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Although predicting temperature variation is important for designing treatment plans for thermal therapies, research in this area is yet to investigate the applicability of prevalent thermal conduction models, such as the Pennes equation, the thermal wave model of bio-heat transfer, and the dual phase lag (DPL) model. To address this shortcoming, we heated a tissue phantom and ex vivo bovine liver tissues with focused ultrasound (FU), measured the temperature response, and compared the results with those predicted by these models. The findings show that, for a homogeneous-tissue phantom, the initial temperature increase is accurately predicted by the Pennes equation at the onset of FU irradiation, although the prediction deviates from the measured temperature with increasing FU irradiation time. For heterogeneous liver tissues, the predicted response is closer to the measured temperature for the non-Fourier models, especially the DPL model. Furthermore, the DPL model accurately predicts the temperature response in biological tissues because it increases the phase lag, which characterizes microstructural thermal interactions. These findings should help to establish more precise clinical treatment plans for thermal therapies. [ABSTRACT FROM AUTHOR]

In this study, we investigated the influence of beam hardening on the dual-energy computed tomography (DECT) values of iodine maps, virtual monoenergetic (VME) images, and virtual non-contrast (VNC) images. 320-row DECT imaging was performed by changing the x-ray tube energy for the first and second rotations. DECT values of 5 mg/mL iodine of the multi-energy CT phantom were compared with and without a 2-mm-thick attenuation rubber layer (~700 HU) wound around the phantom. It was found that the CT density values UH, with/without the rubber layer had statistical differences in the iodine map (184 ± 0.7 versus 186 ± 1.8), VME images (125 ± 0.3 versus 110 ± 0.4), and VNC images (−58 ± 0.7 versus −76 ± 1.7) (p < 0.010 for all). This suggests that iodine mapping may be underestimated by DECT and overestimated by VME imaging because of x-ray beam hardening. The use of VNC images instead of plain CT images requires further investigation because of underestimation. [ABSTRACT FROM AUTHOR]

Phantoms provide valuable test platforms for developing medical devices. Solid materials in particular allow fabrication of stable and robust models. This paper presents a novel, anatomically realistic, multi-layered head phantom made from dielectrically accurate, stable, easily mouldable, lowcost tissue-mimicking materials for testing of microwave diagnostic systems. Also incorporated is a mechanism for inserting reconfigurable lesions and a novel circulatory system modelling physiology. Tissue-mimicking materials composed of graphite, carbon black, and polyurethane with small volumes of acetone or isopropanol were fabricated and dielectric properties were measured across the 1-8.5GHz band. The tissue-mimicking material properties were adjusted until their dielectric properties matched those of reference values for target tissues of interest, thereby emulating: weighted aggregates of head tissues external to the brain, tissues comprising the brain, and blood. 3D printed anatomically realistic head and brain moulds cast the phantom mixtures for each layer. Cylindrical holes in the brain layer allow insertion of pathological lesion phantoms, such as haemorrhages. Tubing embedded in the brain layer forms a symmetrical loop providing a novel simplistic model of circulation. The resulting head phantom is anatomically realistic, dielectrically stable, enables pathology modelling, and has, uniquely, a circulatory loop.This novel head phantom provides a valuable test platform for microwave diagnostic studies. [ABSTRACT FROM AUTHOR]

Phantoms are important tools for image quality control and medical training. Many phantom materials have been proposed for ultrasound; most of them use water as the solvent, but these materials have disadvantages such as dehydration and low temporal stability if not properly stored. To overcome these difficulties, copolymer-in-oil gel was proposed as an inert and stable material; however, speed of sound for these materials is still lower than what is described for most biological tissues. Here, we propose the glycerol dispersion in oil-based gels to modify the acoustic and elastic properties of copolymer-in-oil phantoms. We manufactured copolymer-in-oil gels using styrene-ethylene/butylene-styrene (SEBS) in concentrations 8%-15%. We used 2 types of mineral oils with different viscosities. Glycerol was added in a volume fraction 0%-30% of the total amount of liquid. The acoustic (i.e., speed of sound, attenuation and backscattering) and the mechanical (i.e., density and Young's modulus) properties of the samples were within the range of values observed for soft tissues. The acoustic parameters of the samples were dependent on oil viscosity and glycerol concentration. The speed of sound ranged 1423 m/s - 1502 m/s, while the acoustic attenuation and the ultrasonic backscattering increased by adding glycerol. The density and the Young's moduli were less affected by the presence of glycerol. We conclude that glycerol can be used to control the acoustic parameters of copolymer-in-oil gels. Additionally, it opens the possibility of incorporating other oil-insoluble substances to control further properties of the phantom. [ABSTRACT FROM AUTHOR]

Tissue damage triggers innate immune response mediated by Toll-like receptor 4 (TLR) that recognizes endogenous host danger molecules associated with cell death and tissue inflammation, although the precise role of TLR-4 signaling in muscle tissue repair is still uncertain. Previously, we observed that TLR-4 exerted a protective effect preventing excessive muscular damage induced by Bothrops jararacussu crude venom. This study aimed to evaluate the involvement of TLR-4 at early stages of muscular tissue remodeling in distinct mouse strains after injection of purified snake venom. Muscular injury was induced by injection of 25 µl (0.05 mg/ml) of cardiotoxin (CTX) from Naja mossambica in the gastrocnemius muscle of C3H/HeN (wild-type); C3H/HeJ mice that express a non-functional TLR-4 receptor, C57BL/6 and Tlr4 (B6 background) mice. Comparing to control, Tlr4 mice presented at early stages (3 DPI) of muscle injury mild inflammation with low MMP-9 activity, scarce macrophage infiltration and premature change to anti-inflammatory phenotype, low TNF-α mRNA levels and reduced myogenin expression, with low regeneration and tissue remodeling. The presence of more Ly6C macrophages in Tlr4 mice at 3 DPI indicates that TLR-4 may influence the differentiation into Ly6C or likely affect proliferation of such cells in the muscle. The present study shows that TLR-4 deficiency and genetic background influence the outcome of muscular tissue repair in aseptic lesions and yet still maintaining some level of signaling in the TLR4-mutant mice. [ABSTRACT FROM AUTHOR]

Intermolecular cross-linking of bone collagen is intimately related to the way collagen molecules are arranged in a fibril, imparts certain mechanical properties to the fibril, and may be involved in the initiation of mineralization. Raman microspectroscopy allows the analysis of minimally processed bone blocks and provides simultaneous information on both the mineral and organic matrix (mainly type I collagen) components, with a spatial resolution of ~1 μm. The aim of the present study was to validate Raman spectroscopic parameters describing one of the major mineralizing type I trivalent cross-links, namely pyridinoline (PYD). To achieve this, a series of collagen cross-linked peptides with known PYD content (as determined by HPLC analysis), human bone, porcine skin, predentin and dentin animal model tissues were analyzed by Raman microspectroscopy. The results of the present study confirm that it is feasible to monitor PYD trivalent collagen cross-links by Raman spectroscopic analysis in mineralized tissues, exclusively through a Raman band ~1660 wavenumbers. This allows determination of the relative PYD content in undecalcified bone tissues with a spatial resolution of ~1 μm, thus enabling correlations with histologic and histomorphometric parameters. [ABSTRACT FROM AUTHOR]

Predictive theoretical-numerical modeling of the behavior and evolution of biological tissue is a difficult task since many of the required knowledge tools (experimental, theoretical and numerical) are still not well understood. We present here some methodologies and results specific to multiscale and multiphysics numerical modeling of biological tissues applied to the predictive behavior of cortical veins depending on their local constituents' microstructure and for bone remodeling and reconstruction as a function of the local mechanobiology. Although further work is required to improve the accuracy of the developed models, the proposed approaches highlight their potential usefulness for understanding the mechanical-biological couplings, short and long term predictions of biological evolutions as well as possible further transfer to medical applications. [ABSTRACT FROM AUTHOR]

Objective To externally validate head and neck cancer (HNC) photon-derived normal tissue complication probability (NTCP) models in patients treated with proton beam therapy (PBT). Methods This prospective cohort consisted of HNC patients treated with PBT at a single institution. NTCP models were selected based on the availability of data for validation and evaluated by using the leave-one-out cross-validated area under the curve (AUC) for the receiver operating characteristics curve. Results 192 patients were included. The most prevalent tumor site was oropharynx ( n = 86, 45%), followed by sinonasal ( n = 28), nasopharyngeal ( n = 27) or parotid ( n = 27) tumors. Apart from the prediction of acute mucositis (reduction of AUC of 0.17), the models overall performed well. The validation (PBT) AUC and the published AUC were respectively 0.90 versus 0.88 for feeding tube 6 months PBT; 0.70 versus 0.80 for physician-rated dysphagia 6 months after PBT; 0.70 versus 0.68 for dry mouth 6 months after PBT; and 0.73 versus 0.85 for hypothyroidism 12 months after PBT. Conclusion Although a drop in NTCP model performance was expected for PBT patients, the models showed robustness and remained valid. Further work is warranted, but these results support the validity of the model-based approach for selecting treatment for patients with HNC. [ABSTRACT FROM AUTHOR]

MR-guided high-intensity focussed ultrasound (MRgHIFU) non-invasive ablative surgeries have advanced into clinical trials for treating many pathologies and cancers. A remaining challenge of these surgeries is accurately planning and monitoring tissue heating in the face of patient-specific and dynamic acoustic properties of tissues. Currently, non-invasive measurements of acoustic properties have not been implemented in MRgHIFU treatment planning and monitoring procedures. This methods-driven study presents a technique using MR temperature imaging (MRTI) during low-temperature HIFU sonications to non-invasively estimate sample-specific acoustic absorption and speed of sound values in tissue-mimicking phantoms. Using measured thermal properties, specific absorption rate (SAR) patterns are calculated from the MRTI data and compared to simulated SAR patterns iteratively generated via the Hybrid Angular Spectrum (HAS) method. Once the error between the simulated and measured patterns is minimised, the estimated acoustic property values are compared to the true phantom values obtained via an independent technique. The estimated values are then used to simulate temperature profiles in the phantoms, and compared to experimental temperature profiles. This study demonstrates that trends in acoustic absorption and speed of sound can be non-invasively estimated with average errors of 21% and 1%, respectively. Additionally, temperature predictions using the estimated properties on average match within 1.2 °C of the experimental peak temperature rises in the phantoms. The positive results achieved in tissue-mimicking phantoms presented in this study indicate that this technique may be extended toin vivoapplications, improving HIFU sonication temperature rise predictions and treatment assessment. [ABSTRACT FROM PUBLISHER]

In this article, a non-linear dual-phase-lag (DPL) bio-heat transfer model based on temperature dependent metabolic heat generation rate is derived to analyze the heat transfer phenomena in living tissues during thermal ablation treatment. The numerical solution of the present non-linear problem has been done by finite element Runge-Kutta (4,5) method which combines the essence of Runge-Kutta (4,5) method together with finite difference scheme. Our study demonstrates that at the thermal ablation position temperature predicted by non-linear and linear DPL models show significant differences. A comparison has been made among non-linear DPL, thermal wave and Pennes model and it has been found that non-linear DPL and thermal wave bio-heat model show almost same nature whereas non-linear Pennes model shows significantly different temperature profile at the initial stage of thermal ablation treatment. The effect of Fourier number and Vernotte number (relaxation Fourier number) on temperature profile in presence and absence of externally applied heat source has been studied in detail and it has been observed that the presence of externally applied heat source term highly affects the efficiency of thermal treatment method. [ABSTRACT FROM AUTHOR]

Besides generating faster solutions, parallel computers can be used to solve bigger or more complex problems. In particular, they can be utilized to run simulations at finer resolutions and to model physical phenomena more realistically. We describe in this article the development of a parallel cellular automata algorithm used in the three-dimensional simulation of multicellular tissue growth. Computational models of this genre are becoming ever more important because they provide an alternative approach to continuous models and an ability to describe the dynamics of complex biological systems evolving in time. We report on the different components of the model where cellular automata is used to model different types of cell populations that execute persistent random walks on the computational grid, collide, aggregate, and proliferate until they reach confluence. We elaborate on the main issues encountered in the parallelization of the algorithm as well as its implementation on a parallel machine with a particular focus on maintaining determinism. By delaying the exchange of cells in the shared boundaries between neighboring processors till after all events related to cell division and motion are accounted for in a given time step, good parallel performance results are obtained on a high-performance cluster. [ABSTRACT FROM AUTHOR]

Research in mammalian cell biology often relies on developing in vitro models to enable the growth of cells in the laboratory to investigate a specific biological mechanism or process under different test conditions. The quality of such models and how they represent the behavior of cells in real tissues plays a critical role in the value of the data produced and how it is used. It is particularly important to recognize how the structure of a cell influences its function and how co-culture models can be used to more closely represent the structure of real tissue. In recent years, technologies have been developed to enhance the way in which researchers can grow cells and more readily create tissue-like structures. Here we identify the limitations of culturing mammalian cells by conventional methods on two-dimensional (2D) substrates and review the popular approaches currently available that enable the development of three-dimensional (3D) tissue models in vitro. There are now many ways in which the growth environment for cultured cells can be altered to encourage 3D cell growth. Approaches to 3D culture can be broadly categorized into scaffold-free or scaffold-based culture systems, with scaffolds made from either natural or synthetic materials. There is no one particular solution that currently satisfies all requirements and researchers must select the appropriate method in line with their needs. Using such technology in conjunction with other modern resources in cell biology (e.g. human stem cells) will provide new opportunities to create robust human tissue mimetics for use in basic research and drug discovery. Application of such models will contribute to advancing basic research, increasing the predictive accuracy of compounds, and reducing animal usage in biomedical science. [ABSTRACT FROM AUTHOR]

Herein, the optical adequacy of a tumor model prepared with tumor cells grown on the chorioallantoic membrane (CAM) of a chicken egg is evaluated as an alternative to the mouse tumor model to assess the optimal irradiation conditions in photodynamic therapy (PDT). The optical properties of CAM and mouse tumor tissues were measured with a double integrating sphere and the inverse Monte Carlo technique in the 350- to 1000-nm wavelength range. The hemoglobin and water absorption bands observed in the CAM tumor tissue (10 eggs and 10 tumors) are equal to that of the mouse tumor tissue (8 animals and 8 tumors). The optical intersubject variability of the CAM tumor tissues meets or exceeds that of the mouse tumor tissues, and the reduced scattering coefficient spectra of CAM tumor tissues can be equated with those of mouse tumor tissues. These results confirm that the CAM tumor model is a viable alternative to the mouse tumor model, especially for deriving optimal irradiation conditions in PDT. [ABSTRACT FROM AUTHOR]

Biomedical optical devices are widely used for clinical detection of various tissue anomalies. However, optical measurements have limited accuracy and traceability, partially owing to the lack of effective calibration methods that simulate the actual tissue conditions. To facilitate standardized calibration and performance evaluation of medical optical devices, we develop a three-dimensional fuse deposition modeling (FDM) technique for freeform fabrication of tissue-simulating phantoms. The FDM system uses transparent gel wax as the base material, titanium dioxide (TiO2) powder as the scattering ingredient, and graphite powder as the absorption ingredient. The ingredients are preheated, mixed, and deposited at the designated ratios layer-by-layer to simulate tissue structural and optical heterogeneities. By printing the sections of human brain model based on magnetic resonance images, we demonstrate the capability for simulating tissue structural heterogeneities. By measuring optical properties of multilayered phantoms and comparing with numerical simulation, we demonstrate the feasibility for simulating tissue optical properties. By creating a rat head phantom with embedded vasculature, we demonstrate the potential for mimicking physiologic processes of a living system. [ABSTRACT FROM AUTHOR]

There is a need for a common reference point that will allow for the comparison of the optical properties of tissue-mimicking phantoms. After a brief review of the methods that have been used to measure the phantoms for a contextual backdrop to our approach, this paper reports on the establishment of a standardized double-integrating-sphere platform to measure absorption and reduced scattering coefficients of tissue-mimicking biomedical phantoms. The platform implements a user-friendly graphical user interface in which variations of experimental configurations and model-based analysis are implemented to compute the coefficients based on a modified inverse adding-doubling algorithm allowing a complete uncertainty evaluation. Repeatability and validation of the measurement results of solid phantoms are demonstrated for three samples of different thicknesses, d = 5.08 mm, 7.09 mm, and 9.92 mm, with an absolute error estimate of 4.0% to 5.0% for the absorption coefficient and 11% to 12% for the reduced scattering coefficient (k = 2). The results are in accordance with those provided by the manufacturer. Measurements with different polarization angles of the incident light are also presented, and the resulting optical properties were determined to be equivalent within the estimated uncertainties. [ABSTRACT FROM AUTHOR]

The emerging technique of rapid prototyping with three-dimensional (3-D) printers provides a simple yet revolutionary method for fabricating objects with arbitrary geometry. The use of 3-D printing for generating morphologically biomimetic tissue phantoms based on medical images represents a potentially major advance over existing phantom approaches. Toward the goal of image-defined phantoms, we converted a segmented fundus image of the human retina into a matrix format and edited it to achieve a geometry suitable for printing. Phantoms with vessel-simulating channels were then printed using a photoreactive resin providing biologically relevant turbidity, as determined by spectrophotometry. The morphology of printed vessels was validated by xray microcomputed tomography. Channels were filled with hemoglobin (Hb) solutions undergoing desaturation, and phantoms were imaged with a near-infrared hyperspectral reflectance imaging system. Additionally, a phantom was printed incorporating two disjoint vascular networks at different depths, each filled with Hb solutions at different saturation levels. Light propagation effects noted during these measurements--including the influence of vessel density and depth on Hb concentration and saturation estimates, and the effect of wavelength on vessel visualization depth--were evaluated. Overall, our findings indicated that 3-D-printed biomimetic phantoms hold significant potential as realistic and practical tools for elucidating light--tissue interactions and characterizing biophotonic system performance. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This paper explores methods that make use of visual cues aimed at generating actual haptic sensation to the user, namely pseudo-haptics. We propose a new pseudo-haptic feedback-based method capable of conveying 3D haptic information and combining visual haptics with force feedback to enhance the user's haptic experience. We focused on an application related to tumor identification during palpation and evaluated the proposed method in an experimental study where users interacted with a haptic device and graphical interface while exploring a virtual model of soft tissue, which represented stiffness distribution of a silicone phantom tissue with embedded hard inclusions. The performance of hard inclusion detection using force feedback only, pseudo-haptic feedback only, and the combination of the two feedbacks was compared with the direct hand touch. The combination method and direct hand touch had no significant difference in the detection results. Compared with the force feedback alone, our method increased the sensitivity by 5%, the positive predictive value by 4%, and decreased detection time by 48.7%. The proposed methodology has great potential for robot-assisted minimally invasive surgery and in all applications where remote haptic feedback is needed. [ABSTRACT FROM AUTHOR]

We present a mathematical model of structural reorganisation in a fibre-reinforced composite material in which the fibres are oriented statistically, i.e. obey a probability distribution of orientation. Such a composite material exemplifies a biological tissue (e.g. articular cartilage or a blood vessel) whose soft matrix is reinforced by collagen fibres. The structural reorganisation of the composite takes place as fibres reorient, in response to mechanical stimuli, in order to optimise the stress distribution in the tissue. Our mathematical model is based on the Principle of Virtual Powers and the study of dissipation. Besides incompressibility, our main hypothesis is that the composite is characterised by a probability density distribution that measures the probability of finding a family of fibres aligned along a given direction at a fixed material point. Under this assumption, we describe the reorientation of fibres as the evolution of the most probable direction along which the fibres are aligned. To test our theory, we compare our simulations of a benchmark problem with selected results taken from the literature. [ABSTRACT FROM AUTHOR]

Motivation: RNA sequencing enables allele-specific expression (ASE) studies that complement standard genotype expression studies for common variants and, importantly, also allow measuring the regulatory impact of rare variants. The Genotype-Tissue Expression (GTEx) project is collecting RNA-seq data on multiple tissues of a same set of individuals and novel methods are required for the analysis of these data. Results: We present a statistical method to compare different patterns of ASE across tissues and to classify genetic variants according to their impact on the tissue-wide expression profile. We focus on strong ASE effects that we are expecting to see for protein-truncating variants, but our method can also be adjusted for other types of ASE effects. We illustrate the method with a real data example on a tissue-wide expression profile of a variant causal for lipoid proteinosis, and with a simulation study to assess our method more generally. [ABSTRACT FROM AUTHOR]

Background: Dual-energy computed tomography (DECT) enables tissue discrimination based on the X-ray attenuations at different photon energies emitted by the tube. The spectral dependencies of net X-ray attenuation can be analyzed and used to characterize specific materials.Purpose: To evaluate the capability of DECT to characterize and differentiate high-density materials, using spectral analysis.Material and Methods: Images of phantoms containing iodine, barium, gadolinium, and calcium solutions in five concentrations were obtained from three DECT scanners and with sequential scanning at different kV values from three conventional MDCT devices. DECT studies were performed with commercial dual-source and rapid kV-switching systems, and a spectral-detector CT (SDCT) prototype based on dual-layer detector technology. Spectral maps describing Hounsfield Units (HU) in low- versus high-energy images were calculated and characterizing curves for all materials were compared.Results: Spectral low- to- high energy maps yielded linear curves (R(2) = 0.98-0.999) with increasing slopes for calcium, gadolinium, barium, and iodine, respectively. Slope differences between all material pairs were highest (reaching 45%) for DECT with dual-source (140/80 kV) and rapid kV-switching (60/80 keV), reaching statistical significance (P < 0.05) with most techniques. Slope differences between all material pairs for sequential scanning were lower (reaching 32%). Slope differences lacked statistical significance for iodine-barium with two sequential-acquisition techniques and the dual-source DECT scanner, and the calcium-gadolium pair with the dual-source scanner.Conclusion: All designated techniques for dual-energy scanning provide robust and material-specific spectral characterization and differentiation of barium, iodine, calcium, and gadolinium, though to varying degrees. [ABSTRACT FROM AUTHOR]

Biological specimens are intrinsically three dimensional; however, because of the obscuring effects of light scatter, imaging deep into a tissue volume is problematic. Although efforts to eliminate the scatter by “clearing” the tissue have been ongoing for over a century, there have been a large number of recent innovations. This Review introduces the physical basis for light scatter in tissue, describes the mechanisms underlying various clearing techniques, and discusses several of the major advances in light microscopy for imaging cleared tissue. [ABSTRACT FROM AUTHOR]

We present the optical measurement techniques used in human skin phantom studies. Their accuracy and the sources of errors in microscopic parameters' estimation of the produced phantoms are described. We have produced optical phantoms for the purpose of simulating human skin tissue at the wavelength of 930 nm. Optical coherence tomography was used to measure the thickness and surface roughness and to detect the internal in homogeneities. A more detailed study of phantom surface roughness was carried out with the optical profilometer. Reflectance, transmittance, and collimated transmittance of phantoms were measured using an integrating-sphere spectrometer setup. The scattering and absorption coefficients were calculated with the inverse adding-doubling method. The reduced scattering coefficient at 930 nm was found to be 1.57 ±0.14 mm-1 and the absorption was 0.22 ± 0.03 mm-1. The retrieved optical properties of phantoms are in agree- ment with the data found in the literature for real human tissues. [ABSTRACT FROM AUTHOR]

Problem statement: The temperature variation in heterogeneous three layered biological tissues was investigated. Approach: The blood perfusion was considered to be temperature dependent. The heating modalities were taking to go on simultaneously in each of the regions on the one hand and also sequentially in another arrangement. The asymptotic series solution was modified for the three layers and the matching were done at the interface of the regions where there is electric field effect and where there is none. Results: The result revealed there was a clear difference from the temperature pattern when the heating modality was done simultaneously compared to when done sequentially. The thickness of the tissues layer has effect on temperature pattern. Conclusion: A lot of attention must be taken to determine tissue thermophysical properties before therapy was applied. The regional body heating was preferred to spare surrounding normal tissue as against the whole body heating procedure. Key words: Heterogeneous, steady states, Penne's bio heat equation, perfusion, INTRODUCTION Hyperthermia has been found to be one of effective therapeutic means of destroying cancerous cells. It's an act of heating the tissue volume to a desired temperature range for [...]

Aligned nanofibrous scaffolds hold tremendous potential for the engineering of dense connective tissues. These biomimetic micropatterns direct organized cell-mediated matrix deposition and can be tuned to possess nonlinear and anisotropic mechanical properties. For these scaffolds to function in vivo, however, they must either recapitulate the full dynamic mechanical range of the native tissue upon implantation or must foster cell infiltration and matrix deposition so as to enable construct maturation to meet these criteria. In our recent studies, we noted that cell infiltration into dense aligned structures is limited but could be expedited via the inclusion of a distinct rapidly eroding sacrificial component. In the present study, we sought to further the fabrication of dynamic nanofibrous constructs by combining multiple-fiber populations, each with distinct mechanical characteristics, into a single composite nanofibrous scaffold. Toward this goal, we developed a novel method for the generation of aligned electrospun composites containing rapidly eroding (PEO), moderately degradable (PLGA and PCL/PLGA), and slowly degrading (PCL) fiber populations. We evaluated the mechanical properties of these composites upon formation and with degradation in a physiologic environment. Furthermore, we employed a hyperelastic constrained-mixture model to capture the nonlinear and time-dependent properties of these scaffolds when formed as single-fiber populations or in multipolymer composites. After validating this model, we demonstrated that by carefully selecting fiber populations with differing mechanical properties and altering the relative fraction of each, a wide range of mechanical properties (and degradation characteristics) can be achieved. This advance allows for the rational design of nanofibrous scaffolds to match native tissue properties and will significantly enhance our ability to fabricate replacements for load-bearing tissues of the musculoskeletal system. [DOI: 10.1115/1.3192140] Keywords: electrospinning, fibrous tissue engineering, composite scaffolds, constitutive modeling, temporal properties, mechanical properties

The fibroblast-populated collagen lattice is an attractive model tissue for in vitro studies of cell behavior and as the basis for bioartificial tissues. In spite of its simplicity--containing only collagen and cells--the system is surprisingly difficult to describe mechanically because of the ability of the cells to remodel the matrix, including compaction at short times and synthesis and/or degradation (and cell proliferation) at longer times. The objectives of this work were to measure the equilibrium modulus of fibroblast-populated gels with different collagen and cell concentrations, and to use that characterization as the basis for a theoretical model that could be used to predict gel mechanics based on conditions. Although many, observations were as expected (e.g., the gel compacts more when there are more cells in it, and the gel is stiffer when there is more collagen in it). an unexpected result arose: the final modulus of the gel was not dependent solely on the final composition. Even (fit compacted more than a gel that was originally at a high collagen concentration, a gel that started at a low collagen concentration remained less still than the higher-concentration gel. In light of these results and experimental studies by others, we propose a model in which the gel compaction is not homogeneous but consists instead of extreme densification near the cells in an otherwise unchanged matrix. By treating the dense regions as spherical inclusions, we used classical composite material theory to develop an expression for the modulus of a compacted gel based on the initial collagen density and the final inclusion (i.e., cell) density. The new model fit the data for moderately compacted gels well but broke down, as expected, for larger volume fractions at which the underlying model assumptions did not apply. [DOI: 10.1115/1.4000064]

We propose a novel model for the measurement of a Mueller matrix for biological tissues. Compared with earlier measurement methods, our method can reduce measurement times and can significantly improve measurement efficiency. Our model needs only six intensity measurements to derive all 16 Mueller matrix components of a biological sample in arbitrary pixels. We used the pellicle cell of magnolia as our sample, and the experimental results are identical with those obtained with other methods. We demonstrate that we can obtain Mueller matrix components to recognize different biological tissues in the same visual field rapidly and reliably. OCIS codes: 120.5410, 180.0180.

Impaired transfer of methyl groups via the methionine cycle leads to plasma hyperhomocysteinemia. The tissue sources of plasma homocysteine in vivo have not been quantified nor whether hyperhomocysteinemia is due to increased entry or decreased removal. These issues were addressed in female rats offered diets with either adequate or excess methionine (additional methyl groups) with or without folate and choline (impaired methyl group transfer) for 5 wk. Whole body and tissue metabolism was measured based on isotopomer analysis following infusion with either [1-[sup.13]C,methyl-[sup.2][H.sub.3]]methionine or [U-[sup.13]C]methionine plus [1-[sup.13]C]homocysteine. Although the fraction of intracellular methionine derived from methylation of homocysteine was highest in liver (0.18-0.21), most was retained. In contrast, the pancreas exported to plasma more of methionine synthesized de novo. The pancreas also exported homocysteine to plasma, and this matched the contribution from liver. Synthesis of methionine from homocysteine was reduced in most tissues with excess methionine supply and was also lowered in fiver (P < 0.01) with diets devoid of folate and choline. Plasma homocysteine concentration (P < 0.001) and flux (P = 0.001) increased with folate plus choline deficiency, although the latter still represented < 12% of estimated tissue production. Hyperhomocysteinemia also increased (P < 0.01) the inflow of homocysteine into most tissues, including heart. These findings indicate that a full understanding of hyperhomocysteinemia needs to include metabolism in a variety of organs, rather than an exclusive focus on the liver. Furthermore, the high influx of homocysteine into cardiac tissue may relate to the known association between fiomocysteinemia and hypertension. stable isotopes; isotopomer analysis; homocysteine methylation; metabolic models

A random nonspherical model for biological tissue and cells permits a better description of their optical properties. Rough surface nonspherical particles have been employed to model biological tissue and cells. The phase function, the anisotropy factor of scattering, and the reduced scattering coefficient are derived. The effect of different size distributions is also discussed. The theoretical results show good agreement with experimental data. OCIS codes: 170.3660, 170.4580, 170.6510, 170.1530, 290.0290.

Forward-peaked and large-angle scattering approximations of the radiative transport equation give rise to generalized Fokker-Planck equations whose main feature is the replacement of the integral scattering operator with differential operators in the direction-space variables. Using the [P.sub.N] method, an appraisal of generalized Fokker-Planck equations due to Gonzalez-Rodriguez and Kim [Appl. Opt. 47, 2599-2609 (2008)], Leakeas and Larsen [Nucl. Sci. Eng. 137, 236-250 (2001), and J. Opt. Soc. Am. A 20, 92-98 (2003)], and Pomraning [Math. Models Meth. Appl. Sci. 2, 21-36 (1992)] is carried out by computing the relative error between the backscattered and transmitted surface flux predicted by the generalized Fokker-Planck equations and the transport equation with Henyey-Greenstein phase function for anisotropies ranging from 0 to 1. Generalized Fokker-Planck equations whose scattering operators incorporate large-angle scattering and possess eigenvalues similar to the integral scattering operator with Henyey-Greenstein phase function are found to minimize the relative error in the limit of unit anisotropy. OCIS codes: 000.3860, 000.4430, 030.5620, 170.3660.

We present a versatile chip-based method to inflict microscopic lesions on cellular networks or tissue models. Our approach relies on resistive heating of microstructured conductors to impose highly localized thermal stress on specific regions of a cell network. We show that networks can be precisely dissected into individual subnetworks using a microwire crossbar array. To this end, we pattern a network of actively beating cardiomyocyte-like cells into smaller subunits by inflicting thermal damage along selected wires of the array. We then investigate the activity and functional connectivity of the individual subnetworks using a Ca2+ imaging-based signal propagation analysis. Our results demonstrate the efficient separation of func-tional activity between individual subnetworks on a microscopic level. We believe that the presented tech-nique may become a powerful tool for investigating lesion and regeneration models in cellular networks. [ABSTRACT FROM AUTHOR]

We present a comparative evaluation of two simple diffuse reflectance models for biological tissue applications. One model is based on a widely accepted and used in biomedical optics implementation of diffusion theory, and the other one is based on a semiempirical approach derived from basic physical principles. We test the models on tissue phantoms and on human skin, utilizing a standard six-around-one optical fiber probe for light delivery and collection. We show that both models are suitable for use with an optical fiber probe and illustrate the potential, applicability, and validity range of the models. OCIS codes: 170.3660, 170.6510.

Diffusion tensor magnetic resonance imaging (DT-MRI) permits the noninvasive assessment of tissue microstructure and, with fibre-tracking algorithms, allows for the 3-D trajectories of white matter fasciculi to be reconstructed noninvasively. Probabilistic algorithms allow one to assign a 'confidence' to a given reconstructed pathway--but often rely on a priori assumptions about sources of uncertainty in the data. Bootstrap methods have been proposed as a way of circumventing this problem, deriving the uncertainty from the data themselves--but acquisition times for data amenable to precise and robust bootstrapping are clinically prohibitive. By combining the wild bootstrap, recently introduced to the DT-MRI literature, with tractography, we show how confidence can be assigned to reconstructed trajectories using data collected in a fraction of the time required for regular bootstrapping. We compare in vivo wild bootstrap tracking results with regular tracking results and show that results are comparable. This approach therefore allows users who have collected data sets for use with deterministic tracking algorithms, rather than those specifically designed for bootstrapping, to be able to apply bootstrap analyses and retrospectively assign confidence to their reconstructed trajectories with minimum additional effort. Index Terms--Bootstrap, diffusion tensor, probabilistic, tractography, wild bootstrap.

Scar formation occurs during the late stages of the inflammatory response but, when excessive, produces fibrosis that can lead to functional and structural damage of tissues. Here, we show that the profibrogenic agonist, transforming growth factor [beta]1, transcriptionally decreases expression of Exchange protein activated by cAMP 1 (Epac1) in fibroblasts/fibroblast-like cells from multiple tissues (i.e., cardiac, lung, and skin fibroblasts and hepatic stellate cells). Overexpression of Epac1 inhibits transforming growth factor [beta]1-induced collagen synthesis, indicating that a decrease of Epac1 expression appears to be necessary for the fibrogenic phenotype, an idea supported by evidence that Epac1 expression in cardiac fibroblasts is inhibited after myocardial infarction. Epac and protein kinase A, a second mediator of cAMP action, have opposite effects on migration but both inhibit synthesis of collagen and DNA by fibroblasts. Epac is preferentially activated by low concentrations of cAMP and stimulates migration via the small G protein Rap1 but inhibits collagen synthesis in a Rap1-independent manner. The regulation of Epac expression and activation thus appear to be critical for the integration of pro- and anti-fibrotic signals and for the regulation of fibroblast function. exchange protein activated by cyclic AMP | fibrosis | protein kinase A | tissue remodeling

The fluorescence temporal profile has been studied at the symmetrical point of the target in tissue phantom by a time-resolved fluorescence diffuse optical tomography method. Indocyanine green served as the fluorescence target. The results showed that the geometrical symmetry of the fluorescence peak intensity ratio was broken due to target position. By using this parameter, an unknown target location could be identified for fluorescence targeting and further reconstruction of the fluorescence image in a tissue model. [ABSTRACT FROM PUBLISHER]

We present the discrete prototype version of our wireless telemetry system architecture, which is suitable for custom IC implementation and intended to eventually retrieve blood pressure and volume (PV) data from small animal subjects (e.g., mice, rats). The architecture consists of four system level blocks that are stacked in $$2.475\,{\hbox{cm}}^{3}$$ volume and it weights 4.0 g. The current prototype's size is well suited for commercial implementation inside medium sized animal subjects, for instance, rabbits and larger rats. Transmit power reported in this paper is tested between 0 to $$-$$ 20 dBm by using phantom tissue model. [ABSTRACT FROM AUTHOR]

The pulse oximeter is a popular instrument to monitor the arterial oxygen saturation (SPO2). Although a fingertip-type pulse oximeter is the mainstream one on the market at present, it is still inconvenient for long-term monitoring, in particular, with respect to motion. Therefore, the development of a wearable pulse oximeter, such as a finger base-type pulse oximeter, can effectively solve the above issue. However, the tissue structure of the finger base is complex, and there is lack of detailed information on the effect of the light source and detector placement on measuring SPO2. In this study, the practicability of a ring-type pulse oximeter with a multi-detector was investigated by optical human tissue simulation. The optimal design of a ring-type pulse oximeter that can provide the best efficiency of measuring SPO2 was discussed. The efficiency of ring-type pulse oximeters with a single detector and a multi-detector was also discussed. Finally, a wearable and wireless ring-type pulse oximeter was also implemented to validate the simulation results and was compared with the commercial fingertip-type pulse oximeter. [ABSTRACT FROM AUTHOR]

This study aims to experimentally investigate the impact of vessel stiffness on the flow dynamics of pulsatile vascular flow. Vessel phantoms with elastic walls were fabricated using polyvinyl alcohol cryogel to result in stiffness ranging from 60.9 to 310.3 kPa and tested with pulsatile flows using a flow circulation set-up. Two-dimensional instantaneous and time-dependent flow velocity and shear rate vector fields were measured using ultrasonic particle image velocimetry (EchoPIV). The waveforms of peak velocities measured by EchoPIV were compared with the ultrasonic pulse Doppler spectrum, and the measuring accuracy was validated. The cyclic vessel wall motion and flow pressure were obtained as well. The results showed that vessel stiffening influenced the waveforms resulting from vessel wall distension and flow pressure, and the fields of flow velocity and shear rate. The stiffer vessel had smaller inner diameter variation, larger pulse pressure and median pressure. The velocity and shear rate maximized at peak systole for all vessels. The results showed a decrease in wall shear stress for a stiffer vessel, which can initiate the atherosclerotic process. Our study elucidates the impact of vessel stiffness on several flow dynamic parameters, and also demonstrates the EchoPIV technique to be a useful and powerful tool in cardiovascular research. [ABSTRACT FROM PUBLISHER]

Mechanical characterization of brain tissue at high loading velocities is crucial for modeling Traumatic Brain Injury (TBI). During severe impact conditions, brain tissue experiences compression, tension and shear. Limited experimental data is available for brain tissue in extension at dynamic strain rates. In this research, a High Rate Tension Device (HRTD) was developed to obtain dynamic properties of brain tissue in extension at strain rates of ≤90/s. In vitro tensile tests were performed to obtain properties of brain tissue at strain rates of 30, 60 and 90/s up to 30% strain. The brain tissue showed a stiffer response with increasing strain rates, showing that hyperelastic models are not adequate. Specifically, the tensile engineering stress at 30% strain was 3.1±0.49kPa, 4.3±0.86kPa, 6.5±0.76kPa (mean±SD) at strain rates of 30, 60 and 90/s, respectively. Force relaxation tests in tension were also conducted at different strain magnitudes (10–60% strain) with the average rise time of 24ms, which were used to derive time dependent parameters. One-term Ogden, Fung and Gent models were used to obtain material parameters from the experimental data. Numerical simulations were performed using a one-term Ogden model to analyze hyperelastic behavior of brain tissue up to 30% strain. The material parameters obtained in this study will help to develop biofidelic human brain finite element models, which can subsequently be used to predict brain injuries under impact conditions and as a reconstruction and simulation tool for forensic investigations. [ABSTRACT FROM AUTHOR]

Here we investigate the basic characteristics of the tissue-equivalent phantom thermoluminescence slab dosimeter with synthetic resin type 1 (TEP-TLSD/SR1), a two-dimensional TLD based on TL phosphor Li3B7012:Cu developed by the Urushiyama Research Group. Li3B7O12:Cu has a single glow peak at 120 °C at a heating rate of 0.317 °C s−1. The dose response is linear between 0.1 and 10 Gy. The phosphor, when combined with a synthetic resin, can be molded into 200 mm × 200 mm × 2.5 mm slabs. The system has a Charge Coupled Device (CCD) dependent spatial resolution (pixel pitch) of 640 μm and a pixel response standard deviation of 1.33%. Using simple pixel-based noise compensation, we were able to improve the signal-to-noise ratio (SNR) in the final image. In tests as a TEP, this system gives off axis ratio and percentage dose depth results highly correlated with those of an ion chamber suspended in a water phantom. The TEP-TLSD/SR1 produces similar images to Gafchromic film for X-ray imaging. This TEP-TLSD/SR1 is not only larger than the prototype, but also has a better SNR and improved usability. With further improvements in tissue equivalence, we foresee a system where a TEP and dosimeter are combined into a three-dimensional dosimeter. [ABSTRACT FROM AUTHOR]

A fourth order Debye model is derived using genetic algorithms to represent the dispersive properties of the 17 tissues that form the human head. The derived model gives accurate estimation of the electrical properties of those tissues across the frequency band from 0.1 GHz to 3 GHz that can be used in microwave systems for head imaging. A convolution-based three-dimensional finite-difference time-domain (3D-FDTD) formulation is implemented for modeling the electromagnetic wave propagation in the dispersive head tissues whose frequency dependent properties are represented by the derived fourth-order Debye model. The presented results show that the proposed 3D-FDTD and fourth-order Debye model can accurately show the electromagnetic interaction between a wide band radiation and head tissues with low computational overhead and more accurate results compared with using multi-pole Cole-Cole model. [ABSTRACT FROM PUBLISHER]

Purpose: A scanning acoustic microscope (SAM) uses an ultrasound to image an object by plotting the speed-of-sound (SOS) through tissues on screen. Because hard tissues result in great SOS, SAM can provide data on the tissue elasticity. This paper investigated the utility of SAM in evaluating thyroid lesions. Methods: Formalin-fixed, paraffin sections were scanned with a 120 MHz transducer. SOS through each area was calculated and plotted on the screen to provide histological images, and SOS of each lesion was compared and statistically analyzed. Results: High-concentrated colloids, red blood cells, and collagen fibers showed great SOS, while low-concentrated colloids, parathyroids, lymph follicles, and epithelial tissues including carcinomas demonstrated lower SOS. SAM clearly discriminated structure of thyroid components corresponding to low magnification of light microscopy. Thyroid tumors were classified into three groups by average SOS: the fast group consisted of follicular adenomas/carcinomas and malignant lymphomas; the slow group contained poorly differentiated/undifferentiated carcinomas; and the intermediate group comprised papillary/medullary carcinomas. Fragmented colloids, irregular-shaped follicles, and desmoplastic reactions were observed in the invasive area of surrounding carcinomas. Conclusion: The SAM imaging method had the following benefits: 1) precise images were acquired in a few minutes without special staining; 2) structural irregularity and desmoplastic reactions, which indicated malignancy, were detected; 3) images reflected tissue elasticity, which was statistically comparable among lesions by SOS; 4) follicular functional activity was predictable by converting colloid concentration to SOS; and 5) tumor classification was predictable by SOS because more poorly differentiated carcinomas had a tendency to show lower SOS. [ABSTRACT FROM AUTHOR]

Abstract: Selection of reconstruction parameters has an effect on the image quantification in PET, with an additional contribution from a scanner-specific attenuation correction method. For achieving comparable results in inter- and intra-center comparisons, any existing quantitative differences should be identified and compensated for. In this study, a comparison between PET, PET/CT and PET/MR is performed by using an anatomical brain phantom, to identify and measure the amount of bias caused due to differences in reconstruction and attenuation correction methods especially in PET/MR. Differences were estimated by using visual, qualitative and quantitative analysis. The qualitative analysis consisted of a line profile analysis for measuring the reproduction of anatomical structures and the contribution of the amount of iterations to image contrast. The quantitative analysis consisted of measurement and comparison of 10 anatomical VOIs, where the HRRT was considered as the reference. All scanners reproduced the main anatomical structures of the phantom adequately, although the image contrast on the PET/MR was inferior when using a default clinical brain protocol. Image contrast was improved by increasing the amount of iterations from 2 to 5 while using 33 subsets. Furthermore, a PET/MR-specific bias was detected, which resulted in underestimation of the activity values in anatomical structures closest to the skull, due to the MR-derived attenuation map that ignores the bone. Thus, further improvements for the PET/MR reconstruction and attenuation correction could be achieved by optimization of RAMLA-specific reconstruction parameters and implementation of bone to the attenuation template. [Copyright &y& Elsevier]

Recent examples have highlighted how stem cells have the capability to initiate morphogenesis in vitro; that is, to generate complex structures in culture that closely parallel their in vivo counterparts. Lgr5, the receptor for the Wnt-agonistic R-spondins, marks stem cells in multiple adult organs of mice and humans. In R-spondin-based three-dimensional cultures, these Lgr5 stem cells can grow into ever-expanding epithelial organoids that retain their original organ identity. Single Lgr5 stem cells derived from the intestine can be cultured to build epithelial structures that retain hallmarks of the in vivo epithelium. Here, we review the mechanisms that support this notable example of self-organization and discuss applications of this technology for stem cell research, disease modeling (e.g., for colorectal cancer and cystic fibrosis), and regenerative medicine. [ABSTRACT FROM AUTHOR]

We present a Monte Carlo lookup table (MCLUT)-based inverse model for extracting optical properties from tissue-simulating phantoms. This model is valid for close source-detector separation and highly absorbing tissues. The MCLUT is based entirely on Monte Carlo simulation, which was implemented using a graphics processing unit. We used tissue-simulating phantoms to determine the accuracy of the MCLUT inverse model. Our results show strong agreement between extracted and expected optical properties, with errors rate of 1.74% for extracted reduced scattering values, 0.74% for extracted absorption values, and 2.42% for extracted hemoglobin concentration values. [ABSTRACT FROM AUTHOR]