we propose a possible method to extract the optical activity values for tissues. Both the experimental and simulated results show that, by analyzing the Mueller matrix patterns, the microstructure and optical properties of the medium can be obtained. The characteristic features of Mueller matrix patterns are potentially powerful tools for studying the contrast mechanisms of polarization imaging for medical diagnosis.

  14. Simulation on scattering features of biological tissue based on generated refractive-index model

    International Nuclear Information System (INIS)

    Wang Baoyong; Ding Zhihua

    2011-01-01

    Important information on morphology of biological tissue can be deduced from elastic scattering spectra, and their analyses are based on the known refractive-index model of tissue. In this paper, a new numerical refractive-index model is put forward, and its scattering properties are intensively studied. Spectral decomposition [1] is a widely used method to generate random medium in geology, but it is never used in biology. Biological tissue is different from geology in the sense of random medium. Autocorrelation function describe almost all of features in geology, but biological tissue is not as random as geology, its structure is regular in the sense of fractal geometry [2] , and fractal dimension can be used to describe its regularity under random. Firstly scattering theories of this fractal media are reviewed. Secondly the detailed generation process of refractive-index is presented. Finally the scattering features are simulated in FDTD (Finite Difference Time Domain) Solutions software. From the simulation results, we find that autocorrelation length and fractal dimension controls scattering feature of biological tissue.

  15. Electrical circuit modeling and analysis of microwave acoustic interaction with biological tissues.

    Science.gov (United States)

    Gao, Fei; Zheng, Qian; Zheng, Yuanjin

    2014-05-01

    Numerical study of microwave imaging and microwave-induced thermoacoustic imaging utilizes finite difference time domain (FDTD) analysis for simulation of microwave and acoustic interaction with biological tissues, which is time consuming due to complex grid-segmentation and numerous calculations, not straightforward due to no analytical solution and physical explanation, and incompatible with hardware development requiring circuit simulator such as SPICE. In this paper, instead of conventional FDTD numerical simulation, an equivalent electrical circuit model is proposed to model the microwave acoustic interaction with biological tissues for fast simulation and quantitative analysis in both one and two dimensions (2D). The equivalent circuit of ideal point-like tissue for microwave-acoustic interaction is proposed including transmission line, voltage-controlled current source, envelop detector, and resistor-inductor-capacitor (RLC) network, to model the microwave scattering, thermal expansion, and acoustic generation. Based on which, two-port network of the point-like tissue is built and characterized using pseudo S-parameters and transducer gain. Two dimensional circuit network including acoustic scatterer and acoustic channel is also constructed to model the 2D spatial information and acoustic scattering effect in heterogeneous medium. Both FDTD simulation, circuit simulation, and experimental measurement are performed to compare the results in terms of time domain, frequency domain, and pseudo S-parameters characterization. 2D circuit network simulation is also performed under different scenarios including different sizes of tumors and the effect of acoustic scatterer. The proposed circuit model of microwave acoustic interaction with biological tissue could give good agreement with FDTD simulated and experimental measured results. The pseudo S-parameters and characteristic gain could globally evaluate the performance of tumor detection. The 2D circuit network

  16. Determination of electrical characteristics of body tissues for computational dosimetry studies

    International Nuclear Information System (INIS)

    Silva, Rafael Monteiro da Cruz; Domingues, Luis Adriano M.C.; Neto, Athanasio Mpalantinos; Barbosa, Carlos Ruy Nunez

    2008-01-01

    Increasing public concern about human exposure to electromagnetic fields led to the development of International Exposure Standards, which reflect the actual scientific knowledge on this subject. Existing exposure limits (reference levels), are based on maximum admissible fields or induced currents densities inside human bodies, called basic restrictions. Since those physical quantities can not be readily measured, they must be estimated using techniques of computational dosimetry. These techniques rely on accurate computational modelling of human bodies to establish the relation of external field (electric / magnetic) to induced current (internal field). Nowadays the models available for human body simulation (FEM, FDM,...) are quite accurate, specially when using geometric discretization obtained from medical imaging techniques, however the determination of tissues characteristics (permittivity and conductivity) is still an issue to be dealt with. In current studies the electrical characteristics (permittivity and conductivity) of body tissues are based on values which were obtained from measurements done on tissue simples obtained from dead bodies. However those values may not represent adequately the behaviour of living tissues. In this paper a research designed to characterize the permittivity of human body tissues is presented, consisting of measurements and simulations designed to determine, using indirect methods, the electrical behaviour of living tissues. A study of exposure assessment on a real high voltage transmission line in Brazil, using measured permittivity values combined with a finite element model of the human body is presented in the panel. (author)

  17. Three-Dimensional Normal Human Neural Progenitor Tissue-Like Assemblies: A Model for Persistent Varicell-Zoster Virus Infection and Platform to Study Viral Infectivity and Oxidative Stress and Damage

    Science.gov (United States)

    Goodwin, T. J.; McCarthy, M.; Osterrieder, N.; Cohrs, R. J.; Kaufer, B. B.

    2014-01-01

    The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpesvirus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex threedimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6].

  18. A tool to facilitate clinical biomarker studies - a tissue dictionary based on the Human Protein Atlas

    Directory of Open Access Journals (Sweden)

    Kampf Caroline

    2012-09-01

    Full Text Available Abstract The complexity of tissue and the alterations that distinguish normal from cancer remain a challenge for translating results from tumor biological studies into clinical medicine. This has generated an unmet need to exploit the findings from studies based on cell lines and model organisms to develop, validate and clinically apply novel diagnostic, prognostic and treatment predictive markers. As one step to meet this challenge, the Human Protein Atlas project has been set up to produce antibodies towards human protein targets corresponding to all human protein coding genes and to map protein expression in normal human tissues, cancer and cells. Here, we present a dictionary based on microscopy images created as an amendment to the Human Protein Atlas. The aim of the dictionary is to facilitate the interpretation and use of the image-based data available in the Human Protein Atlas, but also to serve as a tool for training and understanding tissue histology, pathology and cell biology. The dictionary contains three main parts, normal tissues, cancer tissues and cells, and is based on high-resolution images at different magnifications of full tissue sections stained with H & E. The cell atlas is centered on immunofluorescence and confocal microscopy images, using different color channels to highlight the organelle structure of a cell. Here, we explain how this dictionary can be used as a tool to aid clinicians and scientists in understanding the use of tissue histology and cancer pathology in diagnostics and biomarker studies.

  19. The national DBS brain tissue network pilot study: need for more tissue and more standardization.

    Science.gov (United States)

    Vedam-Mai, V; Krock, N; Ullman, M; Foote, K D; Shain, W; Smith, K; Yachnis, A T; Steindler, D; Reynolds, B; Merritt, S; Pagan, F; Marjama-Lyons, J; Hogarth, P; Resnick, A S; Zeilman, P; Okun, M S

    2011-08-01

    Over 70,000 DBS devices have been implanted worldwide; however, there remains a paucity of well-characterized post-mortem DBS brains available to researchers. We propose that the overall understanding of DBS can be improved through the establishment of a Deep Brain Stimulation-Brain Tissue Network (DBS-BTN), which will further our understanding of DBS and brain function. The objectives of the tissue bank are twofold: (a) to provide a complete (clinical, imaging and pathological) database for DBS brain tissue samples, and (b) to make available DBS tissue samples to researchers, which will help our understanding of disease and underlying brain circuitry. Standard operating procedures for processing DBS brains were developed as part of the pilot project. Complete data files were created for individual patients and included demographic information, clinical information, imaging data, pathology, and DBS lead locations/settings. 19 DBS brains were collected from 11 geographically dispersed centers from across the U.S. The average age at the time of death was 69.3 years (51-92, with a standard deviation or SD of 10.13). The male:female ratio was almost 3:1. Average post-mortem interval from death to brain collection was 10.6 h (SD of 7.17). The DBS targets included: subthalamic nucleus, globus pallidus interna, and ventralis intermedius nucleus of the thalamus. In 16.7% of cases the clinical diagnosis failed to match the pathological diagnosis. We provide neuropathological findings from the cohort, and perilead responses to DBS. One of the most important observations made in this pilot study was the missing data, which was approximately 25% of all available data fields. Preliminary results demonstrated the feasibility and utility of creating a National DBS-BTN resource for the scientific community. We plan to improve our techniques to remedy omitted clinical/research data, and expand the Network to include a larger donor pool. We will enhance sample preparation to

  20. Study of trace elements distribution in various tissues structures

    International Nuclear Information System (INIS)

    Kwiatek, W.M.; Marczewska, E.

    1994-01-01

    Many papers have been written during the past ten years about TE study in cancer and normal tissues describing the use of different methods for detection of trace elements. Concentration of TE depends strongly on the sample measured. However, according to our knowledge, the role of TE in cancerous tissue is still known. Therefore, we propose to perform an experiment which will hopefully given us more information about the relationship between the concentration of elements in different tissues. The developing industry localised near Cracow becomes a serious danger for health of it's inhabitants. The negative influence of the air pollution to the living organisms is seen not only in the nature but also in humans. Therefore we want to analyse the trace element contents in the air. Such investigation will give the information about the pollution level in the City. The pollution has its obvious negative influence to health and toxic element concentration level in blood. It is interesting to check if placenta plays an effective role in foetus protection against toxic metals. In order to study this problem, the trace element analysis of placenta tissues will be done by means of synchrotron microbeam. (author). 1 ref

  1. Cellular automata and integrodifferential equation models for cell renewal in mosaic tissues

    Science.gov (United States)

    Bloomfield, J. M.; Sherratt, J. A.; Painter, K. J.; Landini, G.

    2010-01-01

    Mosaic tissues are composed of two or more genetically distinct cell types. They occur naturally, and are also a useful experimental method for exploring tissue growth and maintenance. By marking the different cell types, one can study the patterns formed by proliferation, renewal and migration. Here, we present mathematical modelling suggesting that small changes in the type of interaction that cells have with their local cellular environment can lead to very different outcomes for the composition of mosaics. In cell renewal, proliferation of each cell type may depend linearly or nonlinearly on the local proportion of cells of that type, and these two possibilities produce very different patterns. We study two variations of a cellular automaton model based on simple rules for renewal. We then propose an integrodifferential equation model, and again consider two different forms of cellular interaction. The results of the continuous and cellular automata models are qualitatively the same, and we observe that changes in local environment interaction affect the dynamics for both. Furthermore, we demonstrate that the models reproduce some of the patterns seen in actual mosaic tissues. In particular, our results suggest that the differing patterns seen in organ parenchymas may be driven purely by the process of cell replacement under different interaction scenarios. PMID:20375040

  2. Modeling bioluminescent photon transport in tissue based on Radiosity-diffusion model

    Science.gov (United States)

    Sun, Li; Wang, Pu; Tian, Jie; Zhang, Bo; Han, Dong; Yang, Xin

    2010-03-01

    Bioluminescence tomography (BLT) is one of the most important non-invasive optical molecular imaging modalities. The model for the bioluminescent photon propagation plays a significant role in the bioluminescence tomography study. Due to the high computational efficiency, diffusion approximation (DA) is generally applied in the bioluminescence tomography. But the diffusion equation is valid only in highly scattering and weakly absorbing regions and fails in non-scattering or low-scattering tissues, such as a cyst in the breast, the cerebrospinal fluid (CSF) layer of the brain and synovial fluid layer in the joints. A hybrid Radiosity-diffusion model is proposed for dealing with the non-scattering regions within diffusing domains in this paper. This hybrid method incorporates a priori information of the geometry of non-scattering regions, which can be acquired by magnetic resonance imaging (MRI) or x-ray computed tomography (CT). Then the model is implemented using a finite element method (FEM) to ensure the high computational efficiency. Finally, we demonstrate that the method is comparable with Mont Carlo (MC) method which is regarded as a 'gold standard' for photon transportation simulation.

  3. Discrete vessel heat transfer in perfused tissue - model comparison

    NARCIS (Netherlands)

    Stanczyk, M.; Leeuwen, van G.M.J.; Steenhoven, van A.A.

    2007-01-01

    The aim of this paper is to compare two methods of calculating heat transfer in perfused biological tissue using a discrete vessel description. The methods differ in two important aspects: the representation of the vascular system and the algorithm for calculating the heat flux between tissue and

  4. Toward in vivo lung's tissue incompressibility characterization for tumor motion modeling in radiation therapy

    International Nuclear Information System (INIS)

    Shirzadi, Zahra; Sadeghi-Naini, Ali; Samani, Abbas

    2013-01-01

    Purpose: A novel technique is proposed to characterize lung tissue incompressibility variation during respiration. Estimating lung tissue incompressibility parameter variations resulting from air content variation throughout respiration is critical for computer assisted tumor motion tracking. Continuous tumor motion is a major challenge in lung cancer radiotherapy, especially with external beam radiotherapy. If not accounted for, this motion may lead to areas of radiation overdosage for normal tissue. Given the unavailability of imaging modality that can be used effectively for real-time lung tumor tracking, computer assisted approach based on tissue deformation estimation can be a good alternative. This approach involves lung biomechanical model where its fidelity depends on input tissue properties. This investigation shows that considering variable tissue incompressibility parameter is very important for predicting tumor motion accurately, hence improving the lung radiotherapy outcome. Methods: First, an in silico lung phantom study was conducted to demonstrate the importance of employing variable Poisson's ratio for tumor motion predication. After it was established that modeling this variability is critical for accurate tumor motion prediction, an optimization based technique was developed to estimate lung tissue Poisson's ratio as a function of respiration cycle time. In this technique, the Poisson's ratio and lung pressure value were varied systematically until optimal values were obtained, leading to maximum similarity between acquired and simulated 4D CT lung images. This technique was applied in an ex vivo porcine lung study where simulated images were constructed using the end exhale CT image and deformation fields obtained from the lung's FE modeling of each respiration time increment. To model the tissue, linear elastic and Marlow hyperelastic material models in conjunction with variable Poisson's ratio were used. Results: The phantom study showed that

  5. Tissue Discrimination by Uncorrected Autofluorescence Spectra: A Proof-of-Principle Study for Tissue-Specific Laser Surgery

    Directory of Open Access Journals (Sweden)

    Katja Tangermann-Gerk

    2013-10-01

    Full Text Available Laser surgery provides a number of advantages over conventional surgery. However, it implies large risks for sensitive tissue structures due to its characteristic non-tissue-specific ablation. The present study investigates the discrimination of nine different ex vivo tissue types by using uncorrected (raw autofluorescence spectra for the development of a remote feedback control system for tissue-selective laser surgery. Autofluorescence spectra (excitation wavelength 377 ± 50 nm were measured from nine different ex vivo tissue types, obtained from 15 domestic pig cadavers. For data analysis, a wavelength range between 450 nm and 650 nm was investigated. Principal Component Analysis (PCA and Quadratic Discriminant Analysis (QDA were used to discriminate the tissue types. ROC analysis showed that PCA, followed by QDA, could differentiate all investigated tissue types with AUC results between 1.00 and 0.97. Sensitivity reached values between 93% and 100% and specificity values between 94% and 100%. This ex vivo study shows a high differentiation potential for physiological tissue types when performing autofluorescence spectroscopy followed by PCA and QDA. The uncorrected autofluorescence spectra are suitable for reliable tissue discrimination and have a high potential to meet the challenges necessary for an optical feedback system for tissue-specific laser surgery.

  6. Application of laboratory microtomography to the study of mineralized tissues

    International Nuclear Information System (INIS)

    Elliot, J.C.; Davis, G.R.; Anderson, P.; Wong, F.S.L.; Dowker, S.E.P.; Mercer, C.E.

    1997-01-01

    The principles of microtomography are briefly presented and recent studies of mineralized tissues using laboratory and synchrotron X-ray sources are reviewed. Results are given of investigations undertaken with laboratory systems using either a 1 st generation (single beam of 15 mu m and energy dispersive detector) or a novel 4 th generation system with 2-D detector that can provide 3-D images with vowels of 38x38x38 mu m ''3 of specimens with diameter up to 40 mm. Studies include mineral concentration distributions in cortical bone trabecular structure in a human vertebral body, cracking of bone under compression in situ and root canal obturation and Er: YAG laser application to enamel and dentine. Future applications of microtomography to the study of mineralized tissues and their interaction with biomaterials are discussed.(Author) 31 refs

  7. Experiment K-7-29: Connective Tissue Studies. Part 3; Rodent Tissue Repair: Skeletal Muscle

    Science.gov (United States)

    Stauber, W.; Fritz, V. K.; Burkovskaya, T. E.; Ilyina-Kakueva, E. I.

    1994-01-01

    Myofiber injury-repair was studied in the rat gastrocnemius following a crush injury to the lower leg prior to flight in order to understand if the regenerative responses of muscles are altered by the lack of gravitational forces during Cosmos 2044 flight. After 14 days of flight, the gastrocnemius muscle was removed from the 5 injured flight rodents and various Earth-based treatment groups for comparison. The Earth-based animals consisted of three groups of five rats with injured muscles from a simulated, tail-suspended, and vivarium as well as an uninjured basal group. The gastrocnemius muscle from each was evaluated by histochemical and immunohistochemical techniques to document myofiber, vascular, and connective tissue alterations following injury. In general the repair process was somewhat similar in all injured muscle samples with regard to extracellular matrix organization and myofiber regeneration. Small and large myofibers were present with a newly organized extracellular matrix indicative of myogenesis and muscle regeneration. In the tail-suspended animals, a more complete repair was observed with no enlarged area of non-muscle cells or matrix material visible. In contrast, the muscle samples from the flight animals were less well differentiated with more macrophages and blood vessels in the repair region but small myofibers and proteoglycans, nevertheless, were in their usual configuration. Thus, myofiber repair did vary in muscles from the different groups, but for the most part, resulted in functional muscle tissue.

  8. Viscoelastic properties of bovine orbital connective tissue and fat: constitutive models.

    Science.gov (United States)

    Yoo, Lawrence; Gupta, Vijay; Lee, Choongyeop; Kavehpore, Pirouz; Demer, Joseph L

    2011-12-01

    Reported mechanical properties of orbital connective tissue and fat have been too sparse to model strain-stress relationships underlying biomechanical interactions in strabismus. We performed rheological tests to develop a multi-mode upper convected Maxwell (UCM) model of these tissues under shear loading. From 20 fresh bovine orbits, 30 samples of connective tissue were taken from rectus pulley regions and 30 samples of fatty tissues from the posterior orbit. Additional samples were defatted to determine connective tissue weight proportion, which was verified histologically. Mechanical testing in shear employed a triborheometer to perform: strain sweeps at 0.5-2.0 Hz; shear stress relaxation with 1% strain; viscometry at 0.01-0.5 s(-1) strain rate; and shear oscillation at 1% strain. Average connective tissue weight proportion was 98% for predominantly connective tissue and 76% for fatty tissue. Connective tissue specimens reached a long-term relaxation modulus of 668 Pa after 1,500 s, while corresponding values for fatty tissue specimens were 290 Pa and 1,100 s. Shear stress magnitude for connective tissue exceeded that of fatty tissue by five-fold. Based on these data, we developed a multi-mode UCM model with variable viscosities and time constants, and a damped hyperelastic response that accurately described measured properties of both connective and fatty tissues. Model parameters differed significantly between the two tissues. Viscoelastic properties of predominantly connective orbital tissues under shear loading differ markedly from properties of orbital fat, but both are accurately reflected using UCM models. These viscoelastic models will facilitate realistic global modeling of EOM behavior in binocular alignment and strabismus.

  9. An extended OpenSim knee model for analysis of strains of connective tissues.

    Science.gov (United States)

    Marieswaran, M; Sikidar, Arnab; Goel, Anu; Joshi, Deepak; Kalyanasundaram, Dinesh

    2018-04-17

    OpenSim musculoskeletal models provide an accurate simulation environment that eases limitations of in vivo and in vitro studies. In this work, a biomechanical knee model was formulated with femoral articular cartilages and menisci along with 25 connective tissue bundles representing ligaments and capsules. The strain patterns of the connective tissues in the presence of femoral articular cartilage and menisci in the OpenSim knee model was probed in a first of its kind study. The effect of knee flexion (0°-120°), knee rotation (- 40° to 30°) and knee adduction (- 15° to 15°) on the anterior cruciate, posterior cruciate, medial collateral, lateral collateral ligaments and other connective tissues were studied by passive simulation. Further, a new parameter for assessment of strain namely, the differential inter-bundle strain of the connective tissues were analyzed to provide new insights for injury kinematics. ACL, PCL, LCL and PL was observed to follow a parabolic strain pattern during flexion while MCL represented linear strain patterns. All connective tissues showed non-symmetric parabolic strain variation during rotation. During adduction, the strain variation was linear for the knee bundles except for FL, PFL and TL. Strains higher than 0.1 were observed in most of the bundles during lateral rotation followed by abduction, medial rotation and adduction. In the case of flexion, highest strains were observed in aACL and aPCL. A combination of strains at a flexion of 0° with medial rotation of 30° or a flexion of 80° with rotation of 30° are evaluated as rupture-prone kinematics.

  10. Multiaxial mechanical properties and constitutive modeling of human adipose tissue: a basis for preoperative simulations in plastic and reconstructive surgery.

    Science.gov (United States)

    Sommer, Gerhard; Eder, Maximilian; Kovacs, Laszlo; Pathak, Heramb; Bonitz, Lars; Mueller, Christoph; Regitnig, Peter; Holzapfel, Gerhard A

    2013-11-01

    A preoperative simulation of soft tissue deformations during plastic and reconstructive surgery is desirable to support the surgeon's planning and to improve surgical outcomes. The current development of constitutive adipose tissue models, for the implementation in multilayer computational frameworks for the simulation of human soft tissue deformations, has proved difficult because knowledge of the required mechanical parameters of fat tissue is limited. Therefore, for the first time, human abdominal adipose tissues were mechanically investigated by biaxial tensile and triaxial shear tests. The results of this study suggest that human abdominal adipose tissues under quasi-static and dynamic multiaxial loadings can be characterized as a nonlinear, anisotropic and viscoelastic soft biological material. The nonlinear and anisotropic features are consequences of the material's collagenous microstructure. The aligned collagenous septa observed in histological investigations causes the anisotropy of the tissue. A hyperelastic model used in this study was appropriate to represent the quasi-static multiaxial mechanical behavior of fat tissue. The constitutive parameters are intended to serve as a basis for soft tissue simulations using the finite element method, which is an apparent method for obtaining promising results in the field of plastic and reconstructive surgery. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  11. A systematic study of head tissue inhomogeneity and anisotropy on EEG forward problem computing

    International Nuclear Information System (INIS)

    Bashar, M.R.; Li, Y.; Wen, P.

    2010-01-01

    Full text: In this study, we propose a stochastic method to analyze the effects of inhomogeneous anisotropic tissue conductivity on electroencephalogram (EEG) in forward computation. We apply this method to an inhomogeneous and anisotropic spherical human head model. We apply stochastic finite element method based on Legendre polynomials, Karhunen-Loeve expansion and stochastic Galerkin methods. We apply Volume and Wang's constraints to restrict the anisotropic conductivities for both the white matter (WM) and the skull tissue compartments. The EEGs resulting from deterministic and stochastic FEMs are compared using statistical measurement techniques. Based on these comparisons, we find that EEGs generated by incorporating WM and skull inhomogeneous anisotropic tissue properties individually result in an average of 56.5 and 57.5% relative errors, respectively. Incorporating these tissue properties for both layers together generate 43.5% average relative error. Inhomogeneous scalp tissue causes 27% average relative error and a full inhomogeneous anisotropic model brings in an average of 45.5% relative error. The study results demonstrate that the effects of inhomogeneous anisotropic tissue conductivity are significant on EEG.

  12. An image-based skeletal tissue model for the ICRP reference newborn

    Energy Technology Data Exchange (ETDEWEB)

    Pafundi, Deanna; Lee, Choonsik; Bolch, Wesley [Department of Nuclear and Radiological Engineering, University of Florida, Gainesville, FL (United States); Watchman, Christopher; Bourke, Vincent [Department of Radiation Oncology, University of Arizona, Tucson, AZ (United States); Aris, John [Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL (United States); Shagina, Natalia [Urals Research Center for Radiation Medicine, Chelyabinsk (Russian Federation); Harrison, John; Fell, Tim [Radiation Protection Division, Health Protection Agency, Chilton (United Kingdom)], E-mail: wbolch@ufl.edu

    2009-07-21

    Hybrid phantoms represent a third generation of computational models of human anatomy needed for dose assessment in both external and internal radiation exposures. Recently, we presented the first whole-body hybrid phantom of the ICRP reference newborn with a skeleton constructed from both non-uniform rational B-spline and polygon-mesh surfaces (Lee et al 2007 Phys. Med. Biol. 52 3309-33). The skeleton in that model included regions of cartilage and fibrous connective tissue, with the remainder given as a homogenous mixture of cortical and trabecular bone, active marrow and miscellaneous skeletal tissues. In the present study, we present a comprehensive skeletal tissue model of the ICRP reference newborn to permit a heterogeneous representation of the skeleton in that hybrid phantom set-both male and female-that explicitly includes a delineation of cortical bone so that marrow shielding effects are correctly modeled for low-energy photons incident upon the newborn skeleton. Data sources for the tissue model were threefold. First, skeletal site-dependent volumes of homogeneous bone were obtained from whole-cadaver CT image analyses. Second, selected newborn bone specimens were acquired at autopsy and subjected to micro-CT image analysis to derive model parameters of the marrow cavity and bone trabecular 3D microarchitecture. Third, data given in ICRP Publications 70 and 89 were selected to match reference values on total skeletal tissue mass. Active marrow distributions were found to be in reasonable agreement with those given previously by the ICRP. However, significant differences were seen in total skeletal and site-specific masses of trabecular and cortical bone between the current and ICRP newborn skeletal tissue models. The latter utilizes an age-independent ratio of 80%/20% cortical and trabecular bone for the reference newborn. In the current study, a ratio closer to 40%/60% is used based upon newborn CT and micro-CT skeletal image analyses. These changes in

  13. Impact of Statistical Learning Methods on the Predictive Power of Multivariate Normal Tissue Complication Probability Models

    Energy Technology Data Exchange (ETDEWEB)

    Xu Chengjian, E-mail: c.j.xu@umcg.nl [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schaaf, Arjen van der; Schilstra, Cornelis; Langendijk, Johannes A.; Veld, Aart A. van' t [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands)

    2012-03-15

    Purpose: To study the impact of different statistical learning methods on the prediction performance of multivariate normal tissue complication probability (NTCP) models. Methods and Materials: In this study, three learning methods, stepwise selection, least absolute shrinkage and selection operator (LASSO), and Bayesian model averaging (BMA), were used to build NTCP models of xerostomia following radiotherapy treatment for head and neck cancer. Performance of each learning method was evaluated by a repeated cross-validation scheme in order to obtain a fair comparison among methods. Results: It was found that the LASSO and BMA methods produced models with significantly better predictive power than that of the stepwise selection method. Furthermore, the LASSO method yields an easily interpretable model as the stepwise method does, in contrast to the less intuitive BMA method. Conclusions: The commonly used stepwise selection method, which is simple to execute, may be insufficient for NTCP modeling. The LASSO method is recommended.

  14. Impact of statistical learning methods on the predictive power of multivariate normal tissue complication probability models.

    Science.gov (United States)

    Xu, Cheng-Jian; van der Schaaf, Arjen; Schilstra, Cornelis; Langendijk, Johannes A; van't Veld, Aart A

    2012-03-15

    To study the impact of different statistical learning methods on the prediction performance of multivariate normal tissue complication probability (NTCP) models. In this study, three learning methods, stepwise selection, least absolute shrinkage and selection operator (LASSO), and Bayesian model averaging (BMA), were used to build NTCP models of xerostomia following radiotherapy treatment for head and neck cancer. Performance of each learning method was evaluated by a repeated cross-validation scheme in order to obtain a fair comparison among methods. It was found that the LASSO and BMA methods produced models with significantly better predictive power than that of the stepwise selection method. Furthermore, the LASSO method yields an easily interpretable model as the stepwise method does, in contrast to the less intuitive BMA method. The commonly used stepwise selection method, which is simple to execute, may be insufficient for NTCP modeling. The LASSO method is recommended. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Impact of Statistical Learning Methods on the Predictive Power of Multivariate Normal Tissue Complication Probability Models

    International Nuclear Information System (INIS)

    Xu Chengjian; Schaaf, Arjen van der; Schilstra, Cornelis; Langendijk, Johannes A.; Veld, Aart A. van’t

    2012-01-01

    Purpose: To study the impact of different statistical learning methods on the prediction performance of multivariate normal tissue complication probability (NTCP) models. Methods and Materials: In this study, three learning methods, stepwise selection, least absolute shrinkage and selection operator (LASSO), and Bayesian model averaging (BMA), were used to build NTCP models of xerostomia following radiotherapy treatment for head and neck cancer. Performance of each learning method was evaluated by a repeated cross-validation scheme in order to obtain a fair comparison among methods. Results: It was found that the LASSO and BMA methods produced models with significantly better predictive power than that of the stepwise selection method. Furthermore, the LASSO method yields an easily interpretable model as the stepwise method does, in contrast to the less intuitive BMA method. Conclusions: The commonly used stepwise selection method, which is simple to execute, may be insufficient for NTCP modeling. The LASSO method is recommended.

  16. Biophotonics in diagnosis and modeling of tissue pathologies

    Science.gov (United States)

    Serafetinides, A. A.; Makropoulou, M.; Drakaki, E.

    2008-12-01

    Biophotonics techniques are applied to several fields in medicine and biology. The laser based techniques, such as the laser induced fluorescence (LIF) spectroscopy and the optical coherence tomography (OCT), are of particular importance in dermatology, where the laser radiation could be directly applied to the tissue target (e.g. skin). In addition, OCT resolves architectural tissue properties that might be useful as tumour discrimination parameters for skin as well as for ocular non-invasive visualization. Skin and ocular tissues are complex multilayered and inhomogeneous organs with spatially varying optical properties. This fact complicates the quantitative analysis of the fluorescence and/or light scattering spectra, even from the same tissue sample. To overcome this problem, mathematical simulation is applied for the investigation of the human tissue optical properties, in the visible/infrared range of the spectrum, resulting in a better discrimination of several tissue pathologies. In this work, we present i) a general view on biophotonics applications in diagnosis of human diseases, ii) some specific results on laser spectroscopy techniques, as LIF measurements, applied in arterial and skin pathologies and iii) some experimental and theoretical results on ocular OCT measurements. Regarding the LIF spectroscopy, we examined the autofluorescence properties of several human skin samples, excised from humans undergoing biopsy examination. A nitrogen laser was used as an excitation source, emitting at 337 nm (ultraviolet excitation). Histopathology examination of the samples was also performed, after the laser spectroscopy measurements and the results from the spectroscopic and medical analysis were compared, to differentiate malignancies, e.g. basal cell carcinoma tissue (BCC), from normal skin tissue. Regarding the OCT technique, we correlated human data, obtained from patients undergoing OCT examination, with Monte Carlo simulated cornea and retina tissues

  17. Physical mechanisms of collective expansion in confluent tissues in an Active Vertex Model

    Science.gov (United States)

    Czajkowski, Michael; Bi, Dapeng; Yang, Xingbo; Merkel, Matthias; Manning, M. Lisa; Marchetti, M. Cristina

    Living tissues form many novel patterns due to the active forces exerted by the constituent cells. How these forces combine with proliferation (changing number density) and boundary conditions to control the resultant patterns is an interesting open question. This question arises naturally for in vitro wound healing experiments, where an initially confined monolayer is allowed to expand freely. As the cells interact, proliferate and advance laterally, a characteristic pattern of traction stresses is formed on the substrate. We have developed an Active Vertex Model to make predictions about active confluent tissues with free boundaries. The model incorporates active forces, flocking interactions, and simple rules for cell division within the vertex model geometry. It also exhibits a fluid-solid transition, with qualitatively distinct stress profiles in the solid and in the liquid. Furthermore, under the assumption that cells proliferate more when stretched, we find that polar alignment interactions strongly enhance cell proliferation. Our model suggests that wound healing assays may provide a useful rheological tool for tissues, as well as a novel system for studying the connection between proliferation and flocking. We acknowledge support from NSF-DGE-1068780 and The Simons Foundation for the Investigator Award in MMLS as well as the Targeted Grant in the Mathematical Modeling of Living Systems Number: 342354.

  18. Microangiographic study of the canine dental tissues: a preliminary report

    International Nuclear Information System (INIS)

    Miyabayashi, T.; Morgan, J.P.

    1987-01-01

    A microangiographic study of the dental tissues was performed on one adult mongrel dog to examine the usefulness of the technique. This preliminary study used 30% wt/vol Micropaque suspension which was perfused into the common carotid arteries. After the complete perfusion, the specimen was fixed into a mixture of 10% buffered neutral formalin solution and 95% ethyl alcohol. The mandibular bone with teeth in situ was decalcified. The specimen was embedded in methyl methacrylate. One mm slab sections were made, and then the microangiographs were made. Adequate filling of arterioles was evident on the microangiographs. This technique is shown to be useful in characterizing the nature of the blood supply to the bone and teeth that might be involved in the pathogenesis of radiation-induced injury in the canine dental and periodontal tissues

  19. Necrotizing soft tissue infections - a multicentre, prospective observational study (INFECT)

    DEFF Research Database (Denmark)

    Madsen, M. B.; Skrede, S.; Bruun, T.

    2018-01-01

    these to patient-important outcomes. With this protocol and statistical analysis plan we describe the methods used to obtain data and the details of the planned analyses. Methods: The INFECT study is a multicentre, prospective observational cohort study. Patients with NSTIs are enrolled in five Scandinavian......Background: The INFECT project aims to advance our understanding of the pathophysiological mechanisms in necrotizing soft tissue infections (NSTIs). The INFECT observational study is part of the INFECT project with the aim of studying the clinical profile of patients with NSTIs and correlating...

  20. Study on the neutron dosimetric characteristics of Tissue Equivalent Proportional Counter

    Energy Technology Data Exchange (ETDEWEB)

    Nunomiya, T.; Kim, E.; Kurosawa, T.; Taniguchi, S.; Nakamura, T. [Tohoku Univ., Sendai (Japan). Cyclotron and Radioisotope Center; Tsujimura, N.; Momose, T.; Shinohara, K. [Japan Nuclear Cycle Development Inst., Environment and Safety Division, Tokai Works, Tokai, Ibaraki (Japan)

    1999-03-01

    The neutron dosimetric characteristics of TEPC (Tissue Equivalent Proportional Counter) has been investigated under a cooperative study between Tohoku University and JNC since 1997. This TEPC is a spherical, large volume, single-wire proportional counter (the model LETSW-5, manufactured by Far West Technology, Inc.) and filled with a tissue equivalent gas in a spherical detector of the A-150 tissue equivalent plastic. The TEPC can measure the spectra of absorbed dose in LET and easily estimate the tissue equivalent dose to neutron. This report summarizes the dosimetric characteristics of TEPC to the monoenergetic neutrons with energy from 8 keV to 15 MeV. It is found that TEPC can estimate the ambient dose equivalent, H*(10), with an accuracy from 0.9 to 2 to the neutron above 0.25 MeV and TEPC has a good counting efficiency enough to measure neutron doses with low dose rate at the stray neutron fields. (author)

  1. Reliability of implant surgical guides based on soft-tissue models.

    Science.gov (United States)

    Maney, Pooja; Simmons, David E; Palaiologou, Archontia; Kee, Edwin

    2012-12-01

    The purpose of this study was to determine the accuracy of implant surgical guides fabricated on diagnostic casts. Guides were fabricated with radiopaque rods representing implant positions. Cone beam computerized tomograms were taken with guides in place. Accuracy was evaluated using software to simulate implant placement. Twenty-two sites (47%) were considered accurate (13 of 24 maxillary and 9 of 23 mandibular sites). Soft-tissue models do not always provide sufficient accuracy for fabricating implant surgical guides.

  2. Generalized Beer-Lambert model for near-infrared light propagation in thick biological tissues

    Science.gov (United States)

    Bhatt, Manish; Ayyalasomayajula, Kalyan R.; Yalavarthy, Phaneendra K.

    2016-07-01

    The attenuation of near-infrared (NIR) light intensity as it propagates in a turbid medium like biological tissue is described by modified the Beer-Lambert law (MBLL). The MBLL is generally used to quantify the changes in tissue chromophore concentrations for NIR spectroscopic data analysis. Even though MBLL is effective in terms of providing qualitative comparison, it suffers from its applicability across tissue types and tissue dimensions. In this work, we introduce Lambert-W function-based modeling for light propagation in biological tissues, which is a generalized version of the Beer-Lambert model. The proposed modeling provides parametrization of tissue properties, which includes two attenuation coefficients μ0 and η. We validated our model against the Monte Carlo simulation, which is the gold standard for modeling NIR light propagation in biological tissue. We included numerous human and animal tissues to validate the proposed empirical model, including an inhomogeneous adult human head model. The proposed model, which has a closed form (analytical), is first of its kind in providing accurate modeling of NIR light propagation in biological tissues.

  3. Tools for assessing mitochondrial dynamics in mouse tissues and neurodegenerative models

    Science.gov (United States)

    Pham, Anh H.

    Mitochondria are dynamic organelles that undergo membrane fusion and fission and transport. The dynamic properties of mitochondria are important for regulating mitochondrial function. Defects in mitochondrial dynamics are linked neurodegenerative diseases and affect the development of many tissues. To investigate the role of mitochondrial dynamics in diseases, versatile tools are needed to explore the physiology of these dynamic organelles in multiple tissues. Current tools for monitoring mitochondrial dynamics have been limited to studies in cell culture, which may be inadequate model systems for exploring the network of tissues. Here, we have generated mouse models for monitoring mitochondrial dynamics in a broad spectrum of tissues and cell types. The Photo-Activatable Mitochondrial (PhAM floxed) line enables Cre-inducible expression of a mitochondrial targeted photoconvertible protein, Dendra2 (mito-Dendra2). In the PhAMexcised line, mito-Dendra2 is ubiquitously expressed to facilitate broad analysis of mitochondria at various developmental processes. We have utilized these models to study mitochondrial dynamics in the nigrostriatal circuit of Parkinson's disease (PD) and in the development of skeletal muscles. Increasing evidences implicate aberrant regulation of mitochondrial fusion and fission in models of PD. To assess the function of mitochondrial dynamics in the nigrostriatal circuit, we utilized transgenic techniques to abrogate mitochondrial fusion. We show that deletion of the Mfn2 leads to the degeneration of dopaminergic neurons and Parkinson's-like features in mice. To elucidate the dynamic properties of mitochondria during muscle development, we established a platform for examining mitochondrial compartmentalization in skeletal muscles. This model system may yield clues to the role of mitochondrial dynamics in mitochondrial myopathies.

  4. Three-Dimensional Normal Human Neutral Progenitor Tissue-Like Assemblies: A Model for Persistent Varicella-Zoster Virus Infection and Platform to Study Oxidate Stress and Damage in Multiple Hit Scenarios

    Science.gov (United States)

    Goodwin, Thomas J.; McCarthy, M.; Osterrieder, N.; Cohrs, R. J.; Kaufer, B. B.

    2014-01-01

    The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpes virus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex three-dimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6]. By combining the RFs of microgravity, radiation, and viral infection we will demonstrate that living in the space environment leads to significant physiological consequences for the peripheral and subsequently the central nervous system (PNS, CNS) associated with OSaD generation and consequentially endangers long-duration and exploration-class missions.

  5. MCNP modelling of the wall effects observed in tissue-equivalent proportional counters.

    Science.gov (United States)

    Hoff, J L; Townsend, L W

    2002-01-01

    Tissue-equivalent proportional counters (TEPCs) utilise tissue-equivalent materials to depict homogeneous microscopic volumes of human tissue. Although both the walls and gas simulate the same medium, they respond to radiation differently. Density differences between the two materials cause distortions, or wall effects, in measurements, with the most dominant effect caused by delta rays. This study uses a Monte Carlo transport code, MCNP, to simulate the transport of secondary electrons within a TEPC. The Rudd model, a singly differential cross section with no dependence on electron direction, is used to describe the energy spectrum obtained by the impact of two iron beams on water. Based on the models used in this study, a wall-less TEPC had a higher lineal energy (keV.micron-1) as a function of impact parameter than a solid-wall TEPC for the iron beams under consideration. An important conclusion of this study is that MCNP has the ability to model the wall effects observed in TEPCs.

  6. Electro-mechanical dynamics of spiral waves in a discrete 2D model of human atrial tissue.

    Science.gov (United States)

    Brocklehurst, Paul; Ni, Haibo; Zhang, Henggui; Ye, Jianqiao

    2017-01-01

    We investigate the effect of mechano-electrical feedback and atrial fibrillation induced electrical remodelling (AFER) of cellular ion channel properties on the dynamics of spiral waves in a discrete 2D model of human atrial tissue. The tissue electro-mechanics are modelled using the discrete element method (DEM). Millions of bonded DEM particles form a network of coupled atrial cells representing 2D cardiac tissue, allowing simulations of the dynamic behaviour of electrical excitation waves and mechanical contraction in the tissue. In the tissue model, each cell is modelled by nine particles, accounting for the features of individual cellular geometry; and discrete inter-cellular spatial arrangement of cells is also considered. The electro-mechanical model of a human atrial single-cell was constructed by strongly coupling the electrophysiological model of Colman et al. to the mechanical myofilament model of Rice et al., with parameters modified based on experimental data. A stretch-activated channel was incorporated into the model to simulate the mechano-electrical feedback. In order to investigate the effect of mechano-electrical feedback on the dynamics of spiral waves, simulations of spiral waves were conducted in both the electromechanical model and the electrical-only model in normal and AFER conditions, to allow direct comparison of the results between the models. Dynamics of spiral waves were characterized by tracing their tip trajectories, stability, excitation frequencies and meandering range of tip trajectories. It was shown that the developed DEM method provides a stable and efficient model of human atrial tissue with considerations of the intrinsically discrete and anisotropic properties of the atrial tissue, which are challenges to handle in traditional continuum mechanics models. This study provides mechanistic insights into the complex behaviours of spiral waves and the genesis of atrial fibrillation by showing an important role of the mechano

  7. Electro-mechanical dynamics of spiral waves in a discrete 2D model of human atrial tissue.

    Directory of Open Access Journals (Sweden)

    Paul Brocklehurst

    Full Text Available We investigate the effect of mechano-electrical feedback and atrial fibrillation induced electrical remodelling (AFER of cellular ion channel properties on the dynamics of spiral waves in a discrete 2D model of human atrial tissue. The tissue electro-mechanics are modelled using the discrete element method (DEM. Millions of bonded DEM particles form a network of coupled atrial cells representing 2D cardiac tissue, allowing simulations of the dynamic behaviour of electrical excitation waves and mechanical contraction in the tissue. In the tissue model, each cell is modelled by nine particles, accounting for the features of individual cellular geometry; and discrete inter-cellular spatial arrangement of cells is also considered. The electro-mechanical model of a human atrial single-cell was constructed by strongly coupling the electrophysiological model of Colman et al. to the mechanical myofilament model of Rice et al., with parameters modified based on experimental data. A stretch-activated channel was incorporated into the model to simulate the mechano-electrical feedback. In order to investigate the effect of mechano-electrical feedback on the dynamics of spiral waves, simulations of spiral waves were conducted in both the electromechanical model and the electrical-only model in normal and AFER conditions, to allow direct comparison of the results between the models. Dynamics of spiral waves were characterized by tracing their tip trajectories, stability, excitation frequencies and meandering range of tip trajectories. It was shown that the developed DEM method provides a stable and efficient model of human atrial tissue with considerations of the intrinsically discrete and anisotropic properties of the atrial tissue, which are challenges to handle in traditional continuum mechanics models. This study provides mechanistic insights into the complex behaviours of spiral waves and the genesis of atrial fibrillation by showing an important role of

  8. Bone tissue engineering for spine fusion : An experimental study on ectopic and orthotopic implants in rats

    NARCIS (Netherlands)

    van Gaalen, SM; Dhert, WJA; van den Muysenberg, A; Oner, FC; van Blitterswijk, C; Verbout, AJ; de Bruijn, J.D.

    2004-01-01

    Alternatives to the use of autologous bone as a bone graft in spine surgery are needed. The purpose of this study was to examine tissue-engineered bone constructs in comparison with control scaffolds without cells in a posterior spinal implantation model in rats. Syngeneic bone marrow cells were

  9. Modeling the Human Scarred Heart In Vitro: Toward New Tissue Engineered Models.

    Science.gov (United States)

    Deddens, Janine C; Sadeghi, Amir Hossein; Hjortnaes, Jesper; van Laake, Linda W; Buijsrogge, Marc; Doevendans, Pieter A; Khademhosseini, Ali; Sluijter, Joost P G

    2017-02-01

    Cardiac remodeling is critical for effective tissue healing, however, excessive production and deposition of extracellular matrix components contribute to scarring and failing of the heart. Despite the fact that novel therapies have emerged, there are still no lifelong solutions for this problem. An urgent need exists to improve the understanding of adverse cardiac remodeling in order to develop new therapeutic interventions that will prevent, reverse, or regenerate the fibrotic changes in the failing heart. With recent advances in both disease biology and cardiac tissue engineering, the translation of fundamental laboratory research toward the treatment of chronic heart failure patients becomes a more realistic option. Here, the current understanding of cardiac fibrosis and the great potential of tissue engineering are presented. Approaches using hydrogel-based tissue engineered heart constructs are discussed to contemplate key challenges for modeling tissue engineered cardiac fibrosis and to provide a future outlook for preclinical and clinical applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Use of perfusion bioreactors and large animal models for long bone tissue engineering.

    Science.gov (United States)

    Gardel, Leandro S; Serra, Luís A; Reis, Rui L; Gomes, Manuela E

    2014-04-01

    Tissue engineering and regenerative medicine (TERM) strategies for generation of new bone tissue includes the combined use of autologous or heterologous mesenchymal stem cells (MSC) and three-dimensional (3D) scaffold materials serving as structural support for the cells, that develop into tissue-like substitutes under appropriate in vitro culture conditions. This approach is very important due to the limitations and risks associated with autologous, as well as allogenic bone grafiting procedures currently used. However, the cultivation of osteoprogenitor cells in 3D scaffolds presents several challenges, such as the efficient transport of nutrient and oxygen and removal of waste products from the cells in the interior of the scaffold. In this context, perfusion bioreactor systems are key components for bone TERM, as many recent studies have shown that such systems can provide dynamic environments with enhanced diffusion of nutrients and therefore, perfusion can be used to generate grafts of clinically relevant sizes and shapes. Nevertheless, to determine whether a developed tissue-like substitute conforms to the requirements of biocompatibility, mechanical stability and safety, it must undergo rigorous testing both in vitro and in vivo. Results from in vitro studies can be difficult to extrapolate to the in vivo situation, and for this reason, the use of animal models is often an essential step in the testing of orthopedic implants before clinical use in humans. This review provides an overview of the concepts, advantages, and challenges associated with different types of perfusion bioreactor systems, particularly focusing on systems that may enable the generation of critical size tissue engineered constructs. Furthermore, this review discusses some of the most frequently used animal models, such as sheep and goats, to study the in vivo functionality of bone implant materials, in critical size defects.

  11. Modeling material-degradation-induced elastic property of tissue engineering scaffolds.

    Science.gov (United States)

    Bawolin, N K; Li, M G; Chen, X B; Zhang, W J

    2010-11-01

    The mechanical properties of tissue engineering scaffolds play a critical role in the success of repairing damaged tissues/organs. Determining the mechanical properties has proven to be a challenging task as these properties are not constant but depend upon time as the scaffold degrades. In this study, the modeling of the time-dependent mechanical properties of a scaffold is performed based on the concept of finite element model updating. This modeling approach contains three steps: (1) development of a finite element model for the effective mechanical properties of the scaffold, (2) parametrizing the finite element model by selecting parameters associated with the scaffold microstructure and/or material properties, which vary with scaffold degradation, and (3) identifying selected parameters as functions of time based on measurements from the tests on the scaffold mechanical properties as they degrade. To validate the developed model, scaffolds were made from the biocompatible polymer polycaprolactone (PCL) mixed with hydroxylapatite (HA) nanoparticles and their mechanical properties were examined in terms of the Young modulus. Based on the bulk degradation exhibited by the PCL/HA scaffold, the molecular weight was selected for model updating. With the identified molecular weight, the finite element model developed was effective for predicting the time-dependent mechanical properties of PCL/HA scaffolds during degradation.

  12. Tissue hypoxia during ischemic stroke: adaptive clues from hypoxia-tolerant animal models.

    Science.gov (United States)

    Nathaniel, Thomas I; Williams-Hernandez, Ashley; Hunter, Anan L; Liddy, Caroline; Peffley, Dennis M; Umesiri, Francis E; Imeh-Nathaniel, Adebobola

    2015-05-01

    The treatment and prevention of hypoxic/ischemic brain injury in stroke patients remain a severe and global medical issue. Numerous clinical studies have resulted in a failure to develop chemical neuroprotection for acute, ischemic stroke. Over 150 estimated clinical trials of ischemic stroke treatments have been done, and more than 200 drugs and combinations of drugs for ischemic and hemorrhagic strokes have been developed. Billions of dollars have been invested for new scientific breakthroughs with only limited success. The revascularization of occluded cerebral arteries such as anti-clot treatments of thrombolysis has proven effective, but it can only be used in a 3-4.5h time frame after the onset of a stroke, and not for every patient. This review is about novel insights on how to resist tissue hypoxia from unconventional animal models. Ability to resist tissue hypoxia is an extraordinary ability that is not common in many laboratory animals such as rat and mouse models. For example, we can learn from a naked mole-rat, Chrysemys picta, how to actively regulate brain metabolic activity to defend the brain against fluctuating oxygen tension and acute bouts of oxidative stress following the onset of a stroke. Additionally, a euthermic arctic ground squirrel can teach us how the brain of a stroke patient can remain well oxygenated during tissue hypoxia with no evidence of cellular stress. In this review, we discuss how these animals provide us with a system to gain insight into the possible mechanisms of tissue hypoxia/ischemia. This issue is of clinical significance to stroke patients. We describe specific physiological and molecular adaptations employed by different animals' models of hypoxia tolerance in aquatic and terrestrial environments. We highlight how these adaptations might provide potential clues on strategies to adapt for the clinical management of tissue hypoxia during conditions such as stroke where oxygen demand fails to match the supply. Copyright

  13. Standardized 3D Bioprinting of Soft Tissue Models with Human Primary Cells.

    Science.gov (United States)

    Rimann, Markus; Bono, Epifania; Annaheim, Helene; Bleisch, Matthias; Graf-Hausner, Ursula

    2016-08-01

    Cells grown in 3D are more physiologically relevant than cells cultured in 2D. To use 3D models in substance testing and regenerative medicine, reproducibility and standardization are important. Bioprinting offers not only automated standardizable processes but also the production of complex tissue-like structures in an additive manner. We developed an all-in-one bioprinting solution to produce soft tissue models. The holistic approach included (1) a bioprinter in a sterile environment, (2) a light-induced bioink polymerization unit, (3) a user-friendly software, (4) the capability to print in standard labware for high-throughput screening, (5) cell-compatible inkjet-based printheads, (6) a cell-compatible ready-to-use BioInk, and (7) standard operating procedures. In a proof-of-concept study, skin as a reference soft tissue model was printed. To produce dermal equivalents, primary human dermal fibroblasts were printed in alternating layers with BioInk and cultured for up to 7 weeks. During long-term cultures, the models were remodeled and fully populated with viable and spreaded fibroblasts. Primary human dermal keratinocytes were seeded on top of dermal equivalents, and epidermis-like structures were formed as verified with hematoxylin and eosin staining and immunostaining. However, a fully stratified epidermis was not achieved. Nevertheless, this is one of the first reports of an integrative bioprinting strategy for industrial routine application. © 2015 Society for Laboratory Automation and Screening.

  14. Effect of different BNCT protocols on DNA synthesis in precancerous and normal tissues in an experimental model of oral cancer

    International Nuclear Information System (INIS)

    Heber, Elisa M.; Aromando, Romina; Trivillin, Veronica A.; Itoiz, Maria E.; Kreimann, Erica L.; Schwint, Amanda E.; Nigg, David W.

    2006-01-01

    We previously reported the therapeutic success of different BNCT protocols in the treatment of oral cancer, employing the hamster cheek pouch model. The aim of the present study was to evaluate the effect of these BNCT protocols on DNA synthesis in precancerous and normal tissue in this model and assess the potential lag in the development of second primary tumors in precancerous tissue. The data are relevant to potential control of field cancerized tissue and tolerance of normal tissue. We evaluated DNA synthesis in precancerous and normal pouch tissue 1-30 days post-BNCT mediated by BPA, GB-10 or BPA + GB-10 employing incorporation of bromo-deoxyuridine as an end-point. The BNCT-induced potential lag in the development of second primary tumors in precancerous tissue was monitored. A drastic, statistically significant reduction in DNA synthesis occurred in pacancerous tissue as early as 1 day post-BNCT and was sustained at virtually all time points until 30 days post-BNCT for all protocols. The histological categories evaluated individually within precancerous tissue (dysplasia, hyperplasia and NUMF [no unusual microscopic features]) responded similarly. DNA synthesis in normal tissue treated with BNCT oscillated around the very low pre-treatment values. A BNCT-induced lag in the development of second primary tumors was observed. BNCT induced a drastic fall in DNA synthesis in precancerous tissue that would be associated to the observed lag in the development of second primary tumors. The minimum variations in DNA synthesis in BNCT-treated normal tissue would correlate with the absence of normal tissue radiotoxicity. The present data would contribute to optimize therapeutic efficacy in the treatment of field-cancerized areas. (author)

  15. Application of Tissue Culture and Transformation Techniques in Model Species Brachypodium distachyon.

    Science.gov (United States)

    Sogutmaz Ozdemir, Bahar; Budak, Hikmet

    2018-01-01

    Brachypodium distachyon has recently emerged as a model plant species for the grass family (Poaceae) that includes major cereal crops and forage grasses. One of the important traits of a model species is its capacity to be transformed and ease of growing both in tissue culture and in greenhouse conditions. Hence, plant transformation technology is crucial for improvements in agricultural studies, both for the study of new genes and in the production of new transgenic plant species. In this chapter, we review an efficient tissue culture and two different transformation systems for Brachypodium using most commonly preferred gene transfer techniques in plant species, microprojectile bombardment method (biolistics) and Agrobacterium-mediated transformation.In plant transformation studies, frequently used explant materials are immature embryos due to their higher transformation efficiencies and regeneration capacity. However, mature embryos are available throughout the year in contrast to immature embryos. We explain a tissue culture protocol for Brachypodium using mature embryos with the selected inbred lines from our collection. Embryogenic calluses obtained from mature embryos are used to transform Brachypodium with both plant transformation techniques that are revised according to previously studied protocols applied in the grasses, such as applying vacuum infiltration, different wounding effects, modification in inoculation and cocultivation steps or optimization of bombardment parameters.

  16. Quantitative analysis and comparison study of [18F]AlF-NOTA-PRGD2, [18F]FPPRGD2 and [68Ga]Ga-NOTA-PRGD2 using a reference tissue model.

    Directory of Open Access Journals (Sweden)

    Ning Guo

    Full Text Available With favorable pharmacokinetics and binding affinity for α(vβ(3 integrin, (18F-labeled dimeric cyclic RGD peptide ([(18F]FPPRGD2 has been intensively used as a PET imaging probe for lesion detection and therapy response monitoring. A recently introduced kit formulation method, which uses an (18F-fluoride-aluminum complex labeled RGD tracer ([(18F]AlF-NOTA-PRGD2, provides a strategy for simplifying the labeling procedure to facilitate clinical translation. Meanwhile, an easy-to-prepare (68Ga-labeled NOTA-PRGD2 has also been reported to have promising properties for imaging integrin α(vβ(3. The purpose of this study is to quantitatively compare the pharmacokinetic parameters of [(18F]FPPRGD2, [(18F]AlF-NOTA-PRGD2, and [(68Ga]Ga-NOTA-PRGD2. U87MG tumor-bearing mice underwent 60-min dynamic PET scans following the injection of three tracers. Kinetic parameters were calculated using Logan graphical analysis with reference tissue. Parametric maps were generated using voxel-level modeling. All three compounds showed high binding potential (Bp(ND = k(3/k(4 in tumor voxels. [(18F]AlF-NOTA-PRGD2 showed comparable Bp(ND value (3.75±0.65 with those of [(18F]FPPRGD2 (3.39±0.84 and [(68Ga]Ga-NOTA-PRGD2 (3.09±0.21 (p>0.05. Little difference was found in volume of distribution (V(T among these three RGD tracers in tumor, liver and muscle. Parametric maps showed similar kinetic parameters for all three tracers. We also demonstrated that the impact of non-specific binding could be eliminated in the kinetic analysis. Consequently, kinetic parameter estimation showed more comparable results among groups than static image analysis. In conclusion, [(18F]AlF-NOTA-PRGD2 and [(68Ga]Ga-NOTA-PRGD2 have comparable pharmacokinetics and quantitative parameters compared to those of [(18F]FPPRGD2. Despite the apparent difference in tumor uptake (%ID/g determined from static images and clearance pattern, the actual specific binding component extrapolated from kinetic

  17. Ultrastructural study of tissues surrounding replanted teeth and dental implants.

    Science.gov (United States)

    Shioya, Kazuhiro; Sawada, Takashi; Miake, Yasuo; Inoue, Sadayuki; Yanagisawa, Takaaki

    2009-03-01

    The aim of this study was to describe the ultrastructure of the dentogingival border at replanted teeth and implants. Wistar rats (8 weeks old) were divided into groups for replantation and implantation experiments. In the former, the upper right first molars were extracted and then immediately replanted. In the latter, pure titanium implants were used. All tissues were fixed, demineralized and embedded in epoxy resin for ultrastructural observations. One week after replantation, the junctional epithelium was lost, and the oral sulcular epithelium covered the enamel surface. The amount of the epithelium increased in 2 weeks, and resembled the junctional epithelium, and the internal basal lamina and hemidesmosomes were formed in 4 weeks. One week after implantation, peri-implant epithelium was formed, and in 2 and 4 weeks, this epithelium with aggregated connective tissue cells were observed. In 8 weeks, the peri-implant epithelium receded, and aligned special cells with surrounding elongated fibroblasts and bundles of collagen fibers appeared to seal the implant interface. In replantation of the tooth, the internal basal lamina remained at the surface of the enamel of the replanted tooth, which is likely to be related to regeneration of the junctional epithelium and the attachment apparatus at the epithelium-tooth interface. Following implantation, a layer of cells with characteristics of connective tissue cells, but no junctional epithelium and attachment apparatus, was formed to seal the site of the implant.

  18. Soft tissue deformation modelling through neural dynamics-based reaction-diffusion mechanics.

    Science.gov (United States)

    Zhang, Jinao; Zhong, Yongmin; Gu, Chengfan

    2018-05-30

    Soft tissue deformation modelling forms the basis of development of surgical simulation, surgical planning and robotic-assisted minimally invasive surgery. This paper presents a new methodology for modelling of soft tissue deformation based on reaction-diffusion mechanics via neural dynamics. The potential energy stored in soft tissues due to a mechanical load to deform tissues away from their rest state is treated as the equivalent transmembrane potential energy, and it is distributed in the tissue masses in the manner of reaction-diffusion propagation of nonlinear electrical waves. The reaction-diffusion propagation of mechanical potential energy and nonrigid mechanics of motion are combined to model soft tissue deformation and its dynamics, both of which are further formulated as the dynamics of cellular neural networks to achieve real-time computational performance. The proposed methodology is implemented with a haptic device for interactive soft tissue deformation with force feedback. Experimental results demonstrate that the proposed methodology exhibits nonlinear force-displacement relationship for nonlinear soft tissue deformation. Homogeneous, anisotropic and heterogeneous soft tissue material properties can be modelled through the inherent physical properties of mass points. Graphical abstract Soft tissue deformation modelling with haptic feedback via neural dynamics-based reaction-diffusion mechanics.

  19. Tissue integration of polyacrylamide hydrogel: an experimental study of periurethral, perivesical, and mammary gland tissue in the pig

    DEFF Research Database (Denmark)

    Christensen, Lise H; Nielsen, John B; Mouritsen, Lone

    2008-01-01

    BACKGROUND Polyacrylamide hydrogel (PAAG) is a nondegradable water-based polymer with high viscoelasticity. The gel is used as a tissue filler, the only risk being prolonged infection with anaerobic, contaminating microorganisms if not treated early with broad-spectrum antibiotics. OBJECTIVE...... With silicone gel as reference, PAAG tissue integration and migration was studied in a longitudinal study of the pig. MATERIALS AND METHODS Forty-one pigs were used. PAAG and silicone gel were injected into mammary tissue, and PAAG was injected into urethral or bladder wall or the anal canal. Tissues...... and regional lymph nodes were examined at 1, 1 1/2, 3, 3 1/2, 6, 12, and 14 months, and other lymph nodes and organs were examined at 1, 6, 12, and 14 months. RESULTS PAAG was invaded by macrophages and giant cells that were gradually replaced by a network of fibrous tissue. Silicone gel was seen inside...

  20. Modelling of Soft Connective Tissues to Investigate Female Pelvic Floor Dysfunctions

    Directory of Open Access Journals (Sweden)

    Aroj Bhattarai

    2018-01-01

    Full Text Available After menopause, decreased levels of estrogen and progesterone remodel the collagen of the soft tissues thereby reducing their stiffness. Stress urinary incontinence is associated with involuntary urine leakage due to pathological movement of the pelvic organs resulting from lax suspension system, fasciae, and ligaments. This study compares the changes in the orientation and position of the female pelvic organs due to weakened fasciae, ligaments, and their combined laxity. A mixture theory weighted by respective volume fraction of elastin-collagen fibre compound (5%, adipose tissue (85%, and smooth muscle (5% is adopted to characterize the mechanical behaviour of the fascia. The load carrying response (other than the functional response to the pelvic organs of each fascia component, pelvic organs, muscles, and ligaments are assumed to be isotropic, hyperelastic, and incompressible. Finite element simulations are conducted during Valsalva manoeuvre with weakened tissues modelled by reduced tissue stiffness. A significant dislocation of the urethrovesical junction is observed due to weakness of the fascia (13.89 mm compared to the ligaments (5.47 mm. The dynamics of the pelvic floor observed in this study during Valsalva manoeuvre is associated with urethral-bladder hypermobility, greater levator plate angulation, and positive Q-tip test which are observed in incontinent females.

  1. Modelling of Soft Connective Tissues to Investigate Female Pelvic Floor Dysfunctions.

    Science.gov (United States)

    Bhattarai, Aroj; Staat, Manfred

    2018-01-01

    After menopause, decreased levels of estrogen and progesterone remodel the collagen of the soft tissues thereby reducing their stiffness. Stress urinary incontinence is associated with involuntary urine leakage due to pathological movement of the pelvic organs resulting from lax suspension system, fasciae, and ligaments. This study compares the changes in the orientation and position of the female pelvic organs due to weakened fasciae, ligaments, and their combined laxity. A mixture theory weighted by respective volume fraction of elastin-collagen fibre compound (5%), adipose tissue (85%), and smooth muscle (5%) is adopted to characterize the mechanical behaviour of the fascia. The load carrying response (other than the functional response to the pelvic organs) of each fascia component, pelvic organs, muscles, and ligaments are assumed to be isotropic, hyperelastic, and incompressible. Finite element simulations are conducted during Valsalva manoeuvre with weakened tissues modelled by reduced tissue stiffness. A significant dislocation of the urethrovesical junction is observed due to weakness of the fascia (13.89 mm) compared to the ligaments (5.47 mm). The dynamics of the pelvic floor observed in this study during Valsalva manoeuvre is associated with urethral-bladder hypermobility, greater levator plate angulation, and positive Q-tip test which are observed in incontinent females.

  2. Statistical Modeling of Radiative Transfer and Transient Characteristics for Multilayer Biological Tissue

    Directory of Open Access Journals (Sweden)

    S. Yu. Makarov

    2014-01-01

    and scattering medium. The main absorbers in visible and near-IR spectral range in this case are melanin (contains in pigmented epidermis and blood hemoglobin. Scattering is defined both by the fibrous structure of skin, and by the cell organellеs. The optical characteristics, absorbing and scattering properties of skin, and subcutaneous tissues are rather well studied [6][7][8].The aim of modelling was to have both the stationary distribution of light radiation in multilayer biological tissue and the transitional characteristics corresponding to such biological tissue structure. These characteristics may appear when a biological tissue is subjected to short laser pulses. Discovering of such characteristics and their analysis allows us to formulate a criterion for the validity of stationary models of radiation transfer in multilayer biological tissue. As to transitional characteristics (i.e. time-allowed absorption coefficients in layers, the standard algorithm of the Monte-Carlo method [9][10] was modified to take into consideration a final speed value of light distribution in layers. In such a way, in particular, it was found that time about 60 Ps (for radiation with the wavelength of 633 nm is necessary to obtain the steady-state (stationary values of the absorbed power in skin and subcutaneous tissues. The entire modelling process (based on the i7 processor took about 30 minutes, thus the number of the traceable photons made 100 million.The results obtained for a beam of infinitesimal diameter allowed us to find the solution on distribution of light energy in biological tissue for a laser beam of a final width with a Gaussian profile of intensity. For this purpose, was used the mathematical apparatus of Green function. Its digital representation in this case is a modelling result for a beam of infinitesimal diameter. Since indexes of refraction of the adjacent layers in model were specified to be equal, the received function of integrated intensity for a Gaussian

  3. Extracellular Matrix Hydrogel Promotes Tissue Remodeling, Arteriogenesis, and Perfusion in a Rat Hindlimb Ischemia Model

    Directory of Open Access Journals (Sweden)

    Jessica L. Ungerleider, BS

    2016-01-01

    Full Text Available Although surgical and endovascular revascularization can be performed in peripheral arterial disease (PAD, 40% of patients with critical limb ischemia do not have a revascularization option. This study examines the efficacy and mechanisms of action of acellular extracellular matrix-based hydrogels as a potential novel therapy for treating PAD. We tested the efficacy of using a tissue-specific injectable hydrogel derived from decellularized porcine skeletal muscle (SKM and compared this to a new human umbilical cord-derived matrix (hUC hydrogel, which could have greater potential for tissue regeneration because of the younger age of the tissue source. In a rodent hindlimb ischemia model, both hydrogels were injected 1-week post-surgery and perfusion was regularly monitored with laser speckle contrast analysis to 35 days post-injection. There were significant improvements in hindlimb tissue perfusion and perfusion kinetics with both biomaterials. Histologic analysis indicated that the injected hydrogels were biocompatible, and resulted in arteriogenesis, rather than angiogenesis, as well as improved recruitment of skeletal muscle progenitors. Skeletal muscle fiber morphology analysis indicated that the muscle treated with the tissue-specific SKM hydrogel more closely matched healthy tissue morphology. Whole transcriptome analysis indicated that the SKM hydrogel caused a shift in the inflammatory response, decreased cell death, and increased blood vessel and muscle development. These results show the efficacy of an injectable ECM hydrogel alone as a potential therapy for treating patients with PAD. Our results indicate that the SKM hydrogel improved functional outcomes through stimulation of arteriogenesis and muscle progenitor cell recruitment.

  4. Application of an object-oriented programming paradigm in three-dimensional computer modeling of mechanically active gastrointestinal tissues.

    Science.gov (United States)

    Rashev, P Z; Mintchev, M P; Bowes, K L

    2000-09-01

    The aim of this study was to develop a novel three-dimensional (3-D) object-oriented modeling approach incorporating knowledge of the anatomy, electrophysiology, and mechanics of externally stimulated excitable gastrointestinal (GI) tissues and emphasizing the "stimulus-response" principle of extracting the modeling parameters. The modeling method used clusters of class hierarchies representing GI tissues from three perspectives: 1) anatomical; 2) electrophysiological; and 3) mechanical. We elaborated on the first four phases of the object-oriented system development life-cycle: 1) analysis; 2) design; 3) implementation; and 4) testing. Generalized cylinders were used for the implementation of 3-D tissue objects modeling the cecum, the descending colon, and the colonic circular smooth muscle tissue. The model was tested using external neural electrical tissue excitation of the descending colon with virtual implanted electrodes and the stimulating current density distributions over the modeled surfaces were calculated. Finally, the tissue deformations invoked by electrical stimulation were estimated and represented by a mesh-surface visualization technique.

  5. Differential expression among tissues in morbidly obese individuals using a finite mixture model under BLUP approach

    DEFF Research Database (Denmark)

    Kogelman, Lisette; Trabzuni, Daniah; Bonder, Marc Jan

    effects of the interactions between tissues and probes using BLUP (Best Linear Unbiased Prediction) linear models correcting for gender, which were subsequently used in a finite mixture model to detect DE genes in each tissue. This approach evades the multiple-testing problem and is able to detect...

  6. Topographic modelling of haptic properties of tissue products

    International Nuclear Information System (INIS)

    Rosen, B-G; Fall, A; Farbrot, A; Bergström, P; Rosen, S

    2014-01-01

    The way a product or material feels when touched, haptics, has been shown to be a property that plays an important role when consumers determine the quality of products For tissue products in constant touch with the skin, ''softness'' becomes a primary quality parameter. In the present work, the relationship between topography and the feeling of the surface has been investigated for commercial tissues with varying degree of texture from the low textured crepe tissue to the highly textured embossed- and air-dried tissue products. A trained sensory panel at was used to grade perceived haptic ''roughness''. The technique used to characterize the topography was Digital light projection (DLP) technique, By the use of multivariate statistics, strong correlations between perceived roughness and topography were found with predictability of above 90 percent even though highly textured products were included. Characterization was made using areal ISO 25178-2 topography parameters in combination with non-contacting topography measurement. The best prediction ability was obtained when combining haptic properties with the topography parameters auto-correlation length (Sal), peak material volume (Vmp), core roughness depth (Sk) and the maximum height of the surface (Sz)

  7. Modeling and remodeling of the collagen architecture in cardiovascular tissues

    NARCIS (Netherlands)

    Driessen, N.J.B.

    2006-01-01

    Heart valve replacement by a mechanical or biological prosthesis represents a common surgical therapy for end-stage valvular heart diseases. A critical drawback of these prostheses is the inability to grow, repair and remodel in response to changes in the tissue’s environment. Tissue engineering

  8. Granulocytes and vascularization regulate uterine bleeding and tissue remodeling in a mouse menstruation model.

    Directory of Open Access Journals (Sweden)

    Astrid Menning

    Full Text Available Menstruation-associated disorders negatively interfere with the quality of life of many women. However, mechanisms underlying pathogenesis of menstrual disorders remain poorly investigated up to date. Among others, this is based on a lack of appropriate pre-clinical animal models. We here employ a mouse menstruation model induced by priming mice with gonadal hormones and application of a physical stimulus into the uterus followed by progesterone removal. As in women, these events are accompanied by menstrual-like bleeding and tissue remodeling processes, i.e. disintegration of decidualized endometrium, as well as subsequent repair. We demonstrate that the onset of bleeding coincides with strong upregulation of inflammatory mediators and massive granulocyte influx into the uterus. Uterine granulocytes play a central role in regulating local tissue remodeling since depletion of these cells results in dysregulated expression of matrix modifying enzymes. As described here for the first time, uterine blood loss can be quantified by help of tampon-like cotton pads. Using this novel technique, we reveal that blood loss is strongly reduced upon inhibition of endometrial vascularization and thus, is a key regulator of menstrual bleeding. Taken together, we here identify angiogenesis and infiltrating granulocytes as critical determinants of uterine bleeding and tissue remodeling in a mouse menstruation model. Importantly, our study provides a technical and scientific basis allowing quantification of uterine blood loss in mice and thus, assessment of therapeutic intervention, proving great potential for future use in basic research and drug discovery.

  9. Engraftment of Prevascularized, Tissue Engineered Constructs in a Novel Rabbit Segmental Bone Defect Model

    Directory of Open Access Journals (Sweden)

    Alexandre Kaempfen

    2015-06-01

    Full Text Available The gold standard treatment of large segmental bone defects is autologous bone transfer, which suffers from low availability and additional morbidity. Tissue engineered bone able to engraft orthotopically and a suitable animal model for pre-clinical testing are direly needed. This study aimed to evaluate engraftment of tissue-engineered bone with different prevascularization strategies in a novel segmental defect model in the rabbit humerus. Decellularized bone matrix (Tutobone seeded with bone marrow mesenchymal stromal cells was used directly orthotopically or combined with a vessel and inserted immediately (1-step or only after six weeks of subcutaneous “incubation” (2-step. After 12 weeks, histological and radiological assessment was performed. Variable callus formation was observed. No bone formation or remodeling of the graft through TRAP positive osteoclasts could be detected. Instead, a variable amount of necrotic tissue formed. Although necrotic area correlated significantly with amount of vessels and the 2-step strategy had significantly more vessels than the 1-step strategy, no significant reduction of necrotic area was found. In conclusion, the animal model developed here represents a highly challenging situation, for which a suitable engineered bone graft with better prevascularization, better resorbability and higher osteogenicity has yet to be developed.

  10. Improved numerical modelling of heat transfer in human tissue exposed to RF

    International Nuclear Information System (INIS)

    Prishvin, Mikheil; Zaridze, Revaz; Bit-Babik, Georgi; Faraone, Antonio

    2010-01-01

    Full text: A novel numerical model to simulate thermal response of human body tissues exposed to RF energy is presented in this article. It is based on a new algorithm for the construction of a realistic blood vessel network, a new model of blood flow velocity distribution and an approach to solve the bio-heat equation in human tissue with variable and initially unknown blood temperature distribution. The algorithm generates a discrete 3D representation of both arterial and venous vascular networks and a continuous blood velocity vector field for arbitrary enclosed geome tries required to represent the complex anatomy of human body and blood flow. The results obtained in this article by applying the developed method to realistic exposure con ditions demonstrates relative difference in thermal response of the exposed tissue compared to results obtained by conventional bio-heat equation with constant blood perfusion and temperature. The developed technique may provide more accurate and realistic modelling in thermal dosimetry studies of human body RF exposure.

  11. Stochastic Threshold Exponential (TE) Model for Hematopoietic Tissue Reconstitution Deficit after Radiation Damage.

    Science.gov (United States)

    Scott, B R; Potter, C A

    2014-07-01

    Whole-body exposure to large radiation doses can cause severe loss of hematopoietic tissue cells and threaten life if the lost cells are not replaced in a timely manner through natural repopulation (a homeostatic mechanism). Repopulation to the baseline level N 0 is called reconstitution and a reconstitution deficit (repopulation shortfall) can occur in a dose-related and organ-specific manner. Scott et al. (2013) previously introduced a deterministic version of a threshold exponential (TE) model of tissue-reconstitution deficit at a given follow-up time that was applied to bone marrow and spleen cellularity (number of constituent cells) data obtained 6 weeks after whole-body gamma-ray exposure of female C.B-17 mice. In this paper a more realistic, stochastic version of the TE model is provided that allows radiation response to vary between different individuals. The Stochastic TE model is applied to post gamma-ray-exposure cellularity data previously reported and also to more limited X-ray cellularity data for whole-body irradiated female C.B-17 mice. Results indicate that the population average threshold for a tissue reconstitution deficit appears to be similar for bone marrow and spleen and for 320-kV-spectrum X-rays and Cs-137 gamma rays. This means that 320-kV spectrum X-rays could successfully be used in conducting such studies.

  12. Hybrid cellular automaton modeling of nutrient modulated cell growth in tissue engineering constructs.

    Science.gov (United States)

    Chung, C A; Lin, Tze-Hung; Chen, Shih-Di; Huang, Hsing-I

    2010-01-21

    Mathematic models help interpret experimental results and accelerate tissue engineering developments. We develop in this paper a hybrid cellular automata model that combines the differential nutrient transport equation to investigate the nutrient limited cell construct development for cartilage tissue engineering. Individual cell behaviors of migration, contact inhibition and cell collision, coupled with the cell proliferation regulated by oxygen concentration were carefully studied. Simplified two-dimensional simulations were performed. Using this model, we investigated the influence of cell migration speed on the overall cell growth within in vitro cell scaffolds. It was found that intense cell motility can enhance initial cell growth rates. However, since cell growth is also significantly modulated by the nutrient contents, intense cell motility with conventional uniform cell seeding method may lead to declined cell growth in the final time because concentrated cell population has been growing around the scaffold periphery to block the nutrient transport from outside culture media. Therefore, homogeneous cell seeding may not be a good way of gaining large and uniform cell densities for the final results. We then compared cell growth in scaffolds with various seeding modes, and proposed a seeding mode with cells initially residing in the middle area of the scaffold that may efficiently reduce the nutrient blockage and result in a better cell amount and uniform cell distribution for tissue engineering construct developments.

  13. Modeling fibrous biological tissues with a general invariant that excludes compressed fibers

    Science.gov (United States)

    Li, Kewei; Ogden, Ray W.; Holzapfel, Gerhard A.

    2018-01-01

    Dispersed collagen fibers in fibrous soft biological tissues have a significant effect on the overall mechanical behavior of the tissues. Constitutive modeling of the detailed structure obtained by using advanced imaging modalities has been investigated extensively in the last decade. In particular, our group has previously proposed a fiber dispersion model based on a generalized structure tensor. However, the fiber tension-compression switch described in that study is unable to exclude compressed fibers within a dispersion and the model requires modification so as to avoid some unphysical effects. In a recent paper we have proposed a method which avoids such problems, but in this present study we introduce an alternative approach by using a new general invariant that only depends on the fibers under tension so that compressed fibers within a dispersion do not contribute to the strain-energy function. We then provide expressions for the associated Cauchy stress and elasticity tensors in a decoupled form. We have also implemented the proposed model in a finite element analysis program and illustrated the implementation with three representative examples: simple tension and compression, simple shear, and unconfined compression on articular cartilage. We have obtained very good agreement with the analytical solutions that are available for the first two examples. The third example shows the efficacy of the fibrous tissue model in a larger scale simulation. For comparison we also provide results for the three examples with the compressed fibers included, and the results are completely different. If the distribution of collagen fibers is such that it is appropriate to exclude compressed fibers then such a model should be adopted.

  14. Improving normal tissue complication probability models: the need to adopt a "data-pooling" culture.

    Science.gov (United States)

    Deasy, Joseph O; Bentzen, Søren M; Jackson, Andrew; Ten Haken, Randall K; Yorke, Ellen D; Constine, Louis S; Sharma, Ashish; Marks, Lawrence B

    2010-03-01

    Clinical studies of the dependence of normal tissue response on dose-volume factors are often confusingly inconsistent, as the QUANTEC reviews demonstrate. A key opportunity to accelerate progress is to begin storing high-quality datasets in repositories. Using available technology, multiple repositories could be conveniently queried, without divulging protected health information, to identify relevant sources of data for further analysis. After obtaining institutional approvals, data could then be pooled, greatly enhancing the capability to construct predictive models that are more widely applicable and better powered to accurately identify key predictive factors (whether dosimetric, image-based, clinical, socioeconomic, or biological). Data pooling has already been carried out effectively in a few normal tissue complication probability studies and should become a common strategy. Copyright 2010 Elsevier Inc. All rights reserved.

  15. A biomimetic physiological model for human adipose tissue by adipocytes and endothelial cell cocultures with spatially controlled distribution

    International Nuclear Information System (INIS)

    Yao, Rui; Zhang, Renji; Lin, Feng; Du, Yanan; Luan, Jie

    2013-01-01

    An in vitro model that recapitulates the characteristics of native human adipose tissue would largely benefit pathology studies and therapy development. In this paper, we fabricated a physiological model composed of both human adipocytes and endothelial cells with spatially controlled distribution that biomimics the structure and composition of human adipose tissue. Detailed studies into the cell–cell interactions between the adipocytes and endothelial cells revealed a mutual-enhanced effect which resembles the in vivo routine. Furthermore, comparisons between planar coculture and model coculture demonstrated improved adipocyte function as well as endothelial cell proliferation under the same conditions. This research provided a reliable model for human adipose tissue development studies and potential obesity-related therapy development. (paper)

  16. A dynamic, mechanistic model of metabolism in adipose tissue of lactating dairy cattle.

    Science.gov (United States)

    McNamara, J P; Huber, K; Kenéz, A

    2016-07-01

    Research in dairy cattle biology has resulted in a large body of knowledge on nutrition and metabolism in support of milk production and efficiency. This quantitative knowledge has been compiled in several model systems to balance and evaluate rations and predict requirements. There are also systems models for metabolism and reproduction in the cow that can be used to support research programs. Adipose tissue plays a significant role in the success and efficiency of lactation, and recent research has resulted in several data sets on genomic differences and changes in gene transcription of adipose tissue in dairy cattle. To fully use this knowledge, we need to build and expand mechanistic, dynamic models that integrate control of metabolism and production. Therefore, we constructed a second-generation dynamic, mechanistic model of adipose tissue metabolism of dairy cattle. The model describes the biochemical interconversions of glucose, acetate, β-hydroxybutyrate (BHB), glycerol, C16 fatty acids, and triacylglycerols. Data gathered from our own research and published references were used to set equation forms and parameter values. Acetate, glucose, BHB, and fatty acids are taken up from blood. The fatty acids are activated to the acyl coenzyme A moieties. Enzymatically catalyzed reactions are explicitly described with parameters including maximal velocity and substrate sensitivity. The control of enzyme activity is partially carried out by insulin and norepinephrine, portraying control in the cow. Model behavior was adequate, with sensitive responses to changing substrates and hormones. Increased nutrient uptake and increased insulin stimulate triacylglycerol synthesis, whereas a reduction in nutrient availability or increase in norepinephrine increases triacylglycerol hydrolysis and free fatty acid release to blood. This model can form a basis for more sophisticated integration of existing knowledge and future studies on metabolic efficiency of dairy cattle

  17. Resonance sensor measurements of stiffness variations in prostate tissue in vitro--a weighted tissue proportion model.

    Science.gov (United States)

    Jalkanen, Ville; Andersson, Britt M; Bergh, Anders; Ljungberg, Börje; Lindahl, Olof A

    2006-12-01

    Prostate cancer is the most common type of cancer in men in Europe and the US. The methods to detect prostate cancer are still precarious and new techniques are needed. A piezoelectric transducer element in a feedback system is set to vibrate with its resonance frequency. When the sensor element contacts an object a change in the resonance frequency is observed, and this feature has been utilized in sensor systems to describe physical properties of different objects. For medical applications it has been used to measure stiffness variations due to various patho-physiological conditions. In this study the sensor's ability to measure the stiffness of prostate tissue, from two excised prostatectomy specimens in vitro, was analysed. The specimens were also subjected to morphometric measurements, and the sensor parameter was compared with the morphology of the tissue with linear regression. In the probe impression interval 0.5-1.7 mm, the maximum R(2) > or = 0.60 (p sensor was pressed, the greater, i.e., deeper, volume it sensed. Tissue sections deeper in the tissue were assigned a lower mathematical weighting than sections closer to the sensor probe. It is concluded that cancer increases the measured stiffness as compared with healthy glandular tissue, but areas with predominantly stroma or many stones could be more difficult to differ from cancer.

  18. Heterogeneous Deformable Modeling of Bio-Tissues and Haptic Force Rendering for Bio-Object Modeling

    Science.gov (United States)

    Lin, Shiyong; Lee, Yuan-Shin; Narayan, Roger J.

    This paper presents a novel technique for modeling soft biological tissues as well as the development of an innovative interface for bio-manufacturing and medical applications. Heterogeneous deformable models may be used to represent the actual internal structures of deformable biological objects, which possess multiple components and nonuniform material properties. Both heterogeneous deformable object modeling and accurate haptic rendering can greatly enhance the realism and fidelity of virtual reality environments. In this paper, a tri-ray node snapping algorithm is proposed to generate a volumetric heterogeneous deformable model from a set of object interface surfaces between different materials. A constrained local static integration method is presented for simulating deformation and accurate force feedback based on the material properties of a heterogeneous structure. Biological soft tissue modeling is used as an example to demonstrate the proposed techniques. By integrating the heterogeneous deformable model into a virtual environment, users can both observe different materials inside a deformable object as well as interact with it by touching the deformable object using a haptic device. The presented techniques can be used for surgical simulation, bio-product design, bio-manufacturing, and medical applications.

  19. Nonlinear optics for the study of human scar tissue

    Science.gov (United States)

    Ferro, D. P.; Vieira-Damiani, G.; Adam, R. L.; Cesar, C. L.; Metze, Konradin

    2012-03-01

    Collagen fibers are an essential component of the dynamic process of scarring, which accompanies various diseases. Scar tissue may reveal different morphologic expressions, such as hypertrophic scars or keloids. Collagen fibers can be visualized by fluorescent light when stained with eosin. Second Harmonic Generation (SHG) creates a non linear signal that occurs only in molecules without inversion symmetry and is particularly strong in the collagen fibers arranged in triple helices. The aim of this study was to describe the methodology for the analysis of the density and texture of collagen in keloids, hypertrophic scars and conventional scars. Samples were examined in the National Institute of Science and Technology on Photonics Applied to Cell Biology (INFABIC) at the State University of Campinas. The images were acquired in a multiphoton microscopy LSM 780-NLO Zeiss 40X. Both signals, two-photon fluorescence (TPEF) and SHG, were excited by a Mai-Tai Ti:Sapphire laser at 940 nm. We used a LP490/SP485 NDD filter for SHG, and a BP565-610 NDD filter for fluorescence In each case, ten images were acquired serially (512×512 μm) in Z-stack and joined together to one patchwork-image . Image analysis was performed by a gliding-box-system with in-house made software. Keloids, hypertrophic scars and normal scar tissue show different collagen architecture. Inside an individual case differences of the scar process may be found between central and peripheral parts. In summary, the use of nonlinear optics is a helpful tool for the study of scars tissue.

  20. Experimental Models Used in Fat Grafting Research for Volume Augmentation in Soft Tissue Reconstruction

    Directory of Open Access Journals (Sweden)

    Jorge Lujan-Hernandez

    2017-09-01

    Full Text Available As the popularity of fat grafting research increases, animal models are being used as the source of pre-clinical experimental information for discovery and to enhance techniques. To date, animal models used in this research have not been compared to provide a standardized model. We analyzed publications from 1968–2015 to compare published accounts of animal models in fat grafting research. Data collected included: species used, graft characteristics (donor tissue, recipient area, amount injected, injection technique, time of sacrifice and quantification methods. Mice were most commonly used (56% of studies, with the “athymic nude” strain utilized most frequently (44%. Autologous fat was the most common source of grafted tissue (52%. Subcutaneous dorsum was the most common recipient site (51%. On average, 0.80±0.60 mL of fat was grafted. A single bolus technique was used in 57% of studies. Fat volume assessment was typically completed at the end of the study, occurring at less than 1 week to one year. Graft volume was quantified by weight (63%, usually in conjunction with another analysis. The results demonstrate the current heterogeneity of animal models in this research. We propose that the research community reach a consensus to allow better comparison of techniques and results. One example is the model used in our laboratory and others; this model is described in detail. Eventually, larger animal models may better translate to the human condition but, given increased financial costs and animal facility capability, should be explored when data obtained from small animal studies is exhausted or inconclusive.

  1. Modeling of the metallic port in breast tissue expanders for photon radiotherapy.

    Science.gov (United States)

    Yoon, Jihyung; Xie, Yibo; Heins, David; Zhang, Rui

    2018-03-30

    The purpose of this study was to model the metallic port in breast tissue expanders and to improve the accuracy of dose calculations in a commercial photon treatment planning system (TPS). The density of the model was determined by comparing TPS calculations and ion chamber (IC) measurements. The model was further validated and compared with two widely used clinical models by using a simplified anthropomorphic phantom and thermoluminescent dosimeters (TLD) measurements. Dose perturbations and target coverage for a single postmastectomy radiotherapy (PMRT) patient were also evaluated. The dimensions of the metallic port model were determined to be 1.75 cm in diameter and 5 mm in thickness. The density of the port was adjusted to be 7.5 g/cm 3 which minimized the differences between IC measurements and TPS calculations. Using the simplified anthropomorphic phantom, we found the TPS calculated point doses based on the new model were in agreement with TLD measurements within 5.0% and were more accurate than doses calculated based on the clinical models. Based on the photon treatment plans for a real patient, we found that the metallic port has a negligible dosimetric impact on chest wall, while the port introduced significant dose shadow in skin area. The current clinical port models either overestimate or underestimate the attenuation from the metallic port, and the dose perturbation depends on the plan and the model in a complex way. TPS calculations based on our model of the metallic port showed good agreement with measurements for all cases. This new model could improve the accuracy of dose calculations for PMRT patients who have temporary tissue expanders implanted during radiotherapy and could potentially reduce the risk of complications after the treatment. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

  2. Improved mathematical and computational tools for modeling photon propagation in tissue

    Science.gov (United States)

    Calabro, Katherine Weaver

    Light interacts with biological tissue through two predominant mechanisms: scattering and absorption, which are sensitive to the size and density of cellular organelles, and to biochemical composition (ex. hemoglobin), respectively. During the progression of disease, tissues undergo a predictable set of changes in cell morphology and vascularization, which directly affect their scattering and absorption properties. Hence, quantification of these optical property differences can be used to identify the physiological biomarkers of disease with interest often focused on cancer. Diffuse reflectance spectroscopy is a diagnostic tool, wherein broadband visible light is transmitted through a fiber optic probe into a turbid medium, and after propagating through the sample, a fraction of the light is collected at the surface as reflectance. The measured reflectance spectrum can be analyzed with appropriate mathematical models to extract the optical properties of the tissue, and from these, a set of physiological properties. A number of models have been developed for this purpose using a variety of approaches -- from diffusion theory, to computational simulations, and empirical observations. However, these models are generally limited to narrow ranges of tissue and probe geometries. In this thesis, reflectance models were developed for a much wider range of measurement parameters, and influences such as the scattering phase function and probe design were investigated rigorously for the first time. The results provide a comprehensive understanding of the factors that influence reflectance, with novel insights that, in some cases, challenge current assumptions in the field. An improved Monte Carlo simulation program, designed to run on a graphics processing unit (GPU), was built to simulate the data used in the development of the reflectance models. Rigorous error analysis was performed to identify how inaccuracies in modeling assumptions can be expected to affect the accuracy

  3. Predictive model of thrombospondin-1 and vascular endothelial growth factor in breast tumor tissue.

    Science.gov (United States)

    Rohrs, Jennifer A; Sulistio, Christopher D; Finley, Stacey D

    2016-01-01

    Angiogenesis, the formation of new blood capillaries from pre-existing vessels, is a hallmark of cancer. Thus far, strategies for reducing tumor angiogenesis have focused on inhibiting pro-angiogenic factors, while less is known about the therapeutic effects of mimicking the actions of angiogenesis inhibitors. Thrombospondin-1 (TSP1) is an important endogenous inhibitor of angiogenesis that has been investigated as an anti-angiogenic agent. TSP1 impedes the growth of new blood vessels in many ways, including crosstalk with pro-angiogenic factors. Due to the complexity of TSP1 signaling, a predictive systems biology model would provide quantitative understanding of the angiogenic balance in tumor tissue. Therefore, we have developed a molecular-detailed, mechanistic model of TSP1 and vascular endothelial growth factor (VEGF), a promoter of angiogenesis, in breast tumor tissue. The model predicts the distribution of the angiogenic factors in tumor tissue, revealing that TSP1 is primarily in an inactive, cleaved form due to the action of proteases, rather than bound to its cellular receptors or to VEGF. The model also predicts the effects of enhancing TSP1's interactions with its receptors and with VEGF. To provide additional predictions that can guide the development of new anti-angiogenic drugs, we simulate administration of exogenous TSP1 mimetics that bind specific targets. The model predicts that the CD47-binding TSP1 mimetic dramatically decreases the ratio of receptor-bound VEGF to receptor-bound TSP1, in favor of anti-angiogenesis. Thus, we have established a model that provides a quantitative framework to study the response to TSP1 mimetics.

  4. Phosphorus MRS study in bone and soft-tissue tumors

    International Nuclear Information System (INIS)

    Du Xiangke; Jiang Baoguo

    2000-01-01

    Objective: To study the metabolite changes in bone and soft-tissue tumors using phosphorus MRS for better understanding of the phospholipid metabolite and energy metabolite of tumors, which will provide more information for clinical diagnosis and therapy. Methods: Phosphorus MRS and MRI were performed in 14 bone and soft-tissue tumor patients (benign 6, malignant 8) and 19 healthy volunteers at 2.0 T. The areas under the peak of various metabolite in spectra were measured. The ratios of the other metabolite related to β-ATP, ATP, and Pcr were calculated. Intracellular pH was calculated according to the chemical shift change of Pi relative to Pcr. Results: The ratio of PME/β-ATP, PME/ATP, Pcr/PME in both benign and malignant group, intracellular pH in malignant group and LEP/Pcr in benign group were higher than that of the normal group significantly (P < 0.01). the ratios of Pi/Pcr in benign and malignant group, PDE/ATP, PDE/β-ATP, LET/Pcr, Pi/β-ATP in malignant group and LET/β-ATP in benign group were significantly different from that of the normal group (P < 0.05). Between benign and malignant tumors group, the ratios of Pcr/PME and Intracellular pH were different significantly (P < 0.05). Conclusion: The in vivo phosphorus MRS can non-invasively find abnormal phospholipid metabolite, energy metabolite and pH changes in bone and soft tissue tumors

  5. Photoprotection by pistachio bioactives in a 3-dimensional human skin equivalent tissue model.

    Science.gov (United States)

    Chen, C-Y Oliver; Smith, Avi; Liu, Yuntao; Du, Peng; Blumberg, Jeffrey B; Garlick, Jonathan

    2017-09-01

    Reactive oxygen species (ROS) generated during ultraviolet (UV) light exposure can induce skin damage and aging. Antioxidants can provide protection against oxidative injury to skin via "quenching" ROS. Using a validated 3-dimensional (3D) human skin equivalent (HSE) tissue model that closely mimics human skin, we examined whether pistachio antioxidants could protect HSE against UVA-induced damage. Lutein and γ-tocopherol are the predominant lipophilic antioxidants in pistachios; treatment with these compounds prior to UVA exposure protected against morphological changes to the epithelial and connective tissue compartments of HSE. Pistachio antioxidants preserved overall skin thickness and organization, as well as fibroblast morphology, in HSE exposed to UVA irradiation. However, this protection was not substantiated by the analysis of the proliferation of keratinocytes and apoptosis of fibroblasts. Additional studies are warranted to elucidate the basis of these discordant results and extend research into the potential role of pistachio bioactives promoting skin health.

  6. Proteomic Analyses of the Acute Tissue Response for Explant Rabbit Corneas and Engineered Corneal Tissue Models Following In Vitro Exposure to 1540 nm Laser Light

    National Research Council Canada - National Science Library

    Eurell, T. E; Johnson, T. E; Roach, W. P

    2005-01-01

    Two-dimensional electrophoresis and histomorphometry were used to determine if equivalent protein changes occurred within native rabbit corneas and engineered corneal tissue models following in vitro...

  7. A mechano-biological model of multi-tissue evolution in bone

    Science.gov (United States)

    Frame, Jamie; Rohan, Pierre-Yves; Corté, Laurent; Allena, Rachele

    2017-12-01

    Successfully simulating tissue evolution in bone is of significant importance in predicting various biological processes such as bone remodeling, fracture healing and osseointegration of implants. Each of these processes involves in different ways the permanent or transient formation of different tissue types, namely bone, cartilage and fibrous tissues. The tissue evolution in specific circumstances such as bone remodeling and fracturing healing is currently able to be modeled. Nevertheless, it remains challenging to predict which tissue types and organization can develop without any a priori assumptions. In particular, the role of mechano-biological coupling in this selective tissue evolution has not been clearly elucidated. In this work, a multi-tissue model has been created which simultaneously describes the evolution of bone, cartilage and fibrous tissues. The coupling of the biological and mechanical factors involved in tissue formation has been modeled by defining two different tissue states: an immature state corresponding to the early stages of tissue growth and representing cell clusters in a weakly neo-formed Extra Cellular Matrix (ECM), and a mature state corresponding to well-formed connective tissues. This has allowed for the cellular processes of migration, proliferation and apoptosis to be described simultaneously with the changing ECM properties through strain driven diffusion, growth, maturation and resorption terms. A series of finite element simulations were carried out on idealized cantilever bending geometries. Starting from a tissue composition replicating a mid-diaphysis section of a long bone, a steady-state tissue formation was reached over a statically loaded period of 10,000 h (60 weeks). The results demonstrated that bone formation occurred in regions which are optimally physiologically strained. In two additional 1000 h bending simulations both cartilaginous and fibrous tissues were shown to form under specific geometrical and loading

  8. Evaluation of two endometriosis models by transplantation of human endometrial tissue fragments and human endometrial mesenchymal cells

    Directory of Open Access Journals (Sweden)

    Mina Jafarabadi

    2017-08-01

    Full Text Available Background: The animal models of endometriosis could be a valuable alternative tool for clarifying the etiology of endometriosis. Objective: In this study two endometriosis models at the morphological and molecular levels was evaluated and compared. Materials and Methods: The human endometrial tissues were cut into small fragments then they were randomly considered for transplantation into γ irradiated mice as model A; or they were isolated and cultured up to fourth passages. 2×106 cultured stromal cells were transplanted into γ irradiated mice subcutaneously as model B. twenty days later the ectopic tissues in both models were studied morphologically by Periodic acid-Schiff and hematoxylin and eosin staining. The expression of osteopontin (OPN and matrix metalloproteinase 2 (MMP2 genes were also assessed using real time RT-PCR. 17-β estradiol levels of mice sera were compared before and after transplantation. Results: The endometrial like glands and stromal cells were formed in the implanted subcutaneous tissue of both endometriosis models. The gland sections per cubic millimeter, the expression of OPN and MMP2 genes and the level of 17-β estradiol were higher in model B than model A (p=0.03. Conclusion: Our observation demonstrated that endometrial mesenchymal stromal cells showed more efficiency to establish endometriosis model than human endometrial tissue fragments.

  9. A model of a code of ethics for tissue banks operating in developing countries.

    Science.gov (United States)

    Morales Pedraza, Jorge

    2012-12-01

    Ethical practice in the field of tissue banking requires the setting of principles, the identification of possible deviations and the establishment of mechanisms that will detect and hinder abuses that may occur during the procurement, processing and distribution of tissues for transplantation. This model of a Code of Ethics has been prepared with the purpose of being used for the elaboration of a Code of Ethics for tissue banks operating in the Latin American and the Caribbean, Asia and the Pacific and the African regions in order to guide the day-to-day operation of these banks. The purpose of this model of Code of Ethics is to assist interested tissue banks in the preparation of their own Code of Ethics towards ensuring that the tissue bank staff support with their actions the mission and values associated with tissue banking.

  10. The mechanism of plasma-assisted penetration of NO2- in model tissues

    Science.gov (United States)

    He, Tongtong; Liu, Dingxin; Liu, Zhijie; Liu, Zhichao; Li, Qiaosong; Rong, Mingzhe; Kong, Michael G.

    2017-11-01

    Cold atmospheric plasmas are reportedly capable of enhancing the percutaneous absorption of drugs, which is a development direction of plasma medicine. This motivated us to study how the enhancement effect was realized. In this letter, gelatin gel films were used as surrogates of human tissues, NaNO2 was used as a representative of small-molecule drugs, and cross-field and linear-field plasma jets were used for the purpose of enhancing the penetration of NaNO2 through the gelatin gel films. The permeability of gelatin gel films was quantified by measuring the NO2- concentration in water which was covered by those films. It was found that the gas flow and electric field of cold plasmas played a crucial role in the permeability enhancement of the model tissues, but the effect of gas flow was mainly confined in the surface layer, while the effect of the electric field was holistic. Those effects might be attributed to the localized squeezing of particles by gas flow and the weakening of the ion-dipole interaction by the AC electric field. The enhancement effect decreases with the increasing mass fraction of gelatin because the macromolecules of gelatin could significantly hinder the penetration of small molecules in the model tissues.

  11. Changes in oxygen partial pressure of brain tissue in an animal model of obstructive apnea

    Directory of Open Access Journals (Sweden)

    Torres Marta

    2010-01-01

    Full Text Available Abstract Background Cognitive impairment is one of the main consequences of obstructive sleep apnea (OSA and is usually attributed in part to the oxidative stress caused by intermittent hypoxia in cerebral tissues. The presence of oxygen-reactive species in the brain tissue should be produced by the deoxygenation-reoxygenation cycles which occur at tissue level during recurrent apneic events. However, how changes in arterial blood oxygen saturation (SpO2 during repetitive apneas translate into oxygen partial pressure (PtO2 in brain tissue has not been studied. The objective of this study was to assess whether brain tissue is partially protected from intermittently occurring interruption of O2 supply during recurrent swings in arterial SpO2 in an animal model of OSA. Methods Twenty-four male Sprague-Dawley rats (300-350 g were used. Sixteen rats were anesthetized and non-invasively subjected to recurrent obstructive apneas: 60 apneas/h, 15 s each, for 1 h. A control group of 8 rats was instrumented but not subjected to obstructive apneas. PtO2 in the cerebral cortex was measured using a fast-response oxygen microelectrode. SpO2 was measured by pulse oximetry. The time dependence of arterial SpO2 and brain tissue PtO2 was carried out by Friedman repeated measures ANOVA. Results Arterial SpO2 showed a stable periodic pattern (no significant changes in maximum [95.5 ± 0.5%; m ± SE] and minimum values [83.9 ± 1.3%]. By contrast, brain tissue PtO2 exhibited a different pattern from that of arterial SpO2. The minimum cerebral cortex PtO2 computed during the first apnea (29.6 ± 2.4 mmHg was significantly lower than baseline PtO2 (39.7 ± 2.9 mmHg; p = 0.011. In contrast to SpO2, the minimum and maximum values of PtO2 gradually increased (p 2 were significantly greater relative to baseline and the first apnea dip, respectively. Conclusions These data suggest that the cerebral cortex is partially protected from intermittently occurring interruption of

  12. Nonlinear scattering in hard tissue studied with ultrashort laser pulses

    International Nuclear Information System (INIS)

    Eichler, J.; Kim, B.M.

    2002-01-01

    The back-scattered spectrum of ultrashort laser pulses (800 nm, 0.2 ps) was studied in human dental and other hard tissues in vitro below the ablation threshold. Frequency doubled radiation (SHG), frequency tripled radiation and two-photon fluorescence were detected. The relative yield for these processes was measured for various pulse energies. The dependence of the SHG signal on probe thickness was determined in forward and back scattering geometry. SHG is sensitive to linear polarization of the incident laser radiation. SHG in human teeth was studied in vitro showing larger signals in dentin than in cementum and enamel. In carious areas no SHG signal could be detected. Possible applications of higher harmonic radiation for diagnostics and microscopy are discussed. (orig.)

  13. Model and methods to assess hepatic function from indocyanine green fluorescence dynamical measurements of liver tissue.

    Science.gov (United States)

    Audebert, Chloe; Vignon-Clementel, Irene E

    2018-03-30

    The indocyanine green (ICG) clearance, presented as plasma disappearance rate is, presently, a reliable method to estimate the hepatic "function". However, this technique is not instantaneously available and thus cannot been used intra-operatively (during liver surgery). Near-infrared spectroscopy enables to assess hepatic ICG concentration over time in the liver tissue. This article proposes to extract more information from the liver intensity dynamics by interpreting it through a dedicated pharmacokinetics model. In order to account for the different exchanges between the liver tissues, the proposed model includes three compartments for the liver model (sinusoids, hepatocytes and bile canaliculi). The model output dependency to parameters is studied with sensitivity analysis and solving an inverse problem on synthetic data. The estimation of model parameters is then performed with in-vivo measurements in rabbits (El-Desoky et al. 1999). Parameters for different liver states are estimated, and their link with liver function is investigated. A non-linear (Michaelis-Menten type) excretion rate from the hepatocytes to the bile canaliculi was necessary to reproduce the measurements for different liver conditions. In case of bile duct ligation, the model suggests that this rate is reduced, and that the ICG is stored in the hepatocytes. Moreover, the level of ICG remains high in the blood following the ligation of the bile duct. The percentage of retention of indocyanine green in blood, which is a common test for hepatic function estimation, is also investigated with the model. The impact of bile duct ligation and reduced liver inflow on the percentage of ICG retention in blood is studied. The estimation of the pharmacokinetics model parameters may lead to an evaluation of different liver functions. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Lipid profiling of in vitro cell models of adipogenic differentiation: relationships with mouse adipose tissues

    OpenAIRE

    Liaw, Lucy; Prudovsky, Igor; Koza, Robert A.; Anunciado-Koza, Rea V.; Siviski, Matthew E.; Lindner, Volkhard; Friesel, Robert E.; Rosen, Clifford J.; Baker, Paul R.S.; Simons, Brigitte; Vary, Calvin P.H.

    2016-01-01

    Our objective was to characterize lipid profiles in cell models of adipocyte differentiation in comparison to mouse adipose tissues in vivo. A novel lipid extraction strategy was combined with global lipid profiling using direct infusion and sequential precursor ion fragmentation, termed MS/MSALL. Perirenal and inguinal white adipose tissue and interscapular brown adipose tissues from adult C57BL/6J mice were analyzed. 3T3-L1 preadipocytes, ear mesenchymal progenitor cells, and brown adipose-...

  15. Nanotechnology meets 3D in vitro models: tissue engineered tumors and cancer therapies.

    Science.gov (United States)

    da Rocha, E L; Porto, L M; Rambo, C R

    2014-01-01

    Advances in nanotechnology are providing to medicine a new dimension. Multifunctional nanomaterials with diagnostics and treatment modalities integrated in one nanoparticle or in cooperative nanosystems are promoting new insights to cancer treatment and diagnosis. The recent convergence between tissue engineering and cancer is gradually moving towards the development of 3D disease models that more closely resemble in vivo characteristics of tumors. However, the current nanomaterials based therapies are accomplished mainly in 2D cell cultures or in complex in vivo models. The development of new platforms to evaluate nano-based therapies in parallel with possible toxic effects will allow the design of nanomaterials for biomedical applications prior to in vivo studies. Therefore, this review focuses on how 3D in vitro models can be applied to study tumor biology, nanotoxicology and to evaluate nanomaterial based therapies. © 2013.

  16. Detection of Talaromyces marneffei from Fresh Tissue of an Inhalational Murine Pulmonary Model Using Nested PCR.

    Directory of Open Access Journals (Sweden)

    Yinghui Liu

    Full Text Available Penicilliosis marneffei, often consecutive to the aspiration of Talaromyces marneffei (Penicillium marneffei, continues to be one of the significant causes of morbidity and mortality in immunocompromised patients in endemic regions such as Southeast Asia. Improving the accuracy of diagnosing this disease would aid in reducing the mortality of associated infections. In this study, we developed a stable and reproducible murine pulmonary model that mimics human penicilliosis marneffei using a nebulizer to deliver Talaromyces marneffei (SUMS0152 conidia to the lungs of BALB/c nude mice housed in exposure chamber. Using this model, we further revealed that nested PCR was sensitive and specific for detecting Talaromyces marneffei in bronchoalveolar lavage fluid and fresh tissues. This inhalation model may provide a more representative analysis tool for studying the development of penicilliosis marneffei, in addition to revealing that nested PCR has a predictive value in reflecting pulmonary infection.

  17. Detection of Talaromyces marneffei from Fresh Tissue of an Inhalational Murine Pulmonary Model Using Nested PCR

    Science.gov (United States)

    Liu, Yinghui; Huang, Xiaowen; Yi, Xiuwen; He, Ya; Mylonakis, Eleftherios; Xi, Liyan

    2016-01-01

    Penicilliosis marneffei, often consecutive to the aspiration of Talaromyces marneffei (Penicillium marneffei), continues to be one of the significant causes of morbidity and mortality in immunocompromised patients in endemic regions such as Southeast Asia. Improving the accuracy of diagnosing this disease would aid in reducing the mortality of associated infections. In this study, we developed a stable and reproducible murine pulmonary model that mimics human penicilliosis marneffei using a nebulizer to deliver Talaromyces marneffei (SUMS0152) conidia to the lungs of BALB/c nude mice housed in exposure chamber. Using this model, we further revealed that nested PCR was sensitive and specific for detecting Talaromyces marneffei in bronchoalveolar lavage fluid and fresh tissues. This inhalation model may provide a more representative analysis tool for studying the development of penicilliosis marneffei, in addition to revealing that nested PCR has a predictive value in reflecting pulmonary infection. PMID:26886887

  18. Theoretical study of the fibrous capsule tissue growth around a disk-shaped implant

    KAUST Repository

    Djellouli, Rabia; Mahserejian, Shant; Mokrane, A.; Moussaoui, Mohand; Laleg-Kirati, Taous-Meriem

    2012-01-01

    We analyze the mathematical properties of the fibrous capsule tissue concentration around a disk-shaped implant. We establish stability estimates as well as monotonicity results that illustrate the sensitivity of this growth to the biocompatibility index parameters of the implant. In addition, we prove that the growth of the tissue increases exponentially in time toward an asymptotic regime. We also study the mathematical properties of the solution of the inverse problem consisting in the determination of the values of the biocompatibility index parameters from the knowledge of some fibrous capsule tissue measurements. We prove that this model calibration problem admits a unique solution, and establish a characterization of the index parameters. Furthermore, we demonstrate analytically that such a solution is not continuous with respect to the data, and therefore the considered inverse problem is ill-posed due to the lack of the stability requirement. © 2012 Springer-Verlag.

  19. Theoretical study of the fibrous capsule tissue growth around a disk-shaped implant

    KAUST Repository

    Djellouli, Rabia

    2012-08-19

    We analyze the mathematical properties of the fibrous capsule tissue concentration around a disk-shaped implant. We establish stability estimates as well as monotonicity results that illustrate the sensitivity of this growth to the biocompatibility index parameters of the implant. In addition, we prove that the growth of the tissue increases exponentially in time toward an asymptotic regime. We also study the mathematical properties of the solution of the inverse problem consisting in the determination of the values of the biocompatibility index parameters from the knowledge of some fibrous capsule tissue measurements. We prove that this model calibration problem admits a unique solution, and establish a characterization of the index parameters. Furthermore, we demonstrate analytically that such a solution is not continuous with respect to the data, and therefore the considered inverse problem is ill-posed due to the lack of the stability requirement. © 2012 Springer-Verlag.

  20. Tissue expander stimulated lengthening of arteries (TESLA) induces early endothelial cell proliferation in a novel rodent model.

    Science.gov (United States)

    Potanos, Kristina; Fullington, Nora; Cauley, Ryan; Purcell, Patricia; Zurakowski, David; Fishman, Steven; Vakili, Khashayar; Kim, Heung Bae

    2016-04-01

    We examine the mechanism of aortic lengthening in a novel rodent model of tissue expander stimulated lengthening of arteries (TESLA). A rat model of TESLA was examined with a single stretch stimulus applied at the time of tissue expander insertion with evaluation of the aorta at 2, 4 and 7day time points. Measurements as well as histology and proliferation assays were performed and compared to sham controls. The aortic length was increased at all time points without histologic signs of tissue injury. Nuclear density remained unchanged despite the increase in length suggesting cellular hyperplasia. Cellular proliferation was confirmed in endothelial cell layer by Ki-67 stain. Aortic lengthening may be achieved using TESLA. The increase in aortic length can be achieved without tissue injury and results at least partially from cellular hyperplasia. Further studies are required to define the mechanisms involved in the growth of arteries under increased longitudinal stress. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Modeling skin cooling using optical windows and cryogens during laser induced hyperthermia in a multilayer vascularized tissue

    International Nuclear Information System (INIS)

    Singh, Rupesh; Das, Koushik; Okajima, Junnosuke; Maruyama, Shigenao; Mishra, Subhash C.

    2015-01-01

    This article deals with the spatial and the temporal evolution of tissue temperature during skin surface cooled laser induced hyperthermia. Three different skin surface cooling methodologies viz., optical window contact cooling, cryogenic spray cooling and cryogen cooled optical window contact cooling are considered. Sapphire, yttrium aluminum garnet, lithium tantalate, and magnesium oxide doped lithium niobate are the considered optical windows. The cryogens considered are liquid CO_2 and R1234yf. Heat transfer in the multilayer skin tissue embedded with thermally significant blood vessels pairs is modeled using the Pennes and Weinbaum–Jiji bioheat equations. Weinbaum–Jiji bioheat equation is used for the vascularized tissue. Laser transport in the tissue is modeled using the radiative transfer equation. Axial and radial (skin surface) temperature distributions for different combinations of optical windows and cryogens are analyzed. Liquid CO_2 cooled yttrium aluminum garnet is found to be the best surface cooling mechanism. - Highlights: • Skin surface cooled laser induced hyperthermia is studied. • A multi-layer 2-D cylindrical tissue geometry is considered. • Both Pennes and Weinbaum–Jiji bioheat models are considered. • Laser transport in the tissue is modeled using discrete ordinate method. • Results for 4 optical windows and 2 cryogens for skin cooling are presented.

  2. Modeling microwave electromagnetic field absorption in muscle tissues

    Science.gov (United States)

    Felbacq, D.; Clerjon, S.; Damez, J. L.; Zolla, F.

    2002-07-01

    Absorption of electromagnetic energy in human tissues is an important issue with respect to the safety of low-level exposure. Simulation is a way to a better understanding of electromagnetic dosimetry. This letter presents a comparison between results obtained from a numerical simulation and experimental data of absorbed energy by a muscle. Simulation was done using a bidimensional double-scale homogenization scheme leading to the effective permittivity tensor. Experimental measurements were performed at 10 GHz on bovine muscle, 30 hours after slaughter, thanks to the open-ended rectangular waveguide method. Results show a good agreement between measurements and simulated data.

  3. An Efficient Data-driven Tissue Deformation Model

    DEFF Research Database (Denmark)

    Mosbech, Thomas Hammershaimb; Ersbøll, Bjarne Kjær; Christensen, Lars Bager

    2009-01-01

    empirical data; 10 pig carcasses are subjected to deformation from a controlled source imitating the cutting tool. The tissue deformation is quantified by means of steel markers inserted into the carcass as a three-dimensional lattice. For each subject marker displacements are monitored through two...... find an association between the first principal mode and the lateral movement. Furthermore, there is a link between this and the ratio of meat-fat quantity - a potentially very useful finding since existing tools for carcass grading and sorting measure equivalent quantities....

  4. Identifying and exploiting trait-relevant tissues with multiple functional annotations in genome-wide association studies

    Science.gov (United States)

    Zhang, Shujun

    2018-01-01

    Genome-wide association studies (GWASs) have identified many disease associated loci, the majority of which have unknown biological functions. Understanding the mechanism underlying trait associations requires identifying trait-relevant tissues and investigating associations in a trait-specific fashion. Here, we extend the widely used linear mixed model to incorporate multiple SNP functional annotations from omics studies with GWAS summary statistics to facilitate the identification of trait-relevant tissues, with which to further construct powerful association tests. Specifically, we rely on a generalized estimating equation based algorithm for parameter inference, a mixture modeling framework for trait-tissue relevance classification, and a weighted sequence kernel association test constructed based on the identified trait-relevant tissues for powerful association analysis. We refer to our analytic procedure as the Scalable Multiple Annotation integration for trait-Relevant Tissue identification and usage (SMART). With extensive simulations, we show how our method can make use of multiple complementary annotations to improve the accuracy for identifying trait-relevant tissues. In addition, our procedure allows us to make use of the inferred trait-relevant tissues, for the first time, to construct more powerful SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28 GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and Roadmap. Our results reveal new trait-tissue relevance, pinpoint important annotations that are informative of trait-tissue relationship, and illustrate how we can use the inferred trait-relevant tissues to construct more powerful association tests in the Wellcome trust case control consortium study. PMID:29377896

  5. Identifying and exploiting trait-relevant tissues with multiple functional annotations in genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Xingjie Hao

    2018-01-01

    Full Text Available Genome-wide association studies (GWASs have identified many disease associated loci, the majority of which have unknown biological functions. Understanding the mechanism underlying trait associations requires identifying trait-relevant tissues and investigating associations in a trait-specific fashion. Here, we extend the widely used linear mixed model to incorporate multiple SNP functional annotations from omics studies with GWAS summary statistics to facilitate the identification of trait-relevant tissues, with which to further construct powerful association tests. Specifically, we rely on a generalized estimating equation based algorithm for parameter inference, a mixture modeling framework for trait-tissue relevance classification, and a weighted sequence kernel association test constructed based on the identified trait-relevant tissues for powerful association analysis. We refer to our analytic procedure as the Scalable Multiple Annotation integration for trait-Relevant Tissue identification and usage (SMART. With extensive simulations, we show how our method can make use of multiple complementary annotations to improve the accuracy for identifying trait-relevant tissues. In addition, our procedure allows us to make use of the inferred trait-relevant tissues, for the first time, to construct more powerful SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28 GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and Roadmap. Our results reveal new trait-tissue relevance, pinpoint important annotations that are informative of trait-tissue relationship, and illustrate how we can use the inferred trait-relevant tissues to construct more powerful association tests in the Wellcome trust case control consortium study.

  6. Thick tissue diffusion model with binding to optimize topical staining in fluorescence breast cancer margin imaging

    Science.gov (United States)

    Xu, Xiaochun; Kang, Soyoung; Navarro-Comes, Eric; Wang, Yu; Liu, Jonathan T. C.; Tichauer, Kenneth M.

    2018-03-01

    Intraoperative tumor/surgical margin assessment is required to achieve higher tumor resection rate in breast-conserving surgery. Though current histology provides incomparable accuracy in margin assessment, thin tissue sectioning and the limited field of view of microscopy makes histology too time-consuming for intraoperative applications. If thick tissue, wide-field imaging can provide an acceptable assessment of tumor cells at the surface of resected tissues, an intraoperative protocol can be developed to guide the surgery and provide immediate feedback for surgeons. Topical staining of margins with cancer-targeted molecular imaging agents has the potential to provide the sensitivity needed to see microscopic cancer on a wide-field image; however, diffusion and nonspecific retention of imaging agents in thick tissue can significantly diminish tumor contrast with conventional methods. Here, we present a mathematical model to accurately simulate nonspecific retention, binding, and diffusion of imaging agents in thick tissue topical staining to guide and optimize future thick tissue staining and imaging protocol. In order to verify the accuracy and applicability of the model, diffusion profiles of cancer targeted and untargeted (control) nanoparticles at different staining times in A431 tumor xenografts were acquired for model comparison and tuning. The initial findings suggest the existence of nonspecific retention in the tissue, especially at the tissue surface. The simulator can be used to compare the effect of nonspecific retention, receptor binding and diffusion under various conditions (tissue type, imaging agent) and provides optimal staining and imaging protocols for targeted and control imaging agent.

  7. Biochemical and Tissue Studies on Post Irradiation Recovery in Mammals

    International Nuclear Information System (INIS)

    Abdou, M.I.M.

    2004-01-01

    three main studies were performed in this thesis, namely, mortality and survival study, biochemical studies, and studies on tissue alterations cobalt-60 gamma irradiation for low let was used for the external whole body irradiation of the irradiated animal groups. a total number of animals of 722 virgin female adult wister rats of approximately the same age and weight were used for the three studies that were performed, including the control and irradiated animal groups. the animals were housed and kept with special care at fixed temperature, humidity and diet. the study on mortality and survival included 370 animals divided into control and groups irradiated with 4,5,6,7,8 and 9 Gy. this study was followed up for one year to record the number and date of animal deaths for the different irradiated groups. for the 8 and 9 Gy irradiated groups the follow up ended after 12 weeks and 11 days respectively when animal mortality reached 100%. the maximum percent mortality was noted at the second week (3.3,8,14 and 29%) for the 4,5,6 and 7 Gy irradiated groups respectively. for the 8 and 9 Gy irradiated groups, the maximum percent mortality was noted at the first week (42.9 and 90% respectively). regression equations were applied for the percent of mortality of the 5-8 Gy irradiated groups to estimate the LD 50/30, which was found to be 6.4 Gy

  8. Cyclic Loading of Growing Tissue in a Bioreactor: Mathematical Model and Asymptotic Analysis

    KAUST Repository

    Pohlmeyer, J. V.

    2013-10-24

    A simplified 2D mathematical model for tissue growth within a cyclically-loaded tissue engineering scaffold is presented and analyzed. Such cyclic loading has the potential to improve yield and functionality of tissue such as bone and cartilage when grown on a scaffold within a perfusion bioreactor. The cyclic compression affects the flow of the perfused nutrient, leading to flow properties that are inherently unsteady, though periodic, on a timescale short compared with that of tissue proliferation. A two-timescale analysis based on these well-separated timescales is exploited to derive a closed model for the tissue growth on the long timescale of proliferation. Some sample numerical results are given for the final model, and discussed. © 2013 Society for Mathematical Biology.

  9. Modeling of Nonlinear Propagation in Multi-layer Biological Tissues for Strong Focused Ultrasound

    International Nuclear Information System (INIS)

    Ting-Bo, Fan; Zhen-Bo, Liu; Zhe, Zhang; Dong, Zhang; Xiu-Fen, Gong

    2009-01-01

    A theoretical model of the nonlinear propagation in multi-layered tissues for strong focused ultrasound is proposed. In this model, the spheroidal beam equation (SBE) is utilized to describe the nonlinear sound propagation in each layer tissue, and generalized oblique incidence theory is used to deal with the sound transmission between two layer tissues. Computer simulation is performed on a fat-muscle-liver tissue model under the irradiation of a 1 MHz focused transducer with a large aperture angle of 35°. The results demonstrate that the tissue layer would change the amplitude of sound pressure at the focal region and cause the increase of side petals. (fundamental areas of phenomenology (including applications))

  10. Thermostatic tissue platform for intravital microscopy: 'the hanging drop' model.

    Science.gov (United States)

    Pavlovic, Dragan; Frieling, Helge; Lauer, Kai-Stephan; Bac, Vo Hoai; Richter, Joern; Wendt, Michael; Lehmann, Christian; Usichenko, Taras; Meissner, Konrad; Gruendling, Matthias

    2006-11-01

    Intravital microscopy imposes the particular problem of the combined control of the body temperature of the animal and the local temperature of the observed organ or tissues. We constructed and tested, in the rat ileum microcirculation preparation, a new organ-support platform. The platform consisted of an organ bath filled with physiological solution, and contained a suction tube, a superfusion tube, an intestine-support hand that was attached to a micromanipulator and a thermometer probe. To cover the intestine we used a cover glass plate with a plastic ring glued on its upper surface. After a routine procedure (anaesthesia, monitoring and surgery), the intestine segment (2-3 cm long) was gently exteriorized and placed on the 'hand' of the organ support. A small part of the intestine formed a small 'island' in the bath that was filled with physiological salt solution. The cover glass was secured in place. The physiological salt solution from the superfusion tube, which was pointed to the lower surface of the cover glass, formed a 'hanging drop'. The objective of the microscope was then immersed into distilled water that was formed by the cover glass plastic ring. The 'hanging drop' technique prevented any tissue quenching, ensured undisturbed microcirculation, provided for stable temperature and humidity, and permitted a clear visual field.

  11. Coupled porohyperelastic mass transport (PHEXPT) finite element models for soft tissues using ABAQUS.

    Science.gov (United States)

    Vande Geest, Jonathan P; Simon, B R; Rigby, Paul H; Newberg, Tyler P

    2011-04-01

    Finite element models (FEMs) including characteristic large deformations in highly nonlinear materials (hyperelasticity and coupled diffusive/convective transport of neutral mobile species) will allow quantitative study of in vivo tissues. Such FEMs will provide basic understanding of normal and pathological tissue responses and lead to optimization of local drug delivery strategies. We present a coupled porohyperelastic mass transport (PHEXPT) finite element approach developed using a commercially available ABAQUS finite element software. The PHEXPT transient simulations are based on sequential solution of the porohyperelastic (PHE) and mass transport (XPT) problems where an Eulerian PHE FEM is coupled to a Lagrangian XPT FEM using a custom-written FORTRAN program. The PHEXPT theoretical background is derived in the context of porous media transport theory and extended to ABAQUS finite element formulations. The essential assumptions needed in order to use ABAQUS are clearly identified in the derivation. Representative benchmark finite element simulations are provided along with analytical solutions (when appropriate). These simulations demonstrate the differences in transient and steady state responses including finite deformations, total stress, fluid pressure, relative fluid, and mobile species flux. A detailed description of important model considerations (e.g., material property functions and jump discontinuities at material interfaces) is also presented in the context of finite deformations. The ABAQUS-based PHEXPT approach enables the use of the available ABAQUS capabilities (interactive FEM mesh generation, finite element libraries, nonlinear material laws, pre- and postprocessing, etc.). PHEXPT FEMs can be used to simulate the transport of a relatively large neutral species (negligible osmotic fluid flux) in highly deformable hydrated soft tissues and tissue-engineered materials.

  12. Alveolar ridge augmentation by connective tissue grafting using a pouch method and modified connective tissue technique: A prospective study.

    Science.gov (United States)

    Agarwal, Ashish; Gupta, Narinder Dev

    2015-01-01

    Localized alveolar ridge defect may create physiological and pathological problems. Developments in surgical techniques have made it simpler to change the configuration of a ridge to create a more aesthetic and more easily cleansable shape. The purpose of this study was to compare the efficacy of alveolar ridge augmentation using a subepithelial connective tissue graft in pouch and modified connective tissue graft technique. In this randomized, double blind, parallel and prospective study, 40 non-smoker individuals with 40 class III alveolar ridge defects in maxillary anterior were randomly divided in two groups. Group I received modified connective tissue graft, while group II were treated with subepithelial connective tissue graft in pouch technique. The defect size was measured in its horizontal and vertical dimension by utilizing a periodontal probe in a stone cast at base line, after 3 months, and 6 months post surgically. Analysis of variance and Bonferroni post-hoc test were used for statistical analysis. A two-tailed P connective tissue graft proposed significantly more improvement as compare to connective tissue graft in pouch.

  13. Modeling Protein Structures in Feed and Seed Tissues Using Novel Synchrotron-Based Analytical Technique

    International Nuclear Information System (INIS)

    Yu, P.

    2008-01-01

    Traditional 'wet' chemical analyses usually looks for a specific known component (such as protein) through homogenization and separation of the components of interest from the complex tissue matrix. Traditional 'wet' chemical analyses rely heavily on the use of harsh chemicals and derivatization, therefore altering the native feed protein structures and possibly generating artifacts. The objective of this study was to introduce a novel and non-destructive method to estimate protein structures in feed and seeds within intact tissues using advanced synchrotron-based infrared microspectroscopy (SFTIRM). The experiments were performed at the National Synchrotron Light Source in Brookhaven National Laboratory (US Dept. of Energy, NY). The results show that with synchrotron-based SFTIRM, we are able to localize relatively 'pure' protein without destructions of the feed and seed tissues and qualify protein internal structures in terms of the proportions and ratios of a-helix, β-sheet, random coil and β-turns on a relative basis using multi-peak modeling procedures. These protein structure profile (a-helix, β-sheet, etc.) may influence protein quality and availability in animals. Several examples of feed and seeds were provided. The implications of this study are that we can use this new method to compare internal protein structures between feeds and between seed verities. We can also use this method to detect heat-induced the structural changes of protein in feeds.

  14. A solid tissue phantom for photon migration studies

    International Nuclear Information System (INIS)

    Cubeddu, Rinaldo; Pifferi, Antonio; Taroni, Paola; Torricelli, Alessandro; Valentini, Gianluca

    1997-01-01

    A solid tissue phantom made of agar, Intralipid and black ink is described and characterized. The preparation procedure is fast and easily implemented with standard laboratory equipment. An instrumentation for time-resolved transmittance measurements was used to determine the optical properties of the phantom. The absorption and the reduced scattering coefficients are linear with the ink and Intralipid concentrations, respectively. A systematic decrease of the reduced scattering coefficient dependent on the agar content is observed, but can easily be managed. The phantom is highly homogeneous and shows good repeatability among different preparations. Moreover, agar inclusions can be easily embedded in either solid or liquid matrixes, and no artefacts are caused by the solid - solid or solid - liquid interfaces. This allows one to produce reliable and realistic inhomogeneous phantoms with known optical properties, particularly interesting for studies on optical imaging through turbid media. (author)

  15. Tissue engineering and surgery: from translational studies to human trials

    Directory of Open Access Journals (Sweden)

    Vranckx Jan Jeroen

    2017-06-01

    Full Text Available Tissue engineering was introduced as an innovative and promising field in the mid-1980s. The capacity of cells to migrate and proliferate in growth-inducing medium induced great expectancies on generating custom-shaped bioconstructs for tissue regeneration. Tissue engineering represents a unique multidisciplinary translational forum where the principles of biomaterial engineering, the molecular biology of cells and genes, and the clinical sciences of reconstruction would interact intensively through the combined efforts of scientists, engineers, and clinicians. The anticipated possibilities of cell engineering, matrix development, and growth factor therapies are extensive and would largely expand our clinical reconstructive armamentarium. Application of proangiogenic proteins may stimulate wound repair, restore avascular wound beds, or reverse hypoxia in flaps. Autologous cells procured from biopsies may generate an ‘autologous’ dermal and epidermal laminated cover on extensive burn wounds. Three-dimensional printing may generate ‘custom-made’ preshaped scaffolds – shaped as a nose, an ear, or a mandible – in which these cells can be seeded. The paucity of optimal donor tissues may be solved with off-the-shelf tissues using tissue engineering strategies. However, despite the expectations, the speed of translation of in vitro tissue engineering sciences into clinical reality is very slow due to the intrinsic complexity of human tissues. This review focuses on the transition from translational protocols towards current clinical applications of tissue engineering strategies in surgery.

  16. The establishment of animal model of radiation-skin-burn and its changes of tissue metabolism

    International Nuclear Information System (INIS)

    Lu Xingan; Wu Shiliang; Wang Xiuzhen; Zhou Yinghui; Feng Yizhong; Tian Ye; Peng Miao

    2001-01-01

    The biochemistry metabolic changes of the tissues induced by 60 Co γ radiation or by accelerator β radiation on the animal local tissues were observed. The experiment results were shown as follows: (1) 60 Co γ radiation can induce the metabolic changes of the local tissue and led to ulcer or death. (2) Accelerator β radiation at the same dose of γ radiation can only produce ulcer but no death. (3) The biochemistry metabolic changes of the tissues induced by 60 Co γ radiation are similar to that by β radiation, but as a radiation-burn animal model, the latter is better

  17. Spiral-wave dynamics in a mathematical model of human ventricular tissue with myocytes and fibroblasts.

    Science.gov (United States)

    Nayak, Alok Ranjan; Shajahan, T K; Panfilov, A V; Pandit, Rahul

    2013-01-01

    Cardiac fibroblasts, when coupled functionally with myocytes, can modulate the electrophysiological properties of cardiac tissue. We present systematic numerical studies of such modulation of electrophysiological properties in mathematical models for (a) single myocyte-fibroblast (MF) units and (b) two-dimensional (2D) arrays of such units; our models build on earlier ones and allow for zero-, one-, and two-sided MF couplings. Our studies of MF units elucidate the dependence of the action-potential (AP) morphology on parameters such as [Formula: see text], the fibroblast resting-membrane potential, the fibroblast conductance [Formula: see text], and the MF gap-junctional coupling [Formula: see text]. Furthermore, we find that our MF composite can show autorhythmic and oscillatory behaviors in addition to an excitable response. Our 2D studies use (a) both homogeneous and inhomogeneous distributions of fibroblasts, (b) various ranges for parameters such as [Formula: see text], and [Formula: see text], and (c) intercellular couplings that can be zero-sided, one-sided, and two-sided connections of fibroblasts with myocytes. We show, in particular, that the plane-wave conduction velocity [Formula: see text] decreases as a function of [Formula: see text], for zero-sided and one-sided couplings; however, for two-sided coupling, [Formula: see text] decreases initially and then increases as a function of [Formula: see text], and, eventually, we observe that conduction failure occurs for low values of [Formula: see text]. In our homogeneous studies, we find that the rotation speed and stability of a spiral wave can be controlled either by controlling [Formula: see text] or [Formula: see text]. Our studies with fibroblast inhomogeneities show that a spiral wave can get anchored to a local fibroblast inhomogeneity. We also study the efficacy of a low-amplitude control scheme, which has been suggested for the control of spiral-wave turbulence in mathematical models for cardiac

  18. Loss of mass and performance in skeletal muscle tissue: a continuum model

    Directory of Open Access Journals (Sweden)

    Giantesio Giulia

    2018-02-01

    Full Text Available We present a continuum hyperelastic model which describes the mechanical response of a skeletal muscle tissue when its strength and mass are reduced by aging. Such a reduction is typical of a geriatric syndrome called sarcopenia. The passive behavior of the material is described by a hyperelastic, polyconvex, transversely isotropic strain energy function, and the activation of the muscle is modeled by the so called active strain approach. The loss of ability of activating of an elder muscle is then obtained by lowering of some percentage the active part of the stress, while the loss of mass is modeled through a multiplicative decomposition of the deformation gradient. The obtained stress-strain relations are graphically represented and discussed in order to study some of the effects of sarcopenia.

  19. Lipid Profiling of In Vitro Cell Models of Adipogenic Differentiation: Relationships With Mouse Adipose Tissues.

    Science.gov (United States)

    Liaw, Lucy; Prudovsky, Igor; Koza, Robert A; Anunciado-Koza, Rea V; Siviski, Matthew E; Lindner, Volkhard; Friesel, Robert E; Rosen, Clifford J; Baker, Paul R S; Simons, Brigitte; Vary, Calvin P H

    2016-09-01

    Our objective was to characterize lipid profiles in cell models of adipocyte differentiation in comparison to mouse adipose tissues in vivo. A novel lipid extraction strategy was combined with global lipid profiling using direct infusion and sequential precursor ion fragmentation, termed MS/MS(ALL) . Perirenal and inguinal white adipose tissue and interscapular brown adipose tissues from adult C57BL/6J mice were analyzed. 3T3-L1 preadipocytes, ear mesenchymal progenitor cells, and brown adipose-derived BAT-C1 cells were also characterized. Over 3000 unique lipid species were quantified. Principal component analysis showed that perirenal versus inguinal white adipose tissues varied in lipid composition of triacyl- and diacylglycerols, sphingomyelins, glycerophospholipids and, notably, cardiolipin CL 72:3. In contrast, hexosylceramides and sphingomyelins distinguished brown from white adipose. Adipocyte differentiation models showed broad differences in lipid composition among themselves, upon adipogenic differentiation, and with adipose tissues. Palmitoyl triacylglycerides predominate in 3T3-L1 differentiation models, whereas cardiolipin CL 72:1 and SM 45:4 were abundant in brown adipose-derived cell differentiation models, respectively. MS/MS(ALL) data suggest new lipid biomarkers for tissue-specific lipid contributions to adipogenesis, thus providing a foundation for using in vitro models of adipogenesis to reflect potential changes in adipose tissues in vivo. J. Cell. Biochem. 117: 2182-2193, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. [FTIR study on the normal and cancerous stomach tissues].

    Science.gov (United States)

    Tong, Y; Lin, Y

    2001-06-01

    Tissues of cancerous and corresponding normal stomach were studied by FTIR technique. The results showed that there are obvious differences between FTIR spectra of them in spectral parameters such as frequency, intensity and band shape etc. The changes involving the phosphate symmetric stretching nu s, PO2- and asymmetric stretching nu as, PO2- modes, the CH3 and CH2 groups stretching (nu s, CH2, nu as, CH3) and bending (delta CH2) modes and the C-O stretching nu C-O mode were discussed. In addition, the changes of structure of hydrogen-bonding of nucleic acid and cell proteins and the packing and the conformational structure of the membrance lipids were analysed further. The average wavenumber of band of nu s, PO2- shifted from 1,080.92 cm-1 to 1,085.93 cm-1 and that of nu as, PO2- shifted from 1,239.64 cm-1 to 1,238.73 cm-1 which indicated that the degree of hydrogen-bonding formed by oxygen atom of the phosphodiester groups of nucleic acids was increased. The average wavenumber of band of delta CH2 of membrance lipids shifted from 1,455.23 cm-1 to 1,457.37 cm-1 that suggested that the conformational structure of the methylene chains of membrance lipids is more disordered than in normal tissues. The shift of band of nu C-O of cell proteins from 1,166.08 cm-1 to 1,166.58 cm-1 indicated that the hydrogen-bond of cell proteins become weaker.

  1. A data-driven soft sensor for needle deflection in heterogeneous tissue using just-in-time modelling.

    Science.gov (United States)

    Rossa, Carlos; Lehmann, Thomas; Sloboda, Ronald; Usmani, Nawaid; Tavakoli, Mahdi

    2017-08-01

    Global modelling has traditionally been the approach taken to estimate needle deflection in soft tissue. In this paper, we propose a new method based on local data-driven modelling of needle deflection. External measurement of needle-tissue interactions is collected from several insertions in ex vivo tissue to form a cloud of data. Inputs to the system are the needle insertion depth, axial rotations, and the forces and torques measured at the needle base by a force sensor. When a new insertion is performed, the just-in-time learning method estimates the model outputs given the current inputs to the needle-tissue system and the historical database. The query is compared to every observation in the database and is given weights according to some similarity criteria. Only a subset of historical data that is most relevant to the query is selected and a local linear model is fit to the selected points to estimate the query output. The model outputs the 3D deflection of the needle tip and the needle insertion force. The proposed approach is validated in ex vivo multilayered biological tissue in different needle insertion scenarios. Experimental results in five different case studies indicate an accuracy in predicting needle deflection of 0.81 and 1.24 mm in the horizontal and vertical lanes, respectively, and an accuracy of 0.5 N in predicting the needle insertion force over 216 needle insertions.

  2. Experimental testing and constitutive modeling of the mechanical properties of the swine skin tissue.

    Science.gov (United States)

    Łagan, Sylwia D; Liber-Kneć, Aneta

    2017-01-01

    The aim of the study was an estimation of the possibility of using hyperelastic material models to fit experimental data obtained in the tensile test for the swine skin tissue. The uniaxial tensile tests of samples taken from the abdomen and back of a pig was carried out. The mechanical properties of the skin such as the mean Young's modulus, the mean maximum stress and the mean maximum elongation were calculated. The experimental data have been used to identify the parameters in specific strain-energy functions given in seven constitutive models of hyperelastic materials: neo-Hookean, Mooney-Rivlin, Ogden, Yeoh, Martins, Humphrey and Veronda-Westmann. An analysis of errors in fitting of theoretical and experimental data was done. Comparison of load -displacement curves for the back and abdomen regions of skin taken showed a different scope of both the mean maximum loading forces and the mean maximum elongation. Samples which have been prepared from the abdominal area had lower values of the mean maximum load compared to samples from the spine area. The reverse trend was observed during the analysis of the values of elongation. An analysis of the accuracy of model fitting to the experimental data showed that, the least accurate were the model of neo- -Hookean, model of Mooney-Rivlin for the abdominal region and model of Veronda-Westmann for the spine region. An analysis of seven hyperelastic material models showed good correlations between the experimental and the theoretical data for five models.

  3. Assessing Anticalcification Treatments in Bioprosthetic Tissue by Using the New Zealand Rabbit Intramuscular Model

    Science.gov (United States)

    Wright, Gregory A; Faught, Joelle M; Olin, Jane M

    2009-01-01

    The objective of this work was to demonstrate that the New Zealand White (NZW) rabbit intramuscular model can be used for detecting calcification in bioprosthetic tissue and to compare the calcification in the rabbit to that of native human valves. The rabbit model was compared with the commonly used Sprague–Dawley rat subcutaneous model. Eighteen rabbits and 18 rats were used to assess calcification in bioprosthetic tissue over time (7, 14, 30, and 90 d). The explanted rabbit and rat tissue discs were measured for calcium by using atomic absorption and Raman spectroscopy. Calcium deposits on the human valve explants were assessed by using Raman spectroscopy. The results showed that the NZW rabbit model is robust for detecting calcification in a shorter duration (14 d), with less infection complications, more space to implant tissue groups (thereby reducing animal use numbers), and a more metabolically and mechanically dynamic environment than the rat subcutaneous model . The human explanted valves and rabbit explanted tissue both showed Raman peaks at 960 cm−1 which is representative of hydroxyapatite. Hydroxyapatite is the final calcium and phosphate species in the calcification of bioprosthetic heart valves and rabbit intramuscular implants. The NZW rabbit intramuscular model is an effective model for assessing calcification in bioprosthetic tissue. PMID:19619417

  4. Role of tissue factor and protease-activated receptors in a mouse model of endotoxemia.

    Science.gov (United States)

    Pawlinski, Rafal; Pedersen, Brian; Schabbauer, Gernot; Tencati, Michael; Holscher, Todd; Boisvert, William; Andrade-Gordon, Patricia; Frank, Rolf Dario; Mackman, Nigel

    2004-02-15

    Sepsis is associated with a systemic activation of coagulation and an excessive inflammatory response. Anticoagulants have been shown to inhibit both coagulation and inflammation in sepsis. In this study, we used both genetic and pharmacologic approaches to analyze the role of tissue factor and protease-activated receptors in coagulation and inflammation in a mouse endotoxemia model. We used mice expressing low levels of the procoagulant molecule, tissue factor (TF), to analyze the effects of TF deficiency either in all tissues or selectively in hematopoietic cells. Low TF mice had reduced coagulation, inflammation, and mortality compared with control mice. Similarly, a deficiency of TF expression by hematopoietic cells reduced lipopolysaccharide (LPS)-induced coagulation, inflammation, and mortality. Inhibition of the down-stream coagulation protease, thrombin, reduced fibrin deposition and prolonged survival without affecting inflammation. Deficiency of either protease activated receptor-1 (PAR-1) or protease activated receptor-2 (PAR-2) alone did not affect inflammation or survival. However, a combination of thrombin inhibition and PAR-2 deficiency reduced inflammation and mortality. These data demonstrate that hematopoietic cells are the major pathologic site of TF expression during endotoxemia and suggest that multiple protease-activated receptors mediate crosstalk between coagulation and inflammation.

  5. Electrospun gelatin biopapers as substrate for in vitro bilayer models of blood-brain barrier tissue.

    Science.gov (United States)

    Bischel, Lauren L; Coneski, Peter N; Lundin, Jeffrey G; Wu, Peter K; Giller, Carl B; Wynne, James; Ringeisen, Brad R; Pirlo, Russell K

    2016-04-01

    Gaining a greater understanding of the blood-brain barrier (BBB) is critical for improvement in drug delivery, understanding pathologies that compromise the BBB, and developing therapies to protect the BBB. In vitro human tissue models are valuable tools for studying these issues. The standard in vitro BBB models use commercially available cell culture inserts to generate bilayer co-cultures of astrocytes and endothelial cells (EC). Electrospinning can be used to produce customized cell culture substrates with optimized material composition and mechanical properties with advantages over off-the-shelf materials. Electrospun gelatin is an ideal cell culture substrate because it is a natural polymer that can aid cell attachment and be modified and degraded by cells. Here, we have developed a method to produce cell culture inserts with electrospun gelatin "biopaper" membranes. The electrospun fiber diameter and cross-linking method were optimized for the growth of primary human endothelial cell and primary human astrocyte bilayer co-cultures to model human BBB tissue. BBB co-cultures on biopaper were characterized via cell morphology, trans-endothelial electrical resistance (TEER), and permeability to FITC-labeled dextran and compared to BBB co-cultures on standard cell culture inserts. Over longer culture periods (up to 21 days), cultures on the optimized electrospun gelatin biopapers were found to have improved TEER, decreased permeability, and permitted a smaller separation between co-cultured cells when compared to standard PET inserts. © 2016 Wiley Periodicals, Inc.

  6. A mathematical model for fluid shear-sensitive 3D tissue construct development.

    Science.gov (United States)

    Liu, Dan; Chua, Chee-Kai; Leong, Kah-Fai

    2013-01-01

    This research studies dynamic culture for 3D tissue construct development with computational fluid dynamics. It proposes a mathematical model to evaluate the impact of flow rates and flow shear stress on cell growth in 3D constructs under perfusion. The modeling results show that dynamic flow, even at flow rate as low as 0.002 cm/s, can support much better mass exchange, higher cell number, and more even cell and nutrient distribution compared to static culture. Higher flow rate can further improve nutrient supply and mass exchange in the construct, promoting better nutritious environment and cell proliferation compared to lower flow rate. In addition, consideration of flow shear stress predicts much higher cell number in the construct compared to that without shear consideration. While the nutrient can dominate shear stress in influencing cell proliferation, the shear effect increases with flow rate. The proposed model helps tissue engineers better understand the cell-flow relationship at the molecular level during dynamic culture.

  7. Mathematical models of soft tissue injury repair : towards understanding musculoskeletal disorders

    OpenAIRE

    Dunster, Joanne L.

    2012-01-01

    The process of soft tissue injury repair at the cellular lew I can be decomposed into three phases: acute inflammation including coagulation, proliferation and remodelling. While the later phases are well understood the early phase is less so. We produce a series of new mathematical models for the early phases coagulation and inflammation. The models produced are relevant not only to soft tissue injury repair but also to the many disease states in which coagulation and inflammation play a rol...

  8. Constructing a Computer Model of the Human Eye Based on Tissue Slice Images

    OpenAIRE

    Dai, Peishan; Wang, Boliang; Bao, Chunbo; Ju, Ying

    2010-01-01

    Computer simulation of the biomechanical and biological heat transfer in ophthalmology greatly relies on having a reliable computer model of the human eye. This paper proposes a novel method on the construction of a geometric model of the human eye based on tissue slice images. Slice images were obtained from an in vitro Chinese human eye through an embryo specimen processing methods. A level set algorithm was used to extract contour points of eye tissues while a principle component analysi...

  9. Soft tissue deformation using a Hierarchical Finite Element Model.

    Science.gov (United States)

    Faraci, Alessandro; Bello, Fernando; Darzi, Ara

    2004-01-01

    Simulating soft tissue deformation in real-time has become increasingly important in order to provide a realistic virtual environment for training surgical skills. Several methods have been proposed with the aim of rendering in real-time the mechanical and physiological behaviour of human organs, one of the most popular being Finite Element Method (FEM). In this paper we present a new approach to the solution of the FEM problem introducing the concept of parent and child mesh within the development of a hierarchical FEM. The online selection of the child mesh is presented with the purpose to adapt the mesh hierarchy in real-time. This permits further refinement of the child mesh increasing the detail of the deformation without slowing down the simulation and giving the possibility of integrating force feedback. The results presented demonstrate the application of our proposed framework using a desktop virtual reality (VR) system that incorporates stereo vision with integrated haptics co-location via a desktop Phantom force feedback device.

  10. A composite model including visfatin, tissue polypeptide-specific antigen, hyaluronic acid, and hematological variables for the diagnosis of moderate-to-severe fibrosis in nonalcoholic fatty liver disease: a preliminary study.

    Science.gov (United States)

    Chwist, Alina; Hartleb, Marek; Lekstan, Andrzej; Kukla, Michał; Gutkowski, Krzysztof; Kajor, Maciej

    2014-01-01

    Histopathological risk factors for end-stage liver failure in patients with nonalcoholic fatty liver disease (NAFLD) include nonalcoholic steatohepatitis (NASH) and advanced liver fibrosis. There is a need for noninvasive diagnostic methods for these 2 conditions. The aim of this study was to investigate new laboratory variables with a predictive potential to detect advanced fibrosis (stages 2 and 3) in NAFLD. The study involved 70 patients with histologically proven NAFLD of varied severity. Additional laboratory variables included zonulin, haptoglobin, visfatin, adiponectin, leptin, tissue polypeptide-specific antigen (TPSA), hyaluronic acid, and interleukin 6. Patients with NASH (NAFLD activity score of ≥5) had significantly higher HOMA-IR values and serum levels of visfatin, haptoglobin, and zonulin as compared with those without NASH on histological examination. Advanced fibrosis was found in 16 patients (22.9%) and the risk factors associated with its prevalence were age, the ratio of erythrocyte count to red blood cell distribution width, platelet count, and serum levels of visfatin and TPSA. Based on these variables, we constructed a scoring system that differentiated between NAFLD patients with and without advanced fibrosis with a sensitivity of 75% and specificity of 100% (area under the receiver operating characteristic curve, 0.93). The scoring system based on the above variables allows to predict advanced fibrosis with high sensitivity and specificity. However, its clinical utility should be verified in further studies involving a larger number of patients.

  11. Re-evaluation of model-based light-scattering spectroscopy for tissue spectroscopy

    Science.gov (United States)

    Lau, Condon; Šćepanović, Obrad; Mirkovic, Jelena; McGee, Sasha; Yu, Chung-Chieh; Fulghum, Stephen; Wallace, Michael; Tunnell, James; Bechtel, Kate; Feld, Michael

    2009-01-01

    Model-based light scattering spectroscopy (LSS) seemed a promising technique for in-vivo diagnosis of dysplasia in multiple organs. In the studies, the residual spectrum, the difference between the observed and modeled diffuse reflectance spectra, was attributed to single elastic light scattering from epithelial nuclei, and diagnostic information due to nuclear changes was extracted from it. We show that this picture is incorrect. The actual single scattering signal arising from epithelial nuclei is much smaller than the previously computed residual spectrum, and does not have the wavelength dependence characteristic of Mie scattering. Rather, the residual spectrum largely arises from assuming a uniform hemoglobin distribution. In fact, hemoglobin is packaged in blood vessels, which alters the reflectance. When we include vessel packaging, which accounts for an inhomogeneous hemoglobin distribution, in the diffuse reflectance model, the reflectance is modeled more accurately, greatly reducing the amplitude of the residual spectrum. These findings are verified via numerical estimates based on light propagation and Mie theory, tissue phantom experiments, and analysis of published data measured from Barrett’s esophagus. In future studies, vessel packaging should be included in the model of diffuse reflectance and use of model-based LSS should be discontinued. PMID:19405760

  12. Epidemiological study of soft-tissue sarcomas in Ireland.

    LENUS (Irish Health Repository)

    Bhatt, Nikita

    2015-11-21

    Soft-tissue sarcomas (STS) account for 1% of adult and 7% of pediatric malignancies. Histopathology and classification of these rare tumors requires further refinements. The aim of this paper is to describe the current incidence and survival of STS from 1994 to 2012 in Ireland and compare these with comparably coded international published reports. This is a retrospective, population study based on the data from the National Cancer Registry of Ireland (NCRI). Incidence and relative survival rates for STS in Ireland were generated. Incidence of STS based on gender, age and anatomical location was examined. Annual mean incidence rate (European Age Standardized) in Ireland between 1994 and 2012 was 4.48 ± 0.15 per 100,000 person-years. The overall relative 5-year survival rate of STS for the period 1994-2011 in Ireland was 56%, which was similar to that reported in the U.K. but lower than in most of Europe and U.S.A. Survival rate fluctuated over the period examined, declining slightly in females but showing an increase in males. STS incidence trends in Ireland were comparable to international reports. Survival trends of STS were significantly different between Ireland and other European countries, requiring further study to understand causation.

  13. Tissue alignment enhances remodeling potential of tendon-derived cells - Lessons from a novel microtissue model of tendon scarring.

    Science.gov (United States)

    Foolen, Jasper; Wunderli, Stefania L; Loerakker, Sandra; Snedeker, Jess G

    2018-01-01

    Tendinopathy is a widespread and unresolved clinical challenge, in which associated pain and hampered mobility present a major cause for work-related disability. Tendinopathy associates with a change from a healthy tissue with aligned extracellular matrix (ECM) and highly polarized cells that are connected head-to-tail, towards a diseased tissue with a disorganized ECM and randomly distributed cells, scar-like features that are commonly attributed to poor innate regenerative capacity of the tissue. A fundamental clinical dilemma with this scarring process is whether treatment strategies should focus on healing the affected (disorganized) tissue or strengthen the remaining healthy (anisotropic) tissue. The question was thus asked whether the intrinsic remodeling capacity of tendon-derived cells depends on the organization of the 3D extracellular matrix (isotropic vs anisotropic). Progress in this field is hampered by the lack of suitable in vitro tissue platforms. We aimed at filling this critical gap by creating and exploiting a next generation tissue platform that mimics aspects of the tendon scarring process; cellular response to a gradient in tissue organization from isotropic (scarred/non-aligned) to highly anisotropic (unscarred/aligned) was studied, as was a transient change from isotropic towards highly anisotropic. Strikingly, cells residing in an 'unscarred' anisotropic tissue indicated superior remodeling capacity (increased gene expression levels of collagen, matrix metalloproteinases MMPs, tissue inhibitors of MMPs), when compared to their 'scarred' isotropic counterparts. A numerical model then supported the hypothesis that cellular remodeling capacity may correlate to cellular alignment strength. This in turn may have improved cellular communication, and could thus relate to the more pronounced connexin43 gap junctions observed in anisotropic tissues. In conclusion, increased tissue anisotropy was observed to enhance the cellular potential for

  14. Gelatin-GAG electrospun nanofibrous scaffold for skin tissue engineering: fabrication and modeling of process parameters.

    Science.gov (United States)

    Pezeshki-Modaress, Mohamad; Mirzadeh, Hamid; Zandi, Mojgan

    2015-03-01

    Electrospinning is a very useful technique for producing polymeric nanofibers by applying electrostatic forces. In this study, fabrication of novel gelatin/GAG nanofibrous mats and also the optimization of electrospinning process using response surface methodology were reported. At optimization section, gelatin/GAG blend ratio, applied voltage and feeding rate, their individual and interaction effects on the mean fiber diameter (MFD) and standard deviation of fiber diameter (SDF) were investigated. The obtained model for MFD has a quadratic relationship with gelatin/GAG blend ratio, applied voltage and feeding rate. The interactions of blend ratio and applied voltage and also applied voltage and flow rate were found significant but the interactions of blend ratio and flow rate were ignored. The optimum condition for gelatin/GAG electrospinning was also introduced using the model obtained in this study. The potential use of optimized electrospun mat in skin tissue engineering was evaluated using culturing of human dermal fibroblast cells (HDF). The SEM micrographs of HDF cells on the nanofibrous structure show that fibroblast cells can highly attach, grow and populate on the fabricated scaffold surface. The electrospun gelatin/GAG nanofibrous mats have a potential for using as scaffold for skin, cartilage and cornea tissue engineering. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Metal artifact reduction in CT using tissue-class modeling and adaptive prefiltering

    International Nuclear Information System (INIS)

    Bal, Matthieu; Spies, Lothar

    2006-01-01

    High-density objects such as metal prostheses, surgical clips, or dental fillings generate streak-like artifacts in computed tomography images. We present a novel method for metal artifact reduction by in-painting missing information into the corrupted sinogram. The information is provided by a tissue-class model extracted from the distorted image. To this end the image is first adaptively filtered to reduce the noise content and to smooth out streak artifacts. Consecutively, the image is segmented into different material classes using a clustering algorithm. The corrupted and missing information in the original sinogram is completed using the forward projected information from the tissue-class model. The performance of the correction method is assessed on phantom images. Clinical images featuring a broad spectrum of metal artifacts are studied. Phantom and clinical studies show that metal artifacts, such as streaks, are significantly reduced and shadows in the image are eliminated. Furthermore, the novel approach improves detectability of organ contours. This can be of great relevance, for instance, in radiation therapy planning, where images affected by metal artifacts may lead to suboptimal treatment plans

  16. Development and characterization of a spheroidal coculture model of endothelial cells and fibroblasts for improving angiogenesis in tissue engineering

    DEFF Research Database (Denmark)

    Wenger, Andreas; Kowalewski, Nadja; Stahl, Andreas

    2005-01-01

    Neovascularization is a critical step in tissue engineering applications since implantation of voluminous grafts without sufficient vascularity results in hypoxic cell death of central tissues. We have developed a three-dimensional spheroidal coculture system consisting of human umbilical vein...... endothelial cells (HUVECs) and human primary fibroblasts (hFBs) to improve angiogenesis in tissue engineering applications. Morphological analysis of cryosections from HUVEC/hFB cospheroids revealed a characteristic temporal and spatial organization with HUVECs located in the center of the cospheroid...... to the formation of heterogenic cell contacts between HUVECs and hFBs within the cospheroid. The model system introduced in this study is suitable for the development of a preformed lumenized capillary-like network ex vivo and may therefore be useful for improving angiogenesis in in vivo tissue engineering...

  17. Mammogram synthesis using a 3D simulation. I. Breast tissue model and image acquisition simulation

    International Nuclear Information System (INIS)

    Bakic, Predrag R.; Albert, Michael; Brzakovic, Dragana; Maidment, Andrew D. A.

    2002-01-01

    A method is proposed for generating synthetic mammograms based upon simulations of breast tissue and the mammographic imaging process. A computer breast model has been designed with a realistic distribution of large and medium scale tissue structures. Parameters controlling the size and placement of simulated structures (adipose compartments and ducts) provide a method for consistently modeling images of the same simulated breast with modified position or acquisition parameters. The mammographic imaging process is simulated using a compression model and a model of the x-ray image acquisition process. The compression model estimates breast deformation using tissue elasticity parameters found in the literature and clinical force values. The synthetic mammograms were generated by a mammogram acquisition model using a monoenergetic parallel beam approximation applied to the synthetically compressed breast phantom

  18. Validation of a power-law noise model for simulating small-scale breast tissue

    International Nuclear Information System (INIS)

    Reiser, I; Edwards, A; Nishikawa, R M

    2013-01-01

    We have validated a small-scale breast tissue model based on power-law noise. A set of 110 patient images served as truth. The statistical model parameters were determined by matching the radially averaged power-spectrum of the projected simulated tissue with that of the central tomosynthesis patient breast projections. Observer performance in a signal-known exactly detection task in simulated and actual breast backgrounds was compared. Observers included human readers, a pre-whitening observer model and a channelized Hotelling observer model. For all observers, good agreement between performance in the simulated and actual backgrounds was found, both in the tomosynthesis central projections and the reconstructed images. This tissue model can be used for breast x-ray imaging system optimization. The complete statistical description of the model is provided. (paper)

  19. Computational model-informed design and bioprinting of cell-patterned constructs for bone tissue engineering.

    Science.gov (United States)

    Carlier, Aurélie; Skvortsov, Gözde Akdeniz; Hafezi, Forough; Ferraris, Eleonora; Patterson, Jennifer; Koç, Bahattin; Van Oosterwyck, Hans

    2016-05-17

    Three-dimensional (3D) bioprinting is a rapidly advancing tissue engineering technology that holds great promise for the regeneration of several tissues, including bone. However, to generate a successful 3D bone tissue engineering construct, additional complexities should be taken into account such as nutrient and oxygen delivery, which is often insufficient after implantation in large bone defects. We propose that a well-designed tissue engineering construct, that is, an implant with a specific spatial pattern of cells in a matrix, will improve the healing outcome. By using a computational model of bone regeneration we show that particular cell patterns in tissue engineering constructs are able to enhance bone regeneration compared to uniform ones. We successfully bioprinted one of the most promising cell-gradient patterns by using cell-laden hydrogels with varying cell densities and observed a high cell viability for three days following the bioprinting process. In summary, we present a novel strategy for the biofabrication of bone tissue engineering constructs by designing cell-gradient patterns based on a computational model of bone regeneration, and successfully bioprinting the chosen design. This integrated approach may increase the success rate of implanted tissue engineering constructs for critical size bone defects and also can find a wider application in the biofabrication of other types of tissue engineering constructs.

  20. Calculation of dose distribution in compressible breast tissues using finite element modeling, Monte Carlo simulation and thermoluminescence dosimeters

    Science.gov (United States)

    Mohammadyari, Parvin; Faghihi, Reza; Mosleh-Shirazi, Mohammad Amin; Lotfi, Mehrzad; Rahim Hematiyan, Mohammad; Koontz, Craig; Meigooni, Ali S.

    2015-12-01

    Compression is a technique to immobilize the target or improve the dose distribution within the treatment volume during different irradiation techniques such as AccuBoost® brachytherapy. However, there is no systematic method for determination of dose distribution for uncompressed tissue after irradiation under compression. In this study, the mechanical behavior of breast tissue between compressed and uncompressed states was investigated. With that, a novel method was developed to determine the dose distribution in uncompressed tissue after irradiation of compressed breast tissue. Dosimetry was performed using two different methods, namely, Monte Carlo simulations using the MCNP5 code and measurements using thermoluminescent dosimeters (TLD). The displacement of the breast elements was simulated using a finite element model and calculated using ABAQUS software. From these results, the 3D dose distribution in uncompressed tissue was determined. The geometry of the model was constructed from magnetic resonance images of six different women volunteers. The mechanical properties were modeled by using the Mooney-Rivlin hyperelastic material model. Experimental dosimetry was performed by placing the TLD chips into the polyvinyl alcohol breast equivalent phantom. The results determined that the nodal displacements, due to the gravitational force and the 60 Newton compression forces (with 43% contraction in the loading direction and 37% expansion in the orthogonal direction) were determined. Finally, a comparison of the experimental data and the simulated data showed agreement within 11.5%  ±  5.9%.

  1. Calculation of dose distribution in compressible breast tissues using finite element modeling, Monte Carlo simulation and thermoluminescence dosimeters

    International Nuclear Information System (INIS)

    Mohammadyari, Parvin; Faghihi, Reza; Mosleh-Shirazi, Mohammad Amin; Lotfi, Mehrzad; Hematiyan, Mohammad Rahim; Koontz, Craig; Meigooni, Ali S

    2015-01-01

    Compression is a technique to immobilize the target or improve the dose distribution within the treatment volume during different irradiation techniques such as AccuBoost ® brachytherapy. However, there is no systematic method for determination of dose distribution for uncompressed tissue after irradiation under compression. In this study, the mechanical behavior of breast tissue between compressed and uncompressed states was investigated. With that, a novel method was developed to determine the dose distribution in uncompressed tissue after irradiation of compressed breast tissue. Dosimetry was performed using two different methods, namely, Monte Carlo simulations using the MCNP5 code and measurements using thermoluminescent dosimeters (TLD). The displacement of the breast elements was simulated using a finite element model and calculated using ABAQUS software. From these results, the 3D dose distribution in uncompressed tissue was determined. The geometry of the model was constructed from magnetic resonance images of six different women volunteers. The mechanical properties were modeled by using the Mooney–Rivlin hyperelastic material model. Experimental dosimetry was performed by placing the TLD chips into the polyvinyl alcohol breast equivalent phantom. The results determined that the nodal displacements, due to the gravitational force and the 60 Newton compression forces (with 43% contraction in the loading direction and 37% expansion in the orthogonal direction) were determined. Finally, a comparison of the experimental data and the simulated data showed agreement within 11.5%  ±  5.9%. (paper)

  2. A DTI-based model for TMS using the independent impedance method with frequency-dependent tissue parameters

    Science.gov (United States)

    De Geeter, N.; Crevecoeur, G.; Dupré, L.; Van Hecke, W.; Leemans, A.

    2012-04-01

    Accurate simulations on detailed realistic head models are necessary to gain a better understanding of the response to transcranial magnetic stimulation (TMS). Hitherto, head models with simplified geometries and constant isotropic material properties are often used, whereas some biological tissues have anisotropic characteristics which vary naturally with frequency. Moreover, most computational methods do not take the tissue permittivity into account. Therefore, we calculate the electromagnetic behaviour due to TMS in a head model with realistic geometry and where realistic dispersive anisotropic tissue properties are incorporated, based on T1-weighted and diffusion-weighted magnetic resonance images. This paper studies the impact of tissue anisotropy, permittivity and frequency dependence, using the anisotropic independent impedance method. The results show that anisotropy yields differences up to 32% and 19% of the maximum induced currents and electric field, respectively. Neglecting the permittivity values leads to a decrease of about 72% and 24% of the maximum currents and field, respectively. Implementing the dispersive effects of biological tissues results in a difference of 6% of the maximum currents. The cerebral voxels show limited sensitivity of the induced electric field to changes in conductivity and permittivity, whereas the field varies approximately linearly with frequency. These findings illustrate the importance of including each of the above parameters in the model and confirm the need for accuracy in the applied patient-specific method, which can be used in computer-assisted TMS.

  3. A Comparative Study of Rat Lung Decellularization by Chemical Detergents for Lung Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Hamid Tebyanian

    2017-12-01

    CONCLUSION: Decellularized lung tissue can be used in the laboratory to study various aspects of pulmonary biology and physiology and also, these results can be used in the continued improvement of engineered lung tissue.

  4. Determination and Distribution Study of Pogostone in Rat Tissues by ...

    African Journals Online (AJOL)

    BEH C18 column with acetonitrile-water containing 0.1 % formic acid (55:45, v/v) as the mobile phase, ... Keywords: Ultra-fast liquid chromatography, Tissue distribution, Pogostone, Honokiol, Rats .... sample extraction, storage, and intermittent.

  5. Individualized Human CAD Models: Anthropmetric Morphing and Body Tissue Layering

    Science.gov (United States)

    2014-07-31

    fat thickness may not be uniform and an estimation of this inhomogeneity is integrated into the sub-assemblies of the CAD model. For example, the...Xu X, Endrusick T, Santee W and Kokla M. Simulation of toe thermal responses to cold exposure while wearing protective footwear . SAE 2005

  6. Mechanical properties of brain tissue: characterisation and constitutive modelling

    NARCIS (Netherlands)

    Dommelen, van J.A.W.; Hrapko, M.; Peters, G.W.M.; Kamkin, A.; Kiseleva, I.

    2009-01-01

    The head is often considered as the most critical region of the human body for life-threatening injuries sustained in accidents. In order to develop effective protective measures, a better understanding of the process of injury development in the brain is required. Finite Element (FE) models are

  7. Alveolar ridge augmentation by connective tissue grafting using a pouch method and modified connective tissue technique: A prospective study

    Directory of Open Access Journals (Sweden)

    Ashish Agarwal

    2015-01-01

    Full Text Available Background: Localized alveolar ridge defect may create physiological and pathological problems. Developments in surgical techniques have made it simpler to change the configuration of a ridge to create a more aesthetic and more easily cleansable shape. The purpose of this study was to compare the efficacy of alveolar ridge augmentation using a subepithelial connective tissue graft in pouch and modified connective tissue graft technique. Materials and Methods: In this randomized, double blind, parallel and prospective study, 40 non-smoker individuals with 40 class III alveolar ridge defects in maxillary anterior were randomly divided in two groups. Group I received modified connective tissue graft, while group II were treated with subepithelial connective tissue graft in pouch technique. The defect size was measured in its horizontal and vertical dimension by utilizing a periodontal probe in a stone cast at base line, after 3 months, and 6 months post surgically. Analysis of variance and Bonferroni post-hoc test were used for statistical analysis. A two-tailed P < 0.05 was considered to be statistically significant. Results: Mean values in horizontal width after 6 months were 4.70 ± 0.87 mm, and 4.05 ± 0.89 mm for group I and II, respectively. Regarding vertical heights, obtained mean values were 4.75 ± 0.97 mm and 3.70 ± 0.92 mm for group I and group II, respectively. Conclusion: Within the limitations of this study, connective tissue graft proposed significantly more improvement as compare to connective tissue graft in pouch.

  8. A large-scale study of the ultrawideband microwave dielectric properties of normal breast tissue obtained from reduction surgeries.

    Science.gov (United States)

    Lazebnik, Mariya; McCartney, Leah; Popovic, Dijana; Watkins, Cynthia B; Lindstrom, Mary J; Harter, Josephine; Sewall, Sarah; Magliocco, Anthony; Booske, John H; Okoniewski, Michal; Hagness, Susan C

    2007-05-21

    The efficacy of emerging microwave breast cancer detection and treatment techniques will depend, in part, on the dielectric properties of normal breast tissue. However, knowledge of these properties at microwave frequencies has been limited due to gaps and discrepancies in previously reported small-scale studies. To address these issues, we experimentally characterized the wideband microwave-frequency dielectric properties of a large number of normal breast tissue samples obtained from breast reduction surgeries at the University of Wisconsin and University of Calgary hospitals. The dielectric spectroscopy measurements were conducted from 0.5 to 20 GHz using a precision open-ended coaxial probe. The tissue composition within the probe's sensing region was quantified in terms of percentages of adipose, fibroconnective and glandular tissues. We fit a one-pole Cole-Cole model to the complex permittivity data set obtained for each sample and determined median Cole-Cole parameters for three groups of normal breast tissues, categorized by adipose tissue content (0-30%, 31-84% and 85-100%). Our analysis of the dielectric properties data for 354 tissue samples reveals that there is a large variation in the dielectric properties of normal breast tissue due to substantial tissue heterogeneity. We observed no statistically significant difference between the within-patient and between-patient variability in the dielectric properties.

  9. A large-scale study of the ultrawideband microwave dielectric properties of normal breast tissue obtained from reduction surgeries

    International Nuclear Information System (INIS)

    Lazebnik, Mariya; McCartney, Leah; Popovic, Dijana; Watkins, Cynthia B; Lindstrom, Mary J; Harter, Josephine; Sewall, Sarah; Magliocco, Anthony; Booske, John H; Okoniewski, Michal; Hagness, Susan C

    2007-01-01

    The efficacy of emerging microwave breast cancer detection and treatment techniques will depend, in part, on the dielectric properties of normal breast tissue. However, knowledge of these properties at microwave frequencies has been limited due to gaps and discrepancies in previously reported small-scale studies. To address these issues, we experimentally characterized the wideband microwave-frequency dielectric properties of a large number of normal breast tissue samples obtained from breast reduction surgeries at University of Wisconsin and University of Calgary hospitals. The dielectric spectroscopy measurements were conducted from 0.5 to 20 GHz using a precision open-ended coaxial probe. The tissue composition within the probe's sensing region was quantified in terms of percentages of adipose, fibroconnective and glandular tissues. We fit a one-pole Cole-Cole model to the complex permittivity data set obtained for each sample and determined median Cole-Cole parameters for three groups of normal breast tissues, categorized by adipose tissue content (0-30%, 31-84% and 85-100%). Our analysis of the dielectric properties data for 354 tissue samples reveals that there is a large variation in the dielectric properties of normal breast tissue due to substantial tissue heterogeneity. We observed no statistically significant difference between the within-patient and between-patient variability in the dielectric properties

  10. Ultrasonic characterization of three animal mammary tumors from three-dimensional acoustic tissue models

    Science.gov (United States)

    Mamou, Jonathan M.

    This dissertation investigated how three-dimensional (3D) tissue models can be used to improve ultrasonic tissue characterization (UTC) techniques. Anatomic sites in tissue responsible for ultrasonic scattering are unknown, which limits the potential applications of ultrasound for tumor diagnosis. Accurate 3D models of tumor tissues may help identify the scattering sites. Three mammary tumors were investigated: a rat fibroadenoma, a mouse carcinoma, and a mouse sarcoma. A 3D acoustic tissue model, termed 3D impedance map (3DZM), was carefully constructed from consecutive histologic sections for each tumor. Spectral estimates (scatterer size and acoustic concentration) were obtained from the 3DZMs and compared to the same estimates obtained with ultrasound. Scatterer size estimates for three tumors were found to be similar (within 10%). The 3DZMs were also used to extract tissue-specific scattering models. The scattering models were found to allow clear distinction between the three tumors. This distinction demonstrated that UTC techniques may be helpful for noninvasive clinical tumor diagnosis.

  11. A simulation model for the prediction of tissue:plasma partition coefficients for drug residues in natural casings.

    NARCIS (Netherlands)

    Haritova, A.M.; Fink-Gremmels, J.

    2010-01-01

    Tissue residues arise from the exposure of animals to undesirable substances in animal feed materials and drinking water and to the therapeutic or zootechnical use of veterinary medicinal products. In the framework of this study, an advanced toxicokinetic model was developed to predict the

  12. Comparison of Biocompatibility and Adsorption Properties of Different Plastics for Advanced Microfluidic Cell and Tissue Culture Models

    NARCIS (Netherlands)

    van Midwoud, Paul M.; Janse, Arnout; Merema, M.T.; Groothuis, Geny M. M.; Verpoorte, Elisabeth

    2012-01-01

    Microfluidic technology is providing new routes toward advanced cell and tissue culture models to better understand human biology and disease. Many advanced devices have been made from poly(dimethylsiloxane) (PDMS) to enable experiments, for example, to study drug metabolism by use of precision cut

  13. A hybrid computational model to explore the topological characteristics of epithelial tissues.

    Science.gov (United States)

    González-Valverde, Ismael; García-Aznar, José Manuel

    2017-11-01

    Epithelial tissues show a particular topology where cells resemble a polygon-like shape, but some biological processes can alter this tissue topology. During cell proliferation, mitotic cell dilation deforms the tissue and modifies the tissue topology. Additionally, cells are reorganized in the epithelial layer and these rearrangements also alter the polygon distribution. We present here a computer-based hybrid framework focused on the simulation of epithelial layer dynamics that combines discrete and continuum numerical models. In this framework, we consider topological and mechanical aspects of the epithelial tissue. Individual cells in the tissue are simulated by an off-lattice agent-based model, which keeps the information of each cell. In addition, we model the cell-cell interaction forces and the cell cycle. Otherwise, we simulate the passive mechanical behaviour of the cell monolayer using a material that approximates the mechanical properties of the cell. This continuum approach is solved by the finite element method, which uses a dynamic mesh generated by the triangulation of cell polygons. Forces generated by cell-cell interaction in the agent-based model are also applied on the finite element mesh. Cell movement in the agent-based model is driven by the displacements obtained from the deformed finite element mesh of the continuum mechanical approach. We successfully compare the results of our simulations with some experiments about the topology of proliferating epithelial tissues in Drosophila. Our framework is able to model the emergent behaviour of the cell monolayer that is due to local cell-cell interactions, which have a direct influence on the dynamics of the epithelial tissue. Copyright © 2017 John Wiley & Sons, Ltd.

  14. Pulp tissue in sex determination: A fluorescent microscopic study

    Science.gov (United States)

    Nayar, Amit; Singh, Harkanwal Preet; Leekha, Swati

    2014-01-01

    Aims: To determine and compare the reliability of pulp tissue in determination of sex and to analyze whether caries have any effect on fluorescent body test. Materials and Methods: This study was carried on 50 maxillary and mandibular teeth (25 male teeth and 25 female teeth), which were indicated for extraction. The teeth are categorized into 5 groups, 10 each (5 from males and 5 from females) on the basis of caries progression. The pulp cells are stained with quinacrine hydrochloride and observed with fluorescent microscope for fluorescent body. Gender is determined by identification of Y chromosome fluorescence in dental pulp. Results: Fluorescent bodies were found to be more in sound teeth in males as the caries increase the mean percentage of fluorescent bodies observed decreases in males. We also observed the fluorescent spots in females, and the value of the spot increases in female as the caries progresses, thereby giving false positive results in females. Conclusion: Sex determination by fluorescent staining of the Y chromosome is a reliable technique in teeth with healthy pulps or caries with enamel or up to half way of dentin. Teeth with caries involving pulp cannot be used for sex determination. PMID:25125912

  15. Mathematical Model of Growth Factor Driven Haptotaxis and Proliferation in a Tissue Engineering Scaffold

    KAUST Repository

    Pohlmeyer, J. V.

    2013-01-29

    Motivated by experimental work (Miller et al. in Biomaterials 27(10):2213-2221, 2006, 32(11):2775-2785, 2011) we investigate the effect of growth factor driven haptotaxis and proliferation in a perfusion tissue engineering bioreactor, in which nutrient-rich culture medium is perfused through a 2D porous scaffold impregnated with growth factor and seeded with cells. We model these processes on the timescale of cell proliferation, which typically is of the order of days. While a quantitative representation of these phenomena requires more experimental data than is yet available, qualitative agreement with preliminary experimental studies (Miller et al. in Biomaterials 27(10):2213-2221, 2006) is obtained, and appears promising. The ultimate goal of such modeling is to ascertain initial conditions (growth factor distribution, initial cell seeding, etc.) that will lead to a final desired outcome. © 2013 Society for Mathematical Biology.

  16. Unstable spiral waves and local Euclidean symmetry in a model of cardiac tissue

    International Nuclear Information System (INIS)

    Marcotte, Christopher D.; Grigoriev, Roman O.

    2015-01-01

    This paper investigates the properties of unstable single-spiral wave solutions arising in the Karma model of two-dimensional cardiac tissue. In particular, we discuss how such solutions can be computed numerically on domains of arbitrary shape and study how their stability, rotational frequency, and spatial drift depend on the size of the domain as well as the position of the spiral core with respect to the boundaries. We also discuss how the breaking of local Euclidean symmetry due to finite size effects as well as the spatial discretization of the model is reflected in the structure and dynamics of spiral waves. This analysis allows identification of a self-sustaining process responsible for maintaining the state of spiral chaos featuring multiple interacting spirals

  17. Unstable spiral waves and local Euclidean symmetry in a model of cardiac tissue.

    Science.gov (United States)

    Marcotte, Christopher D; Grigoriev, Roman O

    2015-06-01

    This paper investigates the properties of unstable single-spiral wave solutions arising in the Karma model of two-dimensional cardiac tissue. In particular, we discuss how such solutions can be computed numerically on domains of arbitrary shape and study how their stability, rotational frequency, and spatial drift depend on the size of the domain as well as the position of the spiral core with respect to the boundaries. We also discuss how the breaking of local Euclidean symmetry due to finite size effects as well as the spatial discretization of the model is reflected in the structure and dynamics of spiral waves. This analysis allows identification of a self-sustaining process responsible for maintaining the state of spiral chaos featuring multiple interacting spirals.

  18. Experimental study of apoptosis in the prostate tissue following castration

    Directory of Open Access Journals (Sweden)

    Y Doustar

    2008-02-01

    Full Text Available The Prostate gland is one of the accessory reproductive glands with important physiological functions necessary for successful reproduction. This gland depends on the presence of sex hormones including androgens for its natural function and normal growth and development. So in the case of hyperplasia, hypertrophy or other prostatic disease the most successful and efficient method of treatment is androgenic control that in some cases is unavoidable. The purpose of this study was to investigate the effects of androgenic depletion states by means of castration on the induction of apoptosis in the epithelial glandular cells of the prostate tissue. Two groups of male dogs each containing 5 animals per group were used in this study. The dogs were under observation for 1 month to detect any possible diseases or disorders. After this period the dogs in the treatment group underwent open castration to decrease the levels of the androgenic hormones in the blood while the dogs in the control group were left intact. One week after surgery, the prostate glands of control and treatment animals were collected and used to prepare microscopic sections. The sections were evaluated following staining with TUNEL (TerminaldeoxyNucleotidyl (dUTP transferase-mediated End Labeling and H&E methods. The Mann – Whitney U test was used for statistical analysis. Histopathological studies in the treatment group revealed the presence of various forms of apoptotic cells in the glandular epithelium. Average number of apoptotic cells in ten microscopic fields were significantly higher in the treatment group compared with the control group (p

  19. Potassium titanyl phosphate laser tissue ablation: development and experimental validation of a new numerical model.

    Science.gov (United States)

    Elkhalil, Hossam; Akkin, Taner; Pearce, John; Bischof, John

    2012-10-01

    The photoselective vaporization of prostate (PVP) green light (532 nm) laser is increasingly being used as an alternative to the transurethral resection of prostate (TURP) for treatment of benign prostatic hyperplasia (BPH) in older patients and those who are poor surgical candidates. In order to achieve the goals of increased tissue removal volume (i.e., "ablation" in the engineering sense) and reduced collateral thermal damage during the PVP green light treatment, a two dimensional computational model for laser tissue ablation based on available parameters in the literature has been developed and compared to experiments. The model is based on the control volume finite difference and the enthalpy method with a mechanistically defined energy necessary to ablate (i.e., physically remove) a volume of tissue (i.e., energy of ablation E(ab)). The model was able to capture the general trends experimentally observed in terms of ablation and coagulation areas, their ratio (therapeutic index (TI)), and the ablation rate (AR) (mm(3)/s). The model and experiment were in good agreement at a smaller working distance (WD) (distance from the tissue in mm) and a larger scanning speed (SS) (laser scan speed in mm/s). However, the model and experiment deviated somewhat with a larger WD and a smaller SS; this is most likely due to optical shielding and heat diffusion in the laser scanning direction, which are neglected in the model. This model is a useful first step in the mechanistic prediction of PVP based BPH laser tissue ablation. Future modeling efforts should focus on optical shielding, heat diffusion in the laser scanning direction (i.e., including 3D effects), convective heat losses at the tissue boundary, and the dynamic optical, thermal, and coagulation properties of BPH tissue.

  20. Thermal-mechanical deformation modelling of soft tissues for thermal ablation.

    Science.gov (United States)

    Li, Xin; Zhong, Yongmin; Jazar, Reza; Subic, Aleksandar

    2014-01-01

    Modeling of thermal-induced mechanical behaviors of soft tissues is of great importance for thermal ablation. This paper presents a method by integrating the heating process with thermal-induced mechanical deformations of soft tissues for simulation and analysis of the thermal ablation process. This method combines bio-heat transfer theories, constitutive elastic material law under thermal loads as well as non-rigid motion dynamics to predict and analyze thermal-mechanical deformations of soft tissues. The 3D governing equations of thermal-mechanical soft tissue deformation are discretized by using the finite difference scheme and are subsequently solved by numerical algorithms. Experimental results show that the proposed method can effectively predict the thermal-induced mechanical behaviors of soft tissues, and can be used for the thermal ablation therapy to effectively control the delivered heat energy for cancer treatment.

  1. Active tension network model suggests an exotic mechanical state realized in epithelial tissues

    Science.gov (United States)

    Noll, Nicholas; Mani, Madhav; Heemskerk, Idse; Streichan, Sebastian J.; Shraiman, Boris I.

    2017-12-01

    Mechanical interactions play a crucial role in epithelial morphogenesis, yet understanding the complex mechanisms through which stress and deformation affect cell behaviour remains an open problem. Here we formulate and analyse the active tension network (ATN) model, which assumes that the mechanical balance of cells within a tissue is dominated by cortical tension and introduces tension-dependent active remodelling of the cortex. We find that ATNs exhibit unusual mechanical properties. Specifically, an ATN behaves as a fluid at short times, but at long times supports external tension like a solid. Furthermore, an ATN has an extensively degenerate equilibrium mechanical state associated with a discrete conformal--`isogonal'--deformation of cells. The ATN model predicts a constraint on equilibrium cell geometries, which we demonstrate to approximately hold in certain epithelial tissues. We further show that isogonal modes are observed in the fruit fly embryo, accounting for the striking variability of apical areas of ventral cells and helping understand the early phase of gastrulation. Living matter realizes new and exotic mechanical states, the study of which helps to understand biological phenomena.

  2. Modeling the impact of scaffold architecture and mechanical loading on collagen turnover in engineered cardiovascular tissues.

    Science.gov (United States)

    Argento, G; de Jonge, N; Söntjens, S H M; Oomens, C W J; Bouten, C V C; Baaijens, F P T

    2015-06-01

    The anisotropic collagen architecture of an engineered cardiovascular tissue has a major impact on its in vivo mechanical performance. This evolving collagen architecture is determined by initial scaffold microstructure and mechanical loading. Here, we developed and validated a theoretical and computational microscale model to quantitatively understand the interplay between scaffold architecture and mechanical loading on collagen synthesis and degradation. Using input from experimental studies, we hypothesize that both the microstructure of the scaffold and the loading conditions influence collagen turnover. The evaluation of the mechanical and topological properties of in vitro engineered constructs reveals that the formation of extracellular matrix layers on top of the scaffold surface influences the mechanical anisotropy on the construct. Results show that the microscale model can successfully capture the collagen arrangement between the fibers of an electrospun scaffold under static and cyclic loading conditions. Contact guidance by the scaffold, and not applied load, dominates the collagen architecture. Therefore, when the collagen grows inside the pores of the scaffold, pronounced scaffold anisotropy guarantees the development of a construct that mimics the mechanical anisotropy of the native cardiovascular tissue.

  3. Non-invasive characterization of normal and pathological tissues through dynamic infrared imaging in the hamster cheek pouch oral cancer model

    Science.gov (United States)

    Herrera, María. S.; Monti Hughes, Andrea; Salva, Natalia; Padra, Claudio; Schwint, Amanda; Santa Cruz, Gustavo A.

    2017-05-01

    Biomedical infrared thermography, a non-invasive and functional imaging method, provides information on the normal and abnormal status and response of tissues in terms of spatial and temporal variations in body infrared radiance. It is especially attractive in cancer research due to the hypervascular and hypermetabolic activity of solid tumors. Moreover, healthy tissues like skin or mucosa exposed to radiation can be examined since inflammation, changes in water content, exudation, desquamation, erosion and necrosis, between others, are factors that modify their thermal properties. In this work we performed Dynamic Infrared Imaging (DIRI) to contribute to the understanding and evaluation of normal tissue, tumor and precancerous tissue response and radiotoxicity in an in vivo model, the hamster cheek pouch, exposed to Boron Neutron Capture Therapy. In this study, we particularly focused on the observation of temperature changes under forced transient conditions associated with mass moisture transfer in the tissue-air interface, in each tissue with or without treatment. We proposed a simple mathematical procedure that considerers the heat transfer from tissue to ambient through convection and evaporation to model the transient (exponential decay o recover) thermal study. The data was fitted to determined the characteristic decay and recovery time constants of the temperature as a function of time. Also this model allowed to explore the mass flux of moisture, as a degree of evaporation occurring on the tissue surface. Tissue thermal responses under provocation tests could be used as a non-invasive method to characterize tissue physiology.

  4. From Cell to Tissue Properties-Modeling Skin Electroporation With Pore and Local Transport Region Formation.

    Science.gov (United States)

    Dermol-Cerne, Janja; Miklavcic, Damijan

    2018-02-01

    Current models of tissue electroporation either describe tissue with its bulk properties or include cell level properties, but model only a few cells of simple shapes in low-volume fractions or are in two dimensions. We constructed a three-dimensional model of realistically shaped cells in realistic volume fractions. By using a 'unit cell' model, the equivalent dielectric properties of whole tissue could be calculated. We calculated the dielectric properties of electroporated skin. We modeled electroporation of single cells by pore formation on keratinocytes and on the papillary dermis which gave dielectric properties of the electroporated epidermis and papillary dermis. During skin electroporation, local transport regions are formed in the stratum corneum. We modeled local transport regions and increase in their radii or density which affected the dielectric properties of the stratum corneum. The final model of skin electroporation accurately describes measured electric current and voltage drop on the skin during electroporation with long low-voltage pulses. The model also accurately describes voltage drop on the skin during electroporation with short high-voltage pulses. However, our results indicate that during application of short high-voltage pulses additional processes may occur which increase the electric current. Our model connects the processes occurring at the level of cell membranes (pore formation), at the level of a skin layer (formation of local transport region in the stratum corneum) with the tissue (skin layers) and even level of organs (skin). Using a similar approach, electroporation of any tissue can be modeled, if the morphology of the tissue is known.

  5. Modelling radiation fields of ion beams in tissue-like materials

    International Nuclear Information System (INIS)

    Burigo, Lucas Norberto

    2014-01-01

    Fast nuclei are ionizing radiation which can cause deleterious effects to irradiated cells. The modelling of the interactions of such ions with matter and the related effects are very important to physics, radiobiology, medicine and space science and technology. A powerful method to study the interactions of ionizing radiation with biological systems was developed in the field of microdosimetry. Microdosimetry spectra characterize the energy deposition to objects of cellular size, i.e., a few micrometers. In the present thesis the interaction of ions with tissue-like media was investigated using the Monte Carlo model for Heavy-Ion Therapy (MCHIT) developed at the Frankfurt Institute for Advanced Studies. MCHIT is a Geant4-based application intended to benchmark the physical models of Geant4 and investigate the physical properties of therapeutic ion beams. We have implemented new features in MCHIT in order to calculate microdosimetric quantities characterizing the radiation fields of accelerated nucleons and nuclei. The results of our Monte Carlo simulations were compared with recent experimental microdosimetry data. In addition to microdosimetry calculations with MCHIT, we also investigated the biological properties of ion beams, e.g. their relative biological effectiveness (RBE), by means of the modified Microdosimetric-Kinetic model (MKM). The MKM uses microdosimetry spectra in describing cell response to radiation. MCHIT+MKM allowed us to study the physical and biological properties of ion beams. The main results of the thesis are as follows: MCHIT is able to describe the spatial distribution of the physical dose in tissue-like media and microdosimetry spectra for ions with energies relevant to space research and ion-beam cancer therapy; MCHIT+MKM predicts a reduction of the biological effectiveness of ions propagating in extended medium due to nuclear fragmentation reactions; We predicted favourable biological dose-depth profiles for monoenergetic helium and

  6. Positron range in tissue-equivalent materials: experimental microPET studies

    Science.gov (United States)

    Alva-Sánchez, H.; Quintana-Bautista, C.; Martínez-Dávalos, A.; Ávila-Rodríguez, M. A.; Rodríguez-Villafuerte, M.

    2016-09-01

    In this work an experimental investigation was carried out to study the effect that positron range has over positron emission tomography (PET) scans through measurements of the line spread function (LSF) in tissue-equivalent materials. Line-sources consisted of thin capillary tubes filled with 18F, 13N or 68Ga water-solution inserted along the axis of symmetry of cylindrical phantoms constructed with the tissue-equivalent materials: lung (inhale and exhale), adipose tissue, solid water, trabecular and cortical bone. PET scans were performed with a commercial small-animal PET scanner and image reconstruction was carried out with filtered-backprojection. Line-source distributions were analyzed using radial profiles taken on axial slices from which the spatial resolution was determined through the full-width at half-maximum, tenth-maximum, twentieth-maximum and fiftieth-maximum. A double-Gaussian model of the LSFs was used to fit experimental data which can be incorporated into iterative reconstruction methods. In addition, the maximum activity concentration in the line-sources was determined from reconstructed images and compared to the known values for each case. The experimental data indicates that positron range in different materials has a strong effect on both spatial resolution and activity concentration quantification in PET scans. Consequently, extra care should be taken when computing standard-uptake values in PET scans, in particular when the radiopharmaceutical is taken up by different tissues in the body, and more even so with high-energy positron emitters.

  7. Consent to tissue banking for research: qualitative study and recommendations.

    Science.gov (United States)

    Soto, Carmen; Tarrant, Carolyn; Pritchard-Jones, Kathy; Dixon-Woods, Mary

    2012-07-01

    To explore how families of children with cancer experience giving consent for tissue banking and to produce recommendations on good practice. 79 participants from 42 families (41 mothers, 18 fathers, 20 children and young people with cancer) took part in semistructured interviews to explore their experiences of being approached for consent to tissue banking. Tertiary care facilities for childhood cancer. Families are generally supportive of tissue banking, although they report that it may be difficult for them to consider all the implications when asked for consent. They typically do not want detailed information when consent is sought close to diagnosis, preferring to see tissue banking as part of routine practice. Families often recognise that their consent may not be fully informed, but are content to give consent based on their understanding at the time. Some may want a chance to go over the information and revisit their decision when things have settled. Families' views can inform practical recommendations for optimising the experience of consent for tissue banking. Current guidelines for obtaining consent should be revisited to take account of families' preferences.

  8. Modeling microelectrode biosensors: free-flow calibration can substantially underestimate tissue concentrations.

    Science.gov (United States)

    Newton, Adam J H; Wall, Mark J; Richardson, Magnus J E

    2017-03-01

    Microelectrode amperometric biosensors are widely used to measure concentrations of analytes in solution and tissue including acetylcholine, adenosine, glucose, and glutamate. A great deal of experimental and modeling effort has been directed at quantifying the response of the biosensors themselves; however, the influence that the macroscopic tissue environment has on biosensor response has not been subjected to the same level of scrutiny. Here we identify an important issue in the way microelectrode biosensors are calibrated that is likely to have led to underestimations of analyte tissue concentrations. Concentration in tissue is typically determined by comparing the biosensor signal to that measured in free-flow calibration conditions. In a free-flow environment the concentration of the analyte at the outer surface of the biosensor can be considered constant. However, in tissue the analyte reaches the biosensor surface by diffusion through the extracellular space. Because the enzymes in the biosensor break down the analyte, a density gradient is set up resulting in a significantly lower concentration of analyte near the biosensor surface. This effect is compounded by the diminished volume fraction (porosity) and reduction in the diffusion coefficient due to obstructions (tortuosity) in tissue. We demonstrate this effect through modeling and experimentally verify our predictions in diffusive environments. NEW & NOTEWORTHY Microelectrode biosensors are typically calibrated in a free-flow environment where the concentrations at the biosensor surface are constant. However, when in tissue, the analyte reaches the biosensor via diffusion and so analyte breakdown by the biosensor results in a concentration gradient and consequently a lower concentration around the biosensor. This effect means that naive free-flow calibration will underestimate tissue concentration. We develop mathematical models to better quantify the discrepancy between the calibration and tissue

  9. Quantitative methods for reconstructing tissue biomechanical properties in optical coherence elastography: a comparison study

    International Nuclear Information System (INIS)

    Han, Zhaolong; Li, Jiasong; Singh, Manmohan; Wu, Chen; Liu, Chih-hao; Wang, Shang; Idugboe, Rita; Raghunathan, Raksha; Sudheendran, Narendran; Larin, Kirill V; Aglyamov, Salavat R; Twa, Michael D

    2015-01-01

    We present a systematic analysis of the accuracy of five different methods for extracting the biomechanical properties of soft samples using optical coherence elastography (OCE). OCE is an emerging noninvasive technique, which allows assessment of biomechanical properties of tissues with micrometer spatial resolution. However, in order to accurately extract biomechanical properties from OCE measurements, application of a proper mechanical model is required. In this study, we utilize tissue-mimicking phantoms with controlled elastic properties and investigate the feasibilities of four available methods for reconstructing elasticity (Young’s modulus) based on OCE measurements of an air-pulse induced elastic wave. The approaches are based on the shear wave equation (SWE), the surface wave equation (SuWE), Rayleigh-Lamb frequency equation (RLFE), and finite element method (FEM), Elasticity values were compared with uniaxial mechanical testing. The results show that the RLFE and the FEM are more robust in quantitatively assessing elasticity than the other simplified models. This study provides a foundation and reference for reconstructing the biomechanical properties of tissues from OCE data, which is important for the further development of noninvasive elastography methods. (paper)

  10. Absorption and scattering coefficient dependence of laser-Doppler flowmetry models for large tissue volumes

    International Nuclear Information System (INIS)

    Binzoni, T; Leung, T S; Ruefenacht, D; Delpy, D T

    2006-01-01

    Based on quasi-elastic scattering theory (and random walk on a lattice approach), a model of laser-Doppler flowmetry (LDF) has been derived which can be applied to measurements in large tissue volumes (e.g. when the interoptode distance is >30 mm). The model holds for a semi-infinite medium and takes into account the transport-corrected scattering coefficient and the absorption coefficient of the tissue, and the scattering coefficient of the red blood cells. The model holds for anisotropic scattering and for multiple scattering of the photons by the moving scatterers of finite size. In particular, it has also been possible to take into account the simultaneous presence of both Brownian and pure translational movements. An analytical and simplified version of the model has also been derived and its validity investigated, for the case of measurements in human skeletal muscle tissue. It is shown that at large optode spacing it is possible to use the simplified model, taking into account only a 'mean' light pathlength, to predict the blood flow related parameters. It is also demonstrated that the 'classical' blood volume parameter, derived from LDF instruments, may not represent the actual blood volume variations when the investigated tissue volume is large. The simplified model does not need knowledge of the tissue optical parameters and thus should allow the development of very simple and cost-effective LDF hardware

  11. Connective tissue graft as a biological barrier for guided tissue regeneration in intrabony defects: a histological study in dogs.

    Science.gov (United States)

    Ribeiro, Fernando Salimon; Pontes, Ana Emília Farias; Zuza, Elizangela Partata; da Silva, Vanessa Camila; Lia, Raphael Carlos Comelli; Marcantonio Junior, Elcio

    2015-06-01

    The use of the autogenous periosteal graft as biological barrier has been proposed for periodontal regeneration. The aim of this study was to evaluate the histometric findings of the subepithelial connective tissue graft as barrier in intrabony defects compared to a bioabsorbable membrane. Three-walled intrabony defects were created surgically in the mesial aspect of the right and left maxillary canines in five healthy mongrel dogs. The defects were chronified, and two types of barriers were randomly carried out for guided tissue regeneration in a split-mouth design: the test group with a subepithelial connective tissue graft and the control group with a bioabsorbable membrane. The specimens were processed for histometric analyses of the epithelium (E), connective tissue (CT), newly formed cementum (NC), new bone (NB), and total newly formed tissues (NFT). The test side showed smaller mean of NC (3.6 ± 1.2), NB (2.1 ± 0.7), and NFT (7.7 ± 0.8) than the control group (NC 7.3 ± 0.5; NB 5.3 ± 1.3; NFT 10.1 ± 2.2; P  0.05) and CT (test 2.5 ± 1.1; control 2.0 ± 0.5; P > 0.05) between groups. The bioabsorbable membrane was more effective in maintaining the space for periodontal regeneration than periosteal connective graft when used as barrier. The bioabsorbable membrane showed more favorable regenerative results in intrabony defects in dogs than the subepithelial connective tissue graft as biological barrier.

  12. Numerical modelling of tissue-equivalent proportional counters

    International Nuclear Information System (INIS)

    Segur, P.; Colautti, P.

    1995-01-01

    In this paper a survey is given of the various numerical techniques employed to study the transport of ionising particles inside a TEPC. The first part is devoted to the description of the general concept of particle transport calculations. Thereafter, the different methods available to study transport phenomena and energy deposition in the sensitive volume and in counter walls are described. Finally, the basic ionisation mechanisms which may occur in a counter are described, and the non-equilibrium phenomena which play an important role mainly for counters that are to be used in measurements at the nanodosemeter level are studied. (author)

  13. Three-dimensional hydrogel cell culture systems for modeling neural tissue

    Science.gov (United States)

    Frampton, John

    Two-dimensional (2-D) neural cell culture systems have served as physiological models for understanding the cellular and molecular events that underlie responses to physical and chemical stimuli, control sensory and motor function, and lead to the development of neurological diseases. However, the development of three-dimensional (3-D) cell culture systems will be essential for the advancement of experimental research in a variety of fields including tissue engineering, chemical transport and delivery, cell growth, and cell-cell communication. In 3-D cell culture, cells are provided with an environment similar to tissue, in which they are surrounded on all sides by other cells, structural molecules and adhesion ligands. Cells grown in 3-D culture systems display morphologies and functions more similar to those observed in vivo, and can be cultured in such a way as to recapitulate the structural organization and biological properties of tissue. This thesis describes a hydrogel-based culture system, capable of supporting the growth and function of several neural cell types in 3-D. Alginate hydrogels were characterized in terms of their biomechanical and biochemical properties and were functionalized by covalent attachment of whole proteins and peptide epitopes. Methods were developed for rapid cross-linking of alginate hydrogels, thus permitting the incorporation of cells into 3-D scaffolds without adversely affecting cell viability or function. A variety of neural cell types were tested including astrocytes, microglia, and neurons. Cells remained viable and functional for longer than two weeks in culture and displayed process outgrowth in 3-D. Cell constructs were created that varied in cell density, type and organization, providing experimental flexibility for studying cell interactions and behavior. In one set of experiments, 3-D glial-endothelial cell co-cultures were used to model blood-brain barrier (BBB) structure and function. This co-culture system was

  14. Bubbly vertex dynamics: A dynamical and geometrical model for epithelial tissues with curved cell shapes

    Science.gov (United States)

    Ishimoto, Yukitaka; Morishita, Yoshihiro

    2014-11-01

    In order to describe two-dimensionally packed cells in epithelial tissues both mathematically and physically, there have been developed several sorts of geometrical models, such as the vertex model, the finite element model, the cell-centered model, and the cellular Potts model. So far, in any case, pressures have not neatly been dealt with and the curvatures of the cell boundaries have been even omitted through their approximations. We focus on these quantities and formulate them in the vertex model. Thus, a model with the curvatures is constructed, and its algorithm for simulation is provided. The possible extensions and applications of this model are also discussed.

  15. Nuclear analytical methods for trace element studies in calcified tissues

    International Nuclear Information System (INIS)

    Chaudhry, M.A.; Chaudhry, M.N.

    2001-01-01

    Full text: Various nuclear analytical methods have been developed and applied to determine the elemental composition of calcified tissues (teeth and bones). Fluorine was determined by prompt gamma activation analysis through the 19 F(p,ag) 16 O reaction. Carbon was measured by activation analysis with He-3 ions, and the technique of Proton-Induced X-ray Emission (PIXE) was applied to simultaneously determine Ca, P, and trace elements in well-documented teeth. Dental hard tissues, enamel, dentine, cement, and their junctions, as well as different parts of the same tissue, were examined separately. Furthermore, using a Proton Microprobe, we measured the surface distribution of F and other elements on and around carious lesions on the enamel. The depth profiles of F, and other elements, were also measured right up to the amelodentin junction

  16. A Study of Acute and Chronic Tissue Changes in Surgical and Traumatically-Induced Experimental Models of Knee Joint Injury Using Magnetic Resonance Imaging and Micro-Computed Tomography

    Science.gov (United States)

    Fischenich, Kristine M.; Pauly, Hannah M.; Button, Keith D.; Fajardo, Ryan S.; DeCamp, Charles E.; Haut, Roger C.; Haut Donahue, Tammy L.

    2016-01-01

    Objective The objective of this study was to monitor the progression of joint damage in two animal models of knee joint trauma using two non-invasive, clinically available imaging modalities. Methods A 3-T clinical magnet and micro-computed tomography (mCT) was used to document changes immediately following injury (acute) and post-injury (chronic) at time points of 4, 8, or 12 weeks. Joint damage was recorded at dissection and compared to the chronic magnetic resonance imaging (MRI) record. Fifteen Flemish Giant rabbits were subjected to a single tibiofemoral compressive impact (ACLF), and 18 underwent a combination of anterior cruciate ligament (ACL) and meniscal transection (mACLT). Results All ACLF animals experienced ACL rupture, and 13 also experienced acute meniscal damage. All ACLF and mACLT animals showed meniscal and articular cartilage damages at dissection. Meniscal damage was documented as early as 4 weeks and worsened in 87% of the ACLF animals and 71% of the mACLT animals. Acute cartilage damage also developed further and increased in occurrence with time in both models. A progressive decrease in bone quantity and quality was documented in both models. The MRI data closely aligned with dissection notes suggesting this clinical tool may be a non-invasive method for documenting joint damage in lapine models of knee joint trauma. Conclusions The study investigates the acute to chronic progression of meniscal and cartilage damage at various time points, and chronic changes to the underlying bone in two models of posttraumatic osteoarthritis (PTOA), and highlights the dependency of the model on the location, type, and progression of damage over time. PMID:27756698

  17. Nonviral transfection of adipose tissue stromal cells: an experimental study.

    Science.gov (United States)

    Lopatina, T V; Kalinina, N I; Parfyonova, E V

    2009-04-01

    Delivery of plasmid DNA and interfering RNA into adipose tissue stromal cells was carried out by the methods of lipofection, calcium phosphate method, and by electroporation. The percent of transfected cells after delivery of plasmid DNA by the calcium phosphate method and lipofection was 0 and 15%, respectively, vs. more than 50% after electroporation. Similar results were obtained for delivery of short-strand RNA into cells. These data indicate that electroporation is the most effective method of nonviral transfection of adipose tissue stromal cells.

  18. Contribution of ultrasound forward scattering to tissue structure study

    International Nuclear Information System (INIS)

    Edee, M.K.

    1987-12-01

    In this paper, we show how to get useful information of tissue structure by merely interpreting some experimental graphs such as energy spectral density and autocorrelation function of an ultrasonic beam travelling through tissues. To support these interpretations, we needed just some well-known theorems rather than heavy and complicated mathematical equations, so we measured the dimensions of scatterers within specimens by using the graphical representation of autocorrelation function. We related these measurements to the scattered peaks which appear in energy density spectrum. The values we found were equal to those obtained from biologists within ∼ 15%. (author) 26 refs, 6 figs, tabs

  19. Magnetization transfer analysis of cartilage repair tissue: a preliminary study

    International Nuclear Information System (INIS)

    Palmieri, F.; Keyzer, F. de; Maes, F.; Breuseghem, I. van

    2006-01-01

    To evaluate the magnetization transfer ratio (MTR) after two different cartilage repair procedures, and to compare these data with the MTR of normal cartilage. Twenty-seven patients with a proven cartilage defect were recruited: 13 were treated with autologous chondrocyte implantation (ACI) and 14 were treated with the microfracture technique (MFR). All patients underwent MRI examinations with MT-sequences before the surgical treatment, after 12 months (26 patients) and after 24 months (11 patients). Eleven patients received a complete follow-up study at all three time points (five of the ACI group and six of the MFR group). All images were transferred to a workstation to calculate MTR images. For every MT image set, different ROIs were delineated by two radiologists. Means were calculated per ROI type in the different time frames and in both groups of cartilage repair. The data were analyzed with unpaired t- and ANOVA tests, and by calculating Pearson's correlation coefficient. No significant differences were found in the MTR of fatty bone marrow, muscle and normal cartilage in the different time frames. There was a significant but small difference between the MTR of normal cartilage and the cartilage repair area after 12 months for both procedures. After 24 months, the MTR of ACI repaired cartilage (0.31±0.07) was not significantly different from normal cartilage MTR (0.34±0.05). The MTR of MFR repaired cartilage (0.28±0.02), still showed a significant difference from normal cartilage. The differences between damaged and repaired cartilage MTR are too small to enable MT-imaging to be a useful tool for postoperative follow-up of cartilage repair procedures. There is, however, an evolution towards normal MTR-values in the cartilage repair tissue (especially after ACI repair). (orig.)

  20. Advanced cell culture technology for generation of in vivo-like tissue models

    OpenAIRE

    Przyborski, Stefan

    2017-01-01

    Human tissues are mostly composed of different cell types, that are often highly organised in relation to each other. Often cells are arranged in distinct layers that enable signalling and cell-to-cell interactions. Here we describe the application of scaffold-based technology, that can be used to create advanced organotypic 3D models of various tissue types that more closely resemble in vivo-like conditions (Knight et al., 2011). The scaffold comprises a highly porous polystyrene material, e...

  1. Multivariate Normal Tissue Complication Probability Modeling of Heart Valve Dysfunction in Hodgkin Lymphoma Survivors

    International Nuclear Information System (INIS)

    Cella, Laura; Liuzzi, Raffaele; Conson, Manuel; D’Avino, Vittoria; Salvatore, Marco; Pacelli, Roberto

    2013-01-01

    Purpose: To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced asymptomatic heart valvular defects (RVD). Methods and Materials: Fifty-six patients treated with sequential chemoradiation therapy for Hodgkin lymphoma (HL) were retrospectively reviewed for RVD events. Clinical information along with whole heart, cardiac chambers, and lung dose distribution parameters was collected, and the correlations to RVD were analyzed by means of Spearman's rank correlation coefficient (Rs). For the selection of the model order and parameters for NTCP modeling, a multivariate logistic regression method using resampling techniques (bootstrapping) was applied. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Results: When we analyzed the whole heart, a 3-variable NTCP model including the maximum dose, whole heart volume, and lung volume was shown to be the optimal predictive model for RVD (Rs = 0.573, P<.001, AUC = 0.83). When we analyzed the cardiac chambers individually, for the left atrium and for the left ventricle, an NTCP model based on 3 variables including the percentage volume exceeding 30 Gy (V30), cardiac chamber volume, and lung volume was selected as the most predictive model (Rs = 0.539, P<.001, AUC = 0.83; and Rs = 0.557, P<.001, AUC = 0.82, respectively). The NTCP values increase as heart maximum dose or cardiac chambers V30 increase. They also increase with larger volumes of the heart or cardiac chambers and decrease when lung volume is larger. Conclusions: We propose logistic NTCP models for RVD considering not only heart irradiation dose but also the combined effects of lung and heart volumes. Our study establishes the statistical evidence of the indirect effect of lung size on radio-induced heart toxicity

  2. [Research progress on real-time deformable models of soft tissues for surgery simulation].

    Science.gov (United States)

    Xu, Shaoping; Liu, Xiaoping; Zhang, Hua; Luo, Jie

    2010-04-01

    Biological tissues generally exhibit nonlinearity, anisotropy, quasi-incompressibility and viscoelasticity about material properties. Simulating the behaviour of elastic objects in real time is one of the current objectives of virtual surgery simulation which is still a challenge for researchers to accurately depict the behaviour of human tissues. In this paper, we present a classification of the different deformable models that have been developed. We present the advantages and disadvantages of each one. Finally, we make a comparison of deformable models and perform an evaluation of the state of the art and the future of deformable models.

  3. Modelling organs, tissues, cells and devices using Matlab and Comsol multiphysics

    CERN Document Server

    Dokos, Socrates

    2017-01-01

    This book presents a theoretical and practical overview of computational modeling in bioengineering, focusing on a range of applications including electrical stimulation of neural and cardiac tissue, implantable drug delivery, cancer therapy, biomechanics, cardiovascular dynamics, as well as fluid-structure interaction for modelling of organs, tissues, cells and devices. It covers the basic principles of modeling and simulation with ordinary and partial differential equations using MATLAB and COMSOL Multiphysics numerical software. The target audience primarily comprises postgraduate students and researchers, but the book may also be beneficial for practitioners in the medical device industry.

  4. Computational Modeling for Enhancing Soft Tissue Image Guided Surgery: An Application in Neurosurgery.

    Science.gov (United States)

    Miga, Michael I

    2016-01-01

    With the recent advances in computing, the opportunities to translate computational models to more integrated roles in patient treatment are expanding at an exciting rate. One area of considerable development has been directed towards correcting soft tissue deformation within image guided neurosurgery applications. This review captures the efforts that have been undertaken towards enhancing neuronavigation by the integration of soft tissue biomechanical models, imaging and sensing technologies, and algorithmic developments. In addition, the review speaks to the evolving role of modeling frameworks within surgery and concludes with some future directions beyond neurosurgical applications.

  5. Complete solubilization of formalin-fixed, paraffin-embedded tissue may improve proteomic studies.

    Science.gov (United States)

    Shi, Shan-Rong; Taylor, Clive R; Fowler, Carol B; Mason, Jeffrey T

    2013-04-01

    Tissue-based proteomic approaches (tissue proteomics) are essential for discovering and evaluating biomarkers for personalized medicine. In any proteomics study, the most critical issue is sample extraction and preparation. This problem is especially difficult when recovering proteins from formalin-fixed, paraffin-embedded (FFPE) tissue sections. However, improving and standardizing protein extraction from FFPE tissue is a critical need because of the millions of archival FFPE tissues available in tissue banks worldwide. Recent progress in the application of heat-induced antigen retrieval principles for protein extraction from FFPE tissue has resulted in a number of published FFPE tissue proteomics studies. However, there is currently no consensus on the optimal protocol for protein extraction from FFPE tissue or accepted standards for quantitative evaluation of the extracts. Standardization is critical to ensure the accurate evaluation of FFPE protein extracts by proteomic methods such as reverse phase protein arrays, which is now in clinical use. In our view, complete solubilization of FFPE tissue samples is the best way to achieve the goal of standardizing the recovery of proteins from FFPE tissues. However, further studies are recommended to develop standardized protein extraction methods to ensure quantitative and qualitative reproducibility in the recovery of proteins from FFPE tissues. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. A discrete fibre dispersion method for excluding fibres under compression in the modelling of fibrous tissues.

    Science.gov (United States)

    Li, Kewei; Ogden, Ray W; Holzapfel, Gerhard A

    2018-01-01

    Recently, micro-sphere-based methods derived from the angular integration approach have been used for excluding fibres under compression in the modelling of soft biological tissues. However, recent studies have revealed that many of the widely used numerical integration schemes over the unit sphere are inaccurate for large deformation problems even without excluding fibres under compression. Thus, in this study, we propose a discrete fibre dispersion model based on a systematic method for discretizing a unit hemisphere into a finite number of elementary areas, such as spherical triangles. Over each elementary area, we define a representative fibre direction and a discrete fibre density. Then, the strain energy of all the fibres distributed over each elementary area is approximated based on the deformation of the representative fibre direction weighted by the corresponding discrete fibre density. A summation of fibre contributions over all elementary areas then yields the resultant fibre strain energy. This treatment allows us to exclude fibres under compression in a discrete manner by evaluating the tension-compression status of the representative fibre directions only. We have implemented this model in a finite-element programme and illustrate it with three representative examples, including simple tension and simple shear of a unit cube, and non-homogeneous uniaxial extension of a rectangular strip. The results of all three examples are consistent and accurate compared with the previously developed continuous fibre dispersion model, and that is achieved with a substantial reduction of computational cost. © 2018 The Author(s).

  7. A two-phase model of plantar tissue: a step toward prediction of diabetic foot ulceration.

    Science.gov (United States)

    Sciumè, G; Boso, D P; Gray, W G; Cobelli, C; Schrefler, B A

    2014-11-01

    A new computational model, based on the thermodynamically constrained averaging theory, has been recently proposed to predict tumor initiation and proliferation. A similar mathematical approach is proposed here as an aid in diabetic ulcer prevention. The common aspects at the continuum level are the macroscopic balance equations governing the flow of the fluid phase, diffusion of chemical species, tissue mechanics, and some of the constitutive equations. The soft plantar tissue is modeled as a two-phase system: a solid phase consisting of the tissue cells and their extracellular matrix, and a fluid one (interstitial fluid and dissolved chemical species). The solid phase may become necrotic depending on the stress level and on the oxygen availability in the tissue. Actually, in diabetic patients, peripheral vascular disease impacts tissue necrosis; this is considered in the model via the introduction of an effective diffusion coefficient that governs transport of nutrients within the microvasculature. The governing equations of the mathematical model are discretized in space by the finite element method and in time domain using the θ-Wilson Method. While the full mathematical model is developed in this paper, the example is limited to the simulation of several gait cycles of a healthy foot. Copyright © 2014 John Wiley & Sons, Ltd.

  8. Rapidly dissociated autologous meniscus tissue enhances meniscus healing: An in vitro study.

    Science.gov (United States)

    Numpaisal, Piya-On; Rothrauff, Benjamin B; Gottardi, Riccardo; Chien, Chung-Liang; Tuan, Rocky S

    Treatment of meniscus tears is a persistent challenge in orthopedics. Although cell therapies have shown promise in promoting fibrocartilage formation in in vitro and preclinical studies, clinical application has been limited by the paucity of autologous tissue and the need for ex vivo cell expansion. Rapid dissociation of the free edges of the anterior and posterior meniscus with subsequent implantation in a meniscus lesion may overcome these limitations. The purpose of this study was to explore the effect of rapidly dissociated meniscus tissue in enhancing neotissue formation in a radial meniscus tear, as simulated in an in vitro explant model. All experiments in this study, performed at minimum with biological triplicates, utilized meniscal tissues from hind limbs of young cows. The effect of varying collagenase concentration (0.1%, 0.2% and 0.5% w/v) and treatment duration (overnight and 30 minutes) on meniscus cell viability, organization of the extracellular matrix (ECM), and gene expression was assessed through a cell metabolism assay, microscopic examination, and quantitative real-time reverse transcription polymerase chain reaction analysis, respectively. Thereafter, an explant model of a radial meniscus tear was used to evaluate the effect of a fibrin gel seeded with one of the following: (1) fibrin alone, (2) isolated and passaged (P2) meniscus cells, (3) overnight digested tissue, and (4) rapidly dissociated tissue. The quality of in vitro healing was determined through histological analysis and derivation of an adhesion index. Rapid dissociation in 0.2% collagenase yielded cells with higher levels of metabolism than either 0.1% or 0.5% collagenase. When seeded in a three-dimensional fibrin hydrogel, both overnight digested and rapidly dissociated cells expressed greater levels of collagens type I and II than P2 meniscal cells at 1 week. At 4 and 8 weeks, collagen type II expression remained elevated only in the rapid dissociation group. Histological

  9. Optical techniques for the study of living tissue

    NARCIS (Netherlands)

    Margallo Balbás, E.

    2010-01-01

    The potential of light in diagnosis and therapy has been long recognised. With the advent of scientific progress in our understanding of light propagation and interaction with tissue and parallel major technological advances in how optical energy can be generated, detected and processed, this

  10. Constitutive modeling of an electrospun tubular scaffold used for vascular tissue engineering.

    Science.gov (United States)

    Hu, Jin-Jia

    2015-08-01

    In this study, we sought to model the mechanical behavior of an electrospun tubular scaffold previously reported for vascular tissue engineering with hyperelastic constitutive equations. Specifically, the scaffolds were made by wrapping electrospun polycaprolactone membranes that contain aligned fibers around a mandrel in such a way that they have microstructure similar to the native arterial media. The biaxial stress-stretch data of the scaffolds made of moderately or highly aligned fibers with three different off-axis fiber angles α (30°, 45°, and 60°) were fit by a phenomenological Fung model and a series of structurally motivated models considering fiber directions and fiber angle distributions. In particular, two forms of fiber strain energy in the structurally motivated model for a linear and a nonlinear fiber stress-strain relation, respectively, were tested. An isotropic neo-Hookean strain energy function was also added to the structurally motivated models to examine its contribution. The two forms of fiber strain energy did not result in significantly different goodness of fit for most groups of the scaffolds. The absence of the neo-Hookean term in the structurally motivated model led to obvious nonlinear stress-stretch fits at a greater axial stretch, especially when fitting data from the scaffolds with a small α. Of the models considered, the Fung model had the overall best fitting results; its applications are limited because of its phenomenological nature. Although a structurally motivated model using the nonlinear fiber stress-strain relation with the neo-Hookean term provided fits comparably as good as the Fung model, the values of its model parameters exhibited large within-group variations. Prescribing the dispersion of fiber orientation in the structurally motivated model, however, reduced the variations without compromising the fits and was thus considered to be the best structurally motivated model for the scaffolds. It appeared that the

  11. Differentiation of prostate cancer from normal prostate tissue in an animal model: conventional MRI and dynamic contrast-enhanced MRI

    International Nuclear Information System (INIS)

    Gemeinhardt, O.; Prochnow, D.; Taupitz, M.; Hamm, B.; Beyersdorff, D.; Luedemann, L.; Abramjuk, C.

    2005-01-01

    Purpose: to differentiate orthotopically implanted prostate cancer from normal prostate tissue using magnetic resonance imaging (MRI) and Gd-DTPA-BMA-enhanced dynamic MRI in the rat model. Material and methods: tumors were induced in 15 rats by orthotopic implantation of G subline Dunning rat prostatic tumor cells. MRI was performed 56 to 60 days after tumor cell implantation using T1-weighted spin-echo, T2-weighted turbo SE sequences, and a 2D FLASH sequence for the contrast medium based dynamic study. The interstitial leakage volume, normalized permeability and the permeability surface area product of tumor and healthy prostate were determined quantitatively using a pharmacokinetic model. The results were confirmed by histologic examination. Results: axial T2-weighted TSE images depicted low-intensity areas suspicious for tumor in all 15 animals. The mean tumor volume was 46.5 mm3. In the dynamic study, the suspicious areas in all animals displayed faster and more pronounced signal enhancement than surrounding prostate tissue. The interstitial volume and the permeability surface area product of the tumors increased significantly by 420% (p<0.001) and 424% (p<0.001), respectively, compared to normal prostate tissue, while no significant difference was seen for normalized permeability alone. Conclusion: the results of the present study demonstrate that quantitative analysis of contrast-enhanced dynamic MRI data enables differentiation of small, slowly growing orthotopic prostate cancer from normal prostate tissue in the rat model. (orig.)

  12. Effect of Tissue Heterogeneity on the Transmembrane Potential of Type-1 Spiral Ganglion Neurons: A Simulation Study.

    Science.gov (United States)

    Sriperumbudur, Kiran Kumar; Pau, Hans Wilhelm; van Rienen, Ursula

    2018-03-01

    Electric stimulation of the auditory nerve by cochlear implants has been a successful clinical intervention to treat the sensory neural deafness. In this pathological condition of the cochlea, type-1 spiral ganglion neurons in Rosenthal's canal play a vital role in the action potential initiation. Various morphological studies of the human temporal bones suggest that the spiral ganglion neurons are surrounded by heterogeneous structures formed by a variety of cells and tissues. However, the existing simulation models have not considered the tissue heterogeneity in the Rosenthal's canal while studying the electric field interaction with spiral ganglion neurons. Unlike the existing models, we have implemented the tissue heterogeneity in the Rosenthal's canal using a computationally inexpensive image based method in a two-dimensional finite element model. Our simulation results suggest that the spatial heterogeneity of surrounding tissues influences the electric field distribution in the Rosenthal's canal, and thereby alters the transmembrane potential of the spiral ganglion neurons. In addition to the academic interest, these results are especially useful to understand how the latest tissue regeneration methods such as gene therapy and drug-induced resprouting of peripheral axons, which probably modify the density of the tissues in the Rosenthal's canal, affect the cochlear implant functionality.

  13. A network model of correlated growth of tissue stiffening in pulmonary fibrosis

    Science.gov (United States)

    Oliveira, Cláudio L. N.; Bates, Jason H. T.; Suki, Béla

    2014-06-01

    During the progression of pulmonary fibrosis, initially isolated regions of high stiffness form and grow in the lung tissue due to collagen deposition by fibroblast cells. We have previously shown that ongoing collagen deposition may not lead to significant increases in the bulk modulus of the lung until these local remodeled regions have become sufficiently numerous and extensive to percolate in a continuous path across the entire tissue (Bates et al 2007 Am. J. Respir. Crit. Care Med. 176 617). This model, however, did not include the possibility of spatially correlated deposition of collagen. In the present study, we investigate whether spatial correlations influence the bulk modulus in a two-dimensional elastic network model of lung tissue. Random collagen deposition at a single site is modeled by increasing the elastic constant of the spring at that site by a factor of 100. By contrast, correlated collagen deposition is represented by stiffening the springs encountered along a random walk starting from some initial spring, the rationale being that excess collagen deposition is more likely in the vicinity of an already stiff region. A combination of random and correlated deposition is modeled by performing random walks of length N from randomly selected initial sites, the balance between the two processes being determined by N. We found that the dependence of bulk modulus, B(N,c), on both N and the fraction of stiff springs, c, can be described by a strikingly simple set of empirical equations. For c0.8, B(N,c) is linear in c and independent of N, such that B(N,c)=100\\;{{B}_{0}}-100{{a}_{III}}(1-c){{B}_{0}}, where {{a}_{III}}=2.857. For small concentrations, the physiologically most relevant regime, the forces in the network springs are distributed according to a power law. When c = 0.3, the exponent of this power law increases from -4.5, when N = 1, and saturates to about -2, as N increases above 40. These results suggest that the spatial correlation of

  14. Hormonal regulation of epithelial organization in a three-dimensional breast tissue culture model.

    Science.gov (United States)

    Speroni, Lucia; Whitt, Gregory S; Xylas, Joanna; Quinn, Kyle P; Jondeau-Cabaton, Adeline; Barnes, Clifford; Georgakoudi, Irene; Sonnenschein, Carlos; Soto, Ana M

    2014-01-01

    The establishment of hormone target breast cells in the 1970's resulted in suitable models for the study of hormone control of cell proliferation and gene expression using two-dimensional (2D) cultures. However, to study mammogenesis and breast tumor development in vitro, cells must be able to organize in three-dimensional (3D) structures like in the tissue. We now report the development of a hormone-sensitive 3D culture model for the study of mammogenesis and neoplastic development. Hormone-sensitive T47D breast cancer cells respond to estradiol in a dose-dependent manner by forming complex epithelial structures. Treatment with the synthetic progestagen promegestone, in the presence of estradiol, results in flat epithelial structures that display cytoplasmic projections, a phenomenon reported to precede side-branching. Additionally, as in the mammary gland, treatment with prolactin in the presence of estradiol induces budding structures. These changes in epithelial organization are accompanied by collagen remodeling. Collagen is the major acellular component of the breast stroma and an important player in tumor development and progression. Quantitative analysis of second harmonic generation of collagen fibers revealed that collagen density was more variable surrounding budding and irregularly shaped structures when compared to more regular structures; suggesting that fiber organization in the former is more anisotropic than in the latter. In sum, this new 3D model recapitulates morphogenetic events modulated by mammogenic hormones in the breast, and is suitable for the evaluation of therapeutic agents.

  15. Modeling and cellular studies

    International Nuclear Information System (INIS)

    Anon.

    1982-01-01

    Testing the applicability of mathematical models with carefully designed experiments is a powerful tool in the investigations of the effects of ionizing radiation on cells. The modeling and cellular studies complement each other, for modeling provides guidance for designing critical experiments which must provide definitive results, while the experiments themselves provide new input to the model. Based on previous experimental results the model for the accumulation of damage in Chlamydomonas reinhardi has been extended to include various multiple two-event combinations. Split dose survival experiments have shown that models tested to date predict most but not all the observed behavior. Stationary-phase mammalian cells, required for tests of other aspects of the model, have been shown to be at different points in the cell cycle depending on how they were forced to stop proliferating. These cultures also demonstrate different capacities for repair of sublethal radiation damage

  16. Modeling and optimization of tissue 10B concentration and dosimetry for arbitrary BPA-F infusion schedules in humans

    International Nuclear Information System (INIS)

    Kiger, W.S. III; Newton, T.H.; Palmer, M.R.

    2000-01-01

    Separate compartmental models have been derived for the concentration of 10 B resulting from BPA-F infusion in the central vascular space (i.e., blood or, more appropriately, plasma) and in glioblastoma multiforme and normal brain. By coupling the model for the temporal variation of 10 B concentration in the central vascular space with that for tissue, the dynamic behavior of the 10 B concentration and the resulting dosimetry in the relevant tissues and blood may be predicted for arbitrary infusion schedules. This coupled model may be used as a tool for identifying the optimal time for BNCT irradiation and optimal BPA-F infusion schedule (i.e., temporal targeting) in humans without the need for expensive and time-consuming pharmacokinetic studies for every infusion schedule considered. This model was used to analyze the concentration profiles resulting from a wide range of infusion schedules and their implications for dosimetry. (author)

  17. Mechanical characterization and non-linear elastic modeling of poly(glycerol sebacate) for soft tissue engineering.

    Science.gov (United States)

    Mitsak, Anna G; Dunn, Andrew M; Hollister, Scott J

    2012-07-01

    Scaffold tissue engineering strategies for repairing and replacing soft tissue aim to improve reconstructive and corrective surgical techniques whose limitations include suboptimal mechanical properties, fibrous capsule formation and volume loss due to graft resorption. An effective tissue engineering strategy requires a scaffolding material with low elastic modulus that behaves similarly to soft tissue, which has been characterized as a nonlinear elastic material. The material must also have the ability to be manufactured into specifically designed architectures. Poly(glycerol sebacate) (PGS) is a thermoset elastomer that meets these criteria. We hypothesize that the mechanical properties of PGS can be modulated through curing condition and architecture to produce materials with a range of stiffnesses. To evaluate this hypothesis, we manufactured PGS constructs cured under various conditions and having one of two architectures (solid or porous). Specimens were then tensile tested according to ASTM standards and the data were modeled using a nonlinear elastic Neo-Hookean model. Architecture and testing conditions, including elongation rate and wet versus dry conditions, affected the mechanical properties. Increasing curing time and temperature led to increased tangent modulus and decreased maximum strain for solid constructs. Porous constructs had lower nonlinear elastic properties, as did constructs of both architectures tested under simulated physiological conditions (wetted at 37 °C). Both solid and porous PGS specimens could be modeled well with the Neo-Hookean model. Future studies include comparing PGS properties to other biological tissue types and designing and characterizing PGS scaffolds for regenerating these tissues. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Towards modeling of cardiac micro-structure with catheter-based confocal microscopy: a novel approach for dye delivery and tissue characterization.

    Science.gov (United States)

    Lasher, Richard A; Hitchcock, Robert W; Sachse, Frank B

    2009-08-01

    This work presents a methodology for modeling of cardiac tissue micro-structure. The approach is based on catheter-based confocal imaging systems, which are emerging as tools for diagnosis in various clinical disciplines. A limitation of these systems is that a fluorescent marker must be available in sufficient concentration in the imaged region. We introduce a novel method for the local delivery of fluorescent markers to cardiac tissue based on a hydro-gel carrier brought into contact with the tissue surface. The method was tested with living rabbit cardiac tissue and applied to acquire three-dimensional image stacks with a standard inverted confocal microscope and two-dimensional images with a catheter-based confocal microscope. We processed these image stacks to obtain spatial models and quantitative data on tissue microstructure. Volumes of atrial and ventricular myocytes were 4901 +/- 1713 and 10 299 +/-3598 mum (3) (mean+/-sd), respectively. Atrial and ventricular myocyte volume fractions were 72.4 +/-4.7% and 79.7 +/- 2.9% (mean +/-sd), respectively. Atrial and ventricular myocyte density was 165 571 +/- 55 836 and 86 957 +/- 32 280 cells/mm (3) (mean+/-sd), respectively. These statistical data and spatial descriptions of tissue microstructure provide important input for modeling studies of cardiac tissue function. We propose that the described methodology can also be used to characterize diseased tissue and allows for personalized modeling of cardiac tissue.

  19. Normal Tissue Complication Probability Modeling of Acute Hematologic Toxicity in Cervical Cancer Patients Treated With Chemoradiotherapy

    International Nuclear Information System (INIS)

    Rose, Brent S.; Aydogan, Bulent; Liang, Yun; Yeginer, Mete; Hasselle, Michael D.; Dandekar, Virag; Bafana, Rounak; Yashar, Catheryn M.; Mundt, Arno J.; Roeske, John C.; Mell, Loren K.

    2011-01-01

    Purpose: To test the hypothesis that increased pelvic bone marrow (BM) irradiation is associated with increased hematologic toxicity (HT) in cervical cancer patients undergoing chemoradiotherapy and to develop a normal tissue complication probability (NTCP) model for HT. Methods and Materials: We tested associations between hematologic nadirs during chemoradiotherapy and the volume of BM receiving ≥10 and 20 Gy (V 10 and V 20 ) using a previously developed linear regression model. The validation cohort consisted of 44 cervical cancer patients treated with concurrent cisplatin and pelvic radiotherapy. Subsequently, these data were pooled with data from 37 identically treated patients from a previous study, forming a cohort of 81 patients for normal tissue complication probability analysis. Generalized linear modeling was used to test associations between hematologic nadirs and dosimetric parameters, adjusting for body mass index. Receiver operating characteristic curves were used to derive optimal dosimetric planning constraints. Results: In the validation cohort, significant negative correlations were observed between white blood cell count nadir and V 10 (regression coefficient (β) = -0.060, p = 0.009) and V 20 (β = -0.044, p = 0.010). In the combined cohort, the (adjusted) β estimates for log (white blood cell) vs. V 10 and V 20 were as follows: -0.022 (p = 0.025) and -0.021 (p = 0.002), respectively. Patients with V 10 ≥ 95% were more likely to experience Grade ≥3 leukopenia (68.8% vs. 24.6%, p 20 > 76% (57.7% vs. 21.8%, p = 0.001). Conclusions: These findings support the hypothesis that HT increases with increasing pelvic BM volume irradiated. Efforts to maintain V 10 20 < 76% may reduce HT.

  20. Altered vocal fold kinematics in synthetic self-oscillating models that employ adipose tissue as a lateral boundary condition.

    Science.gov (United States)

    Saidi, Hiba; Erath, Byron D.

    2015-11-01

    The vocal folds play a major role in human communication by initiating voiced sound production. During voiced speech, the vocal folds are set into sustained vibrations. Synthetic self-oscillating vocal fold models are regularly employed to gain insight into flow-structure interactions governing the phonation process. Commonly, a fixed boundary condition is applied to the lateral, anterior, and posterior sides of the synthetic vocal fold models. However, physiological observations reveal the presence of adipose tissue on the lateral surface between the thyroid cartilage and the vocal folds. The goal of this study is to investigate the influence of including this substrate layer of adipose tissue on the dynamics of phonation. For a more realistic representation of the human vocal folds, synthetic multi-layer vocal fold models have been fabricated and tested while including a soft lateral layer representative of adipose tissue. Phonation parameters have been collected and are compared to those of the standard vocal fold models. Results show that vocal fold kinematics are affected by adding the adipose tissue layer as a new boundary condition.

  1. Determination of the axial and circumferential mechanical properties of the skin tissue using experimental testing and constitutive modeling.

    Science.gov (United States)

    Karimi, Alireza; Navidbakhsh, Mahdi; Haghighatnama, Maedeh; Haghi, Afsaneh Motevalli

    2015-01-01

    The skin, being a multi-layered material, is responsible for protecting the human body from the mechanical, bacterial, and viral insults. The skin tissue may display different mechanical properties according to the anatomical locations of a body. However, these mechanical properties in different anatomical regions and at different loading directions (axial and circumferential) of the mice body to date have not been determined. In this study, the axial and circumferential loads were imposed on the mice skin samples. The elastic modulus and maximum stress of the skin tissues were measured before the failure occurred. The nonlinear mechanical behavior of the skin tissues was also computationally investigated through a suitable constitutive equation. Hyperelastic material model was calibrated using the experimental data. Regardless of the anatomic locations of the mice body, the results revealed significantly different mechanical properties in the axial and circumferential directions and, consequently, the mice skin tissue behaves like a pure anisotropic material. The highest elastic modulus was observed in the back skin under the circumferential direction (6.67 MPa), while the lowest one was seen in the abdomen skin under circumferential loading (0.80 MPa). The Ogden material model was narrowly captured the nonlinear mechanical response of the skin at different loading directions. The results help to understand the isotropic/anisotropic mechanical behavior of the skin tissue at different anatomical locations. They also have implications for a diversity of disciplines, i.e., dermatology, cosmetics industry, clinical decision making, and clinical intervention.

  2. Frequency dependence of complex moduli of brain tissue using a fractional Zener model

    International Nuclear Information System (INIS)

    Kohandel, M; Sivaloganathan, S; Tenti, G; Darvish, K

    2005-01-01

    Brain tissue exhibits viscoelastic behaviour. If loading times are substantially short, static tests are not sufficient to determine the complete viscoelastic behaviour of the material, and dynamic test methods are more appropriate. The concept of complex modulus of elasticity is a powerful tool for characterizing the frequency domain behaviour of viscoelastic materials. On the other hand, it is well known that classical viscoelastic models can be generalized by means of fractional calculus to describe more complex viscoelastic behaviour of materials. In this paper, the fractional Zener model is investigated in order to describe the dynamic behaviour of brain tissue. The model is fitted to experimental data of oscillatory shear tests of bovine brain tissue to verify its behaviour and to obtain the material parameters

  3. Experimental comparison study of the tissue characteristics in transjugular intrahepatic portosystemic shunt and vascular stent

    International Nuclear Information System (INIS)

    Lu Qin; An Yanli; Deng Gang; Fang Wen; Zhu Guangyu; Niu Huanzhang; Yu Hui; Li Guozhao; Teng Gaojun; Wang Zhen; Wei Xiaoying

    2009-01-01

    Objective: To investigate the tissue characteristics within vascular stent and transjugular intrahepatic portosystemic shunt(TIPS) on swine and to provide more information for the understanding and prevention of vascular stent and TIPS restenosis. Methods: Animal models for TIPS were built in 6 swine and vascular stents were implanted in iliac veins simultaneously. 14-28 days after the operation, the 6 swine were killed to remove the TIPS and vascular stent and the pathological examinations were performed on the tissues within the shunt and stent. The similarities and differences of the tissues within the shunt and stent were analyzed with Krttskal Wallis test. Results: Restenosis of TIPS occurred in 4 models and complete occlusion were seen in 2, while all vascular stents were patent and coated with a thin layer of intimal tissue. Electron microscopic results showed that the tissues in restenotic TIPS were loose and with more extra matrix and fibers, and less smooth muscle, fibroblastic and myofibroblastic cells with different and irregular shape and rich secretory granules. The tissues in patent TIPS contained more extra fibers, smooth muscle and fibroblastic cells with normal organelle. The intimal tissues in vascular stent contained more fibers and fibroblasts cells, less smooth muscle cells. On immunohistochemical staining, the tissues in restenotic and patent TIPS as well as the intimal tissues in vascular stent had strong positive expression for anti-SMC- actin-α, the expression were gradually weakened for PCNA, the intimal tissues in vascular stent had a strong positive expression for vimentin, while the expression of the tissues in restenotic and patent TIPS were weakened gradually. For myoglobulin, the tissues in restenotic TIPS had weakly positive expression, the expression in patent TIPS and vascular stent were almost negative. Western blot results for TGF-β showed that the absorbance ratios of the intima tissues in vascular stent, normal vascular

  4. Protective ventilation reduces Pseudomonas aeruginosa growth in lung tissue in a porcine pneumonia model.

    Science.gov (United States)

    Sperber, Jesper; Nyberg, Axel; Lipcsey, Miklos; Melhus, Åsa; Larsson, Anders; Sjölin, Jan; Castegren, Markus

    2017-08-31

    Mechanical ventilation with positive end expiratory pressure and low tidal volume, i.e. protective ventilation, is recommended in patients with acute respiratory distress syndrome. However, the effect of protective ventilation on bacterial growth during early pneumonia in non-injured lungs is not extensively studied. The main objectives were to compare two different ventilator settings on Pseudomonas aeruginosa growth in lung tissue and the development of lung injury. A porcine model of severe pneumonia was used. The protective group (n = 10) had an end expiratory pressure of 10 cm H 2 O and a tidal volume of 6 ml x kg -1 . The control group (n = 10) had an end expiratory pressure of 5 cm H 2 O and a tidal volume of 10 ml x kg -1 . 10 11 colony forming units of Pseudomonas aeruginosa were inoculated intra-tracheally at baseline, after which the experiment continued for 6 h. Two animals from each group received only saline, and served as sham animals. Lung tissue samples from each animal were used for bacterial cultures and wet-to-dry weight ratio measurements. The protective group displayed lower numbers of Pseudomonas aeruginosa (p protective group was unchanged (p protective ventilation with lower tidal volume and higher end expiratory pressure has the potential to reduce the pulmonary bacterial burden and the development of lung injury.

  5. Modelling far field pacing for terminating spiral waves pinned to ischaemic heterogeneities in cardiac tissue

    Science.gov (United States)

    Boccia, E.; Luther, S.

    2017-01-01

    In cardiac tissue, electrical spiral waves pinned to a heterogeneity can be unpinned (and eventually terminated) using electric far field pulses and recruiting the heterogeneity as a virtual electrode. While for isotropic media the process of unpinning is much better understood, the case of an anisotropic substrate with different conductivities in different directions still needs intensive investigation. To study the impact of anisotropy on the unpinning process, we present numerical simulations based on the bidomain formulation of the phase I of the Luo and Rudy action potential model modified due to the occurrence of acute myocardial ischaemia. Simulating a rotating spiral wave pinned to an ischaemic heterogeneity, we compare the success of sequences of far field pulses in the isotropic and the anisotropic case for spirals still in transient or in steady rotation states. Our results clearly indicate that the range of pacing parameters resulting in successful termination of pinned spiral waves is larger in anisotropic tissue than in an isotropic medium. This article is part of the themed issue ‘Mathematical methods in medicine: neuroscience, cardiology and pathology’. PMID:28507234

  6. Use of a Rabbit Soft Tissue Chamber Model to Investigate Campylobacter jejuni - Host Interactions

    Directory of Open Access Journals (Sweden)

    Annika eFlint

    2010-11-01

    Full Text Available Despite the prevalence of C. jejuni as an important food borne pathogen, the microbial factors governing its infection process are poorly characterized. In this study, we developed a novel rabbit soft tissue chamber model to investigate C. jejuni interactions with its host. The in vivo transcriptome profile of C. jejuni was monitored as a function of time post-infection by competitive microarray hybridization with cDNA obtained from C. jejuni grown in vitro. Genome-wide expression analysis identified 449 genes expressed at significantly different levels in vivo. Genes implicated to play important roles in early colonization of C. jejuni within the tissue chamber include up-regulation of genes involved in ribosomal protein synthesis and modification, heat shock response, and primary adaptation to the host environment (DccSR regulon. Genes encoding proteins involved in the TCA cycle and flagella related components were found to be significantly down regulated during early colonization. Oxidative stress defense and stringent response genes were found to be maximally induced during the acute infectious phase. Overall, these findings reveal possible mechanisms involved in adaptation of Campylobacter to the host.

  7. Statistical modeling of interfractional tissue deformation and its application in radiation therapy planning

    Science.gov (United States)

    Vile, Douglas J.

    In radiation therapy, interfraction organ motion introduces a level of geometric uncertainty into the planning process. Plans, which are typically based upon a single instance of anatomy, must be robust against daily anatomical variations. For this problem, a model of the magnitude, direction, and likelihood of deformation is useful. In this thesis, principal component analysis (PCA) is used to statistically model the 3D organ motion for 19 prostate cancer patients, each with 8-13 fractional computed tomography (CT) images. Deformable image registration and the resultant displacement vector fields (DVFs) are used to quantify the interfraction systematic and random motion. By applying the PCA technique to the random DVFs, principal modes of random tissue deformation were determined for each patient, and a method for sampling synthetic random DVFs was developed. The PCA model was then extended to describe the principal modes of systematic and random organ motion for the population of patients. A leave-one-out study tested both the systematic and random motion model's ability to represent PCA training set DVFs. The random and systematic DVF PCA models allowed the reconstruction of these data with absolute mean errors between 0.5-0.9 mm and 1-2 mm, respectively. To the best of the author's knowledge, this study is the first successful effort to build a fully 3D statistical PCA model of systematic tissue deformation in a population of patients. By sampling synthetic systematic and random errors, organ occupancy maps were created for bony and prostate-centroid patient setup processes. By thresholding these maps, PCA-based planning target volume (PTV) was created and tested against conventional margin recipes (van Herk for bony alignment and 5 mm fixed [3 mm posterior] margin for centroid alignment) in a virtual clinical trial for low-risk prostate cancer. Deformably accumulated delivered dose served as a surrogate for clinical outcome. For the bony landmark setup

  8. Multiscale Modeling of Antibody Drug Conjugates: Connecting tissue and cellular distribution to whole animal pharmacokinetics and potential implications for efficacy

    Science.gov (United States)

    Cilliers, Cornelius; Guo, Hans; Liao, Jianshan; Christodolu, Nikolas; Thurber, Greg M.

    2016-01-01

    Antibody drug conjugates exhibit complex pharmacokinetics due to their combination of macromolecular and small molecule properties. These issues range from systemic concerns, such as deconjugation of the small molecule drug during the long antibody circulation time or rapid clearance from non-specific interactions, to local tumor tissue heterogeneity, cell bystander effects, and endosomal escape. Mathematical models can be used to study the impact of these processes on overall distribution in an efficient manner, and several types of models have been used to analyze varying aspects of antibody distribution including physiologically based pharmacokinetic (PBPK) models and tissue-level simulations. However, these processes are quantitative in nature and cannot be handled qualitatively in isolation. For example, free antibody from deconjugation of the small molecule will impact the distribution of conjugated antibodies within the tumor. To incorporate these effects into a unified framework, we have coupled the systemic and organ-level distribution of a PBPK model with the tissue-level detail of a distributed parameter tumor model. We used this mathematical model to analyze new experimental results on the distribution of the clinical antibody drug conjugate Kadcyla in HER2 positive mouse xenografts. This model is able to capture the impact of the drug antibody ratio (DAR) on tumor penetration, the net result of drug deconjugation, and the effect of using unconjugated antibody to drive ADC penetration deeper into the tumor tissue. This modeling approach will provide quantitative and mechanistic support to experimental studies trying to parse the impact of multiple mechanisms of action for these complex drugs. PMID:27287046

  9. 3D force control for robotic-assisted beating heart surgery based on viscoelastic tissue model.

    Science.gov (United States)

    Liu, Chao; Moreira, Pedro; Zemiti, Nabil; Poignet, Philippe

    2011-01-01

    Current cardiac surgery faces the challenging problem of heart beating motion even with the help of mechanical stabilizer which makes delicate operation on the heart surface difficult. Motion compensation methods for robotic-assisted beating heart surgery have been proposed recently in literature, but research on force control for such kind of surgery has hardly been reported. Moreover, the viscoelasticity property of the interaction between organ tissue and robotic instrument further complicates the force control design which is much easier in other applications by assuming the interaction model to be elastic (industry, stiff object manipulation, etc.). In this work, we present a three-dimensional force control method for robotic-assisted beating heart surgery taking into consideration of the viscoelastic interaction property. Performance studies based on our D2M2 robot and 3D heart beating motion information obtained through Da Vinci™ system are provided.

  10. A Histopathological Study of Pulmonary Hypertension in Connective Tissue Disease

    Directory of Open Access Journals (Sweden)

    Nobuhito Sasaki

    2011-01-01

    Full Text Available Connective tissue diseases (CTD, such as systemic sclerosis (SSc, systemic lupus erythematosus (SLE, and mixed connective tissue disease (MCTD, develop pulmonary hypertension (PH. Generally all PH cases associated with any CTD are classified into the same PH group. However, histological examination shows both common and specific lesions for each disease. In patients with SLE, fibrosis is generally rare and mild. The findings of PH in SLE are similar to those in primary pulmonary hypertension. Many cases of SSc are accompanied by fibrosis. MCTD is rather close to SSc. Arterial and arteriolar lesions of MCTD are characterized by fibrous intimal thickening. In this review, we describe the pathological features of PH associated with each CTD.

  11. Brief Communication: Tissue-engineered Microenvironment Systems for Modeling Human Vasculature

    Science.gov (United States)

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

    2015-01-01

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

  12. An experimental study on tissue damage following subcutaneous injection of water soluble contrast media

    International Nuclear Information System (INIS)

    Kim, Seung Hyup; Park, Jae Hyung; Kang, Heung Sik; Kim, Chu Wan; Han, Man Chung; Kim, Yong Il

    1989-01-01

    The water soluble contrast media cause tissue necrosis infrequently by extravasation during intravenous injection in various radiological examinations. However, it has not been well documented that what kind and what concentration of contrast media can cause tissue necrosis. And also, the mechanism of tissue necrosis by extravasated contrast media has not been well known. The purpose of this experimental study was to evaluate the frequency and severity of tissue damage following subcutaneous injection of various water soluble contrast media to investigate the characteristics of the contrast media acting on the tissue damage, and to provide the basic data for the clinical application. Meglumine ioxithalamate,sodium and meglumine ioxithalamate, iopromide, iopamidol, ioxaglate,meglumine diatrizoate and sodium diatrizoate of various iodine content and osmolality were injected into subcutaneous tissue of the dorsum of 970 feet of 485 rats. The tissue reaction of injection sites were grossly examined with period from 1 day to 8 weeks after the injection. Representative gross changes were correlated with histologic findings. The results were as follows; 1. The basic tissue damage by extravasated contrast media was acute and chronic inflammatory reaction of the soft tissue with subsequent progress into the hemorrhagic and necrotizing lesion. 2. Lager volume of contrast media caused more severe tissue damage. 3. Contrast media of higher osmolality caused more severe tissue damage. 4. At same osmolality, contrast media of higher iodine content caused more severe tissue damage

  13. Multi-time-scale heat transfer modeling of turbid tissues exposed to short-pulsed irradiations.

    Science.gov (United States)

    Kim, Kyunghan; Guo, Zhixiong

    2007-05-01

    A combined hyperbolic radiation and conduction heat transfer model is developed to simulate multi-time-scale heat transfer in turbid tissues exposed to short-pulsed irradiations. An initial temperature response of a tissue to an ultrashort pulse irradiation is analyzed by the volume-average method in combination with the transient discrete ordinates method for modeling the ultrafast radiation heat transfer. This response is found to reach pseudo steady state within 1 ns for the considered tissues. The single pulse result is then utilized to obtain the temperature response to pulse train irradiation at the microsecond/millisecond time scales. After that, the temperature field is predicted by the hyperbolic heat conduction model which is solved by the MacCormack's scheme with error terms correction. Finally, the hyperbolic conduction is compared with the traditional parabolic heat diffusion model. It is found that the maximum local temperatures are larger in the hyperbolic prediction than the parabolic prediction. In the modeled dermis tissue, a 7% non-dimensional temperature increase is found. After about 10 thermal relaxation times, thermal waves fade away and the predictions between the hyperbolic and parabolic models are consistent.

  14. A genetic algorithm for optimizing multi-pole Debye models of tissue dielectric properties

    International Nuclear Information System (INIS)

    Clegg, J; Robinson, M P

    2012-01-01

    Models of tissue dielectric properties (permittivity and conductivity) enable the interactions of tissues and electromagnetic fields to be simulated, which has many useful applications in microwave imaging, radio propagation, and non-ionizing radiation dosimetry. Parametric formulae are available, based on a multi-pole model of tissue dispersions, but although they give the dielectric properties over a wide frequency range, they do not convert easily to the time domain. An alternative is the multi-pole Debye model which works well in both time and frequency domains. Genetic algorithms are an evolutionary approach to optimization, and we found that this technique was effective at finding the best values of the multi-Debye parameters. Our genetic algorithm optimized these parameters to fit to either a Cole–Cole model or to measured data, and worked well over wide or narrow frequency ranges. Over 10 Hz–10 GHz the best fits for muscle, fat or bone were each found for ten dispersions or poles in the multi-Debye model. The genetic algorithm is a fast and effective method of developing tissue models that compares favourably with alternatives such as the rational polynomial fit. (paper)

  15. Genetic programming based models in plant tissue culture: An addendum to traditional statistical approach.

    Science.gov (United States)

    Mridula, Meenu R; Nair, Ashalatha S; Kumar, K Satheesh

    2018-02-01

    In this paper, we compared the efficacy of observation based modeling approach using a genetic algorithm with the regular statistical analysis as an alternative methodology in plant research. Preliminary experimental data on in vitro rooting was taken for this study with an aim to understand the effect of charcoal and naphthalene acetic acid (NAA) on successful rooting and also to optimize the two variables for maximum result. Observation-based modelling, as well as traditional approach, could identify NAA as a critical factor in rooting of the plantlets under the experimental conditions employed. Symbolic regression analysis using the software deployed here optimised the treatments studied and was successful in identifying the complex non-linear interaction among the variables, with minimalistic preliminary data. The presence of charcoal in the culture medium has a significant impact on root generation by reducing basal callus mass formation. Such an approach is advantageous for establishing in vitro culture protocols as these models will have significant potential for saving time and expenditure in plant tissue culture laboratories, and it further reduces the need for specialised background.

  16. Application of the ultrasound hyperthermia model for a multi-layered tissue system

    International Nuclear Information System (INIS)

    Loerincz, A

    2004-01-01

    This work models the thermal effect of several planar transducers targeting the tumour interactively in a ceramics-coupling-skin-muscle-tumour system. The most important inputs of the model include the following: emitted electric output, J/s; mechanical efficiency, %; number of transducers, pieces; surface area of the transducer, m 2 ; area, m 2 and temperature, K of the cooling surface, attenuation coefficients, Np/cm MHz; specific heats, J/gK; densities, g/cm 3 ; heat conductivities, J/msK; sound velocities m/s; flow rate of blood in the tissues, ml/gtissue/min; sound path in the tissues and in the blood flowing through the tissues, m. From the inputs, a number of intermediate data are determined, e.g. the geometry of the irradiated bodies that are in the path of ultrasound, acoustic hardness, Pas/m; sound reflection and sound transmission occurring at the interfaces, Np; heat exchanger wall thickness of the irradiated bodies, m; heat dissipation and heat exchanger surface areas, m 2 ; flow rate of blood in the tissues located in the path of ultrasound, ml/tissue mass in g/min; and the sound attenuation of the tissues, Np. The amount of generated heat, K/s decreased by the heat energy transported, J/s to the surrounding tissues by blood and heat conductivity, and the actual temperature, K of the irradiated tissue are the output parameters calculated by the model. The output results are available in the form of functions. The expected temperature of the target area, K can be set to either the denaturation temperature or to the respiratory decomposition temperature (43.5 deg. C) without damaging the surrounding tissues by setting in the following parameters properly: electric output power, W; the number and surface area, m 2 of the transducers; the area, m 2 and temperature, K of the cooling surfaces. After further development, the model will be suitable for handling more than three tissue layers, increased blood flow rates different angles of incidence, and

  17. ChainMail based neural dynamics modeling of soft tissue deformation for surgical simulation.

    Science.gov (United States)

    Zhang, Jinao; Zhong, Yongmin; Smith, Julian; Gu, Chengfan

    2017-07-20

    Realistic and real-time modeling and simulation of soft tissue deformation is a fundamental research issue in the field of surgical simulation. In this paper, a novel cellular neural network approach is presented for modeling and simulation of soft tissue deformation by combining neural dynamics of cellular neural network with ChainMail mechanism. The proposed method formulates the problem of elastic deformation into cellular neural network activities to avoid the complex computation of elasticity. The local position adjustments of ChainMail are incorporated into the cellular neural network as the local connectivity of cells, through which the dynamic behaviors of soft tissue deformation are transformed into the neural dynamics of cellular neural network. Experiments demonstrate that the proposed neural network approach is capable of modeling the soft tissues' nonlinear deformation and typical mechanical behaviors. The proposed method not only improves ChainMail's linear deformation with the nonlinear characteristics of neural dynamics but also enables the cellular neural network to follow the principle of continuum mechanics to simulate soft tissue deformation.

  18. Bioheat model evaluations of laser effects on tissues: role of water evaporation and diffusion

    Science.gov (United States)

    Nagulapally, Deepthi; Joshi, Ravi P.; Thomas, Robert J.

    2011-03-01

    A two-dimensional, time-dependent bioheat model is applied to evaluate changes in temperature and water content in tissues subjected to laser irradiation. Our approach takes account of liquid-to-vapor phase changes and a simple diffusive flow of water within the biotissue. An energy balance equation considers blood perfusion, metabolic heat generation, laser absorption, and water evaporation. The model also accounts for the water dependence of tissue properties (both thermal and optical), and variations in blood perfusion rates based on local tissue injury. Our calculations show that water diffusion would reduce the local temperature increases and hot spots in comparison to simple models that ignore the role of water in the overall thermal and mass transport. Also, the reduced suppression of perfusion rates due to tissue heating and damage with water diffusion affect the necrotic depth. Two-dimensional results for the dynamic temperature, water content, and damage distributions will be presented for skin simulations. It is argued that reduction in temperature gradients due to water diffusion would mitigate local refractive index variations, and hence influence the phenomenon of thermal lensing. Finally, simple quantitative evaluations of pressure increases within the tissue due to laser absorption are presented.

  19. Microfluidics Enables Small-Scale Tissue-Based Drug Metabolism Studies With Scarce Human Tissue

    NARCIS (Netherlands)

    van Midwoud, Paul M.; Verpoorte, Elisabeth; Groothuis, Geny M. M.; Merema, M.T.

    2011-01-01

    Early information on the metabolism and toxicity properties of new drug candidates is crucial for selecting the right candidates for further development. Preclinical trials rely on cell-based in vitro tests and animal studies to characterize the in vivo behavior of drug candidates, although neither

  20. Mechanical Model of Geometric Cell and Topological Algorithm for Cell Dynamics from Single-Cell to Formation of Monolayered Tissues with Pattern

    KAUST Repository

    Kachalo, Sëma

    2015-05-14

    Geometric and mechanical properties of individual cells and interactions among neighboring cells are the basis of formation of tissue patterns. Understanding the complex interplay of cells is essential for gaining insight into embryogenesis, tissue development, and other emerging behavior. Here we describe a cell model and an efficient geometric algorithm for studying the dynamic process of tissue formation in 2D (e.g. epithelial tissues). Our approach improves upon previous methods by incorporating properties of individual cells as well as detailed description of the dynamic growth process, with all topological changes accounted for. Cell size, shape, and division plane orientation are modeled realistically. In addition, cell birth, cell growth, cell shrinkage, cell death, cell division, cell collision, and cell rearrangements are now fully accounted for. Different models of cell-cell interactions, such as lateral inhibition during the process of growth, can be studied in detail. Cellular pattern formation for monolayered tissues from arbitrary initial conditions, including that of a single cell, can also be studied in detail. Computational efficiency is achieved through the employment of a special data structure that ensures access to neighboring cells in constant time, without additional space requirement. We have successfully generated tissues consisting of more than 20,000 cells starting from 2 cells within 1 hour. We show that our model can be used to study embryogenesis, tissue fusion, and cell apoptosis. We give detailed study of the classical developmental process of bristle formation on the epidermis of D. melanogaster and the fundamental problem of homeostatic size control in epithelial tissues. Simulation results reveal significant roles of solubility of secreted factors in both the bristle formation and the homeostatic control of tissue size. Our method can be used to study broad problems in monolayered tissue formation. Our software is publicly

  1. Six Conductivity Values to Use in the Bidomain Model of Cardiac Tissue.

    Science.gov (United States)

    Johnston, Barbara M

    2016-07-01

    The aim of this work is to produce a consistent set of six conductivity values for use in the bidomain model of cardiac tissue. Studies in 2007 by Hooks et al. and in 2009 by Caldwell et al. have found that, in the directions longitudinal:transverse:normal (l:t:n) to the cardiac fibers, ratios of bulk conductivities and conduction velocities are each approximately in the ratio 4:2:1. These results are used here as the basis for a method that can find sets of six normalized bidomain conductivity values. It is found that the ratios involving transverse and normal conductivities are quite consistent, allowing new light to be shed on conductivity in the normal direction. For example, it is found that the ratio of transverse to normal conductivity is much greater in the intracellular (i) than the extracellular (e) domain. Using parameter values from experimental studies leads to the proposal of a new nominal six conductivity dataset: gil=2.4, gel=2.4, git=0.35, get=2.0, gin=0.08, and gen=1.1 (all in mS/cm). When it is used to model partial thickness ischaemia, this dataset produces epicardial potential distributions in accord with experimental studies in an animal model. It is, therefore, suggested that the dataset is suitable for use in numerical simulations. Since the bidomain approach is the most commonly used method for modeling cardiac electrophysiological phenomena, new information about conductivity in the normal direction, as well as a consistent set of six conductivity values, is valuable for researchers who perform simulation studies.

  2. Hybrid diffusion and two-flux approximation for multilayered tissue light propagation modeling

    Science.gov (United States)

    Yudovsky, Dmitry; Durkin, Anthony J.

    2011-07-01

    Accurate and rapid estimation of fluence, reflectance, and absorbance in multilayered biological media has been essential in many biophotonics applications that aim to diagnose, cure, or model in vivo tissue. The radiative transfer equation (RTE) rigorously models light transfer in absorbing and scattering media. However, analytical solutions to the RTE are limited even in simple homogeneous or plane media. Monte Carlo simulation has been used extensively to solve the RTE. However, Monte Carlo simulation is computationally intensive and may not be practical for applications that demand real-time results. Instead, the diffusion approximation has been shown to provide accurate estimates of light transport in strongly scattering tissue. The diffusion approximation is a greatly simplified model and produces analytical solutions for the reflectance and absorbance in tissue. However, the diffusion approximation breaks down if tissue is strongly absorbing, which is common in the visible part of the spectrum or in applications that involve darkly pigmented skin and/or high local volumes of blood such as port-wine stain therapy or reconstructive flap monitoring. In these cases, a model of light transfer that can accommodate both strongly and weakly absorbing regimes is required. Here we present a model of light transfer through layered biological media that represents skin with two strongly scattering and one strongly absorbing layer.

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

    Science.gov (United States)

    Lowenthal, Justin; Gerecht, Sharon

    2016-05-06

    Proper blood vessel networks are necessary for constructing and re-constructing tissues, promoting wound healing, and delivering metabolic necessities throughout the body. Conversely, an understanding of vascular dysfunction has provided insight into the pathogenesis and progression of diseases both common and rare. Recent advances in stem cell-based regenerative medicine - including advances in stem cell technologies and related progress in bioscaffold design and complex tissue engineering - have allowed rapid advances in the field of vascular biology, leading in turn to more advanced modeling of vascular pathophysiology and improved engineering of vascularized tissue constructs. In this review we examine recent advances in the field of stem cell-derived vasculature, providing an overview of stem cell technologies as a source for vascular cell types and then focusing on their use in three primary areas: studies of vascular development and angiogenesis, improved disease modeling, and the engineering of vascularized constructs for tissue-level modeling and cell-based therapies. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Bee waxes: a model of characterization for using as base simulator tissue in teletherapy with photons

    International Nuclear Information System (INIS)

    Silva, Rogerio Matias Vidal da; Souza, Divanizia do Nascimento

    2011-01-01

    This paper presents a model of characterization and selection of bee waxes which makes possible to certify the usage viability of that base simulator tissue in the manufacture of appropriated objects for external radiotherapy with mega volt photon beams. The work was divide into three stages, where was evaluated physical and chemical properties besides the aspects related to the capacity of beam attenuation. All the process was carefully accompanied related to the wax origin such as the bee specimen and the flora surrounding the beehives. The chemical composition of the waxes is similar to others simulators usually used in radiotherapy. The behavior of mass attenuation coefficient in the radiotherapeutic energy range is comparable to other simulators, and consequently to the soft tissue. The proposed model is efficient and allows the affirmative that the usage of determined bee wax as base simulator tissue is convenient

  5. The impact of laser ablation on optical soft tissue differentiation for tissue specific laser surgery-an experimental ex vivo study

    Directory of Open Access Journals (Sweden)

    Stelzle Florian

    2012-06-01

    Full Text Available Abstract Background Optical diffuse reflectance can remotely differentiate various bio tissues. To implement this technique in an optical feedback system to guide laser surgery in a tissue-specific way, the alteration of optical tissue properties by laser ablation has to be taken into account. It was the aim of this study to evaluate the general feasibility of optical soft tissue differentiation by diffuse reflectance spectroscopy under the influence of laser ablation, comparing the tissue differentiation results before and after laser intervention. Methods A total of 70 ex vivo tissue samples (5 tissue types were taken from 14 bisected pig heads. Diffuse reflectance spectra were recorded before and after Er:YAG-laser ablation. The spectra were analyzed and differentiated using principal component analysis (PCA, followed by linear discriminant analysis (LDA. To assess the potential of tissue differentiation, area under the curve (AUC, sensitivity and specificity was computed for each pair of tissue types before and after laser ablation, and compared to each other. Results Optical tissue differentiation showed good results before laser exposure (total classification error 13.51%. However, the tissue pair nerve and fat yielded lower AUC results of only 0.75. After laser ablation slightly reduced differentiation results were found with a total classification error of 16.83%. The tissue pair nerve and fat showed enhanced differentiation (AUC: 0.85. Laser ablation reduced the sensitivity in 50% and specificity in 80% of the cases of tissue pair comparison. The sensitivity of nerve–fat differentiation was enhanced by 35%. Conclusions The observed results show the general feasibility of tissue differentiation by diffuse reflectance spectroscopy even under conditions of tissue alteration by laser ablation. The contrast enhancement for the differentiation between nerve and fat tissue after ablation is assumed to be due to laser removal of the

  6. Evaluation of Soft Tissue Sarcoma Tumors Electrical Conductivity Anisotropy Using Diffusion Tensor Imaging for Numerical Modeling on Electroporation

    Directory of Open Access Journals (Sweden)

    Ghazikhanlou-sani K.

    2016-06-01

    Full Text Available Introduction: There is many ways to assessing the electrical conductivity anisotropy of a tumor. Applying the values of tissue electrical conductivity anisotropy is crucial in numerical modeling of the electric and thermal field distribution in electroporation treatments. This study aims to calculate the tissues electrical conductivity anisotropy in patients with sarcoma tumors using diffusion tensor imaging technique. Materials and Method: A total of 3 subjects were involved in this study. All of patients had clinically apparent sarcoma tumors at the extremities. The T1, T2 and DTI images were performed using a 3-Tesla multi-coil, multi-channel MRI system. The fractional anisotropy (FA maps were performed using the FSL (FMRI software library software regarding the DTI images. The 3D matrix of the FA maps of each area (tumor, normal soft tissue and bone/s was reconstructed and the anisotropy matrix was calculated regarding to the FA values. Result: The mean FA values in direction of main axis in sarcoma tumors were ranged between 0.475–0.690. With assumption of isotropy of the electrical conductivity, the FA value of electrical conductivity at each X, Y and Z coordinate axes would be equal to 0.577. The gathered results showed that there is a mean error band of 20% in electrical conductivity, if the electrical conductivity anisotropy not concluded at the calculations. The comparison of FA values showed that there is a significant statistical difference between the mean FA value of tumor and normal soft tissues (P<0.05. Conclusion: DTI is a feasible technique for the assessment of electrical conductivity anisotropy of tissues. It is crucial to quantify the electrical conductivity anisotropy data of tissues for numerical modeling of electroporation treatments.

  7. Lung regeneration by fetal lung tissue implantation in a mouse pulmonary emphysema model.

    Science.gov (United States)

    Uyama, Koh; Sakiyama,