Quantitative Ultrasound for Nondestructive Characterization of Engineered Tissues and Biomaterials

PubMed Central

Dalecki, Diane; Mercado, Karla P.; Hocking, Denise C.

2015-01-01

Non-invasive, non-destructive technologies for imaging and quantitatively monitoring the development of artificial tissues are critical for the advancement of tissue engineering. Current standard techniques for evaluating engineered tissues, including histology, biochemical assays and mechanical testing, are destructive approaches. Ultrasound is emerging as a valuable tool for imaging and quantitatively monitoring the properties of engineered tissues and biomaterials longitudinally during fabrication and post-implantation. Ultrasound techniques are rapid, non-invasive, non-destructive and can be easily integrated into sterile environments necessary for tissue engineering. Furthermore, high-frequency quantitative ultrasound techniques can enable volumetric characterization of the structural, biological, and mechanical properties of engineered tissues during fabrication and post-implantation. This review provides an overview of ultrasound imaging, quantitative ultrasound techniques, and elastography, with representative examples of applications of these ultrasound-based techniques to the field of tissue engineering. PMID:26581347

3D printing of tissue-simulating phantoms as a traceable standard for biomedical optical measurement

NASA Astrophysics Data System (ADS)

Dong, Erbao; Wang, Minjie; Shen, Shuwei; Han, Yilin; Wu, Qiang; Xu, Ronald

2016-01-01

Optical phantoms are commonly used to validate and calibrate biomedical optical devices in order to ensure accurate measurement of optical properties in biological tissue. However, commonly used optical phantoms are based on homogenous materials that reflect neither optical properties nor multi-layer heterogeneities of biological tissue. Using these phantoms for optical calibration may result in significant bias in biological measurement. We propose to characterize and fabricate tissue simulating phantoms that simulate not only the multi-layer heterogeneities but also optical properties of biological tissue. The tissue characterization module detects tissue structural and functional properties in vivo. The phantom printing module generates 3D tissue structures at different scales by layer-by-layer deposition of phantom materials with different optical properties. The ultimate goal is to fabricate multi-layer tissue simulating phantoms as a traceable standard for optimal calibration of biomedical optical spectral devices.

In vivo characterization of colorectal metastases in human liver using diffuse reflectance spectroscopy: toward guidance in oncological procedures

NASA Astrophysics Data System (ADS)

Spliethoff, Jarich W.; de Boer, Lisanne L.; Meier, Mark A. J.; Prevoo, Warner; de Jong, Jeroen; Kuhlmann, Koert; Bydlon, Torre M.; Sterenborg, Henricus J. C. M.; Hendriks, Benno H. W.; Ruers, Theo J. M.

2016-09-01

There is a strong need to develop clinical instruments that can perform rapid tissue assessment at the tip of smart clinical instruments for a variety of oncological applications. This study presents the first in vivo real-time tissue characterization during 24 liver biopsy procedures using diffuse reflectance (DR) spectroscopy at the tip of a core biopsy needle with integrated optical fibers. DR measurements were performed along each needle path, followed by biopsy of the target lesion using the same needle. Interventional imaging was coregistered with the DR spectra. Pathology results were compared with the DR spectroscopy data at the final measurement position. Bile was the primary discriminator between normal liver tissue and tumor tissue. Relative differences in bile content matched with the tissue diagnosis based on histopathological analysis in all 24 clinical cases. Continuous DR measurements during needle insertion in three patients showed that the method can also be applied for biopsy guidance or tumor recognition during surgery. This study provides an important validation step for DR spectroscopy-based tissue characterization in the liver. Given the feasibility of the outlined approach, it is also conceivable to make integrated fiber-optic tools for other clinical procedures that rely on accurate instrument positioning.

Imaging and sensing based on dual-pulse nonlinear photoacoustic contrast: a preliminary study on fatty liver

NASA Astrophysics Data System (ADS)

Tian, Chao; Xie, Zhixing; Fabiilli, Mario; Wang, Xueding

2015-03-01

We developed a simple and effective contrast for tissue characterization based on the recently proposed dual-pulse nonlinear photoacoustic technology. The new contrast takes advantage of the temperature dependence of Grüneisen parameter of tissue and involves a dual-pulse laser excitation process. A short pulse first heats the sample and causes a temperature jump, which then leads to the change of Grüneisen parameter and amplitude of the photoacoustic signal of the second pulse. For different tissues, the induced rate or trend of change is expected to be different, which constitutes the basis of the new contrast. Preliminary phantom experiment in blood and lipid mixtures and in vitro experiment in fatty rat liver have demonstrated that the proposed contrast has the capability of fast characterization of lipid-rich and blood-rich tissues.

Concise Review: Mind the Gap: Challenges in Characterizing and Quantifying Cell- and Tissue-Based Therapies for Clinical Translation

PubMed Central

Rayment, Erin A; Williams, David J

2010-01-01

There are many challenges associated with characterizing and quantifying cells for use in cell- and tissue-based therapies. From a regulatory perspective, these advanced treatments must not only be safe and effective but also be made by high-quality manufacturing processes that allow for on-time delivery of viable products. Although sterility assays can be adapted from conventional bioprocessing, cell- and tissue-based therapies require more stringent safety assessments, especially in relation to use of animal products, immune reaction, and potential instability due to extended culture times. Furthermore, cell manufacturers who plan to use human embryonic stem cells in their therapies need to be particularly stringent in their final purification steps, due to the unrestricted growth potential of these cells. This review summarizes the current issues in characterization and quantification for cell- and tissue-based therapies, dividing these challenges into the regulatory themes of safety, potency, and manufacturing quality. It outlines current assays in use, as well as highlights the limits of many of these product release tests. Mode of action is discussed, with particular reference to in vitro surrogate assays that can be used to provide information to correlate with proposed in vivo patient efficacy. Importantly, this review highlights the requirement for basic research to improve current knowledge on the in vivo fate of these treatments; as well as an improved stakeholder negotiation process to identify the measurement requirements that will ensure the manufacture of the best possible cell- and tissue-based therapies within the shortest timeframe for the most patient benefit. PMID:20333747

Characterizing Uncertainty and Variability in PBPK Models: State of the Science and Needs for Research and Implementation

EPA Science Inventory

Mode-of-action based risk and safety assessments can rely upon tissue dosimetry estimates in animals and humans obtained from physiologically-based pharmacokinetic (PBPK) modeling. However, risk assessment also increasingly requires characterization of uncertainty and variabilit...

Screening prostate cancer using a portable near infrared scanning imaging unit with an optical fiber-based rectal probe

NASA Astrophysics Data System (ADS)

Pu, Yang; Wang, Wubao; Tang, Guichen; Budansky, Yury; Sharonov, Mikhail; Xu, Min; Achilefu, Samuel; Eastham, James A.; Alfano, Robert R.

2012-01-01

A portable near infrared scanning polarization imaging unit with an optical fiber-based rectal probe, namely Photonic Finger, was designed and developed o locate the 3D position of abnormal prostate site inside normal prostate tissue. An inverse algorithm, Optical Tomography using Independent Component Analysis (OPTICA) was improved particularly to unmix the signal from targets (cancerous tissue) embedded in a turbid medium (normal tissue) in the backscattering imaging geometry. Photonic Finger combined with OPTICA was tested to characterize different target(s) inside different tissue medium, including cancerous prostate tissue embedded by large piece of normal tissue.

Characterization of dynamic physiology of the bladder by optical coherence tomography

NASA Astrophysics Data System (ADS)

Yuan, Zhijia; Keng, Kerri; Pan, Rubin; Ren, Hugang; Du, Congwu; Kim, Jason; Pan, Yingtian

2012-03-01

Because of its high spatial resolution and noninvasive imaging capabilities, optical coherence tomography has been used to characterize the morphological details of various biological tissues including urinary bladder and to diagnose their alternations (e.g., cancers). In addition to static morphology, the dynamic features of tissue morphology can provide important information that can be used to diagnose the physiological and functional characteristics of biological tissues. Here, we present the imaging studies based on optical coherence tomography to characterize motion related physiology and functions of rat bladder detrusor muscles and compared the results with traditional biomechanical measurements. Our results suggest that optical coherence tomography is capable of providing quantitative evaluation of contractile functions of intact bladder (without removing bladder epithelium and connective tissue), which is potentially of more clinical relevance for future clinical diagnosis - if incorporated with cystoscopic optical coherence tomography.

Characterization and evaluation of graphene oxide scaffold for periodontal wound healing of class II furcation defects in dog.

PubMed

Kawamoto, Kohei; Miyaji, Hirofumi; Nishida, Erika; Miyata, Saori; Kato, Akihito; Tateyama, Akito; Furihata, Tomokazu; Shitomi, Kanako; Iwanaga, Toshihiko; Sugaya, Tsutomu

2018-01-01

The 3-dimensional scaffold plays a key role in volume and quality of repair tissue in periodontal tissue engineering therapy. We fabricated a novel 3D collagen scaffold containing carbon-based 2-dimensional layered material, named graphene oxide (GO). The aim of this study was to characterize and assess GO scaffold for periodontal tissue healing of class II furcation defects in dog. GO scaffolds were prepared by coating the surface of a 3D collagen sponge scaffold with GO dispersion. Scaffolds were characterized using cytotoxicity and tissue reactivity tests. In addition, GO scaffold was implanted into dog class II furcation defects and periodontal healing was investigated at 4 weeks postsurgery. GO scaffold exhibited low cytotoxicity and enhanced cellular ingrowth behavior and rat bone forming ability. In addition, GO scaffold stimulated healing of dog class II furcation defects. Periodontal attachment formation, including alveolar bone, periodontal ligament-like tissue, and cementum-like tissue, was significantly increased by GO scaffold implantation, compared with untreated scaffold. The results suggest that GO scaffold is biocompatible and possesses excellent bone and periodontal tissue formation ability. Therefore, GO scaffold would be beneficial for periodontal tissue engineering therapy.

Bioelectrical Impedance Methods for Noninvasive Health Monitoring: A Review

PubMed Central

Bera, Tushar Kanti

2014-01-01

Under the alternating electrical excitation, biological tissues produce a complex electrical impedance which depends on tissue composition, structures, health status, and applied signal frequency, and hence the bioelectrical impedance methods can be utilized for noninvasive tissue characterization. As the impedance responses of these tissue parameters vary with frequencies of the applied signal, the impedance analysis conducted over a wide frequency band provides more information about the tissue interiors which help us to better understand the biological tissues anatomy, physiology, and pathology. Over past few decades, a number of impedance based noninvasive tissue characterization techniques such as bioelectrical impedance analysis (BIA), electrical impedance spectroscopy (EIS), electrical impedance plethysmography (IPG), impedance cardiography (ICG), and electrical impedance tomography (EIT) have been proposed and a lot of research works have been conducted on these methods for noninvasive tissue characterization and disease diagnosis. In this paper BIA, EIS, IPG, ICG, and EIT techniques and their applications in different fields have been reviewed and technical perspective of these impedance methods has been presented. The working principles, applications, merits, and demerits of these methods has been discussed in detail along with their other technical issues followed by present status and future trends. PMID:27006932

Validation of Ultrasound Elastography Imaging for Nondestructive Characterization of Stiffer Biomaterials.

PubMed

Zhou, Haoyan; Goss, Monika; Hernandez, Christopher; Mansour, Joseph M; Exner, Agata

2016-05-01

Ultrasound elastography (UE) has been widely used as a "digital palpation" tool to characterize tissue mechanical properties in the clinic. UE benefits from the capability of noninvasively generating 2-D elasticity encoded maps. This spatial distribution of elasticity can be especially useful in the in vivo assessment of tissue engineering scaffolds and implantable drug delivery platforms. However, the detection limitations have not been fully characterized and thus its true potential has not been completely discovered. Characterization studies have focused primarily on the range of moduli corresponding to soft tissues, 20-600 kPa. However, polymeric biomaterials used in biomedical applications such as tissue scaffolds, stents, and implantable drug delivery devices can be much stiffer. In order to explore UE's potential to assess mechanical properties of biomaterials in a broader range of applications, this work investigated the detection limit of UE strain imaging beyond soft tissue range. To determine the detection limit, measurements using standard mechanical testing and UE on the same polydimethylsiloxane samples were compared and statistically evaluated. The broadest detection range found based on the current optimized setup is between 47 kPa and 4 MPa which exceeds the modulus of normal soft tissue suggesting the possibility of using this technique for stiffer materials' mechanical characterization. The detectable difference was found to be as low as 157 kPa depending on sample stiffness and experimental setup.

Development and Feasibility Testing of Image-Guided Minimally Invasive Tissue for Diagnosis Treatment of Benign and Malignant Breast Disease

NASA Technical Reports Server (NTRS)

Jeffrey, Stefanie S.

1999-01-01

Dr. Robert Mah and Dr. Stefanie Jeffrey worked on the development of the NASA Smart Probe in its application as a device to measure and interpret physiologic and image-based parameters of breast tissue. To date the following has been achieved: 1 . Choice of candidate sensors to be tested in breast tissue. 2. Preliminary designs for probe tip, specifically use of different tip shapes, cutting edges, and sensor configuration. 3. Design of sonographic guidance system. 4. Design of data extraction and analysis tool using scanned information of images of the breast tissue to provide a higher dimension of information for breast tissue characterization and interpretation. 5. Initial ex-vivo (fruit and tofu) and in-vivo (rodent) testing to confirm unique substance and tissue characterization by the Smart Probe software.

Algorithms and Results of Eye Tissues Differentiation Based on RF Ultrasound

PubMed Central

Jurkonis, R.; Janušauskas, A.; Marozas, V.; Jegelevičius, D.; Daukantas, S.; Patašius, M.; Paunksnis, A.; Lukoševičius, A.

2012-01-01

Algorithms and software were developed for analysis of B-scan ultrasonic signals acquired from commercial diagnostic ultrasound system. The algorithms process raw ultrasonic signals in backscattered spectrum domain, which is obtained using two time-frequency methods: short-time Fourier and Hilbert-Huang transformations. The signals from selected regions of eye tissues are characterized by parameters: B-scan envelope amplitude, approximated spectral slope, approximated spectral intercept, mean instantaneous frequency, mean instantaneous bandwidth, and parameters of Nakagami distribution characterizing Hilbert-Huang transformation output. The backscattered ultrasound signal parameters characterizing intraocular and orbit tissues were processed by decision tree data mining algorithm. The pilot trial proved that applied methods are able to correctly classify signals from corpus vitreum blood, extraocular muscle, and orbit tissues. In 26 cases of ocular tissues classification, one error occurred, when tissues were classified into classes of corpus vitreum blood, extraocular muscle, and orbit tissue. In this pilot classification parameters of spectral intercept and Nakagami parameter for instantaneous frequencies distribution of the 1st intrinsic mode function were found specific for corpus vitreum blood, orbit and extraocular muscle tissues. We conclude that ultrasound data should be further collected in clinical database to establish background for decision support system for ocular tissue noninvasive differentiation. PMID:22654643

Methodology based on genetic heuristics for in-vivo characterizing the patient-specific biomechanical behavior of the breast tissues

PubMed Central

Lago, M. A.; Rúperez, M. J.; Martínez-Martínez, F.; Martínez-Sanchis, S.; Bakic, P. R.; Monserrat, C.

2015-01-01

This paper presents a novel methodology to in-vivo estimate the elastic constants of a constitutive model proposed to characterize the mechanical behavior of the breast tissues. An iterative search algorithm based on genetic heuristics was constructed to in-vivo estimate these parameters using only medical images, thus avoiding invasive measurements of the mechanical response of the breast tissues. For the first time, a combination of overlap and distance coefficients were used for the evaluation of the similarity between a deformed MRI of the breast and a simulation of that deformation. The methodology was validated using breast software phantoms for virtual clinical trials, compressed to mimic MRI-guided biopsies. The biomechanical model chosen to characterize the breast tissues was an anisotropic neo-Hookean hyperelastic model. Results from this analysis showed that the algorithm is able to find the elastic constants of the constitutive equations of the proposed model with a mean relative error of about 10%. Furthermore, the overlap between the reference deformation and the simulated deformation was of around 95% showing the good performance of the proposed methodology. This methodology can be easily extended to characterize the real biomechanical behavior of the breast tissues, which means a great novelty in the field of the simulation of the breast behavior for applications such as surgical planing, surgical guidance or cancer diagnosis. This reveals the impact and relevance of the presented work. PMID:27103760

Methodology based on genetic heuristics for in-vivo characterizing the patient-specific biomechanical behavior of the breast tissues.

PubMed

Lago, M A; Rúperez, M J; Martínez-Martínez, F; Martínez-Sanchis, S; Bakic, P R; Monserrat, C

2015-11-30

This paper presents a novel methodology to in-vivo estimate the elastic constants of a constitutive model proposed to characterize the mechanical behavior of the breast tissues. An iterative search algorithm based on genetic heuristics was constructed to in-vivo estimate these parameters using only medical images, thus avoiding invasive measurements of the mechanical response of the breast tissues. For the first time, a combination of overlap and distance coefficients were used for the evaluation of the similarity between a deformed MRI of the breast and a simulation of that deformation. The methodology was validated using breast software phantoms for virtual clinical trials, compressed to mimic MRI-guided biopsies. The biomechanical model chosen to characterize the breast tissues was an anisotropic neo-Hookean hyperelastic model. Results from this analysis showed that the algorithm is able to find the elastic constants of the constitutive equations of the proposed model with a mean relative error of about 10%. Furthermore, the overlap between the reference deformation and the simulated deformation was of around 95% showing the good performance of the proposed methodology. This methodology can be easily extended to characterize the real biomechanical behavior of the breast tissues, which means a great novelty in the field of the simulation of the breast behavior for applications such as surgical planing, surgical guidance or cancer diagnosis. This reveals the impact and relevance of the presented work.

Hyaluronic acid-based scaffolds for tissue engineering.

PubMed

Chircov, Cristina; Grumezescu, Alexandru Mihai; Bejenaru, Ludovic Everard

2018-01-01

Hyaluronic acid (HA) is a natural glycosaminoglycan found in the extracellular matrix of most connective tissues. Due to its chemical structure, HA is a hydrophilic polymer and it is characterized by a fast degradation rate. HA-based scaffolds for tissue engineering are intensively studied due to their increased biocompatibility, biodegradability and chemical modification. Depending on the processing technique, scaffolds can be prepared in the form of hydrogels, sponges, cryogels, and injectable hydrogels, all discussed in this review.

Accuracy of the raw-data-based effective atomic numbers and monochromatic CT numbers for contrast medium with a dual-energy CT technique.

PubMed

Kawahara, Daisuke; Ozawa, Shuichi; Yokomachi, Kazushi; Tanaka, Sodai; Higaki, Toru; Fujioka, Chikako; Suzuki, Tatsuhiko; Tsuneda, Masato; Nakashima, Takeo; Ohno, Yoshimi; Nagata, Yasushi

2018-02-01

To evaluate the accuracy of raw-data-based effective atomic number (Z eff ) values and monochromatic CT numbers for contrast material of varying iodine concentrations, obtained using dual-energy CT. We used a tissue characterization phantom and varying concentrations of iodinated contrast medium. A comparison between the theoretical values of Z eff and that provided by the manufacturer was performed. The measured and theoretical monochromatic CT numbers at 40-130 keV were compared. The average difference between the Z eff values of lung (inhale) inserts in the tissue characterization phantom was 81.3% and the average Z eff difference was within 8.4%. The average difference between the Z eff values of the varying concentrations of iodinated contrast medium was within 11.2%. For the varying concentrations of iodinated contrast medium, the differences between the measured and theoretical monochromatic CT values increased with decreasing monochromatic energy. The Z eff and monochromatic CT numbers in the tissue characterization phantom were reasonably accurate. The accuracy of the raw-data-based Z eff values was higher than that of image-based Z eff values in the tissue-equivalent phantom. The accuracy of Z eff values in the contrast medium was in good agreement within the maximum SD found in the iodine concentration range of clinical dynamic CT imaging. Moreover, the optimum monochromatic energy for human tissue and iodinated contrast medium was found to be 70 keV. Advances in knowledge: The accuracy of the Z eff values and monochromatic CT numbers of the contrast medium created by raw-data-based, dual-energy CT could be sufficient in clinical conditions.

Characterization of the Distance Relationship Between Localized Serotonin Receptors and Glia Cells on Fluorescence Microscopy Images of Brain Tissue.

PubMed

Jacak, Jaroslaw; Schaller, Susanne; Borgmann, Daniela; Winkler, Stephan M

2015-08-01

We here present two new methods for the characterization of fluorescent localization microscopy images obtained from immunostained brain tissue sections. Direct stochastic optical reconstruction microscopy images of 5-HT1A serotonin receptors and glial fibrillary acidic proteins in healthy cryopreserved brain tissues are analyzed. In detail, we here present two image processing methods for characterizing differences in receptor distribution on glial cells and their distribution on neural cells: One variant relies on skeleton extraction and adaptive thresholding, the other on k-means based discrete layer segmentation. Experimental results show that both methods can be applied for distinguishing classes of images with respect to serotonin receptor distribution. Quantification of nanoscopic changes in relative protein expression on particular cell types can be used to analyze degeneration in tissues caused by diseases or medical treatment.

Computer-based objective quantitative assessment of pulmonary parenchyma via x-ray CT

NASA Astrophysics Data System (ADS)

Uppaluri, Renuka; McLennan, Geoffrey; Sonka, Milan; Hoffman, Eric A.

1998-07-01

This paper is a review of our recent studies using a texture- based tissue characterization method called the Adaptive Multiple Feature Method. This computerized method is automated and performs tissue classification based upon the training acquired on a set of representative examples. The AMFM has been applied to several different discrimination tasks including normal subjects, subjects with interstitial lung disease, smokers, asbestos-exposed subjects, and subjects with cystic fibrosis. The AMFM has also been applied to data acquired using different scanners and scanning protocols. The AMFM has shown to be successful and better than other existing techniques in discriminating the tissues under consideration. We demonstrate that the AMFM is considerably more sensitive and specific in characterizing the lung, especially in the presence of mixed pathology, as compared to more commonly used methods. Evidence is presented suggesting that the AMFM is highly sensitive to some of the earliest disease processes.

Tissue characterization using electrical impedance spectroscopy data: a linear algebra approach.

PubMed

Laufer, Shlomi; Solomon, Stephen B; Rubinsky, Boris

2012-06-01

In this study, we use a new linear algebra manipulation on electrical impedance spectroscopy measurements to provide real-time information regarding the nature of the tissue surrounding the needle in minimal invasive procedures. Using a Comsol Multiphysics three-dimensional model, a phantom based on ex vivo animal tissue and in vivo animal data, we demonstrate how tissue inhomogeneity can be characterized without any previous knowledge of the electrical properties of the different tissues, except that they should not be linearly dependent on a certain frequency range. This method may have applications in needle biopsies, radiation seeds, or minimally invasive surgery and can reduce the number of computer tomography or magnetic resonance imaging images. We conclude by demonstrating how this mathematical approach can be useful in other applications.

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

PubMed

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.

An intraoperative probe combining positron detection and OCT imaging for ovarian cancer detection and characterization

NASA Astrophysics Data System (ADS)

Yang, Yi; Wang, Tianheng; Biswal, Nrusingh; Kumavor, Patrick; Wang, Xiaohong; Karimeddini, Mozafareddin; Vento, John; Sanders, Melinda; Brewer, Molly; Zhu, Quing

2012-01-01

In this paper, we report an intraoperative approach by combining optical coherence tomography (OCT) and position detection to detect and characterize ovarian cancers. A total of 18 ovaries were studied ex vivo. Based on histopathology result, they were classified into normal and malignant groups, respectively. On average positron count rate of 8.0-fold higher was found between malignant and normal ovaries. OCT imaging of ovaries revealed many detailed morphologic features that could be potentially valuable for detecting early malignant changes in ovarian tissue. Optical scattering coefficients of these ovaries were estimated from OCT A-lines. Normal ovarian tissue showed higher scattering coefficient than that of malignant ovarian tissue. Using a threshold of 2.00 mm-1 for all ovaries, a sensitivity of 100% and a specificity of 100% were achieved. This initial data shows our intraoperative probe based on OCT and positron detection has a great potential for ovarian cancer detection and characterization.

Quantitative characterization of mechanically indented in vivo human skin in adults and infants using optical coherence tomography

NASA Astrophysics Data System (ADS)

Huang, Pin-Chieh; Pande, Paritosh; Shelton, Ryan L.; Joa, Frank; Moore, Dave; Gillman, Elisa; Kidd, Kimberly; Nolan, Ryan M.; Odio, Mauricio; Carr, Andrew; Boppart, Stephen A.

2017-03-01

Influenced by both the intrinsic viscoelasticity of the tissue constituents and the time-evolved redistribution of fluid within the tissue, the biomechanical response of skin can reflect not only localized pathology but also systemic physiology of an individual. While clinical diagnosis of skin pathologies typically relies on visual inspection and manual palpation, a more objective and quantitative approach for tissue characterization is highly desirable. Optical coherence tomography (OCT) is an interferometry-based imaging modality that enables in vivo assessment of cross-sectional tissue morphology with micron-scale resolution, which surpasses those of most standard clinical imaging tools, such as ultrasound imaging and magnetic resonance imaging. This pilot study investigates the feasibility of characterizing the biomechanical response of in vivo human skin using OCT. OCT-based quantitative metrics were developed and demonstrated on the human subject data, where a significant difference between deformed and nondeformed skin was revealed. Additionally, the quantified postindentation recovery results revealed differences between aged (adult) and young (infant) skin. These suggest that OCT has the potential to quantitatively assess the mechanically perturbed skin as well as distinguish different physiological conditions of the skin, such as changes with age or disease.

The acellular matrix (ACM) for bladder tissue engineering: A quantitative magnetic resonance imaging study.

PubMed

Cheng, Hai-Ling Margaret; Loai, Yasir; Beaumont, Marine; Farhat, Walid A

2010-08-01

Bladder acellular matrices (ACMs) derived from natural tissue are gaining increasing attention for their role in tissue engineering and regeneration. Unlike conventional scaffolds based on biodegradable polymers or gels, ACMs possess native biomechanical and many acquired biologic properties. Efforts to optimize ACM-based scaffolds are ongoing and would be greatly assisted by a noninvasive means to characterize scaffold properties and monitor interaction with cells. MRI is well suited to this role, but research with MRI for scaffold characterization has been limited. This study presents initial results from quantitative MRI measurements for bladder ACM characterization and investigates the effects of incorporating hyaluronic acid, a natural biomaterial useful in tissue-engineering and regeneration. Measured MR relaxation times (T(1), T(2)) and diffusion coefficient were consistent with increased water uptake and glycosaminoglycan content observed on biochemistry in hyaluronic acid ACMs. Multicomponent MRI provided greater specificity, with diffusion data showing an acellular environment and T(2) components distinguishing the separate effects of increased glycosaminoglycans and hydration. These results suggest that quantitative MRI may provide useful information on matrix composition and structure, which is valuable in guiding further development using bladder ACMs for organ regeneration and in strategies involving the use of hyaluronic acid.

Mechanical characterization of disordered and anisotropic cellular monolayers

NASA Astrophysics Data System (ADS)

Nestor-Bergmann, Alexander; Johns, Emma; Woolner, Sarah; Jensen, Oliver E.

2018-05-01

We consider a cellular monolayer, described using a vertex-based model, for which cells form a spatially disordered array of convex polygons that tile the plane. Equilibrium cell configurations are assumed to minimize a global energy defined in terms of cell areas and perimeters; energy is dissipated via dynamic area and length changes, as well as cell neighbor exchanges. The model captures our observations of an epithelium from a Xenopus embryo showing that uniaxial stretching induces spatial ordering, with cells under net tension (compression) tending to align with (against) the direction of stretch, but with the stress remaining heterogeneous at the single-cell level. We use the vertex model to derive the linearized relation between tissue-level stress, strain, and strain rate about a deformed base state, which can be used to characterize the tissue's anisotropic mechanical properties; expressions for viscoelastic tissue moduli are given as direct sums over cells. When the base state is isotropic, the model predicts that tissue properties can be tuned to a regime with high elastic shear resistance but low resistance to area changes, or vice versa.

Characterization and evaluation of graphene oxide scaffold for periodontal wound healing of class II furcation defects in dog

PubMed Central

Kawamoto, Kohei; Miyaji, Hirofumi; Nishida, Erika; Miyata, Saori; Kato, Akihito; Tateyama, Akito; Furihata, Tomokazu; Shitomi, Kanako; Iwanaga, Toshihiko; Sugaya, Tsutomu

2018-01-01

Introduction The 3-dimensional scaffold plays a key role in volume and quality of repair tissue in periodontal tissue engineering therapy. We fabricated a novel 3D collagen scaffold containing carbon-based 2-dimensional layered material, named graphene oxide (GO). The aim of this study was to characterize and assess GO scaffold for periodontal tissue healing of class II furcation defects in dog. Materials and methods GO scaffolds were prepared by coating the surface of a 3D collagen sponge scaffold with GO dispersion. Scaffolds were characterized using cytotoxicity and tissue reactivity tests. In addition, GO scaffold was implanted into dog class II furcation defects and periodontal healing was investigated at 4 weeks postsurgery. Results GO scaffold exhibited low cytotoxicity and enhanced cellular ingrowth behavior and rat bone forming ability. In addition, GO scaffold stimulated healing of dog class II furcation defects. Periodontal attachment formation, including alveolar bone, periodontal ligament-like tissue, and cementum-like tissue, was significantly increased by GO scaffold implantation, compared with untreated scaffold. Conclusion The results suggest that GO scaffold is biocompatible and possesses excellent bone and periodontal tissue formation ability. Therefore, GO scaffold would be beneficial for periodontal tissue engineering therapy. PMID:29713167

High Throughput PBPK: Evaluating EPA's Open-Source Data and Tools for Dosimetry and Exposure Reconstruction (SOT)

EPA Science Inventory

To address this need, new tools have been created for characterizing, simulating, and evaluating chemical biokinetics. Physiologically-based pharmacokinetic (PBPK) models provide estimates of chemical exposures that produce potentially hazardous tissue concentrations, while tissu...

Tissue slide-based microRNA characterization of tumors: how detailed could diagnosis become for cancer medicine?

PubMed Central

Sempere, Lorenzo F

2014-01-01

miRNAs are short, non-coding, regulatory RNAs that exert cell type-dependent, context-dependent, transcriptome-wide gene expression control under physiological and pathological conditions. Tissue slide-based assays provide qualitative (tumor compartment) and semi-quantitative (expression levels) information about altered miRNA expression at single-cell resolution in clinical tumor specimens. Reviewed here are key technological advances in the last 5 years that have led to implementation of fully automated, robust and reproducible tissue slide-based assays for in situ miRNA detection on US FDA-approved instruments; recent tissue slide-based discovery studies that suggest potential clinical applications of specific miRNAs in cancer medicine are highlighted; and the challenges in bringing tissue slide-based miRNA assays into the clinic are discussed, including clinical validation, biomarker performance, biomarker space and integration with other biomarkers. PMID:25090088

Starch Turnover and Metabolism during Flower and Early Embryo Development1[CC-BY

PubMed Central

Pazmino, Diana; Gagliardini, Valeria

2016-01-01

The accumulation of starch within photosynthetic tissues and within dedicated storage organs has been characterized extensively in many species, and a function in buffering carbon availability or in fueling later growth phases, respectively, has been proposed. However, developmentally regulated starch turnover within heterotrophic tissues other than dedicated storage organs is poorly characterized, and its function is not well understood. Here, we report on the characterization of starch turnover during flower, early embryo, and silique development in Arabidopsis (Arabidopsis thaliana) using a combined clearing-staining technique on whole-mount tissue. Besides the two previously documented waves of transient starch accumulation in the stamen envelope, occurring during meiosis and pollen mitosis I, we identified a novel, third wave of starch amylogenesis/amylolysis during the last stages of stamen development. To gain insights into the underlying molecular mechanisms, we analyzed publicly available microarray data, which revealed a developmentally coordinated expression of carbohydrate transport and metabolism genes during these waves of transient starch accumulation. Based on this analysis, we characterized starch dynamics in mutants affecting hexose phosphate metabolism and translocation, and identified the Glc-6-phosphate/phosphate antiporter GPT1 as the putative translocator of Glc-6-phosphate for starch biosynthesis in reproductive tissues. Based on these results, we propose a model of starch synthesis within the pollen grain and discuss the nutrient transport route feeding the embryo within the developing seed. PMID:27794100

OCT-based approach to local relaxations discrimination from translational relaxation motions

NASA Astrophysics Data System (ADS)

Matveev, Lev A.; Matveyev, Alexandr L.; Gubarkova, Ekaterina V.; Gelikonov, Grigory V.; Sirotkina, Marina A.; Kiseleva, Elena B.; Gelikonov, Valentin M.; Gladkova, Natalia D.; Vitkin, Alex; Zaitsev, Vladimir Y.

2016-04-01

Multimodal optical coherence tomography (OCT) is an emerging tool for tissue state characterization. Optical coherence elastography (OCE) is an approach to mapping mechanical properties of tissue based on OCT. One of challenging problems in OCE is elimination of the influence of residual local tissue relaxation that complicates obtaining information on elastic properties of the tissue. Alternatively, parameters of local relaxation itself can be used as an additional informative characteristic for distinguishing the tissue in normal and pathological states over the OCT image area. Here we briefly present an OCT-based approach to evaluation of local relaxation processes in the tissue bulk after sudden unloading of its initial pre-compression. For extracting the local relaxation rate we evaluate temporal dependence of local strains that are mapped using our recently developed hybrid phase resolved/displacement-tracking (HPRDT) approach. This approach allows one to subtract the contribution of global displacements of scatterers in OCT scans and separate the temporal evolution of local strains. Using a sample excised from of a coronary arteria, we demonstrate that the observed relaxation of local strains can be reasonably fitted by an exponential law, which opens the possibility to characterize the tissue by a single relaxation time. The estimated local relaxation times are assumed to be related to local biologically-relevant processes inside the tissue, such as diffusion, leaking/draining of the fluids, local folding/unfolding of the fibers, etc. In general, studies of evolution of such features can provide new metrics for biologically-relevant changes in tissue, e.g., in the problems of treatment monitoring.

Noncontact quantitative biomechanical characterization of cardiac muscle using shear wave imaging optical coherence tomography

PubMed Central

Wang, Shang; Lopez, Andrew L.; Morikawa, Yuka; Tao, Ge; Li, Jiasong; Larina, Irina V.; Martin, James F.; Larin, Kirill V.

2014-01-01

We report on a quantitative optical elastographic method based on shear wave imaging optical coherence tomography (SWI-OCT) for biomechanical characterization of cardiac muscle through noncontact elasticity measurement. The SWI-OCT system employs a focused air-puff device for localized loading of the cardiac muscle and utilizes phase-sensitive OCT to monitor the induced tissue deformation. Phase information from the optical interferometry is used to reconstruct 2-D depth-resolved shear wave propagation inside the muscle tissue. Cross-correlation of the displacement profiles at various spatial locations in the propagation direction is applied to measure the group velocity of the shear waves, based on which the Young’s modulus of tissue is quantified. The quantitative feature and measurement accuracy of this method is demonstrated from the experiments on tissue-mimicking phantoms with the verification using uniaxial compression test. The experiments are performed on ex vivo cardiac muscle tissue from mice with normal and genetically altered myocardium. Our results indicate this optical elastographic technique is useful as a noncontact tool to assist the cardiac muscle studies. PMID:25071943

Characterizing the heterogeneity of tumor tissues from spatially resolved molecular measures

PubMed Central

Zavodszky, Maria I.

2017-01-01

Background Tumor heterogeneity can manifest itself by sub-populations of cells having distinct phenotypic profiles expressed as diverse molecular, morphological and spatial distributions. This inherent heterogeneity poses challenges in terms of diagnosis, prognosis and efficient treatment. Consequently, tools and techniques are being developed to properly characterize and quantify tumor heterogeneity. Multiplexed immunofluorescence (MxIF) is one such technology that offers molecular insight into both inter-individual and intratumor heterogeneity. It enables the quantification of both the concentration and spatial distribution of 60+ proteins across a tissue section. Upon bioimage processing, protein expression data can be generated for each cell from a tissue field of view. Results The Multi-Omics Heterogeneity Analysis (MOHA) tool was developed to compute tissue heterogeneity metrics from MxIF spatially resolved tissue imaging data. This technique computes the molecular state of each cell in a sample based on a pathway or gene set. Spatial states are then computed based on the spatial arrangements of the cells as distinguished by their respective molecular states. MOHA computes tissue heterogeneity metrics from the distributions of these molecular and spatially defined states. A colorectal cancer cohort of approximately 700 subjects with MxIF data is presented to demonstrate the MOHA methodology. Within this dataset, statistically significant correlations were found between the intratumor AKT pathway state diversity and cancer stage and histological tumor grade. Furthermore, intratumor spatial diversity metrics were found to correlate with cancer recurrence. Conclusions MOHA provides a simple and robust approach to characterize molecular and spatial heterogeneity of tissues. Research projects that generate spatially resolved tissue imaging data can take full advantage of this useful technique. The MOHA algorithm is implemented as a freely available R script (see supplementary information). PMID:29190747

SH2 Domain Histochemistry.

PubMed

Buhs, Sophia; Nollau, Peter

2017-01-01

Among posttranslational modifications, the phosphorylation of tyrosine residues is a key modification in cell signaling. Because of its biological importance, characterization of the cellular state of tyrosine phosphorylation is of great interest. Based on the unique properties of endogenously expressed SH2 domains recognizing tyrosine phosphorylated signaling proteins with high specificity we have developed an alternative approach, coined SH2 profiling, enabling us to decipher complex patterns of tyrosine phosphorylation in various normal and cancerous tissues. So far, SH2 profiling has largely been applied for the analysis of protein extracts with the limitation that information on spatial distribution and intensity of tyrosine phosphorylation within a tissue is lost. Here, we describe a novel SH2 domain based strategy for differential characterization of the state of tyrosine phosphorylation in formaldehyde-fixed and paraffin-embedded tissues. This approach demonstrates that SH2 domains may serve as very valuable tools for the analysis of the differential state of tyrosine phosphorylation in primary tissues fixed and processed under conditions frequently applied by routine pathology laboratories.

Characterizing optical properties and spatial heterogeneity of human ovarian tissue using spatial frequency domain imaging

NASA Astrophysics Data System (ADS)

Nandy, Sreyankar; Mostafa, Atahar; Kumavor, Patrick D.; Sanders, Melinda; Brewer, Molly; Zhu, Quing

2016-10-01

A spatial frequency domain imaging (SFDI) system was developed for characterizing ex vivo human ovarian tissue using wide-field absorption and scattering properties and their spatial heterogeneities. Based on the observed differences between absorption and scattering images of different ovarian tissue groups, six parameters were quantitatively extracted. These are the mean absorption and scattering, spatial heterogeneities of both absorption and scattering maps measured by a standard deviation, and a fitting error of a Gaussian model fitted to normalized mean Radon transform of the absorption and scattering maps. A logistic regression model was used for classification of malignant and normal ovarian tissues. A sensitivity of 95%, specificity of 100%, and area under the curve of 0.98 were obtained using six parameters extracted from the SFDI images. The preliminary results demonstrate the diagnostic potential of the SFDI method for quantitative characterization of wide-field optical properties and the spatial distribution heterogeneity of human ovarian tissue. SFDI could be an extremely robust and valuable tool for evaluation of the ovary and detection of neoplastic changes of ovarian cancer.

Monoclonal antibodies to murine thrombospondin-1 and thrombospondin-2 reveal differential expression patterns in cancer and low antigen expression in normal tissues

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bujak, Emil; Pretto, Francesca; Ritz, Danilo

2014-09-10

There is a considerable interest for the discovery and characterization of tumor-associated antigens, which may facilitate antibody-based pharmacodelivery strategies. Thrombospondin-1 and thrombospondin-2 are homologous secreted proteins, which have previously been reported to be overexpressed during remodeling typical for wound healing and tumor progression and to possibly play a functional role in cell proliferation, migration and apoptosis. To our knowledge, a complete immunohistochemical characterization of thrombospondins levels in normal rodent tissues has not been reported so far. Using antibody phage technology, we have generated and characterized monoclonal antibodies specific to murine thrombospondin-1 and thrombospondin-2, two antigens which share 62% aminoacid identity.more » An immunofluorescence analysis revealed that both antigens are virtually undetectable in normal mouse tissues, except for a weak staining of heart tissue by antibodies specific to thrombospondin-1. The analysis also showed that thrombospondin-1 was strongly expressed in 5/7 human tumors xenografted in nude mice, while it was only barely detectable in 3/8 murine tumors grafted in immunocompetent mice. By contrast, a high-affinity antibody to thrombospondin-2 revealed a much lower level of expression of this antigen in cancer specimens. Our analysis resolves ambiguities related to conflicting reports on thrombosponding expression in health and disease. Based on our findings, thrombospondin-1 (and not thrombospondin-2) may be considered as a target for antibody-based pharmacodelivery strategies, in consideration of its low expression in normal tissues and its upregulation in cancer. - Highlights: • High affinity monoclonal antibodies to murine and human TSP1 and 2 were raised. • Both antigens are virtually undetectable in normal mouse tissues. • Strong positivity of human tumor xenografts for TSP1 was detected. • Study revealed much lower level of TSP2 expression in cancer specimens. • TSP1 (and not TSP2) may be considered as a target for antibody-based pharmacodelivery.« less

Energy-Based Tissue Fusion for Sutureless Closure: Applications, Mechanisms, and Potential for Functional Recovery.

PubMed

Kramer, Eric A; Rentschler, Mark E

2018-06-04

As minimally invasive surgical techniques progress, the demand for efficient, reliable methods for vascular ligation and tissue closure becomes pronounced. The surgical advantages of energy-based vessel sealing exceed those of traditional, compression-based ligatures in procedures sensitive to duration, foreign bodies, and recovery time alike. Although the use of energy-based devices to seal or transect vasculature and connective tissue bundles is widespread, the breadth of heating strategies and energy dosimetry used across devices underscores an uncertainty as to the molecular nature of the sealing mechanism and induced tissue effect. Furthermore, energy-based techniques exhibit promise for the closure and functional repair of soft and connective tissues in the nervous, enteral, and dermal tissue domains. A constitutive theory of molecular bonding forces that arise in response to supraphysiological temperatures is required in order to optimize and progress the use of energy-based tissue fusion. While rapid tissue bonding has been suggested to arise from dehydration, dipole interactions, molecular cross-links, or the coagulation of cellular proteins, long-term functional tissue repair across fusion boundaries requires that the reaction to thermal damage be tailored to catalyze the onset of biological healing and remodeling. In this review, we compile and contrast findings from published thermal fusion research in an effort to encourage a molecular approach to characterization of the prevalent and promising energy-based tissue bond.

Biological and mechanical interplay at the Macro- and Microscales Modulates the Cell-Niche Fate.

PubMed

Sarig, Udi; Sarig, Hadar; Gora, Aleksander; Krishnamoorthi, Muthu Kumar; Au-Yeung, Gigi Chi Ting; de-Berardinis, Elio; Chaw, Su Yin; Mhaisalkar, Priyadarshini; Bogireddi, Hanumakumar; Ramakrishna, Seeram; Boey, Freddy Yin Chiang; Venkatraman, Subbu S; Machluf, Marcelle

2018-03-02

Tissue development, regeneration, or de-novo tissue engineering in-vitro, are based on reciprocal cell-niche interactions. Early tissue formation mechanisms, however, remain largely unknown given complex in-vivo multifactoriality, and limited tools to effectively characterize and correlate specific micro-scaled bio-mechanical interplay. We developed a unique model system, based on decellularized porcine cardiac extracellular matrices (pcECMs)-as representative natural soft-tissue biomaterial-to study a spectrum of common cell-niche interactions. Model monocultures and 1:1 co-cultures on the pcECM of human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs) were mechano-biologically characterized using macro- (Instron), and micro- (AFM) mechanical testing, histology, SEM and molecular biology aspects using RT-PCR arrays. The obtained data was analyzed using developed statistics, principal component and gene-set analyses tools. Our results indicated biomechanical cell-type dependency, bi-modal elasticity distributions at the micron cell-ECM interaction level, and corresponding differing gene expression profiles. We further show that hMSCs remodel the ECM, HUVECs enable ECM tissue-specific recognition, and their co-cultures synergistically contribute to tissue integration-mimicking conserved developmental pathways. We also suggest novel quantifiable measures as indicators of tissue assembly and integration. This work may benefit basic and translational research in materials science, developmental biology, tissue engineering, regenerative medicine and cancer biomechanics.

Time-resolved photoacoustic measurement for evaluation of viscoelastic properties of biological tissues

NASA Astrophysics Data System (ADS)

Zhao, Yue; Chen, Conggui; Liu, Hongwei; Yang, Sihua; Xing, Da

2016-11-01

In this letter, we proposed a method for viscoelastic characterization of biological tissues based on time-resolved photoacoustic measurement. The theoretical and experimental study was performed on the influence of viscoelasticity effects on photoacoustic generation. Taking the time delay between the photoacoustic signal and the exciting laser, the viscoelasticity distribution of biological tissues can be mapped. To validate our method, gelatin phantoms with different densities were measured. We also applied this method in discrimination between fat and liver to confirm the usefulness of the viscoelastic evaluation. Furthermore, pilot experiments were performed on atherosclerosis artery from an apolipoprotein E-knockout mouse to show the viscoelastic characterization of atherosclerotic plaque. Our results demonstrate that this technique has the potential for visualizing the biomechanical properties and lesions of biological tissues.

Effect of Graphite Concentration on Shear-Wave Speed in Gelatin-Based Tissue-Mimicking Phantoms

PubMed Central

Anderson, Pamela G.; Rouze, Ned C.; Palmeri, Mark L.

2011-01-01

Elasticity-based imaging modalities are becoming popular diagnostic tools in clinical practice. Gelatin-based, tissue mimicking phantoms that contain graphite as the acoustic scattering material are commonly used in testing and validating elasticity-imaging methods to quantify tissue stiffness. The gelatin bloom strength and concentration are used to control phantom stiffness. While it is known that graphite concentration can be modulated to control acoustic attenuation, the impact of graphite concentrationon phantom elasticity has not been characterized in these gelatin phantoms. This work investigates the impact of graphite concentration on phantom shear stiffness as characterized by shear-wave speed measurements using impulsive acoustic-radiation-force excitations. Phantom shear-wave speed increased by 0.83 (m/s)/(dB/(cm MHz)) when increasing the attenuation coefficient slope of the phantom material through increasing graphite concentration. Therefore, gelatin-phantom stiffness can be affected by the conventional ways that attenuation is modulated through graphite concentration in these phantoms. PMID:21710828

Characterizing viscoelastic properties of breast cancer tissue in a mouse model using indentation.

PubMed

Qiu, Suhao; Zhao, Xuefeng; Chen, Jiayao; Zeng, Jianfeng; Chen, Shuangqing; Chen, Lei; Meng, You; Liu, Biao; Shan, Hong; Gao, Mingyuan; Feng, Yuan

2018-03-01

Breast cancer is one of the leading cancer forms affecting females worldwide. Characterizing the mechanical properties of breast cancer tissue is important for diagnosis and uncovering the mechanobiology mechanism. Although most of the studies were based on human cancer tissue, an animal model is still describable for preclinical analysis. Using a custom-build indentation device, we measured the viscoelastic properties of breast cancer tissue from 4T1 and SKBR3 cell lines. A total of 7 samples were tested for each cancer tissue using a mouse model. We observed that a viscoelastic model with 2-term Prony series could best describe the ramp and stress relaxation of the tissue. For long-term responses, the SKBR3 tissues were stiffer in the strain levels of 4-10%, while no significant differences were found for the instantaneous elastic modulus. We also found tissues from both cell lines appeared to be strain-independent for the instantaneous elastic modulus and for the long-term elastic modulus in the strain level of 4-10%. In addition, by inspecting the cellular morphological structure of the two tissues, we found that SKBR3 tissues had a larger volume ratio of nuclei and a smaller volume ratio of extracellular matrix (ECM). Compared with prior cellular mechanics studies, our results indicated that ECM could contribute to the stiffening the tissue-level behavior. The viscoelastic characterization of the breast cancer tissue contributed to the scarce animal model data and provided support for the linear viscoelastic model used for in vivo elastography studies. Results also supplied helpful information for modeling of the breast cancer tissue in the tissue and cellular levels. Copyright © 2018 Elsevier Ltd. All rights reserved.

Microstructure and Mechanical Property of Glutaraldehyde-Treated Porcine Pulmonary Ligament.

PubMed

Chen, Huan; Zhao, Xuefeng; Berwick, Zachary C; Krieger, Joshua F; Chambers, Sean; Kassab, Ghassan S

2016-06-01

There is a significant need for fixed biological tissues with desired structural and material constituents for tissue engineering applications. Here, we introduce the lung ligament as a fixed biological material that may have clinical utility for tissue engineering. To characterize the lung tissue for potential clinical applications, we studied glutaraldehyde-treated porcine pulmonary ligament (n = 11) with multiphoton microscopy (MPM) and conducted biaxial planar experiments to characterize the mechanical property of the tissue. The MPM imaging revealed that there are generally two families of collagen fibers distributed in two distinct layers: The first family largely aligns along the longitudinal direction with a mean angle of θ = 10.7 ± 9.3 deg, while the second one exhibits a random distribution with a mean θ = 36.6 ± 27.4. Elastin fibers appear in some intermediate sublayers with a random orientation distribution with a mean θ = 39.6 ± 23 deg. Based on the microstructural observation, a microstructure-based constitutive law was proposed to model the elastic property of the tissue. The material parameters were identified by fitting the model to the biaxial stress-strain data of specimens, and good fitting quality was achieved. The parameter e0 (which denotes the strain beyond which the collagen can withstand tension) of glutaraldehyde-treated tissues demonstrated low variability implying a relatively consistent collagen undulation in different samples, while the stiffness parameters for elastin and collagen fibers showed relatively greater variability. The fixed tissues presented a smaller e0 than that of fresh specimen, confirming that glutaraldehyde crosslinking increases the mechanical strength of collagen-based biomaterials. The present study sheds light on the biomechanics of glutaraldehyde-treated porcine pulmonary ligament that may be a candidate for tissue engineering.

CHARACTERIZATION OF METABOLITES IN SMALL FISH BIOFLUIDS AND TISSUES BY NMR SPECTROSCOPY

EPA Science Inventory

Nuclear magnetic resonance (NMR) spectroscopy has been utilized for assessing ecotoxicity in small fish models by means of metabolomics. Two fundamental challenges of NMR-based metabolomics are the detection limit and characterization of metabolites (or NMR resonance assignments...

TU-CD-207-01: Characterization of Breast Tissue Composition Using Spectral Mammography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, H; Cho, H; Kumar, N

Purpose: To investigate the feasibility of characterizing the chemical composition of breast tissue, in terms of water and lipid, by using spectral mammography in simulation and postmortem studies. Methods: Analytical simulations were performed to obtain low- and high-energy signals of breast tissue based on previously reported water, lipid, and protein contents. Dual-energy decomposition was used to characterize the simulated breast tissue into water and lipid basis materials and the measured water density was compared to the known value. In experimental studies, postmortem breasts were imaged with a spectral mammography system based on a scanning multi-slit Si strip photon-counting detector. Low-more » and high-energy images were acquired simultaneously from a single exposure by sorting the recorded photons into the corresponding energy bins. Dual-energy material decomposition of the low- and high-energy images yielded individual pixel measurements of breast tissue composition in terms of water and lipid thicknesses. After imaging, each postmortem breast was chemically decomposed into water, lipid and protein. The water density calculated from chemical analysis was used as the reference gold standard. Correlation of the water density measurements between spectral mammography and chemical analysis was analyzed using linear regression. Results: Both simulation and postmortem studies showed good linear correlation between the decomposed water thickness using spectral mammography and chemical analysis. The slope of the linear fitting function in the simulation and postmortem studies were 1.15 and 1.21, respectively. Conclusion: The results indicate that breast tissue composition, in terms of water and lipid, can be accurately measured using spectral mammography. Quantitative breast tissue composition can potentially be used to stratify patients according to their breast cancer risk.« less

Breast Tissue Characterization with Photon-counting Spectral CT Imaging: A Postmortem Breast Study

PubMed Central

Ding, Huanjun; Klopfer, Michael J.; Ducote, Justin L.; Masaki, Fumitaro

2014-01-01

Purpose To investigate the feasibility of breast tissue characterization in terms of water, lipid, and protein contents with a spectral computed tomographic (CT) system based on a cadmium zinc telluride (CZT) photon-counting detector by using postmortem breasts. Materials and Methods Nineteen pairs of postmortem breasts were imaged with a CZT-based photon-counting spectral CT system with beam energy of 100 kVp. The mean glandular dose was estimated to be in the range of 1.8–2.2 mGy. The images were corrected for pulse pile-up and other artifacts by using spectral distortion corrections. Dual-energy decomposition was then applied to characterize each breast into water, lipid, and protein contents. The precision of the three-compartment characterization was evaluated by comparing the composition of right and left breasts, where the standard error of the estimations was determined. The results of dual-energy decomposition were compared by using averaged root mean square to chemical analysis, which was used as the reference standard. Results The standard errors of the estimations of the right-left correlations obtained from spectral CT were 7.4%, 6.7%, and 3.2% for water, lipid, and protein contents, respectively. Compared with the reference standard, the average root mean square error in breast tissue composition was 2.8%. Conclusion Spectral CT can be used to accurately quantify the water, lipid, and protein contents in breast tissue in a laboratory study by using postmortem specimens. © RSNA, 2014 PMID:24814180

Spatial cluster analysis of nanoscopically mapped serotonin receptors for classification of fixed brain tissue

NASA Astrophysics Data System (ADS)

Sams, Michael; Silye, Rene; Göhring, Janett; Muresan, Leila; Schilcher, Kurt; Jacak, Jaroslaw

2014-01-01

We present a cluster spatial analysis method using nanoscopic dSTORM images to determine changes in protein cluster distributions within brain tissue. Such methods are suitable to investigate human brain tissue and will help to achieve a deeper understanding of brain disease along with aiding drug development. Human brain tissue samples are usually treated postmortem via standard fixation protocols, which are established in clinical laboratories. Therefore, our localization microscopy-based method was adapted to characterize protein density and protein cluster localization in samples fixed using different protocols followed by common fluorescent immunohistochemistry techniques. The localization microscopy allows nanoscopic mapping of serotonin 5-HT1A receptor groups within a two-dimensional image of a brain tissue slice. These nanoscopically mapped proteins can be confined to clusters by applying the proposed statistical spatial analysis. Selected features of such clusters were subsequently used to characterize and classify the tissue. Samples were obtained from different types of patients, fixed with different preparation methods, and finally stored in a human tissue bank. To verify the proposed method, samples of a cryopreserved healthy brain have been compared with epitope-retrieved and paraffin-fixed tissues. Furthermore, samples of healthy brain tissues were compared with data obtained from patients suffering from mental illnesses (e.g., major depressive disorder). Our work demonstrates the applicability of localization microscopy and image analysis methods for comparison and classification of human brain tissues at a nanoscopic level. Furthermore, the presented workflow marks a unique technological advance in the characterization of protein distributions in brain tissue sections.

Microstructural and mechanical characterization of scarred vocal folds.

PubMed

Heris, Hossein K; Miri, Amir K; Ghattamaneni, Nageswara R; Li, Nicole Y K; Thibeault, Susan L; Wiseman, Paul W; Mongeau, Luc

2015-02-26

The goal of this study was to characterize the vocal folds microstructure and elasticity using nonlinear laser scanning microscopy and atomic force microscopy-based indentation, respectively. As a pilot study, the vocal folds of fourteen rats were unilaterally injured by full removal of lamina propria; the uninjured folds of the same animals served as controls. The area fraction of collagen fibrils was found to be greater in scarred tissues two months after injury than the uninjured controls. A novel mathematical model was also proposed to relate collagen concentration and tissue bulk modulus. This work presents a first step towards systematic investigation of microstructural and mechanical characteristics in scarred vocal fold tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

Raman-based imaging uncovers the effects of alginate hydrogel implants in spinal cord injury

NASA Astrophysics Data System (ADS)

Galli, Roberta; Tamosaityte, Sandra; Koch, Maria; Sitoci-Ficici, Kerim H.; Later, Robert; Uckermann, Ortrud; Beiermeister, Rudolf; Gelinsky, Michael; Schackert, Gabriele; Kirsch, Matthias; Koch, Edmund; Steiner, Gerald

2015-07-01

The treatment of spinal cord injury by using implants that provide a permissive environment for axonal growth is in the focus of the research for regenerative therapies. Here, Raman-based label-free techniques were applied for the characterization of morphochemical properties of surgically induced spinal cord injury in the rat that received an implant of soft unfunctionalized alginate hydrogel. Raman microspectroscopy followed by chemometrics allowed mapping the different degenerative areas, while multimodal multiphoton microscopy (e.g. the combination of coherent anti-Stokes Raman scattering (CARS), endogenous two-photon fluorescence and second harmonic generation on the same platform) enabled to address the morphochemistry of the tissue at cellular level. The regions of injury, characterized by demyelination and scarring, were retrieved and the distribution of key tissue components was evaluated by Raman mapping. The alginate hydrogel was detected in the lesion up to six months after implantation and had positive effects on the nervous tissue. For instance, multimodal multiphoton microscopy complemented the results of Raman mapping, providing the micromorphology of lipid-rich tissue structures by CARS and enabling to discern lipid-rich regions that contained myelinated axons from degenerative regions characterized by myelin fragmentation and presence of foam cells. These findings demonstrate that Raman-based imaging methods provide useful information for the evaluation of alginate implant effects and have therefore the potential to contribute to new strategies for monitoring degenerative and regenerative processes induced in SCI, thereby improving the effectiveness of therapies.

Multiscale Investigation from Subcellular to Tissue Scale of Onion Epidermal Plant Cell Wall Mechanical Properties

NASA Astrophysics Data System (ADS)

Zamil, Mohammad Shafayet

The physical and mechanical properties of cell walls, their shape, how they are arranged and interact with each other determine the architecture of plant organs and how they mechanically respond to different environmental and loading conditions. Due to the distinctive hierarchy from subcellular to tissue scale, plant materials can exhibit remarkably different mechanical properties. To date, how the subcellular scale arrangement and the mechanical properties of plant cell wall structural constituents give rise to macro or tissue scale mechanical responses is not yet well understood. Although the tissue scale plant cell wall samples are easy to prepare and put to different types of mechanical tests, the hierarchical features that emerge when moving towards a higher scale make it complicated to link the macro scale results to micro or subcellular scale structural components. On the other hand, the microscale size of cell brings formidable challenges to prepare and grip samples and carry mechanical tests under tensile loading at subcellular scale. This study attempted to develop a set of test protocols based on microelectromechanical system (MEMS) tensile testing devices for characterizing plant cell wall materials at different length scales. For the ease of sample preparation and well established database of the composition and conformation of its structural constituents, onion epidermal cell wall profile was chosen as the study material. Based on the results and findings of multiscale mechanical characterization, a framework of architecture-based finite element method (FEM) computational model was developed. The computational model laid the foundation of bridging the subcellular or microscale to the tissue or macroscale mechanical properties. This study suggests that there are important insights of cell wall mechanics and structural features that can only be investigated by carrying tensile characterization of samples not confounded by extracellular parameters. To the best of our knowledge, the plant cell wall at subcellular scale was never characterized under tensile loading. By coupling the structure based multiscale modeling and mechanical characterizations at different length scales, an attempt was made to provide novel insights towards understanding the mechanics and architecture of cell wall. This study also suggests that a multiscale investigation is essential for garnering fundamental insights into the hierarchical deformation of biological systems.

Random Weighting, Strong Tracking, and Unscented Kalman Filter for Soft Tissue Characterization.

PubMed

Shin, Jaehyun; Zhong, Yongmin; Oetomo, Denny; Gu, Chengfan

2018-05-21

This paper presents a new nonlinear filtering method based on the Hunt-Crossley model for online nonlinear soft tissue characterization. This method overcomes the problem of performance degradation in the unscented Kalman filter due to contact model error. It adopts the concept of Mahalanobis distance to identify contact model error, and further incorporates a scaling factor in predicted state covariance to compensate identified model error. This scaling factor is determined according to the principle of innovation orthogonality to avoid the cumbersome computation of Jacobian matrix, where the random weighting concept is adopted to improve the estimation accuracy of innovation covariance. A master-slave robotic indentation system is developed to validate the performance of the proposed method. Simulation and experimental results as well as comparison analyses demonstrate that the efficacy of the proposed method for online characterization of soft tissue parameters in the presence of contact model error.

Ex vivo optical characterization of in vivo grown tissues on dummy sensor implants using double integrating spheres measurement

NASA Astrophysics Data System (ADS)

Sharma, Sandeep; Goodarzi, Mohammad; Aernouts, Ben; Gellynck, Karolien; Vlaminck, Lieven; Bockstaele, Ronny; Cornelissen, Maria; Ramon, Herman; Saeys, Wouter

2014-05-01

Near infrared spectroscopy offers a promising technological platform for continuous glucose monitoring in the human body. NIR measurements can be performed in vivo with an implantable single-chip based optical NIR sensor. However, the application of NIR spectroscopy for accurate estimation of the analyte concentration in highly scattering biological systems still remains a challenge. For instance, a thin tissue layer may grow in the optical path of the sensor. As most biological tissues allow only a small fraction of the collimated light to pass, this might result in a large reduction of the light throughput. To quantify the effect of presence of a thin tissue layer in the optical path, the bulk optical properties of tissue samples grown on sensor dummies which had been implanted for several months in goats were characterized using Double Integrating Spheres and unscattered transmittance measurements. The measured values of diffuse reflectance, diffuse transmittance and collimated transmittance were used as input to Inverse Adding-Doubling algorithm to estimate the bulk optical properties of the samples. The estimates of absorption and scattering coefficients were then used to calculate the light attenuation through a thin tissue layer. Based on the lower reduction in unscattered transmittance and higher absorptivity of glucose molecules, the measurement in the combination band was found to be the better option for the implantable sensor. As the tissues were found to be highly forward scattering with very low unscattered transmittance, the diffuse transmittance measurement based sensor configuration was recommended for the implantable glucose sensor.

Raman imaging at biological interfaces: applications in breast cancer diagnosis.

PubMed

Surmacki, Jakub; Musial, Jacek; Kordek, Radzislaw; Abramczyk, Halina

2013-05-24

One of the most important areas of Raman medical diagnostics is identification and characterization of cancerous and noncancerous tissues. The methods based on Raman scattering has shown significant potential for probing human breast tissue to provide valuable information for early diagnosis of breast cancer. A vibrational fingerprint from the biological tissue provides information which can be used to identify, characterize and discriminate structures in breast tissue, both in the normal and cancerous environment. The paper reviews recent progress in understanding structure and interactions at biological interfaces of the human tissue by using confocal Raman imaging and IR spectroscopy. The important differences between the noncancerous and cancerous human breast tissues were found in regions characteristic for vibrations of carotenoids, fatty acids, proteins, and interfacial water. Particular attention was paid to the role played by unsaturated fatty acids and their derivatives as well as carotenoids and interfacial water. We demonstrate that Raman imaging has reached a clinically relevant level in regard to breast cancer diagnosis applications. The results presented in the paper may have serious implications on understanding mechanisms of interactions in living cells under realistically crowded conditions of biological tissue.

Bone scaffolds with homogeneous and discrete gradient mechanical properties.

PubMed

Jelen, C; Mattei, G; Montemurro, F; De Maria, C; Mattioli-Belmonte, M; Vozzi, G

2013-01-01

Bone TE uses a scaffold either to induce bone formation from surrounding tissue or to act as a carrier or template for implanted bone cells or other agents. We prepared different bone tissue constructs based on collagen, gelatin and hydroxyapatite using genipin as cross-linking agent. The fabricated construct did not present a release neither of collagen neither of genipin over its toxic level in the surrounding aqueous environment. Each scaffold has been mechanically characterized with compression, swelling and creep tests, and their respective viscoelastic mechanical models were derived. Mechanical characterization showed a practically elastic behavior of all samples and that compressive elastic modulus basically increases as content of HA increases, and it is strongly dependent on porosity and water content. Moreover, by considering that gradients in cellular and extracellular architecture as well as in mechanical properties are readily apparent in native tissues, we developed discrete functionally graded scaffolds (discrete FGSs) in order to mimic the graded structure of bone tissue. These new structures were mechanically characterized showing a marked anisotropy as the native bone tissue. Results obtained have shown FGSs could represent valid bone substitutes. Copyright © 2012 Elsevier B.V. All rights reserved.

Image-based metrology of porous tissue engineering scaffolds

NASA Astrophysics Data System (ADS)

Rajagopalan, Srinivasan; Robb, Richard A.

2006-03-01

Tissue engineering is an interdisciplinary effort aimed at the repair and regeneration of biological tissues through the application and control of cells, porous scaffolds and growth factors. The regeneration of specific tissues guided by tissue analogous substrates is dependent on diverse scaffold architectural indices that can be derived quantitatively from the microCT and microMR images of the scaffolds. However, the randomness of pore-solid distributions in conventional stochastic scaffolds presents unique computational challenges. As a result, image-based characterization of scaffolds has been predominantly qualitative. In this paper, we discuss quantitative image-based techniques that can be used to compute the metrological indices of porous tissue engineering scaffolds. While bulk averaged quantities such as porosity and surface are derived directly from the optimal pore-solid delineations, the spatially distributed geometric indices are derived from the medial axis representations of the pore network. The computational framework proposed (to the best of our knowledge for the first time in tissue engineering) in this paper might have profound implications towards unraveling the symbiotic structure-function relationship of porous tissue engineering scaffolds.

Quantitative shear wave imaging optical coherence tomography for noncontact mechanical characterization of myocardium

NASA Astrophysics Data System (ADS)

Wang, Shang; Lopez, Andrew L.; Morikawa, Yuka; Tao, Ge; Li, Jiasong; Larina, Irina V.; Martin, James F.; Larin, Kirill V.

2015-03-01

Optical coherence elastography (OCE) is an emerging low-coherence imaging technique that provides noninvasive assessment of tissue biomechanics with high spatial resolution. Among various OCE methods, the capability of quantitative measurement of tissue elasticity is of great importance for tissue characterization and pathology detection across different samples. Here we report a quantitative OCE technique, termed quantitative shear wave imaging optical coherence tomography (Q-SWI-OCT), which enables noncontact measurement of tissue Young's modulus based on the ultra-fast imaging of the shear wave propagation inside the sample. A focused air-puff device is used to interrogate the tissue with a low-pressure short-duration air stream that stimulates a localized displacement with the scale at micron level. The propagation of this tissue deformation in the form of shear wave is captured by a phase-sensitive OCT system running with the scan of the M-mode imaging over the path of the wave propagation. The temporal characteristics of the shear wave is quantified based on the cross-correlation of the tissue deformation profiles at all the measurement locations, and linear regression is utilized to fit the data plotted in the domain of time delay versus wave propagation distance. The wave group velocity is thus calculated, which results in the quantitative measurement of the Young's modulus. As the feasibility demonstration, experiments are performed on tissuemimicking phantoms with different agar concentrations and the quantified elasticity values with Q-SWI-OCT agree well with the uniaxial compression tests. For functional characterization of myocardium with this OCE technique, we perform our pilot experiments on ex vivo mouse cardiac muscle tissues with two studies, including 1) elasticity difference of cardiac muscle under relaxation and contract conditions and 2) mechanical heterogeneity of the heart introduced by the muscle fiber orientation. Our results suggest the potential of using Q-SWI-OCT as an essential tool for nondestructive biomechanical evaluation of myocardium.

Recent Advances in Extrusion-Based 3D Printing for Biomedical Applications.

PubMed

Placone, Jesse K; Engler, Adam J

2018-04-01

Additive manufacturing, or 3D printing, has become significantly more commonplace in tissue engineering over the past decade, as a variety of new printing materials have been developed. In extrusion-based printing, materials are used for applications that range from cell free printing to cell-laden bioinks that mimic natural tissues. Beyond single tissue applications, multi-material extrusion based printing has recently been developed to manufacture scaffolds that mimic tissue interfaces. Despite these advances, some material limitations prevent wider adoption of the extrusion-based 3D printers currently available. This progress report provides an overview of this commonly used printing strategy, as well as insight into how this technique can be improved. As such, it is hoped that the prospective report guides the inclusion of more rigorous material characterization prior to printing, thereby facilitating cross-platform utilization and reproducibility. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identification and immunophenotypic characterization of normal and pathological mast cells.

PubMed

Morgado, José Mário; Sánchez-Muñoz, Laura; Teodósio, Cristina; Escribano, Luís

2014-01-01

Mast cells (MCs) are secretory cells that are central players in human allergic disease and immune responses. With the exception of a few pathological situations, MCs are usually present at relatively low frequencies in most tissues. Since their first description, MCs in tissues were identified mostly using their morphological characteristics and their typical coloration when stained with aniline dyes. However, increasing availability of highly specific antibodies now permits the use of fluorescence-based flow cytometry as the method of choice for the quantification, characterization, and purification of cells in suspension. This technique allows for a rapid analysis of thousands of events and for the identification of cells present at frequencies as low as one event in 10(6) unwanted cells. This method also permits for simultaneous characterization of multiple antigens at a single-cell level, which is ideal in order to study rare populations of cells like MCs. Here we describe the basis of flow cytometry-based immunophenotyping applied to the study of MC. The protocol focuses on the study of human MCs present in body fluids (mainly bone marrow) but can easily be adapted to study MCs from other tissues and species.

Preparation of silica nanoparticles loaded with nootropics and their in vivo permeation through blood-brain barrier.

PubMed

Jampilek, Josef; Zaruba, Kamil; Oravec, Michal; Kunes, Martin; Babula, Petr; Ulbrich, Pavel; Brezaniova, Ingrid; Opatrilova, Radka; Triska, Jan; Suchy, Pavel

2015-01-01

The blood-brain barrier prevents the passage of many drugs that target the central nervous system. This paper presents the preparation and characterization of silica-based nanocarriers loaded with piracetam, pentoxifylline, and pyridoxine (drugs from the class of nootropics), which are designed to enhance the permeation of the drugs from the circulatory system through the blood-brain barrier. Their permeation was compared with non-nanoparticle drug substances (bulk materials) by means of an in vivo model of rat brain perfusion. The size and morphology of the nanoparticles were characterized by transmission electron microscopy. The content of the drug substances in silica-based nanocarriers was analysed by elemental analysis and UV spectrometry. Microscopic analysis of visualized silica nanocarriers in the perfused brain tissue was performed. The concentration of the drug substances in the tissue was determined by means of UHPLC-DAD/HRMS LTQ Orbitrap XL. It was found that the drug substances in silica-based nanocarriers permeated through the blood brain barrier to the brain tissue, whereas bulk materials were not detected in the brain.

Preparation of Silica Nanoparticles Loaded with Nootropics and Their In Vivo Permeation through Blood-Brain Barrier

PubMed Central

Zaruba, Kamil; Kunes, Martin; Ulbrich, Pavel; Brezaniova, Ingrid; Triska, Jan; Suchy, Pavel

2015-01-01

The blood-brain barrier prevents the passage of many drugs that target the central nervous system. This paper presents the preparation and characterization of silica-based nanocarriers loaded with piracetam, pentoxifylline, and pyridoxine (drugs from the class of nootropics), which are designed to enhance the permeation of the drugs from the circulatory system through the blood-brain barrier. Their permeation was compared with non-nanoparticle drug substances (bulk materials) by means of an in vivo model of rat brain perfusion. The size and morphology of the nanoparticles were characterized by transmission electron microscopy. The content of the drug substances in silica-based nanocarriers was analysed by elemental analysis and UV spectrometry. Microscopic analysis of visualized silica nanocarriers in the perfused brain tissue was performed. The concentration of the drug substances in the tissue was determined by means of UHPLC-DAD/HRMS LTQ Orbitrap XL. It was found that the drug substances in silica-based nanocarriers permeated through the blood brain barrier to the brain tissue, whereas bulk materials were not detected in the brain. PMID:26075264

Design and characterization of a biodegradable composite scaffold for ligament tissue engineering.

PubMed

Hayami, James W S; Surrao, Denver C; Waldman, Stephen D; Amsden, Brian G

2010-03-15

Herein we report on the development and characterization of a biodegradable composite scaffold for ligament tissue engineering based on the fundamental morphological features of the native ligament. An aligned fibrous component was used to mimic the fibrous collagen network and a hydrogel component to mimic the proteoglycan-water matrix of the ligament. The composite scaffold was constructed from cell-adherent, base-etched, electrospun poly(epsilon-caprolactone-co-D,L-lactide) (PCLDLLA) fibers embedded in a noncell-adherent photocrosslinked N-methacrylated glycol chitosan (MGC) hydrogel seeded with primary ligament fibroblasts. Base etching improved cellular adhesion to the PCLDLLA material. Cells within the MGC hydrogel remained viable (72 +/- 4%) during the 4-week culture period. Immunohistochemistry staining revealed ligament ECM markers collagen type I, collagen type III, and decorin organizing and accumulating along the PCLDLLA fibers within the composite scaffolds. On the basis of these results, it was determined that the composite scaffold design was a viable alternative to the current approaches used for ligament tissue engineering and merits further study. (c) 2009 Wiley Periodicals, Inc.

Joint deep shape and appearance learning: application to optic pathway glioma segmentation

NASA Astrophysics Data System (ADS)

Mansoor, Awais; Li, Ien; Packer, Roger J.; Avery, Robert A.; Linguraru, Marius George

2017-03-01

Automated tissue characterization is one of the major applications of computer-aided diagnosis systems. Deep learning techniques have recently demonstrated impressive performance for the image patch-based tissue characterization. However, existing patch-based tissue classification techniques struggle to exploit the useful shape information. Local and global shape knowledge such as the regional boundary changes, diameter, and volumetrics can be useful in classifying the tissues especially in scenarios where the appearance signature does not provide significant classification information. In this work, we present a deep neural network-based method for the automated segmentation of the tumors referred to as optic pathway gliomas (OPG) located within the anterior visual pathway (AVP; optic nerve, chiasm or tracts) using joint shape and appearance learning. Voxel intensity values of commonly used MRI sequences are generally not indicative of OPG. To be considered an OPG, current clinical practice dictates that some portion of AVP must demonstrate shape enlargement. The method proposed in this work integrates multiple sequence magnetic resonance image (T1, T2, and FLAIR) along with local boundary changes to train a deep neural network. For training and evaluation purposes, we used a dataset of multiple sequence MRI obtained from 20 subjects (10 controls, 10 NF1+OPG). To our best knowledge, this is the first deep representation learning-based approach designed to merge shape and multi-channel appearance data for the glioma detection. In our experiments, mean misclassification errors of 2:39% and 0:48% were observed respectively for glioma and control patches extracted from the AVP. Moreover, an overall dice similarity coefficient of 0:87+/-0:13 (0:93+/-0:06 for healthy tissue, 0:78+/-0:18 for glioma tissue) demonstrates the potential of the proposed method in the accurate localization and early detection of OPG.

DNA-damage foci to detect and characterize DNA repair alterations in children treated for pediatric malignancies.

PubMed

Schuler, Nadine; Palm, Jan; Kaiser, Mareike; Betten, Dominik; Furtwängler, Rhoikos; Rübe, Christian; Graf, Norbert; Rübe, Claudia E

2014-01-01

In children diagnosed with cancer, we evaluated the DNA damage foci approach to identify patients with double-strand break (DSB) repair deficiencies, who may overreact to DNA-damaging radio- and chemotherapy. In one patient with Fanconi anemia (FA) suffering relapsing squamous cell carcinomas of the oral cavity we also characterized the repair defect in biopsies of skin, mucosa and tumor. In children with histologically confirmed tumors or leukemias and healthy control-children DSB repair was investigated by counting γH2AX-, 53BP1- and pATM-foci in blood lymphocytes at defined time points after ex-vivo irradiation. This DSB repair capacity was correlated with treatment-related normal-tissue responses. For the FA patient the defective repair was also characterized in tissue biopsies by analyzing DNA damage response proteins by light and electron microscopy. Between tumor-children and healthy control-children we observed significant differences in mean DSB repair capacity, suggesting that childhood cancer is based on genetic alterations affecting DNA repair. Only 1 out of 4 patients with grade-4 normal-tissue toxicities revealed an impaired DSB repair capacity. The defective DNA repair in FA patient was verified in irradiated blood lymphocytes as well as in non-irradiated mucosa and skin biopsies leading to an excessive accumulation of heterochromatin-associated DSBs in rapidly cycling cells. Analyzing human tissues we show that DSB repair alterations predispose to cancer formation at younger ages and affect the susceptibility to normal-tissue toxicities. DNA damage foci analysis of blood and tissue samples allows one to detect and characterize DSB repair deficiencies and enables identification of patients at risk for high-grade toxicities. However, not all treatment-associated normal-tissue toxicities can be explained by DSB repair deficiencies.

Automated characterization of normal and pathologic lung tissue by topological texture analysis of multidetector CT

NASA Astrophysics Data System (ADS)

Boehm, H. F.; Fink, C.; Becker, C.; Reiser, M.

2007-03-01

Reliable and accurate methods for objective quantitative assessment of parenchymal alterations in the lung are necessary for diagnosis, treatment and follow-up of pulmonary diseases. Two major types of alterations are pulmonary emphysema and fibrosis, emphysema being characterized by abnormal enlargement of the air spaces distal to the terminal, nonrespiratory bronchiole, accompanied by destructive changes of the alveolar walls. The main characteristic of fibrosis is coursening of the interstitial fibers and compaction of the pulmonary tissue. With the ability to display anatomy free from superimposing structures and greater visual clarity, Multi-Detector-CT has shown to be more sensitive than the chest radiograph in identifying alterations of lung parenchyma. In automated evaluation of pulmonary CT-scans, quantitative image processing techniques are applied for objective evaluation of the data. A number of methods have been proposed in the past, most of which utilize simple densitometric tissue features based on the mean X-ray attenuation coefficients expressed in terms of Hounsfield Units [HU]. Due to partial volume effects, most of the density-based methodologies tend to fail, namely in cases, where emphysema and fibrosis occur within narrow spatial limits. In this study, we propose a methodology based upon the topological assessment of graylevel distribution in the 3D image data of lung tissue which provides a way of improving quantitative CT evaluation. Results are compared to the more established density-based methods.

3D Riesz-wavelet based Covariance descriptors for texture classification of lung nodule tissue in CT.

PubMed

Cirujeda, Pol; Muller, Henning; Rubin, Daniel; Aguilera, Todd A; Loo, Billy W; Diehn, Maximilian; Binefa, Xavier; Depeursinge, Adrien

2015-01-01

In this paper we present a novel technique for characterizing and classifying 3D textured volumes belonging to different lung tissue types in 3D CT images. We build a volume-based 3D descriptor, robust to changes of size, rigid spatial transformations and texture variability, thanks to the integration of Riesz-wavelet features within a Covariance-based descriptor formulation. 3D Riesz features characterize the morphology of tissue density due to their response to changes in intensity in CT images. These features are encoded in a Covariance-based descriptor formulation: this provides a compact and flexible representation thanks to the use of feature variations rather than dense features themselves and adds robustness to spatial changes. Furthermore, the particular symmetric definite positive matrix form of these descriptors causes them to lay in a Riemannian manifold. Thus, descriptors can be compared with analytical measures, and accurate techniques from machine learning and clustering can be adapted to their spatial domain. Additionally we present a classification model following a "Bag of Covariance Descriptors" paradigm in order to distinguish three different nodule tissue types in CT: solid, ground-glass opacity, and healthy lung. The method is evaluated on top of an acquired dataset of 95 patients with manually delineated ground truth by radiation oncology specialists in 3D, and quantitative sensitivity and specificity values are presented.

Multimodal imaging of vascular grafts using time-resolved fluorescence and ultrasound

NASA Astrophysics Data System (ADS)

Fatakdawala, Hussain; Griffiths, Leigh G.; Wong, Maelene L.; Humphrey, Sterling; Marcu, Laura

2015-02-01

The translation of engineered tissues into clinic requires robust monitoring of tissue development, both in vitro and in vivo. Traditional methods for the same are destructive, inefficient in time and cost and do not allow time-lapse measurements from the same sample or animal. This study reports on the ability of time-resolved fluorescence and ultrasound measurements for non-destructive characterization of explanted tissue engineered vascular grafts. Results show that TRFS and FLIm are able to assess alterations in luminal composition namely elastin, collagen and cellular (hyperplasia) content via changes in fluorescence lifetime values between normal and grafted tissue. These observations are complemented by structural changes observed in UBM pertaining to graft integration and intimal thickness over the grafted region. These results encourage the future application of a catheter-based technique that combines these imaging modalities for non-destructive characterization of vascular grafts in vivo.

Bio-Optics Based Sensation Imaging for Breast Tumor Detection Using Tissue Characterization

PubMed Central

Lee, Jong-Ha; Kim, Yoon Nyun; Park, Hee-Jun

2015-01-01

The tissue inclusion parameter estimation method is proposed to measure the stiffness as well as geometric parameters. The estimation is performed based on the tactile data obtained at the surface of the tissue using an optical tactile sensation imaging system (TSIS). A forward algorithm is designed to comprehensively predict the tactile data based on the mechanical properties of tissue inclusion using finite element modeling (FEM). This forward information is used to develop an inversion algorithm that will be used to extract the size, depth, and Young's modulus of a tissue inclusion from the tactile data. We utilize the artificial neural network (ANN) for the inversion algorithm. The proposed estimation method was validated by a realistic tissue phantom with stiff inclusions. The experimental results showed that the proposed estimation method can measure the size, depth, and Young's modulus of a tissue inclusion with 0.58%, 3.82%, and 2.51% relative errors, respectively. The obtained results prove that the proposed method has potential to become a useful screening and diagnostic method for breast cancer. PMID:25785306

Acoustic Radiation Force Elasticity Imaging in Diagnostic Ultrasound

PubMed Central

Doherty, Joshua R.; Trahey, Gregg E.; Nightingale, Kathryn R.; Palmeri, Mark L.

2013-01-01

The development of ultrasound-based elasticity imaging methods has been the focus of intense research activity since the mid-1990s. In characterizing the mechanical properties of soft tissues, these techniques image an entirely new subset of tissue properties that cannot be derived with conventional ultrasound techniques. Clinically, tissue elasticity is known to be associated with pathological condition and with the ability to image these features in vivo, elasticity imaging methods may prove to be invaluable tools for the diagnosis and/or monitoring of disease. This review focuses on ultrasound-based elasticity imaging methods that generate an acoustic radiation force to induce tissue displacements. These methods can be performed non-invasively during routine exams to provide either qualitative or quantitative metrics of tissue elasticity. A brief overview of soft tissue mechanics relevant to elasticity imaging is provided, including a derivation of acoustic radiation force, and an overview of the various acoustic radiation force elasticity imaging methods. PMID:23549529

Acoustic radiation force elasticity imaging in diagnostic ultrasound.

PubMed

Doherty, Joshua R; Trahey, Gregg E; Nightingale, Kathryn R; Palmeri, Mark L

2013-04-01

The development of ultrasound-based elasticity imaging methods has been the focus of intense research activity since the mid-1990s. In characterizing the mechanical properties of soft tissues, these techniques image an entirely new subset of tissue properties that cannot be derived with conventional ultrasound techniques. Clinically, tissue elasticity is known to be associated with pathological condition and with the ability to image these features in vivo; elasticity imaging methods may prove to be invaluable tools for the diagnosis and/or monitoring of disease. This review focuses on ultrasound-based elasticity imaging methods that generate an acoustic radiation force to induce tissue displacements. These methods can be performed noninvasively during routine exams to provide either qualitative or quantitative metrics of tissue elasticity. A brief overview of soft tissue mechanics relevant to elasticity imaging is provided, including a derivation of acoustic radiation force, and an overview of the various acoustic radiation force elasticity imaging methods.

Quantization of liver tissue in dual kVp computed tomography using linear discriminant analysis

NASA Astrophysics Data System (ADS)

Tkaczyk, J. Eric; Langan, David; Wu, Xiaoye; Xu, Daniel; Benson, Thomas; Pack, Jed D.; Schmitz, Andrea; Hara, Amy; Palicek, William; Licato, Paul; Leverentz, Jaynne

2009-02-01

Linear discriminate analysis (LDA) is applied to dual kVp CT and used for tissue characterization. The potential to quantitatively model both malignant and benign, hypo-intense liver lesions is evaluated by analysis of portal-phase, intravenous CT scan data obtained on human patients. Masses with an a priori classification are mapped to a distribution of points in basis material space. The degree of localization of tissue types in the material basis space is related to both quantum noise and real compositional differences. The density maps are analyzed with LDA and studied with system simulations to differentiate these factors. The discriminant analysis is formulated so as to incorporate the known statistical properties of the data. Effective kVp separation and mAs relates to precision of tissue localization. Bias in the material position is related to the degree of X-ray scatter and partial-volume effect. Experimental data and simulations demonstrate that for single energy (HU) imaging or image-based decomposition pixel values of water-like tissues depend on proximity to other iodine-filled bodies. Beam-hardening errors cause a shift in image value on the scale of that difference sought between in cancerous and cystic lessons. In contrast, projection-based decomposition or its equivalent when implemented on a carefully calibrated system can provide accurate data. On such a system, LDA may provide novel quantitative capabilities for tissue characterization in dual energy CT.

GBM heterogeneity characterization by radiomic analysis of phenotype anatomical planes

NASA Astrophysics Data System (ADS)

Chaddad, Ahmad; Desrosiers, Christian; Toews, Matthew

2016-03-01

Glioblastoma multiforme (GBM) is the most common malignant primary tumor of the central nervous system, characterized among other traits by rapid metastatis. Three tissue phenotypes closely associated with GBMs, namely, necrosis (N), contrast enhancement (CE), and edema/invasion (E), exhibit characteristic patterns of texture heterogeneity in magnetic resonance images (MRI). In this study, we propose a novel model to characterize GBM tissue phenotypes using gray level co-occurrence matrices (GLCM) in three anatomical planes. The GLCM encodes local image patches in terms of informative, orientation-invariant texture descriptors, which are used here to sub-classify GBM tissue phenotypes. Experiments demonstrate the model on MRI data of 41 GBM patients, obtained from the cancer genome atlas (TCGA). Intensity-based automatic image registration is applied to align corresponding pairs of fixed T1˗weighted (T1˗WI) post-contrast and fluid attenuated inversion recovery (FLAIR) images. GBM tissue regions are then segmented using the 3D Slicer tool. Texture features are computed from 12 quantifier functions operating on GLCM descriptors, that are generated from MRI intensities within segmented GBM tissue regions. Various classifier models are used to evaluate the effectiveness of texture features for discriminating between GBM phenotypes. Results based on T1-WI scans showed a phenotype classification accuracy of over 88.14%, a sensitivity of 85.37% and a specificity of 96.1%, using the linear discriminant analysis (LDA) classifier. This model has the potential to provide important characteristics of tumors, which can be used for the sub-classification of GBM phenotypes.

Potential for Imaging Engineered Tissues with X-Ray Phase Contrast

PubMed Central

Appel, Alyssa; Anastasio, Mark A.

2011-01-01

As the field of tissue engineering advances, it is crucial to develop imaging methods capable of providing detailed three-dimensional information on tissue structure. X-ray imaging techniques based on phase-contrast (PC) have great potential for a number of biomedical applications due to their ability to provide information about soft tissue structure without exogenous contrast agents. X-ray PC techniques retain the excellent spatial resolution, tissue penetration, and calcified tissue contrast of conventional X-ray techniques while providing drastically improved imaging of soft tissue and biomaterials. This suggests that X-ray PC techniques are very promising for evaluation of engineered tissues. In this review, four different implementations of X-ray PC imaging are described and applications to tissues of relevance to tissue engineering reviewed. In addition, recent applications of X-ray PC to the evaluation of biomaterial scaffolds and engineered tissues are presented and areas for further development and application of these techniques are discussed. Imaging techniques based on X-ray PC have significant potential for improving our ability to image and characterize engineered tissues, and their continued development and optimization could have significant impact on the field of tissue engineering. PMID:21682604

Characterization and manipulation of the in vivo host response and in vitro macrophage response to synthetic hydrogels

NASA Astrophysics Data System (ADS)

Lynn, Aaron David

Tissue engineering hope to fill the donor gap between patient needing transplantation and donors able to provide organs. Many challenges exist in the engineering of replacement tissues such as cell sourcing and scaffold design. A particularly promising group of scaffolds used extensively in tissue engineering research are based on cross-linked poly(ethylene glycol) (PEG) hydrogels. Materials based on these gels have been selected for their tissue-like high water content, low cell toxicty, mild polymerization conditions and the ease with which their mechanical and chemical properties can be tuned. However, all materials which will ultimately be implanted into will elicit a host response. This reaction is initiated when a wound is created. It leads to bathing of the material in proteins from the blood, recruitment, attachment and interrogation of the material by macrophages, attempted degradation and phagocytosis, macrophage fusion into foreign body giant cells (FBGCs) and ultimately the "walling off" of the implant as a dense collagenous capsule surrounds the material restricting further interactions with the host. This foreign body response (FBR) is well studied and contributes significantly to premature failure of implanted medical devices. The research presented in this thesis aims to characterize the FBR to PEG-based tissue engineering scaffolds with the intention of uncovering mechanisms by which the response can be attenuated. To this end, implantation studies have been performed to gauge the severity of the foreign body response to these hydrogels and to establish to what degree modifications with the cell adhesion peptide alter this reaction in vivo. Additionally, in vitro models were established to study characteristics of the the early (< 1 week), middle (1-2 weeks) and late phases (> 2 weeks) of the FBR. Studies were performed to determine the potentially detrimental effects of macrophage interrogation of a PEG-based skin tissue engineering system containing encapsulated fibroblasts. Finally, preliminary work has been done on a strategy for manipulating macrophage interactions with tissue engineering hydrogels utilizing a novel hydrogel coating system. This provides some of the first correlations between in vivo host responses and in vitro macrophage responses to PEG-based tissue engineering materials.

Raman imaging at biological interfaces: applications in breast cancer diagnosis

PubMed Central

2013-01-01

Background One of the most important areas of Raman medical diagnostics is identification and characterization of cancerous and noncancerous tissues. The methods based on Raman scattering has shown significant potential for probing human breast tissue to provide valuable information for early diagnosis of breast cancer. A vibrational fingerprint from the biological tissue provides information which can be used to identify, characterize and discriminate structures in breast tissue, both in the normal and cancerous environment. Results The paper reviews recent progress in understanding structure and interactions at biological interfaces of the human tissue by using confocal Raman imaging and IR spectroscopy. The important differences between the noncancerous and cancerous human breast tissues were found in regions characteristic for vibrations of carotenoids, fatty acids, proteins, and interfacial water. Particular attention was paid to the role played by unsaturated fatty acids and their derivatives as well as carotenoids and interfacial water. Conclusions We demonstrate that Raman imaging has reached a clinically relevant level in regard to breast cancer diagnosis applications. The results presented in the paper may have serious implications on understanding mechanisms of interactions in living cells under realistically crowded conditions of biological tissue. PMID:23705882

Characterizing lamina propria of human gastric mucosa by multiphoton microscopy

NASA Astrophysics Data System (ADS)

Liu, Y. C.; Yang, H. Q.; Chen, G.; Zhuo, S. M.; Chen, J. X.; Yan, J.

2011-01-01

Lamina propria (LP) of gastric mucosa plays an important role in progression of gastric cancer because of the site at where inflammatory reactions occur. Multiphoton imaging has been recently employed for microscopic examination of intact tissue. In this paper, using multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG), high resolution multiphoton microscopic images of lamina propria (LP) are obtained in normal human gastric mucosa at excitation wavelength λex = 800 nm. The main source of tissue TPEF originated from the cells of gastric glands, and loose connective tissue, collagen, produced SHG signals. Our results demonstrated that MPM can be effective for characterizing the microstructure of LP in human gastric mucosa. The findings will be helpful for diagnosing and staging early gastric cancer in the clinics.

Surface characterization of retinal tissues for the enhancement of vitreoretinal surgical methods

NASA Astrophysics Data System (ADS)

Valentin-Rodriguez, Celimar

Diabetic retinopathy is the most common ophthalmic complication of diabetes and the leading cause of blindness among adults, ages 30 to 70. Surgery to remove scar tissue in the eye is the only corrective treatment once the retina is affected. Visual recovery is often hampered by retinal trauma during surgery and by low patient compliance. Our work in this project aimed to improve vitreoretinal surgical methods from information gathered by sensitive surface analysis of pre-retinal tissues found at the vitreoretinal interface. Atomic force microscopy characterization of human retinal tissues revealed that surgically excised inner limiting membrane (ILM) has a heterogeneous surface and is mainly composed of globular and fibrous structures. ILM tissues also show low adhesion for clean unmodified surfaces as opposed to those with functional groups attractive to those on the ILM surface, due to their charge. Based on these observations, layer-by-layer films with embedded gold nanoparticles with a positive outer charge were designed. These modifications increased the adhesion between surgical instruments and ILM by increasing the roughness and tuning the film surface charge. These films proved to be stable under physiological conditions. Finally, the effect of vital dyes on the topographical characteristics of ILMs was characterized and new imaging modes to further reveal ILM topography were utilized. Roughness and adhesion force data suggest that second generation dyes have no effect on the surface nanostructure of ILMs, but increase adhesion at the tip sample interface. This project clearly illustrates that physicochemical information from tissues can be used to rationally re-design surgical procedures, in this case for tissue removal purposes. This rational design method can be applied to other soft tissue excision procedures as is the case of cataract surgery or laparoscopic removal of endometrial tissue.

Tissue Anisotropy Modeling Using Soft Composite Materials.

PubMed

Chanda, Arnab; Callaway, Christian

2018-01-01

Soft tissues in general exhibit anisotropic mechanical behavior, which varies in three dimensions based on the location of the tissue in the body. In the past, there have been few attempts to numerically model tissue anisotropy using composite-based formulations (involving fibers embedded within a matrix material). However, so far, tissue anisotropy has not been modeled experimentally. In the current work, novel elastomer-based soft composite materials were developed in the form of experimental test coupons, to model the macroscopic anisotropy in tissue mechanical properties. A soft elastomer matrix was fabricated, and fibers made of a stiffer elastomer material were embedded within the matrix material to generate the test coupons. The coupons were tested on a mechanical testing machine, and the resulting stress-versus-stretch responses were studied. The fiber volume fraction (FVF), fiber spacing, and orientations were varied to estimate the changes in the mechanical responses. The mechanical behavior of the soft composites was characterized using hyperelastic material models such as Mooney-Rivlin's, Humphrey's, and Veronda-Westmann's model and also compared with the anisotropic mechanical behavior of the human skin, pelvic tissues, and brain tissues. This work lays the foundation for the experimental modelling of tissue anisotropy, which combined with microscopic studies on tissues can lead to refinements in the simulation of localized fiber distribution and orientations, and enable the development of biofidelic anisotropic tissue phantom materials for various tissue engineering and testing applications.

Tissue Anisotropy Modeling Using Soft Composite Materials

PubMed Central

Callaway, Christian

2018-01-01

Soft tissues in general exhibit anisotropic mechanical behavior, which varies in three dimensions based on the location of the tissue in the body. In the past, there have been few attempts to numerically model tissue anisotropy using composite-based formulations (involving fibers embedded within a matrix material). However, so far, tissue anisotropy has not been modeled experimentally. In the current work, novel elastomer-based soft composite materials were developed in the form of experimental test coupons, to model the macroscopic anisotropy in tissue mechanical properties. A soft elastomer matrix was fabricated, and fibers made of a stiffer elastomer material were embedded within the matrix material to generate the test coupons. The coupons were tested on a mechanical testing machine, and the resulting stress-versus-stretch responses were studied. The fiber volume fraction (FVF), fiber spacing, and orientations were varied to estimate the changes in the mechanical responses. The mechanical behavior of the soft composites was characterized using hyperelastic material models such as Mooney-Rivlin's, Humphrey's, and Veronda-Westmann's model and also compared with the anisotropic mechanical behavior of the human skin, pelvic tissues, and brain tissues. This work lays the foundation for the experimental modelling of tissue anisotropy, which combined with microscopic studies on tissues can lead to refinements in the simulation of localized fiber distribution and orientations, and enable the development of biofidelic anisotropic tissue phantom materials for various tissue engineering and testing applications. PMID:29853996

Identification of tissular origin of particles based on autofluorescence multispectral image analysis at the macroscopic scale

NASA Astrophysics Data System (ADS)

Corcel, Mathias; Devaux, Marie-Françoise; Guillon, Fabienne; Barron, Cécile

2017-06-01

Powders produced from plant materials are heterogeneous in relation to native plant heterogeneity, and during grinding, dissociation often occurred at the tissue scale. The tissue composition of powdery samples could be modified through dry fractionation diagrams and impact their end-uses properties. If tissue identification is often made on native plant structure, this characterization is not straightforward in destructured samples such powders. Taking advantage of the autofluorescence properties of cell wall components, multispectral image acquisition is envisioned to identify the tissular origin of particles. Images were acquired on maize stem sections and ground tissues isolated from the same stem by hand dissection. The variability in fluorescence intensity profiles was analysed using principal component analysis. The correspondence between fluorescence profiles and the different tissues observed in maize sections was assessed based on histology or known compositional heterogeneity. Similar variability was encountered in fluorescence profiles extracted from powder leading to the potential ability to predict tissular origin based on this autofluorescence multispectral signal.

The diagnostic capability of laser induced fluorescence in the characterization of excised breast tissues

NASA Astrophysics Data System (ADS)

Galmed, A. H.; Elshemey, Wael M.

2017-08-01

Differentiating between normal, benign and malignant excised breast tissues is one of the major worldwide challenges that need a quantitative, fast and reliable technique in order to avoid personal errors in diagnosis. Laser induced fluorescence (LIF) is a promising technique that has been applied for the characterization of biological tissues including breast tissue. Unfortunately, only few studies have adopted a quantitative approach that can be directly applied for breast tissue characterization. This work provides a quantitative means for such characterization via introduction of several LIF characterization parameters and determining the diagnostic accuracy of each parameter in the differentiation between normal, benign and malignant excised breast tissues. Extensive analysis on 41 lyophilized breast samples using scatter diagrams, cut-off values, diagnostic indices and receiver operating characteristic (ROC) curves, shows that some spectral parameters (peak height and area under the peak) are superior for characterization of normal, benign and malignant breast tissues with high sensitivity (up to 0.91), specificity (up to 0.91) and accuracy ranking (highly accurate).

High Definition Confocal Imaging Modalities for the Characterization of Tissue-Engineered Substitutes.

PubMed

Mayrand, Dominique; Fradette, Julie

2018-01-01

Optimal imaging methods are necessary in order to perform a detailed characterization of thick tissue samples from either native or engineered tissues. Tissue-engineered substitutes are featuring increasing complexity including multiple cell types and capillary-like networks. Therefore, technical approaches allowing the visualization of the inner structural organization and cellular composition of tissues are needed. This chapter describes an optical clearing technique which facilitates the detailed characterization of whole-mount samples from skin and adipose tissues (ex vivo tissues and in vitro tissue-engineered substitutes) when combined with spectral confocal microscopy and quantitative analysis on image renderings.

Analyzing Remodeling of Cardiac Tissue: A Comprehensive Approach Based on Confocal Microscopy and 3D Reconstructions

PubMed Central

Sachse, F. B.

2015-01-01

Microstructural characterization of cardiac tissue and its remodeling in disease is a crucial step in many basic research projects. We present a comprehensive approach for three-dimensional characterization of cardiac tissue at the submicrometer scale. We developed a compression-free mounting method as well as labeling and imaging protocols that facilitate acquisition of three-dimensional image stacks with scanning confocal microscopy. We evaluated the approach with normal and infarcted ventricular tissue. We used the acquired image stacks for segmentation, quantitative analysis and visualization of important tissue components. In contrast to conventional mounting, compression-free mounting preserved cell shapes, capillary lumens and extracellular laminas. Furthermore, the new approach and imaging protocols resulted in high signal-to-noise ratios at depths up to 60 μm. This allowed extensive analyses revealing major differences in volume fractions and distribution of cardiomyocytes, blood vessels, fibroblasts, myofibroblasts and extracellular space in control versus infarct border zone. Our results show that the developed approach yields comprehensive data on microstructure of cardiac tissue and its remodeling in disease. In contrast to other approaches, it allows quantitative assessment of all major tissue components. Furthermore, we suggest that the approach will provide important data for physiological models of cardiac tissue at the submicrometer scale. PMID:26399990

Dielectric Characterization of PCL-Based Thermoplastic Materials for Microwave Diagnostic and Therapeutic Applications

PubMed Central

Aguilar, Suzette M.; Shea, Jacob D.; Al-Joumayly, Mudar A.; Van Veen, Barry D.; Behdad, Nader; Hagness, Susan C.

2011-01-01

We propose the use of a polycaprolactone (PCL)-based thermoplastic mesh as a tissue-immobilization interface for microwave imaging and microwave hyperthermia treatment. An investigation of the dielectric properties of two PCL-based thermoplastic materials in the frequency range of 0.5 – 3.5 GHz is presented. The frequency-dependent dielectric constant and effective conductivity of the PCL-based thermoplastics are characterized using measurements of microstrip transmission lines fabricated on substrates comprised of the thermoplastic meshes. We also examine the impact of the presence of a PCL-based thermoplastic mesh on microwave breast imaging. We use a numerical test bed comprised of a previously reported three-dimensional anatomically realistic breast phantom and a multi-frequency microwave inverse scattering algorithm. We demonstrate that the PCL-based thermoplastic material and the assumed biocompatible medium of vegetable oil are sufficiently well matched such that the PCL layer may be neglected by the imaging solution without sacrificing imaging quality. Our results suggest that PCL-based thermoplastics are promising materials as tissue immobilization structures for microwave diagnostic and therapeutic applications. PMID:21622068

Characterization of tissue response to radiofrequency ablation using 3D model-based analysis of interventional MR images

NASA Astrophysics Data System (ADS)

Weinberg, Brent D.; Lazebnik, Roee S.; Breen, Michael S.; Lewin, Jonathan S.; Wilson, David L.

2003-05-01

Using magnetic resonance imaging (MRI), real-time guidance is feasible for radiofrequency (RF) current ablation of pathologic tissue. Lesions have a characteristic two-zone appearance: an inner core (Zone I) surrounded by a hyper-intense rim (Zone II). A better understanding of both the immediate (hyper-acute) and delayed (sub-acute) physiological response of the target tissue will aid development of minimally invasive tumor treatment strategies. We performed in vivo RF ablations in a rabbit thigh model and characterized the tissue response to treatment through contrast enhanced (CE) T1 and T2 weighted MR images at two time points. We measured zonal grayscale changes as well as zone volume changes using a 3D computationally fitted globally deformable parametric model. Comparison over time demonstrated an increase in the volume of both the inner necrotic core (mean 56.5% increase) and outer rim (mean 16.8% increase) of the lesion. Additionally, T2 images of the lesion exhibited contrast greater than or equal to CE T1 (mean 35% improvement). This work establishes a foundation for the clinical use of T2 MR images coupled with a geometric model of the ablation for noninvasive lesion monitoring and characterization.

Development and characterization of a tissue-mimicking material for high-intensity focused ultrasound.

PubMed

King, Randy L; Liu, Yunbo; Maruvada, Subha; Herman, Bruce A; Wear, Keith A; Harris, Gerald R

2011-07-01

A tissue-mimicking material (TMM) for the acoustic and thermal characterization of high-intensity focused ultrasound (HIFU) devices has been developed. The material is a high-temperature hydrogel matrix (gellan gum) combined with different sizes of aluminum oxide particles and other chemicals. The ultrasonic properties (attenuation coefficient, speed of sound, acoustical impedance, and the thermal conductivity and diffusivity) were characterized as a function of temperature from 20 to 70°C. The backscatter coefficient and nonlinearity parameter B/A were measured at room temperature. Importantly, the attenuation coefficient has essentially linear frequency dependence, as is the case for most mammalian tissues at 37°C. The mean value is 0.64f(0.95) dB·cm(-1) at 20°C, based on measurements from 2 to 8 MHz. Most of the other relevant physical parameters are also close to the reported values, although backscatter signals are low compared with typical human soft tissues. Repeatable and consistent temperature elevations of 40°C were produced under 20-s HIFU exposures in the TMM. This TMM is appropriate for developing standardized dosimetry techniques, validating numerical models, and determining the safety and efficacy of HIFU devices.

Small-window parametric imaging based on information entropy for ultrasound tissue characterization

PubMed Central

Tsui, Po-Hsiang; Chen, Chin-Kuo; Kuo, Wen-Hung; Chang, King-Jen; Fang, Jui; Ma, Hsiang-Yang; Chou, Dean

2017-01-01

Constructing ultrasound statistical parametric images by using a sliding window is a widely adopted strategy for characterizing tissues. Deficiency in spatial resolution, the appearance of boundary artifacts, and the prerequisite data distribution limit the practicability of statistical parametric imaging. In this study, small-window entropy parametric imaging was proposed to overcome the above problems. Simulations and measurements of phantoms were executed to acquire backscattered radiofrequency (RF) signals, which were processed to explore the feasibility of small-window entropy imaging in detecting scatterer properties. To validate the ability of entropy imaging in tissue characterization, measurements of benign and malignant breast tumors were conducted (n = 63) to compare performances of conventional statistical parametric (based on Nakagami distribution) and entropy imaging by the receiver operating characteristic (ROC) curve analysis. The simulation and phantom results revealed that entropy images constructed using a small sliding window (side length = 1 pulse length) adequately describe changes in scatterer properties. The area under the ROC for using small-window entropy imaging to classify tumors was 0.89, which was higher than 0.79 obtained using statistical parametric imaging. In particular, boundary artifacts were largely suppressed in the proposed imaging technique. Entropy enables using a small window for implementing ultrasound parametric imaging. PMID:28106118

Small-window parametric imaging based on information entropy for ultrasound tissue characterization

NASA Astrophysics Data System (ADS)

Tsui, Po-Hsiang; Chen, Chin-Kuo; Kuo, Wen-Hung; Chang, King-Jen; Fang, Jui; Ma, Hsiang-Yang; Chou, Dean

2017-01-01

Constructing ultrasound statistical parametric images by using a sliding window is a widely adopted strategy for characterizing tissues. Deficiency in spatial resolution, the appearance of boundary artifacts, and the prerequisite data distribution limit the practicability of statistical parametric imaging. In this study, small-window entropy parametric imaging was proposed to overcome the above problems. Simulations and measurements of phantoms were executed to acquire backscattered radiofrequency (RF) signals, which were processed to explore the feasibility of small-window entropy imaging in detecting scatterer properties. To validate the ability of entropy imaging in tissue characterization, measurements of benign and malignant breast tumors were conducted (n = 63) to compare performances of conventional statistical parametric (based on Nakagami distribution) and entropy imaging by the receiver operating characteristic (ROC) curve analysis. The simulation and phantom results revealed that entropy images constructed using a small sliding window (side length = 1 pulse length) adequately describe changes in scatterer properties. The area under the ROC for using small-window entropy imaging to classify tumors was 0.89, which was higher than 0.79 obtained using statistical parametric imaging. In particular, boundary artifacts were largely suppressed in the proposed imaging technique. Entropy enables using a small window for implementing ultrasound parametric imaging.

Method And Apparatus For Examining A Tissue Using The Spectral Wing Emission Therefrom Induced By Visible To Infrared Photoexcitation.

DOEpatents

Alfano, Robert R.; Demos, Stavros G.; Zhang, Gang

2003-12-16

Method and an apparatus for examining a tissue using the spectral wing emission therefrom induced by visible to infrared photoexcitation. In one aspect, the method is used to characterize the condition of a tissue sample and comprises the steps of (a) photoexciting the tissue sample with substantially monochromatic light having a wavelength of at least 600 nm; and (b) using the resultant far red and near infrared spectral wing emission (SW) emitted from the tissue sample to characterize the condition of the tissue sample. In one embodiment, the substantially monochromatic photoexciting light is a continuous beam of light, and the resultant steady-state far red and near infrared SW emission from the tissue sample is used to characterize the condition of the tissue sample. In another embodiment, the substantially monochromatic photoexciting light is a light pulse, and the resultant time-resolved far red and near infrared SW emission emitted from the tissue sample is used to characterize the condition of the tissue sample. In still another embodiment, the substantially monochromatic photoexciting light is a polarized light pulse, and the parallel and perpendicular components of the resultant polarized time-resolved SW emission emitted from the tissue sample are used to characterize the condition of the tissue sample.

Tissue characterization with ballistic photons: counting scattering and/or absorption centres

NASA Astrophysics Data System (ADS)

Corral, F.; Strojnik, M.; Paez, G.

2015-03-01

We describe a new method to separate ballistic from the scattered photons for optical tissue characterization. It is based on the hypothesis that the scattered photons acquire a phase delay. The photons passing through the sample without scattering or absorption preserve their coherence so they may participate in interference. We implement a Mach-Zehnder experimental setup where the ballistic photons pass through the sample with the delay caused uniquely by the sample indices of refraction. We incorporate a movable mirror on the piezoelectric actuator in the sample arm to detect the amplitude of the modulation term. We present the theory that predicts the path-integrated (or total) concentration of the scattering and absorption centres. The proposed technique may characterize samples with transmission attenuation of ballistic photons by a factor of 10-14.

Development and characterization of a PHB-HV-based 3D scaffold for a tissue engineering and cell-therapy combinatorial approach for spinal cord injury regeneration.

PubMed

Ribeiro-Samy, Silvina; Silva, Nuno A; Correlo, Vitor M; Fraga, Joana S; Pinto, Luísa; Teixeira-Castro, Andreia; Leite-Almeida, Hugo; Almeida, Armando; Gimble, Jeffrey M; Sousa, Nuno; Salgado, António J; Reis, Rui L

2013-11-01

Spinal cord injury (SCI) leads to devastating neurological deficits. Several tissue engineering (TE)-based approaches have been investigated for repairing this condition. Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB-HV) is found to be particularly attractive for TE applications due to its properties, such as biodegradability, biocompatibility, thermoplasticity and piezoelectricity. Hence, this report addresses the development and characterization of PHB-HV-based 3D scaffolds, produced by freeze-drying, aimed to SCI treatment. The obtained scaffolds reveal an anisotropic morphology with a fully interconnected network of pores. In vitro studies demonstrate a lack of cytotoxic effect of PHB-HV scaffolds. Direct contact assays also reveal their ability to support the culture of CNS-derived cells and mesenchymal-like stem cells from different sources. Finally, histocompatibility studies show that PHB-HV scaffolds are well tolerated by the host tissue, and do not negatively impact the left hindlimb locomotor function recovery. Therefore results herein presented suggest that PHB-HV scaffolds may be suitable for SCI treatment. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Robust and fast characterization of OCT-based optical attenuation using a novel frequency-domain algorithm for brain cancer detection

NASA Astrophysics Data System (ADS)

Yuan, Wu; Kut, Carmen; Liang, Wenxuan; Li, Xingde

2017-03-01

Cancer is known to alter the local optical properties of tissues. The detection of OCT-based optical attenuation provides a quantitative method to efficiently differentiate cancer from non-cancer tissues. In particular, the intraoperative use of quantitative OCT is able to provide a direct visual guidance in real time for accurate identification of cancer tissues, especially these without any obvious structural layers, such as brain cancer. However, current methods are suboptimal in providing high-speed and accurate OCT attenuation mapping for intraoperative brain cancer detection. In this paper, we report a novel frequency-domain (FD) algorithm to enable robust and fast characterization of optical attenuation as derived from OCT intensity images. The performance of this FD algorithm was compared with traditional fitting methods by analyzing datasets containing images from freshly resected human brain cancer and from a silica phantom acquired by a 1310 nm swept-source OCT (SS-OCT) system. With graphics processing unit (GPU)-based CUDA C/C++ implementation, this new attenuation mapping algorithm can offer robust and accurate quantitative interpretation of OCT images in real time during brain surgery.

Integrated sensor biopsy device for real time tissue metabolism analysis

NASA Astrophysics Data System (ADS)

Delgado Alonso, Jesus; Lieberman, Robert A.; DiCarmine, Paul M.; Berry, David; Guzman, Narciso; Marpu, Sreekar B.

2018-02-01

Current methods for guiding cancer biopsies rely almost exclusively on images derived from X-ray, ultrasound, or magnetic resonance, which essentially characterize suspected lesions based only on tissue density. This paper presents a sensor integrated biopsy device for in situ tissue analysis that will enable biopsy teams to measure local tissue chemistry in real time during biopsy procedures, adding a valuable new set of parameters to augment and extend conventional image guidance. A first demonstrator integrating three chemical and biochemical sensors was tested in a mice strain that is a spontaneous breast cancer model. In all cases, the multisensory probe was able to discriminate between healthy tissue, the edge of the tumor, and total insertion inside the cancer tissue, recording real-time information about tissue metabolism.

Characterization of benign thyroid nodules with HyperSPACE (Hyper Spectral Analysis for Characterization in Echography) before and after percutaneous laser ablation: a pilot study.

PubMed

Granchi, Simona; Vannacci, Enrico; Biagi, Elena

2017-04-22

To evaluate the capability of the HyperSPACE (Hyper SPectral Analysis for Characterization in Echography) method in tissue characterization, in order to provide information for the laser treatment of benign thyroid nodules in respect of conventional B-mode images and elastography. The method, based on the spectral analysis of the raw radiofrequency ultrasonic signal, was applied to characterize the nodule before and after laser treatment. Thirty patients (25 females and 5 males, age between 37 and 81 years) with thyroid benign nodule at cytology (Thyr 2) were evaluated by conventional ultrasonography, elastography, and HyperSPACE, before and after laser ablation. The images processed by HyperSPACE exhibit different color distributions that are referred to different tissue features. By calculating the percentages of the color coverages, the analysed nodules were subdivided into 3 groups. Each nodule belonging to the same group experienced, on average, similar necrosis extension. The nodules exhibit different Configurations (colors) distributions that could be indicative of the response of nodular tissue to the laser treatmentConclusions: HyperSPACEcan characterize benign nodules by providing additional information in respect of conventional ultrasound and elastography which is useful for support in the laser treatment of nodules in order to increase the probability of success.

Multiparameter thermo-mechanical OCT-based characterization of laser-induced cornea reshaping

NASA Astrophysics Data System (ADS)

Zaitsev, Vladimir Yu.; Matveyev, Alexandr L.; Matveev, Lev A.; Gelikonov, Grigory V.; Vitkin, Alex; Omelchenko, Alexander I.; Baum, Olga I.; Shabanov, Dmitry V.; Sovetsky, Alexander A.; Sobol, Emil N.

2017-02-01

Phase-sensitive optical coherence tomography (OCT) is used for visualizing dynamic and cumulative strains and corneashape changes during laser-produced tissue heating. Such non-destructive (non-ablative) cornea reshaping can be used as a basis of emerging technologies of laser vision correction. In experiments with cartilaginous samples, polyacrilamide phantoms and excised rabbit eyes we demonstrate ability of the developed OCT system to simultaneously characterize transient and cumulated strain distributions, surface displacements, scattering tissue properties and possibility of temperature estimation via thermal-expansion measurements. The proposed approach can be implemented in perspective real-time OCT systems for ensuring safety of new methods of laser reshaping of cornea.

Brain palpation from physiological vibrations using MRI.

PubMed

Zorgani, Ali; Souchon, Rémi; Dinh, Au-Hoang; Chapelon, Jean-Yves; Ménager, Jean-Michel; Lounis, Samir; Rouvière, Olivier; Catheline, Stefan

2015-10-20

We present a magnetic resonance elastography approach for tissue characterization that is inspired by seismic noise correlation and time reversal. The idea consists of extracting the elasticity from the natural shear waves in living tissues that are caused by cardiac motion, blood pulsatility, and any muscle activity. In contrast to other magnetic resonance elastography techniques, this noise-based approach is, thus, passive and broadband and does not need any synchronization with sources. The experimental demonstration is conducted in a calibrated phantom and in vivo in the brain of two healthy volunteers. Potential applications of this "brain palpation" approach for characterizing brain anomalies and diseases are foreseen.

Optical characterization of tissue mimicking phantoms by a vertical double integrating sphere system

NASA Astrophysics Data System (ADS)

Han, Yilin; Jia, Qiumin; Shen, Shuwei; Liu, Guangli; Guo, Yuwei; Zhou, Ximing; Chu, Jiaru; Zhao, Gang; Dong, Erbao; Allen, David W.; Lemaillet, Paul; Xu, Ronald

2016-03-01

Accurate characterization of absorption and scattering properties for biologic tissue and tissue-simulating materials enables 3D printing of traceable tissue-simulating phantoms for medical spectral device calibration and standardized medical optical imaging. Conventional double integrating sphere systems have several limitations and are suboptimal for optical characterization of liquid and soft materials used in 3D printing. We propose a vertical double integrating sphere system and the associated reconstruction algorithms for optical characterization of phantom materials that simulate different human tissue components. The system characterizes absorption and scattering properties of liquid and solid phantom materials in an operating wavelength range from 400 nm to 1100 nm. Absorption and scattering properties of the phantoms are adjusted by adding titanium dioxide powder and India ink, respectively. Different material compositions are added in the phantoms and characterized by the vertical double integrating sphere system in order to simulate the human tissue properties. Our test results suggest that the vertical integrating sphere system is able to characterize optical properties of tissue-simulating phantoms without precipitation effect of the liquid samples or wrinkling effect of the soft phantoms during the optical measurement.

Solid tissue simulating phantoms having absorption at 970 nm for diffuse optics

NASA Astrophysics Data System (ADS)

Kennedy, Gordon T.; Lentsch, Griffin R.; Trieu, Brandon; Ponticorvo, Adrien; Saager, Rolf B.; Durkin, Anthony J.

2017-07-01

Tissue simulating phantoms can provide a valuable platform for quantitative evaluation of the performance of diffuse optical devices. While solid phantoms have been developed for applications related to characterizing exogenous fluorescence and intrinsic chromophores such as hemoglobin and melanin, we report the development of a poly(dimethylsiloxane) (PDMS) tissue phantom that mimics the spectral characteristics of tissue water. We have developed these phantoms to mimic different water fractions in tissue, with the purpose of testing new devices within the context of clinical applications such as burn wound triage. Compared to liquid phantoms, cured PDMS phantoms are easier to transport and use and have a longer usable life than gelatin-based phantoms. As silicone is hydrophobic, 9606 dye was used to mimic the optical absorption feature of water in the vicinity of 970 nm. Scattering properties are determined by adding titanium dioxide, which yields a wavelength-dependent scattering coefficient similar to that observed in tissue in the near-infrared. Phantom properties were characterized and validated using the techniques of inverse adding-doubling and spatial frequency domain imaging. Results presented here demonstrate that we can fabricate solid phantoms that can be used to simulate different water fractions.

Quantitative proteomic characterization of the lung extracellular matrix in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis.

PubMed

Åhrman, Emma; Hallgren, Oskar; Malmström, Lars; Hedström, Ulf; Malmström, Anders; Bjermer, Leif; Zhou, Xiao-Hong; Westergren-Thorsson, Gunilla; Malmström, Johan

2018-03-01

Remodeling of the extracellular matrix (ECM) is a common feature in lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Here, we applied a sequential tissue extraction strategy to describe disease-specific remodeling of human lung tissue in disease, using end-stages of COPD and IPF. Our strategy was based on quantitative comparison of the disease proteomes, with specific focus on the matrisome, using data-independent acquisition and targeted data analysis (SWATH-MS). Our work provides an in-depth proteomic characterization of human lung tissue during impaired tissue remodeling. In addition, we show important quantitative and qualitative effects of the solubility of matrisome proteins. COPD was characterized by a disease-specific increase in ECM regulators, metalloproteinase inhibitor 3 (TIMP3) and matrix metalloproteinase 28 (MMP-28), whereas for IPF, impairment in cell adhesion proteins, such as collagen VI and laminins, was most prominent. For both diseases, we identified increased levels of proteins involved in the regulation of endopeptidase activity, with several proteins belonging to the serpin family. The established human lung quantitative proteome inventory and the construction of a tissue-specific protein assay library provides a resource for future quantitative proteomic analyses of human lung tissues. We present a sequential tissue extraction strategy to determine changes in extractability of matrisome proteins in end-stage COPD and IPF compared to healthy control tissue. Extensive quantitative analysis of the proteome changes of the disease states revealed altered solubility of matrisome proteins involved in ECM regulators and cell-ECM communication. The results highlight disease-specific remodeling mechanisms associated with COPD and IPF. Copyright © 2018 Elsevier B.V. All rights reserved.

[Micro/nano-engineering to control growth of neuronal cells and tissue engineering applied to the central nervous system].

PubMed

Béduer, Amélie; Vaysse, Laurence; Loubinoux, Isabelle; Vieu, Christophe

2013-01-01

Central nervous system pathologies are often characterized by the loss of cell populations. A promising therapy now being developed consists in using bioactive materials, associating grafted cells to biopolymers which provide a scaffold for the in vitro building of new tissues, to be implanted in vivo. In the present article, the state of the art of this field, at crossroads between microtechnology and neuroscience, is described in detail; thereafter our own approach and results about interactions between adult human neural stem cells and microstructured polymers are summarized and discussed. In a second part, some central nervous system repair strategies, based on cerebral tissue engineering, are presented. We will report the main results of our studies to work out and characterize in vivo a cerebral bioprosthesis. © Société de Biologie, 2014.

Methods of Soft Tissue Emulsification Using a Mechanism of Ultrasonic Atomization Inside Gas or Vapor Cavities and Associated Systems and Devices

NASA Technical Reports Server (NTRS)

Bailey, Michael R. (Inventor); Simon, Julianna C. (Inventor); Crum, Lawrence A. (Inventor); Khokhlova, Vera A. (Inventor); Wang, Yak-Nam (Inventor); Sapozhnikov, Oleg A. (Inventor); Khokhlova, Tatiana D. (Inventor)

2016-01-01

The present technology is directed to methods of soft tissue emulsification using a mechanism of ultrasonic atomization inside gas or vapor cavities, and associated systems and devices. In several embodiments, for example, a method of non-invasively treating tissue includes pulsing ultrasound energy from the ultrasound source toward the target site in tissue. The ultrasound source is configured to emit high intensity focused ultrasound (HIFU) waves. The target site comprises a pressure-release interface of a gas or vapor cavity located within the tissue. The method continues by generating shock waves in the tissue to induce a lesion in the tissue at the target site. The method additionally includes characterizing the lesion based on a degree of at least one of a mechanical or thermal ablation of the tissue.

Semitransparent bandages based on chitosan and extracellular matrix for photochemical tissue bonding.

PubMed

Frost, Samuel J; Mawad, Damia; Wuhrer, Richard; Myers, Simon; Lauto, Antonio

2018-01-22

Extracellular matrices (ECMs) are often used in reconstructive surgery to enhance tissue regeneration and remodeling. Sutures and staples are currently used to fix ECMs to tissue although they can be invasive devices. Other sutureless and less invasive techniques, such as photochemical tissue bonding, cannot be coupled to ECMs because of their intrinsic opacity to light. We succeeded in fabricating a biocompatible and adhesive device that is based on ovine forestomach matrix (OFM) and a chitosan adhesive. The natural opacity of the OFM has been overcome by adding the adhesive into the matrix that allows for the light to effectively penetrate through it. The OFM-chitosan device is semitransparent (attenuation length ~ 106 µm) and can be photoactivated by green light to bond to tissue. This device does not require sutures or staples and guarantees a bonding strength of ~ 23 kPa. A new semitransparent and biocompatible bandage has been successfully fabricated and characterized for sutureless tissue bonding.

Fluorescence tomography characterization for sub-surface imaging with protoporphyrin IX

PubMed Central

Kepshire, Dax; Davis, Scott C.; Dehghani, Hamid; Paulsen, Keith D.; Pogue, Brian W.

2009-01-01

Optical imaging of fluorescent objects embedded in a tissue simulating medium was characterized using non-contact based approaches to fluorescence remittance imaging (FRI) and sub-surface fluorescence diffuse optical tomography (FDOT). Using Protoporphyrin IX as a fluorescent agent, experiments were performed on tissue phantoms comprised of typical in-vivo tumor to normal tissue contrast ratios, ranging from 3.5:1 up to 10:1. It was found that tomographic imaging was able to recover interior inclusions with high contrast relative to the background; however, simple planar fluorescence imaging provided a superior contrast to noise ratio. Overall, FRI performed optimally when the object was located on or close to the surface and, perhaps most importantly, FDOT was able to recover specific depth information about the location of embedded regions. The results indicate that an optimal system for localizing embedded fluorescent regions should combine fluorescence reflectance imaging for high sensitivity and sub-surface tomography for depth detection, thereby allowing more accurate localization in all three directions within the tissue. PMID:18545571

Elastic-viscoplastic modeling of soft biological tissues using a mixed finite element formulation based on the relative deformation gradient.

PubMed

Weickenmeier, J; Jabareen, M

2014-11-01

The characteristic highly nonlinear, time-dependent, and often inelastic material response of soft biological tissues can be expressed in a set of elastic-viscoplastic constitutive equations. The specific elastic-viscoplastic model for soft tissues proposed by Rubin and Bodner (2002) is generalized with respect to the constitutive equations for the scalar quantity of the rate of inelasticity and the hardening parameter in order to represent a general framework for elastic-viscoplastic models. A strongly objective integration scheme and a new mixed finite element formulation were developed based on the introduction of the relative deformation gradient-the deformation mapping between the last converged and current configurations. The numerical implementation of both the generalized framework and the specific Rubin and Bodner model is presented. As an example of a challenging application of the new model equations, the mechanical response of facial skin tissue is characterized through an experimental campaign based on the suction method. The measurement data are used for the identification of a suitable set of model parameters that well represents the experimentally observed tissue behavior. Two different measurement protocols were defined to address specific tissue properties with respect to the instantaneous tissue response, inelasticity, and tissue recovery. Copyright © 2014 John Wiley & Sons, Ltd.

Combining laser-assisted microdissection (LAM) and RNA-seq allows to perform a comprehensive transcriptomic analysis of epidermal cells of Arabidopsis embryo.

PubMed

Sakai, Kaori; Taconnat, Ludivine; Borrega, Nero; Yansouni, Jennifer; Brunaud, Véronique; Paysant-Le Roux, Christine; Delannoy, Etienne; Martin Magniette, Marie-Laure; Lepiniec, Loïc; Faure, Jean Denis; Balzergue, Sandrine; Dubreucq, Bertrand

2018-01-01

Genome-wide characterization of tissue- or cell-specific gene expression is a recurrent bottleneck in biology. We have developed a sensitive approach based on ultra-low RNA sequencing coupled to laser assisted microdissection for analyzing different tissues of the small Arabidopsis embryo. We first characterized the number of genes detected according to the quantity of tissue yield and total RNA extracted. Our results revealed that as low as 0.02 mm 2 of tissue and 50 pg of total RNA can be used without compromising the number of genes detected. The optimised protocol was used to compare the epidermal versus mesophyll cell transcriptomes of cotyledons at the torpedo-shaped stage of embryo development. The approach was validated by the recovery of well-known epidermal genes such AtML1 or AtPDF2 and genes involved in flavonoid and cuticular waxes pathways. Moreover, the interest and sensitivity of this approach were highlighted by the characterization of several transcription factors preferentially expressed in epidermal cells. This technical advance unlocks some current limitations of transcriptomic analyses and allows to investigate further and efficiently new biological questions for which only a very small amounts of cells need to be isolated. For instance, it paves the way to increasing the spatial accuracy of regulatory networks in developing small embryo of Arabidopsis or other plant tissues.

Automated tissue characterization of in vivo atherosclerotic plaques by intravascular optical coherence tomography images

PubMed Central

Ughi, Giovanni Jacopo; Adriaenssens, Tom; Sinnaeve, Peter; Desmet, Walter; D’hooge, Jan

2013-01-01

Intravascular optical coherence tomography (IVOCT) is rapidly becoming the method of choice for the in vivo investigation of coronary artery disease. While IVOCT visualizes atherosclerotic plaques with a resolution <20µm, image analysis in terms of tissue composition is currently performed by a time-consuming manual procedure based on the qualitative interpretation of image features. We illustrate an algorithm for the automated and systematic characterization of IVOCT atherosclerotic tissue. The proposed method consists in a supervised classification of image pixels according to textural features combined with the estimated value of the optical attenuation coefficient. IVOCT images of 64 plaques, from 49 in vivo IVOCT data sets, constituted the algorithm’s training and testing data sets. Validation was obtained by comparing automated analysis results to the manual assessment of atherosclerotic plaques. An overall pixel-wise accuracy of 81.5% with a classification feasibility of 76.5% and per-class accuracy of 89.5%, 72.1% and 79.5% for fibrotic, calcified and lipid-rich tissue respectively, was found. Moreover, measured optical properties were in agreement with previous results reported in literature. As such, an algorithm for automated tissue characterization was developed and validated using in vivo human data, suggesting that it can be applied to clinical IVOCT data. This might be an important step towards the integration of IVOCT in cardiovascular research and routine clinical practice. PMID:23847728

Engineering a functional three-dimensional human cardiac tissue model for drug toxicity screening.

PubMed

Lu, Hong Fang; Leong, Meng Fatt; Lim, Tze Chiun; Chua, Ying Ping; Lim, Jia Kai; Du, Chan; Wan, Andrew C A

2017-05-11

Cardiotoxicity is one of the major reasons for clinical drug attrition. In vitro tissue models that can provide efficient and accurate drug toxicity screening are highly desired for preclinical drug development and personalized therapy. Here, we report the fabrication and characterization of a human cardiac tissue model for high throughput drug toxicity studies. Cardiac tissues were fabricated via cellular self-assembly of human transgene-free induced pluripotent stem cells-derived cardiomyocytes in pre-fabricated polydimethylsiloxane molds. The formed tissue constructs expressed cardiomyocyte-specific proteins, exhibited robust production of extracellular matrix components such as laminin, collagen and fibronectin, aligned sarcomeric organization, and stable spontaneous contractions for up to 2 months. Functional characterization revealed that the cardiac cells cultured in 3D tissues exhibited higher contraction speed and rate, and displayed a significantly different drug response compared to cells cultured in age-matched 2D monolayer. A panel of clinically relevant compounds including antibiotic, antidiabetic and anticancer drugs were tested in this study. Compared to conventional viability assays, our functional contractility-based assays were more sensitive in predicting drug-induced cardiotoxic effects, demonstrating good concordance with clinical observations. Thus, our 3D cardiac tissue model shows great potential to be used for early safety evaluation in drug development and drug efficiency testing for personalized therapy.

Autofluorescence lifetime imaging during transoral robotic surgery: a clinical validation study of tumor detection (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lagarto, João. L.; Phipps, Jennifer E.; Unger, Jakob; Faller, Leta M.; Gorpas, Dimitris; Ma, Dinglong M.; Bec, Julien; Moore, Michael G.; Bewley, Arnaud F.; Yankelevich, Diego R.; Sorger, Jonathan M.; Farwell, Gregory D.; Marcu, Laura

2017-02-01

Autofluorescence lifetime spectroscopy is a promising non-invasive label-free tool for characterization of biological tissues and shows potential to report structural and biochemical alterations in tissue owing to pathological transformations. In particular, when combined with fiber-optic based instruments, autofluorescence lifetime measurements can enhance intraoperative diagnosis and provide guidance in surgical procedures. We investigate the potential of a fiber-optic based multi-spectral time-resolved fluorescence spectroscopy instrument to characterize the autofluorescence fingerprint associated with histologic, morphologic and metabolic changes in tissue that can provide real-time contrast between healthy and tumor regions in vivo and guide clinicians during resection of diseased areas during transoral robotic surgery. To provide immediate feedback to the surgeons, we employ tracking of an aiming beam that co-registers our point measurements with the robot camera images and allows visualization of the surgical area augmented with autofluorescence lifetime data in the surgeon's console in real-time. For each patient, autofluorescence lifetime measurements were acquired from normal, diseased and surgically altered tissue, both in vivo (pre- and post-resection) and ex vivo. Initial results indicate tumor and normal regions can be distinguished based on changes in lifetime parameters measured in vivo, when the tumor is located superficially. In particular, results show that autofluorescence lifetime of tumor is shorter than that of normal tissue (p < 0.05, n = 3). If clinical diagnostic efficacy is demonstrated throughout this on-going study, we believe that this method has the potential to become a valuable tool for real-time intraoperative diagnosis and guidance during transoral robot assisted cancer removal interventions.

Photoacoustic phasoscopy super-contrast imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Fei; Feng, Xiaohua; Zheng, Yuanjin, E-mail: yjzheng@ntu.edu.sg

2014-05-26

Phasoscopy is a recently proposed concept correlating electromagnetic (EM) absorption and scattering properties based on energy conservation. Phase information can be extracted from EM absorption induced acoustic wave and scattered EM wave for biological tissue characterization. In this paper, an imaging modality, termed photoacoustic phasoscopy imaging (PAPS), is proposed and verified experimentally based on phasoscopy concept with laser illumination. Both endogenous photoacoustic wave and scattered photons are collected simultaneously to extract the phase information. The PAPS images are then reconstructed on vessel-mimicking phantom and ex vivo porcine tissues to show significantly improved contrast than conventional photoacoustic imaging.

TU-AB-BRC-03: Accurate Tissue Characterization for Monte Carlo Dose Calculation Using Dual-and Multi-Energy CT Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lalonde, A; Bouchard, H

Purpose: To develop a general method for human tissue characterization with dual-and multi-energy CT and evaluate its performance in determining elemental compositions and the associated proton stopping power relative to water (SPR) and photon mass absorption coefficients (EAC). Methods: Principal component analysis is used to extract an optimal basis of virtual materials from a reference dataset of tissues. These principal components (PC) are used to perform two-material decomposition using simulated DECT data. The elemental mass fraction and the electron density in each tissue is retrieved by measuring the fraction of each PC. A stoichiometric calibration method is adapted to themore » technique to make it suitable for clinical use. The present approach is compared with two others: parametrization and three-material decomposition using the water-lipid-protein (WLP) triplet. Results: Monte Carlo simulations using TOPAS for four reference tissues shows that characterizing them with only two PC is enough to get a submillimetric precision on proton range prediction. Based on the simulated DECT data of 43 references tissues, the proposed method is in agreement with theoretical values of protons SPR and low-kV EAC with a RMS error of 0.11% and 0.35%, respectively. In comparison, parametrization and WLP respectively yield RMS errors of 0.13% and 0.29% on SPR, and 2.72% and 2.19% on EAC. Furthermore, the proposed approach shows potential applications for spectral CT. Using five PC and five energy bins reduces the SPR RMS error to 0.03%. Conclusion: The proposed method shows good performance in determining elemental compositions from DECT data and physical quantities relevant to radiotherapy dose calculation and generally shows better accuracy and unbiased results compared to reference methods. The proposed method is particularly suitable for Monte Carlo calculations and shows promise in using more than two energies to characterize human tissue with CT.« less

Reconstruction and Analysis of Human Kidney-Specific Metabolic Network Based on Omics Data

PubMed Central

Zhang, Ai-Di; Dai, Shao-Xing; Huang, Jing-Fei

2013-01-01

With the advent of the high-throughput data production, recent studies of tissue-specific metabolic networks have largely advanced our understanding of the metabolic basis of various physiological and pathological processes. However, for kidney, which plays an essential role in the body, the available kidney-specific model remains incomplete. This paper reports the reconstruction and characterization of the human kidney metabolic network based on transcriptome and proteome data. In silico simulations revealed that house-keeping genes were more essential than kidney-specific genes in maintaining kidney metabolism. Importantly, a total of 267 potential metabolic biomarkers for kidney-related diseases were successfully explored using this model. Furthermore, we found that the discrepancies in metabolic processes of different tissues are directly corresponding to tissue's functions. Finally, the phenotypes of the differentially expressed genes in diabetic kidney disease were characterized, suggesting that these genes may affect disease development through altering kidney metabolism. Thus, the human kidney-specific model constructed in this study may provide valuable information for the metabolism of kidney and offer excellent insights into complex kidney diseases. PMID:24222897

Photoacoustic physio-chemical analysis and its implementation in deep tissue with a catheter setup

NASA Astrophysics Data System (ADS)

Xu, Guan; Meng, Zhou-xian; Lin, Jian-die D.; Cheng, Qian; Wang, Xueding

2015-03-01

Photoacoustic (PA) measurements encode the information associated with both physical microstructures and chemical contents in biological tissues. A two-dimensional physio-chemical spectrogram (PCS) can be formulated by combining the power spectra of PA signals acquired at a series of optical wavelengths. The analysis of PCS, or namely PA physio-chemical analysis (PAPCA), enables the quantification of the relative concentrations and the spatial distributions of a variety of chemical components in the tissue. This study validated the feasibility of PAPCA in characterizing liver conditions during the progression of non-alcoholic fatty liver disease. A catheter based setup facilitating measurement in deep tissues was also tested.

Catheter based mid-infrared reflectance and reflectance generated absorption spectroscopy

DOEpatents

Holman, Hoi-Ying N

2013-10-29

A method of characterizing conditions in a tissue, by (a) providing a catheter that has a light source that emits light in selected wavenumbers within the range of mid-IR spectrum; (b) directing the light from the catheter to an area of tissue at a location inside a blood vessel of a subject; (c) collecting light reflected from the location and generating a reflectance spectra; and (d) comparing the reflectance spectra to a reference spectra of normal tissue, whereby a location having an increased number of absorbance peaks at said selected wavenumbers indicates a tissue inside the blood vessel containing a physiological marker for atherosclerosis.

Characterization and classification of oral tissues using excitation and emission matrix: a statistical modeling approach

NASA Astrophysics Data System (ADS)

Kanniyappan, Udayakumar; Gnanatheepaminstein, Einstein; Prakasarao, Aruna; Dornadula, Koteeswaran; Singaravelu, Ganesan

2017-02-01

Cancer is one of the most common human threats around the world and diagnosis based on optical spectroscopy especially fluorescence technique has been established as the standard approach among scientist to explore the biochemical and morphological changes in tissues. In this regard, the present work aims to extract spectral signatures of the various fluorophores present in oral tissues using parallel factor analysis (PARAFAC). Subsequently, the statistical analysis also to be performed to show its diagnostic potential in distinguishing malignant, premalignant from normal oral tissues. Hence, the present study may lead to the possible and/or alternative tool for oral cancer diagnosis.

Raman Imaging of Plant Cell Walls in Sections of Cucumis sativus

PubMed Central

Zeise, Ingrid; Heiner, Zsuzsanna; Holz, Sabine; Joester, Maike; Büttner, Carmen

2018-01-01

Raman microspectra combine information on chemical composition of plant tissues with spatial information. The contributions from the building blocks of the cell walls in the Raman spectra of plant tissues can vary in the microscopic sub-structures of the tissue. Here, we discuss the analysis of 55 Raman maps of root, stem, and leaf tissues of Cucumis sativus, using different spectral contributions from cellulose and lignin in both univariate and multivariate imaging methods. Imaging based on hierarchical cluster analysis (HCA) and principal component analysis (PCA) indicates different substructures in the xylem cell walls of the different tissues. Using specific signals from the cell wall spectra, analysis of the whole set of different tissue sections based on the Raman images reveals differences in xylem tissue morphology. Due to the specifics of excitation of the Raman spectra in the visible wavelength range (532 nm), which is, e.g., in resonance with carotenoid species, effects of photobleaching and the possibility of exploiting depletion difference spectra for molecular characterization in Raman imaging of plants are discussed. The reported results provide both, specific information on the molecular composition of cucumber tissue Raman spectra, and general directions for future imaging studies in plant tissues. PMID:29370089

Raman Imaging of Plant Cell Walls in Sections of Cucumis sativus.

PubMed

Zeise, Ingrid; Heiner, Zsuzsanna; Holz, Sabine; Joester, Maike; Büttner, Carmen; Kneipp, Janina

2018-01-25

Raman microspectra combine information on chemical composition of plant tissues with spatial information. The contributions from the building blocks of the cell walls in the Raman spectra of plant tissues can vary in the microscopic sub-structures of the tissue. Here, we discuss the analysis of 55 Raman maps of root, stem, and leaf tissues of Cucumis sativus , using different spectral contributions from cellulose and lignin in both univariate and multivariate imaging methods. Imaging based on hierarchical cluster analysis (HCA) and principal component analysis (PCA) indicates different substructures in the xylem cell walls of the different tissues. Using specific signals from the cell wall spectra, analysis of the whole set of different tissue sections based on the Raman images reveals differences in xylem tissue morphology. Due to the specifics of excitation of the Raman spectra in the visible wavelength range (532 nm), which is, e.g., in resonance with carotenoid species, effects of photobleaching and the possibility of exploiting depletion difference spectra for molecular characterization in Raman imaging of plants are discussed. The reported results provide both, specific information on the molecular composition of cucumber tissue Raman spectra, and general directions for future imaging studies in plant tissues.

Raman spectroscopy in biomedicine – non-invasive in vitro analysis of cells and extracellular matrix components in tissues

PubMed Central

Brauchle, Eva; Schenke-Layland, Katja

2013-01-01

Raman spectroscopy is an established laser-based technology for the quality assurance of pharmaceutical products. Over the past few years, Raman spectroscopy has become a powerful diagnostic tool in the life sciences. Raman spectra allow assessment of the overall molecular constitution of biological samples, based on specific signals from proteins, nucleic acids, lipids, carbohydrates, and inorganic crystals. Measurements are non-invasive and do not require sample processing, making Raman spectroscopy a reliable and robust method with numerous applications in biomedicine. Moreover, Raman spectroscopy allows the highly sensitive discrimination of bacteria. Rama spectra retain information on continuous metabolic processes and kinetics such as lipid storage and recombinant protein production. Raman spectra are specific for each cell type and provide additional information on cell viability, differentiation status, and tumorigenicity. In tissues, Raman spectroscopy can detect major extracellular matrix components and their secondary structures. Furthermore, the non-invasive characterization of healthy and pathological tissues as well as quality control and process monitoring of in vitro-engineered matrix is possible. This review provides comprehensive insight to the current progress in expanding the applicability of Raman spectroscopy for the characterization of living cells and tissues, and serves as a good reference point for those starting in the field. PMID:23161832

TSAPA: identification of tissue-specific alternative polyadenylation sites in plants.

PubMed

Ji, Guoli; Chen, Moliang; Ye, Wenbin; Zhu, Sheng; Ye, Congting; Su, Yaru; Peng, Haonan; Wu, Xiaohui

2018-06-15

Alternative polyadenylation (APA) is now emerging as a widespread mechanism modulated tissue-specifically, which highlights the need to define tissue-specific poly(A) sites for profiling APA dynamics across tissues. We have developed an R package called TSAPA based on the machine learning model for identifying tissue-specific poly(A) sites in plants. A feature space including more than 200 features was assembled to specifically characterize poly(A) sites in plants. The classification model in TSAPA can be customized by selecting desirable features or classifiers. TSAPA is also capable of predicting tissue-specific poly(A) sites in unannotated intergenic regions. TSAPA will be a valuable addition to the community for studying dynamics of APA in plants. https://github.com/BMILAB/TSAPA. Supplementary data are available at Bioinformatics online.

Emergence of tissue mechanics from cellular processes: shaping a fly wing

NASA Astrophysics Data System (ADS)

Merkel, Matthias; Etournay, Raphael; Popovic, Marko; Nandi, Amitabha; Brandl, Holger; Salbreux, Guillaume; Eaton, Suzanne; Jülicher, Frank

Nowadays, biologistsare able to image biological tissueswith up to 10,000 cells in vivowhere the behavior of each individual cell can be followed in detail.However, how precisely large-scale tissue deformation and stresses emerge from cellular behavior remains elusive. Here, we study this question in the developing wing of the fruit fly. To this end, we first establish a geometrical framework that exactly decomposes tissue deformation into contributions by different kinds of cellular processes. These processes comprise cell shape changes, cell neighbor exchanges, cell divisions, and cell extrusions. As the key idea, we introduce a tiling of the cellular network into triangles. This approach also reveals that tissue deformation can also be created by correlated cellular motion. Based on quantifications using these concepts, we developed a novel continuum mechanical model for the fly wing. In particular, our model includes active anisotropic stresses and a delay in the response of cell rearrangements to material stresses. A different approach to study the emergence of tissue mechanics from cellular behavior are cell-based models. We characterize the properties of a cell-based model for 3D tissues that is a hybrid between single particle models and the so-called vertex models.

Bioanalytical and chemical sensors using living taste, olfactory, and neural cells and tissues: a short review.

PubMed

Wu, Chunsheng; Lillehoj, Peter B; Wang, Ping

2015-11-07

Biosensors utilizing living tissues and cells have recently gained significant attention as functional devices for chemical sensing and biochemical analysis. These devices integrate biological components (i.e. single cells, cell networks, tissues) with micro-electro-mechanical systems (MEMS)-based sensors and transducers. Various types of cells and tissues derived from natural and bioengineered sources have been used as recognition and sensing elements, which are generally characterized by high sensitivity and specificity. This review summarizes the state of the art in tissue- and cell-based biosensing platforms with an emphasis on those using taste, olfactory, and neural cells and tissues. Many of these devices employ unique integration strategies and sensing schemes based on sensitive transducers including microelectrode arrays (MEAs), field effect transistors (FETs), and light-addressable potentiometric sensors (LAPSs). Several groups have coupled these hybrid biosensors with microfluidics which offers added benefits of small sample volumes and enhanced automation. While this technology is currently limited to lab settings due to the limited stability of living biological components, further research to enhance their robustness will enable these devices to be employed in field and clinical settings.

Surface-enhanced Raman scattering of rat tissues.

PubMed

Aydin, Omer; Kahraman, Mehmet; Kiliç, Ertuğul; Culha, Mustafa

2009-06-01

Surface-enhanced Raman scattering (SERS) is proven to be a powerful tool for investigation of biological structures. In this study, tissues obtained from different rat organs are examined using SERS. The tissue samples are crushed with a pestle after sudden freezing in liquid nitrogen and mixed with a concentrated colloidal silver nanoparticle suspension. The reproducibility of SERS spectra acquired from several tissue samples from different organs is demonstrated. The collected spectra are comparatively evaluated based on the physiological function of the organ from which the tissue is obtained. The spectra from the tissues show significant differences and indicate that they can be used for tissue characterization and differentiation. The identification of the origins of the bands on the spectra is also attempted. This study suggests that SERS can be used to monitor the changes at the molecular level during metabolic changes in an organ or tissue as a result of a disease or another cause.

Colorization and Automated Segmentation of Human T2 MR Brain Images for Characterization of Soft Tissues

PubMed Central

Attique, Muhammad; Gilanie, Ghulam; Hafeez-Ullah; Mehmood, Malik S.; Naweed, Muhammad S.; Ikram, Masroor; Kamran, Javed A.; Vitkin, Alex

2012-01-01

Characterization of tissues like brain by using magnetic resonance (MR) images and colorization of the gray scale image has been reported in the literature, along with the advantages and drawbacks. Here, we present two independent methods; (i) a novel colorization method to underscore the variability in brain MR images, indicative of the underlying physical density of bio tissue, (ii) a segmentation method (both hard and soft segmentation) to characterize gray brain MR images. The segmented images are then transformed into color using the above-mentioned colorization method, yielding promising results for manual tracing. Our color transformation incorporates the voxel classification by matching the luminance of voxels of the source MR image and provided color image by measuring the distance between them. The segmentation method is based on single-phase clustering for 2D and 3D image segmentation with a new auto centroid selection method, which divides the image into three distinct regions (gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) using prior anatomical knowledge). Results have been successfully validated on human T2-weighted (T2) brain MR images. The proposed method can be potentially applied to gray-scale images from other imaging modalities, in bringing out additional diagnostic tissue information contained in the colorized image processing approach as described. PMID:22479421

Magneto-photo-acoustic imaging

PubMed Central

Qu, Min; Mallidi, Srivalleesha; Mehrmohammadi, Mohammad; Truby, Ryan; Homan, Kimberly; Joshi, Pratixa; Chen, Yun-Sheng; Sokolov, Konstantin; Emelianov, Stanislav

2011-01-01

Magneto-photo-acoustic imaging, a technique based on the synergy of magneto-motive ultrasound, photoacoustic and ultrasound imaging, is introduced. Hybrid nanoconstructs, liposomes encapsulating gold nanorods and iron oxide nanoparticles, were used as a dual-contrast agent for magneto-photo-acoustic imaging. Tissue-mimicking phantom and macrophage cells embedded in ex vivo porcine tissue were used to demonstrate that magneto-photo-acoustic imaging is capable of visualizing the location of cells or tissues labeled with dual-contrast nanoparticles with sufficient contrast, excellent contrast resolution and high spatial resolution in the context of the anatomical structure of the surrounding tissues. Therefore, magneto-photo-acoustic imaging is capable of identifying the nanoparticle-labeled pathological regions from the normal tissue, providing a promising platform to noninvasively diagnose and characterize pathologies. PMID:21339883

Detection of experimental brain tumors using time-resolved laser-induced fluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Thompson, Reid C.; Black, Keith L.; Kateb, Babak; Marcu, Laura

2002-05-01

Time-Resolved Laser-Induced Fluorescence Spectroscopy (TR-LIFS) has the potential to provide a non- invasive characterization and detection of tumors. We utilized TR-LIFS to detect gliomas in-vivo in the rat C6 glioma model. Time-resolved emission spectra of both normal brain and tumor were analyzed to determine if unique fluorescence signatures could be used to distinguish the two. Fluorescence parameters derived from both spectral and time domain were used for tissue characterization. Our results show that in the rat C6 glioma model, TR-LIFS can be used to differentiate brain tumors from normal tissue (gray and white mater) based upon time- resolved fluorescence signatures seen in brain tumors.

Mechanics of ultrasound elastography

PubMed Central

Li, Guo-Yang

2017-01-01

Ultrasound elastography enables in vivo measurement of the mechanical properties of living soft tissues in a non-destructive and non-invasive manner and has attracted considerable interest for clinical use in recent years. Continuum mechanics plays an essential role in understanding and improving ultrasound-based elastography methods and is the main focus of this review. In particular, the mechanics theories involved in both static and dynamic elastography methods are surveyed. They may help understand the challenges in and opportunities for the practical applications of various ultrasound elastography methods to characterize the linear elastic, viscoelastic, anisotropic elastic and hyperelastic properties of both bulk and thin-walled soft materials, especially the in vivo characterization of biological soft tissues. PMID:28413350

Emergence of Scaffold-free Approaches for Tissue Engineering Musculoskeletal Cartilages

PubMed Central

DuRaine, Grayson D.; Brown, Wendy E.; Hu, Jerry C.; Athanasiou, Kyriacos A.

2014-01-01

This review explores scaffold-free methods as an additional paradigm for tissue engineering. Musculoskeletal cartilages –for example articular cartilage, meniscus, temporomandibular joint disc, and intervertebral disc – are characterized by low vascularity and cellularity, and are amenable to scaffold-free tissue engineering approaches. Scaffold-free approaches, particularly the self-assembling process, mimic elements of developmental processes underlying these tissues. Discussed are various scaffold-free approaches for musculoskeletal cartilage tissue engineering, such as cell sheet engineering, aggregation, and the self-assembling process, as well as the availability and variety of cells used. Immunological considerations are of particular importance as engineered tissues are frequently of allogeneic, if not xenogeneic, origin. Factors that enhance the matrix production and mechanical properties of these engineered cartilages are also reviewed, as the fabrication of biomimetically suitable tissues is necessary to replicate function and ensure graft survival in vivo. The concept of combining scaffold-free and scaffold-based tissue engineering methods to address clinical needs is also discussed. Inasmuch as scaffold-based musculoskeletal tissue engineering approaches have been employed as a paradigm to generate engineered cartilages with appropriate functional properties, scaffold-free approaches are emerging as promising elements of a translational pathway not only for musculoskeletal cartilages but for other tissues as well. PMID:25331099

Morphological respiratory diffusion capacity of the lungs of ball pythons (Python regius).

PubMed

Starck, J Matthias; Aupperle, Heike; Kiefer, Ingmar; Weimer, Isabel; Krautwald-Junghanns, Maria-Elisabeth; Pees, Michael

2012-08-01

This study aims at a functional and morphological characterization of the lung of a boid snake. In particular, we were interested to see if the python's lungs are designed with excess capacity as compared to resting and working oxygen demands. Therefore, the morphological respiratory diffusion capacity of ball pythons (Python regius) was examined following a stereological, hierarchically nested approach. The volume of the respiratory exchange tissue was determined using computed tomography. Tissue compartments were quantified using stereological methods on light microscopic images. The tissue diffusion barrier for oxygen transport was characterized and measured using transmission electron micrographs. We found a significant negative correlation between body mass and the volume of respiratory tissue; the lungs of larger snakes had relatively less respiratory tissue. Therefore, mass-specific respiratory tissue was calculated to exclude effects of body mass. The volume of the lung that contains parenchyma was 11.9±5.0mm(3)g(-1). The volume fraction, i.e., the actual pulmonary exchange tissue per lung parenchyma, was 63.22±7.3%; the total respiratory surface was, on average, 0.214±0.129m(2); it was significantly negatively correlated to body mass, with larger snakes having proportionally smaller respiratory surfaces. For the air-blood barrier, a harmonic mean of 0.78±0.05μm was found, with the epithelial layer representing the thickest part of the barrier. Based on these findings, a median diffusion capacity of the tissue barrier ( [Formula: see text] ) of 0.69±0.38ml O(2)min(-1)mmHg(-1) was calculated. Based on published values for blood oxygen concentration, a total oxygen uptake capacity of 61.16mlO(2)min(-1)kg(-1) can be assumed. This value exceeds the maximum demand for oxygen in ball pythons by a factor of 12. We conclude that healthy individuals of P. regius possess a considerable spare capacity for tissue oxygen exchange. Copyright © 2012 Elsevier GmbH. All rights reserved.

Association of spirochetal infection with Morgellons disease.

PubMed

Middelveen, Marianne J; Burugu, Divya; Poruri, Akhila; Burke, Jennie; Mayne, Peter J; Sapi, Eva; Kahn, Douglas G; Stricker, Raphael B

2013-01-01

Morgellons disease (MD) is an emerging multisystem illness characterized by skin lesions with unusual filaments embedded in or projecting from epithelial tissue. Filament formation results from abnormal keratin and collagen expression by epithelial-based keratinocytes and fibroblasts. Recent research comparing MD to bovine digital dermatitis, an animal infectious disease with similar skin features, provided clues that spirochetal infection could play an important role in the human disease as it does in the animal illness. Based on histological staining, immunofluorescent staining, electron microscopic imaging and polymerase chain reaction, we report the detection of Borrelia spirochetes in dermatological tissue of  four randomly-selected MD patients. The association of MD with spirochetal infection provides evidence that this infection may be a significant factor in the illness and refutes claims that MD lesions are self-inflicted and that people suffering from this disorder are delusional. Molecular characterization of the Borrelia spirochetes found in MD patients is warranted.

Association of spirochetal infection with Morgellons disease

PubMed Central

Stricker, Raphael B

2013-01-01

Morgellons disease (MD) is an emerging multisystem illness characterized by skin lesions with unusual filaments embedded in or projecting from epithelial tissue. Filament formation results from abnormal keratin and collagen expression by epithelial-based keratinocytes and fibroblasts. Recent research comparing MD to bovine digital dermatitis, an animal infectious disease with similar skin features, provided clues that spirochetal infection could play an important role in the human disease as it does in the animal illness. Based on histological staining, immunofluorescent staining, electron microscopic imaging and polymerase chain reaction, we report the detection of Borrelia spirochetes in dermatological tissue of  four randomly-selected MD patients. The association of MD with spirochetal infection provides evidence that this infection may be a significant factor in the illness and refutes claims that MD lesions are self-inflicted and that people suffering from this disorder are delusional. Molecular characterization of the Borrelia spirochetes found in MD patients is warranted. PMID:24715950

In situ ultrahigh-resolution optical coherence tomography characterization of eye bank corneal tissue processed for lamellar keratoplasty.

PubMed

Brown, Jamin S; Wang, Danling; Li, Xiaoli; Baluyot, Florence; Iliakis, Bernie; Lindquist, Thomas D; Shirakawa, Rika; Shen, Tueng T; Li, Xingde

2008-08-01

To use optical coherence tomography (OCT) as a noninvasive tool to perform in situ characterization of eye bank corneal tissue processed for lamellar keratoplasty. A custom-built ultrahigh-resolution OCT (UHR-OCT) was used to characterize donor corneal tissue that had been processed for lamellar keratoplasty. Twenty-seven donor corneas were analyzed. Four donor corneas were used as controls, whereas the rest were processed into donor corneal buttons for lamellar transplantation by using hand dissection, a microkeratome, or a femtosecond laser. UHR-OCT was also used to noninvasively characterize and monitor the viable corneal tissue immersed in storage medium over 3 weeks. The UHR-OCT captured high-resolution images of the donor corneal tissue in situ. This noninvasive technique showed the changes in donor corneal tissue morphology with time while in storage medium. The characteristics of the lamellar corneal tissue with each processing modality were clearly visible by UHR-OCT. The in situ characterization of the femtosecond laser-cut corneal tissue was noted to have more interface debris than shown by routine histology. The effects of the femtosecond laser microcavitation bubbles on the corneal tissue were well visualized at the edges of the lamellar flap while in storage medium. The results of our feasibility study show that UHR-OCT can provide superb, in situ microstructural characterization of eye bank corneal tissue noninvasively. The UHR-OCT interface findings and corneal endothelial disc thickness uniformity analysis are valuable information that may be used to optimize the modalities and parameters for lamellar tissue processing. The UHR-OCT is a powerful approach that will allow us to further evaluate the tissue response to different processing techniques for posterior lamellar keratoplasty. It may also provide information that can be used to correlate with postoperative clinical outcomes. UHR-OCT has the potential to become a routine part of tissue analysis for any eye bank or centers creating customized lamellar corneal tissue for transplantation.

Multicenter validation of cancer gene panel-based next-generation sequencing for translational research and molecular diagnostics.

PubMed

Hirsch, B; Endris, V; Lassmann, S; Weichert, W; Pfarr, N; Schirmacher, P; Kovaleva, V; Werner, M; Bonzheim, I; Fend, F; Sperveslage, J; Kaulich, K; Zacher, A; Reifenberger, G; Köhrer, K; Stepanow, S; Lerke, S; Mayr, T; Aust, D E; Baretton, G; Weidner, S; Jung, A; Kirchner, T; Hansmann, M L; Burbat, L; von der Wall, E; Dietel, M; Hummel, M

2018-04-01

The simultaneous detection of multiple somatic mutations in the context of molecular diagnostics of cancer is frequently performed by means of amplicon-based targeted next-generation sequencing (NGS). However, only few studies are available comparing multicenter testing of different NGS platforms and gene panels. Therefore, seven partner sites of the German Cancer Consortium (DKTK) performed a multicenter interlaboratory trial for targeted NGS using the same formalin-fixed, paraffin-embedded (FFPE) specimen of molecularly pre-characterized tumors (n = 15; each n = 5 cases of Breast, Lung, and Colon carcinoma) and a colorectal cancer cell line DNA dilution series. Detailed information regarding pre-characterized mutations was not disclosed to the partners. Commercially available and custom-designed cancer gene panels were used for library preparation and subsequent sequencing on several devices of two NGS different platforms. For every case, centrally extracted DNA and FFPE tissue sections for local processing were delivered to each partner site to be sequenced with the commercial gene panel and local bioinformatics. For cancer-specific panel-based sequencing, only centrally extracted DNA was analyzed at seven sequencing sites. Subsequently, local data were compiled and bioinformatics was performed centrally. We were able to demonstrate that all pre-characterized mutations were re-identified correctly, irrespective of NGS platform or gene panel used. However, locally processed FFPE tissue sections disclosed that the DNA extraction method can affect the detection of mutations with a trend in favor of magnetic bead-based DNA extraction methods. In conclusion, targeted NGS is a very robust method for simultaneous detection of various mutations in FFPE tissue specimens if certain pre-analytical conditions are carefully considered.

Multi-component nanofibrous scaffolds with tunable properties for bone tissue engineering

NASA Astrophysics Data System (ADS)

Jose, Moncy V.

Bone is a highly complex tissue which is an integral part of vertebrates and hence any damage has a major negative effect on the quality of life. Tissue engineering is regarded as an ideal route to resolve the issues related to the scarcity of tissue and organ for transplantation. Apart from cell line and growth factors, the choice of materials and fabrication technique for scaffold are equally important. The goal of this work was to develop a multi-component nanofibrous scaffold based on a synthetic polymer (poly(lactic-co-glycolide) (PLGA)), a biopolymer (collagen) and a biomineral (nano-hydroxyapatite (nano-HA)) by electrospinning technique, which mimics the nanoscopic, chemical, and anisotropic features of bone. Preliminary studies involved fabrication of nanocomposite scaffolds based on PLGA and nano-HA. Morphological and mechanical characterizations revealed that at low concentrations, nano-HA acted as reinforcements, whereas at higher concentrations the presence of aggregation was detrimental to the scaffold. Hydrolytic degradation studies revealed the scaffold had a little mass loss and the mechanical property was maintained for a period of 6 weeks. This study was followed by evaluation of a blend system based on PLGA and collagen. Collagen addition provides hydrophilicity and the necessary cell binding sites in PLGA. The structural characterization revealed that the blend had limited interactions between the two components. The mechanical characterization revealed that with increasing collagen concentration, there was a decline in mechanical properties. However, crosslinking of the blend system, with carbodiimide (EDC) resulted in improving the mechanical properties of the scaffolds. A multi-component system was developed by adding different concentrations of nano-HA to a fixed PLGA/collagen blend composition (80/20). Morphological and mechanical characterizations revealed properties similar to the PLGA/HA system. Cyto-compatibility studies revealed favorable cell adhesion and proliferation. Protein adsorption studies showed the higher surface area as well as the presence of collagen resulted in higher fibronectin and vitronectin adsorption. Crosslinking by EDC resulted in enhanced mechanical property in hydrated state and enhanced degradation stability. These results suggest that such a multi-component system can take advantage of the mechanical benefit available from the individual components and also provide specific biological cues necessary for a successful scaffold.

Controlling tissue microenvironments: biomimetics, transport phenomena, and reacting systems.

PubMed

Fisher, Robert J; Peattie, Robert A

2007-01-01

The reconstruction of tissues ex vivo and production of cells capable of maintaining a stable performance for extended time periods in sufficient quantity for synthetic or therapeutic purposes are primary objectives of tissue engineering. The ability to characterize and manipulate the cellular microenvironment is critical for successful implementation of such cell-based bioengineered systems. As a result, knowledge of fundamental biomimetics, transport phenomena, and reaction engineering concepts is essential to system design and development. Once the requirements of a specific tissue microenvironment are understood, the biomimetic system specifications can be identified and a design implemented. Utilization of novel membrane systems that are engineered to possess unique transport and reactive features is one successful approach presented here. The limited availability of tissue or cells for these systems dictates the need for microscale reactors. A capstone illustration based on cellular therapy for type 1 diabetes mellitus via encapsulation techniques is presented as a representative example of this approach, to stress the importance of integrated systems.

Fresh broad (Vicia faba) tissue homogenate-based biosensor for determination of phenolic compounds.

PubMed

Ozcan, Hakki Mevlut; Sagiroglu, Ayten

2014-08-01

In this study, a novel fresh broad (Vicia faba) tissue homogenate-based biosensor for determination of phenolic compounds was developed. The biosensor was constructed by immobilizing tissue homogenate of fresh broad (Vicia faba) on to glassy carbon electrode. For the stability of the biosensor, general immobilization techniques were used to secure the fresh broad tissue homogenate in gelatin-glutaraldehyde cross-linking matrix. In the optimization and characterization studies, the amount of fresh broad tissue homogenate and gelatin, glutaraldehyde percentage, optimum pH, optimum temperature and optimum buffer concentration, thermal stability, interference effects, linear range, storage stability, repeatability and sample applications (Wine, beer, fruit juices) were also investigated. Besides, the detection ranges of thirteen phenolic compounds were obtained with the help of the calibration graphs. A typical calibration curve for the sensor revealed a linear range of 5-60 μM catechol. In reproducibility studies, variation coefficient (CV) and standard deviation (SD) were calculated as 1.59%, 0.64×10(-3) μM, respectively.

[Systemic lupus erythematosus and pregnancy].

PubMed

Basheva, S; Nikolov, A; Stoilov, R; Stoilov, N

2012-01-01

Connective-tissue disorders, also referred to as collagen-vascular disorders, are characterized by autoantibody-mediated connective-tissue abnormalities. These are also called immune-complex diseases because many involve deposition of immune complexes in specific organ or tissue sites. Some of these disorders are characterized by sterile inflammation, especially of the skin, joints, blood vessels, and kidneys, and are referred to as rheumatic diseases. For inexplicable reasons, many rheumatic diseases primarily affect women. Another major category of connective-tissue diseases includes inherited disorders of bone, skin, cartilage, blood vessels. Examples include Marfan syndrome, osteogenesis imperfecta, and Ehlers-Danlos syndrome. Lupus erythematosus (LE) is the main and most important disease in the group of systemic connective tissue diseases. It is heterogeneous, multiple organs autoimmune inflammatory disease with complex pathogenesis, which is the result of interaction between the susceptible genes and environmental factors that lead to abnormal immune response. In this review will consider: its incidence, pathogenesis, clinical forms and clinical features and diagnosis set based on generally accepted clinical criteria developed by the American College of Rheumatology (ACR), the course of pregnancy in patients suffering from LE, the most common complications of LE during pregnancy and antiphospholipid syndrome as part of LE.

Modeling and measurement of tissue elastic moduli using optical coherence elastography

NASA Astrophysics Data System (ADS)

Liang, Xing; Oldenburg, Amy L.; Crecea, Vasilica; Kalyanam, Sureshkumar; Insana, Michael F.; Boppart, Stephen A.

2008-02-01

Mechanical forces play crucial roles in tissue growth, patterning and development. To understand the role of mechanical stimuli, biomechanical properties are of great importance, as well as our ability to measure biomechanical properties of developing and engineered tissues. To enable these measurements, a novel non-invasive, micron-scale and high-speed Optical Coherence Elastography (OCE) system has been developed utilizing a titanium:sapphire based spectral-domain Optical Coherence Tomography (OCT) system and a mechanical wave driver. This system provides axial resolution of 3 microns, transverse resolution of 13 microns, and an acquisition rate as high as 25,000 lines per second. External lowfrequency vibrations are applied to the samples in the system. Step and sinusoidal steady-state responses are obtained to first characterize the OCE system and then characterize samples. Experimental results of M-mode OCE on silicone phantoms and human breast tissues are obtained, which correspond to biomechanical models developed for this analysis. Quantified results from the OCE system correspond directly with results from an indentation method from a commercial. With micron-scale resolution and a high-speed acquisition rate, our OCE system also has the potential to rapidly measure dynamic 3-D tissue biomechanical properties.

Hierarchical brain tissue segmentation and its application in multiple sclerosis and Alzheimer's disease

NASA Astrophysics Data System (ADS)

Lei, Tianhu; Udupa, Jayaram K.; Moonis, Gul; Schwartz, Eric; Balcer, Laura

2005-04-01

Based on Fuzzy Connectedness (FC) object delineation principles and algorithms, a hierarchical brain tissue segmentation technique has been developed for MR images. After MR image background intensity inhomogeneity correction and intensity standardization, three FC objects for cerebrospinal fluid (CSF), gray matter (GM), and white matter (WM) are generated via FC object delineation, and an intracranial (IC) mask is created via morphological operations. Then, the IC mask is decomposed into parenchymal (BP) and CSF masks, while the BP mask is separated into WM and GM masks. WM mask is further divided into pure and dirty white matter masks (PWM and DWM). In Multiple Sclerosis studies, a severe white matter lesion (LS) mask is defined from DWM mask. Based on the segmented brain tissue images, a histogram-based method has been developed to find disease-specific, image-based quantitative markers for characterizing the macromolecular manifestation of the two diseases. These same procedures have been applied to 65 MS (46 patients and 19 normal subjects) and 25 AD (15 patients and 10 normal subjects) data sets, each of which consists of FSE PD- and T2-weighted MR images. Histograms representing standardized PD and T2 intensity distributions and their numerical parameters provide an effective means for characterizing the two diseases. The procedures are systematic, nearly automated, robust, and the results are reproducible.

From impedance theory to needle electrode guidance in tissue

NASA Astrophysics Data System (ADS)

Kalvøy, Håvard; Høyum, Per; Grimnes, Sverre; Martinsen, Ørjan G.

2010-04-01

Fast access to blood vessels or other tissues/organs can be crucial in clinical or acute medical treatment. We have developed a method for needle guidance for use in different types of applications. The feasibility of an automatic application for fast access to blood vessels during acute cardiac arrest, based on this method, has been evaluated. Suited electrode setups were found by development of needle electrode models used in simulation and sensitivity analyses. In vitro measurements were done both to determine the fundamental properties of the electrodes for use in the models and to confirm the simulation results. Development of algorithms for tissue characterization and differentiation was based on in vivo impedance measurement in porcine models and confirmed in human tissue in vivo. Feasibility was proven by application prototyping and impedance data presented as invasive Electrical Impedance Tomography (iEIT). Our conclusion is that this method can be utilized in a wide range of clinical applications.

Magnetic mapping of iron in rodent spleen

PubMed Central

Blissett, Angela R.; Ollander, Brooke; Penn, Brittany; McTigue, Dana M.; Agarwal, Gunjan

2016-01-01

Evaluation of iron distribution and density in biological tissues is important to understand the pathogenesis of a variety of diseases and the fate of exogenously administered iron-based carriers and contrast agents. Iron distribution in tissues is typically characterized via histochemical (Perl’s) stains or immunohistochemistry for ferritin, the major iron storage protein. A more accurate mapping of iron can be achieved via ultrastructural transmission electron microscopy (TEM) based techniques, which involve stringent sample preparation conditions. In this study, we elucidate the capability of magnetic force microscopy (MFM) as a label-free technique to map iron at the nanoscale level in rodent spleen tissue. We complemented and compared our MFM results with those obtained using Perl’s staining and TEM. Our results show how MFM mapping corresponded to sizes of iron-rich lysosomes at a resolution comparable to that of TEM. In addition MFM is compatible with tissue sections commonly prepared for routine histology. PMID:27890658

Quantitative Evaluation of Atherosclerotic Plaque Using Ultrasound Tissue Characterization.

NASA Astrophysics Data System (ADS)

Yigiter, Ersin

Evaluation of therapeutic methods directed toward interrupting and/or delaying atherogenesis is impeded by the lack of a reliable, non-invasive means for monitoring progression or regression of disease. The ability to characterize the predominant component of plaque may be very valuable in the study of this disease's natural history. The earlier the lesion, the more likely is lipid to be the predominant component. Progression of plaque is usually by way of overgrowth of fibrous tissues around the fatty pool. Calcification is usually a feature of the older or complicated lesion. To explore the feasibility of using ultrasound to characterize plaque we have conducted measurements of the acoustical properties of various atherosclerotic lesions found in freshly excised samples of human abdominal aorta. Our objective has been to determine whether or not the acoustical properties of plaque correlate with the type and/or chemical composition of plaque and, if so, to define a measurement scheme which could be done in-vivo and non-invasively. Our current data base consists of individual tissue samples from some 200 different aortas. Since each aorta yields between 10 to 30 tissue samples for study, we have data on some 4,468 different lesions or samples. Measurements of the acoustical properties of plaque were found to correlate well with the chemical composition of plaque. In short, measurements of impedance and attenuation seem sufficient to classify plaque as to type and to composition. Based on the in-vitro studies, the parameter of attenuation was selected as a means of classifying the plaque. For these measurements, an intravascular ultrasound scanner was modified according to our specifications. Signal processing algorithms were developed which would analyze the complex ultrasound waveforms and estimate tissue properties such as attenuation. Various methods were tried to estimate the attenuation from the pulse-echo backscattered signal. Best results were obtained by comparing averaged power spectra in small time windows at different depths for a series of A-lines. Comparisons between consequent averaged spectra at different depths provided the magnitude and frequency dependence of attenuation. Non-invasive characterization of the physical state of the tissue with quantitative ultrasound holds great promise for the extension of the diagnostic power of conventional B-mode imaging.

Application of supervised and unsupervised tools to direct effects-based monitoring efforts in the Great Lakes areas of concern: Maumee River, Ohio

EPA Science Inventory

Effects-based approaches that employ molecular and tissue level tools to detect and characterize biological responses to contaminants can be a useful complement to chemical monitoring approaches. When the source/type of contamination is known, a predetermined, or supervised, set...

Swine transcriptome characterization by combined Iso-Seq and RNA-seq for annotating the emerging long read-based reference genome

USDA-ARS?s Scientific Manuscript database

PacBio long-read sequencing technology is increasingly popular in genome sequence assembly and transcriptome cataloguing. Recently, a new-generation pig reference genome was assembled based on long reads from this technology. To finely annotate this genome assembly, transcriptomes of nine tissues fr...

Methodology of citrate-based biomaterial development and application

NASA Astrophysics Data System (ADS)

Tran, M. Richard

Biomaterials play central roles in modern strategies of regenerative medicine and tissue engineering. Attempts to find tissue-engineered solutions to cure various injuries or diseases have led to an enormous increase in the number of polymeric biomaterials over the past decade. The breadth of new materials arises from the multiplicity of anatomical locations, cell types, and mode of application, which all place application-specific requirements on the biomaterial. Unfortunately, many of the currently available biodegradable polymers are limited in their versatility to meet the wide range of requirements for tissue engineering. Therefore, a methodology of biomaterial development, which is able to address a broad spectrum of requirements, would be beneficial to the biomaterial field. This work presents a methodology of citrate-based biomaterial design and application to meet the multifaceted needs of tissue engineering. We hypothesize that (1) citric acid, a non-toxic metabolic product of the body (Krebs Cycle), can be exploited as a universal multifunctional monomer and reacted with various diols to produce a new class of soft biodegradable elastomers with the flexibility to tune the material properties of the resulting material to meet a wide range of requirements; (2) the newly developed citrate-based polymers can be used as platform biomaterials for the design of novel tissue engineering scaffolding; and (3) microengineering approaches in the form thin scaffold sheets, microchannels, and a new porogen design can be used to generate complex cell-cell and cell-microenvironment interactions to mimic tissue complexity and architecture. To test these hypotheses, we first developed a methodology of citrate-based biomaterial development through the synthesis and characterization of a family of in situ crosslinkable and urethane-doped elastomers, which are synthesized using simple, cost-effective strategies and offer a variety methods to tailor the material properties to meet the needs of a particular application. Next, we introduced a new porogen generation technique, and showed the potential application of the newly developed materials through the fabrication and characterization of scaffold sheets, multiphasic small diameter vascular grafts, and multichanneled nerve guides. Finally, the in vivo applications of citrate-based materials are exemplified through the evaluation of peripheral nerve regeneration using multichanneled guides and the ability to assist in injection-based endoscopic mucosal resection therapy. The results presented in this work show that citric acid can be utilized as a cornerstone in the development of novel biodegradable materials, and combined with microengineering approaches to produce the next generation of tissue engineering scaffolding. These enabling new biomaterials and scaffolding strategies should address many of the existing challenges in tissue engineering and advance the field as a whole.

Characterization of in vitro glucuronidation clearance of a range of drugs in human kidney microsomes: comparison with liver and intestinal glucuronidation and impact of albumin.

PubMed

Gill, Katherine L; Houston, J Brian; Galetin, Aleksandra

2012-04-01

Previous studies have shown the importance of the addition of albumin for characterization of hepatic glucuronidation in vitro; however, no reports exist on the effects of albumin on renal or intestinal microsomal glucuronidation assays. This study characterized glucuronidation clearance (CL(int, UGT)) in human kidney, liver, and intestinal microsomes in the presence and absence of bovine serum albumin (BSA) for seven drugs with differential UDP-glucuronosyltransferase (UGT) 1A9 and UGT2B7 specificity, namely, diclofenac, ezetimibe, gemfibrozil, mycophenolic acid, naloxone, propofol, and telmisartan. The impact of renal CL(int, UGT) on accuracy of in vitro-in vivo extrapolation (IVIVE) of glucuronidation clearance was investigated. Inclusion of 1% BSA for acidic drugs and 2% for bases/neutral drugs in incubations was found to be suitable for characterization of CL(int, UGT) in different tissues. Although BSA increased CL(int, UGT) in all tissues, the extent was tissue- and drug-dependent. Scaled CL(int, UGT) in the presence of BSA ranged from 2.22 to 207, 0.439 to 24.4, and 0.292 to 23.8 ml · min(-1) · g tissue(-1) in liver, kidney, and intestinal microsomes. Renal CL(int, UGT) (per gram of tissue) was up to 2-fold higher in comparison with that for liver for UGT1A9 substrates; in contrast, CL(int, UGT) for UGT2B7 substrates represented approximately one-third of hepatic estimates. Scaled renal CL(int, UGT) (in the presence of BSA) was up to 30-fold higher than intestinal glucuronidation for the drugs investigated. Use of in vitro data obtained in the presence of BSA and inclusion of renal clearance improved the IVIVE of glucuronidation clearance, with 50% of drugs predicted within 2-fold of observed values. Characterization and consideration of kidney CL(int, UGT) is particularly important for UGT1A9 substrates.

Characterization of the anisotropic mechanical behavior of human abdominal wall connective tissues.

PubMed

Astruc, Laure; De Meulaere, Maurice; Witz, Jean-François; Nováček, Vit; Turquier, Frédéric; Hoc, Thierry; Brieu, Mathias

2018-06-01

Abdominal wall sheathing tissues are commonly involved in hernia formation. However, there is very limited work studying mechanics of all tissues from the same donor which prevents a complete understanding of the abdominal wall behavior and the differences in these tissues. The aim of this study was to investigate the differences between the mechanical properties of the linea alba and the anterior and posterior rectus sheaths from a macroscopic point of view. Eight full-thickness human anterior abdominal walls of both genders were collected and longitudinal and transverse samples were harvested from the three sheathing connective tissues. The total of 398 uniaxial tensile tests was conducted and the mechanical characteristics of the behavior (tangent rigidities for small and large deformations) were determined. Statistical comparisons highlighted heterogeneity and non-linearity in behavior of the three tissues under both small and large deformations. High anisotropy was observed under small and large deformations with higher stress in the transverse direction. Variabilities in the mechanical properties of the linea alba according to the gender and location were also identified. Finally, data dispersion correlated with microstructure revealed that macroscopic characterization is not sufficient to fully describe behavior. Microstructure consideration is needed. These results provide a better understanding of the mechanical behavior of the abdominal wall sheathing tissues as well as the directions for microstructure-based constitutive model. Copyright © 2018 Elsevier Ltd. All rights reserved.

Colloidal gas aphron foams: A novel approach to a hydrogel based tissue engineered myocardial patch

NASA Astrophysics Data System (ADS)

Johnson, Elizabeth Edna

Cardiovascular disease currently affects an estimated 58 million Americans and is the leading cause of death in the US. Over 2.3 million Americans are currently living with heart failure a leading cause of which is acute myocardial infarction, during which a part of the heart muscle is damaged beyond repair. There is a great need to develop treatments for damaged heart tissue. One potential therapy involves replacement of nonfunctioning scar tissue with a patch of healthy, functioning tissue. A tissue engineered cardiac patch would be ideal for such an application. Tissue engineering techniques require the use of porous scaffolds, which serve as a 3-D template for initial cell attachment and grow-th leading to tissue formation. The scaffold must also have mechanical properties closely matching those of the tissues at the site of implantation. Our research presents a new approach to meet these design requirements. A unique interaction between poly(vinyl alcohol) and amino acids has been discovered by our lab, resulting in the production of novel gels. These unique synthetic hydrogels along with one natural hydrogel, alginate (derived from brown seaweed), have been coupled with a new approach to tissue scaffold fabrication using solid colloidal gas aphrons (CGAs). CGAs are colloidal foams containing uniform bubbles with diameters on the order of micrometers. Upon solidification the GCAs form a porous, 3-D network suitable for a tissue scaffold. The project encompasses four specific aims: (I) characterize hydrogel formation mechanism, (II) use colloidal gas aphrons to produce hydrogel scaffolds, (III) chemically and physically characterize scaffold materials and (IV) optimize and evaluate scaffold biocompatibility.

Ultrasonic technique for characterizing skin burns

DOEpatents

Goans, Ronald E.; Cantrell, Jr., John H.; Meyers, F. Bradford; Stambaugh, Harry D.

1978-01-01

This invention, a method for ultrasonically determining the depth of a skin burn, is based on the finding that the acoustical impedance of burned tissue differs sufficiently from that of live tissue to permit ultrasonic detection of the interface between the burn and the underlying unburned tissue. The method is simple, rapid, and accurate. As compared with conventional practice, it provides the important advantage of permitting much earlier determination of whether a burn is of the first, second, or third degree. In the case of severe burns, the usual two - to three-week delay before surgery may be reduced to about 3 days or less.

A physics-based algorithm for real-time simulation of electrosurgery procedures in minimally invasive surgery.

PubMed

Lu, Zhonghua; Arikatla, Venkata S; Han, Zhongqing; Allen, Brian F; De, Suvranu

2014-12-01

High-frequency electricity is used in the majority of surgical interventions. However, modern computer-based training and simulation systems rely on physically unrealistic models that fail to capture the interplay of the electrical, mechanical and thermal properties of biological tissue. We present a real-time and physically realistic simulation of electrosurgery by modelling the electrical, thermal and mechanical properties as three iteratively solved finite element models. To provide subfinite-element graphical rendering of vaporized tissue, a dual-mesh dynamic triangulation algorithm based on isotherms is proposed. The block compressed row storage (BCRS) structure is shown to be critical in allowing computationally efficient changes in the tissue topology due to vaporization. We have demonstrated our physics-based electrosurgery cutting algorithm through various examples. Our matrix manipulation algorithms designed for topology changes have shown low computational cost. Our simulator offers substantially greater physical fidelity compared to previous simulators that use simple geometry-based heat characterization. Copyright © 2013 John Wiley & Sons, Ltd.

Synthesis and characterization of nanocomposite scaffolds based on triblock copolymer of L-lactide, ε-caprolactone and nano-hydroxyapatite for bone tissue engineering.

PubMed

Torabinejad, Bahman; Mohammadi-Rovshandeh, Jamshid; Davachi, Seyed Mohammad; Zamanian, Ali

2014-09-01

The employment of biodegradable polymer scaffolds is one of the main approaches for achieving a tissue engineered construct to reproduce bone tissues, which provide a three dimensional template to regenerate desirable tissues for different applications. The main goal of this study is to design a novel triblock scaffold reinforced with nano-hydroxyapatite (nHA) for hard tissue engineering using gas foaming/salt leaching method with minimum solvent usage. With this end in view, the biodegradable triblock copolymers of l-lactide and ε-caprolactone with different mol% were synthesized by ring-opening polymerization method in the presence of Sn(Oct)2 catalyst as initiator and ethylene glycol as co-initiator. The chemical compositions of biodegradable copolymers were characterized by means of FTIR and NMR. The thermal and crystallization behaviors of copolymers were characterized using TGA and DSC thermograms. Moreover, nano-hydroxyapatite was synthesized by the chemical precipitation process and was thoroughly characterized by FTIR, XRD and TEM. Additionally, the nanocomposites with different contents of nHA were prepared by mixing triblock copolymer with nHA. Mechanical properties of the prepared nanocomposites were evaluated by stress-strain measurements. It was found that the nanocomposite with 30% of nHA showed the optimum result. Therefore, nanocomposite scaffolds with 30% nHA were fabricated by gas foaming/salt leaching method and SEM images were used to observe the microstructure and morphology of nanocomposites and nanocomposite scaffolds before and after cell culture. The in-vitro and cell culture tests were also carried out to further evaluate the biological properties. The results revealed that the porous scaffolds were biocompatible to the osteoblast cells because the cells spread and grew well. The resultant nanocomposites could be considered as good candidates for use in bone tissue engineering. Copyright © 2014 Elsevier B.V. All rights reserved.

Development and characterization of a handheld hyperspectral Raman imaging probe system for molecular characterization of tissue on mesoscopic scales.

PubMed

St-Arnaud, Karl; Aubertin, Kelly; Strupler, Mathias; Madore, Wendy-Julie; Grosset, Andrée-Anne; Petrecca, Kevin; Trudel, Dominique; Leblond, Frédéric

2018-01-01

Raman spectroscopy is a promising cancer detection technique for surgical guidance applications. It can provide quantitative information relating to global tissue properties associated with structural, metabolic, immunological, and genetic biochemical phenomena in terms of molecular species including amino acids, lipids, proteins, and nucleic acid (DNA). To date in vivo Raman spectroscopy systems mostly included probes and biopsy needles typically limited to single-point tissue interrogation over a scale between 100 and 500 microns. The development of wider field handheld systems could improve tumor localization for a range of open surgery applications including brain, ovarian, and skin cancers. Here we present a novel Raman spectroscopy implementation using a coherent imaging bundle of fibers to create a probe capable of reconstructing molecular images over mesoscopic fields of view. Detection is performed using linear scanning with a rotation mirror and an imaging spectrometer. Different slits widths were tested at the entrance of the spectrometer to optimize spatial and spectral resolution while preserving sufficient signal-to-noise ratios to detect the principal Raman tissue features. The nonbiological samples, calcite and polytetrafluoroethylene (PTFE), were used to characterize the performance of the system. The new wide-field probe was tested on ex vivo samples of calf brain and swine tissue. Raman spectral content of both tissue types were validated with data from the literature and compared with data acquired with a single-point Raman spectroscopy probe. The single-point probe was used as the gold standard against which the new instrument was benchmarked as it has already been thoroughly validated for biological tissue characterization. We have developed and characterized a practical noncontact handheld Raman imager providing tissue information at a spatial resolution of 115 microns over a field of view >14 mm 2 and a spectral resolution of 6 cm -1 over the whole fingerprint region. Typical integration time to acquire an entire Raman image over swine tissue was set to approximately 100 s. Spectra acquired with both probes (single-point and wide-field) showed good agreement, with a Pearson correlation factor >0.85 over different tissue categories. Protein and lipid content of imaged tissue were manifested into the measured spectra which correlated well with previous findings in the literature. An example of quantitative molecular map is presented for swine tissue and calf brain based on the ratio of protein-to-lipid content showing clear delineations between white and gray matter as well as between adipose and muscle tissue. We presented the development of a Raman imaging probe with a field of view of a few millimeters and a spatial resolution consistent with standard surgical imaging methods using an imaging bundle. Spectra acquired with the newly developed system on swine tissue and calf brain correlated well with an establish single-point probe and observed spectral features agreed with previous finding in the literature. The imaging probe has demonstrated its ability to reconstruct molecular images of soft tissues. The approach presented here has a lot of potential for the development of surgical Raman imaging probe to guide the surgeon during cancer surgery. © 2017 American Association of Physicists in Medicine.

The landscape of genomic imprinting across diverse adult human tissues

PubMed Central

Baran, Yael; Subramaniam, Meena; Biton, Anne; Tukiainen, Taru; Tsang, Emily K.; Rivas, Manuel A.; Pirinen, Matti; Gutierrez-Arcelus, Maria; Smith, Kevin S.; Kukurba, Kim R.; Zhang, Rui; Eng, Celeste; Torgerson, Dara G.; Urbanek, Cydney; Li, Jin Billy; Rodriguez-Santana, Jose R.; Burchard, Esteban G.; Seibold, Max A.; MacArthur, Daniel G.; Montgomery, Stephen B.; Zaitlen, Noah A.; Lappalainen, Tuuli

2015-01-01

Genomic imprinting is an important regulatory mechanism that silences one of the parental copies of a gene. To systematically characterize this phenomenon, we analyze tissue specificity of imprinting from allelic expression data in 1582 primary tissue samples from 178 individuals from the Genotype-Tissue Expression (GTEx) project. We characterize imprinting in 42 genes, including both novel and previously identified genes. Tissue specificity of imprinting is widespread, and gender-specific effects are revealed in a small number of genes in muscle with stronger imprinting in males. IGF2 shows maternal expression in the brain instead of the canonical paternal expression elsewhere. Imprinting appears to have only a subtle impact on tissue-specific expression levels, with genes lacking a systematic expression difference between tissues with imprinted and biallelic expression. In summary, our systematic characterization of imprinting in adult tissues highlights variation in imprinting between genes, individuals, and tissues. PMID:25953952

Trickle-bed root culture bioreactor design and scale-up: growth, fluid-dynamics, and oxygen mass transfer.

PubMed

Ramakrishnan, Divakar; Curtis, Wayne R

2004-10-20

Trickle-bed root culture reactors are shown to achieve tissue concentrations as high as 36 g DW/L (752 g FW/L) at a scale of 14 L. Root growth rate in a 1.6-L reactor configuration with improved operational conditions is shown to be indistinguishable from the laboratory-scale benchmark, the shaker flask (mu=0.33 day(-1)). These results demonstrate that trickle-bed reactor systems can sustain tissue concentrations, growth rates and volumetric biomass productivities substantially higher than other reported bioreactor configurations. Mass transfer and fluid dynamics are characterized in trickle-bed root reactors to identify appropriate operating conditions and scale-up criteria. Root tissue respiration goes through a minimum with increasing liquid flow, which is qualitatively consistent with traditional trickle-bed performance. However, liquid hold-up is much higher than traditional trickle-beds and alternative correlations based on liquid hold-up per unit tissue mass are required to account for large changes in biomass volume fraction. Bioreactor characterization is sufficient to carry out preliminary design calculations that indicate scale-up feasibility to at least 10,000 liters.

Metabolic profiles are principally different between cancers of the liver, pancreas and breast.

PubMed

Budhu, Anuradha; Terunuma, Atsushi; Zhang, Geng; Hussain, S Perwez; Ambs, Stefan; Wang, Xin Wei

2014-01-01

Molecular profiling of primary tumors may facilitate the classification of patients with cancer into more homogenous biological groups to aid clinical management. Metabolomic profiling has been shown to be a powerful tool in characterizing the biological mechanisms underlying a disease but has not been evaluated for its ability to classify cancers by their tissue of origin. Thus, we assessed metabolomic profiling as a novel tool for multiclass cancer characterization. Global metabolic profiling was employed to identify metabolites in paired tumor and non-tumor liver (n=60), breast (n=130) and pancreatic (n=76) tissue specimens. Unsupervised principal component analysis showed that metabolites are principally unique to each tissue and cancer type. Such a difference can also be observed even among early stage cancers, suggesting a significant and unique alteration of global metabolic pathways associated with each cancer type. Our global high-throughput metabolomic profiling study shows that specific biochemical alterations distinguish liver, pancreatic and breast cancer and could be applied as cancer classification tools to differentiate tumors based on tissue of origin.

Hard X-ray submicrometer tomography of human brain tissue at Diamond Light Source

NASA Astrophysics Data System (ADS)

Khimchenko, A.; Bikis, C.; Schulz, G.; Zdora, M.-C.; Zanette, I.; Vila-Comamala, J.; Schweighauser, G.; Hench, J.; Hieber, S. E.; Deyhle, H.; Thalmann, P.; Müller, B.

2017-06-01

There is a lack of the necessary methodology for three-dimensional (3D) investigation of soft tissues with cellular resolution without staining or tissue transformation. Synchrotron radiation based hard X-ray in-line phase contrast tomography using single-distance phase reconstruction (SDPR) provides high spatial resolution and density contrast for the visualization of individual cells using a standard specimen preparation and data reconstruction. In this study, we demonstrate the 3D characterization of a formalin-fixed paraffin-embedded (FFPE) human cerebellum specimen by SDPR at the Diamond-Manchester Imaging Branchline I13-2 (Diamond Light Source, UK) at pixel sizes down to 0.45 μm. The approach enables visualization of cerebellar layers (Stratum moleculare and Stratum granulosum), the 3D characterization of individual cells (Purkinje, stellate and granule cells) and can even resolve some subcellular structures (nucleus and nucleolus of Purkinje cells). The tomographic results are qualitatively compared to hematoxylin and eosin (H&E) stained histological sections. We demonstrate the potential benefits of hard X-ray microtomography for the investigations of biological tissues in comparison to conventional histology.

Detection of free and covalently bound microcystins in different tissues (liver, intestines, gills, and muscles) of rainbow trout (Oncorhynchus mykiss) by liquid chromatography-tandem mass spectrometry: method characterization.

PubMed

Cadel-Six, Sabrina; Moyenga, David; Magny, Stéphanie; Trotereau, Sophie; Edery, Marc; Krys, Sophie

2014-02-01

So far only a few publications have explored the development of extraction methods of cyanotoxin extracted from complex matrices. With regard to cyanobacterial microcystins (MCs), the data on the contamination of the flesh of aquatic organisms is hard to compare and very limited due to the lack of validated methods. In recent years, evidence that both free and bound fractions of toxin are found in these tissues has highlighted the need to develop effective methods of quantification. Several techniques do exist, but only the Lemieux oxidation has so far been used to investigate complex tissue matrices. In this study, protocols based on the Lemieux approach were adapted for the quantitative chemical analysis of free MC-LR and MMPB derived from bound toxin in the tissues of juvenile trout gavaged with MC-LR. Afterwards, the NF V03 110 guideline was used to characterize the protocols elaborated and evaluate their effectiveness. Copyright © 2013. Published by Elsevier Ltd.

Mechanical characterization of the mouse diaphragm with optical coherence elastography reveals fibrosis-related change of direction-dependent muscle tissue stiffness

NASA Astrophysics Data System (ADS)

Wang, Shang; Loehr, James A.; Larina, Irina V.; Rodney, George G.; Larin, Kirill V.

2016-03-01

The diaphragm, composed of skeletal muscle, plays an important role in respiration through its dynamic contraction. Genetic and molecular studies of the biomechanics of mouse diaphragm can provide great insights into an improved understanding and potential treatment of the disorders that lead to diaphragm dysfunction (i.e. muscular dystrophy). However, due to the small tissue size, mechanical assessment of mouse diaphragm tissue under its proper physiological conditions has been challenging. Here, we present the application of noncontact optical coherence elastography (OCE) for quantitative elastic characterization of ex vivo mouse diaphragm. Phase-sensitive optical coherence tomography was combined with a focused air-puff system to capture and measure the elastic wave propagation from tissue surface. Experiments were performed on wildtype and dystrophic mouse diaphragm tissues containing different levels of fibrosis. The OCE measurements of elastic wave propagation were conducted along both the longitudinal and transverse axis of the muscle fibers. Cross-correlation of the temporal displacement profiles from different spatial locations was utilized to obtain the propagation time delay, which was used to calculate the wave group velocity and to further quantify the tissue Young's modulus. Prior to and after OCE assessment, peak tetanic force was measured to monitor viability of the tissue during the elasticity measurements. Our experimental results indicate a positive correlation between fibrosis level and tissue stiffness, suggesting this elastic-wave-based OCE method could be a useful tool to monitor mechanical properties of skeletal muscle under physiological and pathological conditions.

Molecular analysis of infectious bursal disease virus from bursal tissues collected on FTA filter paper.

PubMed

Moscoso, Hugo; Alvarado, Ivan; Hofacre, Charles L

2006-09-01

We investigated the feasibility of using FTA filter cards for the storage of bursas of Fabricius containing infectious bursal disease virus (IBDV) and for IBDV detection by reverse transcriptase (RT)-polymerase chain reaction (PCR), and characterization by restriction fragment length polymorphism (RFLP) or nucleotide sequencing. The FTA card is a cotton-based cellulose membrane containing lyophilized chemicals that lyses many types of bacteria and viruses. IBDV was inactivated upon contact with the FTA as shown by the inability of the virus to be propagated in embryonating chicken eggs. Viral RNA in minced bursas or stamped bursas could be amplified by RT-PCR (VP2 gene fragment, 248 base pairs) after storage on FTA for at least 15 days at room temperature or 8 mo at -20 C. Analytical sensitivity of the test was between 0.5-5 ng of RNA template or 5 x 10(1) mean tissue culture infective dose (TCID50)/FTA spot. Detection rate of IBDV in domestic clinical samples collected on FTA or collected by the non-FTA standard procedure was 36.7% and 41.7%, respectively, which represents 88% agreement. Detection of IBDV from FTA cards inoculated with bursal tissues in the laboratory or in the field was 36.7% and 37.1%, respectively. Detection of IBDV from FTA samples when the cards were inoculated with bursal tissues and sent through customs into the United States was 32.9%. Analysis of the amplified products showed that molecular characterization of IBDV by RFLP or nucleotide sequencing is feasible in bursas stored on FTA at 25 C for 1-3 mo or at -20 C for at least 8 mo. The use of FTA for the collection of bursal tissues and simultaneous inactivation of IBDV allows the movement of specimens within the United States and also from outside the United States in compliance with federal regulations and in a manner adequate for molecular characterization.

The hallmarks of breast cancer by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Abramczyk, H.; Surmacki, J.; Brożek-Płuska, B.; Morawiec, Z.; Tazbir, M.

2009-04-01

This paper presents new biological results on ex vivo breast tissue based on Raman spectroscopy and demonstrates its power as diagnostic tool with the key advantage in breast cancer research. The results presented here demonstrate the ability of Raman spectroscopy to accurately characterize cancer tissue and distinguish between normal, malignant and benign types. The goal of the paper is to develop the diagnostic ability of Raman spectroscopy in order to find an optical marker of cancer in the breast tissue. Applications of Raman spectroscopy in breast cancer research are in the early stages of development in the world. To the best of our knowledge, this paper is one of the most statistically reliable reports (1100 spectra, 99 patients) on Raman spectroscopy-based diagnosis of breast cancers among the world women population.

A Liver-centric Multiscale Modeling Framework for Xenobiotics ...

EPA Pesticide Factsheets

We describe a multi-scale framework for modeling acetaminophen-induced liver toxicity. Acetaminophen is a widely used analgesic. Overdose of acetaminophen can result in liver injury via its biotransformation into toxic product, which further induce massive necrosis. Our study focuses on developing a multi-scale computational model to characterize both phase I and phase II metabolism of acetaminophen, by bridging Physiologically Based Pharmacokinetic (PBPK) modeling at the whole body level, cell movement and blood flow at the tissue level and cell signaling and drug metabolism at the sub-cellular level. To validate the model, we estimated our model parameters by fi?tting serum concentrations of acetaminophen and its glucuronide and sulfate metabolites to experiments, and carried out sensitivity analysis on 35 parameters selected from three modules. Our study focuses on developing a multi-scale computational model to characterize both phase I and phase II metabolism of acetaminophen, by bridging Physiologically Based Pharmacokinetic (PBPK) modeling at the whole body level, cell movement and blood flow at the tissue level and cell signaling and drug metabolism at the sub-cellular level. This multiscale model bridges the CompuCell3D tool used by the Virtual Tissue project with the httk tool developed by the Rapid Exposure and Dosimetry project.

High-throughput bone and cartilage micropellet manufacture, followed by assembly of micropellets into biphasic osteochondral tissue.

PubMed

Babur, Betul Kul; Futrega, Kathryn; Lott, William B; Klein, Travis Jacob; Cooper-White, Justin; Doran, Michael Robert

2015-09-01

Engineered biphasic osteochondral tissues may have utility in cartilage defect repair. As bone-marrow-derived mesenchymal stem/stromal cells (MSC) have the capacity to make both bone-like and cartilage-like tissues, they are an ideal cell population for use in the manufacture of osteochondral tissues. Effective differentiation of MSC to bone-like and cartilage-like tissues requires two unique medium formulations and this presents a challenge both in achieving initial MSC differentiation and in maintaining tissue stability when the unified osteochondral tissue is subsequently cultured in a single medium formulation. In this proof-of-principle study, we used an in-house fabricated microwell platform to manufacture thousands of micropellets formed from 166 MSC each. We then characterized the development of bone-like and cartilage-like tissue formation in the micropellets maintained for 8-14 days in sequential combinations of osteogenic or chondrogenic induction medium. When bone-like or cartilage-like micropellets were induced for only 8 days, they displayed significant phenotypic changes when the osteogenic or chondrogenic induction medium, respectively, was swapped. Based on these data, we developed an extended 14-day protocol for the pre-culture of bone-like and cartilage-like micropellets in their respective induction medium. Unified osteochondral tissues were formed by layering 12,000 osteogenic micropellets and 12,000 chondrogenic micropellets into a biphasic structure and then further culture in chondrogenic induction medium. The assembled tissue was cultured for a further 8 days and characterized via histology. The micropellets had amalgamated into a continuous structure with distinctive bone-like and cartilage-like regions. This proof-of-concept study demonstrates the feasibility of micropellet assembly for the formation of osteochondral-like tissues for possible use in osteochondral defect repair.

Dosimetric and radiobiological characterizations of prostate intensity-modulated radiotherapy and volumetric-modulated arc therapy: A single-institution review of ninety cases

PubMed Central

Khan, Muhammad Isa; Jiang, Runqing; Kiciak, Alexander; ur Rehman, Jalil; Afzal, Muhammad; Chow, James C. L.

2016-01-01

This study reviewed prostate volumetric-modulated arc therapy (VMAT) plans with intensity-modulated radiotherapy (IMRT) plans after prostate IMRT technique was replaced by VMAT in an institution. Characterizations of dosimetry and radiobiological variation in prostate were determined based on treatment plans of 40 prostate IMRT patients (planning target volume = 77.8–335 cm3) and 50 VMAT patients (planning target volume = 120–351 cm3) treated before and after 2013, respectively. Both IMRT and VMAT plans used the same dose-volume criteria in the inverse planning optimization. Dose-volume histogram, mean doses of target and normal tissues (rectum, bladder and femoral heads), dose-volume points (D99% of planning target volume; D30%, D50%, V30 Gy and V35 Gy of rectum and bladder; D5%, V14 Gy, V22 Gy of femoral heads), conformity index (CI), homogeneity index (HI), gradient index (GI), prostate tumor control probability (TCP), and rectal normal tissue complication probability (NTCP) based on the Lyman-Burman-Kutcher algorithm were calculated for each IMRT and VMAT plan. From our results, VMAT plan was found better due to its higher (1.05%) CI, lower (0.83%) HI and (0.75%) GI than IMRT. Comparing doses in normal tissues between IMRT and VMAT, it was found that IMRT mostly delivered higher doses of about 1.05% to the normal tissues than VMAT. Prostate TCP and rectal NTCP were found increased (1%) for VMAT than IMRT. It is seen that VMAT technique can decrease the dose-volume evaluation criteria for the normal tissues. Based on our dosimetric and radiobiological results in treatment plans, it is concluded that our VMAT implementation could produce comparable or slightly better target coverage and normal tissue sparing with a faster treatment time in prostate radiotherapy. PMID:27651562

Fabrication and characterization of biotissue-mimicking phantoms in the THz frequency range

NASA Astrophysics Data System (ADS)

Liakhov, E.; Smolyanskaya, O.; Popov, A.; Odlyanitskiy, E.; Balbekin, N.; Khodzitsky, M.

2016-08-01

The study revealed the most promising candidates for phantoms mimicking different biological tissues in the terahertz frequency range. Closest to biological tissues in terms of the refractive index appeared to be gelatin-based gels; in terms of the absorption coefficient they were agar-based gels. Gelatin is more stable in time, but requires special storage conditions to limit water evaporation. The dense structure of the agar-based phantom allows its use without mold and risk of damage. However, agar is a nutrient medium for bacteria and its parameters degrade even when the phantom form and water content are retained. Use of liquid suspensions of lecithin and milk powder are found to be extremely limited.

Three-dimensional modeling and quantitative analysis of gap junction distributions in cardiac tissue.

PubMed

Lackey, Daniel P; Carruth, Eric D; Lasher, Richard A; Boenisch, Jan; Sachse, Frank B; Hitchcock, Robert W

2011-11-01

Gap junctions play a fundamental role in intercellular communication in cardiac tissue. Various types of heart disease including hypertrophy and ischemia are associated with alterations of the spatial arrangement of gap junctions. Previous studies applied two-dimensional optical and electron-microscopy to visualize gap junction arrangements. In normal cardiomyocytes, gap junctions were primarily found at cell ends, but can be found also in more central regions. In this study, we extended these approaches toward three-dimensional reconstruction of gap junction distributions based on high-resolution scanning confocal microscopy and image processing. We developed methods for quantitative characterization of gap junction distributions based on analysis of intensity profiles along the principal axes of myocytes. The analyses characterized gap junction polarization at cell ends and higher-order statistical image moments of intensity profiles. The methodology was tested in rat ventricular myocardium. Our analysis yielded novel quantitative data on gap junction distributions. In particular, the analysis demonstrated that the distributions exhibit significant variability with respect to polarization, skewness, and kurtosis. We suggest that this methodology provides a quantitative alternative to current approaches based on visual inspection, with applications in particular in characterization of engineered and diseased myocardium. Furthermore, we propose that these data provide improved input for computational modeling of cardiac conduction.

Whole-Lesion Apparent Diffusion Coefficient-Based Entropy-Related Parameters for Characterizing Cervical Cancers: Initial Findings.

PubMed

Guan, Yue; Li, Weifeng; Jiang, Zhuoran; Chen, Ying; Liu, Song; He, Jian; Zhou, Zhengyang; Ge, Yun

2016-12-01

This study aimed to develop whole-lesion apparent diffusion coefficient (ADC)-based entropy-related parameters of cervical cancer to preliminarily assess intratumoral heterogeneity of this lesion in comparison to adjacent normal cervical tissues. A total of 51 women (mean age, 49 years) with cervical cancers confirmed by biopsy underwent 3-T pelvic diffusion-weighted magnetic resonance imaging with b values of 0 and 800 s/mm 2 prospectively. ADC-based entropy-related parameters including first-order entropy and second-order entropies were derived from the whole tumor volume as well as adjacent normal cervical tissues. Intraclass correlation coefficient, Wilcoxon test with Bonferroni correction, Kruskal-Wallis test, and receiver operating characteristic curve were used for statistical analysis. All the parameters showed excellent interobserver agreement (all intraclass correlation coefficients  > 0.900). Entropy, entropy(H) 0 , entropy(H) 45 , entropy(H) 90 , entropy(H) 135 , and entropy(H) mean were significantly higher, whereas entropy(H) range and entropy(H) std were significantly lower in cervical cancers compared to adjacent normal cervical tissues (all P <.0001). Kruskal-Wallis test showed that there were no significant differences among the values of various second-order entropies including entropy(H) 0, entropy(H) 45 , entropy(H) 90 , entropy(H) 135 , and entropy(H) mean. All second-order entropies had larger area under the receiver operating characteristic curve than first-order entropy in differentiating cervical cancers from adjacent normal cervical tissues. Further, entropy(H) 45 , entropy(H) 90 , entropy(H) 135 , and entropy(H) mean had the same largest area under the receiver operating characteristic curve of 0.867. Whole-lesion ADC-based entropy-related parameters of cervical cancers were developed successfully, which showed initial potential in characterizing intratumoral heterogeneity in comparison to adjacent normal cervical tissues. Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Review of Quantitative Ultrasound: Envelope Statistics and Backscatter Coefficient Imaging and Contributions to Diagnostic Ultrasound.

PubMed

Oelze, Michael L; Mamou, Jonathan

2016-02-01

Conventional medical imaging technologies, including ultrasound, have continued to improve over the years. For example, in oncology, medical imaging is characterized by high sensitivity, i.e., the ability to detect anomalous tissue features, but the ability to classify these tissue features from images often lacks specificity. As a result, a large number of biopsies of tissues with suspicious image findings are performed each year with a vast majority of these biopsies resulting in a negative finding. To improve specificity of cancer imaging, quantitative imaging techniques can play an important role. Conventional ultrasound B-mode imaging is mainly qualitative in nature. However, quantitative ultrasound (QUS) imaging can provide specific numbers related to tissue features that can increase the specificity of image findings leading to improvements in diagnostic ultrasound. QUS imaging can encompass a wide variety of techniques including spectral-based parameterization, elastography, shear wave imaging, flow estimation, and envelope statistics. Currently, spectral-based parameterization and envelope statistics are not available on most conventional clinical ultrasound machines. However, in recent years, QUS techniques involving spectral-based parameterization and envelope statistics have demonstrated success in many applications, providing additional diagnostic capabilities. Spectral-based techniques include the estimation of the backscatter coefficient (BSC), estimation of attenuation, and estimation of scatterer properties such as the correlation length associated with an effective scatterer diameter (ESD) and the effective acoustic concentration (EAC) of scatterers. Envelope statistics include the estimation of the number density of scatterers and quantification of coherent to incoherent signals produced from the tissue. Challenges for clinical application include correctly accounting for attenuation effects and transmission losses and implementation of QUS on clinical devices. Successful clinical and preclinical applications demonstrating the ability of QUS to improve medical diagnostics include characterization of the myocardium during the cardiac cycle, cancer detection, classification of solid tumors and lymph nodes, detection and quantification of fatty liver disease, and monitoring and assessment of therapy.

Review of quantitative ultrasound: envelope statistics and backscatter coefficient imaging and contributions to diagnostic ultrasound

PubMed Central

Oelze, Michael L.; Mamou, Jonathan

2017-01-01

Conventional medical imaging technologies, including ultrasound, have continued to improve over the years. For example, in oncology, medical imaging is characterized by high sensitivity, i.e., the ability to detect anomalous tissue features, but the ability to classify these tissue features from images often lacks specificity. As a result, a large number of biopsies of tissues with suspicious image findings are performed each year with a vast majority of these biopsies resulting in a negative finding. To improve specificity of cancer imaging, quantitative imaging techniques can play an important role. Conventional ultrasound B-mode imaging is mainly qualitative in nature. However, quantitative ultrasound (QUS) imaging can provide specific numbers related to tissue features that can increase the specificity of image findings leading to improvements in diagnostic ultrasound. QUS imaging techniques can encompass a wide variety of techniques including spectral-based parameterization, elastography, shear wave imaging, flow estimation and envelope statistics. Currently, spectral-based parameterization and envelope statistics are not available on most conventional clinical ultrasound machines. However, in recent years QUS techniques involving spectral-based parameterization and envelope statistics have demonstrated success in many applications, providing additional diagnostic capabilities. Spectral-based techniques include the estimation of the backscatter coefficient, estimation of attenuation, and estimation of scatterer properties such as the correlation length associated with an effective scatterer diameter and the effective acoustic concentration of scatterers. Envelope statistics include the estimation of the number density of scatterers and quantification of coherent to incoherent signals produced from the tissue. Challenges for clinical application include correctly accounting for attenuation effects and transmission losses and implementation of QUS on clinical devices. Successful clinical and pre-clinical applications demonstrating the ability of QUS to improve medical diagnostics include characterization of the myocardium during the cardiac cycle, cancer detection, classification of solid tumors and lymph nodes, detection and quantification of fatty liver disease, and monitoring and assessment of therapy. PMID:26761606

Material Characterization of Microsphere-Based Scaffolds with Encapsulated Raw Materials

PubMed Central

Sridharan, BanuPriya; Mohan, Neethu; Berkland, Cory J.; Detamore, Michael S.

2016-01-01

“Raw materials,” or materials capable of serving both as building blocks and as signals, which are often but not always natural materials, are taking center stage in biomaterials for contemporary regenerative medicine. In osteochondral tissue engineering, a field leveraging the underlying bone to facilitate cartilage regeneration, common raw materials include chondroitin sulfate (CS) for cartilage and β-tricalcium phosphate (TCP) for bone. Building on our previous work with gradient scaffolds based on microspheres, here we delved deeper into the characterization of individual components. In the current study, the release of CS and TCP from poly(D,L-lactic-co-glycolic acid) (PLGA) microsphere-based scaffolds was evaluated over a time period of 4 weeks. Raw material encapsulated groups were compared to ‘blank’ groups and evaluated for surface topology, molecular weight, and mechanical performance as a function of time. The CS group may have led to increased surface porosity, and the addition of CS improved the mechanical performance of the scaffold. The finding that CS was completely released into the surrounding media by 4 weeks has a significant impact on future in vivo studies, given rapid bioavailability. The addition of TCP seemed to contribute to the rough external appearance of the scaffold. The current study provides an introduction to degradation patterns of homogenous raw material encapsulated scaffolds, providing characterization data to advance the field of microsphere-based scaffolds in tissue engineering. PMID:27040236

Spiral waves characterization: Implications for an automated cardiodynamic tissue characterization.

PubMed

Alagoz, Celal; Cohen, Andrew R; Frisch, Daniel R; Tunç, Birkan; Phatharodom, Saran; Guez, Allon

2018-07-01

Spiral waves are phenomena observed in cardiac tissue especially during fibrillatory activities. Spiral waves are revealed through in-vivo and in-vitro studies using high density mapping that requires special experimental setup. Also, in-silico spiral wave analysis and classification is performed using membrane potentials from entire tissue. In this study, we report a characterization approach that identifies spiral wave behaviors using intracardiac electrogram (EGM) readings obtained with commonly used multipolar diagnostic catheters that perform localized but high-resolution readings. Specifically, the algorithm is designed to distinguish between stationary, meandering, and break-up rotors. The clustering and classification algorithms are tested on simulated data produced using a phenomenological 2D model of cardiac propagation. For EGM measurements, unipolar-bipolar EGM readings from various locations on tissue using two catheter types are modeled. The distance measure between spiral behaviors are assessed using normalized compression distance (NCD), an information theoretical distance. NCD is a universal metric in the sense it is solely based on compressibility of dataset and not requiring feature extraction. We also introduce normalized FFT distance (NFFTD) where compressibility is replaced with a FFT parameter. Overall, outstanding clustering performance was achieved across varying EGM reading configurations. We found that effectiveness in distinguishing was superior in case of NCD than NFFTD. We demonstrated that distinct spiral activity identification on a behaviorally heterogeneous tissue is also possible. This report demonstrates a theoretical validation of clustering and classification approaches that provide an automated mapping from EGM signals to assessment of spiral wave behaviors and hence offers a potential mapping and analysis framework for cardiac tissue wavefront propagation patterns. Copyright © 2018 Elsevier B.V. All rights reserved.

Characterization of the fecal and mucosa-associated microbiota in dogs with colorectal epithelial tumors.

PubMed

Herstad, Kristin Marie Valand; Moen, Aina Elisabeth Fossum; Gaby, John Christian; Moe, Lars; Skancke, Ellen

2018-01-01

Colorectal epithelial tumors occur spontaneously in dogs, and the pathogenesis seems to parallel that of humans. The development of human colorectal tumorigenesis has been linked to alterations in the composition of the intestinal microbiota. This study characterized the fecal- and mucosa-associated microbiota in dogs with colorectal epithelial tumors (n = 10). The fecal microbiota was characterized by 16S rDNA analysis and compared with that of control dogs (n = 13). We also determined the mucosa-associated microbiota composition in colonic tumor tissue (n = 8) and in adjacent non-tumor tissue (n = 5) by 16S rDNA- and rRNA profiling. The fecal microbial community structure in dogs with tumors was different from that of control samples and was distinguished by oligotypes affiliated with Enterobacteriaceae, Bacteroides, Helicobacter, Porphyromonas, Peptostreptococcus and Streptococcus, and lower abundance of Ruminococcaceae, Slackia, Clostridium XI and Faecalibacterium. The overall community structure and populations of mucosal bacteria were not different based on either the 16S rDNA or the 16S rRNA profile in tumor tissue vs. adjacent non-tumor tissue. However, the proportion of live, potentially active bacteria appeared to be higher in non-tumor tissue compared with tumor tissue and included Slackia, Roseburia, unclass. Ruminococcaeceae, unclass. Lachnospiraceae and Oscillibacter. Colorectal tumors are rarely diagnosed in dogs, but despite this limitation, we were able to show that dogs with colorectal tumors have distinct fecal microbiota profiles. These initial results support the need for future case-control studies that are adequately powered, as well as age-matched and breed-matched, in order to evaluate the influence of bacteria on colorectal cancer etiopathogenesis and to determine whether the bacteria may have potential as biomarkers in clinical settings.

Bacterial and diazotrophic diversities of endophytes in Dendrobium catenatum determined through barcoded pyrosequencing.

PubMed

Li, Ou; Xiao, Rong; Sun, Lihua; Guan, Chenglin; Kong, Dedong; Hu, Xiufang

2017-01-01

As an epiphyte orchid, Dendrobium catenatum relies on microorganisms for requisite nutrients. Metagenome pyrosequencing based on 16S rRNA and nifH genes was used to characterize the bacterial and diazotrophic communities associated with D. catenatum collected from 5 districts in China. Based on Meta-16S rRNA sequencing, 22 bacterial phyla and 699 genera were identified, distributed as 125 genera from 8 phyla and 319 genera from 10 phyla shared by all the planting bases and all the tissues, respectively. The predominant Proteobacteria varied from 71.81% (GZ) to 96.08% (YN), and Delftia (10.39-38.42%), Burkholderia (2.71-15.98%), Escherichia/Shigella (4.90-25.12%), Pseudomonas (2.68-30.72%) and Sphingomonas (1.83-2.05%) dominated in four planting bases. Pseudomonas (17.94-22.06%), Escherichia/Shigella (6.59-11.59%), Delftia (9.65-22.14%) and Burkholderia (3.12-11.05%) dominated in all the tissues. According to Meta-nifH sequencing, 4 phyla and 45 genera were identified, while 17 genera and 24 genera from 4 phyla were shared by all the planting bases and all the tissues, respectively. Burkholderia and Bradyrhizobium were the most popular in the planting bases, followed by Methylovirgula and Mesorhizobium. Mesorhizobium was the most popular in different tissues, followed by Beijerinckia, Xanthobacter, and Burkholderia. Among the genera, 39 were completely overlapped with the results based on the 16S rRNA gene. In conclusion, abundant bacteria and diazotrophs were identified in common in different tissues of D. catenatum from five planting bases, which might play a great role in the supply of nutrients such as nitrogen. The exact abundance of phylum and genus on the different tissues from different planting bases need deeper sequencing with more samples.

Flexible biodegradable citrate-based polymeric step-index optical fiber.

PubMed

Shan, Dingying; Zhang, Chenji; Kalaba, Surge; Mehta, Nikhil; Kim, Gloria B; Liu, Zhiwen; Yang, Jian

2017-10-01

Implanting fiber optical waveguides into tissue or organs for light delivery and collection is among the most effective ways to overcome the issue of tissue turbidity, a long-standing obstacle for biomedical optical technologies. Here, we report a citrate-based material platform with engineerable opto-mechano-biological properties and demonstrate a new type of biodegradable, biocompatible, and low-loss step-index optical fiber for organ-scale light delivery and collection. By leveraging the rich designability and processibility of citrate-based biodegradable polymers, two exemplary biodegradable elastomers with a fine refractive index difference and yet matched mechanical properties and biodegradation profiles were developed. Furthermore, we developed a two-step fabrication method to fabricate flexible and low-loss (0.4 db/cm) optical fibers, and performed systematic characterizations to study optical, spectroscopic, mechanical, and biodegradable properties. In addition, we demonstrated the proof of concept of image transmission through the citrate-based polymeric optical fibers and conducted in vivo deep tissue light delivery and fluorescence sensing in a Sprague-Dawley (SD) rat, laying the groundwork for realizing future implantable devices for long-term implantation where deep-tissue light delivery, sensing and imaging are desired, such as cell, tissue, and scaffold imaging in regenerative medicine and in vivo optogenetic stimulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

New Image-Based Techniques for Prostate Biopsy and Treatment

DTIC Science & Technology

2012-04-01

C-arm fluoroscopy, MICCAI 2011, Toronto, Canada, 2011. 4) Poster Presentation: Prostate Cancer Probability Estimation Based on DCE- DTI Features...and P. Kozlowski, “Prostate Cancer Probability Estimation Based on DCE- DTI Features and Support Vector Machine Classification,” Annual Meeting of... DTI ), which characterize the de-phasing of the MR signal caused by molecular diffusion. Prostate cancer causes a pathological change in the tissue

Improved Characterization of Healthy and Malignant Tissue by NMR Line-Shape Relaxation Correlations

PubMed Central

Peemoeller, H.; Shenoy, R.K.; Pintar, M.M.; Kydon, D.W.; Inch, W.R.

1982-01-01

We performed a relaxation-line-shape correlation NMR experiment on muscle, liver, kidney, and spleen tissues of healthy mice and of mouse tumor tissue. In each tissue studied, five spin groups were resolved and characterized by their relaxation parameters. We report a previously uncharacterized semi-solid spin group and discuss briefly the value of this method for the identification of malignant tissues. PMID:7104438

A constitutive model for the mechanical characterization of the plantar fascia.

PubMed

Natali, Arturo N; Pavan, Piero G; Stecco, Carla

2010-10-01

A constitutive model is proposed to describe the mechanical behavior of the plantar fascia. The mechanical characterization of the plantar fascia regards the role in the foot biomechanics and it is involved in many alterations of its functional behavior, both of mechanical and nonmechanical origin. The structural conformation of the plantar fascia in its middle part is characterized by the presence of collagen fibers reinforcing the tissue along a preferential orientation, which is that supporting the major loading. According to this anatomical evidence, the tissue is described by developing an isotropic fiber-reinforced constitutive model and since the elastic response of the fascia is here considered, the constitutive model is based on the theory of hyperelasticity. The model is consistent with a kinematical description of large strains mechanical behavior, which is typical of soft tissues. A fitting procedure of the constitutive model is implemented making use of experimental curves taken from the literature and referring to specimens of human plantar fascia. A satisfactory fitting of the tensile behavior of the plantar fascia has been performed, showing that the model correctly interprets the mechanical behavior of the tissue in the light of comparison to experimental data at disposal. A critical analysis of the model with respect to the problem of the identification of the constitutive parameters is proposed as the basis for planning a future experimental investigation of mechanical behavior of the plantar fascia.

A FSI-based structural approach for micromechanical characterization of adipose tissue

NASA Astrophysics Data System (ADS)

Seyfi, Behzad; Sabzalinejad, Masoumeh; Haddad, Seyed M. H.; Fatouraee, Nasser; Samani, Abbas

2017-03-01

This paper presents a novel computational method for micromechanical modeling of adipose tissue. The model can be regarded as the first step for developing an inversion based framework that uses adipose stiffness data obtained from elastography to determine its microstructural alterations. Such information can be used as biomarkers for diseases associated with adipose tissue microstructure alteration (e.g. adipose tissue fibrosis and inflammation in obesity). In contrast to previous studies, the presented model follows a multiphase structure which accounts for both solid and fluid components as well as their mechanical interaction. In the model, the lipid droplets and extracellular matrix were considered as the fluid and solid phase, respectively. As such, the fluid-structure interaction (FSI) problem was solved using finite element method. In order to gain insight into how microstructural characteristics influence the macro scale mechanical properties of the adipose tissue, a compression mechanical test was simulated using the FSI model and its results were fitted to corresponding experimental data. The simulation procedure was performed for adipocytes in healthy conditions while the stiffness of extracellular matrix in normal adipose tissue was found by varying it systematically within an optimization process until the simulation response agreed with experimental data. Results obtained in this study are encouraging and show the capability of the proposed model to capture adipose tissue macroscale mechanical behavior based on its microstructure under health and different pathological conditions.

Gingival Mesenchymal Stem/Progenitor Cells: A Unique Tissue Engineering Gem

PubMed Central

Fawzy El-Sayed, Karim M.; Dörfer, Christof E.

2016-01-01

The human gingiva, characterized by its outstanding scarless wound healing properties, is a unique tissue and a pivotal component of the periodontal apparatus, investing and surrounding the teeth in their sockets in the alveolar bone. In the last years gingival mesenchymal stem/progenitor cells (G-MSCs), with promising regenerative and immunomodulatory properties, have been isolated and characterized from the gingival lamina propria. These cells, in contrast to other mesenchymal stem/progenitor cell sources, are abundant, readily accessible, and easily obtainable via minimally invasive cell isolation techniques. The present review summarizes the current scientific evidence on G-MSCs' isolation, their characterization, the investigated subpopulations, the generated induced pluripotent stem cells- (iPSC-) like G-MSCs, their regenerative properties, and current approaches for G-MSCs' delivery. The review further demonstrates their immunomodulatory properties, the transplantation preconditioning attempts via multiple biomolecules to enhance their attributes, and the experimental therapeutic applications conducted to treat multiple diseases in experimental animal models in vivo. G-MSCs show remarkable tissue reparative/regenerative potential, noteworthy immunomodulatory properties, and primary experimental therapeutic applications of G-MSCs are very promising, pointing at future biologically based therapeutic techniques, being potentially superior to conventional clinical treatment modalities. PMID:27313628

Characterizing and optimizing poly-l-lactide-co-ε-caprolactone membranes for urothelial tissue engineering

PubMed Central

Sartoneva, Reetta; Haaparanta, Anne-Marie; Lahdes-Vasama, Tuija; Mannerström, Bettina; Kellomäki, Minna; Salomäki, Minna; Sándor, George; Seppänen, Riitta; Miettinen, Susanna; Haimi, Suvi

2012-01-01

Different synthetic biomaterials such as polylactide (PLA), polycaprolactone and poly-l-lactide-co-ε-caprolactone (PLCL) have been studied for urothelial tissue engineering, with favourable results. The aim of this research was to further optimize the growth surface for human urothelial cells (hUCs) by comparing different PLCL-based membranes: smooth (s) and textured (t) PLCL and knitted PLA mesh with compression-moulded PLCL (cPLCL). The effects of topographical texturing on urothelial cell response and mechanical properties under hydrolysis were studied. The main finding was that both sPLCL and tPLCL supported hUC growth significantly better than cPLCL. Interestingly, tPLCL gave no significant advantage to hUC attachment or proliferation compared with sPLCL. However, during the 14 day assessment period, the majority of cells were viable and maintained phenotype on all the membranes studied. The material characterization exhibited potential mechanical characteristics of sPLCL and tPLCL for urothelial applications. Furthermore, the highest elongation of tPLCL supports the use of this kind of texturing. In conclusion, in light of our cell culture results and mechanical characterization, both sPLCL and tPLCL should be further studied for urothelial tissue engineering. PMID:22896571

Characterization of water molecular state in in-vivo thick tissues using diffuse optical spectroscopic imaging

NASA Astrophysics Data System (ADS)

Chung, So Hyun

Structural changes in water molecules are related to physiological, anatomical and pathological properties of tissues. Near infrared (NIR) optical absorption methods are sensitive to water; however, detailed characterization of water in thick tissues is difficult to achieve because subtle spectral shifts can be obscured by multiple light scattering. In the NIR, a water absorption peak is observed around 975 nm. The precise NIR peak's shape and position are highly sensitive to water molecular disposition. A bound water index (BWI) was developed that quantifies the spectral shift and shape changes observed in tissue water absorption spectra measured by broadband diffuse optical spectroscopic imaging (DOSI). DOSI quantitatively measures light absorption and scattering spectra in cm-deep tissues and therefore reveals bound water spectral shifts. BWI as a water state index was validated by comparing broadband DOSI to MRI and a conductivity cell using bound water phantoms. Non-invasive BWI measurements of malignant and normal tissues in 18 subjects showed a significantly higher fraction of free water in malignant tissues (p<0.0001) compared to normal tissues. BWI showed potential as a prognostic index based on high correlations with tumor grade and size. An algorithm for absolute temperature measurements in deep tissues was developed based on resolving opposing effects of water vibrational frequency shifts due to macromolecular binding. DOSI measures absolute temperature with a difference of 1.1+/-0.91°C from a thermistor. Deep tissue temperature measured in forearms during cold-stress was consistent with previously reported invasively-measured deep tissue temperature. Finally, the BWI was compared to Apparent Diffusion Coefficient (ADC) of diffusion weighted MRI in 9 breast cancer patients. The BWI and ADC correlated (R=0.8, p=<0.01) and both parameters decreased with increasing bulk water content in cancer tissues. Although BWI and ADC are positively correlated in vivo, BWI appears to be more sensitive to free water in the extracellular matrix while ADC reflects increased tumor cellularity. The relationship between ADC, BWI and bulk water concentration suggests that both parameters have potential for assessing tumor histopathological grade. My results confirm the importance of water as a critical tissue component that can potentially provide unique insight into the molecular pathophysiology of cancer.

Coregistered FDG PET/CT-based textural characterization of head and neck cancer for radiation treatment planning.

PubMed

Yu, Huan; Caldwell, Curtis; Mah, Katherine; Mozeg, Daniel

2009-03-01

Coregistered fluoro-deoxy-glucose (FDG) positron emission tomography/computed tomography (PET/CT) has shown potential to improve the accuracy of radiation targeting of head and neck cancer (HNC) when compared to the use of CT simulation alone. The objective of this study was to identify textural features useful in distinguishing tumor from normal tissue in head and neck via quantitative texture analysis of coregistered 18F-FDG PET and CT images. Abnormal and typical normal tissues were manually segmented from PET/CT images of 20 patients with HNC and 20 patients with lung cancer. Texture features including some derived from spatial grey-level dependence matrices (SGLDM) and neighborhood gray-tone-difference matrices (NGTDM) were selected for characterization of these segmented regions of interest (ROIs). Both K nearest neighbors (KNNs) and decision tree (DT)-based KNN classifiers were employed to discriminate images of abnormal and normal tissues. The area under the curve (AZ) of receiver operating characteristics (ROC) was used to evaluate the discrimination performance of features in comparison to an expert observer. The leave-one-out and bootstrap techniques were used to validate the results. The AZ of DT-based KNN classifier was 0.95. Sensitivity and specificity for normal and abnormal tissue classification were 89% and 99%, respectively. In summary, NGTDM features such as PET Coarseness, PET Contrast, and CT Coarseness extracted from FDG PET/CT images provided good discrimination performance. The clinical use of such features may lead to improvement in the accuracy of radiation targeting of HNC.

Detecting changes in ultrasound backscattered statistics by using Nakagami parameters: Comparisons of moment-based and maximum likelihood estimators.

PubMed

Lin, Jen-Jen; Cheng, Jung-Yu; Huang, Li-Fei; Lin, Ying-Hsiu; Wan, Yung-Liang; Tsui, Po-Hsiang

2017-05-01

The Nakagami distribution is an approximation useful to the statistics of ultrasound backscattered signals for tissue characterization. Various estimators may affect the Nakagami parameter in the detection of changes in backscattered statistics. In particular, the moment-based estimator (MBE) and maximum likelihood estimator (MLE) are two primary methods used to estimate the Nakagami parameters of ultrasound signals. This study explored the effects of the MBE and different MLE approximations on Nakagami parameter estimations. Ultrasound backscattered signals of different scatterer number densities were generated using a simulation model, and phantom experiments and measurements of human liver tissues were also conducted to acquire real backscattered echoes. Envelope signals were employed to estimate the Nakagami parameters by using the MBE, first- and second-order approximations of MLE (MLE 1 and MLE 2 , respectively), and Greenwood approximation (MLE gw ) for comparisons. The simulation results demonstrated that, compared with the MBE and MLE 1 , the MLE 2 and MLE gw enabled more stable parameter estimations with small sample sizes. Notably, the required data length of the envelope signal was 3.6 times the pulse length. The phantom and tissue measurement results also showed that the Nakagami parameters estimated using the MLE 2 and MLE gw could simultaneously differentiate various scatterer concentrations with lower standard deviations and reliably reflect physical meanings associated with the backscattered statistics. Therefore, the MLE 2 and MLE gw are suggested as estimators for the development of Nakagami-based methodologies for ultrasound tissue characterization. Copyright © 2017 Elsevier B.V. All rights reserved.

Simultaneous Analysis of Anthocyanin and Non-Anthocyanin Flavonoid in Various Tissues of Different Lotus (Nelumbo) Cultivars by HPLC-DAD-ESI-MSn

PubMed Central

Chen, Sha; Xiang, Yue; Deng, Jiao; Liu, Yanling; Li, Shaohua

2013-01-01

A validated HPLC-DAD-ESI-MSn method for the analysis of non-anthocyanin flavonoids was applied to nine different tissues of twelve lotus genotypes of Nelumbo nucifera and N. lutea, together with an optimized anthocyanin extraction and separation protocol for lotus petals. A total of five anthocyanins and twenty non-anthocyanin flavonoids was identified and quantified. Flavonoid contents and compositions varied with cultivar and tissue and were used as a basis to divide tissues into three groups characterized by kaempferol and quercetin derivatives. Influences on flower petal coloration were investigated by principal components analyses. High contents of kaempferol glycosides were detected in the petals of N. nucifera while high quercetin glycoside concentrations occurred in N. lutea. Based on these results, biosynthetic pathways leading to specific compounds in lotus tissues are deduced through metabolomic analysis of different genotypes and tissues and correlations among flavonoid compounds. PMID:23646125

The characterization of neural tissue ablation rate and corresponding heat affected zone of a 2 micron Tm3+ doped fiber laser(Conference Presentation)

NASA Astrophysics Data System (ADS)

Marques, Andrew J.; Jivraj, Jamil; Reyes, Robnier; Ramjist, Joel; Gu, Xijia J.; Yang, Victor X. D.

2017-02-01

Tissue removal using electrocautery is standard practice in neurosurgery since tissue can be cut and cauterized simultaneously. Thermally mediated tissue ablation using lasers can potentially possess the same benefits but with increased precision. However, given the critical nature of the spine, brain, and nerves, the effects of direct photo-thermal interaction on neural tissue needs to be known, yielding not only high precision of tissue removal but also increased control of peripheral heat damage. The proposed use of lasers as a neurosurgical tool requires that a common ground is found between ablation rates and resulting peripheral heat damage. Most surgical laser systems rely on the conversion of light energy into heat resulting in both desirable and undesirable thermal damage to the targeted tissue. Classifying the distribution of thermal energy in neural tissue, and thus characterizing the extent of undesirable thermal damage, can prove to be exceptionally challenging considering its highly inhomogenous composition when compared to other tissues such as muscle and bone. Here we present the characterization of neural tissue ablation rate and heat affected zone of a 1.94 micron thulium doped fiber laser for neural tissue ablation. In-Vivo ablation of porcine cerebral cortex is performed. Ablation volumes are studied in association with laser parameters. Histological samples are taken and examined to characterize the extent of peripheral heat damage.

Portable, Fiber-Based, Diffuse Reflection Spectroscopy (DRS) Systems for Estimating Tissue Optical Properties.

PubMed

Vishwanath, Karthik; Chang, Kevin; Klein, Daniel; Deng, Yu Feng; Chang, Vivide; Phelps, Janelle E; Ramanujam, Nimmi

2011-02-01

Steady-state diffuse reflection spectroscopy is a well-studied optical technique that can provide a noninvasive and quantitative method for characterizing the absorption and scattering properties of biological tissues. Here, we compare three fiber-based diffuse reflection spectroscopy systems that were assembled to create a light-weight, portable, and robust optical spectrometer that could be easily translated for repeated and reliable use in mobile settings. The three systems were built using a broadband light source and a compact, commercially available spectrograph. We tested two different light sources and two spectrographs (manufactured by two different vendors). The assembled systems were characterized by their signal-to-noise ratios, the source-intensity drifts, and detector linearity. We quantified the performance of these instruments in extracting optical properties from diffuse reflectance spectra in tissue-mimicking liquid phantoms with well-controlled optical absorption and scattering coefficients. We show that all assembled systems were able to extract the optical absorption and scattering properties with errors less than 10%, while providing greater than ten-fold decrease in footprint and cost (relative to a previously well-characterized and widely used commercial system). Finally, we demonstrate the use of these small systems to measure optical biomarkers in vivo in a small-animal model cancer therapy study. We show that optical measurements from the simple portable system provide estimates of tumor oxygen saturation similar to those detected using the commercial system in murine tumor models of head and neck cancer.

Measurement of the hyperelastic properties of 44 pathological ex vivo breast tissue samples

NASA Astrophysics Data System (ADS)

O'Hagan, Joseph J.; Samani, Abbas

2009-04-01

The elastic and hyperelastic properties of biological soft tissues have been of interest to the medical community. There are several biomedical applications where parameters characterizing such properties are critical for a reliable clinical outcome. These applications include surgery planning, needle biopsy and brachtherapy where tissue biomechanical modeling is involved. Another important application is interpreting nonlinear elastography images. While there has been considerable research on the measurement of the linear elastic modulus of small tissue samples, little research has been conducted for measuring parameters that characterize the nonlinear elasticity of tissues included in tissue slice specimens. This work presents hyperelastic measurement results of 44 pathological ex vivo breast tissue samples. For each sample, five hyperelastic models have been used, including the Yeoh, N = 2 polynomial, N = 1 Ogden, Arruda-Boyce, and Veronda-Westmann models. Results show that the Yeoh, polynomial and Ogden models are the most accurate in terms of fitting experimental data. The results indicate that almost all of the parameters corresponding to the pathological tissues are between two times to over two orders of magnitude larger than those of normal tissues, with C11 showing the most significant difference. Furthermore, statistical analysis indicates that C02 of the Yeoh model, and C11 and C20 of the polynomial model have very good potential for cancer classification as they show statistically significant differences for various cancer types, especially for invasive lobular carcinoma. In addition to the potential for use in cancer classification, the presented data are very important for applications such as surgery planning and virtual reality based clinician training systems where accurate nonlinear tissue response modeling is required.

The landscape of genomic imprinting across diverse adult human tissues.

PubMed

Baran, Yael; Subramaniam, Meena; Biton, Anne; Tukiainen, Taru; Tsang, Emily K; Rivas, Manuel A; Pirinen, Matti; Gutierrez-Arcelus, Maria; Smith, Kevin S; Kukurba, Kim R; Zhang, Rui; Eng, Celeste; Torgerson, Dara G; Urbanek, Cydney; Li, Jin Billy; Rodriguez-Santana, Jose R; Burchard, Esteban G; Seibold, Max A; MacArthur, Daniel G; Montgomery, Stephen B; Zaitlen, Noah A; Lappalainen, Tuuli

2015-07-01

Genomic imprinting is an important regulatory mechanism that silences one of the parental copies of a gene. To systematically characterize this phenomenon, we analyze tissue specificity of imprinting from allelic expression data in 1582 primary tissue samples from 178 individuals from the Genotype-Tissue Expression (GTEx) project. We characterize imprinting in 42 genes, including both novel and previously identified genes. Tissue specificity of imprinting is widespread, and gender-specific effects are revealed in a small number of genes in muscle with stronger imprinting in males. IGF2 shows maternal expression in the brain instead of the canonical paternal expression elsewhere. Imprinting appears to have only a subtle impact on tissue-specific expression levels, with genes lacking a systematic expression difference between tissues with imprinted and biallelic expression. In summary, our systematic characterization of imprinting in adult tissues highlights variation in imprinting between genes, individuals, and tissues. © 2015 Baran et al.; Published by Cold Spring Harbor Laboratory Press.

Image Analysis Algorithms for Immunohistochemical Assessment of Cell Death Events and Fibrosis in Tissue Sections

PubMed Central

Krajewska, Maryla; Smith, Layton H.; Rong, Juan; Huang, Xianshu; Hyer, Marc L.; Zeps, Nikolajs; Iacopetta, Barry; Linke, Steven P.; Olson, Allen H.; Reed, John C.; Krajewski, Stan

2009-01-01

Cell death is of broad physiological and pathological importance, making quantification of biochemical events associated with cell demise a high priority for experimental pathology. Fibrosis is a common consequence of tissue injury involving necrotic cell death. Using tissue specimens from experimental mouse models of traumatic brain injury, cardiac fibrosis, and cancer, as well as human tumor specimens assembled in tissue microarray (TMA) format, we undertook computer-assisted quantification of specific immunohistochemical and histological parameters that characterize processes associated with cell death. In this study, we demonstrated the utility of image analysis algorithms for color deconvolution, colocalization, and nuclear morphometry to characterize cell death events in tissue specimens: (a) subjected to immunostaining for detecting cleaved caspase-3, cleaved poly(ADP-ribose)-polymerase, cleaved lamin-A, phosphorylated histone H2AX, and Bcl-2; (b) analyzed by terminal deoxyribonucleotidyl transferase–mediated dUTP nick end labeling assay to detect DNA fragmentation; and (c) evaluated with Masson's trichrome staining. We developed novel algorithm-based scoring methods and validated them using TMAs as a high-throughput format. The proposed computer-assisted scoring methods for digital images by brightfield microscopy permit linear quantification of immunohistochemical and histochemical stainings. Examples are provided of digital image analysis performed in automated or semiautomated fashion for successful quantification of molecular events associated with cell death in tissue sections. (J Histochem Cytochem 57:649–663, 2009) PMID:19289554

Metal-clad waveguide characterization for contact-based light transmission into tissue

NASA Astrophysics Data System (ADS)

Chininis, Jeffrey; Whiteside, Paul; Hunt, Heather K.

2016-02-01

As contemporary laser dermatology procedures, like tattoo removal and skin resurfacing, become more popular, the complications of their operation are also becoming more prevalent. Frequent incidences of over-exposure, ocular injury, and excessive thermal damage represent mounting concerns for those seeking such procedures; moreover, each of these problems is a direct consequence of the standard, free-space method of laser transmission predominantly used in clinical settings. Therefore, an alternative method of light transmission is needed to minimize these problems. Here, we demonstrate and characterize an alternative method that uses planar waveguides to deliver light into sample tissue via direct contact. To do this, slab substrates made from glass were clad in layers of titanium and silver, constraining the light within the waveguide along the waveguide's length. By creating active areas on the waveguide surface, the propagating light could then optically tunnel into the tissue sample, when the waveguide was brought into contact with the tissue. SEM and EDS were used to characterize the metal film thickness and deposition rates onto the glass substrates. Laser light from a Q-switched Nd:YAG source operating at 532nm was coupled into the waveguide and transmitted into samples of pig skin. The amount of light transmitted was measured using photoacoustics techniques, in conjunction with a photodiode and integrating sphere. Transmitting light into tissue in this manner effectively resolves or circumvents the complications caused by free-space propagation methods as it reduces the operating distance to 0, which prevents hazardous back-reflections and allows for the ready incorporation of contact cooling technologies.

An actuated force feedback-enabled laparoscopic instrument for robotic-assisted surgery.

PubMed

Moradi Dalvand, Mohsen; Shirinzadeh, Bijan; Shamdani, Amir Hossein; Smith, Julian; Zhong, Yongmin

2014-03-01

Robotic-assisted minimally invasive surgery systems not only have the advantages of traditional laparoscopic instruments but also have other important advantages, including restoring the surgeon's hand-eye coordination and improving the surgeon's precision by filtering hand tremors. Unfortunately, these benefits have come at the expense of the surgeon's ability to feel. Various solutions for restoring this feature have been proposed. An actuated modular force feedback-enabled laparoscopic instrument was proposed that is able to measure tip-tissue lateral interaction forces as well as normal grasping forces. The instrument has also the capability to adjust the grasping direction inside the patient body. In order to measure the interaction forces, strain gauges were employed. A series of finite element analyses were performed to gain an understanding of the actual magnitude of surface strains where gauges are applied. The strain gauge bridge configurations were calibrated. A series of experiments was conducted and the results were analysed. The modularity feature of the proposed instrument makes it interchangeable between various tip types of different functionalities (e.g. cutter, grasper, dissector). Calibration results of the strain gauges incorporated into the tube and at the base of the instrument presented the monotonic responses for these strain gauge configurations. Experimental results from tissue probing and tissue characterization experiments verified the capability of the proposed instrument in measuring lateral probing forces and characterizing artificial tissue samples of varying stiffness. The proposed instrument can improve the quality of palpation and characterization of soft tissues of varying stiffness by restoring sense of touch in robotic assisted minimally invasive surgery operations. Copyright © 2013 John Wiley & Sons, Ltd.

Histologic analysis of fetal bovine derived acellular dermal matrix in tissue expander breast reconstruction.

PubMed

Gaster, Richard S; Berger, Aaron J; Monica, Stefanie D; Sweeney, Robert T; Endress, Ryan; Lee, Gordon K

2013-04-01

This study seeks to determine human host response to fetal bovine acellular dermal matrix (ADM) in staged implant-based breast reconstruction. A prospective study was performed for patients undergoing immediate breast reconstruction with tissue expander placement and SurgiMend acellular fetal bovine dermis. At the time of exchange for permanent implant, we obtained tissue specimens of SurgiMend and native capsule. Histological and immunohistochemical assays were performed to characterize the extent of ADM incorporation/degradation, host cell infiltration, neovascularization, inflammation, and host replacement of acellular fetal bovine collagen. Seventeen capsules from 12 patients were included in our study. The average "implantation" time of SurgiMend was 7.8 months (range, 2-23 months). Histological analysis of the biopsy of tissue revealed rare infiltration of host inflammatory cells, even at 23 months. One patient had an infection requiring removal of the tissue expander at 2 months. Contracture, inflammatory changes, edema, and polymorphonuclear leukocyte infiltration were rare in the ADM. An acellular capsule was seen in many cases, at the interface of SurgiMend with the tissue expander. SurgiMend demonstrated a very infrequent inflammatory response. An antibody specific to bovine collagen allowed for direct identification of bovine collagen separate from human collagen. Cellular infiltration and neovascularization of SurgiMend correlated with the quality of the mastectomy skin flap rather than the duration of implantation. Future studies are needed to further characterize the molecular mechanisms underlying tissue incorporation of this product.

Assessment and characterization of in situ rotator cuff biomechanics

NASA Astrophysics Data System (ADS)

Trent, Erika A.; Bailey, Lane; Mefleh, Fuad N.; Raikar, Vipul P.; Shanley, Ellen; Thigpen, Charles A.; Dean, Delphine; Kwartowitz, David M.

2013-03-01

Rotator cuff disease is a degenerative disorder that is a common, costly, and often debilitating, ranging in severity from partial thickness tear, which may cause pain, to total rupture, leading to loss in function. Currently, clinical diagnosis and determination of disease extent relies primarily on subjective assessment of pain, range of motion, and possibly X-ray or ultrasound images. The final treatment plan however is at the discretion of the clinician, who often bases their decision on personal experiences, and not quantitative standards. The use of ultrasound for the assessment of tissue biomechanics is established, such as in ultrasound elastography, where soft tissue biomechanics are measured. Few studies have investigated the use of ultrasound elastography in the characterization of musculoskeletal biomechanics. To assess tissue biomechanics we have developed a device, which measures the force applied to the underlying musculotendentious tissue while simultaneously obtaining the related ultrasound images. In this work, the musculotendinous region of the infraspinatus of twenty asymptomatic male organized baseball players was examined to access the variability in tissue properties within a single patient and across a normal population. Elastic moduli at percent strains less than 15 were significantly different than those above 15 percent strain within the normal population. No significant difference in tissue properties was demonstrated within a single patient. This analysis demonstrated elastic moduli are variable across individuals and incidence. Therefore threshold elastic moduli will likely be a function of variation in local-tissue moduli as opposed to a specific global value.

[Esophageal sarcomatoid carcinoma: report of a case with morphological, immunohistochemical and molecular study].

PubMed

Regragui, Asmaa; Lakhdar, Hind; Abderrahman Alaoui Belabbas, Moulay; Amrani, Meryem; Gamra, Lamia; Alaoui Belabbas, Mohamed

2004-05-01

Sarcomatoïd carcinoma is a rare tumor of the esophagus, characterized macroscopically by a polypoid aspect and histologically by the association of spindle cell carcinoma with sarcomatous pleomorphic component. We report here a case of esophagus sarcomatoïd carcinoma. Diagnosis was based on immunohistochemical analysis of tIssue samples. Human papillomavirus (HVP) detection by PCR amplification of DNA extracted from tumoral tIssue was negative, ruling out the role of HPV infection in this tumor.

Advances in Cell and Gene-based Therapies for Cystic Fibrosis Lung Disease

PubMed Central

Oakland, Mayumi; Sinn, Patrick L; McCray Jr, Paul B

2012-01-01

Cystic fibrosis (CF) is a disease characterized by airway infection, inflammation, remodeling, and obstruction that gradually destroy the lungs. Direct delivery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene to airway epithelia may offer advantages, as the tissue is accessible for topical delivery of vectors. Yet, physical and host immune barriers in the lung present challenges for successful gene transfer to the respiratory tract. Advances in gene transfer approaches, tissue engineering, and novel animal models are generating excitement within the CF research field. This review discusses current challenges and advancements in viral and nonviral vectors, cell-based therapies, and CF animal models. PMID:22371844

Toxicological evaluation of Cd-based fluorescent nanoprobes by means of in vivo studies

NASA Astrophysics Data System (ADS)

Farias, Patricia M. A.; Ma-Hock, Lan; Landsiedel, Robert; van Ravenzwaay, Bennard

2018-02-01

Cadmium still represents a stigma for many research- and/or industrial applications. Some deleterious effects are attributed to Cadmium. In the present work, highly fluorescent Cadmium sulfide quantum dots are investigated by e.g. physical-chemical characterization. Most important however is their application as fluorescent probes for bio-imaging in living cells and tissues. This work presents their toxicological evaluation by means of in vivo studies. Bio-imaging experiments are performed without any pre-treatment. The toxicological studies performed, strongly indicate that the use of Cadmium based nanoparticles as fluorescent probes may be nonhazardous and not induce side effects for cells/tissues.

Dynamic tissue analysis using time- and wavelength-resolved fluorescence spectroscopy for atherosclerosis diagnosis

PubMed Central

Sun, Yinghua; Sun, Yang; Stephens, Douglas; Xie, Hongtao; Phipps, Jennifer; Saroufeem, Ramez; Southard, Jeffrey; Elson, Daniel S.; Marcu, Laura

2011-01-01

Simultaneous time- and wavelength-resolved fluorescence spectroscopy (STWRFS) was developed and tested for the dynamic characterization of atherosclerotic tissue ex vivo and arterial vessels in vivo. Autofluorescence, induced by a 337 nm, 700 ps pulsed laser, was split to three wavelength sub-bands using dichroic filters, with each sub-band coupled into a different length of optical fiber for temporal separation. STWRFS allows for fast recording/analysis (few microseconds) of time-resolved fluorescence emission in these sub-bands and rapid scanning. Distinct compositions of excised human atherosclerotic aorta were clearly discriminated over scanning lengths of several centimeters based on fluorescence lifetime and the intensity ratio between 390 and 452 nm. Operation of STWRFS blood flow was further validated in pig femoral arteries in vivo using a single-fiber probe integrated with an ultrasound imaging catheter. Current results demonstrate the potential of STWRFS as a tool for real-time optical characterization of arterial tissue composition and for atherosclerosis research and diagnosis. PMID:21369214

Characterization of a novel anthropomorphic plastinated lung phantom

PubMed Central

Yoon, Sungwon; Henry, Robert W.; Bouley, Donna M.; Bennett, N. Robert; Fahrig, Rebecca

2008-01-01

Phantoms are widely used during the development of new imaging systems and algorithms. For development and optimization of new imaging systems such as tomosynthesis, where conventional image quality metrics may not be applicable, a realistic phantom that can be used across imaging systems is desirable. A novel anthropomorphic lung phantom was developed by plastination of an actual pig lung. The plastinated phantom is characterized and compared with reference to in vivo images of the same tissue prior to plastination using high resolution 3D CT. The phantom is stable over time and preserves the anatomical features and relative locations of the in vivo sample. The volumes for different tissue types in the phantom are comparable to the in vivo counterparts, and CT numbers for different tissue types fall within a clinically useful range. Based on the measured CT numbers, the phantom cardiac tissue experienced a 92% decrease in bulk density and the phantom pulmonary tissue experienced a 78% decrease in bulk density compared to their in vivo counterparts. By-products in the phantom from the room temperature vulcanizing silicone and plastination process are also identified. A second generation phantom, which eliminates most of the by-products, is presented. Such anthropomorphic phantoms can be used to evaluate a wide range of novel imaging systems. PMID:19175148

Measurement of vibration-induced volumetric strain in the human lung.

PubMed

Hirsch, Sebastian; Posnansky, Oleg; Papazoglou, Sebastian; Elgeti, Thomas; Braun, Jürgen; Sack, Ingolf

2013-03-01

Noninvasive image-based measurement of intrinsic tissue pressure is of great interest in the diagnosis and characterization of diseases. Therefore, we propose to exploit the capability of phase-contrast MRI to measure three-dimensional vector fields of tissue motion for deriving volumetric strain induced by external vibration. Volumetric strain as given by the divergence of mechanical displacement fields is related to tissue compressibility and is thus sensitive to the state of tissue pressure. This principle is demonstrated by the measurement of three-dimensional vector fields of 50-Hz oscillations in a compressible agarose phantom and in the lungs of nine healthy volunteers. In the phantom, the magnitude of the oscillating divergence increased by about 400% with 4.8 bar excess air pressure, corresponding to an effective-medium compression modulus of 230 MPa. In lungs, the averaged divergence magnitude increased in all volunteers (N = 9) between 7 and 78% from expiration to inspiration. Measuring volumetric strain by MRI provides a compression-sensitive parameter of tissue mechanics, which varies with the respiratory state in the lungs. In future clinical applications for diagnosis and characterization of lung emphysema, fibrosis, or cancer, divergence-sensitive MRI may serve as a noninvasive marker sensitive to disease-related alterations of regional elastic recoil pressure in the lungs. Copyright © 2012 Wiley Periodicals, Inc.

Micrometer-sized iron oxide particle labeling of mesenchymal stem cells for magnetic resonance imaging-based monitoring of cartilage tissue engineering.

PubMed

Saldanha, Karl J; Doan, Ryan P; Ainslie, Kristy M; Desai, Tejal A; Majumdar, Sharmila

2011-01-01

To examine mesenchymal stem cell (MSC) labeling with micrometer-sized iron oxide particles (MPIOs) for magnetic resonance imaging (MRI)-based tracking and its application to monitoring articular cartilage regeneration. Rabbit MSCs were labeled using commercial MPIOs. In vitro MRI was performed with gradient echo (GRE) and spin echo (SE) sequences at 3T and quantitatively characterized using line profile and region of interest analysis. Ex vivo MRI of hydrogel-encapsulated labeled MSCs implanted within a bovine knee was performed with spoiled GRE (SPGR) and T(1ρ) sequences. Fluorescence microscopy, labeling efficiency, and chondrogenesis of MPIO-labeled cells were also examined. MPIO labeling results in efficient contrast uptake and signal loss that can be visualized and quantitatively characterized via MRI. SPGR imaging of implanted cells results in ex vivo detection within native tissue, and T(1ρ) imaging is unaffected by the presence of labeled cells immediately following implantation. MPIO labeling does not affect quantitative glycosaminoglycan production during chondrogenesis, but iron aggregation hinders extracellular matrix visualization. This aggregation may result from excess unincorporated particles following labeling and is an issue that necessitates further investigation. This study demonstrates the promise of MPIO labeling for monitoring cartilage regeneration and highlights its potential in the development of cell-based tissue engineering strategies. Published by Elsevier Inc.

Histology-validated x-ray tomography for imaging human coronary arteries

NASA Astrophysics Data System (ADS)

Buscema, Marzia; Schulz, Georg; Deyhle, Hans; Khimchenko, Anna; Matviykiv, Sofiya; Holme, Margaret N.; Hipp, Alexander; Beckmann, Felix; Saxer, Till; Michaud, Katarzyna; Müller, Bert

2016-10-01

Heart disease is the number one cause of death worldwide. To improve therapy and patient outcome, the knowledge of anatomical changes in terms of lumen morphology and tissue composition of constricted arteries is crucial for designing a localized drug delivery to treat atherosclerosis disease. Traditional tissue characterization by histology is a pivotal tool, although it brings disadvantages such as vessel morphology modification during decalcification and slicing. X-ray tomography in absorption and phase contrast modes yields a deep understanding in blood vessel anatomy in healthy and diseased stages: measurements in absorption mode make visible highly absorbing tissue components including cholesterol plaques, whereas phase contrast tomography gains better contrast of the soft tissue components such as vessel walls. Established synchrotron radiation-based micro-CT techniques ensure high performance in terms of 3D visualization of highly absorbing and soft tissues.

An integrated inverse model-experimental approach to determine soft tissue three-dimensional constitutive parameters: application to post-infarcted myocardium.

PubMed

Avazmohammadi, Reza; Li, David S; Leahy, Thomas; Shih, Elizabeth; Soares, João S; Gorman, Joseph H; Gorman, Robert C; Sacks, Michael S

2018-02-01

Knowledge of the complete three-dimensional (3D) mechanical behavior of soft tissues is essential in understanding their pathophysiology and in developing novel therapies. Despite significant progress made in experimentation and modeling, a complete approach for the full characterization of soft tissue 3D behavior remains elusive. A major challenge is the complex architecture of soft tissues, such as myocardium, which endows them with strongly anisotropic and heterogeneous mechanical properties. Available experimental approaches for quantifying the 3D mechanical behavior of myocardium are limited to preselected planar biaxial and 3D cuboidal shear tests. These approaches fall short in pursuing a model-driven approach that operates over the full kinematic space. To address these limitations, we took the following approach. First, based on a kinematical analysis and using a given strain energy density function (SEDF), we obtained an optimal set of displacement paths based on the full 3D deformation gradient tensor. We then applied this optimal set to obtain novel experimental data from a 1-cm cube of post-infarcted left ventricular myocardium. Next, we developed an inverse finite element (FE) simulation of the experimental configuration embedded in a parameter optimization scheme for estimation of the SEDF parameters. Notable features of this approach include: (i) enhanced determinability and predictive capability of the estimated parameters following an optimal design of experiments, (ii) accurate simulation of the experimental setup and transmural variation of local fiber directions in the FE environment, and (iii) application of all displacement paths to a single specimen to minimize testing time so that tissue viability could be maintained. Our results indicated that, in contrast to the common approach of conducting preselected tests and choosing an SEDF a posteriori, the optimal design of experiments, integrated with a chosen SEDF and full 3D kinematics, leads to a more robust characterization of the mechanical behavior of myocardium and higher predictive capabilities of the SEDF. The methodology proposed and demonstrated herein will ultimately provide a means to reliably predict tissue-level behaviors, thus facilitating organ-level simulations for efficient diagnosis and evaluation of potential treatments. While applied to myocardium, such developments are also applicable to characterization of other types of soft tissues.

Banking brain tissue for research.

PubMed

Klioueva, Natasja; Bovenberg, Jasper; Huitinga, Inge

2017-01-01

Well-characterized human brain tissue is crucial for scientific breakthroughs in research of the human brain and brain diseases. However, the collection, characterization, management, and accessibility of brain human tissue are rather complex. Well-characterized human brain tissue is often provided from private, sometimes small, brain tissue collections by (neuro)pathologic experts. However, to meet the increasing demand for human brain tissue from the scientific community, many professional brain-banking activities aiming at both neurologic and psychiatric diseases as well as healthy controls are currently being initiated worldwide. Professional biobanks are open-access and in many cases run donor programs. They are therefore costly and need effective business plans to guarantee long-term sustainability. Here we discuss the ethical, legal, managerial, and financial aspects of professional brain banks. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of Photoacoustic Signals in Photosynthetic and Nonphotosynthetic Leaf Tissues of Variegated Pelargonium zonale

NASA Astrophysics Data System (ADS)

Veljović-Jovanović, S.; Vidović, M.; Morina, F.; Prokić, Lj.; Todorović, D. M.

2016-09-01

Green-white variegated leaves of Pelargonium zonale were studied using the photoacoustic method. Our aim was to characterize photosynthetically active green tissue and nonphotosynthetically active white tissue by the photoacoustic amplitude signals. We observed lower stomatal conductance and higher leaf temperature in white tissue than in green tissue. Besides these thermal differences, significantly higher absorbance in green tissue was based on chlorophyll and carotenoids which were absent in white tissue. However, optical properties of epidermal layers of both tissues were equal. The photoacoustic amplitude of white tissue was over four times higher compared to green tissue, which was correlated with lower stomatal conductance. In addition, at frequencies >700 Hz, the significant differences between the photoacoustic signals of green and white tissue were obtained. We identified the photoacoustic signal deriving from photosynthetic oxygen evolution in green tissue, using high intensity of red light modulated at 10 Hz. Moreover, the photoacoustic amplitude of green tissue increased progressively with time which corresponded to the period of induction of photosynthetic oxygen evolution. For the first time, very high frequencies (1 kHz to 5 kHz) were applied on leaf material.

Accurate tissue characterization in low-dose CT imaging with pure iterative reconstruction.

PubMed

Murphy, Kevin P; McLaughlin, Patrick D; Twomey, Maria; Chan, Vincent E; Moloney, Fiachra; Fung, Adrian J; Chan, Faimee E; Kao, Tafline; O'Neill, Siobhan B; Watson, Benjamin; O'Connor, Owen J; Maher, Michael M

2017-04-01

We assess the ability of low-dose hybrid iterative reconstruction (IR) and 'pure' model-based IR (MBIR) images to maintain accurate Hounsfield unit (HU)-determined tissue characterization. Standard-protocol (SP) and low-dose modified-protocol (MP) CTs were contemporaneously acquired in 34 Crohn's disease patients referred for CT. SP image reconstruction was via the manufacturer's recommendations (60% FBP, filtered back projection; 40% ASiR, Adaptive Statistical iterative Reconstruction; SP-ASiR40). MP data sets underwent four reconstructions (100% FBP; 40% ASiR; 70% ASiR; MBIR). Three observers measured tissue volumes using HU thresholds for fat, soft tissue and bone/contrast on each data set. Analysis was via SPSS. Inter-observer agreement was strong for 1530 datapoints (rs > 0.9). MP-MBIR tissue volume measurement was superior to other MP reconstructions and closely correlated with the reference SP-ASiR40 images for all tissue types. MP-MBIR superiority was most marked for fat volume calculation - close SP-ASiR40 and MP-MBIR Bland-Altman plot correlation was seen with the lowest average difference (336 cm 3 ) when compared with other MP reconstructions. Hounsfield unit-determined tissue volume calculations from MP-MBIR images resulted in values comparable to SP-ASiR40 calculations and values that are superior to MP-ASiR images. Accuracy of estimation of volume of tissues (e.g. fat) using segmentation software on low-dose CT images appears optimal when reconstructed with pure IR. © 2016 The Royal Australian and New Zealand College of Radiologists.

Prevention of Phenytoin-Induced Gingival Overgrowth by Lovastatin in Mice

PubMed Central

Assaggaf, Mohammad A.; Kantarci, Alpdogan; Sume, Siddika S.; Trackman, Philip C.

2016-01-01

Drug-induced gingival overgrowth is caused by the antiseizure medication phenytoin, calcium channel blockers, and ciclosporin. Characteristics of these drug-induced gingival overgrowth lesions differ. We evaluate the ability of a mouse model to mimic human phenytoin-induced gingival overgrowth and assess the ability of a drug to prevent its development. Lovastatin was chosen based on previous analyses of tissue-specific regulation of CCN2 production in human gingival fibroblasts and the known roles of CCN2 in promoting fibrosis and epithelial to mesenchymal transition. Data indicate that anterior gingival tissue overgrowth occurred in phenytoin-treated mice based on gross tissue observations and histomorphometry of tissue sections. Molecular markers of epithelial plasticity and fibrosis were regulated by phenytoin in gingival epithelial tissues and in connective tissues similar to that seen in humans. Lovastatin attenuated epithelial gingival tissue growth in phenytoin-treated mice and altered the expressions of markers for epithelial to mesenchymal transition. Data indicate that phenytoin-induced gingival overgrowth in mice mimics molecular aspects of human gingival overgrowth and that lovastatin normalizes the tissue morphology and the expression of the molecular markers studied. Data are consistent with characterization of phenytoin-induced human gingival overgrowth in vivo and in vitro characteristics of cultured human gingival epithelial and connective tissue cells. Findings suggest that statins may serve to prevent or attenuate phenytoin-induced human gingival overgrowth, although specific human studies are required. PMID:25843680

Non-invasive tissue temperature measurements based on quantitative diffuse optical spectroscopy (DOS) of water.

PubMed

Chung, S H; Cerussi, A E; Merritt, S I; Ruth, J; Tromberg, B J

2010-07-07

We describe the development of a non-invasive method for quantitative tissue temperature measurements using Broadband diffuse optical spectroscopy (DOS). Our approach is based on well-characterized opposing shifts in near-infrared (NIR) water absorption spectra that appear with temperature and macromolecular binding state. Unlike conventional reflectance methods, DOS is used to generate scattering-corrected tissue water absorption spectra. This allows us to separate the macromolecular bound water contribution from the thermally induced spectral shift using the temperature isosbestic point at 996 nm. The method was validated in intralipid tissue phantoms by correlating DOS with thermistor measurements (R=0.96) with a difference of 1.1+/-0.91 degrees C over a range of 28-48 degrees C. Once validated, thermal and hemodynamic (i.e. oxy- and deoxy-hemoglobin concentration) changes were measured simultaneously and continuously in human subjects (forearm) during mild cold stress. DOS-measured arm temperatures were consistent with previously reported invasive deep tissue temperature studies. These results suggest that DOS can be used for non-invasive, co-registered measurements of absolute temperature and hemoglobin parameters in thick tissues, a potentially important approach for optimizing thermal diagnostics and therapeutics.

Assessment of Microcirculatory Hemoglobin Levels in Normal and Diabetic Subjects using Diffuse Reflectance Spectroscopy in the Visible Region — a Pilot Study

NASA Astrophysics Data System (ADS)

Sujatha, N.; Anand, B. S. Suresh; Nivetha, K. Bala; Narayanamurthy, V. B.; Seshadri, V.; Poddar, R.

2015-07-01

Light-based diagnostic techniques provide a minimally invasive way for selective biomarker estimation when tissues transform from a normal to a malignant state. Spectroscopic techniques based on diffuse reflectance characterize the changes in tissue hemoglobin/oxygenation levels during the tissue transformation process. Recent clinical investigations have shown that changes in tissue oxygenation and microcirculation are observed in diabetic subjects in the initial and progressive stages. In this pilot study, we discuss the potential of diffuse reflectance spectroscopy (DRS) in the visible (Vis) range to differentiate the skin microcirculatory hemoglobin levels between normal and advanced diabetic subjects with and without neuropathy. Average concentration of hemoglobin as well as hemoglobin oxygen saturation within the probed tissue volume is estimated for a total of four different sites in the foot sole. The results indicate a statistically significant decrease in average total hemoglobin and increase in hemoglobin oxygen saturation levels for diabetic foot compared with a normal foot. The present study demonstrates the ability of reflectance spectroscopy in the Vis range to determine and differentiate the changes in tissue hemoglobin and hemoglobin oxygen saturation levels in normal and diabetic subjects.

Characterization of bone tissue using microstrip antennas.

PubMed

Barros, Jannayna D; de Oliveira, Jose Josemar; da Silva, Sandro G

2010-01-01

The use of electromagnetic waves in the characterization of biological tissues has been conducted since the nineteenth century after the confirmation that electric and magnetic fields can interact with biological materials. In this paper, electromagnetic waves are used to characterize tissues with different levels of bone mass. In this way, one antenna array on microstrip lines was used. It can be seen that bones with different mass has different behavior in microwave frequencies.

Torsional Ultrasound Sensor Optimization for Soft Tissue Characterization

PubMed Central

Melchor, Juan; Muñoz, Rafael; Rus, Guillermo

2017-01-01

Torsion mechanical waves have the capability to characterize shear stiffness moduli of soft tissue. Under this hypothesis, a computational methodology is proposed to design and optimize a piezoelectrics-based transmitter and receiver to generate and measure the response of torsional ultrasonic waves. The procedure employed is divided into two steps: (i) a finite element method (FEM) is developed to obtain a transmitted and received waveform as well as a resonance frequency of a previous geometry validated with a semi-analytical simplified model and (ii) a probabilistic optimality criteria of the design based on inverse problem from the estimation of robust probability of detection (RPOD) to maximize the detection of the pathology defined in terms of changes of shear stiffness. This study collects different options of design in two separated models, in transmission and contact, respectively. The main contribution of this work describes a framework to establish such as forward, inverse and optimization procedures to choose a set of appropriate parameters of a transducer. This methodological framework may be generalizable for other different applications. PMID:28617353

Cell-based and biomaterial approaches to connective tissue repair

NASA Astrophysics Data System (ADS)

Stalling, Simone Suzette

Connective tissue injuries of skin, tendon and ligament, heal by a reparative process in adults, filling the wound site with fibrotic, disorganized scar tissue that poorly reflects normal tissue architecture or function. Conversely, fetal skin and tendon have been shown to heal scarlessly. Complete regeneration is not intrinsically ubiquitous to all fetal tissues; fetal diaphragmatic and gastrointestinal injuries form scars. In vivo studies suggest that the presence of fetal fibroblasts is essential for scarless healing. In the orthopaedic setting, adult anterior cruciate ligament (ACL) heals poorly; however, little is known about the regenerative capacity of fetal ACL or fetal ACL fibroblasts. We characterized in vitro wound healing properties of fetal and adult ACL fibroblasts demonstrating that fetal ACL fibroblasts migrate faster and elaborate greater quantities of type I collagen, suggesting the healing potential of the fetal ACL may not be intrinsically poor. Similar to fetal ACL fibroblasts, fetal dermal fibroblasts also exhibit robust cellular properties. We investigated the age-dependent effects of dermal fibroblasts on tendon-to-bone healing in rat supraspinatus tendon injuries, a reparative injury model. We hypothesized delivery of fetal dermal fibroblasts would increase tissue organization and mechanical properties in comparison to adult dermal fibroblasts. However, at 1 and 8 weeks, the presence of dermal fibroblasts, either adult or fetal, had no significant effect on tissue histology or mechanical properties. There was a decreasing trend in cross-sectional area of repaired tendons treated with fetal dermal fibroblasts in comparison to adult, but this finding was not significant in comparison to controls. Finally, we synthesized a novel polysaccharide, methacrylated methylcellulose (MA-MC), and fabricated hydrogels using a well-established photopolymerization technique. We characterized the physical and mechanical properties of MA-MC hydrogels in vitro as well as in a subcutaneous mouse model. Stable MA-MC hydrogels, of varying weight percentages, demonstrated tunable swelling and mechanical properties in the absence of cytotoxic degradation products. In vivo, 6wt% MA-MC hydrogels maintained their shape and mechanical integrity while eliciting a minimal inflammatory response; highly desirable properties for soft tissue reconstruction. These cellulose-based photopolymerizable hydrogels can be further optimized for drug delivery and tissue engineering applications to enhance wound repair.

Comparative metabolomic and ionomic approach for abundant fishes in estuarine environments of Japan

PubMed Central

Yoshida, Seiji; Date, Yasuhiro; Akama, Makiko; Kikuchi, Jun

2014-01-01

Environmental metabolomics or ionomics is widely used to characterize the effects of environmental stressors on the health of aquatic organisms. However, most studies have focused on liver and muscle tissues of fish, and little is known about how the other organs are affected by environmental perturbations and effects such as metal pollutants or eutrophication. We examined the metabolic and mineral profiles of three kinds of abundant fishes in estuarine ecosystem, yellowfin goby, urohaze-goby, and juvenile Japanese seabass sampled from Tsurumi River estuary, Japan. Multivariate analyses, including nuclear magnetic resonance-based metabolomics and inductively coupled plasma optical emission spectrometry-based ionomics approaches, revealed that the profiles were clustered according to differences among body tissues rather than differences in body size, sex, and species. The metabolic and mineral profiles of the muscle and fin tissues, respectively, suggest that these tissues are most appropriate for evaluating environmental perturbations. Such analyses will be highly useful in evaluating the environmental variation and diversity in aquatic ecosystems. PMID:25387575

Fluorescence spectroscopy using indocyanine green for lymph node mapping

NASA Astrophysics Data System (ADS)

Haj-Hosseini, Neda; Behm, Pascal; Shabo, Ivan; Wârdell, Karin

2014-02-01

The principles of cancer treatment has for years been radical resection of the primary tumor. In the oncologic surgeries where the affected cancer site is close to the lymphatic system, it is as important to detect the draining lymph nodes for metastasis (lymph node mapping). As a replacement for conventional radioactive labeling, indocyanine green (ICG) has shown successful results in lymph node mapping; however, most of the ICG fluorescence detection techniques developed are based on camera imaging. In this work, fluorescence spectroscopy using a fiber-optical probe was evaluated on a tissue-like ICG phantom with ICG concentrations of 6-64 μM and on breast tissue from five patients. Fiber-optical based spectroscopy was able to detect ICG fluorescence at low intensities; therefore, it is expected to increase the detection threshold of the conventional imaging systems when used intraoperatively. The probe allows spectral characterization of the fluorescence and navigation in the tissue as opposed to camera imaging which is limited to the view on the surface of the tissue.

Fast blood flow monitoring in deep tissues with real-time software correlators

PubMed Central

Wang, Detian; Parthasarathy, Ashwin B.; Baker, Wesley B.; Gannon, Kimberly; Kavuri, Venki; Ko, Tiffany; Schenkel, Steven; Li, Zhe; Li, Zeren; Mullen, Michael T.; Detre, John A.; Yodh, Arjun G.

2016-01-01

We introduce, validate and demonstrate a new software correlator for high-speed measurement of blood flow in deep tissues based on diffuse correlation spectroscopy (DCS). The software correlator scheme employs standard PC-based data acquisition boards to measure temporal intensity autocorrelation functions continuously at 50 – 100 Hz, the fastest blood flow measurements reported with DCS to date. The data streams, obtained in vivo for typical source-detector separations of 2.5 cm, easily resolve pulsatile heart-beat fluctuations in blood flow which were previously considered to be noise. We employ the device to separate tissue blood flow from tissue absorption/scattering dynamics and thereby show that the origin of the pulsatile DCS signal is primarily flow, and we monitor cerebral autoregulation dynamics in healthy volunteers more accurately than with traditional instrumentation as a result of increased data acquisition rates. Finally, we characterize measurement signal-to-noise ratio and identify count rate and averaging parameters needed for optimal performance. PMID:27231588

Exploring the potential of polyurethane-based soft foam as cell-free scaffold for soft tissue regeneration.

PubMed

Gerges, Irini; Tamplenizza, Margherita; Martello, Federico; Recordati, Camilla; Martelli, Cristina; Ottobrini, Luisa; Tamplenizza, Mariacaterina; Guelcher, Scott A; Tocchio, Alessandro; Lenardi, Cristina

2018-06-01

Reconstructive treatment after trauma and tumor resection would greatly benefit from an effective soft tissue regeneration. The use of cell-free scaffolds for adipose tissue regeneration in vivo is emerging as an attractive alternative to tissue-engineered constructs, since this approach avoids complications due to cell manipulation and lack of synchronous vascularization. In this study, we developed a biodegradable polyurethane-based scaffold for soft tissue regeneration, characterized by an exceptional combination between softness and resilience. Exploring the potential as a cell-free scaffold required profound understanding of the impact of its intrinsic physico-chemical properties on the biological performance in vivo. We investigated the effect of the scaffold's hydrophilic character, degradation kinetics, and internal morphology on (i) the local inflammatory response and activation of MGCs (foreign body response); (ii) its ability to promote rapid vascularisation, cell infiltration and migration through the scaffold over time; and (iii) the grade of maturation of the newly formed tissue into vascularized soft tissue in a murine model. The study revealed that soft tissue regeneration in vivo proceeded by gradual infiltration of undifferentiated mesenchymal cells though the periphery toward the center of the scaffold, where the rapid formation of a functional and well-formed vascular network supported cell viability overtime. Exploring the potential of polyurethane-based soft foam as cell-free scaffold for soft tissue regeneration. In this work, we address the unmet need for synthetic functional soft tissue substitutes that provide adequate biological and mechanical support to soft tissue. We developed a series of flexible cross-linked polyurethane copolymer scaffolds with remarkable fatigue-resistance and tunable physico-chemical properties for soft tissue regeneration in vivo. Accordingly, we could extend the potential of this class of biomaterials, which was so far confined for bone and osteochondral tissue regeneration, to other types of connective tissue. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Construction of Reference Data for Tissue Characterization of Arterial Wall Based on Elasticity Images

NASA Astrophysics Data System (ADS)

Inagaki, Jun; Hasegawa, Hideyuki; Kanai, Hiroshi; Ichiki, Masataka; Tezuka, Fumiaki

2005-06-01

Previously, we developed the phased tracking method [H. Kanai et al.: IEEE Trans. Ultrason. Ferroelectr. Freq. Control 43 (1996) 791] for measuring the minute change in thickness during one heartbeat and the elasticity of the arterial wall. By comparing pathological images with elasticity images measured with ultrasound, elasticity distributions for respective tissues in the arterial wall were determined. We have already measured the elasticity distributions for lipids and fibrous tissues (mixtures of smooth-muscle and collagen fiber) [H. Kanai et al.: Circulation 107 (2003) 3018]. In this study, elasticity distributions were measured for blood clots and calcified tissues. We discuss whether these elasticity distributions, which were measuerd in vitro, can be used as reference data for classifying cross-sectional elasticity images measured in vivo into respective tissues. In addition to the measurement of elasticity distributions, correlations between collagen content and elasticity were investigated with respect to fibrous tissue to estimate the collagen and smooth-muscle content based on elasticity. Collagen and smooth-muscle content may be important factors in determining the stability of the fibrous cap of atherosclerotic plaque. Therefore, correlations between elasticity and elements of the tissue in the arterial wall may provide useful information for the noninvasive diagnosis of plaque vulnerability.

The theory behind the full scattering profile

NASA Astrophysics Data System (ADS)

Feder, Idit; Duadi, Hamootal; Fixler, Dror

2018-02-01

Optical methods for extracting properties of tissues are commonly used. These methods are non-invasive, cause no harm to the patient and are characterized by high speed. The human tissue is a turbid media hence it poses a challenge for different optical methods. In addition the analysis of the emitted light requires calibration for achieving accuracy information. Most of the methods analyze the reflected light based on their phase and amplitude or the transmitted light. We suggest a new optical method for extracting optical properties of cylindrical tissues based on their full scattering profile (FSP), which means the angular distribution of the reemitted light. The FSP of cylindrical tissues is relevant for biomedical measurement of fingers, earlobes or pinched tissues. We found the iso-pathlength (IPL) point, a point on the surface of the cylinder medium where the light intensity remains constant and does not depend on the reduced scattering coefficient of the medium, but rather depends on the spatial structure and the cylindrical geometry. However, a similar behavior was also previously reported in reflection from a semi-infinite medium. Moreover, we presented a linear dependency between the radius of the tissue and the point's location. This point can be used as a self-calibration point and thus improve the accuracy of optical tissue measurements. This natural phenomenon has not been investigated before. We show this phenomenon theoretically, based on the diffusion theory, which is supported by our simulation results using Monte Carlo simulation.

Characterization of Cerebral White Matter Properties Using Quantitative Magnetic Resonance Imaging Stains

PubMed Central

Hurley, Samuel A.; Samsonov, Alexey A.; Adluru, Nagesh; Hosseinbor, Ameer Pasha; Mossahebi, Pouria; Tromp, Do P.M.; Zakszewski, Elizabeth; Field, Aaron S.

2011-01-01

Abstract The image contrast in magnetic resonance imaging (MRI) is highly sensitive to several mechanisms that are modulated by the properties of the tissue environment. The degree and type of contrast weighting may be viewed as image filters that accentuate specific tissue properties. Maps of quantitative measures of these mechanisms, akin to microstructural/environmental-specific tissue stains, may be generated to characterize the MRI and physiological properties of biological tissues. In this article, three quantitative MRI (qMRI) methods for characterizing white matter (WM) microstructural properties are reviewed. All of these measures measure complementary aspects of how water interacts with the tissue environment. Diffusion MRI, including diffusion tensor imaging, characterizes the diffusion of water in the tissues and is sensitive to the microstructural density, spacing, and orientational organization of tissue membranes, including myelin. Magnetization transfer imaging characterizes the amount and degree of magnetization exchange between free water and macromolecules like proteins found in the myelin bilayers. Relaxometry measures the MRI relaxation constants T1 and T2, which in WM have a component associated with the water trapped in the myelin bilayers. The conduction of signals between distant brain regions occurs primarily through myelinated WM tracts; thus, these methods are potential indicators of pathology and structural connectivity in the brain. This article provides an overview of the qMRI stain mechanisms, acquisition and analysis strategies, and applications for these qMRI stains. PMID:22432902

Characterization of Human Mammary Epithelial Stem Cells

DTIC Science & Technology

2010-10-01

This term reflects the method used to detect murine mammary stem cells which is based on their individual ability to regenerate an entire mammary tree......mammary stem cells. We now describe a method for detecting an analogous subpopulation in normal human mammary tissue. Dissociated cells are suspended

Infrared fiber optic probes for evaluation of musculoskeletal tissue pathology

NASA Astrophysics Data System (ADS)

Padalkar, Mugdha; McGoverin, Cushla; Onigbanjo, Quam; Spencer, Richard; Barbash, Scott; Kropf, Eric; Pleshko, Nancy

2014-03-01

Musculoskeletal pathology of the knee commonly occurs with aging and as a result of injury. The incidence of anterior cruciate ligament (ACL) injuries continues to increase annually, and may precede the eventual onset of osteoarthritis (OA), a debilitating and prevalent disease characterized by cartilage degeneration. Early detection of OA remains elusive, with current imaging methods lacking adequate sensitivity to detect early pathologic cartilage changes. We used mid- and near- infrared (IR) spectroscopy through arthroscopic-based fiber-optic devices to assess cartilage damage and differentiate tendon from ligament. Mid-IR spectroscopy is characterized by distinct bands and low penetration depth (< 10 μm) and near-IR spectroscopy is characterized by complex overlapping bands and greater penetration depths (< 1 cm). We have found that combined mid- and near-IR analysis greatly extends the information available through either in the analysis of soft tissues, including cartilage, ligaments and tendons. We discuss here basic science studies and the potential for translation to clinical research with novel arthroscopic probes.

Generation of a total of 6483 expressed sequence tags from 60 day-old bovine whole fetus and fetal placenta.

PubMed

Oishi, M; Gohma, H; Lejukole, H Y; Taniguchi, Y; Yamada, T; Suzuki, K; Shinkai, H; Uenishi, H; Yasue, H; Sasaki, Y

2004-05-01

Expressed sequence tags (ESTs) generated based on characterization of clones isolated randomly from cDNA libraries are used to study gene expression profiles in specific tissues and to provide useful information for characterizing tissue physiology. In this study, two directionally cloned cDNA libraries were constructed from 60 day-old bovine whole fetus and fetal placenta. We have characterized 5357 and 1126 clones, and then identified 3464 and 795 unique sequences for the fetus and placenta cDNA libraries: 1851 and 504 showed homology to already identified genes, and 1613 and 291 showed no significant matches to any of the sequences in DNA databases, respectively. Further, we found 94 unique sequences overlapping in both the fetus and the placenta, leading to a catalog of 4165 genes expressed in 60 day-old fetus and placenta. The catalog is used to examine expression profile of genes in 60 day-old bovine fetus and placenta.

Establishment and characterization of Xenopus oviduct cells in primary culture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marsh, J.; Tata, J.R.

1987-11-01

Based on previously established procedure of Xenopus hepatocytes, the authors describe tubular oviduct cells in primary culture which continue to secrete substantial quantities of egg jelly for several days, as can be visualized microscopically. Freshly isolated cells exhibited a culture shock response, from which they recovered by the third day in culture. This recovery was characterized by (a) the diminished synthesis of heat shock proteins hsp 70 and hsp 85, (b) the cessation of the drop in number of estrogen receptor, and (c) the enhanced rate of synthesis of cellular and secreted proteins. The oviduct estrogen receptor had the samemore » characteristics as those in other estrogen target tissues and was present in the same amount as in adult female Xenopus hepatocytes. The successful establishment and characterization of primary cultures of both liver and oviduct cells now fulfill the conditions required for investigating the basis for tissue specificity of regulation by estrogen of Xenopus egg protein gene expression in primary cell culture.« less

Gelatin/Carboxymethyl chitosan based scaffolds for dermal tissue engineering applications.

PubMed

Agarwal, Tarun; Narayan, Rajan; Maji, Somnath; Behera, Shubhanath; Kulanthaivel, Senthilguru; Maiti, Tapas Kumar; Banerjee, Indranil; Pal, Kunal; Giri, Supratim

2016-12-01

The present study delineates the preparation, characterization and application of gelatin-carboxymethyl chitosan scaffolds for dermal tissue engineering. The effect of carboxymethyl chitosan and gelatin ratio was evaluated for variations in their physico-chemical-biological characteristics and drug release kinetics. The scaffolds were prepared by freeze drying method and characterized by SEM and FTIR. The study revealed that the scaffolds were highly porous with pore size ranging between 90 and 170μm, had high water uptake (400-1100%) and water retention capacity (>300%). The collagenase mediated degradation of the scaffolds was dependent on the amount of gelatin present in the formulation. A slight yet significant variation in their biological characteristics was also observed. All the formulations supported adhesion, spreading, growth and proliferation of 3T3 mouse fibroblasts. The cells seeded on the scaffolds also demonstrated expression of collagen type I, HIF1α and VEGF, providing a clue regarding their growth and proliferation along with potential to support angiogenesis during wound healing. In addition, the scaffolds showed sustained ampicillin and bovine serum albumin release, confirming their suitability as a therapeutic delivery vehicle during wound healing. All together, the results suggest that gelatin-carboxymethyl chitosan based scaffolds could be a suitable matrix for dermal tissue engineering applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Extraction and characterization of collagen from Antarctic and Sub-Antarctic squid and its potential application in hybrid scaffolds for tissue engineering.

PubMed

Coelho, Rui C G; Marques, Ana L P; Oliveira, Sara M; Diogo, Gabriela S; Pirraco, Rogério P; Moreira-Silva, Joana; Xavier, José C; Reis, Rui L; Silva, Tiago H; Mano, João F

2017-09-01

Collagen is the most abundant protein found in mammals and it exhibits a low immunogenicity, high biocompatibility and biodegradability when compared with others natural polymers. For this reason, it has been explored for the development of biologically instructive biomaterials with applications for tissue substitution and regeneration. Marine origin collagen has been pursued as an alternative to the more common bovine and porcine origins. This study focused on squid (Teuthoidea: Cephalopoda), particularly the Antarctic squid Kondakovia longimana and the Sub-Antarctic squid Illex argentinus as potential collagen sources. In this study, collagen has been isolated from the skins of the squids using acid-based and pepsin-based protocols, with the higher yield being obtained from I. argentinus in the presence of pepsin. The produced collagen has been characterized in terms of physicochemical properties, evidencing an amino acid profile similar to the one of calf collagen, but exhibiting a less preserved structure, with hydrolyzed portions and a lower melting temperature. Pepsin-soluble collagen isolated from I. argentinus was selected for further evaluation of biomedical potential, exploring its incorporation on poly-ε-caprolactone (PCL) 3D printed scaffolds for the development of hybrid scaffolds for tissue engineering, exhibiting hierarchical features. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of a convenient ex vivo model for the study of the transcorneal permeation of drugs: histological and permeability evaluation.

PubMed

Pescina, Silvia; Govoni, Paolo; Potenza, Arianna; Padula, Cristina; Santi, Patrizia; Nicoli, Sara

2015-01-01

In this paper, an ex vivo model for the study of the transcorneal permeation of drugs, based on porcine tissues, was evaluated. The setup is characterized by ease of realization, absence of O₂ and CO₂ bubbling and low cost; additionally, the large availability of porcine tissue permits a high throughput. Histological images showed the comparability between porcine and human corneas and confirmed the effectiveness of the isolation procedure. A new de-epithelization procedure based on a thermal approach was also set up to simulate cornea permeability in pathological conditions. The procedure did not affect the integrity of the underlying layers and allowed the characterization of the barrier properties of epithelium and stroma. Six compounds with different physicochemical properties were tested: fluorescein, atenolol, propranolol, diclofenac, ganciclovir and lidocaine. The model highlighted the barrier function played by epithelium toward the diffusion of hydrophilic compounds and the permselectivity with regard to more lipophilic molecules. In particular, positively charged compounds showed a significantly higher transcorneal permeability than negatively charged compounds. The comparability of results with literature data supports the goodness and the robustness of the model, especially taking into account the behavior of fluorescein, which is generally considered a marker of tissue integrity. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Design of Xylose-Based Semisynthetic Polyurethane Tissue Adhesives with Enhanced Bioactivity Properties.

PubMed

Balcioglu, Sevgi; Parlakpinar, Hakan; Vardi, Nigar; Denkbas, Emir Baki; Karaaslan, Merve Goksin; Gulgen, Selam; Taslidere, Elif; Koytepe, Suleyman; Ates, Burhan

2016-02-01

Developing biocompatible tissue adhesives with high adhesion properties is a highly desired goal of the tissue engineering due to adverse effects of the sutures. Therefore, our work involves synthesis, characterization, adhesion properties, protein adsorption, in vitro biodegradation, in vitro and in vivo biocompatibility properties of xylose-based semisynthetic polyurethane (NPU-PEG-X) bioadhesives. Xylose-based semisynthetic polyurethanes were developed by the reaction among 4,4'-methylenebis(cyclohexyl isocyanate) (MCI), xylose and polyethylene glycol 200 (PEG). Synthesized polyurethanes (PUs) showed good thermal stability and high adhesion strength. The highest values in adhesion strength were measured as 415.0 ± 48.8 and 94.0 ± 2.8 kPa for aluminum substrate and muscle tissue in 15% xylose containing PUs (NPU-PEG-X-15%), respectively. The biodegradation of NPU-PEG-X-15% was also determined as 19.96 ± 1.04% after 8 weeks of incubation. Relative cell viability of xylose containing PU was above 86%. Moreover, 10% xylose containing NPU-PEG-X (NPU-PEG-X-10%) sample has favorable tissue response, and inflammatory reaction between 1 and 6 weeks implantation period. With high adhesiveness and biocompatibility properties, NPU-PEG-X can be used in the medical field as supporting materials for preventing the fluid leakage after abdominal surgery or wound closure.

Gelatin- and starch-based hydrogels. Part B: In vitro mesenchymal stem cell behavior on the hydrogels.

PubMed

Van Nieuwenhove, Ine; Salamon, Achim; Adam, Stefanie; Dubruel, Peter; Van Vlierberghe, Sandra; Peters, Kirsten

2017-04-01

Tissue regeneration often occurs only to a limited extent. By providing a three-dimensional matrix serving as a surrogate extracellular matrix that promotes adult stem cell adhesion, proliferation and differentiation, scaffold-guided tissue regeneration aims at overcoming this limitation. In this study, we applied hydrogels made from crosslinkable gelatin, the hydrolyzed form of collagen, and functionalized starch which were characterized in depth and optimized as described in Van Nieuwenhove et al., 2016. "Gelatin- and Starch-Based Hydrogels. Part A: Hydrogel Development, Characterization and Coating", Carbohydrate Polymers 152:129-39. Collagen is the main structural protein in animal connective tissue and the most abundant protein in mammals. Starch is a carbohydrate consisting of a mixture of amylose and amylopectin. Hydrogels were developed with varying chemical composition (ratio of starch to gelatin applied) and different degrees of methacrylation of the applied gelatin phase. The hydrogels used exhibited no adverse effect on viability of the stem cells cultured on them. Moreover, initial cell adhesion did not differ significantly between them, while the strongest proliferation was observed on the hydrogel with the highest degree of cross-linking. On the least crosslinked and thus most flexible hydrogels, the highest degree of adipogenic differentiation was found, while osteogenic differentiation was the strongest on the most rigid, starch-blended hydrogels. Hydrogel coating with extracellular matrix compounds aggrecan or fibronectin prior to cell seeding exhibited no significant effects. Thus, gelatin-based hydrogels can be optimized regarding maximum promotion of either adipogenic or osteogenic stem cell differentiation in vitro, which makes them promising candidates for in vivo evaluation in clinical studies aiming at either soft or hard tissue regeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Compressed single pixel imaging in the spatial frequency domain

PubMed Central

Torabzadeh, Mohammad; Park, Il-Yong; Bartels, Randy A.; Durkin, Anthony J.; Tromberg, Bruce J.

2017-01-01

Abstract. We have developed compressed sensing single pixel spatial frequency domain imaging (cs-SFDI) to characterize tissue optical properties over a wide field of view (35  mm×35  mm) using multiple near-infrared (NIR) wavelengths simultaneously. Our approach takes advantage of the relatively sparse spatial content required for mapping tissue optical properties at length scales comparable to the transport scattering length in tissue (ltr∼1  mm) and the high bandwidth available for spectral encoding using a single-element detector. cs-SFDI recovered absorption (μa) and reduced scattering (μs′) coefficients of a tissue phantom at three NIR wavelengths (660, 850, and 940 nm) within 7.6% and 4.3% of absolute values determined using camera-based SFDI, respectively. These results suggest that cs-SFDI can be developed as a multi- and hyperspectral imaging modality for quantitative, dynamic imaging of tissue optical and physiological properties. PMID:28300272

Plasticity within stem cell hierarchies in mammalian epithelia.

PubMed

Tetteh, Paul W; Farin, Henner F; Clevers, Hans

2015-02-01

Tissue homeostasis and regeneration are fueled by resident stem cells that have the capacity to self-renew, and to generate all the differentiated cell types that characterize a particular tissue. Classical models of such cellular hierarchies propose that commitment and differentiation occur unidirectionally, with the arrows 'pointing away' from the stem cell. Recent studies, all based on genetic lineage tracing, describe various strategies employed by epithelial stem cell hierarchies to replace damaged or lost cells. While transdifferentiation from one tissue type into another ('metaplasia') appears to be generally forbidden in nonpathological contexts, plasticity within an individual tissue stem cell hierarchy may be much more common than previously appreciated. In this review, we discuss recent examples of such plasticity in selected mammalian epithelia, highlighting the different modes of regeneration and their implications for our understanding of cellular hierarchy and tissue self-renewal. Copyright © 2014 Elsevier Ltd. All rights reserved.

A novel gellan-PVA nanofibrous scaffold for skin tissue regeneration: Fabrication and characterization.

PubMed

Vashisth, Priya; Nikhil, Kumar; Roy, Partha; Pruthi, Parul A; Singh, Rajesh P; Pruthi, Vikas

2016-01-20

In this investigation, we have introduced novel electrospun gellan based nanofibers as a hydrophilic scaffolding material for skin tissue regeneration. These nanofibers were fabricated using a blend mixture of gellan with polyvinyl alcohol (PVA). PVA reduced the repulsive force of resulting solution and lead to formation of uniform fibers with improved nanostructure. Field emission scanning electron microscopy (FESEM) confirmed the average diameter of nanofibers down to 50 nm. The infrared spectra (IR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis evaluated the crosslinking, thermal stability and highly crystalline nature of gellan-PVA nanofibers, respectively. Furthermore, the cell culture studies using human dermal fibroblast (3T3L1) cells established that these gellan based nanofibrous scaffold could induce improved cell adhesion and enhanced cell growth than conventionally proposed gellan based hydrogels and dry films. Importantly, the nanofibrous scaffold are biodegradable and could be potentially used as a temporary substrate/or biomedical graft to induce skin tissue regeneration. Copyright © 2015 Elsevier Ltd. All rights reserved.

A three-dimensional bioprinting system for use with a hydrogel-based biomaterial and printing parameter characterization.

PubMed

Song, Seung-Joon; Choi, Jaesoon; Park, Yong-Doo; Lee, Jung-Joo; Hong, So Young; Sun, Kyung

2010-11-01

Bioprinting is an emerging technology for constructing tissue or bioartificial organs with complex three-dimensional (3D) structures. It provides high-precision spatial shape forming ability on a larger scale than conventional tissue engineering methods, and simultaneous multiple components composition ability. Bioprinting utilizes a computer-controlled 3D printer mechanism for 3D biological structure construction. To implement minimal pattern width in a hydrogel-based bioprinting system, a study on printing characteristics was performed by varying printer control parameters. The experimental results showed that printing pattern width depends on associated printer control parameters such as printing flow rate, nozzle diameter, and nozzle velocity. The system under development showed acceptable feasibility of potential use for accurate printing pattern implementation in tissue engineering applications and is another example of novel techniques for regenerative medicine based on computer-aided biofabrication system. © 2010, Copyright the Authors. Artificial Organs © 2010, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Characterization of In Vitro Glucuronidation Clearance of a Range of Drugs in Human Kidney Microsomes: Comparison with Liver and Intestinal Glucuronidation and Impact of Albumin

PubMed Central

Gill, Katherine L.; Houston, J. Brian

2012-01-01

Previous studies have shown the importance of the addition of albumin for characterization of hepatic glucuronidation in vitro; however, no reports exist on the effects of albumin on renal or intestinal microsomal glucuronidation assays. This study characterized glucuronidation clearance (CLint, UGT) in human kidney, liver, and intestinal microsomes in the presence and absence of bovine serum albumin (BSA) for seven drugs with differential UDP-glucuronosyltransferase (UGT) 1A9 and UGT2B7 specificity, namely, diclofenac, ezetimibe, gemfibrozil, mycophenolic acid, naloxone, propofol, and telmisartan. The impact of renal CLint, UGT on accuracy of in vitro-in vivo extrapolation (IVIVE) of glucuronidation clearance was investigated. Inclusion of 1% BSA for acidic drugs and 2% for bases/neutral drugs in incubations was found to be suitable for characterization of CLint, UGT in different tissues. Although BSA increased CLint, UGT in all tissues, the extent was tissue- and drug-dependent. Scaled CLint, UGT in the presence of BSA ranged from 2.22 to 207, 0.439 to 24.4, and 0.292 to 23.8 ml · min−1 · g tissue−1 in liver, kidney, and intestinal microsomes. Renal CLint, UGT (per gram of tissue) was up to 2-fold higher in comparison with that for liver for UGT1A9 substrates; in contrast, CLint, UGT for UGT2B7 substrates represented approximately one-third of hepatic estimates. Scaled renal CLint, UGT (in the presence of BSA) was up to 30-fold higher than intestinal glucuronidation for the drugs investigated. Use of in vitro data obtained in the presence of BSA and inclusion of renal clearance improved the IVIVE of glucuronidation clearance, with 50% of drugs predicted within 2-fold of observed values. Characterization and consideration of kidney CLint, UGT is particularly important for UGT1A9 substrates. PMID:22275465

Super-lncRNAs: identification of lncRNAs that target super-enhancers via RNA:DNA:DNA triplex formation.

PubMed

Soibam, Benjamin

2017-11-01

Super-enhancers are characterized by high levels of Mediator binding and are major contributors to the expression of their associated genes. They exhibit high levels of local chromatin interactions and a higher order of local chromatin organization. On the other hand, lncRNAs can localize to specific DNA sites by forming a RNA:DNA:DNA triplex, which in turn can contribute to local chromatin organization. In this paper, we characterize a new class of lncRNAs called super-lncRNAs that target super-enhancers and which can contribute to the local chromatin organization of the super-enhancers. Using a logistic regression model based on the number of RNA:DNA:DNA triplex sites a lncRNA forms within the super-enhancer, we identify 442 unique super-lncRNA transcripts in 27 different human cell and tissue types; 70% of these super-lncRNAs were tissue restricted. They primarily harbor a single triplex-forming repeat domain, which forms an RNA:DNA:DNA triplex with multiple anchor DNA sites (originating from transposable elements) within the super-enhancers. Super-lncRNAs can be grouped into 17 different clusters based on the tissue or cell lines they target. Super-lncRNAs in a particular cluster share common short structural motifs and their corresponding super-enhancer targets are associated with gene ontology terms pertaining to the tissue or cell line. Super-lncRNAs may use these structural motifs to recruit and transport necessary regulators (such as transcription factors and Mediator complexes) to super-enhancers, influence chromatin organization, and act as spatial amplifiers for key tissue-specific genes associated with super-enhancers. © 2017 Soibam; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Office-Based Elastographic Technique for Quantifying Mechanical Properties of Skeletal Muscle

PubMed Central

Ballyns, Jeffrey J.; Turo, Diego; Otto, Paul; Shah, Jay P.; Hammond, Jennifer; Gebreab, Tadesse; Gerber, Lynn H.; Sikdar, Siddhartha

2012-01-01

Objectives Our objectives were to develop a new, efficient, and easy-to-administer approach to ultrasound elastography and assess its ability to provide quantitative characterization of viscoelastic properties of skeletal muscle in an outpatient clinical environment. We sought to show its validity and clinical utility in assessing myofascial trigger points, which are associated with myofascial pain syndrome. Methods Ultrasound imaging was performed while the muscle was externally vibrated at frequencies in the range of 60 to 200 Hz using a handheld vibrator. The spatial gradient of the vibration phase yielded the shear wave speed, which is related to the viscoelastic properties of tissue. The method was validated using a calibrated experimental phantom, the biceps brachii muscle in healthy volunteers (n = 6), and the upper trapezius muscle in symptomatic patients with axial neck pain (n = 13) and asymptomatic (pain-free) control participants (n = 9). Results Using the experimental phantom, our method was able to quantitatively measure the shear moduli with error rates of less than 20%. The mean shear modulus ± SD in the normal biceps brachii measured 12.5 ± 3.4 kPa, within the range of published values using more sophisticated methods. Shear wave speeds in active myofascial trigger points and the surrounding muscle tissue were significantly higher than those in normal tissue at high frequency excitations (>100 Hz; P < .05). Conclusions Off-the-shelf office-based equipment can be used to quantitatively characterize skeletal muscle viscoelastic properties with estimates comparable to those using more sophisticated methods. Our preliminary results using this method indicate that patients with spontaneous neck pain and symptomatic myofascial trigger points have increased tissue heterogeneity at the trigger point site and the surrounding muscle tissue. PMID:22837285

Office-based elastographic technique for quantifying mechanical properties of skeletal muscle.

PubMed

Ballyns, Jeffrey J; Turo, Diego; Otto, Paul; Shah, Jay P; Hammond, Jennifer; Gebreab, Tadesse; Gerber, Lynn H; Sikdar, Siddhartha

2012-08-01

Our objectives were to develop a new, efficient, and easy-to-administer approach to ultrasound elastography and assess its ability to provide quantitative characterization of viscoelastic properties of skeletal muscle in an outpatient clinical environment. We sought to show its validity and clinical utility in assessing myofascial trigger points, which are associated with myofascial pain syndrome. Ultrasound imaging was performed while the muscle was externally vibrated at frequencies in the range of 60 to 200 Hz using a handheld vibrator. The spatial gradient of the vibration phase yielded the shear wave speed, which is related to the viscoelastic properties of tissue. The method was validated using a calibrated experimental phantom, the biceps brachii muscle in healthy volunteers (n = 6), and the upper trapezius muscle in symptomatic patients with axial neck pain (n = 13) and asymptomatic (pain-free) control participants (n = 9). Using the experimental phantom, our method was able to quantitatively measure the shear moduli with error rates of less than 20%. The mean shear modulus ± SD in the normal biceps brachii measured 12.5 ± 3.4 kPa, within the range of published values using more sophisticated methods. Shear wave speeds in active myofascial trigger points and the surrounding muscle tissue were significantly higher than those in normal tissue at high frequency excitations (>100 Hz; P < .05). Off-the-shelf office-based equipment can be used to quantitatively characterize skeletal muscle viscoelastic properties with estimates comparable to those using more sophisticated methods. Our preliminary results using this method indicate that patients with spontaneous neck pain and symptomatic myofascial trigger points have increased tissue heterogeneity at the trigger point site and the surrounding muscle tissue.

Novel methods of time-resolved fluorescence data analysis for in-vivo tissue characterization: application to atherosclerosis.

PubMed

Jo, J A; Fang, Q; Papaioannou, T; Qiao, J H; Fishbein, M C; Dorafshar, A; Reil, T; Baker, D; Freischlag, J; Marcu, L

2004-01-01

This study investigates the ability of new analytical methods of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) data to characterize tissue in-vivo, such as the composition of atherosclerotic vulnerable plaques. A total of 73 TR-LIFS measurements were taken in-vivo from the aorta of 8 rabbits, and subsequently analyzed using the Laguerre deconvolution technique. The investigated spots were classified as normal aorta, thin or thick lesions, and lesions rich in either collagen or macrophages/foam-cells. Different linear and nonlinear classification algorithms (linear discriminant analysis, stepwise linear discriminant analysis, principal component analysis, and feedforward neural networks) were developed using spectral and TR features (ratios of intensity values and Laguerre expansion coefficients, respectively). Normal intima and thin lesions were discriminated from thick lesions (sensitivity >90%, specificity 100%) using only spectral features. However, both spectral and time-resolved features were necessary to discriminate thick lesions rich in collagen from thick lesions rich in foam cells (sensitivity >85%, specificity >93%), and thin lesions rich in foam cells from normal aorta and thin lesions rich in collagen (sensitivity >85%, specificity >94%). Based on these findings, we believe that TR-LIFS information derived from the Laguerre expansion coefficients can provide a valuable additional dimension for in-vivo tissue characterization.

Development and in vivo evaluation of self-microemulsion as delivery system for α-mangostin.

PubMed

Xu, Wen-Ke; Jiang, Hui; Yang, Kui; Wang, Ya-Qin; Zhang, Qian; Zuo, Jian

2017-03-01

α-Mangostin (MG) is a versatile bioactive compound isolated from mangosteen and possesses significant pharmacokinetic shortages. To augment the potential clinical efficacy, MG-loaded self-microemulsion (MG-SME) was designed and prepared in this study, and its potential as a drug loading system was evaluated based on the pharmacokinetic performance and tissue distribution feature. The formula of MG-SME was optimized by an orthogonal test under the guidance of ternary phase diagram, and the prepared MG-SME was characterized by encapsulation efficiency, size distribution, and morphology. Optimized high performance liquid chromatography method was employed to determine concentrations of MG and characterize the pharmacokinetic and tissue distribution features of MG in rodents. It was found that diluted MG-SME was characterized as spherical particles with a mean diameter of 24.6 nm and an encapsulation efficiency of 87.26%. The delivery system enhanced the area under the curve of MG by 4.75 times and increased the distribution in lymphatic organs. These findings suggested that SME as a nano-sized delivery system efficiently promoted the digestive tract absorption of MG and modified its distribution in tissues. The targeting feature and high oral bioavailability of MG-SME promised a good clinical efficacy, especially for immune diseases. Copyright © 2017. Published by Elsevier Taiwan.

Physiologically based pharmacokinetic model of amphotericin B disposition in rats following administration of deoxycholate formulation (Fungizone®): pooled analysis of published data.

PubMed

Kagan, Leonid; Gershkovich, Pavel; Wasan, Kishor M; Mager, Donald E

2011-06-01

The time course of tissue distribution of amphotericin B (AmB) has not been sufficiently characterized despite its therapeutic importance and an apparent disconnect between plasma pharmacokinetics and clinical outcomes. The goals of this work were to develop and evaluate a physiologically based pharmacokinetic (PBPK) model to characterize the disposition properties of AmB administered as deoxycholate formulation in healthy rats and to examine the utility of the PBPK model for interspecies scaling of AmB pharmacokinetics. AmB plasma and tissue concentration-time data, following single and multiple intravenous administration of Fungizone® to rats, from several publications were combined for construction of the model. Physiological parameters were fixed to literature values. Various structural models for single organs were evaluated, and the whole-body PBPK model included liver, spleen, kidney, lung, heart, gastrointestinal tract, plasma, and remainder compartments. The final model resulted in a good simultaneous description of both single and multiple dose data sets. Incorporation of three subcompartments for spleen and kidney tissues was required for capturing a prolonged half-life in these organs. The predictive performance of the final PBPK model was assessed by evaluating its utility in predicting pharmacokinetics of AmB in mice and humans. Clearance and permeability-surface area terms were scaled with body weight. The model demonstrated good predictions of plasma AmB concentration-time profiles for both species. This modeling framework represents an important basis that may be further utilized for characterization of formulation- and disease-related factors in AmB pharmacokinetics and pharmacodynamics.

Few-mode fiber detection for tissue characterization in optical coherence tomography

NASA Astrophysics Data System (ADS)

Eugui, Pablo; Lichtenegger, Antonia; Augustin, Marco; Harper, Danielle J.; Fialová, Stanislava; Wartak, Andreas; Hitzenberger, Christoph K.; Baumann, Bernhard

2017-07-01

A few-mode fiber based detection for OCT systems is presented. The capability of few-mode fibers for delivering light through different fiber paths enables the application of these fibers for angular scattering tissue character- ization. Since the optical path lengths traveled in the fiber change between the fiber modes, the OCT image information will be reconstructed at different depth positions, separating the directly backscattered light from the light scattered at other angles. Using the proposed method, the relation between the angle of reflection from the sample and the respective modal intensity distribution was investigated. The system was demonstrated for imaging ex-vivo brain tissue samples of patients with Alzheimer's disease.

Biodegradable polydepsipeptides.

PubMed

Feng, Yakai; Guo, Jintang

2009-02-01

This paper reviews the synthesis, characterization, biodegradation and usage of bioresorbable polymers based on polydepsipeptides. The ring-opening polymerization of morpholine-2,5-dione derivatives using organic Sn and enzyme lipase is discussed. The dependence of the macroscopic properties of the block copolymers on their structure is also presented. Bioresorbable polymers based on polydepsipeptides could be used as biomaterials in drug controlled release, tissue engineering scaffolding and shape-memory materials.

Viral tropism and pathology associated with viral hemorrhagic septicemia in larval and juvenile Pacific herring

USGS Publications Warehouse

Lovy, Jan; Lewis, N.L.; Hershberger, P.K.; Bennett, W.; Meyers, T.R.; Garver, K.A.

2012-01-01

Viral hemorrhagic septicemia virus (VHSV) genotype IVa causes mass mortality in wild Pacific herring, a species of economic value, in the Northeast Pacific Ocean. Young of the year herring are particularly susceptible and can be carriers of the virus. To understand its pathogenesis, tissue and cellular tropisms of VHSV in larval and juvenile Pacific herring were investigated with immunohistochemistry, transmission electron microscopy, and viral tissue titer. In larval herring, early viral tropism for epithelial tissues (6d post-exposure) was indicated by foci of epidermal thickening that contained heavy concentrations of virus. This was followed by a cellular tropism for fibroblasts within the fin bases and the dermis, but expanded to cells of the kidney, liver, pancreas, gastrointestinal tract and meninges in the brain. Among wild juvenile herring that underwent a VHS epizootic in the laboratory, the disease was characterized by acute and chronic phases of death. Fish that died during the acute phase had systemic infections in tissues including the submucosa of the gastrointestinal tract, spleen, kidney, liver, and meninges. The disease then transitioned into a chronic phase that was characterized by the appearance of neurological signs including erratic and corkscrew swimming and darkening of the dorsal skin. During the chronic phase viral persistence occurred in nervous tissues including meninges and brain parenchymal cells and in one case in peripheral nerves, while virus was mostly cleared from the other tissues. The results demonstrate the varying VHSV tropisms dependent on the timing of infection and the importance of neural tissues for the persistence and perpetuation of chronic infections in Pacific herring.

A Computational Clonal Analysis of the Developing Mouse Limb Bud

PubMed Central

Marcon, Luciano; Arqués, Carlos G.; Torres, Miguel S.; Sharpe, James

2011-01-01

A comprehensive spatio-temporal description of the tissue movements underlying organogenesis would be an extremely useful resource to developmental biology. Clonal analysis and fate mappings are popular experiments to study tissue movement during morphogenesis. Such experiments allow cell populations to be labeled at an early stage of development and to follow their spatial evolution over time. However, disentangling the cumulative effects of the multiple events responsible for the expansion of the labeled cell population is not always straightforward. To overcome this problem, we develop a novel computational method that combines accurate quantification of 2D limb bud morphologies and growth modeling to analyze mouse clonal data of early limb development. Firstly, we explore various tissue movements that match experimental limb bud shape changes. Secondly, by comparing computational clones with newly generated mouse clonal data we are able to choose and characterize the tissue movement map that better matches experimental data. Our computational analysis produces for the first time a two dimensional model of limb growth based on experimental data that can be used to better characterize limb tissue movement in space and time. The model shows that the distribution and shapes of clones can be described as a combination of anisotropic growth with isotropic cell mixing, without the need for lineage compartmentalization along the AP and PD axis. Lastly, we show that this comprehensive description can be used to reassess spatio-temporal gene regulations taking tissue movement into account and to investigate PD patterning hypothesis. PMID:21347315

Signal transduction and oxidative processes in sinonasal polyposis.

PubMed

Cannady, Steven B; Batra, Pete S; Leahy, Rachel; Citardi, Martin J; Janocha, Allison; Ricci, Kristin; Comhair, Suzy A A; Bodine, Melanie; Wang, Zeneng; Hazen, Stanley L; Erzurum, Serpil C

2007-12-01

Nasal polyposis is characterized by impaired regulation of nasal tissue growth and is associated with chronic inflammation, sinus infections, and low levels of nitric oxide (NO). Based on its critical role in mediating cell growth and antimicrobial function, decrease of NO levels has been implicated in the pathogenesis of nasal polyposis. We sought to evaluate mechanisms for the low NO level in polyposis, including factors regulating NO synthase (NOS) expression and activity and NO consumptive processes in nasal epithelial cells and nasal lavage fluid. Eighteen patients with nasal polyposis and 8 healthy control subjects were studied. Nasal brushings, nasal lavage fluid, and nasal biopsy specimens were collected and analyzed. NO metabolite levels (nitrite and nitrate) in nasal lavage fluid from patients with polyps were less than those in control subjects, but activation of signal transduction and inducer of transcription 1, which regulates inducible NOS gene expression and protein expression, was present at higher levels in polyp than in healthy control tissue. Levels of arginine, methylarginine, and endogenous NOS inhibitors were similar between polyp and control tissue. In contrast, superoxide dismutase activity of polyp tissues was lower than that seen in control tissue and associated with increased nitrotyrosine, a biomarker of oxidant consumptive products of NO. Taken together, these data suggest that the nasal polyp environment is characterized by abnormalities in NO metabolism that might predispose to altered regulation of tissue growth and infection. Identification of NO metabolic abnormalities might lead to novel treatments for sinonasal polyposis targeted against the pathways identified within this study.

Characterization of inter-tissue and inter-strain variability of TCE glutathione conjugation metabolites DCVG, DCVC, and NAcDCVC in the mouse.

PubMed

Luo, Yu-Syuan; Furuya, Shinji; Chiu, Weihsueh; Rusyn, Ivan

2018-01-01

Trichloroethylene (TCE) is a ubiquitous environmental toxicant that is a liver and kidney carcinogen. Conjugation of TCE with glutathione (GSH) leads to formation of nepthrotoxic and mutagenic metabolites postulated to be critical for kidney cancerdevelopment; however, relatively little is known regarding their tissue levels as previous analytical methods for their detection lacked sensitivity. Here, an LC-MS/MS-based method for simultaneous detection of S-(1,2-dichlorovinyl)-glutathione (DCVG), S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NAcDCVC) in multiple mouse tissues was developed. This analytical method is rapid, sensitive (limits of detection (LOD) 3-30 fmol across metabolites and tissues), and robust to quantify all three metabolites in liver, kidneys, and serum. The method was used to characterize inter-tissue and inter-strain variability in formation of conjugative metabolites of TCE. Single oral dose of TCE (24, 240 or 800 mg/kg) was administered to male mice from 20 inbred strains of Collaborative Cross. Inter-strain variability in the levels of DCVG, DCVC, and NAcDCVC (GSD = 1.6-2.9) was observed. Whereas NAcDCVC was distributed equally among analyzed tissues, highest levels of DCVG were detected in liver and DCVC in kidneys. Evidence indicated that inter-strain variability in conjugative metabolite formation of TCE might affect susceptibility to adverse health effects and that this method might aid in filling data gaps in human health assessment of TCE.

Characterization of focal muscle compression under impact loading

NASA Astrophysics Data System (ADS)

Butler, B. J.; Sory, D. R.; Nguyen, T.-T. N.; Proud, W. G.; Williams, A.; Brown, K. A.

2017-01-01

In modern wars over 70% of combat wounds are to the extremities. These injuries are characterized by disruption and contamination of the limb soft tissue envelope. The extent of this tissue trauma and contamination determine the outcome of the extremity injury. In military injury, common post-traumatic complications at amputation sites include heterotopic ossification (formation of bone in soft tissue), and severe soft tissue and bone infections. We are currently developing a model of soft tissue injury that recreates pathologies observed in combat injuries. Here we present characterization of a controlled focal compression of the rabbit flexor carpi ulnaris (FCU) muscle group. The FCU was previously identified as a suitable site for studying impact injury because its muscle belly can easily be mobilized from the underlying bone without disturbing anatomical alignment in the limb. We show how macroscopic changes in tissue organization, as visualized using optical microscopy, can be correlated with data from temporally resolved traces of loading conditions.

Infused polymers for cell sheet release

NASA Astrophysics Data System (ADS)

Juthani, Nidhi; Howell, Caitlin; Ledoux, Haylea; Sotiri, Irini; Kelso, Susan; Kovalenko, Yevgen; Tajik, Amanda; Vu, Thy L.; Lin, Jennifer J.; Sutton, Amy; Aizenberg, Joanna

2016-05-01

Tissue engineering using whole, intact cell sheets has shown promise in many cell-based therapies. However, current systems for the growth and release of these sheets can be expensive to purchase or difficult to fabricate, hindering their widespread use. Here, we describe a new approach to cell sheet release surfaces based on silicone oil-infused polydimethylsiloxane. By coating the surfaces with a layer of fibronectin (FN), we were able to grow mesenchymal stem cells to densities comparable to those of tissue culture polystyrene controls (TCPS). Simple introduction of oil underneath an edge of the sheet caused it to separate from the substrate. Characterization of sheets post-transfer showed that they retain their FN layer and morphology, remain highly viable, and are able to grow and proliferate normally after transfer. We expect that this method of cell sheet growth and detachment may be useful for low-cost, flexible, and customizable production of cellular layers for tissue engineering.

Infused polymers for cell sheet release

PubMed Central

Juthani, Nidhi; Howell, Caitlin; Ledoux, Haylea; Sotiri, Irini; Kelso, Susan; Kovalenko, Yevgen; Tajik, Amanda; Vu, Thy L.; Lin, Jennifer J.; Sutton, Amy; Aizenberg, Joanna

2016-01-01

Tissue engineering using whole, intact cell sheets has shown promise in many cell-based therapies. However, current systems for the growth and release of these sheets can be expensive to purchase or difficult to fabricate, hindering their widespread use. Here, we describe a new approach to cell sheet release surfaces based on silicone oil-infused polydimethylsiloxane. By coating the surfaces with a layer of fibronectin (FN), we were able to grow mesenchymal stem cells to densities comparable to those of tissue culture polystyrene controls (TCPS). Simple introduction of oil underneath an edge of the sheet caused it to separate from the substrate. Characterization of sheets post-transfer showed that they retain their FN layer and morphology, remain highly viable, and are able to grow and proliferate normally after transfer. We expect that this method of cell sheet growth and detachment may be useful for low-cost, flexible, and customizable production of cellular layers for tissue engineering. PMID:27189419

Infused polymers for cell sheet release.

PubMed

Juthani, Nidhi; Howell, Caitlin; Ledoux, Haylea; Sotiri, Irini; Kelso, Susan; Kovalenko, Yevgen; Tajik, Amanda; Vu, Thy L; Lin, Jennifer J; Sutton, Amy; Aizenberg, Joanna

2016-05-18

Tissue engineering using whole, intact cell sheets has shown promise in many cell-based therapies. However, current systems for the growth and release of these sheets can be expensive to purchase or difficult to fabricate, hindering their widespread use. Here, we describe a new approach to cell sheet release surfaces based on silicone oil-infused polydimethylsiloxane. By coating the surfaces with a layer of fibronectin (FN), we were able to grow mesenchymal stem cells to densities comparable to those of tissue culture polystyrene controls (TCPS). Simple introduction of oil underneath an edge of the sheet caused it to separate from the substrate. Characterization of sheets post-transfer showed that they retain their FN layer and morphology, remain highly viable, and are able to grow and proliferate normally after transfer. We expect that this method of cell sheet growth and detachment may be useful for low-cost, flexible, and customizable production of cellular layers for tissue engineering.

Intrinsic fluorescence of protein in turbid media using empirical relation based on Monte Carlo lookup table

NASA Astrophysics Data System (ADS)

Einstein, Gnanatheepam; Udayakumar, Kanniyappan; Aruna, Prakasarao; Ganesan, Singaravelu

2017-03-01

Fluorescence of Protein has been widely used in diagnostic oncology for characterizing cellular metabolism. However, the intensity of fluorescence emission is affected due to the absorbers and scatterers in tissue, which may lead to error in estimating exact protein content in tissue. Extraction of intrinsic fluorescence from measured fluorescence has been achieved by different methods. Among them, Monte Carlo based method yields the highest accuracy for extracting intrinsic fluorescence. In this work, we have attempted to generate a lookup table for Monte Carlo simulation of fluorescence emission by protein. Furthermore, we fitted the generated lookup table using an empirical relation. The empirical relation between measured and intrinsic fluorescence is validated using tissue phantom experiments. The proposed relation can be used for estimating intrinsic fluorescence of protein for real-time diagnostic applications and thereby improving the clinical interpretation of fluorescence spectroscopic data.

A sparsity-based simplification method for segmentation of spectral-domain optical coherence tomography images

NASA Astrophysics Data System (ADS)

Meiniel, William; Gan, Yu; Olivo-Marin, Jean-Christophe; Angelini, Elsa

2017-08-01

Optical coherence tomography (OCT) has emerged as a promising image modality to characterize biological tissues. With axio-lateral resolutions at the micron-level, OCT images provide detailed morphological information and enable applications such as optical biopsy and virtual histology for clinical needs. Image enhancement is typically required for morphological segmentation, to improve boundary localization, rather than enrich detailed tissue information. We propose to formulate image enhancement as an image simplification task such that tissue layers are smoothed while contours are enhanced. For this purpose, we exploit a Total Variation sparsity-based image reconstruction, inspired by the Compressed Sensing (CS) theory, but specialized for images with structures arranged in layers. We demonstrate the potential of our approach on OCT human heart and retinal images for layers segmentation. We also compare our image enhancement capabilities to the state-of-the-art denoising techniques.

Unified quantitative characterization of epithelial tissue development

PubMed Central

Guirao, Boris; Rigaud, Stéphane U; Bosveld, Floris; Bailles, Anaïs; López-Gay, Jesús; Ishihara, Shuji; Sugimura, Kaoru

2015-01-01

Understanding the mechanisms regulating development requires a quantitative characterization of cell divisions, rearrangements, cell size and shape changes, and apoptoses. We developed a multiscale formalism that relates the characterizations of each cell process to tissue growth and morphogenesis. Having validated the formalism on computer simulations, we quantified separately all morphogenetic events in the Drosophila dorsal thorax and wing pupal epithelia to obtain comprehensive statistical maps linking cell and tissue scale dynamics. While globally cell shape changes, rearrangements and divisions all significantly participate in tissue morphogenesis, locally, their relative participations display major variations in space and time. By blocking division we analyzed the impact of division on rearrangements, cell shape changes and tissue morphogenesis. Finally, by combining the formalism with mechanical stress measurement, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our formalism provides a novel and rigorous approach to uncover mechanisms governing tissue development. DOI: http://dx.doi.org/10.7554/eLife.08519.001 PMID:26653285

Ex Vivo Characterization of Canine Liver Tissue Viscoelasticity Following High Intensity Focused Ultrasound (HIFU) Ablation

PubMed Central

Shahmirzadi, Danial; Hou, Gary Y.; Chen, Jiangang; Konofagou, Elisa E.

2014-01-01

Elasticity imaging has shown great promise in detecting High Intensity Focused Ultrasound (HIFU) lesions based on their distinct biomechanical properties. However, quantitative mechanical properties of the tissue and the optimal intensity for obtaining the best contrast parameters remain scarce. In this study, fresh canine livers were ablated using combinations of ISPTA intensities of 5.55, 7.16 and 9.07 kW/cm2 and time durations of 10 and 30 s ex vivo; leading to six groups of ablated tissues. Biopsy samples were then interrogated using dynamic shear mechanical testing within the range of 0.1-10 Hz to characterize the post-ablation tissue viscoelastic properties. All mechanical parameters were found to be frequency dependent. Compared to the unablated cases, all six groups of ablated tissues showed statistically-significant higher complex shear modulus and shear viscosity. However, among the ablated groups, both complex shear modulus and shear viscosity were found to monotonically increase in groups 1-4 (5.55 kW/cm2 for 10 s, 7.16 kW/cm2 for 10 s, 9.07 kW/cm2 & 10 s, and 5.55 kW/cm2 & 30 s, respectively), but decrease in groups 5 and 6 (7.16 kW/cm2 for 30 s, and 9.07 kW/cm2 for 30 s, respectively). For groups 5 and 6, the temperature was expected to exceed the boiling point, and therefore, the decreased stiffening could be due to the compromised integrity of the tissue microstructure. Future studies are needed to estimate the tissue mechanical properties in vivo and perform real-time monitoring of tissue alterations during ablation. PMID:24315395

Characterization of elasticity and hydration of composite hydrogel based on collagen-iota carrageenan as a corneal tissue engineering

NASA Astrophysics Data System (ADS)

Rinawati, M.; Triastuti, J.; Pursetyo, K. T.

2018-04-01

The cornea is a refractive element of the eye that serves to continue the stimulation of light into the eye it has a clear, transparent, elastic and relatively thick tissue. Factors caused corneal blindness, are dystrophy, keratoconus, corneal scaring. Hydrogels can be made from polysaccharide derivatives that have gelation properties such as iota carrageenan. Therefore, it is a need to develop composite hydrogel based collagen-iota carragenan as an engineeried corneal tissue with high elasticity and hydration properties. Collagen hydrogel has a maximum water content an has equlibrium up to 40 %, less than the human cornea, 81 % and under normal hydration conditions, the human cornea can transmit 87 % of visible light. In addition, the refractive index on the surface of the cornea with air is 1.375-1.380. Based on this study, it is necessary to conduct research on the development and composition of hydrogel composite collagen-iota carrageen hydrogen based on. The best result was K5 (5:5) treatment, which has the equilibrium water content of 87.07 % and viscosity of 10.7346 Pa.s.

Characterizing white matter tissue in large strain via asymmetric indentation and inverse finite element modeling.

PubMed

Feng, Yuan; Lee, Chung-Hao; Sun, Lining; Ji, Songbai; Zhao, Xuefeng

2017-01-01

Characterizing the mechanical properties of white matter is important to understand and model brain development and injury. With embedded aligned axonal fibers, white matter is typically modeled as a transversely isotropic material. However, most studies characterize the white matter tissue using models with a single anisotropic invariant or in a small-strain regime. In this study, we combined a single experimental procedure - asymmetric indentation - with inverse finite element (FE) modeling to estimate the nearly incompressible transversely isotropic material parameters of white matter. A minimal form comprising three parameters was employed to simulate indentation responses in the large-strain regime. The parameters were estimated using a global optimization procedure based on a genetic algorithm (GA). Experimental data from two indentation configurations of porcine white matter, parallel and perpendicular to the axonal fiber direction, were utilized to estimate model parameters. Results in this study confirmed a strong mechanical anisotropy of white matter in large strain. Further, our results suggested that both indentation configurations are needed to estimate the parameters with sufficient accuracy, and that the indenter-sample friction is important. Finally, we also showed that the estimated parameters were consistent with those previously obtained via a trial-and-error forward FE method in the small-strain regime. These findings are useful in modeling and parameterization of white matter, especially under large deformation, and demonstrate the potential of the proposed asymmetric indentation technique to characterize other soft biological tissues with transversely isotropic properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

Stromal cell-based immunotherapy in transplantation.

PubMed

Charles, Ronald; Lu, Lina; Qian, Shiguang; Fung, John J

2011-12-01

Organs are composed of parenchymal cells that characterize organ function and nonparenchymal cells that are composed of cells in transit, as well as tissue connective tissue, also referred to as tissue stromal cells. It was originally thought that these tissue stromal cells provided only structural and functional support for parenchymal cells and were relatively inert. However, we have come to realize that tissue stromal cells, not restricted to in the thymus and lymphoid organs, also play an active role in modulating the immune system and its response to antigens. The recognition of these elements and the elucidation of their mechanisms of action have provided valuable insight into peripheral immune regulation. Extrapolation of these principles may allow us to utilize their potential for clinical application. In this article, we will summarize a number of tissue stromal elements/cell types that have been shown to induce hyporesponsiveness to transplants. We will also discuss the mechanisms by which these stromal cells create a tolerogenic environment, which in turn results in long-term allograft survival.

On the Use of Machine Learning Techniques for the Mechanical Characterization of Soft Biological Tissues.

PubMed

Cilla, M; Pérez-Rey, I; Martínez, M A; Peña, Estefania; Martínez, Javier

2018-06-23

Motivated by the search for new strategies for fitting a material model, a new approach is explored in the present work. The use of numerical and complex algorithms based on machine learning techniques such as support vector machines for regression, bagged decision trees and artificial neural networks is proposed for solving the parameter identification of constitutive laws for soft biological tissues. First, the mathematical tools were trained with analytical uniaxial data (circumferential and longitudinal directions) as inputs, and their corresponding material parameters of the Gasser, Ogden and Holzapfel strain energy function as outputs. The train and test errors show great efficiency during the training process in finding correlations between inputs and outputs; besides, the correlation coefficients were very close to 1. Second, the tool was validated with unseen observations of analytical circumferential and longitudinal uniaxial data. The results show an excellent agreement between the prediction of the material parameters of the SEF and the analytical curves. Finally, data from real circumferential and longitudinal uniaxial tests on different cardiovascular tissues were fitted, thus the material model of these tissues was predicted. We found that the method was able to consistently identify model parameters, and we believe that the use of these numerical tools could lead to an improvement in the characterization of soft biological tissues. This article is protected by copyright. All rights reserved.

Age estimation based on aspartic acid racemization in elastin from the yellow ligaments.

PubMed

Ritz-Timme, S; Laumeier, I; Collins, M

2003-04-01

The yellow ligaments of the spine are characterized by an exceptionally high content of elastin, a protein with a proved longevity in several human tissues. This unique biochemical composition suggested a suitability of yellow ligaments for age estimation based on aspartic acid racemization (AAR), which was tested by determination of AAR in total tissue specimens and in purified elastin from yellow ligaments of individuals of known age. AAR was found to increase with age in both sample sets. The purified elastin samples exhibited a much faster kinetics than the total tissue, with ca. 3.7-4.6-fold higher apparent rates. The relationship between AAR and age was much closer in the purified elastin samples ( r=0.96-0.99) and it can therefore be used as a basis for biochemical age estimation. The analysis of total tissue samples cannot be recommended since the AAR values can be strongly influenced even by slight, histologically non-detectable variations in the collagen content. Age estimation based on AAR in purified elastin from yellow ligaments may be a valuable additional tool in the identification of unidentified cadavers, especially in cases where other methods cannot be applied (e.g. no available teeth, body parts).

Bacterial and diazotrophic diversities of endophytes in Dendrobium catenatum determined through barcoded pyrosequencing

PubMed Central

Li, Ou; Sun, Lihua; Guan, Chenglin; Kong, Dedong

2017-01-01

As an epiphyte orchid, Dendrobium catenatum relies on microorganisms for requisite nutrients. Metagenome pyrosequencing based on 16S rRNA and nifH genes was used to characterize the bacterial and diazotrophic communities associated with D. catenatum collected from 5 districts in China. Based on Meta-16S rRNA sequencing, 22 bacterial phyla and 699 genera were identified, distributed as 125 genera from 8 phyla and 319 genera from 10 phyla shared by all the planting bases and all the tissues, respectively. The predominant Proteobacteria varied from 71.81% (GZ) to 96.08% (YN), and Delftia (10.39–38.42%), Burkholderia (2.71–15.98%), Escherichia/Shigella (4.90–25.12%), Pseudomonas (2.68–30.72%) and Sphingomonas (1.83–2.05%) dominated in four planting bases. Pseudomonas (17.94–22.06%), Escherichia/Shigella (6.59–11.59%), Delftia (9.65–22.14%) and Burkholderia (3.12–11.05%) dominated in all the tissues. According to Meta-nifH sequencing, 4 phyla and 45 genera were identified, while 17 genera and 24 genera from 4 phyla were shared by all the planting bases and all the tissues, respectively. Burkholderia and Bradyrhizobium were the most popular in the planting bases, followed by Methylovirgula and Mesorhizobium. Mesorhizobium was the most popular in different tissues, followed by Beijerinckia, Xanthobacter, and Burkholderia. Among the genera, 39 were completely overlapped with the results based on the 16S rRNA gene. In conclusion, abundant bacteria and diazotrophs were identified in common in different tissues of D. catenatum from five planting bases, which might play a great role in the supply of nutrients such as nitrogen. The exact abundance of phylum and genus on the different tissues from different planting bases need deeper sequencing with more samples. PMID:28931073

Design and characterization of a dead-time regime enhanced early photon projection imaging system

NASA Astrophysics Data System (ADS)

Sinha, L.; Fogarty, M.; Zhou, W.; Giudice, A.; Brankov, J. G.; Tichauer, K. M.

2018-04-01

Scattering of visible and near-infrared light in biological tissue reduces spatial resolution for imaging of tissues thicker than 100 μm. In this study, an optical projection imaging system is presented and characterized that exploits the dead-time characteristics typical of photon counting modules based on single photon avalanche diodes (SPADs). With this system, it is possible to attenuate the detection of more scattered late-arriving photons, such that detection of less scattered early-arriving photons can be enhanced with increased light intensity, without being impeded by the maximum count rate of the SPADs. The system has the potential to provide transmittance-based anatomical information or fluorescence-based functional information (with slight modification in the instrumentation) of biological samples with improved resolution in the mesoscopic domain (0.1-2 cm). The system design, calibration, stability, and performance were evaluated using simulation and experimental phantom studies. The proposed system allows for the detection of very-rare early-photons at a higher frequency and with a better signal-to-noise ratio. The experimental results demonstrated over a 3.4-fold improvement in the spatial resolution using early photon detection vs. conventional detection, and a 1000-fold improvement in imaging time using enhanced early detection vs. conventional early photon detection in a 4-mm thick phantom with a tissue-equivalent absorption coefficient of μa = 0.05 mm-1 and a reduced scattering coefficient of μs' = 5 mm-1.

Morph-X-Select: Morphology-based tissue aptamer selection for ovarian cancer biomarker discovery

PubMed Central

Wang, Hongyu; Li, Xin; Volk, David E.; Lokesh, Ganesh L.-R.; Elizondo-Riojas, Miguel-Angel; Li, Li; Nick, Alpa M.; Sood, Anil K.; Rosenblatt, Kevin P.; Gorenstein, David G.

2016-01-01

High affinity aptamer-based biomarker discovery has the advantage of simultaneously discovering an aptamer affinity reagent and its target biomarker protein. Here, we demonstrate a morphology-based tissue aptamer selection method that enables us to use tissue sections from individual patients and identify high-affinity aptamers and their associated target proteins in a systematic and accurate way. We created a combinatorial DNA aptamer library that has been modified with thiophosphate substitutions of the phosphate ester backbone at selected 5′dA positions for enhanced nuclease resistance and targeting. Based on morphological assessment, we used image-directed laser microdissection (LMD) to dissect regions of interest bound with the thioaptamer (TA) library and further identified target proteins for the selected TAs. We have successfully identified and characterized the lead candidate TA, V5, as a vimentin-specific sequence that has shown specific binding to tumor vasculature of human ovarian tissue and human microvascular endothelial cells. This new Morph-X-Select method allows us to select high-affinity aptamers and their associated target proteins in a specific and accurate way, and could be used for personalized biomarker discovery to improve medical decision-making and to facilitate the development of targeted therapies to achieve more favorable outcomes. PMID:27839510

Models of temporal enhanced ultrasound data for prostate cancer diagnosis: the impact of time-series order

NASA Astrophysics Data System (ADS)

Nahlawi, Layan; Goncalves, Caroline; Imani, Farhad; Gaed, Mena; Gomez, Jose A.; Moussa, Madeleine; Gibson, Eli; Fenster, Aaron; Ward, Aaron D.; Abolmaesumi, Purang; Mousavi, Parvin; Shatkay, Hagit

2017-03-01

Recent studies have shown the value of Temporal Enhanced Ultrasound (TeUS) imaging for tissue characterization in transrectal ultrasound-guided prostate biopsies. Here, we present results of experiments designed to study the impact of temporal order of the data in TeUS signals. We assess the impact of variations in temporal order on the ability to automatically distinguish benign prostate-tissue from malignant tissue. We have previously used Hidden Markov Models (HMMs) to model TeUS data, as HMMs capture temporal order in time series. In the work presented here, we use HMMs to model malignant and benign tissues; the models are trained and tested on TeUS signals while introducing variation to their temporal order. We first model the signals in their original temporal order, followed by modeling the same signals under various time rearrangements. We compare the performance of these models for tissue characterization. Our results show that models trained over the original order-preserving signals perform statistically significantly better for distinguishing between malignant and benign tissues, than those trained on rearranged signals. The performance degrades as the amount of temporal-variation increases. Specifically, accuracy of tissue characterization decreases from 85% using models trained on original signals to 62% using models trained and tested on signals that are completely temporally-rearranged. These results indicate the importance of order in characterization of tissue malignancy from TeUS data.

In-Depth Characterization and Validation of Human Urine Metabolomes Reveal Novel Metabolic Signatures of Lower Urinary Tract Symptoms

NASA Astrophysics Data System (ADS)

Hao, Ling; Greer, Tyler; Page, David; Shi, Yatao; Vezina, Chad M.; Macoska, Jill A.; Marker, Paul C.; Bjorling, Dale E.; Bushman, Wade; Ricke, William A.; Li, Lingjun

2016-08-01

Lower urinary tract symptoms (LUTS) are a range of irritative or obstructive symptoms that commonly afflict aging population. The diagnosis is mostly based on patient-reported symptoms, and current medication often fails to completely eliminate these symptoms. There is a pressing need for objective non-invasive approaches to measure symptoms and understand disease mechanisms. We developed an in-depth workflow combining urine metabolomics analysis and machine learning bioinformatics to characterize metabolic alterations and support objective diagnosis of LUTS. Machine learning feature selection and statistical tests were combined to identify candidate biomarkers, which were statistically validated with leave-one-patient-out cross-validation and absolutely quantified by selected reaction monitoring assay. Receiver operating characteristic analysis showed highly-accurate prediction power of candidate biomarkers to stratify patients into disease or non-diseased categories. The key metabolites and pathways may be possibly correlated with smooth muscle tone changes, increased collagen content, and inflammation, which have been identified as potential contributors to urinary dysfunction in humans and rodents. Periurethral tissue staining revealed a significant increase in collagen content and tissue stiffness in men with LUTS. Together, our study provides the first characterization and validation of LUTS urinary metabolites and pathways to support the future development of a urine-based diagnostic test for LUTS.

Tracing molecular dephasing in biological tissue

NASA Astrophysics Data System (ADS)

Mokim, M.; Carruba, C.; Ganikhanov, F.

2017-10-01

We demonstrate the quantitative spectroscopic characterization and imaging of biological tissue using coherent time-domain microscopy with a femtosecond resolution. We identify tissue constituents and perform dephasing time (T2) measurements of characteristic Raman active vibrations. This was shown in subcutaneous mouse fat embedded within collagen rich areas of the dermis and the muscle connective tissue. The demonstrated equivalent spectral resolution (<0.3 cm-1) is an order of magnitude better compared to commonly used frequency-domain methods for characterization of biological media. This provides with the important dimensions and parameters in biological media characterization and can become an effective tool in detecting minute changes in the bio-molecular composition and environment that is critical for molecular level diagnosis.

Breast composition measurement with a cadmium-zinc-telluride based spectral computed tomography system

PubMed Central

Ding, Huanjun; Ducote, Justin L.; Molloi, Sabee

2012-01-01

Purpose: To investigate the feasibility of breast tissue composition in terms of water, lipid, and protein with a cadmium-zinc-telluride (CZT) based computed tomography (CT) system to help better characterize suspicious lesions. Methods: Simulations and experimental studies were performed using a spectral CT system equipped with a CZT-based photon-counting detector with energy resolution. Simulations of the figure-of-merit (FOM), the signal-to-noise ratio (SNR) of the dual energy image with respect to the square root of mean glandular dose (MGD), were performed to find the optimal configuration of the experimental acquisition parameters. A calibration phantom 3.175 cm in diameter was constructed from polyoxymethylene plastic with cylindrical holes that were filled with water and oil. Similarly, sized samples of pure adipose and pure lean bovine tissues were used for the three-material decomposition. Tissue composition results computed from the images were compared to the chemical analysis data of the tissue samples. Results: The beam energy was selected to be 100 kVp with a splitting energy of 40 keV. The tissue samples were successfully decomposed into water, lipid, and protein contents. The RMS error of the volumetric percentage for the three-material decomposition, as compared to data from the chemical analysis, was estimated to be approximately 5.7%. Conclusions: The results of this study suggest that the CZT-based photon-counting detector may be employed in the CT system to quantify the water, lipid, and protein mass densities in tissue with a relatively good agreement. PMID:22380361

A PDMS-Based Conical-Well Microelectrode Array for Surface Stimulation and Recording of Neural Tissues

PubMed Central

Guo, Liang; Meacham, Kathleen W.; Hochman, Shawn

2012-01-01

A method for fabricating polydimethylsiloxane (PDMS)-based microelectrode arrays (MEAs) featuring novel conical-well microelectrodes is described. The fabrication technique is reliable and efficient, and facilitates controllability over both the depth and the slope of the conical wells. Because of the high PDMS elasticity (as compared to other MEA substrate materials), this type of compliant MEA is promising for acute and chronic implantation in applications that benefit from conformable device contact with biological tissue surfaces and from minimal tissue damage. The primary advantage of the conical-well microelectrodes—when compared to planar electrodes—is that they provide an improved contact on tissue surface, which potentially provides isolation of the electrode microenvironment for better electrical interfacing. The raised wells increase the uniformity of current density distributions at both the electrode and tissue surfaces, and they also protect the electrode material from mechanical damage (e.g. from rubbing against the tissue). Using this technique, electrodes have been fabricated with diameters as small as 10µm and arrays have been fabricated with center-to-center electrode spacings of 60µm. Experimental results are presented, describing electrode-profile characterization, electrode-impedance measurement, and MEA-performance evaluation on fiber bundle recruitment in spinal cord white matter. PMID:20550983

Influence of Tissue Microstructure on Shear Wave Speed Measurements in Plane Shear Wave Elastography: A Computational Study in Lossless Fibrotic Liver Media.

PubMed

Wang, Yu; Jiang, Jingfeng

2018-01-01

Shear wave elastography (SWE) has been used to measure viscoelastic properties for characterization of fibrotic livers. In this technique, external mechanical vibrations or acoustic radiation forces are first transmitted to the tissue being imaged to induce shear waves. Ultrasonically measured displacement/velocity is then utilized to obtain elastographic measurements related to shear wave propagation. Using an open-source wave simulator, k-Wave, we conducted a case study of the relationship between plane shear wave measurements and the microstructure of fibrotic liver tissues. Particularly, three different virtual tissue models (i.e., a histology-based model, a statistics-based model, and a simple inclusion model) were used to represent underlying microstructures of fibrotic liver tissues. We found underlying microstructures affected the estimated mean group shear wave speed (SWS) under the plane shear wave assumption by as much as 56%. Also, the elastic shear wave scattering resulted in frequency-dependent attenuation coefficients and introduced changes in the estimated group SWS. Similarly, the slope of group SWS changes with respect to the excitation frequency differed as much as 78% among three models investigated. This new finding may motivate further studies examining how elastic scattering may contribute to frequency-dependent shear wave dispersion and attenuation in biological tissues.

A Novel Haptic Interactive Approach to Simulation of Surgery Cutting Based on Mesh and Meshless Models

PubMed Central

Liu, Peter X.; Lai, Pinhua; Xu, Shaoping; Zou, Yanni

2018-01-01

In the present work, the majority of implemented virtual surgery simulation systems have been based on either a mesh or meshless strategy with regard to soft tissue modelling. To take full advantage of the mesh and meshless models, a novel coupled soft tissue cutting model is proposed. Specifically, the reconstructed virtual soft tissue consists of two essential components. One is associated with surface mesh that is convenient for surface rendering and the other with internal meshless point elements that is used to calculate the force feedback during cutting. To combine two components in a seamless way, virtual points are introduced. During the simulation of cutting, the Bezier curve is used to characterize smooth and vivid incision on the surface mesh. At the same time, the deformation of internal soft tissue caused by cutting operation can be treated as displacements of the internal point elements. Furthermore, we discussed and proved the stability and convergence of the proposed approach theoretically. The real biomechanical tests verified the validity of the introduced model. And the simulation experiments show that the proposed approach offers high computational efficiency and good visual effect, enabling cutting of soft tissue with high stability. PMID:29850006

Photoacoustic biopsy: a feasibility study

NASA Astrophysics Data System (ADS)

Xu, Guan; Tomlins, Scott A.; Siddiqui, Javed; Davis, Mandy A.; Kunju, Lakshmi P.; Wei, John T.; Wang, Xueding

2015-03-01

Photoacoustic (PA) measurements encode the information associated with both physical microstructures and chemical contents in biological tissues. A two-dimensional physio-chemical spectrogram (PCS) can be formulated by combining the power spectra of PA signals acquired at a series of optical wavelengths. The analysis of PCS, or namely PA physio-chemical analysis (PAPCA), enables the quantification of the concentrations and the spatial distributions of a variety of chemical components in the tissue. The chemical components and their distribution are the two major features observed in the biopsy procedures which have been regarded as the gold standard of the diagnosis of many diseases. Taking non-alcoholic fatty liver disease and prostate cancer for example, this study investigates the feasibility of PAPCA in characterizing the histopathological changes in the diseased conditions in biological tissue. A catheter based setup facilitating measurement in deep tissues was also proposed and tested.

Quantitative assessment of submicron scale anisotropy in tissue multifractality by scattering Mueller matrix in the framework of Born approximation

NASA Astrophysics Data System (ADS)

Das, Nandan Kumar; Dey, Rajib; Chakraborty, Semanti; Panigrahi, Prasanta K.; Meglinski, Igor; Ghosh, Nirmalya

2018-04-01

A number of tissue-like disordered media exhibit local anisotropy of scattering in the scaling behavior. Scaling behavior contains wealth of fractal or multifractal properties. We demonstrate that the spatial dielectric fluctuations in a sample of biological tissue exhibit multifractal anisotropy. Multifractal anisotropy encoded in the wavelength variation of the light scattering Mueller matrix and manifesting as an intriguing spectral diattenuation effect. We developed an inverse method for the quantitative assessment of the multifractal anisotropy. The method is based on the processing of relevant Mueller matrix elements in Fourier domain by using Born approximation, followed by the multifractal analysis. The approach promises for probing subtle micro-structural changes in biological tissues associated with the cancer and precancer, as well as for non-destructive characterization of a wide range of scattering materials.

Determination of the pathological state of skin samples by optical polarimetry parameters

NASA Astrophysics Data System (ADS)

Fanjul-Vélez, F.; Ortega-Quijano, N.; Buelta, L.; Arce-Diego, J. L.

2008-11-01

Polarimetry is widely known to involve a series of powerful optical techniques that characterize the polarization behaviour of a sample. In this work, we propose a method for applying polarimetric procedures to the characterization of biological tissues, in order to differentiate between healthy and pathologic tissues on a polarimetric basis. Usually, medical morphology diseases are diagnosed based on histological alterations of the tissue. The fact that these alterations will be reflected in polarization information highlights the suitability of polarimetric procedures for diagnostic purposes. The analysis is mainly focused on the depolarization properties of the media, as long as the internal structure strongly affects the polarization state of the light that interacts with the sample. Therefore, a method is developed in order to determine the correlation between pathological ultraestructural characteristics and the subsequent variations in the polarimetric parameters of the backscattered light. This study is applied to three samples of porcine skin corresponding to a healthy region, a mole, and a cancerous region. The results show that the method proposed is indeed an adequate technique in order to achieve an early, accurate and effective cancer detection.

Ex vivo characterization of normal and adenocarcinoma colon samples by Mueller matrix polarimetry.

PubMed

Ahmad, Iftikhar; Ahmad, Manzoor; Khan, Karim; Ashraf, Sumara; Ahmad, Shakil; Ikram, Masroor

2015-05-01

Mueller matrix polarimetry along with polar decomposition algorithm was employed for the characterization of ex vivo normal and adenocarcinoma human colon tissues by polarized light in the visible spectral range (425-725 nm). Six derived polarization metrics [total diattenuation (DT ), retardance (RT ), depolarization(ΔT ), linear diattenuation (DL), retardance (δ), and depolarization (ΔL)] were compared for normal and adenocarcinoma colon tissue samples. The results show that all six polarimetric properties for adenocarcinoma samples were significantly higher as compared to the normal samples for all wavelengths. The Wilcoxon rank sum test illustrated that total retardance is a good candidate for the discrimination of normal and adenocarcinoma colon samples. Support vector machine classification for normal and adenocarcinoma based on the four polarization properties spectra (ΔT , ΔL, RT ,and δ) yielded 100% accuracy, sensitivity, and specificity, while both DTa nd DL showed 66.6%, 33.3%, and 83.3% accuracy, sensitivity, and specificity, respectively. The combination of polarization analysis and given classification methods provides a framework to distinguish the normal and cancerous tissues.

An Optimized Table-Top Small-Angle X-ray Scattering Set-up for the Nanoscale Structural Analysis of Soft Matter

NASA Astrophysics Data System (ADS)

Sibillano, T.; de Caro, L.; Altamura, D.; Siliqi, D.; Ramella, M.; Boccafoschi, F.; Ciasca, G.; Campi, G.; Tirinato, L.; di Fabrizio, E.; Giannini, C.

2014-11-01

The paper shows how a table top superbright microfocus laboratory X-ray source and an innovative restoring-data algorithm, used in combination, allow to analyze the super molecular structure of soft matter by means of Small Angle X-ray Scattering ex-situ experiments. The proposed theoretical approach is aimed to restore diffraction features from SAXS profiles collected from low scattering biomaterials or soft tissues, and therefore to deal with extremely noisy diffraction SAXS profiles/maps. As biological test cases we inspected: i) residues of exosomes' drops from healthy epithelial colon cell line and colorectal cancer cells; ii) collagen/human elastin artificial scaffolds developed for vascular tissue engineering applications; iii) apoferritin protein in solution. Our results show how this combination can provide morphological/structural nanoscale information to characterize new artificial biomaterials and/or to get insight into the transition between healthy and pathological tissues during the progression of a disease, or to morphologically characterize nanoscale proteins, based on SAXS data collected in a room-sized laboratory.

Developing High-Frequency Quantitative Ultrasound Techniques to Characterize Three-Dimensional Engineered Tissues

NASA Astrophysics Data System (ADS)

Mercado, Karla Patricia E.

Tissue engineering holds great promise for the repair or replacement of native tissues and organs. Further advancements in the fabrication of functional engineered tissues are partly dependent on developing new and improved technologies to monitor the properties of engineered tissues volumetrically, quantitatively, noninvasively, and nondestructively over time. Currently, engineered tissues are evaluated during fabrication using histology, biochemical assays, and direct mechanical tests. However, these techniques destroy tissue samples and, therefore, lack the capability for real-time, longitudinal monitoring. The research reported in this thesis developed nondestructive, noninvasive approaches to characterize the structural, biological, and mechanical properties of 3-D engineered tissues using high-frequency quantitative ultrasound and elastography technologies. A quantitative ultrasound technique, using a system-independent parameter known as the integrated backscatter coefficient (IBC), was employed to visualize and quantify structural properties of engineered tissues. Specifically, the IBC was demonstrated to estimate cell concentration and quantitatively detect differences in the microstructure of 3-D collagen hydrogels. Additionally, the feasibility of an ultrasound elastography technique called Single Tracking Location Acoustic Radiation Force Impulse (STL-ARFI) imaging was demonstrated for estimating the shear moduli of 3-D engineered tissues. High-frequency ultrasound techniques can be easily integrated into sterile environments necessary for tissue engineering. Furthermore, these high-frequency quantitative ultrasound techniques can enable noninvasive, volumetric characterization of the structural, biological, and mechanical properties of engineered tissues during fabrication and post-implantation.

Quantitative Analysis of Microbicide Concentrations in Fluids, Gels and Tissues Using Confocal Raman Spectroscopy

PubMed Central

Chuchuen, Oranat; Henderson, Marcus H.; Sykes, Craig; Kim, Min Sung; Kashuba, Angela D. M.; Katz, David F.

2013-01-01

Topical vaginal anti-HIV microbicides are an important focus in female-based strategies to prevent the sexual transmission of HIV. Understanding microbicide pharmacokinetics is essential to development, characterization and implementation of efficacious microbicide drug delivery formulations. Current methods to measure drug concentrations in tissue (e.g., LC-MS/MS, liquid chromatography coupled with tandem mass spectrometry) are highly sensitive, but destructive and complex. This project explored the use of confocal Raman spectroscopy to detect microbicide drugs and to measure their local concentrations in fluids, drug delivery gels, and tissues. We evaluated three candidate microbicide drugs: tenofovir, Dapivirine and IQP-0528. Measurements were performed in freshly excised porcine buccal tissue specimens, gel vehicles and fluids using two Horiba Raman microscopes, one of which is confocal. Characteristic spectral peak calibrations for each drug were obtained using serial dilutions in the three matrices. These specific Raman bands demonstrated strong linear concentration dependences in the matrices and were characterized with respect to their unique vibrational signatures. At least one specific Raman feature was identified for each drug as a marker band for detection in tissue. Sensitivity of detection was evaluated in the three matrices. A specific peak was also identified for tenofovir diphosphate, the anti-HIV bioactive product of tenofovir after phosphorylation in host cells. Z-scans of drug concentrations vs. depth in excised tissue specimens, incubated under layers of tenofovir solution in a Transwell assay, showed decreasing concentration with depth from the surface into the tissue. Time-dependent concentration profiles were obtained from tissue samples incubated in the Transwell assay, for times ranging 30 minutes - 6 hours. Calibrations and measurements from tissue permeation studies for tenofovir showed good correlation with gold standard LC-MS/MS data. These results demonstrate that confocal Raman spectroscopy holds promise as a tool for practical, minimally invasive, label-free measurement of microbicide drug concentrations in fluids, gels and tissues. PMID:24386455

Optical biopsy fiber-based fluorescence spectroscopy instrumentation

NASA Astrophysics Data System (ADS)

Katz, Alvin; Ganesan, Singaravelu; Yang, Yuanlong; Tang, Gui C.; Budansky, Yury; Celmer, Edward J.; Savage, Howard E.; Schantz, Stimson P.; Alfano, Robert R.

1996-04-01

Native fluorescence spectroscopy of biomolecules has emerged as a new modality to the medical community in characterizing the various physiological conditions of tissues. In the past several years, many groups have been working to introduce the spectroscopic methods to diagnose cancer. Researchers have successfully used native fluorescence to distinguish cancerous from normal tissue samples in rat and human tissue. We have developed three generations of instruments, called the CD-scan, CD-ratiometer and CD-map, to allow the medical community to use optics for diagnosing tissue. Using ultraviolet excitation and emission spectral measurements on both normal and cancerous tissue of the breast, gynecology, colon, and aerodigestive tract can be separated. For example, from emission intensities at 340 nm to 440 nm (300 nm excitation), a statistically consistent difference between malignant tissue and normal or benign tissue is observed. In order to utilize optical biopsy techniques in a clinical setting, the CD-scan instrument was developed, which allows for rapid and reliable in-vitro and in-vivo florescence measurements of the aerodigestive tract with high accuracy. The instrumentation employs high sensitivity detection techniques which allows for lamp excitation, small diameter optical fiber probes; the higher spatial resolution afforded by the small diameter probes can increase the ability to detect smaller tumors. The fiber optic probes allow for usage in the aerodigestive tract, cervix and colon. Needle based fiber probes have been developed for in-vivo detection of breast cancer.

Viscoelastic Properties of Human Tracheal Tissues.

PubMed

Safshekan, Farzaneh; Tafazzoli-Shadpour, Mohammad; Abdouss, Majid; Shadmehr, Mohammad B

2017-01-01

The physiological performance of trachea is highly dependent on its mechanical behavior, and therefore, the mechanical properties of its components. Mechanical characterization of trachea is key to succeed in new treatments such as tissue engineering, which requires the utilization of scaffolds which are mechanically compatible with the native human trachea. In this study, after isolating human trachea samples from brain-dead cases and proper storage, we assessed the viscoelastic properties of tracheal cartilage, smooth muscle, and connective tissue based on stress relaxation tests (at 5% and 10% strains for cartilage and 20%, 30%, and 40% for smooth muscle and connective tissue). After investigation of viscoelastic linearity, constitutive models including Prony series for linear viscoelasticity and quasi-linear viscoelastic, modified superposition, and Schapery models for nonlinear viscoelasticity were fitted to the experimental data to find the best model for each tissue. We also investigated the effect of age on the viscoelastic behavior of tracheal tissues. Based on the results, all three tissues exhibited a (nonsignificant) decrease in relaxation rate with increasing the strain, indicating viscoelastic nonlinearity which was most evident for cartilage and with the least effect for connective tissue. The three-term Prony model was selected for describing the linear viscoelasticity. Among different models, the modified superposition model was best able to capture the relaxation behavior of the three tracheal components. We observed a general (but not significant) stiffening of tracheal cartilage and connective tissue with aging. No change in the stress relaxation percentage with aging was observed. The results of this study may be useful in the design and fabrication of tracheal tissue engineering scaffolds.

Overcoming sampling depth variations in the analysis of broadband hyperspectral images of breast tissue (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kho, Esther; de Boer, Lisanne L.; Van de Vijver, Koen K.; Sterenborg, Henricus J. C. M.; Ruers, Theo J. M.

2017-02-01

Worldwide, up to 40% of the breast conserving surgeries require additional operations due to positive resection margins. We propose to reduce this percentage by using hyperspectral imaging for resection margin assessment during surgery. Spectral hypercubes were collected from 26 freshly excised breast specimens with a pushbroom camera (900-1700nm). Computer simulations of the penetration depth in breast tissue suggest a strong variation in sampling depth ( 0.5-10 mm) over this wavelength range. This was confirmed with a breast tissue mimicking phantom study. Smaller penetration depths are observed in wavelength regions with high water and/or fat absorption. Consequently, tissue classification based on spectral analysis over the whole wavelength range becomes complicated. This is especially a problem in highly inhomogeneous human tissue. We developed a method, called derivative imaging, which allows accurate tissue analysis, without the impediment of dissimilar sampling volumes. A few assumptions were made based on previous research. First, the spectra acquired with our camera from breast tissue are mainly shaped by fat and water absorption. Second, tumor tissue contains less fat and more water than healthy tissue. Third, scattering slopes of different tissue types are assumed to be alike. In derivative imaging, the derivatives are calculated of wavelengths a few nanometers apart; ensuring similar penetration depths. The wavelength choice determines the accuracy of the method and the resolution. Preliminary results on 3 breast specimens indicate a classification accuracy of 93% when using wavelength regions characterized by water and fat absorption. The sampling depths at these regions are 1mm and 5mm.

High strain-rate soft material characterization via inertial cavitation

NASA Astrophysics Data System (ADS)

Estrada, Jonathan B.; Barajas, Carlos; Henann, David L.; Johnsen, Eric; Franck, Christian

2018-03-01

Mechanical characterization of soft materials at high strain-rates is challenging due to their high compliance, slow wave speeds, and non-linear viscoelasticity. Yet, knowledge of their material behavior is paramount across a spectrum of biological and engineering applications from minimizing tissue damage in ultrasound and laser surgeries to diagnosing and mitigating impact injuries. To address this significant experimental hurdle and the need to accurately measure the viscoelastic properties of soft materials at high strain-rates (103-108 s-1), we present a minimally invasive, local 3D microrheology technique based on inertial microcavitation. By combining high-speed time-lapse imaging with an appropriate theoretical cavitation framework, we demonstrate that this technique has the capability to accurately determine the general viscoelastic material properties of soft matter as compliant as a few kilopascals. Similar to commercial characterization algorithms, we provide the user with significant flexibility in evaluating several constitutive laws to determine the most appropriate physical model for the material under investigation. Given its straightforward implementation into most current microscopy setups, we anticipate that this technique can be easily adopted by anyone interested in characterizing soft material properties at high loading rates including hydrogels, tissues and various polymeric specimens.

Wear Debris Characterization and Corresponding Biological Response: Artificial Hip and Knee Joints

PubMed Central

Nine, Md J.; Choudhury, Dipankar; Hee, Ay Ching; Mootanah, Rajshree; Osman, Noor Azuan Abu

2014-01-01

Wear debris, of deferent sizes, shapes and quantities, generated in artificial hip and knees is largely confined to the bone and joint interface. This debris interacts with periprosthetic tissue and may cause aseptic loosening. The purpose of this review is to summarize and collate findings of the recent demonstrations on debris characterization and their biological response that influences the occurrence in implant migration. A systematic review of peer-reviewed literature is performed, based on inclusion and exclusion criteria addressing mainly debris isolation, characterization, and biologic responses. Results show that debris characterization largely depends on their appropriate and accurate isolation protocol. The particles are found to be non-uniform in size and non-homogeneously distributed into the periprosthetic tissues. In addition, the sizes, shapes, and volumes of the particles are influenced by the types of joints, bearing geometry, material combination, and lubricant. Phagocytosis of wear debris is size dependent; high doses of submicron-sized particles induce significant level of secretion of bone resorbing factors. However, articles on wear debris from engineered surfaces (patterned and coated) are lacking. The findings suggest considering debris morphology as an important parameter to evaluate joint simulator and newly developed implant materials. PMID:28788496

Depth-resolved dual-beamlet vibrometry based on Fourier domain low coherence interferometry

PubMed Central

Choudhury, Niloy; Chen, Fangyi; Wang, Ruikang K.; Jacques, Steven L.; Nuttall, Alfred L.

2013-01-01

Abstract. We present an optical vibrometer based on delay-encoded, dual-beamlet phase-sensitive Fourier domain interferometric system to provide depth-resolved subnanometer scale vibration information from scattering biological specimens. System characterization, calibration, and preliminary vibrometry with biological specimens were performed. The proposed system has the potential to provide both amplitude and direction of vibration of tissue microstructures on a single two-dimensional plane. PMID:23455961

Current regulatory issues in cell and tissue therapy.

PubMed

Burger, S R

2003-01-01

Cell-based therapies have grown dramatically in power and scope in recent years. Once limited to blood and BM transplantation, these therapies now encompass tissue repair and regeneration, metabolic support, gene replacement, and immune effector functions, with established and investigational clinical applications in disorders affecting nearly every tissue and organ system. The complexity and novel applications of human cells, tissues, and cellular and tissue-based products (HCT/Ps), however, present potential risks for adverse events. The US Food and Drug Administration, responding to these concerns, has established a tiered, risk-based regulatory structure, in which more rigorous controls and safeguards are required for products thought to pose increased risk. The proposed good tissue practices (GTP) rule and existing good manufacturing practices (GMP) requirements form the principal elements of this regulatory framework. The proposed GTPs are intended to prevent HCT/P contamination with infectious disease agents, and to ensure that these cells and tissues maintain their integrity and function. GMPs focus on production of safe, pure, and potent products, and entail a higher level of process control and product characterization. All HCT/Ps will be required to comply with GTPs. HCT/Ps considered to present greater risks of adverse events, however, will be subject to both GTPs and GMPs, and must obtain premarket approval using the Investigational New Drug (IND) mechanism established for biologics. Although these requirements will present significant challenges for clinician- investigators and laboratories producing HCT/Ps, the regulations fundamentally support good clinical care by increasing safety and control, and enable good science by improving the quality and reliability of data.

Chitosan/silk fibroin-based, Schwann cell-derived extracellular matrix-modified scaffolds for bridging rat sciatic nerve gaps.

PubMed

Gu, Yun; Zhu, Jianbin; Xue, Chengbin; Li, Zhenmeiyu; Ding, Fei; Yang, Yumin; Gu, Xiaosong

2014-02-01

Extracellular matrix (ECM) plays a prominent role in establishing and maintaining an ideal microenvironment for tissue regeneration, and ECM scaffolds are used as a feasible alternative to cellular and molecular therapy in the fields of tissue engineering. Because of their advantages over tissue-derived ECM scaffolds, cultured cell-derived ECM scaffolds are beginning to attract attention, but they have been scarcely studied for peripheral nerve repair. Here we aimed to develop a tissue engineered nerve scaffold by reconstituting nerve cell-derived ECM with natural biomaterials. A protocol was adopted to prepare and characterize the cultured Schwann cell (SC)-derived ECM. A chitosan conduit and silk fibroin (SF) fibers were prepared, cultured with SCs for ECM deposition, and subjected to decellularization, followed by assembly into a chitosan/SF-based, SC-derived ECM-modified scaffold, which was used to bridge a 10 mm rat sciatic nerve gap. The results from morphological analysis as well as electrophysiological examination indicated that regenerative outcomes achieved by our developed scaffold were similar to those by an acellular nerve graft (namely a nerve tissue-derived ECM scaffold), but superior to those by a plain chitosan/SF scaffold. Moreover, blood and histopathological parameters confirmed the safety of scaffold modification by SC-derived ECM. Therefore, a hybrid scaffold based on joint use of acellular and classical biomaterials represents a promising approach to nerve tissue engineering. Copyright © 2013 Elsevier Ltd. All rights reserved.

Research on Navy-Related Combat Casualty Care Issues, Navy Operational-Related Injuries and Illnesses and Approaches to Enhance Navy/Marine Corps Personnel Combat Performance.

DTIC Science & Technology

1998-06-01

role of bone morphogenetic protein (BMP) receptors in bone regeneration in periodontal tissues . Tissue samples for these studies are in the accrual...34 Characterization of Bone Morphogenetic Protein Receptors in Oral Tissues " collection of clinical samples will proceed in preparation for assay. • Relative to the...transcribed. • Relative to the project * Characterization of Bone Morphogenetic Protein Receptors in Oral Tissues ", collection of clinical samples is

Atomic force microscopy-based characterization and design of biointerfaces

NASA Astrophysics Data System (ADS)

Alsteens, David; Gaub, Hermann E.; Newton, Richard; Pfreundschuh, Moritz; Gerber, Christoph; Müller, Daniel J.

2017-03-01

Atomic force microscopy (AFM)-based methods have matured into a powerful nanoscopic platform, enabling the characterization of a wide range of biological and synthetic biointerfaces ranging from tissues, cells, membranes, proteins, nucleic acids and functional materials. Although the unprecedented signal-to-noise ratio of AFM enables the imaging of biological interfaces from the cellular to the molecular scale, AFM-based force spectroscopy allows their mechanical, chemical, conductive or electrostatic, and biological properties to be probed. The combination of AFM-based imaging and spectroscopy structurally maps these properties and allows their 3D manipulation with molecular precision. In this Review, we survey basic and advanced AFM-related approaches and evaluate their unique advantages and limitations in imaging, sensing, parameterizing and designing biointerfaces. It is anticipated that in the next decade these AFM-related techniques will have a profound influence on the way researchers view, characterize and construct biointerfaces, thereby helping to solve and address fundamental challenges that cannot be addressed with other techniques.

Conformal piezoelectric systems for clinical and experimental characterization of soft tissue biomechanics

NASA Astrophysics Data System (ADS)

Dagdeviren, Canan; Shi, Yan; Joe, Pauline; Ghaffari, Roozbeh; Balooch, Guive; Usgaonkar, Karan; Gur, Onur; Tran, Phat L.; Crosby, Jessi R.; Meyer, Marcin; Su, Yewang; Chad Webb, R.; Tedesco, Andrew S.; Slepian, Marvin J.; Huang, Yonggang; Rogers, John A.

2015-07-01

Mechanical assessment of soft biological tissues and organs has broad relevance in clinical diagnosis and treatment of disease. Existing characterization methods are invasive, lack microscale spatial resolution, and are tailored only for specific regions of the body under quasi-static conditions. Here, we develop conformal and piezoelectric devices that enable in vivo measurements of soft tissue viscoelasticity in the near-surface regions of the epidermis. These systems achieve conformal contact with the underlying complex topography and texture of the targeted skin, as well as other organ surfaces, under both quasi-static and dynamic conditions. Experimental and theoretical characterization of the responses of piezoelectric actuator-sensor pairs laminated on a variety of soft biological tissues and organ systems in animal models provide information on the operation of the devices. Studies on human subjects establish the clinical significance of these devices for rapid and non-invasive characterization of skin mechanical properties.

Recent developments in tissue-type imaging (TTI) for planning and monitoring treatment of prostate cancer.

PubMed

Feleppa, Ernest J; Porter, Christopher R; Ketterling, Jeffrey; Lee, Paul; Dasgupta, Shreedevi; Urban, Stella; Kalisz, Andrew

2004-07-01

Because current methods of imaging prostate cancer are inadequate, biopsies cannot be effectively guided and treatment cannot be effectively planned and targeted. Therefore, our research is aimed at ultrasonically characterizing cancerous prostate tissue so that we can image it more effectively and thereby provide improved means of detecting, treating and monitoring prostate cancer. We base our characterization methods on spectrum analysis of radiofrequency (rf) echo signals combined with clinical variables such as prostate-specific antigen (PSA). Tissue typing using these parameters is performed by artificial neural networks. We employed and evaluated different approaches to data partitioning into training, validation, and test sets and different neural network configuration options. In this manner, we sought to determine what neural network configuration is optimal for these data and also to assess possible bias that might exist due to correlations among different data entries among the data for a given patient. The classification efficacy of each neural network configuration and data-partitioning method was measured using relative-operating-characteristic (ROC) methods. Neural network classification based on spectral parameters combined with clinical data generally produced ROC-curve areas of 0.80 compared to curve areas of 0.64 for conventional transrectal ultrasound imaging combined with clinical data. We then used the optimal neural network configuration to generate lookup tables that translate local spectral parameter values and global clinical-variable values into pixel values in tissue-type images (TTIs). TTIs continue to show cancerous regions successfully, and may prove to be particularly useful clinically in combination with other ultrasonic and nonultrasonic methods, e.g., magnetic-resonance spectroscopy.

Recent Developments in Tissue-type Imaging(TTI) for Planning and Monitoring Treatment of Prostate Cancer

PubMed Central

Feleppa, Ernest J.; Porter, Christopher R.; Ketterling, Jeffrey; Lee, Paul; Dasgupta, Shreedevi; Urban, Stella; Kalisz, Andrew

2006-01-01

Because current methods of imaging prostate cancer are inadequate, biopsies cannot be effectively guided and treatment cannot be effectively planned and targeted. Therefore, our research is aimed at ultrasonically characterizing cancerous prostate tissue so that we can image it more effectively and thereby provide improved means of detecting, treating and monitoring prostate cancer. We base our characterization methods on spectrum analysis of radio frequency (rf) echo signals combined with clinical variables such as prostate-specific antigen (PSA). Tissue typing using these parameters is performed by artificial neural networks. We employedand evaluated different approaches to data partitioning into training, validation, and test sets and different neural network configuration options. In this manner, we sought to determine what neural network configuration is optimal for these data and also to assess possible bias that might exist due to correlations among different data entries among the data for a given patient. The classification efficacy of each neural network configuration and data-partitioning method was measured using relative-operating-characteristic (ROC) methods. Neural network classification based on spectral parameters combined with clinical data generally produced ROC-curve areas of 0.80 compared to curve areas of 0.64 for conventional transrectal ultrasound imaging combined with clinical data. We then used the optimal neural network configuration to generate lookup tables that translate local spectral parameter values and global clinical-variable values into pixel values in tissue-type images (TTIs). TTIs continue to show can cerous regions successfully, and may prove to be particularly useful clinically in combination with other ultrasonic and nonultrasonic methods, e.g., magnetic-resonance spectroscopy. PMID:15754797

Modeling of the contrast-enhanced perfusion test in liver based on the multi-compartment flow in porous media.

PubMed

Rohan, Eduard; Lukeš, Vladimír; Jonášová, Alena

2018-01-24

The paper deals with modeling the liver perfusion intended to improve quantitative analysis of the tissue scans provided by the contrast-enhanced computed tomography (CT). For this purpose, we developed a model of dynamic transport of the contrast fluid through the hierarchies of the perfusion trees. Conceptually, computed time-space distributions of the so-called tissue density can be compared with the measured data obtained from CT; such a modeling feedback can be used for model parameter identification. The blood flow is characterized at several scales for which different models are used. Flows in upper hierarchies represented by larger branching vessels are described using simple 1D models based on the Bernoulli equation extended by correction terms to respect the local pressure losses. To describe flows in smaller vessels and in the tissue parenchyma, we propose a 3D continuum model of porous medium defined in terms of hierarchically matched compartments characterized by hydraulic permeabilities. The 1D models corresponding to the portal and hepatic veins are coupled with the 3D model through point sources, or sinks. The contrast fluid saturation is governed by transport equations adapted for the 1D and 3D flow models. The complex perfusion model has been implemented using the finite element and finite volume methods. We report numerical examples computed for anatomically relevant geometries of the liver organ and of the principal vascular trees. The simulated tissue density corresponding to the CT examination output reflects a pathology modeled as a localized permeability deficiency.

Vibrational Micro-Spectroscopy of Human Tissues Analysis: Review.

PubMed

Bunaciu, Andrei A; Hoang, Vu Dang; Aboul-Enein, Hassan Y

2017-05-04

Vibrational spectroscopy (Infrared (IR) and Raman) and, in particular, micro-spectroscopy and micro-spectroscopic imaging have been used to characterize developmental changes in tissues, to monitor these changes in cell cultures and to detect disease and drug-induced modifications. The conventional methods for biochemical and histophatological tissue characterization necessitate complex and "time-consuming" sample manipulations and the results are rarely quantifiable. The spectroscopy of molecular vibrations using mid-IR or Raman techniques has been applied to samples of human tissue. This article reviews the application of these vibrational spectroscopic techniques for analysis of biological tissue published between 2005 and 2015.

Dextran and gelatin based photocrosslinkable tissue adhesive.

PubMed

Wang, Tao; Nie, Jun; Yang, Dongzhi

2012-11-06

A two-component tissue adhesive based on biocompatible and bio-degradable polymers (oxidized urethane dextran (Dex-U-AD) and gelatin) was prepared and photocrosslinked under the ultraviolet (UV) irradiation. The adhesive could adhere to surface of gelatin, which simulated the human tissue steadily. The structures of above Dex-U-AD were characterized by FTIR, (1)H NMR spectroscopy and XRD. The adhesion property of result products was evaluated by lap-shear test. The maximum adhesion strength could reach to 4.16±0.72 MPa which was significantly higher than that of fibrin glue. The photopolymerization process of Dex-U-AD/gelatin was monitored by real time infrared spectroscopy (RTIR). It took less than 5 min to complete the curing process. The cytotoxicity of Dex-U-AD/gelatin also was evaluated which indicated that Dex-U-AD/gelatin gels were nontoxic to L929 cell. The relationship between all the above-mentioned properties and degree of oxidization of Dex-U-AD was assessed. The obtained products have the potential to serve as tissue adhesive in the future. Copyright © 2012 Elsevier Ltd. All rights reserved.

Using radiance predicted by the P3 approximation in a spherical geometry to predict tissue optical properties

NASA Astrophysics Data System (ADS)

Dickey, Dwayne J.; Moore, Ronald B.; Tulip, John

2001-01-01

For photodynamic therapy of solid tumors, such as prostatic carcinoma, to be achieved, an accurate model to predict tissue parameters and light dose must be found. Presently, most analytical light dosimetry models are fluence based and are not clinically viable for tissue characterization. Other methods of predicting optical properties, such as Monet Carlo, are accurate but far too time consuming for clinical application. However, radiance predicted by the P3-Approximation, an anaylitical solution to the transport equation, may be a viable and accurate alternative. The P3-Approximation accurately predicts optical parameters in intralipid/methylene blue based phantoms in a spherical geometry. The optical parameters furnished by the radiance, when introduced into fluence predicted by both P3- Approximation and Grosjean Theory, correlate well with experimental data. The P3-Approximation also predicts the optical properties of prostate tissue, agreeing with documented optical parameters. The P3-Approximation could be the clinical tool necessary to facilitate PDT of solid tumors because of the limited number of invasive measurements required and the speed in which accurate calculations can be performed.

Magnetic resonance brain tissue segmentation based on sparse representations

NASA Astrophysics Data System (ADS)

Rueda, Andrea

2015-12-01

Segmentation or delineation of specific organs and structures in medical images is an important task in the clinical diagnosis and treatment, since it allows to characterize pathologies through imaging measures (biomarkers). In brain imaging, segmentation of main tissues or specific structures is challenging, due to the anatomic variability and complexity, and the presence of image artifacts (noise, intensity inhomogeneities, partial volume effect). In this paper, an automatic segmentation strategy is proposed, based on sparse representations and coupled dictionaries. Image intensity patterns are singly related to tissue labels at the level of small patches, gathering this information in coupled intensity/segmentation dictionaries. This dictionaries are used within a sparse representation framework to find the projection of a new intensity image onto the intensity dictionary, and the same projection can be used with the segmentation dictionary to estimate the corresponding segmentation. Preliminary results obtained with two publicly available datasets suggest that the proposal is capable of estimating adequate segmentations for gray matter (GM) and white matter (WM) tissues, with an average overlapping of 0:79 for GM and 0:71 for WM (with respect to original segmentations).

Simultaneous characterization of pancreatic stellate cells and other pancreatic components within three-dimensional tissue environment during chronic pancreatitis

NASA Astrophysics Data System (ADS)

Hu, Wenyan; Fu, Ling

2013-05-01

Pancreatic stellate cells (PSCs) and other pancreatic components that play a critical role in exocrine pancreatic diseases are generally identified separately by conventional studies, which provide indirect links between these components. Here, nonlinear optical microscopy was evaluated for simultaneous characterization of these components within a three-dimensional (3-D) tissue environment, primarily based on multichannel detection of intrinsic optical emissions and cell morphology. Fresh rat pancreatic tissues harvested at 1 day, 7 days, and 28 days after induction of chronic pancreatitis were imaged, respectively. PSCs, inflammatory cells, blood vessels, and collagen fibers were identified simultaneously. The PSCs at day 1 of chronic pancreatitis showed significant enlargement compared with those in normal pancreas (p<0.001, analysis of variance linear contrast; n=8 for each group). Pathological events relating to these components were observed, including presence of inflammatory cells, deposited collagen, and phenotype conversion of PSCs. We demonstrate that label-free nonlinear optical microscopy is an efficient tool for dissecting PSCs and other pancreatic components coincidently within 3-D pancreatic tissues. It is a prospect for intravital observation of dynamic events under natural physiological conditions, and might help uncover the key mechanisms of exocrine pancreatic diseases, leading to more effective treatments.

Automated detection of esophageal dysplasia in in vivo optical coherence tomography images of the human esophagus

NASA Astrophysics Data System (ADS)

Kassinopoulos, Michalis; Dong, Jing; Tearney, Guillermo J.; Pitris, Costas

2018-02-01

Catheter-based Optical Coherence Tomography (OCT) devices allow real-time and comprehensive imaging of the human esophagus. Hence, they provide the potential to overcome some of the limitations of endoscopy and biopsy, allowing earlier diagnosis and better prognosis for esophageal adenocarcinoma patients. However, the large number of images produced during every scan makes manual evaluation of the data exceedingly difficult. In this study, we propose a fully automated tissue characterization algorithm, capable of discriminating normal tissue from Barrett's Esophagus (BE) and dysplasia through entire three-dimensional (3D) data sets, acquired in vivo. The method is based on both the estimation of the scatterer size of the esophageal epithelial cells, using the bandwidth of the correlation of the derivative (COD) method, as well as intensity-based characteristics. The COD method can effectively estimate the scatterer size of the esophageal epithelium cells in good agreement with the literature. As expected, both the mean scatterer size and its standard deviation increase with increasing severity of disease (i.e. from normal to BE to dysplasia). The differences in the distribution of scatterer size for each tissue type are statistically significant, with a p value of < 0.0001. However, the scatterer size by itself cannot be used to accurately classify the various tissues. With the addition of intensity-based statistics the correct classification rates for all three tissue types range from 83 to 100% depending on the lesion size.

Predictive analysis of optical ablation in several dermatological tumoral tissues

NASA Astrophysics Data System (ADS)

Fanjul-Vélez, F.; Blanco-Gutiérrez, A.; Salas-García, I.; Ortega-Quijano, N.; Arce-Diego, J. L.

2013-06-01

Optical techniques for treatment and characterization of biological tissues are revolutionizing several branches of medical praxis, for example in ophthalmology or dermatology. The non-invasive, non-contact and non-ionizing character of optical radiation makes it specially suitable for these applications. Optical radiation can be employed in medical ablation applications, either for tissue resection or surgery. Optical ablation may provide a controlled and clean cut on a biological tissue. This is particularly relevant in tumoral tissue resection, where a small amount of cancerous cells could make the tumor appear again. A very important aspect of tissue optical ablation is then the estimation of the affected volume. In this work we propose a complete predictive model of tissue ablation that provides an estimation of the resected volume. The model is based on a Monte Carlo approach for the optical propagation of radiation inside the tissue, and a blow-off model for tissue ablation. This model is applied to several types of dermatological tumoral tissues, specifically squamous cells, basocellular and infiltrative carcinomas. The parameters of the optical source are varied and the estimated resected volume is calculated. The results for the different tumor types are presented and compared. This model can be used for surgical planning, in order to assure the complete resection of the tumoral tissue.

Isolation and characterization of mouse innate lymphoid cells.

PubMed

Halim, Timotheus Y F; Takei, Fumio

2014-08-01

Innate lymphoid cells (ILCs) are rare populations of cytokine-producing lymphocytes and are divided into three groups, namely ILC1, ILC2, and ILC3, based on the cytokines that they produce. They comprise less than 1% of lymphocytes in mucosal tissues and express no unique cell surface markers. Therefore, they can only be identified by combinations of multiple cell surface markers and further characterized by cytokine production in vitro. Thus, multicolor flow cytometry is the only reliable method to purify and characterize ILCs. Here we describe the methods for cell preparation, flow cytometric analysis, and purification of murine ILC2 and ILC3. Copyright © 2014 John Wiley & Sons, Inc.

TU-F-BRB-01: Resolving and Characterizing Breathing Motion for Radiotherapy with MRI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tryggestad, E.

The current clinical standard of organ respiratory imaging, 4D-CT, is fundamentally limited by poor soft-tissue contrast and imaging dose. These limitations are potential barriers to beneficial “4D” radiotherapy methods which optimize the target and OAR dose-volume considering breathing motion but rely on a robust motion characterization. Conversely, MRI imparts no known radiation risk and has excellent soft-tissue contrast. MRI-based motion management is therefore highly desirable and holds great promise to improve radiotherapy of moving cancers, particularly in the abdomen. Over the past decade, MRI techniques have improved significantly, making MR-based motion management clinically feasible. For example, cine MRI has highmore » temporal resolution up to 10 f/s and has been used to track and/or characterize tumor motion, study correlation between external and internal motions. New MR technologies, such as 4D-MRI and MRI hybrid treatment machines (i.e. MR-linac or MR-Co60), have been recently developed. These technologies can lead to more accurate target volume determination and more precise radiation dose delivery via direct tumor gating or tracking. Despite all these promises, great challenges exist and the achievable clinical benefit of MRI-based tumor motion management has yet to be fully explored, much less realized. In this proposal, we will review novel MR-based motion management methods and technologies, the state-of-the-art concerning MRI development and clinical application and the barriers to more widespread adoption. Learning Objectives: Discuss the need of MR-based motion management for improving patient care in radiotherapy. Understand MR techniques for motion imaging and tumor motion characterization. Understand the current state of the art and future steps for clinical integration. Henry Ford Health System holds research agreements with Philips Healthcare. Research sponsored in part by a Henry Ford Health System Internal Mentored Grant.« less

In silico simulation and in vitro evaluation of an elastomeric scaffold using ultrasonic shear wave imaging

NASA Astrophysics Data System (ADS)

Yu, Jiao; Nie, Erwei; Zhu, Yanying; Hong, Yi

2018-03-01

Biodegradable elastomeric scaffolds for soft tissue repair represent a growing area of biomaterials research. Mechanical strength is one of the key factors to consider in the evaluation of candidate materials and the designs for tissue scaffolds. It is desirable to develop non-invasive evaluation methods of the mechanical property of scaffolds which would provide options for monitoring temporal mechanical property changes in situ. In this paper, we conduct in silico simulation and in vitro evaluation of an elastomeric scaffold using a novel ultrasonic shear wave imaging (USWI). The scaffold is fabricated from a biodegradable elastomer, poly(carbonate urethane) urea using salt leaching method. A numerical simulation is performed to test the robustness of the developed inversion algorithm for the elasticity map reconstruction which will be implemented in the phantom experiment. The generation and propagation of shear waves in a homogeneous tissue-mimicking medium with a circular scaffold inclusion is simulated and the elasticity map is well reconstructed. A PVA phantom experiment is performed to test the ability of USWI combined with the inversion algorithm to non-invasively characterize the mechanical property of a porous, biodegradable elastomeric scaffold. The elastic properties of the tested scaffold can be easily differentiated from the surrounding medium in the reconstructed image. The ability of the developed method to identify the edge of the scaffold and characterize the elasticity distribution is demonstrated. Preliminary results in this pilot study support the idea of applying the USWI based method for non-invasive elasticity characterization of tissue scaffolds.

78 FR 26639 - Proposed Collection; 60-Day Comment Request: Financial Sustainability of Human Tissue Biobanking...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-07

... and tailored support for national and international biobanks. The survey will collect a combination of structured, quantitative, and free-text descriptive data that characterize the type and maturity of... Collection: The purpose of this web- based survey is to collect information regarding the challenges that...

Optical-Based Artificial Palpation Sensors for Lesion Characterization

PubMed Central

Lee, Jong-Ha; Kim, Yoon Nyun; Ku, Jeonghun; Park, Hee-Jun

2013-01-01

Palpation techniques are widely used in medical procedures to detect the presence of lumps or tumors in the soft breast tissues. Since these procedures are very subjective and depend on the skills of the physician, it is imperative to perform detailed a scientific study in order to develop more efficient medical sensors to measure and generate palpation parameters. In this research, we propose an optical-based, artificial palpation sensor for lesion characterization. This has been developed using a multilayer polydimethylsiloxane optical waveguide. Light was generated at the critical angle to reflect totally within the flexible and transparent waveguide. When a waveguide was compressed by an external force, its contact area would deform and cause the light to scatter. The scattered light was captured by a high-resolution camera and saved as an image format. To test the performance of the proposed system, we used a realistic tissue phantom with embedded hard inclusions. The experimental results show that the proposed sensor can detect inclusions and provide the relative value of size, depth, and Young's modulus of an inclusion. PMID:23966198

Novel keratin modified bacterial cellulose nanocomposite production and characterization for skin tissue engineering.

PubMed

Keskin, Zalike; Sendemir Urkmez, Aylin; Hames, E Esin

2017-06-01

As it is known that bacterial cellulose (BC) is a biocompatible and natural biopolymer due to which it has a large set of biomedical applications. But still it lacks some desired properties, which limits its uses in many other applications. Therefore, the properties of BC need to be boosted up to an acceptable level. Here in this study for the first time, a new natural nanocomposite was produced by the incorporating keratin (isolated from human hair) to the BC (produced by Acetobacter xylinum) to enhance dermal fibroblast cells' attachment. Two different approaches were used in BC based nanocomposite production: in situ and post modifications. BC/keratin nanocomposites were characterized using SEM, FTIR, EDX, XRD, DSC and XPS analyses. Both production methods have yielded successful results for production of BC based nanocomposite-containing keratin. In vitro cell culture experiments performed with human skin keratinocytes and human skin fibroblast cells indicate the potential of the novel BC/keratin nanocomposites for use in skin tissue engineering. Copyright © 2017 Elsevier B.V. All rights reserved.

Dental hard tissue characterization using laser-based ultrasonics

NASA Astrophysics Data System (ADS)

Blodgett, David W.; Massey, Ward L.

2003-07-01

Dental health care and research workers require a means of imaging the structures within teeth in vivo. One critical need is the detection of tooth decay in its early stages. If decay can be detected early enough, the process can be monitored and interventional procedures, such as fluoride washes and controlled diet, can be initiated to help re-mineralize the tooth. Currently employed x-ray imaging is limited in its ability to visualize interfaces and incapable of detecting decay at a stage early enough to avoid invasive cavity preparation followed by a restoration. To this end, non-destructive and non-contact in vitro measurements on extracted human molars using laser-based ultrasonics are presented. Broadband ultrasonic waves are excited in the extracted sections by using a pulsed carbon-dioxide (CO2) laser operating in a region of high optical absorption in the dental hard tissues. Optical interferometric detection of the ultrasonic wave surface displacements in accomplished with a path-stabilized Michelson-type interferometer. Results for bulk and surface in-vitro characterization of caries are presented on extracted molars with pre-existing caries.

Identification and thermochemical analysis of high-lignin feedstocks for biofuel and biochemical production

PubMed Central

2011-01-01

Background Lignin is a highly abundant biopolymer synthesized by plants as a complex component of plant secondary cell walls. Efforts to utilize lignin-based bioproducts are needed. Results Herein we identify and characterize the composition and pyrolytic deconstruction characteristics of high-lignin feedstocks. Feedstocks displaying the highest levels of lignin were identified as drupe endocarp biomass arising as agricultural waste from horticultural crops. By performing pyrolysis coupled to gas chromatography-mass spectrometry, we characterized lignin-derived deconstruction products from endocarp biomass and compared these with switchgrass. By comparing individual pyrolytic products, we document higher amounts of acetic acid, 1-hydroxy-2-propanone, acetone and furfural in switchgrass compared to endocarp tissue, which is consistent with high holocellulose relative to lignin. By contrast, greater yields of lignin-based pyrolytic products such as phenol, 2-methoxyphenol, 2-methylphenol, 2-methoxy-4-methylphenol and 4-ethyl-2-methoxyphenol arising from drupe endocarp tissue are documented. Conclusions Differences in product yield, thermal decomposition rates and molecular species distribution among the feedstocks illustrate the potential of high-lignin endocarp feedstocks to generate valuable chemicals by thermochemical deconstruction. PMID:22018114

Mathematical modeling of reflectance and intrinsic fluorescence for cancer detection in human pancreatic tissue

NASA Astrophysics Data System (ADS)

Wilson, Robert H.; Chandra, Malavika; Scheiman, James; Simeone, Diane; McKenna, Barbara; Purdy, Julianne; Mycek, Mary-Ann

2009-02-01

Pancreatic adenocarcinoma has a five-year survival rate of only 4%, largely because an effective procedure for early detection has not been developed. In this study, mathematical modeling of reflectance and fluorescence spectra was utilized to quantitatively characterize differences between normal pancreatic tissue, pancreatitis, and pancreatic adenocarcinoma. Initial attempts at separating the spectra of different tissue types involved dividing fluorescence by reflectance, and removing absorption artifacts by applying a "reverse Beer-Lambert factor" when the absorption coefficient was modeled as a linear combination of the extinction coefficients of oxy- and deoxy-hemoglobin. These procedures demonstrated the need for a more complete mathematical model to quantitatively describe fluorescence and reflectance for minimally-invasive fiber-based optical diagnostics in the pancreas.

Genetic effects on gene expression across human tissues

PubMed Central

2017-01-01

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease. PMID:29022597

Characterization of Focal Muscle Compression Under Impact Loading

NASA Astrophysics Data System (ADS)

Butler, Ben; Sory, David; Nguyen, Thuy-Tien; Curry, Richard; Clasper, Jon; Proud, William; Williams, Alun; Brown, Kate

2015-06-01

The pattern of battle injuries sustained in modern wars shows that over 70% of combat wounds are to the extremities. These injuries are characterized by disruption and contamination of the limb soft tissue envelope. The extent of this tissue trauma and contamination determine the outcome in extremity injury. In military injury, common post-traumatic complications at amputation sites include heterotopic ossification (formation of bone in soft tissue), and severe soft tissue and bone infections. We are currently developing a model of soft tissue injury that recreates pathologies observed in combat injuries. Here we present characterization of a controlled focal compression of the rabbit flexor carpi ulnaris (FCU) muscle group. The FCU was previously identified as a suitable site for studying impact injury because its muscle belly can easily be mobilized from the underlying bone without disturbing anatomical alignment in the limb. We show how macroscopic changes in tissue organization, as visualized using optical microscopy, can be correlated with data from temporally resolved traces of loading conditions. Funding provided by the Royal British Legion.

Genetic effects on gene expression across human tissues.

PubMed

Battle, Alexis; Brown, Christopher D; Engelhardt, Barbara E; Montgomery, Stephen B

2017-10-11

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.

Time-dependent diffusion MRI in cancer: tissue modeling and applications

NASA Astrophysics Data System (ADS)

Reynaud, Olivier

2017-11-01

In diffusion weighted imaging (DWI), the apparent diffusion coefficient has been recognized as a useful and sensitive surrogate for cell density, paving the way for non-invasive tumor staging, and characterization of treatment efficacy in cancer. However, microstructural parameters, such as cell size, density and/or compartmental diffusivities affect diffusion in various fashions, making of conventional DWI a sensitive but non-specific probe into changes happening at cellular level. Alternatively, tissue complexity can be probed and quantified using the time dependence of diffusion metrics, sometimes also referred to as temporal diffusion spectroscopy when only using oscillating diffusion gradients. Time-dependent diffusion (TDD) is emerging as a strong candidate for specific and non-invasive tumor characterization. Despite the lack of a general analytical solution for all diffusion times / frequencies, TDD can be probed in various regimes where systems simplify in order to extract relevant information about tissue microstructure. The fundamentals of TDD are first reviewed (a) in the short time regime, disentangling structural and diffusive tissue properties, and (b) near the tortuosity limit, assuming weakly heterogeneous media near infinitely long diffusion times. Focusing on cell bodies (as opposed to neuronal tracts), a simple but realistic model for intracellular diffusion can offer precious insight on diffusion inside biological systems, at all times. Based on this approach, the main three geometrical models implemented so far (IMPULSED, POMACE, VERDICT) are reviewed. Their suitability to quantify cell size, intra- and extracellular spaces (ICS and ECS) and diffusivities are assessed. The proper modeling of tissue membrane permeability – hardly a newcomer in the field, but lacking applications - and its impact on microstructural estimates are also considered. After discussing general issues with tissue modeling and microstructural parameter estimation (i.e. fitting), potential solutions are detailed. The in vivo applications of this new, non-invasive, specific approach in cancer are reviewed, ranging from the characterization of gliomas in rodent brains and observation of time-dependence in breast tissue lesions and prostate cancer, to the recent preclinical evaluation of new treatments efficacy. It is expected that clinical applications of TDD will strongly benefit the community in terms of non-invasive cancer screening.

De novo transcriptome assembly and characterization of nine tissues of Lonicera japonica to identify potential candidate genes involved in chlorogenic acid, luteolosides, and secoiridoid biosynthesis pathways.

PubMed

Rai, Amit; Kamochi, Hidetaka; Suzuki, Hideyuki; Nakamura, Michimi; Takahashi, Hiroki; Hatada, Tomoki; Saito, Kazuki; Yamazaki, Mami

2017-01-01

Lonicera japonica is one of the most important medicinal plants with applications in traditional Chinese and Japanese medicine for thousands of years. Extensive studies on the constituents of L. japonica extracts have revealed an accumulation of pharmaceutically active metabolite classes, such as chlorogenic acid, luteolin and other flavonoids, and secoiridoids, which impart characteristic medicinal properties. Despite being a rich source of pharmaceutically active metabolites, little is known about the biosynthetic enzymes involved, and their expression profile across different tissues of L. japonica. In this study, we performed de novo transcriptome assembly for L. japonica, representing transcripts from nine different tissues. A total of 22 Gbps clean RNA-seq reads from nine tissues of L. japonica were used, resulting in 243,185 unigenes, with 99,938 unigenes annotated based on a homology search using blastx against the NCBI-nr protein database. Unsupervised principal component analysis and correlation studies using transcript expression data from all nine tissues of L. japonica showed relationships between tissues, explaining their association at different developmental stages. Homologs for all genes associated with chlorogenic acid, luteolin, and secoiridoid biosynthesis pathways were identified in the L. japonica transcriptome assembly. Expression of unigenes associated with chlorogenic acid was enriched in stems and leaf-2, unigenes from luteolin were enriched in stems and flowers, while unigenes from secoiridoid metabolic pathways were enriched in leaf-1 and shoot apex. Our results showed that different tissues of L. japonica are enriched with sets of unigenes associated with specific pharmaceutically important metabolic pathways and, therefore, possess unique medicinal properties. The present study will serve as a resource for future attempts for functional characterization of enzyme coding genes within key metabolic processes.

Peptide Probe for Crystalline Hydroxyapatite: In Situ Detection of Biomineralization

NASA Astrophysics Data System (ADS)

Cicerone, Marcus; Becker, Matthew; Simon, Carl; Chatterjee, Kaushik

2009-03-01

While cells template mineralization in vitro and in vivo, specific detection strategies that impart chemical and structural information on this process have proven elusive. Recently we have developed an in situ based peptide probe via phage display methods that is specific to crystalline hydroxyapatite (HA). We are using this in fluorescence based assays to characterize mineralization. One application being explored is the screening of tissue engineering scaffolds for their ability to support osteogenesis. Specifically, osteoblasts are being cultured in hydrogel scaffolds possessing property gradients to provide a test bed for the HA peptide probe. Hydrogel properties that support osteogenesis and HA deposition will be identified using the probe to demonstrate its utility in optimizing design of tissue scaffolds.

Biomechanical properties of the forefoot plantar soft tissue as measured by an optical coherence tomography-based air-jet indentation system and tissue ultrasound palpation system.

PubMed

Chao, Clare Y L; Zheng, Yong-Ping; Huang, Yan-Ping; Cheing, Gladys L Y

2010-07-01

The forefoot medial plantar area withstand high plantar pressure during locomotion, and is a common site that develops foot lesion problems among elderly people. The aims of the present study were to (1) determine the correlation between the biomechanical properties of forefoot medial plantar soft tissue measured by a newly developed optical coherence tomography-based air-jet indentation system and by tissue ultrasound palpation system, and (2) to compare the biomechanical properties of plantar soft tissues of medial forefoot between a young and old adult group. Thirty healthy subjects were classified as the young or older group. The biomechanical properties of plantar soft tissues measured at the forefoot by the air-jet indentation system and tissue ultrasound palpation system were performed, and the correlation of the findings obtained in the two systems were compared. A strong positive correlation was obtained from the findings in the two systems (r=0.88, P<0.001). The forefoot plantar soft tissue of the older group was significantly stiffer at the second metatarsal head and thinner at both metatarsal heads than that of the young group (all P<0.05). The stiffness coefficient at the second metatarsal head was 28% greater than that at the first metatarsal head in both study groups. Older subjects showed a loss of elasticity and reduced thickness in their forefoot plantar soft tissue, with the second metatarsal head displaying stiffer and thicker plantar tissue than the first metatarsal head. The air-jet indentation system is a useful instrument for characterizing the biomechanical properties of soft tissue. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation.

PubMed

Allen, Joselyn N; Dey, Adwitia; Nissly, Ruth; Fraser, James; Yu, Shan; Balandaram, Gayathri; Peters, Jeffrey M; Hankey-Giblin, Pamela A

2017-04-03

Obesity promotes a chronic inflammatory state that is largely mediated by tissue-resident macrophages as well as monocyte-derived macrophages. Diet-induced obesity (DIO) is a valuable model in studying the role of macrophage heterogeneity; however, adequate macrophage isolations are difficult to acquire from inflamed tissues. In this protocol, we outline the isolation steps and necessary troubleshooting guidelines derived from our studies for obtaining a suitable population of tissue-resident macrophages from mice following 18 weeks of high-fat (HFD) or high-fat/high-cholesterol (HFHCD) diet intervention. This protocol focuses on three hallmark tissues studied in obesity and atherosclerosis including the liver, white adipose tissues (WAT), and the aorta. We highlight how dualistic usage of flow cytometry can achieve a new dimension of isolation and characterization of tissue-resident macrophages. A fundamental section of this protocol addresses the intricacies underlying tissue-specific enzymatic digestions and macrophage isolation, and subsequent cell-surface antibody staining for flow cytometric analysis. This protocol addresses existing complexities underlying fluorescent-activated cell sorting (FACS) and presents clarifications to these complexities so as to obtain broad range characterization from adequately sorted cell populations. Alternate enrichment methods are included for sorting cells, such as the dense liver, allowing for flexibility and time management when working with FACS. In brief, this protocol aids the researcher to evaluate macrophage heterogeneity from a multitude of inflamed tissues in a given study and provides insightful troubleshooting tips that have been successful for favorable cellular isolation and characterization of immune cells in DIO-mediated inflammation.

Harnessing biomechanics to develop cartilage regeneration strategies.

PubMed

Athanasiou, Kyriacos A; Responte, Donald J; Brown, Wendy E; Hu, Jerry C

2015-02-01

As this review was prepared specifically for the American Society of Mechanical Engineers H.R. Lissner Medal, it primarily discusses work toward cartilage regeneration performed in Dr. Kyriacos A. Athanasiou's laboratory over the past 25 years. The prevalence and severity of degeneration of articular cartilage, a tissue whose main function is largely biomechanical, have motivated the development of cartilage tissue engineering approaches informed by biomechanics. This article provides a review of important steps toward regeneration of articular cartilage with suitable biomechanical properties. As a first step, biomechanical and biochemical characterization studies at the tissue level were used to provide design criteria for engineering neotissues. Extending this work to the single cell and subcellular levels has helped to develop biochemical and mechanical stimuli for tissue engineering studies. This strong mechanobiological foundation guided studies on regenerating hyaline articular cartilage, the knee meniscus, and temporomandibular joint (TMJ) fibrocartilage. Initial tissue engineering efforts centered on developing biodegradable scaffolds for cartilage regeneration. After many years of studying scaffold-based cartilage engineering, scaffoldless approaches were developed to address deficiencies of scaffold-based systems, resulting in the self-assembling process. This process was further improved by employing exogenous stimuli, such as hydrostatic pressure, growth factors, and matrix-modifying and catabolic agents, both singly and in synergistic combination to enhance neocartilage functional properties. Due to the high cell needs for tissue engineering and the limited supply of native articular chondrocytes, costochondral cells are emerging as a suitable cell source. Looking forward, additional cell sources are investigated to render these technologies more translatable. For example, dermis isolated adult stem (DIAS) cells show potential as a source of chondrogenic cells. The challenging problem of enhanced integration of engineered cartilage with native cartilage is approached with both familiar and novel methods, such as lysyl oxidase (LOX). These diverse tissue engineering strategies all aim to build upon thorough biomechanical characterizations to produce functional neotissue that ultimately will help combat the pressing problem of cartilage degeneration. As our prior research is reviewed, we look to establish new pathways to comprehensively and effectively address the complex problems of musculoskeletal cartilage regeneration.

Two-tier tissue decomposition for histopathological image representation and classification.

PubMed

Gultekin, Tunc; Koyuncu, Can Fahrettin; Sokmensuer, Cenk; Gunduz-Demir, Cigdem

2015-01-01

In digital pathology, devising effective image representations is crucial to design robust automated diagnosis systems. To this end, many studies have proposed to develop object-based representations, instead of directly using image pixels, since a histopathological image may contain a considerable amount of noise typically at the pixel-level. These previous studies mostly employ color information to define their objects, which approximately represent histological tissue components in an image, and then use the spatial distribution of these objects for image representation and classification. Thus, object definition has a direct effect on the way of representing the image, which in turn affects classification accuracies. In this paper, our aim is to design a classification system for histopathological images. Towards this end, we present a new model for effective representation of these images that will be used by the classification system. The contributions of this model are twofold. First, it introduces a new two-tier tissue decomposition method for defining a set of multityped objects in an image. Different than the previous studies, these objects are defined combining texture, shape, and size information and they may correspond to individual histological tissue components as well as local tissue subregions of different characteristics. As its second contribution, it defines a new metric, which we call dominant blob scale, to characterize the shape and size of an object with a single scalar value. Our experiments on colon tissue images reveal that this new object definition and characterization provides distinguishing representation of normal and cancerous histopathological images, which is effective to obtain more accurate classification results compared to its counterparts.

Creation and Characterization of an Ultrasound and CT Phantom for Non-invasive Ultrasound Thermometry Calibration

PubMed Central

Lai, Chun-Yen; Kruse, Dustin E.; Ferrara, Katherine W.; Caskey, Charles F.

2014-01-01

Ultrasound thermometry provides noninvasive two-dimensional (2-D) temperature monitoring, and in this paper, we have investigated the use of computed tomography (CT) radiodensity to characterize tissues to improve the accuracy of ultrasound thermometry. Agarose-based tissue-mimicking phantoms were created with glyceryl trioleate (a fat-mimicking material) concentration of 0, 10, 20, 30, 40, and 50%. The speed of sound (SOS) of the phantoms was measured over a temperature range of 22.1–41.1°C. CT images of the phantoms were acquired by a clinical dedicated breast CT scanner, followed by calculation of the Hounsfield units (HU). The phantom was heated with a therapeutic acoustic pulse (1.54 MHz), while RF data were acquired with a 10-MHz linear-array transducer. 2-D speckle tracking was used to calculate the thermal strain offline. The tissue dependent thermal strain parameter required for ultrasound thermometry was analyzed and correlated with CT radiodensity, followed by validation of the temperature prediction. Results showed that the change in SOS with the temperature increase was opposite in sign between the 0–10% and 20–50% trioleate phantoms. The inverse of the tissue dependent thermal strain parameter of the phantoms was correlated with the CT radiodensity (R2 = 0.99). A blinded ultrasound thermometry study on phantoms with a trioleate range of 5–35% demonstrated the capability to estimate the tissue dependent thermal strain parameter and estimate temperature with error less than ~1°C. In conclusion, CT radiodensity may provide a method for improving ultrasound thermometry in heterogeneous tissues. PMID:24107918

Tumor characterization in small animals using magnetic resonance-guided dynamic contrast enhanced diffuse optical tomography

NASA Astrophysics Data System (ADS)

Lin, Yuting; Thayer, Dave; Nalcioglu, Orhan; Gulsen, Gultekin

2011-10-01

We present a magnetic resonance (MR)-guided near-infrared dynamic contrast enhanced diffuse optical tomography (DCE-DOT) system for characterization of tumors using an optical contrast agent (ICG) and a MR contrast agent [Gd-diethylenetriaminepentaacetic acid (DTPA)] in a rat model. Both ICG and Gd-DTPA are injected and monitored simultaneously using a combined MRI-DOT system, resulting in accurate co-registration between two imaging modalities. Fisher rats bearing R3230 breast tumor are imaged using this hybrid system. For the first time, enhancement kinetics of the exogenous contrast ICG is recovered from the DCE-DOT data using MR anatomical a priori information. As tumors grow, they undergo necrosis and the tissue transforms from viable to necrotic. The results show that the physiological changes between viable and necrotic tissue can be differentiated more accurately based on the ICG enhancement kinetics when MR anatomical information is utilized.

Time domain diffuse optical spectroscopy: In vivo quantification of collagen in breast tissue

NASA Astrophysics Data System (ADS)

Taroni, Paola; Pifferi, Antonio; Quarto, Giovanna; Farina, Andrea; Ieva, Francesca; Paganoni, Anna Maria; Abbate, Francesca; Cassano, Enrico; Cubeddu, Rinaldo

2015-05-01

Time-resolved diffuse optical spectroscopy provides non-invasively the optical characterization of highly diffusive media, such as biological tissues. Light pulses are injected into the tissue and the effects of light propagation on re-emitted pulses are interpreted with the diffusion theory to assess simultaneously tissue absorption and reduced scattering coefficients. Performing spectral measurements, information on tissue composition and structure is derived applying the Beer law to the measured absorption and an empiric approximation to Mie theory to the reduced scattering. The absorption properties of collagen powder were preliminarily measured in the range of 600-1100 nm using a laboratory set-up for broadband time-resolved diffuse optical spectroscopy. Optical projection images were subsequently acquired in compressed breast geometry on 218 subjects, either healthy or bearing breast lesions, using a portable instrument for optical mammography that operates at 7 wavelengths selected in the range 635-1060 nm. For all subjects, tissue composition was estimated in terms of oxy- and deoxy-hemoglobin, water, lipids, and collagen. Information on tissue microscopic structure was also derived. Good correlation was obtained between mammographic breast density (a strong risk factor for breast cancer) and an optical index based on collagen content and scattering power (that accounts mostly for tissue collagen). Logistic regression applied to all optically derived parameters showed that subjects at high risk for developing breast cancer for their high breast density can effectively be identified based on collagen content and scattering parameters. Tissue composition assessed in breast lesions with a perturbative approach indicated that collagen and hemoglobin content are significantly higher in malignant lesions than in benign ones.

Characterization of human oral tissues based on quantitative analysis of optical coherence tomography images

NASA Astrophysics Data System (ADS)

Salehi, Hassan S.; Kosa, Ali; Mahdian, Mina; Moslehpour, Saeid; Alnajjar, Hisham; Tadinada, Aditya

2017-02-01

In this paper, five types of tissues, human enamel, human cortical bone, human trabecular bone, muscular tissue, and fatty tissue were imaged ex vivo using optical coherence tomography (OCT). The specimens were prepared in blocks of 5 x 5 x 3 mm (width x length x height). The OCT imaging system was a swept source OCT system operating at wavelengths ranging between 1250 nm and 1360 nm with an average power of 18 mW and a scan rate of 50 to 100 kHz. The imaging probe was placed on top of a 2 x 2 cm stabilizing device to maintain a standard distance from the samples. Ten image samples from each type of tissue were obtained. To acquire images with minimum inhomogeneity, imaging was performed multiple times at different points. Based on the observed texture differences between OCT images of soft and hard tissues, spatial and spectral features were quantitatively extracted from the OCT images. The Radon transform from angles of 0 deg to 90 deg was computed, averaged over all the angles, normalized to peak at unity, and then fitted with Gaussian function. The mean absolute values of the spatial frequency components of the OCT image were considered as a feature, where 2-D fast Fourier transform (FFT) was done to OCT images. These OCT features can reliably differentiate between a range of hard and soft tissues, and could be extremely valuable in assisting dentists for in vivo evaluation of oral tissues and early detection of pathologic changes in tissues.

Effects of geometry and cell-matrix interactions on the mechanics of 3D engineered microtissues

NASA Astrophysics Data System (ADS)

Bose, Prasenjit; Eyckmans, Jeroen; Chen, Christopher; Reich, Daniel

Approaches to measure and control cell-extracellular matrix (ECM) interactions in a dynamic mechanical environment are important both for studies of mechanobiology and for tissue design for bioengineering applications. We have developed a microtissue-based platform capable of controlling the ECM alignment of 3D engineered microtissues while simultaneously permitting measurement of cellular contractile forces and the tissues' mechanical properties. The tissues self-assemble from cell-laden collagen gels placed in micro-fabricated wells containing sets of flexible elastic pillars. Tissue geometry and ECM alignment are controlled by the pillars' number, shape and location. Optical tracking of the pillars provides readout of the tissues' contractile forces. Magnetic materials bound to selected pillars allow quasi-static or dynamic stretching of the tissue, and together with simultaneous measurements of the tissues' local dynamic strain field, enable characterization of the mechanical properties of the system, including their degree of anisotropy. Results on the effects of symmetry and degree of ECM alignment and organization on the role of cell-ECM interactions in determining tissue mechanical properties will be discussed. This work is supported by NSF CMMI-1463011 and CMMI-1462710.

Quantitative diagnostics of soft tissue through viscoelastic characterization using time-based instrumented palpation.

PubMed

Palacio-Torralba, Javier; Hammer, Steven; Good, Daniel W; Alan McNeill, S; Stewart, Grant D; Reuben, Robert L; Chen, Yuhang

2015-01-01

Although palpation has been successfully employed for centuries to assess soft tissue quality, it is a subjective test, and is therefore qualitative and depends on the experience of the practitioner. To reproduce what the medical practitioner feels needs more than a simple quasi-static stiffness measurement. This paper assesses the capacity of dynamic mechanical palpation to measure the changes in viscoelastic properties that soft tissue can exhibit under certain pathological conditions. A diagnostic framework is proposed to measure elastic and viscous behaviors simultaneously using a reduced set of viscoelastic parameters, giving a reliable index for quantitative assessment of tissue quality. The approach is illustrated on prostate models reconstructed from prostate MRI scans. The examples show that the change in viscoelastic time constant between healthy and cancerous tissue is a key index for quantitative diagnostics using point probing. The method is not limited to any particular tissue or material and is therefore useful for tissue where defining a unique time constant is not trivial. The proposed framework of quantitative assessment could become a useful tool in clinical diagnostics for soft tissue. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

3D printing for the design and fabrication of polymer-based gradient scaffolds.

PubMed

Bracaglia, Laura G; Smith, Brandon T; Watson, Emma; Arumugasaamy, Navein; Mikos, Antonios G; Fisher, John P

2017-07-01

To accurately mimic the native tissue environment, tissue engineered scaffolds often need to have a highly controlled and varied display of three-dimensional (3D) architecture and geometrical cues. Additive manufacturing in tissue engineering has made possible the development of complex scaffolds that mimic the native tissue architectures. As such, architectural details that were previously unattainable or irreproducible can now be incorporated in an ordered and organized approach, further advancing the structural and chemical cues delivered to cells interacting with the scaffold. This control over the environment has given engineers the ability to unlock cellular machinery that is highly dependent upon the intricate heterogeneous environment of native tissue. Recent research into the incorporation of physical and chemical gradients within scaffolds indicates that integrating these features improves the function of a tissue engineered construct. This review covers recent advances on techniques to incorporate gradients into polymer scaffolds through additive manufacturing and evaluate the success of these techniques. As covered here, to best replicate different tissue types, one must be cognizant of the vastly different types of manufacturing techniques available to create these gradient scaffolds. We review the various types of additive manufacturing techniques that can be leveraged to fabricate scaffolds with heterogeneous properties and discuss methods to successfully characterize them. Additive manufacturing techniques have given tissue engineers the ability to precisely recapitulate the native architecture present within tissue. In addition, these techniques can be leveraged to create scaffolds with both physical and chemical gradients. This work offers insight into several techniques that can be used to generate graded scaffolds, depending on the desired gradient. Furthermore, it outlines methods to determine if the designed gradient was achieved. This review will help to condense the abundance of information that has been published on the creation and characterization of gradient scaffolds and to provide a single review discussing both methods for manufacturing gradient scaffolds and evaluating the establishment of a gradient. Copyright © 2017. Published by Elsevier Ltd.

Structured light imaging system for structural and optical characterization of 3D tissue-simulating phantoms

NASA Astrophysics Data System (ADS)

Liu, Songde; Smith, Zach; Xu, Ronald X.

2016-10-01

There is a pressing need for a phantom standard to calibrate medical optical devices. However, 3D printing of tissue-simulating phantom standard is challenged by lacking of appropriate methods to characterize and reproduce surface topography and optical properties accurately. We have developed a structured light imaging system to characterize surface topography and optical properties (absorption coefficient and reduced scattering coefficient) of 3D tissue-simulating phantoms. The system consisted of a hyperspectral light source, a digital light projector (DLP), a CMOS camera, two polarizers, a rotational stage, a translation stage, a motion controller, and a personal computer. Tissue-simulating phantoms with different structural and optical properties were characterized by the proposed imaging system and validated by a standard integrating sphere system. The experimental results showed that the proposed system was able to achieve pixel-level optical properties with a percentage error of less than 11% for absorption coefficient and less than 7% for reduced scattering coefficient for phantoms without surface curvature. In the meanwhile, 3D topographic profile of the phantom can be effectively reconstructed with an accuracy of less than 1% deviation error. Our study demonstrated that the proposed structured light imaging system has the potential to characterize structural profile and optical properties of 3D tissue-simulating phantoms.

Effects of heat transfer and energy absorption in the ablation of biological tissues by pulsetrain-burst (>100 MHz) ultrafast laser processing

NASA Astrophysics Data System (ADS)

Forrester, Paul; Bol, Kieran; Lilge, Lothar; Marjoribanks, Robin

2006-09-01

Energy absorption and heat transfer are important factors for regulating the effects of ablation of biological tissues. Heat transfer to surrounding material may be desirable when ablating hard tissue, such as teeth or bone, since melting can produce helpful material modifications. However, when ablating soft tissue it is important to minimize heat transfer to avoid damage to healthy tissue - for example, in eye refractive surgery (e.g., Lasik), nanosecond pulses produce gross absorption and heating in tissue, leading to shockwaves, which kill and thin the non-replicating epithelial cells on the inside of the cornea; ultrafast pulses are recognized to reduce this effect. Using a laser system that delivers 1ps pulses in 10μs pulsetrains at 133MHz we have studied a range of heat- and energy-transfer effects on hard and soft tissue. We describe the ablation of tooth dentin and enamel under various conditions to determine the ablation rate and chemical changes that occur. Furthermore, we characterize the impact of pulsetrain-burst treatment of collagen-based tissue to determine more efficient methods of energy transfer to soft tissues. By studying the optical science of laser tissue interaction we hope to be able to make qualitative improvements to medical treatments using lasers.

Synthesis and Primary Characterization of Self-Assembled Peptide-Based Hydrogels

PubMed Central

Nagarkar, Radhika P.; Schneider, Joel P.

2009-01-01

Summary Hydrogels based on peptide self-assembly form an important class of biomaterials that find application in tissue engineering and drug delivery. It is essential to prepare peptides with high purity to achieve batch-to-batch consistency affording hydrogels with reproducible properties. Automated solid-phase peptide synthesis coupled with optimized Fmoc (9-fluorenylmethoxycarbonyl) chemistry to obtain peptides in high yield and purity is discussed. Details of isolating a desired peptide from crude synthetic mixtures and assessment of the peptide’s final purity by high-performance liquid chromatography and mass spectrometry are provided. Beyond the practical importance of synthesis and primary characterization, techniques used to investigate the properties of hydrogels are briefly discussed. PMID:19031061

2-hydroxyethyl metahcrylate/gelatin based superporous hydrogels for tissue regeneration

NASA Astrophysics Data System (ADS)

Tomić, Simonida Lj.; Babić, Marija M.; Vuković, Jovana S.; Perišić, Marija D.; Filipović, Vuk V.; Davidović, Sladjana Z.; Filipović, Jovanka M.

2016-05-01

In this study, superporous hydrogels were synthesized by free radical polymerization of 2-hydroxyethyl methacrylate without and in the presence of gelatin. Highly porous hydrogel structures were obtained by two different techniques: using a gas blowing agent, sodium bicarbonate, and a cryogenic treatment followed by freeze-drying. After the gel synthesis, gelatin molecules were covalently immobilised onto PHEMA via glytaraldehyde activation. All samples were characterized for morphological, mechanical, swelling and antibacterial properties. The results obtained show that samples with gelatin show better properties in comparison with PHEMA samples, which make these materials highly attractive for developing hydrogel scaffolds for tissue regeneration.

An Anisotropic Multiphysics Model for Intervertebral Disk

PubMed Central

Gao, Xin; Zhu, Qiaoqiao; Gu, Weiyong

2016-01-01

Intervertebral disk (IVD) is the largest avascular structure in human body, consisting of three types of charged hydrated soft tissues. Its mechanical behavior is nonlinear and anisotropic, due mainly to nonlinear interactions among different constituents within tissues. In this study, a more realistic anisotropic multiphysics model was developed based on the continuum mixture theory and employed to characterize the couplings of multiple physical fields in the IVD. Numerical simulations demonstrate that this model is capable of systematically predicting the mechanical and electrochemical signals within the disk under various loading conditions, which is essential in understanding the mechanobiology of IVD. PMID:27099402

Isolation and culture of human multipotent stromal cells from the pancreas.

PubMed

Seeberger, Karen L; Eshpeter, Alana; Korbutt, Gregory S

2011-01-01

Mesenchymal stem cells, also termed multipotent mesenchymal stromal cells (MSCs), can be isolated from most adult tissues. Although the exact origin of MSCs expanded from the human pancreas has not been resolved, we have developed protocols to isolate and expand MSCs from human pancreatic tissue that remains after islet procurement. Similar to techniques used to isolate MSCs from bone marrow, pancreatic MSCs are isolated based on their cell adherence, expression of several cell surface antigens, and multilineage differentiation. The protocols for isolating, characterizing, and differentiating MSCs from the pancreas are presented in this chapter.

Analysis of Pre-Analytic Factors Affecting the Success of Clinical Next-Generation Sequencing of Solid Organ Malignancies.

PubMed

Chen, Hui; Luthra, Rajyalakshmi; Goswami, Rashmi S; Singh, Rajesh R; Roy-Chowdhuri, Sinchita

2015-08-28

Application of next-generation sequencing (NGS) technology to routine clinical practice has enabled characterization of personalized cancer genomes to identify patients likely to have a response to targeted therapy. The proper selection of tumor sample for downstream NGS based mutational analysis is critical to generate accurate results and to guide therapeutic intervention. However, multiple pre-analytic factors come into play in determining the success of NGS testing. In this review, we discuss pre-analytic requirements for AmpliSeq PCR-based sequencing using Ion Torrent Personal Genome Machine (PGM) (Life Technologies), a NGS sequencing platform that is often used by clinical laboratories for sequencing solid tumors because of its low input DNA requirement from formalin fixed and paraffin embedded tissue. The success of NGS mutational analysis is affected not only by the input DNA quantity but also by several other factors, including the specimen type, the DNA quality, and the tumor cellularity. Here, we review tissue requirements for solid tumor NGS based mutational analysis, including procedure types, tissue types, tumor volume and fraction, decalcification, and treatment effects.

Relationship Between Speed of Sound in and Density of Normal and Diseased Rat Livers

NASA Astrophysics Data System (ADS)

Hachiya, Hiroyuki; Ohtsuki, Shigeo; Tanaka, Motonao

1994-05-01

Speed of sound is an important acoustic parameter for quantitative characterization of living tissues. In this paper, the relationship between speed of sound in and density of rat liver tissues are investigated. The speed of sound was measured by the nondeformable technique based on frequency-time analysis of a 3.5 MHz pulse response. The speed of sound in normal livers varied minimally between individuals and was not related to body weight or age. In liver tissues which were administered CCl4, the speed of sound was lower than the speed of sound in normal tissues. The relationship between speed of sound and density in normal, fatty and cirrhotic livers can be fitted well on the line which is estimated using the immiscible liquid model assuming a mixture of normal liver and fat tissues. For 3.5 MHz ultrasound, it is considered that the speed of sound in fresh liver with fatty degeneration is responsible for the fat content and is not strongly dependent on the degree of fibrosis.

How the growth rate of host cells affects cancer risk in a deterministic way

NASA Astrophysics Data System (ADS)

Draghi, Clément; Viger, Louise; Denis, Fabrice; Letellier, Christophe

2017-09-01

It is well known that cancers are significantly more often encountered in some tissues than in other ones. In this paper, by using a deterministic model describing the interactions between host, effector immune and tumor cells at the tissue level, we show that this can be explained by the dependency of tumor growth on parameter values characterizing the type as well as the state of the tissue considered due to the "way of life" (environmental factors, food consumption, drinking or smoking habits, etc.). Our approach is purely deterministic and, consequently, the strong correlation (r = 0.99) between the number of detectable growing tumors and the growth rate of cells from the nesting tissue can be explained without evoking random mutation arising during DNA replications in nonmalignant cells or "bad luck". Strategies to limit the mortality induced by cancer could therefore be well based on improving the way of life, that is, by better preserving the tissue where mutant cells randomly arise.

Rapid approach to analyze biochemical variation in rat organs by ATR FTIR spectroscopy

NASA Astrophysics Data System (ADS)

Staniszewska, Emilia; Malek, Kamilla; Baranska, Malgorzata

2014-01-01

ATR FTIR spectra were collected from rat tissue homogenates (myocardium, brain, liver, lung, intestine, and kidney) to analyze their biochemical content. Based on the second derivative of an average spectral profile it was possible to assign bands e.g. to triglycerides and cholesterol esters, proteins, phosphate macromolecules (DNA, RNA, phospholipids, phosphorylated proteins) and others (glycogen, lactate). Peaks in the region of 1600-1700 cm-1 related to amide I mode revealed the secondary structure of proteins. The collected spectra do not characterize morphological structure of the investigated tissues but show their different composition. The comparison of spectral information gathered from FTIR spectra of the homogenates and those obtained previously from FTIR imaging of the tissue sections implicates that the presented here approach can be successfully employed in the investigations of biochemical variation in animal tissues. Moreover, it can be used in the pharmacological and pharmacokinetic studies to correlate the overall biochemical status of the tissue with the pathological changes it has undergone.

New environmentally friendly MSPD solid support based on golden mussel shell: characterization and application for extraction of organic contaminants from mussel tissue.

PubMed

Rombaldi, Caroline; de Oliveira Arias, Jean Lucas; Hertzog, Gabriel Ianzer; Caldas, Sergiane Souza; Vieira, João P; Primel, Ednei Gilberto

2015-06-01

The use of golden mussel shells as a solid support in vortex-assisted matrix solid-phase dispersion (MSPD) was evaluated for the first time for extraction of residues of 11 pesticides and nine pharmaceutical and personal care products from mussel tissue samples. After they had been washed, dried, and milled, the mussel shells were characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, infrared spectroscopy, and Brunauer-Emmett-Teller analysis. The MSPD procedure with analysis by liquid chromatography-tandem mass spectrometry allowed the determination of target analytes at trace concentrations (nanograms per gram), with mean recoveries ranging from 61 to 107 % and relative standard deviations lower than 18 %. The optimized method consisted of dispersion of 0.5 g of mussel tissue, 0.5 g of NaSO4, and 0.5 g of golden mussel shell for 5 min, and subsequent extraction with 5 mL of ethyl acetate. The matrix effect was evaluated, and a low effect was found for all compounds. The results showed that mussel shell is an effective material and a less expensive material than materials that have traditionally been used, i.e., it may be used in the MSPD dispersion step during the extraction of pesticides and pharmaceutical and personal care products from golden mussel tissues. Graphical Abstract Vortex-assited matrix solid-phase dispersion for extraction of 11 pesticides and 9 PPCPs care products from mussel tissue samples.

Ultrasonic Characterization of the Linear Elastic Properties of Myocardium and Other Anisotropic Soft Tissues

NASA Astrophysics Data System (ADS)

Hoffmeister, Brentley Keith

1995-01-01

This thesis seeks to contribute to a better understanding of the physics of interaction of ultrasonic waves with inhomogeneous and anisotropic media, one example of which is the human heart. The clinical success of echocardiography has generated a considerable interest in the development of ultrasonic techniques to measure the elastic properties of heart tissue. It is hypothesized that the elastic properties of myocardium are influenced by the interstitial content and organization of collagen. Collagen, which is the main component of tendon, interconnects the muscle cells of the heart to form locally unidirectional myofibers. This thesis therefore employs ultrasonic techniques to characterize the linear elastic properties of both heart and tendon. The linear elastic properties of tissues possessing a unidirectional arrangement of fibers may be described in terms of five independent elastic stiffness coefficients. Three of these coefficients were determined for formalin fixed specimens of bovine Achilles tendon and human myocardium by measuring the velocity of longitudinal mode ultrasonic pulses as a function of angle of propagation relative to the fiber axis of the tissue. The remaining two coefficients were determined by measuring the velocity of transverse mode ultrasonic waves through these tissues. To overcome technical difficulties associated with the extremely high attenuation of transverse mode waves at low megahertz frequencies, a novel measurement system was developed based on the sampled continuous wave technique. Results of these measurements were used to assess the influence of interstitial collagen, and to model the mechanical properties of heart wall.

Online multispectral fluorescence lifetime values estimation and overlay onto tissue white-light video frames

NASA Astrophysics Data System (ADS)

Gorpas, Dimitris; Ma, Dinglong; Bec, Julien; Yankelevich, Diego R.; Marcu, Laura

2016-03-01

Fluorescence lifetime imaging has been shown to be a robust technique for biochemical and functional characterization of tissues and to present great potential for intraoperative tissue diagnosis and guidance of surgical procedures. We report a technique for real-time mapping of fluorescence parameters (i.e. lifetime values) onto the location from where the fluorescence measurements were taken. This is achieved by merging a 450 nm aiming beam generated by a diode laser with the excitation light in a single delivery/collection fiber and by continuously imaging the region of interest with a color CMOS camera. The interrogated locations are then extracted from the acquired frames via color-based segmentation of the aiming beam. Assuming a Gaussian profile of the imaged aiming beam, the segmentation results are fitted to ellipses that are dynamically scaled at the full width of three automatically estimated thresholds (50%, 75%, 90%) of the Gaussian distribution's maximum value. This enables the dynamic augmentation of the white-light video frames with the corresponding fluorescence decay parameters. A fluorescence phantom and fresh tissue samples were used to evaluate this method with motorized and hand-held scanning measurements. At 640x512 pixels resolution the area of interest augmented with fluorescence decay parameters can be imaged at an average 34 frames per second. The developed method has the potential to become a valuable tool for real-time display of optical spectroscopy data during continuous scanning applications that subsequently can be used for tissue characterization and diagnosis.

Ultrasonic technique for imaging tissue vibrations: preliminary results.

PubMed

Sikdar, Siddhartha; Beach, Kirk W; Vaezy, Shahram; Kim, Yongmin

2005-02-01

We propose an ultrasound (US)-based technique for imaging vibrations in the blood vessel walls and surrounding tissue caused by eddies produced during flow through narrowed or punctured arteries. Our approach is to utilize the clutter signal, normally suppressed in conventional color flow imaging, to detect and characterize local tissue vibrations. We demonstrate the feasibility of visualizing the origin and extent of vibrations relative to the underlying anatomy and blood flow in real-time and their quantitative assessment, including measurements of the amplitude, frequency and spatial distribution. We present two signal-processing algorithms, one based on phase decomposition and the other based on spectral estimation using eigen decomposition for isolating vibrations from clutter, blood flow and noise using an ensemble of US echoes. In simulation studies, the computationally efficient phase-decomposition method achieved 96% sensitivity and 98% specificity for vibration detection and was robust to broadband vibrations. Somewhat higher sensitivity (98%) and specificity (99%) could be achieved using the more computationally intensive eigen decomposition-based algorithm. Vibration amplitudes as low as 1 mum were measured accurately in phantom experiments. Real-time tissue vibration imaging at typical color-flow frame rates was implemented on a software-programmable US system. Vibrations were studied in vivo in a stenosed femoral bypass vein graft in a human subject and in a punctured femoral artery and incised spleen in an animal model.

A high-throughput comparative characterization of laser-induced soft tissue damage using 3D digital microscopy.

PubMed

Das, Debobrato; Reed, Stephanie; Klokkevold, Perry R; Wu, Benjamin M

2013-02-01

3D digital microscopy was used to develop a rapid alternative approach to quantify the effects of specific laser parameters on soft tissue ablation and charring in vitro without the use of conventional tissue processing techniques. Two diode lasers operating at 810 and 980 nm wavelengths were used to ablate three tissue types (bovine liver, turkey breast, and bovine muscle) at varying laser power (0.3, 1.0, and 2.0 W) and velocities (1-50 mm/s). Spectrophotometric analyses were performed on each tissue to determine tissue-specific absorption coefficients and were considered in creating wavelength-dependent energy attenuation models to evaluate minimum heat of tissue ablations. 3D surface contour profiles characterizing tissue damage revealed that ablation depth and tissue charring increased with laser power and decreased with lateral velocity independent of wavelength and tissue type. While bovine liver ablation and charring were statistically higher at 810 than 980 nm (p < 0.05), turkey breast and bovine muscle ablated and charred more at 980 than 810 nm (p < 0.05). Spectrophotometric analysis revealed that bovine liver tissue had a greater tissue-specific absorption coefficient at 810 than 980 nm, while turkey breast and bovine muscle had a larger absorption coefficient at 980 nm (p < 0.05). This rapid 3D microscopic analysis of robot-driven laser ablation yielded highly reproducible data that supported well-defined trends related to laser-tissue interactions and enabled high throughput characterization of many laser-tissue permutations. Since 3D microscopy quantifies entire lesions without altering the tissue specimens, conventional and immunohistologic techniques can be used, if desired, to further interrogate specific sections of the digitized lesions.

Analysis of the Human Prostate-Specific Proteome Defined by Transcriptomics and Antibody-Based Profiling Identifies TMEM79 and ACOXL as Two Putative, Diagnostic Markers in Prostate Cancer

PubMed Central

O'Hurley, Gillian; Busch, Christer; Fagerberg, Linn; Hallström, Björn M.; Stadler, Charlotte; Tolf, Anna; Lundberg, Emma; Schwenk, Jochen M.; Jirström, Karin; Bjartell, Anders; Gallagher, William M.; Uhlén, Mathias; Pontén, Fredrik

2015-01-01

To better understand prostate function and disease, it is important to define and explore the molecular constituents that signify the prostate gland. The aim of this study was to define the prostate specific transcriptome and proteome, in comparison to 26 other human tissues. Deep sequencing of mRNA (RNA-seq) and immunohistochemistry-based protein profiling were combined to identify prostate specific gene expression patterns and to explore tissue biomarkers for potential clinical use in prostate cancer diagnostics. We identified 203 genes with elevated expression in the prostate, 22 of which showed more than five-fold higher expression levels compared to all other tissue types. In addition to previously well-known proteins we identified two poorly characterized proteins, TMEM79 and ACOXL, with potential to differentiate between benign and cancerous prostatic glands in tissue biopsies. In conclusion, we have applied a genome-wide analysis to identify the prostate specific proteome using transcriptomics and antibody-based protein profiling to identify genes with elevated expression in the prostate. Our data provides a starting point for further functional studies to explore the molecular repertoire of normal and diseased prostate including potential prostate cancer markers such as TMEM79 and ACOXL. PMID:26237329

Preparation and characterization of a three-dimensional printed scaffold based on a functionalized polyester for bone tissue engineering applications.

PubMed

Seyednejad, Hajar; Gawlitta, Debby; Dhert, Wouter J A; van Nostrum, Cornelus F; Vermonden, Tina; Hennink, Wim E

2011-05-01

At present there is a strong need for suitable scaffolds that meet the requirements for bone tissue engineering applications. The objective of this study was to investigate the suitability of porous scaffolds based on a hydroxyl functionalized polymer, poly(hydroxymethylglycolide-co-ε-caprolactone) (pHMGCL), for tissue engineering. In a recent study this polymer was shown to be a promising material for bone regeneration. The scaffolds consisting of pHMGCL or poly(ε-caprolactone) (PCL) were produced by means of a rapid prototyping technique (three-dimensional plotting) and were shown to have a high porosity and an interconnected pore structure. The thermal and mechanical properties of both scaffolds were investigated and human mesenchymal stem cells were seeded onto the scaffolds to evaluate the cell attachment properties, as well as cell viability and differentiation. It was shown that the cells filled the pores of the pHMGCL scaffold within 7 days and displayed increased metabolic activity when compared with cells cultured in PCL scaffolds. Importantly, pHMGCL scaffolds supported osteogenic differentiation. Therefore, scaffolds based on pHMGCL are promising templates for bone tissue engineering applications. Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Terahertz transmission vs reflection imaging and model-based characterization for excised breast carcinomas.

PubMed

Bowman, Tyler; El-Shenawee, Magda; Campbell, Lucas K

2016-09-01

This work presents experimental and analytical comparison of terahertz transmission and reflection imaging modes for assessing breast carcinoma in excised paraffin-embedded human breast tissue. Modeling for both transmission and reflection imaging is developed. The refractive index and absorption coefficient of the tissue samples are obtained. The reflection measurements taken at the system's fixed oblique angle of 30° are shown to be a hybridization of TE and TM modes. The models are validated with transmission spectroscopy at fixed points on fresh bovine muscle and fat tissues. Images based on the calculated absorption coefficient and index of refraction of bovine tissue are successfully compared with the terahertz magnitude and phase measured in the reflection mode. The validated techniques are extended to 20 and 30 μm slices of fixed human lobular carcinoma and infiltrating ductal carcinoma mounted on polystyrene microscope slides in order to investigate the terahertz differentiation of the carcinoma with non-cancerous tissue. Both transmission and reflection imaging show clear differentiation in carcinoma versus healthy tissue. However, when using the reflection mode, in the calculation of the thin tissue properties, the absorption is shown to be sensitive to small phase variations that arise due to deviations in slide and tissue thickness and non-ideal tissue adhesion. On the other hand, the results show that the transmission mode is much less sensitive to these phase variations. The results also demonstrate that reflection imaging provides higher resolution and more clear margins between cancerous and fibroglandular regions, cancerous and fatty regions, and fibroglandular and fatty tissue regions. In addition, more features consistent with high power pathology images are exhibited in the reflection mode images.

Ex vivo applications of multiphoton microscopy in urology

NASA Astrophysics Data System (ADS)

Jain, Manu; Mukherjee, Sushmita

2016-03-01

Background: Routine urological surgery frequently requires rapid on-site histopathological tissue evaluation either during biopsy or intra-operative procedure. However, resected tissue needs to undergo processing, which is not only time consuming but may also create artifacts hindering real-time tissue assessment. Likewise, pathologist often relies on several ancillary methods, in addition to H&E to arrive at a definitive diagnosis. Although, helpful these techniques are tedious and time consuming and often show overlapping results. Therefore, there is a need for an imaging tool that can rapidly assess tissue in real-time at cellular level. Multiphoton microscopy (MPM) is one such technique that can generate histology-quality images from fresh and fixed tissue solely based on their intrinsic autofluorescence emission, without the need for tissue processing or staining. Design: Fresh tissue sections (neoplastic and non-neoplastic) from biopsy and surgical specimens of bladder and kidney were obtained. Unstained deparaffinized slides from biopsy of medical kidney disease and oncocytic renal neoplasms were also obtained. MPM images were acquired using with an Olympus FluoView FV1000MPE system. After imaging, fresh tissues were submitted for routine histopathology. Results: Based on the architectural and cellular details of the tissue, MPM could characterize normal components of bladder and kidney. Neoplastic tissue could be differentiated from non-neoplastic tissue and could be further classified as per histopathological convention. Some of the tumors had unique MPM signatures not otherwise seen on H&E sections. Various subtypes of glomerular lesions were identified as well as renal oncocytic neoplasms were differentiated on unstained deparaffinized slides. Conclusions: We envision MPM to become an integral part of regular diagnostic workflow for rapid assessment of tissue. MPM can be used to evaluate the adequacy of biopsies and triage tissues for ancillary studies. It can also be used as an adjunct to frozen section analysis for intra-operative margin assessment. Further, it can play an important role for pathologist for guiding specimen grossing, selecting tissue for tumor banking and as a rapid ancillary diagnostic tool.

Surgical Reconstruction of Lower Face Degloving.

PubMed

Faria, Paulo Esteves Pinto; de Souza Carvalho, Abrahão Cavalcante Gomes; Masalskas, Bárbara; Chihara, Letícia; Sant'Ana, Eduardo; Filho, Osvaldo Magro

2016-10-01

One of the most impressive soft tissue injuries is the facial degloving, normally associated with industrial machines and traffic accidents. This injury is characterized by the separation of the skin and cartilage from the bones, compromising the soft tissues correlated in the trauma area, nerves, and blood vessels. A 28-year-old patient, male, was referred to Araçatuba's Santa Casa Hospital, after a motorcycle accident, hitting his face on the sidewalk. The patient was conscious, oriented, denying fainting and unconsciousness during the accident, and complaining of pain in the nasal region of the face. The suture of wounds was performed using 5-0 absorbable sutures for muscle planes, and reconstruction of the septum and nasal cartilages. The skin was sutured with interrupted stitches using 6-0 nylon. After reducing the edema, a slight increase in alar base was observed. Subsequently, the alar base cinch suture was performed aiming to bring the alar bases to a measure of 34.0 mm in diameter. As a conclusion, the knowledge of the anatomy of the region involved, the healing of tissues, and suture techniques for the facial region process were critical to the successful treatment. The evaluation of the alar base in degloving cases can involve aesthetic features.

Early breast cancer screening using iron/iron oxide-based nanoplatforms with sub-femtomolar limits of detection.

PubMed

Udukala, Dinusha N; Wang, Hongwang; Wendel, Sebastian O; Malalasekera, Aruni P; Samarakoon, Thilani N; Yapa, Asanka S; Abayaweera, Gayani; Basel, Matthew T; Maynez, Pamela; Ortega, Raquel; Toledo, Yubisela; Bossmann, Leonie; Robinson, Colette; Janik, Katharine E; Koper, Olga B; Li, Ping; Motamedi, Massoud; Higgins, Daniel A; Gadbury, Gary; Zhu, Gaohong; Troyer, Deryl L; Bossmann, Stefan H

2016-01-01

Proteases, including matrix metalloproteinases (MMPs), tissue serine proteases, and cathepsins (CTS) exhibit numerous functions in tumor biology. Solid tumors are characterized by changes in protease expression levels by tumor and surrounding tissue. Therefore, monitoring protease levels in tissue samples and liquid biopsies is a vital strategy for early cancer detection. Water-dispersable Fe/Fe3O4-core/shell based nanoplatforms for protease detection are capable of detecting protease activity down to sub-femtomolar limits of detection. They feature one dye (tetrakis(carboxyphenyl)porphyrin (TCPP)) that is tethered to the central nanoparticle by means of a protease-cleavable consensus sequence and a second dye (Cy 5.5) that is directly linked. Based on the protease activities of urokinase plasminogen activator (uPA), MMPs 1, 2, 3, 7, 9, and 13, as well as CTS B and L, human breast cancer can be detected at stage I by means of a simple serum test. By monitoring CTS B and L stage 0 detection may be achieved. This initial study, comprised of 46 breast cancer patients and 20 apparently healthy human subjects, demonstrates the feasibility of protease-activity-based liquid biopsies for early cancer diagnosis.

Early breast cancer screening using iron/iron oxide-based nanoplatforms with sub-femtomolar limits of detection

PubMed Central

Samarakoon, Thilani N; Yapa, Asanka S; Abayaweera, Gayani; Basel, Matthew T; Maynez, Pamela; Ortega, Raquel; Toledo, Yubisela; Bossmann, Leonie; Robinson, Colette; Janik, Katharine E; Koper, Olga B; Li, Ping; Motamedi, Massoud; Higgins, Daniel A; Gadbury, Gary

2016-01-01

Summary Proteases, including matrix metalloproteinases (MMPs), tissue serine proteases, and cathepsins (CTS) exhibit numerous functions in tumor biology. Solid tumors are characterized by changes in protease expression levels by tumor and surrounding tissue. Therefore, monitoring protease levels in tissue samples and liquid biopsies is a vital strategy for early cancer detection. Water-dispersable Fe/Fe3O4-core/shell based nanoplatforms for protease detection are capable of detecting protease activity down to sub-femtomolar limits of detection. They feature one dye (tetrakis(carboxyphenyl)porphyrin (TCPP)) that is tethered to the central nanoparticle by means of a protease-cleavable consensus sequence and a second dye (Cy 5.5) that is directly linked. Based on the protease activities of urokinase plasminogen activator (uPA), MMPs 1, 2, 3, 7, 9, and 13, as well as CTS B and L, human breast cancer can be detected at stage I by means of a simple serum test. By monitoring CTS B and L stage 0 detection may be achieved. This initial study, comprised of 46 breast cancer patients and 20 apparently healthy human subjects, demonstrates the feasibility of protease-activity-based liquid biopsies for early cancer diagnosis. PMID:27335730

Modular assembly of thick multifunctional cardiac patches

PubMed Central

Fleischer, Sharon; Shapira, Assaf; Feiner, Ron; Dvir, Tal

2017-01-01

In cardiac tissue engineering cells are seeded within porous biomaterial scaffolds to create functional cardiac patches. Here, we report on a bottom-up approach to assemble a modular tissue consisting of multiple layers with distinct structures and functions. Albumin electrospun fiber scaffolds were laser-patterned to create microgrooves for engineering aligned cardiac tissues exhibiting anisotropic electrical signal propagation. Microchannels were patterned within the scaffolds and seeded with endothelial cells to form closed lumens. Moreover, cage-like structures were patterned within the scaffolds and accommodated poly(lactic-co-glycolic acid) (PLGA) microparticulate systems that controlled the release of VEGF, which promotes vascularization, or dexamethasone, an anti-inflammatory agent. The structure, morphology, and function of each layer were characterized, and the tissue layers were grown separately in their optimal conditions. Before transplantation the tissue and microparticulate layers were integrated by an ECM-based biological glue to form thick 3D cardiac patches. Finally, the patches were transplanted in rats, and their vascularization was assessed. Because of the simple modularity of this approach, we believe that it could be used in the future to assemble other multicellular, thick, 3D, functional tissues. PMID:28167795

Photoactivated methods for enabling cartilage-to-cartilage tissue fixation

NASA Astrophysics Data System (ADS)

Sitterle, Valerie B.; Roberts, David W.

2003-06-01

The present study investigates whether photoactivated attachment of cartilage can provide a viable method for more effective repair of damaged articular surfaces by providing an alternative to sutures, barbs, or fibrin glues for initial fixation. Unlike artificial materials, biological constructs do not possess the initial strength for press-fitting and are instead sutured or pinned in place, typically inducing even more tissue trauma. A possible alternative involves the application of a photosensitive material, which is then photoactivated with a laser source to attach the implant and host tissues together in either a photothermal or photochemical process. The photothermal version of this method shows potential, but has been almost entirely applied to vascularized tissues. Cartilage, however, exhibits several characteristics that produce appreciable differences between applying and refining these techniques when compared to previous efforts involving vascularized tissues. Preliminary investigations involving photochemical photosensitizers based on singlet oxygen and electron transfer mechanisms are discussed, and characterization of the photodynamic effects on bulk collagen gels as a simplified model system using FTIR is performed. Previous efforts using photothermal welding applied to cartilaginous tissues are reviewed.

Method for Separation of Blood Vessels on the Three-Color Images of Biological Tissues

NASA Astrophysics Data System (ADS)

Lisenko, S. A.

2017-07-01

A new technology was developed to improve the visibility of blood vessels on images of tissues of hollow human organs(the alimentary tract and respiratory system) based on the relation between the color components of the image, the scattering properties of the tissue, and its hemoglobin content. A statistical operator was presented to convert the three-color image of the tissue into a parametric map objectively characterizing the concentration of hemoglobin in the tissue regardless of the illumination and shooting conditions. An algorithm for obtaining conversion parameters for image systems with known spectral characteristics was presented. An image of a multilayer multiple-scattering medium modeling bronchial tissue was synthesized and was used to evaluate the efficiency of the proposed conversion system. It was shown that the conversion made it possible to increase the contrast of the blood vessels by almost two orders of magnitude, to significantly improve the clarity of the display of their borders, and to eliminate almost completely the influence of background and nonuniform illumination of the medium in comparison with the original image.

Biomechanical paradigm and interpretation of female pelvic floor conditions before a treatment

PubMed Central

Lucente, Vincent; van Raalte, Heather; Murphy, Miles; Egorov, Vladimir

2017-01-01

Background Further progress in restoring a woman’s health may be possible if a patient with a damaged pelvic floor could undergo medical imaging and biomechanical diagnostic tests. The results of such tests could contribute to the analysis of multiple treatment options and suggest the optimal one for that patient. Aim To develop a new approach for the biomechanical characterization of vaginal conditions, muscles, and connective tissues in the female pelvic floor. Methods Vaginal tactile imaging (VTI) allows biomechanical assessment of the soft tissue along the entire length of the anterior, posterior, and lateral vaginal walls at rest, with manually applied deflection pressures and with muscle contraction, muscle relaxation, and Valsalva maneuver. VTI allows a large body of measurements to evaluate individual variations in tissue elasticity, support defects, as well as pelvic muscle function. Presuming that 1) the female pelvic floor organs are suspended by ligaments against which muscles contract to open or close the outlets and 2) damaged ligaments weaken the support and may reduce the force of muscle contraction, we made an attempt to characterize multiple pelvic floor structures from VTI data. Results All of the 138 women enrolled in the study were successfully examined with the VTI. The study subjects have had normal pelvic support or pelvic organ prolapse (stages I–IV). The average age of this group of subjects was 60±15 years. We transposed a set of 31 VTI parameters into a quantitative characterization of pelvic muscles and ligamentous structures. Interpretation of the acquired VTI data for normal pelvic floor support and prolapse conditions is proposed based on biomechanical assessment of the functional anatomy. Conclusion Vaginal tactile imaging allows biomechanical characterization of female pelvic floor structures and tissues in vivo, which may help to optimize treatment of the diseased conditions such as prolapse, incontinence, atrophy, and some forms of pelvic pain. PMID:28831274

Characterization of a Honeycomb-Like Scaffold With Dielectrophoresis-Based Patterning for Tissue Engineering.

PubMed

Huan, Zhijie; Chu, Henry K; Yang, Jie; Sun, Dong

2017-04-01

Seeding and patterning of cells with an engineered scaffold is a critical process in artificial tissue construction and regeneration. To date, many engineered scaffolds exhibit simple intrinsic designs, which fail to mimic the geometrical complexity of native tissues. In this study, a novel scaffold that can automatically seed cells into multilayer honeycomb patterns for bone tissue engineering application was designed and examined. The scaffold incorporated dielectrophoresis for noncontact manipulation of cells and intrinsic honeycomb architectures were integrated in each scaffold layer. When a voltage was supplied to the stacked scaffold layers, three-dimensional electric fields were generated, thereby manipulating cells to form into honeycomb-like cellular patterns for subsequent culture. The biocompatibility of the scaffold material was confirmed through the cell viability test. Experiments were conducted to evaluate the cell viability during DEP patterning at different voltage amplitudes, frequencies, and manipulating time. Three different mammalian cells were examined and the effects of the cell size and the cell concentration on the resultant cellular patterns were evaluated. Results showed that the proposed scaffold structure was able to construct multilayer honeycomb cellular patterns in a manner similar to the natural tissue. This honeycomb-like scaffold and the dielectrophoresis-based patterning technique examined in this study could provide the field with a promising tool to enhance seeding and patterning of a wide range of cells for the development of high-quality artificial tissues.

Joint learning of ultrasonic backscattering statistical physics and signal confidence primal for characterizing atherosclerotic plaques using intravascular ultrasound.

PubMed

Sheet, Debdoot; Karamalis, Athanasios; Eslami, Abouzar; Noël, Peter; Chatterjee, Jyotirmoy; Ray, Ajoy K; Laine, Andrew F; Carlier, Stephane G; Navab, Nassir; Katouzian, Amin

2014-01-01

Intravascular Ultrasound (IVUS) is a predominant imaging modality in interventional cardiology. It provides real-time cross-sectional images of arteries and assists clinicians to infer about atherosclerotic plaques composition. These plaques are heterogeneous in nature and constitute fibrous tissue, lipid deposits and calcifications. Each of these tissues backscatter ultrasonic pulses and are associated with a characteristic intensity in B-mode IVUS image. However, clinicians are challenged when colocated heterogeneous tissue backscatter mixed signals appearing as non-unique intensity patterns in B-mode IVUS image. Tissue characterization algorithms have been developed to assist clinicians to identify such heterogeneous tissues and assess plaque vulnerability. In this paper, we propose a novel technique coined as Stochastic Driven Histology (SDH) that is able to provide information about co-located heterogeneous tissues. It employs learning of tissue specific ultrasonic backscattering statistical physics and signal confidence primal from labeled data for predicting heterogeneous tissue composition in plaques. We employ a random forest for the purpose of learning such a primal using sparsely labeled and noisy samples. In clinical deployment, the posterior prediction of different lesions constituting the plaque is estimated. Folded cross-validation experiments have been performed with 53 plaques indicating high concurrence with traditional tissue histology. On the wider horizon, this framework enables learning of tissue-energy interaction statistical physics and can be leveraged for promising clinical applications requiring tissue characterization beyond the application demonstrated in this paper. Copyright © 2013 Elsevier B.V. All rights reserved.

Technical Note: Radiological properties of tissue surrogates used in a multimodality deformable pelvic phantom for MR-guided radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Niebuhr, Nina I., E-mail: n.niebuhr@dkfz.de; Johnen, Wibke; Güldaglar, Timur

Purpose: Phantom surrogates were developed to allow multimodal [computed tomography (CT), magnetic resonance imaging (MRI), and teletherapy] and anthropomorphic tissue simulation as well as materials and methods to construct deformable organ shapes and anthropomorphic bone models. Methods: Agarose gels of variable concentrations and loadings were investigated to simulate various soft tissue types. Oils, fats, and Vaseline were investigated as surrogates for adipose tissue and bone marrow. Anthropomorphic shapes of bone and organs were realized using 3D-printing techniques based on segmentations of patient CT-scans. All materials were characterized in dual energy CT and MRI to adapt CT numbers, electron density, effectivemore » atomic number, as well as T1- and T2-relaxation times to patient and literature values. Results: Soft tissue simulation could be achieved with agarose gels in combination with a gadolinium-based contrast agent and NaF to simulate muscle, prostate, and tumor tissues. Vegetable oils were shown to be a good representation for adipose tissue in all modalities. Inner bone was realized using a mixture of Vaseline and K{sub 2}HPO{sub 4}, resulting in both a fatty bone marrow signal in MRI and inhomogeneous areas of low and high attenuation in CT. The high attenuation of outer bone was additionally adapted by applying gypsum bandages to the 3D-printed hollow bone case with values up to 1200 HU. Deformable hollow organs were manufactured using silicone. Signal loss in the MR images based on the conductivity of the gels needs to be further investigated. Conclusions: The presented surrogates and techniques allow the customized construction of multimodality, anthropomorphic, and deformable phantoms as exemplarily shown for a pelvic phantom, which is intended to study adaptive treatment scenarios in MR-guided radiation therapy.« less

Technical Note: Radiological properties of tissue surrogates used in a multimodality deformable pelvic phantom for MR-guided radiotherapy.

PubMed

Niebuhr, Nina I; Johnen, Wibke; Güldaglar, Timur; Runz, Armin; Echner, Gernot; Mann, Philipp; Möhler, Christian; Pfaffenberger, Asja; Jäkel, Oliver; Greilich, Steffen

2016-02-01

Phantom surrogates were developed to allow multimodal [computed tomography (CT), magnetic resonance imaging (MRI), and teletherapy] and anthropomorphic tissue simulation as well as materials and methods to construct deformable organ shapes and anthropomorphic bone models. Agarose gels of variable concentrations and loadings were investigated to simulate various soft tissue types. Oils, fats, and Vaseline were investigated as surrogates for adipose tissue and bone marrow. Anthropomorphic shapes of bone and organs were realized using 3D-printing techniques based on segmentations of patient CT-scans. All materials were characterized in dual energy CT and MRI to adapt CT numbers, electron density, effective atomic number, as well as T1- and T2-relaxation times to patient and literature values. Soft tissue simulation could be achieved with agarose gels in combination with a gadolinium-based contrast agent and NaF to simulate muscle, prostate, and tumor tissues. Vegetable oils were shown to be a good representation for adipose tissue in all modalities. Inner bone was realized using a mixture of Vaseline and K2HPO4, resulting in both a fatty bone marrow signal in MRI and inhomogeneous areas of low and high attenuation in CT. The high attenuation of outer bone was additionally adapted by applying gypsum bandages to the 3D-printed hollow bone case with values up to 1200 HU. Deformable hollow organs were manufactured using silicone. Signal loss in the MR images based on the conductivity of the gels needs to be further investigated. The presented surrogates and techniques allow the customized construction of multimodality, anthropomorphic, and deformable phantoms as exemplarily shown for a pelvic phantom, which is intended to study adaptive treatment scenarios in MR-guided radiation therapy.

Multiscale quantification of tissue spiculation and distortion for detection of architectural distortion and spiculated mass in mammography

NASA Astrophysics Data System (ADS)

Lao, Zhiqiang; Zheng, Xin

2011-03-01

This paper proposes a multiscale method to quantify tissue spiculation and distortion in mammography CAD systems that aims at improving the sensitivity in detecting architectural distortion and spiculated mass. This approach addresses the difficulty of predetermining the neighborhood size for feature extraction in characterizing lesions demonstrating spiculated mass/architectural distortion that may appear in different sizes. The quantification is based on the recognition of tissue spiculation and distortion pattern using multiscale first-order phase portrait model in texture orientation field generated by Gabor filter bank. A feature map is generated based on the multiscale quantification for each mammogram and two features are then extracted from the feature map. These two features will be combined with other mass features to provide enhanced discriminate ability in detecting lesions demonstrating spiculated mass and architectural distortion. The efficiency and efficacy of the proposed method are demonstrated with results obtained by applying the method to over 500 cancer cases and over 1000 normal cases.

Identification and characterization of gadolinium(III) complexes in biological tissue extracts.

PubMed

Kahakachchi, Chethaka L; Moore, Dennis A

2010-07-01

The gadolinium species present in a rat kidney following intravenous administration of a gadolinium-based magnetic resonance contrast agent (Optimark™, Gadoversetamide injection) to a rat was examined in the present study. The major gadolinium species in the supernatant of the rat kidney tissue extracts was determined by reversed-phase liquid chromatography with online inductively coupled plasma optical emission spectrometry (HPLC-ICP-OES). The identity of the compound was established by liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) detection. The principal gadolinium(III) complex in a rat kidney tissue extract was identified as Gd-DTPA-BMEA 24 Hrs and 7 days after a single intravenous injection of Optimark™ (gadoversetamide; Gd-DTPA-BMEA) at a dose of 5 mmol Gd/kg body weight. The study demonstrated for the first time the feasibility of the use of two complementary techniques, HPLC-ICP-OES and HPLC-ESI-MS to study the in vivo behavior of gadolinium-based magnetic resonance contrast media.

Content and distribution of noncollagenous matrix proteins in bone and cementum: relationship to speed of formation and collagen packing density.

PubMed

Nanci, A

1999-06-30

The organic matrix of collagen-based calcified tissues consists of a supporting collagen meshwork and various noncollagenous matrix proteins (NCPs). Together, they contribute to determining the structure and biomechanical properties of the tissue. Their respective organization and interrelation can advantageously be examined by immunocytochemistry, an approach which allows correlation of composition with structure. The aim of this article is to review postembedding immuno- and lectin-gold-labeling data on the characterization of the noncollagenous compartment in rat and human bone and cementum, and on its relationship to collagen. The two major NCPs, bone sialoprotein and osteopontin, generally codistribute and accumulate in cement lines and in the spaces among the mineralized collagen fibrils. However, there are variations in their distribution and density of labeling throughout the tissue. Indeed, bone and cementum can form in environments that are either poor or enriched in NCPs. The amount of NCPs generally correlates with bone and cementum types and with speed of formation of the tissue and packing density of collagen fibrils. Taken together, the data suggest that production of both collagenous and noncollagenous constituents can be "modulated" during formation of collagen-based calcified tissues. It is concluded that, in addition to structural and compositional parameters, tissue dynamics must be taken into consideration in order to understand the significance of the apparent accumulation of NCPs at some sites and to determine the mechanisms of normal and pathological calcified tissue formation. Copyright 1999 Academic Press.

Laser-induced tissue fluorescence in radiofrequency tissue-fusion characterization.

PubMed

Su, Lei; Fonseca, Martina B; Arya, Shobhit; Kudo, Hiromi; Goldin, Robert; Hanna, George B; Elson, Daniel S

2014-01-01

Heat-induced tissue fusion is an important procedure in modern surgery and can greatly reduce trauma, complications, and mortality during minimally invasive surgical blood vessel anastomosis, but it may also have further benefits if applied to other tissue types such as small and large intestine anastomoses. We present a tissue-fusion characterization technology using laser-induced fluorescence spectroscopy, which provides further insight into tissue constituent variations at the molecular level. In particular, an increase of fluorescence intensity in 450- to 550-nm range for 375- and 405-nm excitation suggests that the collagen cross-linking in fused tissues increased. Our experimental and statistical analyses showed that, by using fluorescence spectral data, good fusion could be differentiated from other cases with an accuracy of more than 95%. This suggests that the fluorescence spectroscopy could be potentially used as a feedback control method in online tissue-fusion monitoring.

Psychiatric Brain Banking: Three Perspectives on Current Trends and Future Directions

PubMed Central

Deep-Soboslay, Amy; Benes, Francine M.; Haroutunian, Vahram; Ellis, Justin K.; Kleinman, Joel E.; Hyde, Thomas M.

2011-01-01

Introduction The study of postmortem human brain tissue is central to the advancement of the neurobiological studies of psychiatric illness, particularly for the study of brain-specific isoforms and molecules. Methods The state-of-the-art methods and recommendations for maintaining a successful brain bank for psychiatric disorders are discussed, using the convergence of viewpoints from three brain collections, the National Institute of Mental Health Brain Collection (NIMH), the Harvard Brain Tissue Resource Center (HBTRC), and the Mt. Sinai School of Medicine Brain Bank (MSSM-BB), with diverse research interests and divergent approaches to tissue acquisition. Results While the NIMH obtains donations from medical examiners for its collection, and places particular emphasis on clinical diagnosis, toxicology, and building lifespan control cohorts, the HBTRC is uniquely designed as a repository whose sole purpose is to collect large-volume, high quality brain tissue from community-based donors based on relationships across an expansive nationwide network, and places emphasis on the accessibility of its bank in disseminating tissue and related data to research groups worldwide. The MSSM-BB collection has shown that, with dedication, prospective recruitment is a successful approach to tissue donation, and places particular emphasis on rigorous clinical diagnosis through antemortem contact with donors. The MSSM-BB places great importance on stereological tissue sampling methods for neuroanatomical studies, and frozen tissue sampling approaches that enable multiple assessments (RNA, DNA, protein, enzyme activity, binding, etc.) of the same tissue block. Promising scientific approaches for elucidating the molecular and cellular pathways in brain that may contribute to schizophrenia and/or bipolar disorder, such as cell culture techniques and microarray-based gene expression and genotyping studies are briefly discussed. Conclusions Despite unique perspectives from three established brain collections, there is a consensus that (1) diverse strategies for tissue acquisition, (2) rigor in tissue and diagnostic characterization, (3) the importance of sample accessibility, and (4) continual application of innovative scientific approaches to the study of brain tissue are all integral to the success and future of psychiatric brain banking. The future of neuropsychiatric research depends upon in the availability of high quality brain specimens from large numbers of subjects, including non-psychiatric controls. PMID:20673875

Numerical investigation of oxygen transport by hemoglobin-based carriers through microvessels.

PubMed

Hyakutake, Toru; Kishimoto, Takumi

2017-12-01

The small size of hemoglobin-based oxygen carriers (HBOCs) may expand the realm of new treatment possibilities for various circulatory diseases. The parametric evaluation of HBOC performance for oxygen transport within tissue is essential for effectively characterizing its performance for each circulatory disease assessed. Thus, the overarching objective of this present study was to numerically investigate the reaction-diffusion phenomenon of oxygenated HBOCs and oxygen on tissues through microvessels. We considered dissociation rate coefficients, oxygen affinity, and diffusion coefficients due to Brownian motion as the biophysical parameters for estimating HBOC performance for oxygen transport. A two-dimensional computational domain, including vessel and tissue regions, was, therefore, accordingly assumed. It was observed that HBOC flows in a microvessel with a diameter of 25 μm and a length of 1 mm, and that the dissociated oxygen diffuses to the tissue region. The results indicated that oxyhemoglobin saturation and partial oxygen tension in a downstream region changed according to each biophysical parameter of HBOC. Moreover, the change in oxygen consumption rate in the tissue region had considerable influence on the oxyhemoglobin saturation level within the vessel. Comparison between simulation results and existing in vitro experimental data of actual HBOCs and RBC showed qualitatively good agreement. These results provide important information for the effective design of robust HBOCs in future.

Comparison of mechanical behavior between implant-simulated bone tissue and implant-jaw bone tissue interfaces based on Pull Out testing

NASA Astrophysics Data System (ADS)

Lopez, C.; Muñoz, J. C.; Pinillos, J. C.

2013-11-01

The main purpose of this research was to achieve a better understanding of the relationship within the mechanical properties of human cadaver jaw bone with kind D2 density regarding a substitute polymer to simulate bone tissue, proposed by the ASTM, to evaluate orthopedic implants. However, despite the existence of several densities of foams and his mechanical characterization has been classified into different degrees of tissue densities to simulate cancellous and cortical bone, the value of the densities are different contrasted with the densities of bone tissue, making difficult to establish direct relationship about mechanical behavior between the polymer and the bone material, and therefore no clear criteria known for choosing the polymeric foam which describes the mechanical behavior of tissue for a specific or particular study. To understand such behavior from bone tissue regarding the polymer samples, on this research was a dental implant inserted into the samples, and subjected to destructive Pull Out test according to ASTM F543The Pull Out strength was compared between implant-jawbone and implant-rigid polyurethane foam interfaces. Thus, the test pieces with mechanical behavior similar to bone tissue, enabling an approximation to choose degree appropriate of polymer to replace the bone tissue in future trials biomechanical.

Design and Fabrication of an MRI-Compatible, Autonomous Incubation System.

PubMed

Khalilzad-Sharghi, Vahid; Xu, Huihui

2015-10-01

Tissue engineers have long sought access to an autonomous, imaging-compatible tissue incubation system that, with minimum operator handling, can provide real-time visualization and quantification of cells, tissue constructs, and organs. This type of screening system, capable of operating noninvasively to validate tissue, can overcome current limitations like temperature shock, unsustainable cellular environments, sample contamination, and handling/stress. However, this type of system has been a major challenge, until now. Here, we describe the design, fabrication, and characterization of an innovative, autonomous incubation system that is compatible with a 9.4 T magnetic resonance imaging (MRI) scanner. Termed the e-incubator (patent pending; application number: 13/953,984), this microcontroller-based system is integrated into an MRI scanner and noninvasively screens cells and tissue cultures in an environment where temperature, pH, and media/gas handling are regulated. The 4-week study discussed herein details the continuous operation of the e-incubator for a tissue-engineered osteogenic construct, validated by LIVE/DEAD(®) cell assays and histology. The evolving MR quantitative parameters of the osteogenic construct were used as biomarkers for bone tissue engineering and to further validate the quality of the product noninvasively before harvesting. Importantly, the e-incubator reliably facilitates culturing cells and tissue constructs to create engineered tissues and/or investigate disease therapies.

Characterization of the Embryogenic Tissue of the Norway Spruce Including a Transition Layer between the Tissue and the Culture Medium by Magnetic Resonance Imaging

NASA Astrophysics Data System (ADS)

Kořínek, R.; Mikulka, J.; Hřib, J.; Hudec, J.; Havel, L.; Bartušek, K.

2017-02-01

The paper describes the visualization of the cells (ESEs) and mucilage (ECMSN) in an embryogenic tissue via magnetic resonance imaging (MRI) relaxometry measurement combined with the subsequent multi-parametric segmentation. The computed relaxometry maps T1 and T2 show a thin layer (transition layer) between the culture medium and the embryogenic tissue. The ESEs, mucilage, and transition layer differ in their relaxation times T1 and T2; thus, these times can be used to characterize the individual parts within the embryogenic tissue. The observed mean values of the relaxation times T1 and T2 of the ESEs, mucilage, and transition layer are as follows: 1469 ± 324 and 53 ± 10 ms, 1784 ± 124 and 74 ± 8 ms, 929 ± 164 and 32 ± 4.7 ms, respectively. The multi-parametric segmentation exploiting the T1 and T2 relaxation times as a classifier shows the distribution of the ESEs and mucilage within the embryogenic tissue. The discussed T1 and T2 indicators can be utilized to characterize both the growth-related changes in an embryogenic tissue and the effect of biotic/abiotic stresses, thus potentially becoming a distinctive indicator of the state of any examined embryogenic tissue.

Tissue refractometry using Hilbert phase microscopy.

PubMed

Lue, Niyom; Bewersdorf, Joerg; Lessard, Mark D; Badizadegan, Kamran; Dasari, Ramachandra R; Feld, Michael S; Popescu, Gabriel

2007-12-15

We present, for the first time to our knowledge, quantitative phase images associated with unstained 5 mum thick tissue slices of mouse brain, spleen, and liver. The refractive properties of the tissue are retrieved in terms of the average refractive index and its spatial variation. We find that the average refractive index varies significantly with tissue type, such that the brain is characterized by the lowest value and the liver by the highest. The spatial power spectra of the phase images reveal power law behavior with different exponents for each tissue type. This approach opens a new possibility for stain-free characterization of tissues, where the diagnostic power is provided by the intrinsic refractive properties of the biological structure. We present results obtained for liver tissue affected by a lysosomal storage disease and show that our technique can quantify structural changes during this disease development.

Endoscopic Ultrasound Elastography: Current Clinical Use in Pancreas.

PubMed

Mondal, Utpal; Henkes, Nichole; Patel, Sandeep; Rosenkranz, Laura

2016-08-01

Elastography is a newer technique for the assessment of tissue elasticity using ultrasound. Cancerous tissue is known to be stiffer (hence, less elastic) than corresponding healthy tissue, and as a result, could be identified in an elasticity-based imaging. Ultrasound elastography has been used in the breast, thyroid, and cervix to differentiate malignant from benign neoplasms and to guide or avoid unnecessary biopsies. In the liver, elastography has enabled a noninvasive and reliable estimate of fibrosis. Endoscopic ultrasound has become a robust diagnostic and therapeutic tool for the management of pancreatic diseases. The addition of elastography to endoscopic ultrasound enabled further characterization of pancreas lesions, and several European and Asian studies have reported encouraging results. The current clinical role of endoscopic ultrasound elastography in the management of pancreas disorders and related literature are reviewed.

Proteomic analysis of tissue samples in translational breast cancer research.

PubMed

Gromov, Pavel; Moreira, José M A; Gromova, Irina

2014-06-01

In the last decade, many proteomic technologies have been applied, with varying success, to the study of tissue samples of breast carcinoma for protein expression profiling in order to discover protein biomarkers/signatures suitable for: characterization and subtyping of tumors; early diagnosis, and both prognosis and prediction of outcome of chemotherapy. The purpose of this review is to critically appraise what has been achieved to date using proteomic technologies and to bring forward novel strategies - based on the analysis of clinically relevant samples - that promise to accelerate the translation of basic discoveries into the daily breast cancer clinical practice. In particular, we address major issues in experimental design by reviewing the strengths and weaknesses of current proteomic strategies in the context of the analysis of human breast tissue specimens.

Anthropomorphic breast phantoms for preclinical imaging evaluation with transmission or emission imaging

NASA Astrophysics Data System (ADS)

Tornai, Martin P.; McKinley, Randolph L.; Bryzmialkiewicz, Caryl N.; Cutler, Spencer J.; Crotty, Dominic J.

2005-04-01

With the development of several classes of dedicated emission and transmission imaging technologies utilizing ionizing radiation for improved breast cancer detection and in vivo characterization, it is extremely useful to have available anthropomorphic breast phantoms in a variety of shapes, sizes and malleability prior to clinical imaging. These anthropomorphic phantoms can be used to evaluate the implemented imaging approaches given a known quantity, the phantom, and to evaluate the variability of the measurement due to the imaging system chain. Thus, we have developed a set of fillable and incompressible breast phantoms ranging in volume from 240 to 1730mL with nipple-to-chest distances from 3.8 to 12cm. These phantoms are mountable and exchangeable on either a uniform chest plate or anthropomorphic torso phantom containing tissue equivalent bones and surface tissue. Another fillable ~700mL breast phantom with solid anterior chest plate is intentionally compressible, and can be used for direct comparisons between standard planar imaging approaches using mild-to-severe compression, partially compressed tomosynthesis, and uncompressed computed mammotomography applications. These phantoms can be filled with various fluids (water and oil based liquids) to vary the fatty tissue background composition. Shaped cellulose sponges with two cell densities are fabricated and can be added to the breasts to simulate connective tissue. Additionally, microcalcifications can be simulated by peppering slits in the sponges with oyster shell fragments. These phantoms have a utility in helping to evaluate clinical imaging paradigms with known input object parameters using basic imaging characterization, in an effort to further evaluate contemporary and next generation imaging tools. They may additionally provide a means to collect known data samples for task based optimization studies.

Non invasive radiofrequency diagnostics of cancer. The Bioscanner — Trimprob technology and clinical applications

NASA Astrophysics Data System (ADS)

Vedruccio, Clarbruno; Ricci Vedruccio, Carla

2011-12-01

A new paper by Pokorny, Vedruccio, Cifra, Kucera, titled Cancer physics: Diagnostics based on damped cellular elasto-electrical vibrations in microtubules, recently available on Eur. Biophys. J., discloses the mechanism of active grown cancer tissues interaction with a Non- Linear Resonance Interaction (NLRI) Bioscanner Trimprob diagnostic device that is certified and ready to be used to investigate suspected cases of disease and cancer. This technology spreads early capabilities of cancer detection by means of low level radiofrequency oscillations in UHF band. The system is based on an unique and extremely innovative non- linear radiofrequency oscillator working on 462-465 MHz plus the harmonics. The diseased tissues suspected of cancer, are irradiated by means of a handy probe near field emission, while a spectrum analyzer placed in the far field detects by means of a small antenna, the oscillator interaction within the tissues. The Bioscanner is characterized by a high dynamic range, in the order of 30 or more decibel, and is useful for detection of small cancer agglomerates, if used by a well trained operator. At the resonance, the free running oscillator locks-in on the specific interaction frequency, in a sharp frequency window centered on 462 MHz; the resulting effect is evidenced by a deep decrease of the 462 MHz spectral line propagation in the far field around the oscillator probe. The NLRI provides a selective characterization, like a sort of a electronic biopsy response of biologic tissues in support of modern imaging diagnostics. Further to existing literature describing methods for cancer detections by means of electromagnetic fields this paper shows this innovative in vivo medical diagnostic equipment and some clinical applications.

Fabrication and characterization of highly porous barium titanate based scaffold coated by Gel/HA nanocomposite with high piezoelectric coefficient for bone tissue engineering applications.

PubMed

Ehterami, Arian; Kazemi, Mansure; Nazari, Bahareh; Saraeian, Payam; Azami, Mahmoud

2018-03-01

It is well established that the piezoelectric effect plays an important physiological role in bone growth, remodeling and fracture healing. Barium titanate, as a well-known piezoelectric ceramic, is especially an attractive material as a scaffold for bone tissue engineering applications. In this regard, we tried to fabricate a highly porous barium titanate based scaffolds by foam replication method and polarize them by applying an external electric field. In order to enhance the mechanical and biological properties, polarized/non-polarized scaffolds were coated with gelatin and nanostructured HA and characterized for their morphologies, porosities, piezoelectric and mechanical properties. The results showed that the compressive strength and piezoelectric coefficient of porous scaffolds increased with the increase of sintering temperature. After being coated with Gel/HA nanocomposite, the interconnected porous structure and pore size of the scaffolds almost remain unchanged while the Gel/nHA-coated scaffolds exhibited enhanced compressive strength and elastic modulus compared with the uncoated samples. Also, the effect of polarizing and coating of optimal scaffolds on adhesion, viability, and proliferation of the MG63 osteoblast-like cell line was evaluated by scanning electron microscope (SEM) and MTT assay. The cell culture experiments revealed that developed scaffolds had good biocompatibility and cells were able to adhere, proliferate and migrate into pores of the scaffolds. Furthermore, cell density was significantly higher in the coated scaffolds at all tested time-points. These results indicated that highly porous barium titanate scaffolds coated with Gel/HA nanocomposite has great potential in tissue engineering applications for bone tissue repair and regeneration. Copyright © 2018 Elsevier Ltd. All rights reserved.

Clustering methods applied in the detection of Ki67 hot-spots in whole tumor slide images: an efficient way to characterize heterogeneous tissue-based biomarkers.

PubMed

Lopez, Xavier Moles; Debeir, Olivier; Maris, Calliope; Rorive, Sandrine; Roland, Isabelle; Saerens, Marco; Salmon, Isabelle; Decaestecker, Christine

2012-09-01

Whole-slide scanners allow the digitization of an entire histological slide at very high resolution. This new acquisition technique opens a wide range of possibilities for addressing challenging image analysis problems, including the identification of tissue-based biomarkers. In this study, we use whole-slide scanner technology for imaging the proliferating activity patterns in tumor slides based on Ki67 immunohistochemistry. Faced with large images, pathologists require tools that can help them identify tumor regions that exhibit high proliferating activity, called "hot-spots" (HSs). Pathologists need tools that can quantitatively characterize these HS patterns. To respond to this clinical need, the present study investigates various clustering methods with the aim of identifying Ki67 HSs in whole tumor slide images. This task requires a method capable of identifying an unknown number of clusters, which may be highly variable in terms of shape, size, and density. We developed a hybrid clustering method, referred to as Seedlink. Compared to manual HS selections by three pathologists, we show that Seedlink provides an efficient way of detecting Ki67 HSs and improves the agreement among pathologists when identifying HSs. Copyright © 2012 International Society for Advancement of Cytometry.

Non-linear imaging and characterization of atherosclerotic arterial tissue using combined two photon fluorescence, second-harmonic generation and CARS microscopy

NASA Astrophysics Data System (ADS)

Cicchi, Riccardo; Matthäus, Christian; Meyer, Tobias; Lattermann, Annika; Dietzek, Benjamin; Brehm, Bernhard R.; Popp, Jürgen; Pavone, Francesco S.

2014-02-01

Atherosclerosis is among the most widespread cardiovascular diseases and one of the leading cause of death in the Western World. Characterization of arterial tissue in atherosclerotic condition is extremely interesting from the diagnostic point of view. Routinely used diagnostic methods, such as histopathological examination, are limited to morphological analysis of the examined tissues, whereas an exhaustive characterization requires a morpho-functional approach. Multimodal non-linear microscopy has the potential to bridge this gap by providing morpho-functional information on the examined tissues in a label-free way. Here we employed multiple non-linear microscopy techniques, including CARS, TPF, and SHG to provide intrinsic optical contrast from various tissue components in both arterial wall and atherosclerotic plaques. CARS and TPF microscopy were used to respectively image lipid depositions within plaques and elastin in the arterial wall. Cholesterol deposition in the lumen and collagen in the arterial wall were selectively imaged by SHG microscopy and distinguished by forward-backward SHG ratio. Image pattern analysis allowed characterizing collagen organization in different tissue regions. Different values of fiber mean size, distribution and anisotropy are calculated for lumen and media prospectively allowing for automated classification of atherosclerotic lesions. The presented method represents a promising diagnostic tool for evaluating atherosclerotic tissue and has the potential to find a stable place in clinical setting as well as to be applied in vivo in the near future.

Establishment and characterization of novel epithelial-like cell lines derived from human periodontal ligament tissue in vitro.

PubMed

Tansriratanawong, Kallapat; Ishikawa, Hiroshi; Toyomura, Junko; Sato, Soh

2017-10-01

In this study, novel human-derived epithelial-like cells (hEPLCs) lines were established from periodontal ligament (PDL) tissues, which were composed of a variety of cell types and exhibited complex cellular activities. To elucidate the putative features distinguishing these from epithelial rest of Malassez (ERM), we characterized hEPLCs based on cell lineage markers and tight junction protein expression. The aim of this study was, therefore, to establish and characterize hEPLCs lines from PDL tissues. The hEPLCs were isolated from PDL of third molar teeth. Cellular morphology and cell organelles were observed thoroughly. The characteristics of epithelial-endothelial-mesenchymal-like cells were compared in several markers by gene expression and immunofluorescence, to ERM and human umbilical-vein endothelial cells (HUVECs). The resistance between cellular junctions was assessed by transepithelial electron resistance, and inflammatory cytokines were detected by ELISA after infecting hEPLCs with periodontopathic bacteria. The hEPLCs developed into small epithelial-like cells in pavement appearance similar to ERM. However, gene expression patterns and immunofluorescence results were different from ERM and HUVECs, especially in tight junction markers (Claudin, ZO-1, and Occludins), and endothelial markers (vWF, CD34). The transepithelial electron resistance indicated higher resistance in hEPLCs, as compared to ERM. Periodontopathic bacteria were phagocytosed with upregulation of inflammatory cytokine secretion within 24 h. In conclusion, hEPLCs that were derived using the single cell isolation method formed tight multilayers colonies, as well as strongly expressed tight junction markers in gene expression and immunofluorescence. Novel hEPLCs lines exhibited differently from ERM, which might provide some specific functions such as metabolic exchange and defense mechanism against bacterial invasion in periodontal tissue.

Ultrasound Tissue Characterization of Vulnerable Atherosclerotic Plaque

PubMed Central

Picano, Eugenio; Paterni, Marco

2015-01-01

A thrombotic occlusion of the vessel fed by ruptured coronary atherosclerotic plaque may result in unstable angina, myocardial infarction or death, whereas embolization from a plaque in carotid arteries may result in transient ischemic attack or stroke. The atherosclerotic plaque prone to such clinical events is termed high-risk or vulnerable plaque, and its identification in humans before it becomes symptomatic has been elusive to date. Ultrasonic tissue characterization of the atherosclerotic plaque is possible with different techniques—such as vascular, transesophageal, and intravascular ultrasound—on a variety of arterial segments, including carotid, aorta, and coronary districts. The image analysis can be based on visual, video-densitometric or radiofrequency methods and identifies three distinct textural patterns: hypo-echoic (corresponding to lipid- and hemorrhage-rich plaque), iso- or moderately hyper-echoic (fibrotic or fibro-fatty plaque), and markedly hyperechoic with shadowing (calcific plaque). Hypoechoic or dishomogeneous plaques, with spotty microcalcification and large plaque burden, with plaque neovascularization and surface irregularities by contrast-enhanced ultrasound, are more prone to clinical complications than hyperechoic, extensively calcified, homogeneous plaques with limited plaque burden, smooth luminal plaque surface and absence of neovascularization. Plaque ultrasound morphology is important, along with plaque geometry, in determining the atherosclerotic prognostic burden in the individual patient. New quantitative methods beyond backscatter (to include speed of sound, attenuation, strain, temperature, and high order statistics) are under development to evaluate vascular tissues. Although not yet ready for widespread clinical use, tissue characterization is listed by the American Society of Echocardiography roadmap to 2020 as one of the most promising fields of application in cardiovascular ultrasound imaging, offering unique opportunities for the early detection and treatment of atherosclerotic disease. PMID:25950760

SU-F-T-398: Improving Radiotherapy Treatment Planning Using Dual Energy Computed Tomography Based Tissue Characterization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomic, N; Bekerat, H; Seuntjens, J

Purpose: Both kVp settings and geometric distribution of various materials lead to significant change of the HU values, showing the largest discrepancy for high-Z materials and for the lowest CT scanning kVp setting. On the other hand, the dose distributions around low-energy brachytherapy sources are highly dependent on the architecture and composition of tissue heterogeneities in and around the implant. Both measurements and Monte Carlo calculations show that improper tissue characterization may lead to calculated dose errors of 90% for low energy and around 10% for higher energy photons. We investigated the ability of dual-energy CT (DECT) to characterize moremore » accurately tissue equivalent materials. Methods: We used the RMI-467 heterogeneity phantom scanned in DECT mode with 3 different set-ups: first, we placed high electron density (ED) plugs within the outer ring of the phantom; then we arranged high ED plugs within the inner ring; and finally ED plugs were randomly distributed. All three setups were scanned with the same DECT technique using a single-source DECT scanner with fast kVp switching (Discovery CT750HD; GE Healthcare). Images were transferred to a GE Advantage workstation for DECT analysis. Spectral Hounsfield unit curves (SHUACs) were then generated from 50 to 140-keV, in 10-keV increments, for each plug. Results: The dynamic range of Hounsfield units shrinks with increased photon energy as the attenuation coefficients decrease. Our results show that the spread of HUs for the three different geometrical setups is the smallest at 80 keV. Furthermore, among all the energies and all materials presented, the largest difference appears at high Z tissue equivalent plugs. Conclusion: Our results suggest that dose calculations at both megavoltage and low photon energies could benefit in the vicinity of bony structures if the 80 keV reconstructed monochromatic CT image is used with the DECT protocol utilized in this work.« less

Regeneration of soft and hard tissue periodontal defects.

PubMed

Caffesse, Raúl G; de la Rosa, Manuel; Mota, Luis F

2002-10-01

Periodontitis is characterized by the formation of periodontal pockets and bone loss. Although the basic treatment emphasizes the control of bacterial plaque, the clinician is confronted with the need to correct soft and/or hard tissue defects that develop as a consequence of the disease. This article reviews the current status of regenerative approaches in treating soft and hard tissue defects (based mainly on findings from our own laboratory) and assessed the global applicability of these procedures. Many different techniques have been suggested to treat those defects with, in general, a high degree of success. From the present knowledge it can be concluded that periodontal soft and hard tissue regeneration is possible. Treatment of areas with localized gingival recession or insufficient keratinized gingiva can be achieved with soft tissue grafts or pedicle flaps, as well as with the use of dermal allografts. The treatment of hard tissue defects around teeth and implants can be approached using different types of bone grafts, guided tissue or bone regeneration, or a combination of these. The predictability of many of these therapies, however, still needs to be improved. Since most of these techniques are sensitive, specific, and expensive, their present universal application is limited.

Visualizing molecular polar order in tissues via electromechanical coupling

PubMed Central

Denning, Denise; Alilat, Sofiane; Habelitz, Stefan; Fertala, Andrzej; Rodriguez, Brian J.

2015-01-01

Electron microscopy (EM) and atomic force microscopy (AFM) techniques have long been used to characterize collagen fibril ordering and alignment in connective tissues. These techniques, however, are unable to map collagen fibril polarity, i.e., the polar orientation that is directed from the amine to the carboxyl termini. Using a voltage modulated AFM-based technique called piezoresponse force microscopy (PFM), we show it is possible to visualize both the alignment of collagen fibrils within a tissue and the polar orientation of the fibrils with minimal sample preparation. We demonstrate the technique on rat tail tendon and porcine eye tissues in ambient conditions. In each sample, fibrils are arranged into domains whereby neighboring domains exhibit opposite polarizations, which in some cases extend to the individual fibrillar level. Uniform polarity has not been observed in any of the tissues studied. Evidence of anti-parallel ordering of the amine to carboxyl polarity in bundles of fibrils or in individual fibrils is found in all tissues, which has relevance for understanding mechanical and biofunctional properties and the formation of connective tissues. The technique can be applied to any biological material containing piezoelectric biopolymers or polysaccharides. PMID:22985991

Linking Mechanics and Statistics in Epidermal Tissues

NASA Astrophysics Data System (ADS)

Kim, Sangwoo; Hilgenfeldt, Sascha

2015-03-01

Disordered cellular structures, such as foams, polycrystals, or living tissues, can be characterized by quantitative measurements of domain size and topology. In recent work, we showed that correlations between size and topology in 2D systems are sensitive to the shape (eccentricity) of the individual domains: From a local model of neighbor relations, we derived an analytical justification for the famous empirical Lewis law, confirming the theory with experimental data from cucumber epidermal tissue. Here, we go beyond this purely geometrical model and identify mechanical properties of the tissue as the root cause for the domain eccentricity and thus the statistics of tissue structure. The simple model approach is based on the minimization of an interfacial energy functional. Simulations with Surface Evolver show that the domain statistics depend on a single mechanical parameter, while parameter fluctuations from cell to cell play an important role in simultaneously explaining the shape distribution of cells. The simulations are in excellent agreement with experiments and analytical theory, and establish a general link between the mechanical properties of a tissue and its structure. The model is relevant to diagnostic applications in a variety of animal and plant tissues.

Contact inhibition of locomotion determines cell-cell and cell-substrate forces in tissues.

PubMed

Zimmermann, Juliane; Camley, Brian A; Rappel, Wouter-Jan; Levine, Herbert

2016-03-08

Cells organized in tissues exert forces on their neighbors and their environment. Those cellular forces determine tissue homeostasis as well as reorganization during embryonic development and wound healing. To understand how cellular forces are generated and how they can influence the tissue state, we develop a particle-based simulation model for adhesive cell clusters and monolayers. Cells are contractile, exert forces on their substrate and on each other, and interact through contact inhibition of locomotion (CIL), meaning that cell-cell contacts suppress force transduction to the substrate and propulsion forces align away from neighbors. Our model captures the traction force patterns of small clusters of nonmotile cells and larger sheets of motile Madin-Darby canine kidney (MDCK) cells. In agreement with observations in a spreading MDCK colony, the cell density in the center increases as cells divide and the tissue grows. A feedback between cell density, CIL, and cell-cell adhesion gives rise to a linear relationship between cell density and intercellular tensile stress and forces the tissue into a nonmotile state characterized by a broad distribution of traction forces. Our model also captures the experimentally observed tissue flow around circular obstacles, and CIL accounts for traction forces at the edge.

Intraoperative near-infrared autofluorescence imaging of parathyroid glands.

PubMed

Ladurner, Roland; Sommerey, Sandra; Arabi, Nora Al; Hallfeldt, Klaus K J; Stepp, Herbert; Gallwas, Julia K S

2017-08-01

To identify parathyroid glands intraoperatively by exposing their autofluorescence using near-infrared light. Fluorescence imaging was carried out during minimally invasive and open parathyroid and thyroid surgery. After identification, the parathyroid glands as well as the surrounding tissue were exposed to near-infrared (NIR) light with a wavelength of 690-770 nm using a modified Karl Storz near-infrared/indocyanine green (NIR/ICG) endoscopic system. Parathyroid tissue was expected to show near-infrared autofluorescence, captured in the blue channel of the camera. Whenever possible the visual identification of parathyroid tissue was confirmed histologically. In preliminary investigations, using the original NIR/ICG endoscopic system we noticed considerable interference of light in the blue channel overlying the autofluorescence. Therefore, we modified the light source by interposing additional filters. In a second series, we investigated 35 parathyroid glands from 25 patients. Twenty-seven glands were identified correctly based on NIR autofluorescence. Regarding the extent of autofluorescence, there were no noticeable differences between parathyroid adenomas, hyperplasia and normal parathyroid glands. In contrast, thyroid tissue, lymph nodes and adipose tissue revealed no substantial autofluorescence. Parathyroid tissue is characterized by showing autofluorescence in the near-infrared spectrum. This effect can be used to distinguish parathyroid glands from other cervical tissue entities.

In vivo quantification of motion in liver parenchyma and its application in shistosomiasis tissue characterization

NASA Astrophysics Data System (ADS)

Badawi, Ahmed M.; Hashem, Ahmed M.; Youssef, Abou-Bakr M.; Abdel-Wahab, Mohamed F.

1995-03-01

Schistosomiasis is a major problem in Egypt, despite an active control program it is estimated to exist in about 1/3 of the population. Deposition of less functioning fibrous tissues in the liver is the major contributory factor to the hepatic pathology. Fibrous tissues consist of a complex array of connective matrix material and a variety of collagen isotopes. As a result of an increased stromal density (collagen content), the parenchyma became more ectogenic and less elastic (hard). In this study we investigated the effect of cardiac mechanical impulses from the heart and aorta on the kinetics of the liver parenchyma. Under conditions of controlled patient movements and suspended respiration, a 30 frame per second of 588 X 512 ultrasound images (cineloop, 32 pels per cm) are captured from an aTL ultrasound machine then digitized. The image acquisition is triggered by the R wave of the ECG of the patient. The motion that has a forced oscillation form in the liver parenchyma is quantified by tracking of small box (20 - 30 pels) in 16 directions for all the successive 30 frames. The tracking was done using block matching techniques (the max correlation between boxes in time, frequency domains, and the minimum SAD (sum absolute difference) between boxes). The motion is quantified for many regions at different positions within the liver parenchyma for 80 cases of variable degrees of schisto., cirrhotic livers, and for normal livers. The velocity of the tissue is calculated from the displacement (quantified motion), time between frames, and the scan time for the ultrasound scanner. We found that the motion in liver parenchyma is small in the order of very few millimeters, and the attenuation of the mechanical wave for one ECG cycle is higher in the schisto. and cirrhotic livers than in the normal ones. Finally quantification of motion in liver parenchyma due to cardiac impulses under controlled limb movement and respiration may be of value in the characterization of schisto. (elasticity based not scattering based). This value could be used together with the wide varieties of quantitative tissue characterization parameters for pathology differentiation and for differentiating subclasses of cirrhosis as well as the determination of the extent of bilharzial affection.

Thyroid tissue constituents characterization and application to in vivo studies by broadband (600-1200 nm) diffuse optical spectroscopy

NASA Astrophysics Data System (ADS)

Konugolu Venkata Sekar, Sanathana; Farina, Andrea; dalla Mora, Alberto; Taroni, Paola; Lindner, Claus; Mora, Mireia; Farzam, Parisa; Pagliazzi, Marco; Squarcia, Mattia; Halperin, Irene; Hanzu, Felicia A.; Dehghani, Hamid; Durduran, Turgut; Pifferi, Antonio

2017-07-01

We present the first broadband (600-1100 nm) diffuse optical characterization of thyroglobulin and tyrosine, which are thyroid-specific tissue constituents. In-vivo measurements at the thyroid region enabled their quantification for functional and diagnostic applications.

Separation and characterization of needle and xylem maritime pine proteins.

PubMed

Costa, P; Pionneau, C; Bauw, G; Dubos, C; Bahrmann, N; Kremer, A; Frigerio, J M; Plomion, C

1999-01-01

Two-dimensional gel electrophoresis (2-DE) and image analysis are currently used for proteome analysis in maritime pine (Pinus pinaster Ait.). This study presents a database of expressed proteins extracted from needles and xylem, two important tissues for growth and wood formation. Electrophoresis was carried out by isoelectric focusing (IEF) in the first dimension and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in the second. Silver staining made it possible to detect an average of 900 and 600 spots on 2-DE gels from needles and xylem, respectively. A total of 28 xylem and 35 needle proteins were characterized by internal peptide microsequencing. Out of these 63 proteins, 57 (90%) could be identified based on amino acid similarity with known proteins, of which 24 (42%) have already been described in conifers. Overall comparison of both tissues indicated that 29% and 36% of the spots were specific to xylem and needles, respectively, while the other spots were of identical molecular weight and isoelectric point. The homology of spot location in 2-DE patterns was further validated by sequence analysis of proteins present in both tissues. A proteomic database of maritime pine is accessible on the internet (http://www.pierroton.inra.fr/genetics/2D/).

Cloning, characterization, expression and comparative analysis of pig Golgi membrane sphingomyelin synthase 1.

PubMed

Guillén, Natalia; Navarro, María A; Surra, Joaquín C; Arnal, Carmen; Fernández-Juan, Marta; Cebrián-Pérez, Jose Alvaro; Osada, Jesús

2007-02-15

Pig sphingomyelin synthase 1 (SMS1) cDNA was cloned, characterized and compared to the human ortholog. Porcine protein consists of 413 amino acids and displays a 97% sequence identity with human protein. A phylogenic tree of proteins reveals that porcine SMS1 is more closely related to bovine and rodent proteins than to human. Analysis of protein mass was higher than the theoretical prediction based on amino acid sequence suggesting a kind of posttranslational modification. Quantitative representation of tissue distribution obtained by real-time RT-PCR showed that it was widely expressed although important variations in levels were obtained among organs. Thus, the cardiovascular system, especially the heart, showed the highest value of all the tissues studied. Regional differences of expression were observed in the central nervous system and intestinal tract. Analysis of the hepatic mRNA and protein expressions of SMS1 following turpentine treatment revealed a progressive decrease in the former paralleled by a decrease in the protein concentration. These findings indicate the variation in expression in the different tissues might suggest a different requirement of Golgi sphingomyelin for the specific function in each organ and a regulation of the enzyme in response to turpentine-induced hepatic injury.

Coregistered three-dimensional ultrasound and photoacoustic imaging system for ovarian tissue characterization

PubMed Central

Aguirre, Andres; Guo, Puyun; Gamelin, John; Yan, Shikui; Sanders, Mary M.; Brewer, Molly; Zhu, Quing

2009-01-01

Ovarian cancer has the highest mortality of all gynecologic cancers, with a five-year survival rate of only 30% or less. Current imaging techniques are limited in sensitivity and specificity in detecting early stage ovarian cancer prior to its widespread metastasis. New imaging techniques that can provide functional and molecular contrasts are needed to reduce the high mortality of this disease. One such promising technique is photoacoustic imaging. We develop a 1280-element coregistered 3-D ultrasound and photoacoustic imaging system based on a 1.75-D acoustic array. Volumetric images over a scan range of 80 deg in azimuth and 20 deg in elevation can be achieved in minutes. The system has been used to image normal porcine ovarian tissue. This is an important step toward better understanding of ovarian cancer optical properties obtained with photoacoustic techniques. To the best of our knowledge, such data are not available in the literature. We present characterization measurements of the system and compare coregistered ultrasound and photoacoustic images of ovarian tissue to histological images. The results show excellent coregistration of ultrasound and photoacoustic images. Strong optical absorption from vasculature, especially highly vascularized corpora lutea and low absorption from follicles, is demonstrated. PMID:19895116

Synthesis and characterization of a Hyaluronan-polyethylene copolymer for biomedical applications.

PubMed

Oldinski, Rachael A; Cranson, Cody N; James, Susan P

2010-08-01

Hyaluronan (HA)-based biomaterials are of interest for bone and cartilage tissue engineering because HA plays an important role in orthopedic tissue development, function, and repair. The goal of this project was to develop a biomaterial that incorporated the constituents of both a hydrogel and a hydrophobic polymer for biomedical applications. A series of amphiphilic graft copolymers consisting of HA, a glycosaminoglycan, and high-density polyethylene (HDPE), that is, HA-co-HDPE, were fabricated. The chemical characteristics, physical and viscoelastic properties, and cytocompatibility of novel HA-co-HDPE materials were characterized via Fourier Transform infrared (FTIR) spectroscopy, solid state nuclear magnetic resonance (ssNMR) spectroscopy, differential scanning calorimetry (DSC), dynamic shear testing, and an in vitro human osteoblast cell study. The esterification reaction between HA and functionalized HDPE resulted in semicrystalline, insoluble powder. The dynamic shear properties of HA-co-HDPE concentrated solutions were more like natural proteoglycans than the HA control. HA-co-HDPE was successfully compression molded into disks that swelled upon hydration. Osteoblasts were viable and expressed the osteoblast phenotype after 7 days of culture on HA-co-HDPE materials. These HA-co-HDPE materials may have several biomaterial applications in saline suspension or molded form, including orthopedic tissue repair.

The human laryngeal microbiome: effects of cigarette smoke and reflux.

PubMed

Jetté, Marie E; Dill-McFarland, Kimberly A; Hanshew, Alissa S; Suen, Garret; Thibeault, Susan L

2016-10-24

Prolonged diffuse laryngeal inflammation from smoking and/or reflux is commonly diagnosed as chronic laryngitis and treated empirically with expensive drugs that have not proven effective. Shifts in microbiota have been associated with many inflammatory diseases, though little is known about how resident microbes may contribute to chronic laryngitis. We sought to characterize the core microbiota of disease-free human laryngeal tissue and to investigate shifts in microbial community membership associated with exposure to cigarette smoke and reflux. Using 454 pyrosequencing of the 16S rRNA gene, we compared bacterial communities of laryngeal tissue biopsies collected from 97 non-treatment-seeking volunteers based on reflux and smoking status. The core community was characterized by a highly abundant OTU within the family Comamonadaceae found in all laryngeal tissues. Smokers demonstrated less microbial diversity than nonsmokers, with differences in relative abundances of OTUs classified as Streptococcus, unclassified Comamonadaceae, Cloacibacterium, and Helicobacter. Reflux status did not affect microbial diversity nor community structure nor composition. Comparison of healthy laryngeal microbial communities to benign vocal fold disease samples revealed greater abundance of Streptococcus in benign vocal fold disease suggesting that mucosal dominance by Streptococcus may be a factor in disease etiology.

A diffusion model-free framework with echo time dependence for free-water elimination and brain tissue microstructure characterization.

PubMed

Molina-Romero, Miguel; Gómez, Pedro A; Sperl, Jonathan I; Czisch, Michael; Sämann, Philipp G; Jones, Derek K; Menzel, Marion I; Menze, Bjoern H

2018-03-23

The compartmental nature of brain tissue microstructure is typically studied by diffusion MRI, MR relaxometry or their correlation. Diffusion MRI relies on signal representations or biophysical models, while MR relaxometry and correlation studies are based on regularized inverse Laplace transforms (ILTs). Here we introduce a general framework for characterizing microstructure that does not depend on diffusion modeling and replaces ill-posed ILTs with blind source separation (BSS). This framework yields proton density, relaxation times, volume fractions, and signal disentanglement, allowing for separation of the free-water component. Diffusion experiments repeated for several different echo times, contain entangled diffusion and relaxation compartmental information. These can be disentangled by BSS using a physically constrained nonnegative matrix factorization. Computer simulations, phantom studies, together with repeatability and reproducibility experiments demonstrated that BSS is capable of estimating proton density, compartmental volume fractions and transversal relaxations. In vivo results proved its potential to correct for free-water contamination and to estimate tissue parameters. Formulation of the diffusion-relaxation dependence as a BSS problem introduces a new framework for studying microstructure compartmentalization, and a novel tool for free-water elimination. © 2018 International Society for Magnetic Resonance in Medicine.

Isolation and characterization of human mesenchymal stem cells derived from synovial fluid by magnetic-activated cell sorting (MACS).

PubMed

Jia, Zhaofeng; Liang, Yujie; Xu, Xiao; Li, Xingfu; Liu, Qisong; Ou, Yangkan; Duan, Li; Zhu, Weimin; Lu, Wei; Xiong, Jianyi; Wang, Daping

2018-03-01

Mesenchymal stem cells (MSCs) are the primary source of cells used for cell-based therapy in tissue engineering. MSCs are found in synovial fluid, a source that could be conveniently used for cartilage tissue engineering. However, the purification and characterization of SF-MSCs has been poorly documented in the literature. Here, we outline an easy-to-perform approach for the isolation and culture of MSCs derived from human synovial fluid (hSF-MSCs). We have successfully purified hSF-MSCs using magnetic-activated cell sorting (MACS) using the MSC surface marker, CD90. Purified SF-MSCs demonstrate significant renewal capacity following several passages in culture. Furthermore, we demonstrated that MACS-sorted CD90 + cells could differentiated into osteoblasts, adipocytes, and chondrocytes in vitro. In addition, we show that these cells can generate cartilage tissue in micromass culture as well. This study demonstrates that MACS is a useful tool that can be used for the purification of hSF-MSCs from synovial fluid. The proliferation properties and ability to differentiate into chondrocytes make these hSF-MSCs a promising source of stem cells for applications in cartilage repair. © 2017 International Federation for Cell Biology.

TMV-Gate vectors: Gateway compatible tobacco mosaic virus based expression vectors for functional analysis of proteins

PubMed Central

Kagale, Sateesh; Uzuhashi, Shihomi; Wigness, Merek; Bender, Tricia; Yang, Wen; Borhan, M. Hossein; Rozwadowski, Kevin

2012-01-01

Plant viral expression vectors are advantageous for high-throughput functional characterization studies of genes due to their capability for rapid, high-level transient expression of proteins. We have constructed a series of tobacco mosaic virus (TMV) based vectors that are compatible with Gateway technology to enable rapid assembly of expression constructs and exploitation of ORFeome collections. In addition to the potential of producing recombinant protein at grams per kilogram FW of leaf tissue, these vectors facilitate either N- or C-terminal fusions to a broad series of epitope tag(s) and fluorescent proteins. We demonstrate the utility of these vectors in affinity purification, immunodetection and subcellular localisation studies. We also apply the vectors to characterize protein-protein interactions and demonstrate their utility in screening plant pathogen effectors. Given its broad utility in defining protein properties, this vector series will serve as a useful resource to expedite gene characterization efforts. PMID:23166857

Abdominal Tumor Characterization and Recognition Using Superior-Order Cooccurrence Matrices, Based on Ultrasound Images

PubMed Central

Mitrea, Delia; Mitrea, Paulina; Nedevschi, Sergiu; Badea, Radu; Lupsor, Monica; Socaciu, Mihai; Golea, Adela; Hagiu, Claudia; Ciobanu, Lidia

2012-01-01

The noninvasive diagnosis of the malignant tumors is an important issue in research nowadays. Our purpose is to elaborate computerized, texture-based methods for performing computer-aided characterization and automatic diagnosis of these tumors, using only the information from ultrasound images. In this paper, we considered some of the most frequent abdominal malignant tumors: the hepatocellular carcinoma and the colonic tumors. We compared these structures with the benign tumors and with other visually similar diseases. Besides the textural features that proved in our previous research to be useful in the characterization and recognition of the malignant tumors, we improved our method by using the grey level cooccurrence matrix and the edge orientation cooccurrence matrix of superior order. As resulted from our experiments, the new textural features increased the malignant tumor classification performance, also revealing visual and physical properties of these structures that emphasized the complex, chaotic structure of the corresponding tissue. PMID:22312411

The Xeno-glycomics database (XDB): a relational database of qualitative and quantitative pig glycome repertoire.

PubMed

Park, Hae-Min; Park, Ju-Hyeong; Kim, Yoon-Woo; Kim, Kyoung-Jin; Jeong, Hee-Jin; Jang, Kyoung-Soon; Kim, Byung-Gee; Kim, Yun-Gon

2013-11-15

In recent years, the improvement of mass spectrometry-based glycomics techniques (i.e. highly sensitive, quantitative and high-throughput analytical tools) has enabled us to obtain a large dataset of glycans. Here we present a database named Xeno-glycomics database (XDB) that contains cell- or tissue-specific pig glycomes analyzed with mass spectrometry-based techniques, including a comprehensive pig glycan information on chemical structures, mass values, types and relative quantities. It was designed as a user-friendly web-based interface that allows users to query the database according to pig tissue/cell types or glycan masses. This database will contribute in providing qualitative and quantitative information on glycomes characterized from various pig cells/organs in xenotransplantation and might eventually provide new targets in the α1,3-galactosyltransferase gene-knock out pigs era. The database can be accessed on the web at http://bioinformatics.snu.ac.kr/xdb.

Material Separation Using Dual-Energy CT: Current and Emerging Applications.

PubMed

Patino, Manuel; Prochowski, Andrea; Agrawal, Mukta D; Simeone, Frank J; Gupta, Rajiv; Hahn, Peter F; Sahani, Dushyant V

2016-01-01

Dual-energy (DE) computed tomography (CT) offers the opportunity to generate material-specific images on the basis of the atomic number Z and the unique mass attenuation coefficient of a particular material at different x-ray energies. Material-specific images provide qualitative and quantitative information about tissue composition and contrast media distribution. The most significant contribution of DE CT-based material characterization comes from the capability to assess iodine distribution through the creation of an image that exclusively shows iodine. These iodine-specific images increase tissue contrast and amplify subtle differences in attenuation between normal and abnormal tissues, improving lesion detection and characterization in the abdomen. In addition, DE CT enables computational removal of iodine influence from a CT image, generating virtual noncontrast images. Several additional materials, including calcium, fat, and uric acid, can be separated, permitting imaging assessment of metabolic imbalances, elemental deficiencies, and abnormal deposition of materials within tissues. The ability to obtain material-specific images from a single, contrast-enhanced CT acquisition can complement the anatomic knowledge with functional information, and may be used to reduce the radiation dose by decreasing the number of phases in a multiphasic CT examination. DE CT also enables generation of energy-specific and virtual monochromatic images. Clinical applications of DE CT leverage both material-specific images and virtual monochromatic images to expand the current role of CT and overcome several limitations of single-energy CT. (©)RSNA, 2016.

Concise Review: Mesenchymal Stem Cells for Functional Cartilage Tissue Engineering: Taking Cues from Chondrocyte‐Based Constructs

PubMed Central

Tan, Andrea R.

2017-01-01

Abstract Osteoarthritis, the most prevalent form of joint disease, afflicts 9% of the U.S. population over the age of 30 and costs the economy nearly $100 billion annually in healthcare and socioeconomic costs. It is characterized by joint pain and dysfunction, though the pathophysiology remains largely unknown. Due to its avascular nature and limited cellularity, articular cartilage exhibits a poor intrinsic healing response following injury. As such, significant research efforts are aimed at producing engineered cartilage as a cell‐based approach for articular cartilage repair. However, the knee joint is mechanically demanding, and during injury, also a milieu of harsh inflammatory agents. The unforgiving mechano‐chemical environment requires tissue replacements that are capable of bearing such burdens. The use of mesenchymal stem cells (MSCs) for cartilage tissue engineering has emerged as a promising cell source due to their ease of isolation, capacity to readily expand in culture, and ability to undergo lineage‐specific differentiation into chondrocytes. However, to date, very few studies utilizing MSCs have successfully recapitulated the structural and functional properties of native cartilage, exposing the difficult process of uniformly differentiating stem cells into desired cell fates and maintaining the phenotype during in vitro culture and after in vivo implantation. To address these shortcomings, here, we present a concise review on modulating stem cell behavior, tissue development and function using well‐developed techniques from chondrocyte‐based cartilage tissue engineering. Stem Cells Translational Medicine 2017;6:1295–1303 PMID:28177194

Myocardial Tissue Characterization by Magnetic Resonance Imaging

PubMed Central

Ferreira, Vanessa M.; Piechnik, Stefan K.; Robson, Matthew D.; Neubauer, Stefan

2014-01-01

Cardiac magnetic resonance (CMR) imaging is a well-established noninvasive imaging modality in clinical cardiology. Its unsurpassed accuracy in defining cardiac morphology and function and its ability to provide tissue characterization make it well suited for the study of patients with cardiac diseases. Late gadolinium enhancement was a major advancement in the development of tissue characterization techniques, allowing the unique ability of CMR to differentiate ischemic heart disease from nonischemic cardiomyopathies. Using T2-weighted techniques, areas of edema and inflammation can be identified in the myocardium. A new generation of myocardial mapping techniques are emerging, enabling direct quantitative assessment of myocardial tissue properties in absolute terms. This review will summarize recent developments involving T1-mapping and T2-mapping techniques and focus on the clinical applications and future potential of these evolving CMR methodologies. PMID:24576837

X-ray micro-tomography for investigations of brain tissues on cellular level

NASA Astrophysics Data System (ADS)

Khimchenko, Anna; Schulz, Georg; Deyhle, Hans; Thalmann, Peter; Zanette, Irene; Zdora, Marie-Christine; Bikis, Christos; Hipp, Alexander; Hieber, Simone E.; Schweighauser, Gabriel; Hench, Jürgen; Müller, Bert

2016-10-01

X-ray imaging in absorption contrast mode is well established for hard tissue visualization. However, performance for lower density materials is limited due to a reduced contrast. Our aim is three-dimensional (3D) characterization of micro-morphology of human brain tissues down to (sub-)cellular resolution within a laboratory environment. Using the laboratory-based microtomography (μCT) system nanotom m (GE Sensing and Inspection Technologies GmbH, Wunstorf, Germany) and synchrotron radiation at the Diamond-Manchester Imaging Branchline I13-2 (Diamond Light Source, Didcot, UK), we have acquired 3D data with a resolution down to 0.45 μm for visualization of a human cerebellum specimen down to cellular level. We have shown that all selected modalities, namely laboratory-based absorption contrast micro-tomography (LBμCT), synchrotron radiation based in-line single distance phase contrast tomography (SDPR) and synchrotron radiation based single-grating interferometry (GI), can reach cellular resolution for tissue samples with a size in the mm-range. The results are discussed qualitatively in comparison to optical microscopy of haematoxylin and eosin (HE) stained sections. As phase contrast yields to a better data quality for soft tissues and in order to overcome restrictions of limited beamline access for phase contrast measurements, we have equipped the μCT system nanotom m with a double-grating phase contrast set-up. Preliminary experimental results of a knee sample consisting of a bony part and a cartilage demonstrate that phase contrast data exhibits better quality compared to absorption contrast. Currently, the set-up is under adjustment. It is expected that cellular resolution would also be achieved. The questions arise (1) what would be the quality gain of laboratory-based phase contrast in comparison to laboratory-based absorption contrast tomography and (2) could laboratory-based phase contrast data provide comparable results to synchrotron radiation based phase contrast data.

A generalized gamma mixture model for ultrasonic tissue characterization.

PubMed

Vegas-Sanchez-Ferrero, Gonzalo; Aja-Fernandez, Santiago; Palencia, Cesar; Martin-Fernandez, Marcos

2012-01-01

Several statistical models have been proposed in the literature to describe the behavior of speckles. Among them, the Nakagami distribution has proven to very accurately characterize the speckle behavior in tissues. However, it fails when describing the heavier tails caused by the impulsive response of a speckle. The Generalized Gamma (GG) distribution (which also generalizes the Nakagami distribution) was proposed to overcome these limitations. Despite the advantages of the distribution in terms of goodness of fitting, its main drawback is the lack of a closed-form maximum likelihood (ML) estimates. Thus, the calculation of its parameters becomes difficult and not attractive. In this work, we propose (1) a simple but robust methodology to estimate the ML parameters of GG distributions and (2) a Generalized Gama Mixture Model (GGMM). These mixture models are of great value in ultrasound imaging when the received signal is characterized by a different nature of tissues. We show that a better speckle characterization is achieved when using GG and GGMM rather than other state-of-the-art distributions and mixture models. Results showed the better performance of the GG distribution in characterizing the speckle of blood and myocardial tissue in ultrasonic images.

A Generalized Gamma Mixture Model for Ultrasonic Tissue Characterization

PubMed Central

Palencia, Cesar; Martin-Fernandez, Marcos

2012-01-01

Several statistical models have been proposed in the literature to describe the behavior of speckles. Among them, the Nakagami distribution has proven to very accurately characterize the speckle behavior in tissues. However, it fails when describing the heavier tails caused by the impulsive response of a speckle. The Generalized Gamma (GG) distribution (which also generalizes the Nakagami distribution) was proposed to overcome these limitations. Despite the advantages of the distribution in terms of goodness of fitting, its main drawback is the lack of a closed-form maximum likelihood (ML) estimates. Thus, the calculation of its parameters becomes difficult and not attractive. In this work, we propose (1) a simple but robust methodology to estimate the ML parameters of GG distributions and (2) a Generalized Gama Mixture Model (GGMM). These mixture models are of great value in ultrasound imaging when the received signal is characterized by a different nature of tissues. We show that a better speckle characterization is achieved when using GG and GGMM rather than other state-of-the-art distributions and mixture models. Results showed the better performance of the GG distribution in characterizing the speckle of blood and myocardial tissue in ultrasonic images. PMID:23424602

Toxicokinetic and Dosimetry Modeling Tools for Exposure ...

EPA Pesticide Factsheets

New technologies and in vitro testing approaches have been valuable additions to risk assessments that have historically relied solely on in vivo test results. Compared to in vivo methods, in vitro high throughput screening (HTS) assays are less expensive, faster and can provide mechanistic insights on chemical action. However, extrapolating from in vitro chemical concentrations to target tissue or blood concentrations in vivo is fraught with uncertainties, and modeling is dependent upon pharmacokinetic variables not measured in in vitro assays. To address this need, new tools have been created for characterizing, simulating, and evaluating chemical toxicokinetics. Physiologically-based pharmacokinetic (PBPK) models provide estimates of chemical exposures that produce potentially hazardous tissue concentrations, while tissue microdosimetry PK models relate whole-body chemical exposures to cell-scale concentrations. These tools rely on high-throughput in vitro measurements, and successful methods exist for pharmaceutical compounds that determine PK from limited in vitro measurements and chemical structure-derived property predictions. These high throughput (HT) methods provide a more rapid and less resource–intensive alternative to traditional PK model development. We have augmented these in vitro data with chemical structure-based descriptors and mechanistic tissue partitioning models to construct HTPBPK models for over three hundred environmental and pharmace

Mesenchymal Stem Cells for Cartilage Regeneration of TMJ Osteoarthritis

PubMed Central

Li, Hongyu; Xu, Xin; Ye, Ling; Zhou, Xuedong

2017-01-01

Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disease, characterized by progressive cartilage degradation, subchondral bone remodeling, synovitis, and chronic pain. Due to the limited self-healing capacity in condylar cartilage, traditional clinical treatments have limited symptom-modifying and structure-modifying effects to restore impaired cartilage as well as other TMJ tissues. In recent years, stem cell-based therapy has raised much attention as an alternative approach towards tissue repair and regeneration. Mesenchymal stem cells (MSCs), derived from the bone marrow, synovium, and even umbilical cord, play a role as seed cells for the cartilage regeneration of TMJ OA. MSCs possess multilineage differentiation potential, including chondrogenic differentiation as well as osteogenic differentiation. In addition, the trophic modulations of MSCs exert anti-inflammatory and immunomodulatory effects under aberrant conditions. Furthermore, MSCs combined with appropriate scaffolds can form cartilaginous or even osseous compartments to repair damaged tissue and impaired function of TMJ. In this review, we will briefly discuss the pathogenesis of cartilage degeneration in TMJ OA and emphasize the potential sources of MSCs and novel approaches for the cartilage regeneration of TMJ OA, particularly focusing on the MSC-based therapy and tissue engineering. PMID:29123550

Biophysical interpretation and ex-vivo characterization of scattered light from tumor-associated breast stroma

NASA Astrophysics Data System (ADS)

Laughney, Ashley; Krishnaswamy, Venkat; Schwab, Mary; Wells, Wendy A.; Paulsen, Keith D.; Pogue, Brian W.

2009-02-01

The purpose of this study was to extract scatter parameters related to tissue ultra-structures from freshly excised breast tissue and to assess whether evident changes in scatter across diagnostic categories is primarily influenced by variation in the composition of each tissues subtypes or by physical remodeling of the extra-cellular environment. Pathologists easily distinguish between epithelium, stroma and adipose tissues, so this classification was adopted for macroscopic subtype classification. Micro-sampling reflectance spectroscopy was used to characterize single-backscattered photons from fresh, excised tumors and normal reduction specimens with sub-millimeter resolution. Phase contrast microscopy (sub-micron resolution) was used to characterize forward-scattered light through frozen tissue from the DHMC Tissue Bank, representing normal, benign and malignant breast tissue, sectioned at 10 microns. The packing density and orientation of collagen fibers in the extracellular matrix (ECM) associated with invasive, normal and benign epithelium was evaluated using transmission electron microscopy (TEM). Regions of interest (ROIs) in the H&E stained tissues were identified for analysis, as outlined by a pathologist as the gold standard. We conclude that the scatter parameters associated with tumor specimens (Npatients=6, Nspecimens=13) significantly differs from that of normal reductions (Npatients=6, Nspecimens=10). Further, tissue subtypes may be identified by their scatter spectra at sub-micron resolution. Stromal tissue scatters significantly more than the epithelial cells embedded in its ECM and adipose tissue scatters much less. However, the scatter signature of the stroma at the sub-micron level is not particularly differentiating in terms of a diagnosis.

Characterization of scatter in digital mammography from use of Monte Carlo simulations and comparison to physical measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leon, Stephanie M., E-mail: Stephanie.Leon@uth.tmc.edu; Wagner, Louis K.; Brateman, Libby F.

2014-11-01

Purpose: Monte Carlo simulations were performed with the goal of verifying previously published physical measurements characterizing scatter as a function of apparent thickness. A secondary goal was to provide a way of determining what effect tissue glandularity might have on the scatter characteristics of breast tissue. The overall reason for characterizing mammography scatter in this research is the application of these data to an image processing-based scatter-correction program. Methods: MCNPX was used to simulate scatter from an infinitesimal pencil beam using typical mammography geometries and techniques. The spreading of the pencil beam was characterized by two parameters: mean radial extentmore » (MRE) and scatter fraction (SF). The SF and MRE were found as functions of target, filter, tube potential, phantom thickness, and the presence or absence of a grid. The SF was determined by separating scatter and primary by the angle of incidence on the detector, then finding the ratio of the measured scatter to the total number of detected events. The accuracy of the MRE was determined by placing ring-shaped tallies around the impulse and fitting those data to the point-spread function (PSF) equation using the value for MRE derived from the physical measurements. The goodness-of-fit was determined for each data set as a means of assessing the accuracy of the physical MRE data. The effect of breast glandularity on the SF, MRE, and apparent tissue thickness was also considered for a limited number of techniques. Results: The agreement between the physical measurements and the results of the Monte Carlo simulations was assessed. With a grid, the SFs ranged from 0.065 to 0.089, with absolute differences between the measured and simulated SFs averaging 0.02. Without a grid, the range was 0.28–0.51, with absolute differences averaging −0.01. The goodness-of-fit values comparing the Monte Carlo data to the PSF from the physical measurements ranged from 0.96 to 1.00 with a grid and 0.65 to 0.86 without a grid. Analysis of the data suggested that the nongrid data could be better described by a biexponential function than the single exponential used here. The simulations assessing the effect of breast composition on SF and MRE showed only a slight impact on these quantities. When compared to a mix of 50% glandular/50% adipose tissue, the impact of substituting adipose or glandular breast compositions on the apparent thickness of the tissue was about 5%. Conclusions: The findings show agreement between the physical measurements published previously and the Monte Carlo simulations presented here; the resulting data can therefore be used more confidently for an application such as image processing-based scatter correction. The findings also suggest that breast composition does not have a major impact on the scatter characteristics of breast tissue. Application of the scatter data to the development of a scatter-correction software program can be simplified by ignoring the variations in density among breast tissues.« less

Stable phantom materials for ultrasound and optical imaging.

PubMed

Cabrelli, Luciana C; Pelissari, Pedro I B G B; Deana, Alessandro M; Carneiro, Antonio A O; Pavan, Theo Z

2017-01-21

Phantoms mimicking the specific properties of biological tissues are essential to fully characterize medical devices. Water-based materials are commonly used to manufacture phantoms for ultrasound and optical imaging techniques. However, these materials have disadvantages, such as easy degradation and low temporal stability. In this study, we propose an oil-based new tissue-mimicking material for ultrasound and optical imaging, with the advantage of presenting low temporal degradation. A styrene-ethylene/butylene-styrene (SEBS) copolymer in mineral oil samples was made varying the SEBS concentration between 5%-15%, and low-density polyethylene (LDPE) between 0%-9%. Acoustic properties, such as the speed of sound and the attenuation coefficient, were obtained using frequencies ranging from 1-10 MHz, and were consistent with that of soft tissues. These properties were controlled varying SEBS and LDPE concentration. To characterize the optical properties of the samples, the diffuse reflectance and transmittance were measured. Scattering and absorption coefficients ranging from 400 nm-1200 nm were calculated for each compound. SEBS gels are a translucent material presenting low optical absorption and scattering coefficients in the visible region of the spectrum, but the presence of LDPE increased the turbidity. Adding LDPE increased the absorption and scattering of the phantom materials. Ultrasound and photoacoustic images of a heterogeneous phantom made of LDPE/SEBS containing a spherical inclusion were obtained. Annatto dye was added to the inclusion to enhance the optical absorbance. The results suggest that copolymer gels are promising for ultrasound and optical imaging, making them also potentially useful for photoacoustic imaging.

Stable phantom materials for ultrasound and optical imaging

NASA Astrophysics Data System (ADS)

Cabrelli, Luciana C.; Pelissari, Pedro I. B. G. B.; Deana, Alessandro M.; Carneiro, Antonio A. O.; Pavan, Theo Z.

2017-01-01

Phantoms mimicking the specific properties of biological tissues are essential to fully characterize medical devices. Water-based materials are commonly used to manufacture phantoms for ultrasound and optical imaging techniques. However, these materials have disadvantages, such as easy degradation and low temporal stability. In this study, we propose an oil-based new tissue-mimicking material for ultrasound and optical imaging, with the advantage of presenting low temporal degradation. A styrene-ethylene/butylene-styrene (SEBS) copolymer in mineral oil samples was made varying the SEBS concentration between 5%-15%, and low-density polyethylene (LDPE) between 0%-9%. Acoustic properties, such as the speed of sound and the attenuation coefficient, were obtained using frequencies ranging from 1-10 MHz, and were consistent with that of soft tissues. These properties were controlled varying SEBS and LDPE concentration. To characterize the optical properties of the samples, the diffuse reflectance and transmittance were measured. Scattering and absorption coefficients ranging from 400 nm-1200 nm were calculated for each compound. SEBS gels are a translucent material presenting low optical absorption and scattering coefficients in the visible region of the spectrum, but the presence of LDPE increased the turbidity. Adding LDPE increased the absorption and scattering of the phantom materials. Ultrasound and photoacoustic images of a heterogeneous phantom made of LDPE/SEBS containing a spherical inclusion were obtained. Annatto dye was added to the inclusion to enhance the optical absorbance. The results suggest that copolymer gels are promising for ultrasound and optical imaging, making them also potentially useful for photoacoustic imaging.

Purification, Characterization, and Cloning of Cinnamyl Alcohol Dehydrogenase in Loblolly Pine (Pinus taeda L.) 1

PubMed Central

O'Malley, David M.; Porter, Stephanie; Sederoff, Ronald R.

1992-01-01

Cinnamyl alcohol dehydrogenase (CAD, EC 1.1.1. 195) has been purified to homogeneity from differentiating xylem tissue and developing seeds of loblolly pine (Pinus taeda L.). The enzyme is a dimer with a native molecular weight of 82,000 and a subunit molecular weight of 44,000, and is the only form of CAD involved in lignification in differentiating xylem. High levels of loblolly pine CAD enzyme were found in nonlignifying seed tissue. Characterization of the enzyme from both seeds and xylem demonstrated that the enzyme is the same in both tissues. The enzyme has a high affinity for coniferaldehyde (Km = 1.7 micromolar) compared with sinapaldehyde (Km in excess of 100 micromolar). Kinetic data strongly suggest that coniferin is a noncompetitive inhibitor of CAD enzyme activity. Protein sequences were obtained for the N-terminus (28 amino acids) and for two other peptides. Degenerate oligonucleotide primers based on the protein sequences were used to amplify by polymerase chain reaction a 1050 base pair DNA fragment from xylem cDNA. Nucleotide sequence from the cloned DNA fragment coded for the N-terminal protein sequence and an internal peptide of CAD. The N-terminal protein sequence has little similarity with the λCAD4 clone isolated from bean (MH Walter, J Grima-Pettenati, C Grand, AM Boudet, CJ Lamb [1988] Proc Natl Acad Sci USA 86:5546-5550), which has homology with malic enzyme. ImagesFigure 2Figure 3 PMID:16668801

Purification, Characterization, and Cloning of Cinnamyl Alcohol Dehydrogenase in Loblolly Pine (Pinus taeda L.).

PubMed

O'malley, D M; Porter, S; Sederoff, R R

1992-04-01

Cinnamyl alcohol dehydrogenase (CAD, EC 1.1.1. 195) has been purified to homogeneity from differentiating xylem tissue and developing seeds of loblolly pine (Pinus taeda L.). The enzyme is a dimer with a native molecular weight of 82,000 and a subunit molecular weight of 44,000, and is the only form of CAD involved in lignification in differentiating xylem. High levels of loblolly pine CAD enzyme were found in nonlignifying seed tissue. Characterization of the enzyme from both seeds and xylem demonstrated that the enzyme is the same in both tissues. The enzyme has a high affinity for coniferaldehyde (K(m) = 1.7 micromolar) compared with sinapaldehyde (K(m) in excess of 100 micromolar). Kinetic data strongly suggest that coniferin is a noncompetitive inhibitor of CAD enzyme activity. Protein sequences were obtained for the N-terminus (28 amino acids) and for two other peptides. Degenerate oligonucleotide primers based on the protein sequences were used to amplify by polymerase chain reaction a 1050 base pair DNA fragment from xylem cDNA. Nucleotide sequence from the cloned DNA fragment coded for the N-terminal protein sequence and an internal peptide of CAD. The N-terminal protein sequence has little similarity with the lambdaCAD4 clone isolated from bean (MH Walter, J Grima-Pettenati, C Grand, AM Boudet, CJ Lamb [1988] Proc Natl Acad Sci USA 86:5546-5550), which has homology with malic enzyme.

Interconnected porosity analysis by 3D X-ray microtomography and mechanical behavior of biomimetic organic-inorganic composite materials.

PubMed

Alonso-Sierra, S; Velázquez-Castillo, R; Millán-Malo, B; Nava, R; Bucio, L; Manzano-Ramírez, A; Cid-Luna, H; Rivera-Muñoz, E M

2017-11-01

Hydroxyapatite-based materials have been used for dental and biomedical applications. They are commonly studied due to their favorable response presented when used for replacement of bone tissue. Those materials should be porous enough to allow cell penetration, internal tissue growth, vascular incursion and nutrient supply. Furthermore, their morphology should be designed to guide the growth of new bone tissue in anatomically applicable ways. In this work, the mechanical performance and 3D X-ray microtomography (X-ray μCT) study of a biomimetic, organic-inorganic composite material, based on hydroxyapatite, with physicochemical, structural, morphological and mechanical properties very similar to those of natural bone tissue is reported. Ceramic pieces in different shapes and several porous sizes were produced using a Modified Gel Casting Method. Pieces with a controlled and 3D hierarchical interconnected porous structure were molded by adding polymethylmethacrylate microspheres. Subsequently, they were subject to a thermal treatment to remove polymers and to promote a sinterization of the ceramic particles, obtaining a HAp scaffold with controlled porosity. Then, two different organic phases were used to generate an organic-inorganic composite material, so gelatin and collagen, which was extracted from bovine tail, were used. The biomimetic organic-inorganic composite material was characterized by Scanning Electron Microscopy, Energy Dispersive X-ray Spectroscopy, X-ray Diffraction, Fourier Transform Infrared Spectroscopy and 3D X-ray microtomography techniques. Mechanical properties were characterized in compression tests, obtaining a dramatic and synergic increment in the mechanical properties due to the chemical and physical interactions between the two phases and to the open-cell cellular behavior of the final composite material; the maximum compressive strength obtained corresponds to about 3 times higher than that reported for natural cancellous bone. The pore size distribution obtained could be capable to allow cell penetration, internal tissue in-growth, vascular incursion and nutrient supply and this material has tremendous potential for use as a replacement of bone tissue or in the manufacture and molding of prosthesis with desired shapes. Copyright © 2017 Elsevier B.V. All rights reserved.

Tissue refractometry using Hilbert phase microscopy

PubMed Central

Lue, Niyom; Bewersdorf, Joerg; Lessard, Mark D.; Badizadegan, Kamran; Dasari, Ramachandra R.; Feld, Michael S.; Popescu, Gabriel

2009-01-01

We present, for the first time to our knowledge, quantitative phase images associated with unstained 5 μm thick tissue slices of mouse brain, spleen, and liver. The refractive properties of the tissue are retrieved in terms of the average refractive index and its spatial variation. We find that the average refractive index varies significantly with tissue type, such that the brain is characterized by the lowest value and the liver by the highest. The spatial power spectra of the phase images reveal power law behavior with different exponents for each tissue type. This approach opens a new possibility for stain-free characterization of tissues, where the diagnostic power is provided by the intrinsic refractive properties of the biological structure. We present results obtained for liver tissue affected by a lysosomal storage disease and show that our technique can quantify structural changes during this disease development. PMID:18087529

Hyperspectral interventional imaging for enhanced tissue visualization and discrimination combining band selection methods.

PubMed

Nouri, Dorra; Lucas, Yves; Treuillet, Sylvie

2016-12-01

Hyperspectral imaging is an emerging technology recently introduced in medical applications inasmuch as it provides a powerful tool for noninvasive tissue characterization. In this context, a new system was designed to be easily integrated in the operating room in order to detect anatomical tissues hardly noticed by the surgeon's naked eye. Our LCTF-based spectral imaging system is operative over visible, near- and middle-infrared spectral ranges (400-1700 nm). It is dedicated to enhance critical biological tissues such as the ureter and the facial nerve. We aim to find the best three relevant bands to create a RGB image to display during the intervention with maximal contrast between the target tissue and its surroundings. A comparative study is carried out between band selection methods and band transformation methods. Combined band selection methods are proposed. All methods are compared using different evaluation criteria. Experimental results show that the proposed combined band selection methods provide the best performance with rich information, high tissue separability and short computational time. These methods yield a significant discrimination between biological tissues. We developed a hyperspectral imaging system in order to enhance some biological tissue visualization. The proposed methods provided an acceptable trade-off between the evaluation criteria especially in SWIR spectral band that outperforms the naked eye's capacities.

Bone Marrow-derived Mesenchymal Stem Cells (MSCs) as a Selective Delivery Vehicle for a PSA-Activated Protoxin for Advanced Prostate Cancer

DTIC Science & Technology

2013-03-01

tissue have been optimized • Optimization of flow cytometry-based analyses to characterize co- incident expression of multiple MSC-related markers on a...CA). Mouse anti-human vimentin (clone LN-6) was purchased from Sigma-Aldrich (St. Louis, MO). Goat anti-mouse Alexa Fluor 488, Roswell Park

Characterization of a dielectric barrier discharge in controlled atmosphere

NASA Astrophysics Data System (ADS)

Kogelheide, Friederike; Offerhaus, Björn; Bibinov, Nikita; Bracht, Vera; Smith, Ryan; Lackmann, Jan-Wilm; Awakowicz, Peter; Stapelmann, Katharina; Bimap Team; Aept Team

2016-09-01

Non-thermal atmospheric-pressure plasmas are advantageous for various biomedical applications as they make a contact- and painless therapy possible. Due to the potential medical relevance of such plasma sources further understanding of the chemical and physical impact on biological tissue regarding the efficacy and health-promoting effect is necessary. The knowledge of properties and effects offers the possibility to configure plasmas free of risk for humans. Therefore, tailoring the discharge chemistry in regard to resulting oxidative and nitrosative effects on biological tissue by adjusting different parameters is of growing interest. In order to ensure stable conditions for the characterization of the discharge, the used dielectric barrier discharge was mounted in a vessel. Absolutely calibrated optical emission spectroscopy was carried out to analyze the electron density and the reduced electric field. The rather oxygen-based discharge was tuned towards a more nitrogen-based discharge by adjusting several parameters as reactive nitrogen species are known to promote wound healing. Furthermore, the impact of an ozone-free discharge has to be studied. This work was funded by the German Research Foundation (DFG) with the packet grant PAK 816 `Plasma Cell Interaction in Dermatology'.

Biotransformation of tissue-specific hormone tibolone with fungal culture Trichothecium roseum

NASA Astrophysics Data System (ADS)

Shah, Syed Adnan Ali; Sultan, Sadia; Zaimi bin Mohd Noor, M.

2013-06-01

Whole cells based biotransformation is an important tool for bioconversion of steroids. It can be used to synthesize biologically potent compounds with diverse structures. Biotransformation of tissue-specific hormone tibolone (1) with Trichothecium roseum (ATCC 13411) has being carried out for the first time. Two new and three known metabolites 2-6 were isolated from fermentation of tibolone (1) with Trichothecium roseum and their structures were characterized by 2D NMR spectroscopy and mass spectrometry. The relative stereochemistry of new metabolites 5 and 6 was deduced by 2D NOESY experiments. The effect of cultures on tibolone structural modifications and time-course studies has also been conducted.

Photoacoustic and ultrasound dual-modality imaging of human peripheral joints

NASA Astrophysics Data System (ADS)

Xu, Guan; Rajian, Justin R.; Girish, Gandikota; Kaplan, Mariana J.; Fowlkes, J. Brian; Carson, Paul L.; Wang, Xueding

2013-01-01

A photoacoustic (PA) and ultrasound (US) dual modality system, for imaging human peripheral joints, is introduced. The system utilizes a commercial US unit for both US control imaging and PA signal acquisition. Preliminary in vivo evaluation of the system, on normal volunteers, revealed that this system can recover both the structural and functional information of intra- and extra-articular tissues. Confirmed by the control US images, the system, on the PA mode, can differentiate tendon from surrounding soft tissue based on the endogenous optical contrast. Presenting both morphological and pathological information in joint, this system holds promise for diagnosis and characterization of inflammatory joint diseases such as rheumatoid arthritis.

Non-invasive Characterization of the Histopathologic Features of Pulmonary Nodules of the Lung Adenocarcinoma Spectrum using Computer Aided Nodule Assessment and Risk Yield (CANARY) – a Pilot Study

PubMed Central

Maldonado, Fabien; Boland, Jennifer M.; Raghunath, Sushravya; Aubry, Marie Christine; Bartholmai, Brian J.; deAndrade, Mariza; Hartman, Thomas E.; Karwoski, Ronald A.; Rajagopalan, Srinivasan; Sykes, Anne-Marie; Yang, Ping; Yi, Eunhee S.; Robb, Richard A.; Peikert, Tobias

2013-01-01

Introduction Pulmonary nodules of the adenocarcinoma spectrum are characterized by distinctive morphological and radiological features and variable prognosis. Non-invasive high-resolution computed-tomography (HRCT)-based risk stratification tools are needed to individualize their management. Methods Radiological measurements of histopathologic tissue invasion were developed in a training set of 54 pulmonary nodules of the adenocarcinoma spectrum and validated in 86 consecutively resected nodules. Nodules were isolated and characterized by computer-aided analysis and data were analyzed by Spearman correlation, sensitivity, specificity as well as the positive and negative predictive values. Results Computer Aided Nodule Assessment and Risk Yield (CANARY) can non-invasively characterize pulmonary nodules of the adenocarcinoma spectrum. Unsupervised clustering analysis of HRCT data identified 9 unique exemplars representing the basic radiologic building blocks of these lesions. The exemplar distribution within each nodule correlated well with the proportion of histologic tissue invasion, Spearman R=0.87,p < 0.0001 and 0.89,p < 0.0001 for the training and the validation set, respectively. Clustering of the exemplars in three-dimensional space corresponding to tissue invasion and lepidic growth was used to develop a CANARY decision algorithm, which successfully categorized these pulmonary nodules as “aggressive” (invasive adenocarcinoma) or “indolent” (adenocarcinoma in situ and minimally invasive adenocarcinoma). Sensitivity, specificity, positive predictive value and negative predictive value of this approach for the detection of “aggressive” lesions were 95.4%, 96.8%, 95.4% and 96.8%, respectively in the training set and 98.7%, 63.6%, 94.9% and 87.5%, respectively in the validation set. Conclusion CANARY represents a promising tool to non-invasively risk stratify pulmonary nodules of the adenocarcinoma spectrum. PMID:23486265

Fuzzy similarity measures for ultrasound tissue characterization

NASA Astrophysics Data System (ADS)

Emara, Salem M.; Badawi, Ahmed M.; Youssef, Abou-Bakr M.

1995-03-01

Computerized ultrasound tissue characterization has become an objective means for diagnosis of diseases. It is difficult to differentiate diffuse liver diseases, namely cirrhotic and fatty liver from a normal one, by visual inspection from the ultrasound images. The visual criteria for differentiating diffused diseases is rather confusing and highly dependent upon the sonographer's experience. The need for computerized tissue characterization is thus justified to quantitatively assist the sonographer for accurate differentiation and to minimize the degree of risk from erroneous interpretation. In this paper we used the fuzzy similarity measure as an approximate reasoning technique to find the maximum degree of matching between an unknown case defined by a feature vector and a family of prototypes (knowledge base). The feature vector used for the matching process contains 8 quantitative parameters (textural, acoustical, and speckle parameters) extracted from the ultrasound image. The steps done to match an unknown case with the family of prototypes (cirr, fatty, normal) are: Choosing the membership functions for each parameter, then obtaining the fuzzification matrix for the unknown case and the family of prototypes, then by the linguistic evaluation of two fuzzy quantities we obtain the similarity matrix, then by a simple aggregation method and the fuzzy integrals we obtain the degree of similarity. Finally, we find that the similarity measure results are comparable to the neural network classification techniques and it can be used in medical diagnosis to determine the pathology of the liver and to monitor the extent of the disease.

Near-infrared bulk optical properties of goat wound tissue and human serum: consequences for an implantable optical glucose sensor.

PubMed

Aernouts, Ben; Sharma, Sandeep; Gellynck, Karolien; Vlaminck, Lieven; Cornelissen, Maria; Saeys, Wouter

2016-10-01

Near-infrared (NIR) spectroscopy offers a promising technological platform for continuous glucose monitoring in the human body. Moreover, these measurements could be performed in vivo with an implantable single-chip based optical sensor. However, a thin tissue layer may grow in the optical path of the sensor. As most biological tissues are highly scattering, they only allow a small fraction of the collimated light to pass, significantly reducing the light throughput. To quantify the effect of a thin tissue layer in the optical path, the bulk optical properties of serum and tissue samples grown on implanted dummy sensors were characterized using double integrating sphere and unscattered transmittance measurements. The estimated bulk optical properties were then used to calculate the light attenuation through a thin tissue layer. The combination band of glucose was found to be the better option, relative to the first overtone band, as the absorptivity of glucose molecules is higher, while the reduction in unscattered transmittance due to tissue growth is less. Additionally, as the wound tissue was found to be highly scattering, the unscattered transmittance of the tissue layer is expected to be very low. Therefore, a sensor configuration which measures the diffuse transmittance and/or reflectance instead was recommended. (a) Dummy sensor; (b) explanted dummy sensor in tissue lump; (c) removal of dummy sensor from tissue lump; and (d) 900 µm slices of tissue lump. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Real-Time Assessment of Mechanical Tissue Trauma in Surgery.

PubMed

Chandler, James H; Mushtaq, Faisal; Moxley-Wyles, Benjamin; West, Nicholas P; Taylor, Gregory W; Culmer, Peter R

2017-10-01

This work presents a method to assess and prevent tissue trauma in real-time during surgery. Tissue trauma occurs routinely during laparoscopic surgery with potentially severe consequences. As such, it is crucial that a surgeon is able to regulate the pressure exerted by surgical instruments. We propose a novel method to assess the onset of tissue trauma by considering the mechanical response of tissue as it is loaded in real-time. We conducted a parametric study using a lab-based grasping model and differing load conditions. Mechanical stress-time data were analyzed to characterize the tissue response to grasps. Qualitative and quantitative histological analyses were performed to inspect damage characteristics of the tissue under different load conditions. These were correlated against the mechanical measures to identify the nature of trauma onset with respect to our predictive metric. Results showed increasing tissue trauma with load and a strong correlation with the mechanical response of the tissue. Load rate and load history also showed a clear effect on tissue response. The proposed method for trauma assessment was effective in identifying damage. The metric can be normalized with respect to loading rate and history, making it feasible in the unconstrained environment of intraoperative surgery. This work demonstrates that tissue trauma can be predicted using mechanical measures in real-time. Applying this technique to laparoscopic tools has the potential to reduce unnecessary tissue trauma and its associated complications by indicating through user feedback or actively regulating the mechanical impact of surgical instruments.

Fatty Acid Composition of Muscle, Adipose Tissue and Liver from Muskoxen (Ovibos moschatus) Living in West Greenland

PubMed Central

Alves, Susana P.; Raundrup, Katrine; Cabo, Ângelo; Bessa, Rui J. B.; Almeida, André M.

2015-01-01

Information about lipid content and fatty acid (FA) composition of muskoxen (Ovibos moschatos) edible tissues is very limited in comparison to other meat sources. Thus, this work aims to present the first in-depth characterization of the FA profile of meat, subcutaneous adipose tissue and liver of muskoxen living in West Greenland. Furthermore, we aim to evaluate the effect of sex in the FA composition of these edible tissues. Samples from muscle (Longissimus dorsi), subcutaneous adipose tissue and liver were collected from female and male muskoxen, which were delivered at the butchery in Kangerlussuaq (West Greenland) during the winter hunting season. The lipid content of muscle, adipose tissue and liver averaged 284, 846 and 173 mg/g of dry tissue, respectively. This large lipid contents confirms that in late winter, when forage availability is scarce, muskoxen from West Greenland still have high fat reserves, demonstrating that they are well adapted to seasonal feed restriction. A detailed characterization of FA and dimethylacetal composition of muskoxen muscle, subcutaneous adipose tissue and liver showed that there are little differences on FA composition between sexes. Nevertheless, the 18:1cis-9 was the most abundant FA in muscle and adipose tissue, reaching 43% of total FA in muscle. The high content of 18:1cis-9 suggests that it can be selectively stored in muskoxen tissues. Regarding the nutritional composition of muskoxen edible tissues, they are not a good source of polyunsaturated FA; however, they may contribute to a higher fat intake. Information about the FA composition of muskoxen meat and liver is scarce, so this work can contribute to the characterization of the nutritional fat properties of muskoxen edible tissues and can be also useful to update food composition databases. PMID:26678792

Estrogen receptor-independent catechol estrogen binding activity: protein binding studies in wild-type, Estrogen receptor-alpha KO, and aromatase KO mice tissues.

PubMed

Philips, Brian J; Ansell, Pete J; Newton, Leslie G; Harada, Nobuhiro; Honda, Shin-Ichiro; Ganjam, Venkataseshu K; Rottinghaus, George E; Welshons, Wade V; Lubahn, Dennis B

2004-06-01

Primary evidence for novel estrogen signaling pathways is based upon well-documented estrogenic responses not inhibited by estrogen receptor antagonists. In addition to 17beta-E2, the catechol estrogen 4-hydroxyestradiol (4OHE2) has been shown to elicit biological responses independent of classical estrogen receptors in estrogen receptor-alpha knockout (ERalphaKO) mice. Consequently, our research was designed to biochemically characterize the protein(s) that could be mediating the biological effects of catechol estrogens using enzymatically synthesized, radiolabeled 4-hydroxyestrone (4OHE1) and 4OHE2. Scatchard analyses identified a single class of high-affinity (K(d) approximately 1.6 nM), saturable cytosolic binding sites in several ERalphaKO estrogen-responsive tissues. Specific catechol estrogen binding was competitively inhibited by unlabeled catechol estrogens, but not by 17beta-E2 or the estrogen receptor antagonist ICI 182,780. Tissue distribution studies indicated significant binding differences both within and among various tissues in wild-type, ERalphaKO, and aromatase knockout female mice. Ligand metabolism experiments revealed extensive metabolism of labeled catechol estrogen, suggesting that catechol estrogen metabolites were responsible for the specific binding. Collectively, our data provide compelling evidence for the interaction of catechol estrogen metabolites with a novel binding protein that exhibits high affinity, specificity, and selective tissue distribution. The extensive biochemical characterization of this binding protein indicates that this protein may be a receptor, and thus may mediate ERalpha/beta-independent effects of catechol estrogens and their metabolites.

Spatial Systems Lipidomics Reveals Nonalcoholic Fatty Liver Disease Heterogeneity

PubMed Central

2018-01-01

Hepatocellular lipid accumulation characterizes nonalcoholic fatty liver disease (NAFLD). However, the types of lipids associated with disease progression are debated, as is the impact of their localization. Traditional lipidomics analysis using liver homogenates or plasma dilutes and averages lipid concentrations, and does not provide spatial information about lipid distribution. We aimed to characterize the distribution of specific lipid species related to NAFLD severity by performing label-free molecular analysis by mass spectrometry imaging (MSI). Fresh frozen liver biopsies from obese subjects undergoing bariatric surgery (n = 23) with various degrees of NAFLD were cryosectioned and analyzed by matrix-assisted laser desorption/ionization (MALDI)-MSI. Molecular identification was verified by tandem MS. Tissue sections were histopathologically stained, annotated according to the Kleiner classification, and coregistered with the MSI data set. Lipid pathway analysis was performed and linked to local proteome networks. Spatially resolved lipid profiles showed pronounced differences between nonsteatotic and steatotic tissues. Lipid identification and network analyses revealed phosphatidylinositols and arachidonic acid metabolism in nonsteatotic regions, whereas low–density lipoprotein (LDL) and very low–density lipoprotein (VLDL) metabolism was associated with steatotic tissue. Supervised and unsupervised discriminant analysis using lipid based classifiers outperformed simulated analysis of liver tissue homogenates in predicting steatosis severity. We conclude that lipid composition of steatotic and nonsteatotic tissue is highly distinct, implying that spatial context is important for understanding the mechanisms of lipid accumulation in NAFLD. MSI combined with principal component–linear discriminant analysis linking lipid and protein pathways represents a novel tool enabling detailed, comprehensive studies of the heterogeneity of NAFLD. PMID:29570976

Characterization of articular cartilage by combining microscopic analysis with a fibril-reinforced finite-element model.

PubMed

Julkunen, Petro; Kiviranta, Panu; Wilson, Wouter; Jurvelin, Jukka S; Korhonen, Rami K

2007-01-01

Load-bearing characteristics of articular cartilage are impaired during tissue degeneration. Quantitative microscopy enables in vitro investigation of cartilage structure but determination of tissue functional properties necessitates experimental mechanical testing. The fibril-reinforced poroviscoelastic (FRPVE) model has been used successfully for estimation of cartilage mechanical properties. The model includes realistic collagen network architecture, as shown by microscopic imaging techniques. The aim of the present study was to investigate the relationships between the cartilage proteoglycan (PG) and collagen content as assessed by quantitative microscopic findings, and model-based mechanical parameters of the tissue. Site-specific variation of the collagen network moduli, PG matrix modulus and permeability was analyzed. Cylindrical cartilage samples (n=22) were harvested from various sites of the bovine knee and shoulder joints. Collagen orientation, as quantitated by polarized light microscopy, was incorporated into the finite-element model. Stepwise stress-relaxation experiments in unconfined compression were conducted for the samples, and sample-specific models were fitted to the experimental data in order to determine values of the model parameters. For comparison, Fourier transform infrared imaging and digital densitometry were used for the determination of collagen and PG content in the same samples, respectively. The initial and strain-dependent fibril network moduli as well as the initial permeability correlated significantly with the tissue collagen content. The equilibrium Young's modulus of the nonfibrillar matrix and the strain dependency of permeability were significantly associated with the tissue PG content. The present study demonstrates that modern quantitative microscopic methods in combination with the FRPVE model are feasible methods to characterize the structure-function relationships of articular cartilage.

Variation in primary and culture-expanded cells derived from connective tissue progenitors in human bone marrow space, bone trabecular surface and adipose tissue.

PubMed

Qadan, Maha A; Piuzzi, Nicolas S; Boehm, Cynthia; Bova, Wesley; Moos, Malcolm; Midura, Ronald J; Hascall, Vincent C; Malcuit, Christopher; Muschler, George F

2018-03-01

Connective tissue progenitors (CTPs) embody the heterogeneous stem and progenitor cell populations present in native tissue. CTPs are essential to the formation and remodeling of connective tissue and represent key targets for tissue-engineering and cell-based therapies. To better understand and characterize CTPs, we aimed to compare the (i) concentration and prevalence, (ii) early in vitro biological behavior and (iii) expression of surface-markers and transcription factors among cells derived from marrow space (MS), trabecular surface (TS), and adipose tissues (AT). Cancellous-bone and subcutaneous-adipose tissues were collected from 8 patients. Cells were isolated and cultured. Colony formation was assayed using Colonyze software based on ASTM standards. Cell concentration ([Cell]), CTP concentration ([CTP]) and CTP prevalence (P CTP ) were determined. Attributes of culture-expanded cells were compared based on (i) effective proliferation rate and (ii) expression of surface-markers CD73, CD90, CD105, SSEA-4, SSEA-3, SSEA-1/CD15, Cripto-1, E-Cadherin/CD324, Ep-CAM/CD326, CD146, hyaluronan and transcription factors Oct3/4, Sox-2 and Nanog using flow cytometry. Mean [Cell], [CTP] and P CTP were significantly different between MS and TS samples (P = 0.03, P = 0.008 and P= 0.0003), respectively. AT-derived cells generated the highest mean total cell yield at day 6 of culture-4-fold greater than TS and more than 40-fold greater than MS per million cells plated. TS colonies grew with higher mean density than MS colonies (290 ± 11 versus 150 ± 11 cell per mm 2 ; P = 0.0002). Expression of classical-mesenchymal stromal cell (MSC) markers was consistently recorded (>95%) from all tissue sources, whereas all the other markers were highly variable. The prevalence and biological potential of CTPs are different between patients and tissue sources and lack variation in classical MSC markers. Other markers are more likely to discriminate differences between cell populations in biological performance. Understanding the underlying reasons for variation in the concentration, prevalence, marker expression and biological potential of CTPs between patients and source tissues and determining the means of managing this variation will contribute to the rational development of cell-based clinical diagnostics and targeted cell-based therapies. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Fractional Derivative Models for Ultrasonic Characterization of Polymer and Breast Tissue Viscoelasticity

PubMed Central

Coussot, Cecile; Kalyanam, Sureshkumar; Yapp, Rebecca; Insana, Michael F.

2009-01-01

The viscoelastic response of hydropolymers, which include glandular breast tissues, may be accurately characterized for some applications with as few as 3 rheological parameters by applying the Kelvin-Voigt fractional derivative (KVFD) modeling approach. We describe a technique for ultrasonic imaging of KVFD parameters in media undergoing unconfined, quasi-static, uniaxial compression. We analyze the KVFD parameter values in simulated and experimental echo data acquired from phantoms and show that the KVFD parameters may concisely characterize the viscoelastic properties of hydropolymers. We then interpret the KVFD parameter values for normal and cancerous breast tissues and hypothesize that this modeling approach may ultimately be applied to tumor differentiation. PMID:19406700

TU-F-BRB-03: Clinical Implementation of MR-Based Motion Management

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glide-Hurst, C.

The current clinical standard of organ respiratory imaging, 4D-CT, is fundamentally limited by poor soft-tissue contrast and imaging dose. These limitations are potential barriers to beneficial “4D” radiotherapy methods which optimize the target and OAR dose-volume considering breathing motion but rely on a robust motion characterization. Conversely, MRI imparts no known radiation risk and has excellent soft-tissue contrast. MRI-based motion management is therefore highly desirable and holds great promise to improve radiotherapy of moving cancers, particularly in the abdomen. Over the past decade, MRI techniques have improved significantly, making MR-based motion management clinically feasible. For example, cine MRI has highmore » temporal resolution up to 10 f/s and has been used to track and/or characterize tumor motion, study correlation between external and internal motions. New MR technologies, such as 4D-MRI and MRI hybrid treatment machines (i.e. MR-linac or MR-Co60), have been recently developed. These technologies can lead to more accurate target volume determination and more precise radiation dose delivery via direct tumor gating or tracking. Despite all these promises, great challenges exist and the achievable clinical benefit of MRI-based tumor motion management has yet to be fully explored, much less realized. In this proposal, we will review novel MR-based motion management methods and technologies, the state-of-the-art concerning MRI development and clinical application and the barriers to more widespread adoption. Learning Objectives: Discuss the need of MR-based motion management for improving patient care in radiotherapy. Understand MR techniques for motion imaging and tumor motion characterization. Understand the current state of the art and future steps for clinical integration. Henry Ford Health System holds research agreements with Philips Healthcare. Research sponsored in part by a Henry Ford Health System Internal Mentored Grant.« less

TU-F-BRB-00: MRI-Based Motion Management for RT

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

The current clinical standard of organ respiratory imaging, 4D-CT, is fundamentally limited by poor soft-tissue contrast and imaging dose. These limitations are potential barriers to beneficial “4D” radiotherapy methods which optimize the target and OAR dose-volume considering breathing motion but rely on a robust motion characterization. Conversely, MRI imparts no known radiation risk and has excellent soft-tissue contrast. MRI-based motion management is therefore highly desirable and holds great promise to improve radiotherapy of moving cancers, particularly in the abdomen. Over the past decade, MRI techniques have improved significantly, making MR-based motion management clinically feasible. For example, cine MRI has highmore » temporal resolution up to 10 f/s and has been used to track and/or characterize tumor motion, study correlation between external and internal motions. New MR technologies, such as 4D-MRI and MRI hybrid treatment machines (i.e. MR-linac or MR-Co60), have been recently developed. These technologies can lead to more accurate target volume determination and more precise radiation dose delivery via direct tumor gating or tracking. Despite all these promises, great challenges exist and the achievable clinical benefit of MRI-based tumor motion management has yet to be fully explored, much less realized. In this proposal, we will review novel MR-based motion management methods and technologies, the state-of-the-art concerning MRI development and clinical application and the barriers to more widespread adoption. Learning Objectives: Discuss the need of MR-based motion management for improving patient care in radiotherapy. Understand MR techniques for motion imaging and tumor motion characterization. Understand the current state of the art and future steps for clinical integration. Henry Ford Health System holds research agreements with Philips Healthcare. Research sponsored in part by a Henry Ford Health System Internal Mentored Grant.« less

An electrical impedance tomography (EIT) multi-electrode needle-probe device for local assessment of heterogeneous tissue impeditivity.

PubMed

Meroni, Davide; Maglioli, Camilla Carpano; Bovio, Dario; Greco, Francesco G; Aliverti, Andrea

2017-07-01

Electrical Impedance Tomography (EIT) is an image reconstruction technique applied in medicine for the electrical imaging of living tissues. In literature there is the evidence that a large resistivity variation related to the differences of the human tissues exists. As a result of this interest for the electrical characterization of the biological samples, recently the attention is also focused on the identification and characterization of the human tissue, by studying the homogeneity of its structure. An 8 electrodes needle-probe device has been developed with the intent of identifying the structural inhomogeneities under the surface layers. Ex-vivo impeditivity measurements, by placing the needle-probe in 5 different patterns of fat and lean porcine tissue, were performed, and impeditivity maps were obtained by EIDORS open source software for image reconstruction in electrical impedance. The values composing the maps have been analyzed, pointing out a good tissue discrimination, and the conformity with the real images. We conclude that this device is able to perform impeditivity maps matching to reality for position and orientation. In all the five patterns presented is possible to identify and replicate correctly the heterogeneous tissue under test. This new procedure can be helpful to the medical staff to completely characterize the biological sample, in different unclear situations.

Motivation, characterization, and strategy for tissue engineering the temporomandibular joint disc.

PubMed

Detamore, Michael S; Athanasiou, Kyriacos A

2003-12-01

The purpose of this review is to serve as the standard point of reference in guiding researchers investigating the tissue engineering of the temporomandibular joint (TMJ) disc. Tissue engineering of the TMJ disc is in its infancy, and currently there exists a gap between the tissue engineering community and the TMJ characterization community. The primary goal is to help bridge that gap by consolidating the characterization studies here as a reference to researchers attempting to tissue engineer the TMJ disc. A brief review of TMJ anatomy is provided, along with a description of relevant pathology, current treatment, and a rationale for engineering the TMJ disc. The biochemical composition and organization of the disc are reviewed, including glycosaminoglycan (GAG) and collagen content. The collagen of the disc is almost exclusively type I and primarily runs anteroposteriorly through the center and in a ringlike fashion around the periphery. The GAG content is approximately an order of magnitude less than that of hyaline cartilage, and although the distribution is not entirely clear, it seems as though chondroitin and dermatan sulfate are by far the primary GAGs. Cellular characterization and mechanical properties under compression, tension, and shear are reviewed as well. The cells of the disc are not chondrocytes, but rather resemble fibrocytes and fibrochondrocytes and may be of the same lineage. Mechanically, the disc is certainly anisotropic and nonhomogeneous. Finally, a review of efforts in tissue engineering and cell culture studies of the disc is provided and we close with a description of the direction we envision/propose for successful tissue engineering of the TMJ disc.

Photoacoustic characterization of the left atrium wall: healthy and ablated tissue (Conference Presentation)

NASA Astrophysics Data System (ADS)

Iskander-Rizk, Sophinese; Kruizinga, Pieter; van der Steen, Antonius F. W.; van Soest, Gijs

2017-03-01

Radio-frequency ablation (RFA) creates a thermal lesion in the atrial wall, with clearly recognizable optical and structural changes to the tissue. This can be detected by photoacoustic (PA) imaging, and used for monitoring of lesion depth, lesion functionality, and limiting excessive ablation. Porcine left atrium tissue can be split into three visually distinguishable regions, a thick white endocardium, pinkish myocardium and a thin gelatinous epicardium. In this study, we characterize the layered left atrium tissue in terms of the relevant photoacoustic parameters (wavelength, frequency content, imaging depth, lesion contrast). Previous studies in the literature targeted the photoacoustic characterization of fresh and ablated ventricular myocardium in the range of 650nm to 900nm. In this study we target the characterization of fresh and ablated left atrial tissue from 410nm to 1000nm, including the endocardium and epicardium. We generate the photoacoustic signals using a tunable pulsed laser source, and record those signals using either a broadband 1 mm hydrophone or a L12-3v transducer connected to the Verasonics machine for more realistic conditions. Initial experiments on fresh porcine tissue show that the presence of the endocardium and epicardium layers do affect the photoacoustic signal received. The signal recorded is representative of the difference in optical and mechanical properties between the layers. Ablated and non-ablated tissue also present differences in spectra. The determined optical contrast could be used in the PA monitoring of RFA lesion to monitor the extension of the lesion to the edge of the myocardium-epicardium border avoiding complications related to over ablation.

Textural characterization of histopathological images for oral sub-mucous fibrosis detection.

PubMed

Krishnan, M Muthu Rama; Shah, Pratik; Choudhary, Anirudh; Chakraborty, Chandan; Paul, Ranjan Rashmi; Ray, Ajoy K

2011-10-01

In the field of quantitative microscopy, textural information plays a significant role very often in tissue characterization and diagnosis, in addition to morphology and intensity. The aim of this work is to improve the classification accuracy based on textural features for the development of a computer assisted screening of oral sub-mucous fibrosis (OSF). In fact, a systematic approach is introduced in order to grade the histopathological tissue sections into normal, OSF without dysplasia and OSF with dysplasia, which would help the oral onco-pathologists to screen the subjects rapidly. In totality, 71 textural features are extracted from epithelial region of the tissue sections using various wavelet families, Gabor-wavelet, local binary pattern, fractal dimension and Brownian motion curve, followed by preprocessing and segmentation. Wavelet families contribute a common set of 9 features, out of which 8 are significant and other 61 out of 62 obtained from the rest of the extractors are also statistically significant (p<0.05) in discriminating the three stages. Based on mean distance criteria, the best wavelet family (i.e., biorthogonal3.1 (bior3.1)) is selected for classifier design. support vector machine (SVM) is trained by 146 samples based on 69 textural features and its classification accuracy is computed for each of the combinations of wavelet family and rest of the extractors. Finally, it has been investigated that bior3.1 wavelet coefficients leads to higher accuracy (88.38%) in combination with LBP and Gabor wavelet features through three-fold cross validation. Results are shown and discussed in detail. It is shown that combining more than one texture measure instead of using just one might improve the overall accuracy. Copyright © 2011 Elsevier Ltd. All rights reserved.

Multispectral tissue characterization for intestinal anastomosis optimization.

PubMed

Cha, Jaepyeong; Shademan, Azad; Le, Hanh N D; Decker, Ryan; Kim, Peter C W; Kang, Jin U; Krieger, Axel

2015-10-01

Intestinal anastomosis is a surgical procedure that restores bowel continuity after surgical resection to treat intestinal malignancy, inflammation, or obstruction. Despite the routine nature of intestinal anastomosis procedures, the rate of complications is high. Standard visual inspection cannot distinguish the tissue subsurface and small changes in spectral characteristics of the tissue, so existing tissue anastomosis techniques that rely on human vision to guide suturing could lead to problems such as bleeding and leakage from suturing sites. We present a proof-of-concept study using a portable multispectral imaging (MSI) platform for tissue characterization and preoperative surgical planning in intestinal anastomosis. The platform is composed of a fiber ring light-guided MSI system coupled with polarizers and image analysis software. The system is tested on ex vivo porcine intestine tissue, and we demonstrate the feasibility of identifying optimal regions for suture placement.

Adipose tissue derived mesenchymal stem cells for musculoskeletal repair in veterinary medicine

PubMed Central

Arnhold, Stefan; Wenisch, Sabine

2015-01-01

Adipose tissue derived stem cells (ASCs) are mesenchymal stem cells which can be obtained from different adipose tissue sources within the body. It is an abundant cell pool, which is easy accessible and the cells can be obtained in large numbers, cultivated and expanded in vitro and prepared for tissue engineering approaches, especially for skeletal tissue repair. In the recent years this cell population has attracted a great amount of attention among researchers in human as well as in veterinary medicine. In the meantime ASCs have been well characterized and their use in regenerative medicine is very well established. This review focuses on the characterization of ASCs for their use for tissue engineering approaches especially in veterinary medicine and also highlights a selection of clinical trials on the basis of ASCs as the relevant cell source. PMID:25973326

Adipose tissue derived mesenchymal stem cells for musculoskeletal repair in veterinary medicine.

PubMed

Arnhold, Stefan; Wenisch, Sabine

2015-01-01

Adipose tissue derived stem cells (ASCs) are mesenchymal stem cells which can be obtained from different adipose tissue sources within the body. It is an abundant cell pool, which is easy accessible and the cells can be obtained in large numbers, cultivated and expanded in vitro and prepared for tissue engineering approaches, especially for skeletal tissue repair. In the recent years this cell population has attracted a great amount of attention among researchers in human as well as in veterinary medicine. In the meantime ASCs have been well characterized and their use in regenerative medicine is very well established. This review focuses on the characterization of ASCs for their use for tissue engineering approaches especially in veterinary medicine and also highlights a selection of clinical trials on the basis of ASCs as the relevant cell source.

Multispectral tissue characterization for intestinal anastomosis optimization

PubMed Central

Cha, Jaepyeong; Shademan, Azad; Le, Hanh N. D.; Decker, Ryan; Kim, Peter C. W.; Kang, Jin U.; Krieger, Axel

2015-01-01

Abstract. Intestinal anastomosis is a surgical procedure that restores bowel continuity after surgical resection to treat intestinal malignancy, inflammation, or obstruction. Despite the routine nature of intestinal anastomosis procedures, the rate of complications is high. Standard visual inspection cannot distinguish the tissue subsurface and small changes in spectral characteristics of the tissue, so existing tissue anastomosis techniques that rely on human vision to guide suturing could lead to problems such as bleeding and leakage from suturing sites. We present a proof-of-concept study using a portable multispectral imaging (MSI) platform for tissue characterization and preoperative surgical planning in intestinal anastomosis. The platform is composed of a fiber ring light-guided MSI system coupled with polarizers and image analysis software. The system is tested on ex vivo porcine intestine tissue, and we demonstrate the feasibility of identifying optimal regions for suture placement. PMID:26440616

A Dual-Mode Bioreactor System for Tissue Engineered Vascular Models.

PubMed

Bono, N; Meghezi, S; Soncini, M; Piola, M; Mantovani, D; Fiore, Gianfranco Beniamino

2017-06-01

In the past decades, vascular tissue engineering has made great strides towards bringing engineered vascular tissues to the clinics and, in parallel, obtaining in-lab tools for basic research. Herein, we propose the design of a novel dual-mode bioreactor, useful for the fabrication (construct mode) and in vitro stimulation (culture mode) of collagen-based tubular constructs. Collagen-based gels laden with smooth muscle cells (SMCs) were molded directly within the bioreactor culture chamber. Based on a systematic characterization of the bioreactor culture mode, constructs were subjected to 10% cyclic strain at 0.5 Hz for 5 days. The effects of cyclic stimulation on matrix re-arrangement and biomechanical/viscoelastic properties were examined and compared vs. statically cultured constructs. A thorough comparison of cell response in terms of cell localization and expression of contractile phenotypic markers was carried out as well. We found that cyclic stimulation promoted cell-driven collagen matrix bi-axial compaction, enhancing the mechanical strength of strained samples with respect to static controls. Moreover, cyclic strain positively affected SMC behavior: cells maintained their contractile phenotype and spread uniformly throughout the whole wall thickness. Conversely, static culture induced a noticeable polarization of cell distribution to the outer rim of the constructs and a sharp reduction in total cell density. Overall, coupling the use of a novel dual-mode bioreactor with engineered collagen-gel-based tubular constructs demonstrated to be an interesting technology to investigate the modulation of cell and tissue behavior under controlled mechanically conditioned in vitro maturation.

In vivo interstitial glucose characterization and monitoring in the skin by ATR-FTIR spectroscopy

NASA Astrophysics Data System (ADS)

Skrebova Eikje, Natalja

2011-03-01

Successful development of real-time non-invasive glucose monitoring would represent a major advancement not only in the treatment and management of patients with diabetes mellitus and carbohydrate metabolism disorders, but also for understanding in those biochemical, metabolic and (patho-)physiological processes of glucose at the molecular level in vivo. Here, ATR-FTIR spectroscopy technique has been challenged not only for in vivo measurement of interstitial glucose levels, but also for their non-invasive molecular qualitative and quantitative comparative characterization in the skin tissue. The results, based on calculated mean values of determined 5 glucose-specific peaks in the glucose-related 1000-1160 cm-1 region, showed intra- and inter-subject differences in interstitial glucose activity levels with their changes at different times and doses of OGTT, while raising questions about the relationships between interstitial and blood glucose levels. In conclusion, the introduction of ATR-FTIR spectroscopy technique has opened up an access to the interstitial fluid space in the skin tissue for interstitial glucose characterization and monitoring in vivo. Though interstitial versus blood glucose monitoring has different characteristics, it can be argued that accurate and precise measurements of interstitial glucose levels may be more important clinically.

Biological and MRI characterization of biomimetic ECM scaffolds for cartilage tissue regeneration.

PubMed

Ravindran, Sriram; Kotecha, Mrignayani; Huang, Chun-Chieh; Ye, Allen; Pothirajan, Padmabharathi; Yin, Ziying; Magin, Richard; George, Anne

2015-12-01

Osteoarthritis is the most common joint disorder affecting millions of people. Most scaffolds developed for cartilage regeneration fail due to vascularization and matrix mineralization. In this study we present a chondrogenic extracellular matrix (ECM) incorporated collagen/chitosan scaffold (chondrogenic ECM scaffold) for potential use in cartilage regenerative therapy. Biochemical characterization showed that these scaffolds possess key pro-chondrogenic ECM components and growth factors. MRI characterization showed that the scaffolds possess mechanical properties and diffusion characteristics important for cartilage tissue regeneration. In vivo implantation of the chondrogenic ECM scaffolds with bone marrow derived mesenchymal stem cells (MSCs) triggered chondrogenic differentiation of the MSCs without the need for external stimulus. Finally, results from in vivo MRI experiments indicate that the chondrogenic ECM scaffolds are stable and possess MR properties on par with native cartilage. Based on our results, we envision that such ECM incorporated scaffolds have great potential in cartilage regenerative therapy. Additionally, our validation of MR parameters with histology and biochemical analysis indicates the ability of MRI techniques to track the progress of our ECM scaffolds non-invasively in vivo; highlighting the translatory potential of this technology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterization of the Optical Properties of Turbid Media by Supervised Learning of Scattering Patterns.

PubMed

Hassaninia, Iman; Bostanabad, Ramin; Chen, Wei; Mohseni, Hooman

2017-11-10

Fabricated tissue phantoms are instrumental in optical in-vitro investigations concerning cancer diagnosis, therapeutic applications, and drug efficacy tests. We present a simple non-invasive computational technique that, when coupled with experiments, has the potential for characterization of a wide range of biological tissues. The fundamental idea of our approach is to find a supervised learner that links the scattering pattern of a turbid sample to its thickness and scattering parameters. Once found, this supervised learner is employed in an inverse optimization problem for estimating the scattering parameters of a sample given its thickness and scattering pattern. Multi-response Gaussian processes are used for the supervised learning task and a simple setup is introduced to obtain the scattering pattern of a tissue sample. To increase the predictive power of the supervised learner, the scattering patterns are filtered, enriched by a regressor, and finally characterized with two parameters, namely, transmitted power and scaled Gaussian width. We computationally illustrate that our approach achieves errors of roughly 5% in predicting the scattering properties of many biological tissues. Our method has the potential to facilitate the characterization of tissues and fabrication of phantoms used for diagnostic and therapeutic purposes over a wide range of optical spectrum.

Characterization of the mechanical properties of resected porcine organ tissue using optical fiber photoelastic polarimetry.

PubMed

Hudnut, Alexa W; Babaei, Behzad; Liu, Sonya; Larson, Brent K; Mumenthaler, Shannon M; Armani, Andrea M

2017-10-01

Characterizing the mechanical behavior of living tissue presents an interesting challenge because the elasticity varies by eight orders of magnitude, from 50Pa to 5GPa. In the present work, a non-destructive optical fiber photoelastic polarimetry system is used to analyze the mechanical properties of resected samples from porcine liver, kidney, and pancreas. Using a quasi-linear viscoelastic fit, the elastic modulus values of the different organ systems are determined. They are in agreement with previous work. In addition, a histological assessment of compressed and uncompressed tissues confirms that the tissue is not damaged during testing.

Photoacoustic resonance spectroscopy for biological tissue characterization

NASA Astrophysics Data System (ADS)

Gao, Fei; Feng, Xiaohua; Zheng, Yuanjin; Ohl, Claus-Dieter

2014-06-01

By "listening to photons," photoacoustics allows the probing of chromosomes in depth beyond the optical diffusion limit. Here we report the photoacoustic resonance effect induced by multiburst modulated laser illumination, which is theoretically modeled as a damped mass-string oscillator and a resistor-inductor-capacitor (RLC) circuit. Through sweeping the frequency of multiburst modulated laser, the photoacoustic resonance effect is observed experimentally on phantoms and porcine tissues. Experimental results demonstrate different spectra for each phantom and tissue sample to show significant potential for spectroscopic analysis, fusing optical absorption and mechanical vibration properties. Unique RLC circuit parameters are extracted to quantitatively characterize phantom and biological tissues.

Combining fibre optic Raman spectroscopy and tactile resonance measurement for tissue characterization

NASA Astrophysics Data System (ADS)

Candefjord, Stefan; Nyberg, Morgan; Jalkanen, Ville; Ramser, Kerstin; Lindahl, Olof A.

2010-12-01

Tissue characterization is fundamental for identification of pathological conditions. Raman spectroscopy (RS) and tactile resonance measurement (TRM) are two promising techniques that measure biochemical content and stiffness, respectively. They have potential to complement the golden standard--histological analysis. By combining RS and TRM, complementary information about tissue content can be obtained and specific drawbacks can be avoided. The aim of this study was to develop a multivariate approach to compare RS and TRM information. The approach was evaluated on measurements at the same points on porcine abdominal tissue. The measurement points were divided into five groups by multivariate analysis of the RS data. A regression analysis was performed and receiver operating characteristic (ROC) curves were used to compare the RS and TRM data. TRM identified one group efficiently (area under ROC curve 0.99). The RS data showed that the proportion of saturated fat was high in this group. The regression analysis showed that stiffness was mainly determined by the amount of fat and its composition. We concluded that RS provided additional, important information for tissue identification that was not provided by TRM alone. The results are promising for development of a method combining RS and TRM for intraoperative tissue characterization.

Predictive analysis of thermal distribution and damage in thermotherapy on biological tissue

NASA Astrophysics Data System (ADS)

Fanjul-Vélez, Félix; Arce-Diego, José Luis

2007-05-01

The use of optical techniques is increasing the possibilities and success of medical praxis in certain cases, either in tissue characterization or treatment. Photodynamic therapy (PDT) or low intensity laser treatment (LILT) are two examples of the latter. Another very interesting implementation is thermotherapy, which consists of controlling temperature increase in a pathological biological tissue. With this method it is possible to provoke an improvement on specific diseases, but a previous analysis of treatment is needed in order for the patient not to suffer any collateral damage, an essential point due to security margins in medical procedures. In this work, a predictive analysis of thermal distribution in a biological tissue irradiated by an optical source is presented. Optical propagation is based on a RTT (Radiation Transport Theory) model solved via a numerical Monte Carlo method, in a multi-layered tissue. Data obtained are included in a bio-heat equation that models heat transference, taking into account conduction, convection, radiation, blood perfusion and vaporization depending on the specific problem. Spatial-temporal differential bio-heat equation is solved via a numerical finite difference approach. Experimental temperature distributions on animal tissue irradiated by laser radiation are shown. From thermal distribution in tissue, thermal damage is studied, based on an Arrhenius analysis, as a way of predicting harmful effects. The complete model can be used for concrete treatment proposals, as a way of predicting treatment effects and consequently decide which optical source parameters are appropriate for the specific disease, mainly wavelength and optical power, with reasonable security margins in the process.

Automated classification and visualization of healthy and pathological dental tissues based on near-infrared hyper-spectral imaging

NASA Astrophysics Data System (ADS)

Usenik, Peter; Bürmen, Miran; Vrtovec, Tomaž; Fidler, Aleš; Pernuš, Franjo; Likar, Boštjan

2011-03-01

Despite major improvements in dental healthcare and technology, dental caries remains one of the most prevalent chronic diseases of modern society. The initial stages of dental caries are characterized by demineralization of enamel crystals, commonly known as white spots which are difficult to diagnose. If detected early enough, such demineralization can be arrested and reversed by non-surgical means through well established dental treatments (fluoride therapy, anti-bacterial therapy, low intensity laser irradiation). Near-infrared (NIR) hyper-spectral imaging is a new promising technique for early detection of demineralization based on distinct spectral features of healthy and pathological dental tissues. In this study, we apply NIR hyper-spectral imaging to classify and visualize healthy and pathological dental tissues including enamel, dentin, calculus, dentin caries, enamel caries and demineralized areas. For this purpose, a standardized teeth database was constructed consisting of 12 extracted human teeth with different degrees of natural dental lesions imaged by NIR hyper-spectral system, X-ray and digital color camera. The color and X-ray images of teeth were presented to a clinical expert for localization and classification of the dental tissues, thereby obtaining the gold standard. Principal component analysis was used for multivariate local modeling of healthy and pathological dental tissues. Finally, the dental tissues were classified by employing multiple discriminant analysis. High agreement was observed between the resulting classification and the gold standard with the classification sensitivity and specificity exceeding 85 % and 97 %, respectively. This study demonstrates that NIR hyper-spectral imaging has considerable diagnostic potential for imaging hard dental tissues.

Initial Biochemical Characterization of Cells Derived from Human Periodontium and Their In vitro Response to Platelet-Derived Growth Factor, Epidermal Growth Factor and Transforming Growth Factor-Beta

DTIC Science & Technology

1988-05-01

Periodontal disease is characterized by a loss of connective tissue...obtained for bone cells and fibroblasts. • " S,. O. ipr’ 0 II. LITERATURE REVIEW A . Periodontal Regeneration Periodontal disease is characterized by a ...fracture are felt to involve a similar sequence of cellular events. Since periodontal disease also involves the loss of soft tissue structures, such

Mechanical characterization of soft materials using transparent indenter testing system and finite element simulation

NASA Astrophysics Data System (ADS)

Xuan, Yue

Background. Soft materials such as polymers and soft tissues have diverse applications in bioengineering, medical care, and industry. Quantitative mechanical characterization of soft materials at multiscales is required to assure that appropriate mechanical properties are presented to support the normal material function. Indentation test has been widely used to characterize soft material. However, the measurement of in situ contact area is always difficult. Method of Approach. A transparent indenter method was introduced to characterize the nonlinear behaviors of soft materials under large deformation. This approach made the direct measurement of contact area and local deformation possible. A microscope was used to capture the contact area evolution as well as the surface deformation. Based on this transparent indenter method, a novel transparent indentation measurement systems has been built and multiple soft materials including polymers and pericardial tissue have been characterized. Seven different indenters have been used to study the strain distribution on the contact surface, inner layer and vertical layer. Finite element models have been built to simulate the hyperelastic and anisotropic material behaviors. Proper material constants were obtained by fitting the experimental results. Results.Homogeneous and anisotropic silicone rubber and porcine pericardial tissue have been examined. Contact area and local deformation were measured by real time imaging the contact interface. The experimental results were compared with the predictions from the Hertzian equations. The accurate measurement of contact area results in more reliable Young's modulus, which is critical for soft materials. For the fiber reinforced anisotropic silicone rubber, the projected contact area under a hemispherical indenter exhibited elliptical shape. The local surface deformation under indenter was mapped using digital image correlation program. Punch test has been applied to thin films of silicone rubber and porcine pericardial tissue and results were analyzed using the same method. Conclusions. The transparent indenter testing system can effectively reduce the material properties measurement error by directly measuring the contact radii. The contact shape can provide valuable information for the anisotropic property of the material. Local surface deformation including contact surface, inner layer and vertical plane can be accurately tracked and mapped to study the strain distribution. The potential usage of the transparent indenter measurement system to investigate biological and biomaterials was verified. The experimental data including the real-time contact area combined with the finite element simulation would be powerful tool to study mechanical properties of soft materials and their relation to microstructure, which has potential in pathologies study such as tissue repair and surgery plan. Key words: transparent indenter, large deformation, soft material, anisotropic.

High-resolution vascular tissue characterization in mice using 55 MHz ultrasound hybrid imaging

PubMed Central

Mahmoud, Ahmed M.; Sandoval, Cesar; Teng, Bunyen; Schnermann, Jurgen B.; Martin, Karen H.; Mustafa, S. Jamal; Mukdadi, Osama M.

2012-01-01

Ultrasound and Duplex ultrasonography in particular are routinely used to diagnose cardiovascular disease (CVD), which is the leading cause of morbidity and mortality worldwide. However, these techniques may not be able to characterize vascular tissue compositional changes due to CVD. This work describes an ultrasound-based hybrid imaging technique that can be used for vascular tissue characterization and the diagnosis of atherosclerosis. Ultrasound radiofrequency (RF) data were acquired and processed in time, frequency, and wavelet domains to extract six parameters including time integrated backscatter (TIB), time variance (Tvar), time entropy (TE), frequency integrated backscatter (FIB), wavelet root mean square value (Wrms), and wavelet integrated backscatter (WIB). Each parameter was used to reconstruct an image co-registered to morphological B-scan. The combined set of hybrid images were used to characterize vascular tissue in vitro and in vivo using three mouse models including control (C57BL/6), and atherosclerotic apolipoprotein E-knockout (APOE-KO) and APOE/A1 adenosine receptor double knockout (DKO) mice. The technique was tested using high-frequency ultrasound including single-element (center frequency = 55 MHz) and commercial array (center frequency = 40 MHz) systems providing superior spatial resolutions of 24 μm and 40 μm, respectively. Atherosclerotic vascular lesions in the APOE-KO mouse exhibited the highest values (contrast) of −10.11 ± 1.92 dB, −12.13 ± 2.13 dB, −7.54 ± 1.45 dB, −5.10 ± 1.06 dB, −5.25 ± 0.94 dB, and −10.23 ± 2.12 dB in TIB, Tvar, TE, FIB, Wrms, WIB hybrid images (n = 10, p < 0.05), respectively. Control segments of normal vascular tissue showed the lowest values of −20.20 ± 2.71 dB, −22.54 ± 4.54 dB, −14.94 ± 2.05 dB, −9.64 ± 1.34 dB, −10.20 ± 1.27 dB, and −19.36 ± 3.24 dB in same hybrid images (n = 6, p < 0.05). Results from both histology and optical images showed good agreement with ultrasound findings within a maximum error of 3.6% in lesion estimation. This study demonstrated the feasibility of a high-resolution hybrid imaging technique to diagnose atherosclerosis and characterize plaque components in mouse. In the future, it can be easily implemented on commercial ultrasound systems and eventually translated into clinics as a screening tool for atherosclerosis and the assessment of vulnerable plaques. PMID:23218908

Development of HIV-1 Rectal-Specific Microbicides and Colonic Tissue Evaluation

PubMed Central

Dezzutti, Charlene S.; Russo, Julie; Wang, Lin; Abebe, Kaleab Z.; Li, Jie; Friend, David R.; McGowan, Ian M.; Rohan, Lisa C.

2014-01-01

The gastrointestinal tract is structurally and functionally different from the vagina. Thus, the paradigm of topical microbicide development and evaluation has evolved to include rectal microbicides (RMs). Our interest was to create unique RM formulations to safely and effectively deliver antiretroviral drugs to mucosal tissue. RMs were designed to include those that spread and coat all surfaces of the rectum and distal colon rapidly (liquid) and those that create a deformable, erodible barrier and remain localized at the administration site (gel). Tenofovir (TFV) (1%) was formulated as an aqueous thermoreversible fluid and a carbopol-based aqueous hydrogel. Lipid-based liquid and gel formulations were prepared for UC781 (0.1%) using isopropyl myristate and GTCC (Caprylic/Capric Triglycerides), respectively. Formulations were characterized for pH, viscosity, osmolality, and drug content. Pre-clinical testing incorporated ex vivo colonic tissue obtained through surgical resections and flexible sigmoidoscopy (flex sig). As this was the first time using tissue from both sources side-by-side, the ability to replicate HIV-1 was compared. Efficacy of the RM formulations was tested by applying the products with HIV-1 directly to polarized colonic tissue and following viral replication. Safety of the formulations was determined by MTT assay and histology. All products had a neutral pH and were isoosmolar. While HIV-1BaL and HIV-1JR-CSF alone and in the presence of semen had similar replication trends between surgically resected and flex sig tissues, the magnitude of viral replication was significantly better in flex sig tissues. Both TFV and UC781 formulations protected the colonic tissue, regardless of tissue source, from HIV-1 and retained tissue viability and architecture. Our in vitro and ex vivo results show successful formulation of unique RMs. Moreover, the results of flex sig and surgically resected tissues were comparable suggesting the incorporation of both in pre-clinical testing algorithms. PMID:25025306

Development of HIV-1 rectal-specific microbicides and colonic tissue evaluation.

PubMed

Dezzutti, Charlene S; Russo, Julie; Wang, Lin; Abebe, Kaleab Z; Li, Jie; Friend, David R; McGowan, Ian M; Rohan, Lisa C

2014-01-01

The gastrointestinal tract is structurally and functionally different from the vagina. Thus, the paradigm of topical microbicide development and evaluation has evolved to include rectal microbicides (RMs). Our interest was to create unique RM formulations to safely and effectively deliver antiretroviral drugs to mucosal tissue. RMs were designed to include those that spread and coat all surfaces of the rectum and distal colon rapidly (liquid) and those that create a deformable, erodible barrier and remain localized at the administration site (gel). Tenofovir (TFV) (1%) was formulated as an aqueous thermoreversible fluid and a carbopol-based aqueous hydrogel. Lipid-based liquid and gel formulations were prepared for UC781 (0.1%) using isopropyl myristate and GTCC (Caprylic/Capric Triglycerides), respectively. Formulations were characterized for pH, viscosity, osmolality, and drug content. Pre-clinical testing incorporated ex vivo colonic tissue obtained through surgical resections and flexible sigmoidoscopy (flex sig). As this was the first time using tissue from both sources side-by-side, the ability to replicate HIV-1 was compared. Efficacy of the RM formulations was tested by applying the products with HIV-1 directly to polarized colonic tissue and following viral replication. Safety of the formulations was determined by MTT assay and histology. All products had a neutral pH and were isoosmolar. While HIV-1BaL and HIV-1JR-CSF alone and in the presence of semen had similar replication trends between surgically resected and flex sig tissues, the magnitude of viral replication was significantly better in flex sig tissues. Both TFV and UC781 formulations protected the colonic tissue, regardless of tissue source, from HIV-1 and retained tissue viability and architecture. Our in vitro and ex vivo results show successful formulation of unique RMs. Moreover, the results of flex sig and surgically resected tissues were comparable suggesting the incorporation of both in pre-clinical testing algorithms.

A minimal model of epithelial tissue dynamics and its application to the corneal epithelium

NASA Astrophysics Data System (ADS)

Henkes, Silke; Matoz-Fernandez, Daniel; Kostanjevec, Kaja; Coburn, Luke; Sknepnek, Rastko; Collinson, J. Martin; Martens, Kirsten

Epithelial cell sheets are characterized by a complex interplay of active drivers, including cell motility, cell division and extrusion. Here we construct a particle-based minimal model tissue with only division/death dynamics and show that it always corresponds to a liquid state with a single dynamic time scale set by the division rate, and that no glassy phase is possible. Building on this, we construct an in-silico model of the mammalian corneal epithelium as such a tissue confined to a hemisphere bordered by the limbal stem cell zone. With added cell motility dynamics we are able to explain the steady-state spiral migration on the cornea, including the central vortex defect, and quantitatively compare it to eyes obtained from mice that are X-inactivation mosaic for LacZ.

Adipose Tissue Plasticity During Catch-Up Fat Driven by Thrifty Metabolism

PubMed Central

Summermatter, Serge; Marcelino, Helena; Arsenijevic, Denis; Buchala, Antony; Aprikian, Olivier; Assimacopoulos-Jeannet, Françoise; Seydoux, Josiane; Montani, Jean-Pierre; Solinas, Giovanni; Dulloo, Abdul G.

2009-01-01

OBJECTIVE Catch-up growth, a risk factor for later type 2 diabetes, is characterized by hyperinsulinemia, accelerated body-fat recovery (catch-up fat), and enhanced glucose utilization in adipose tissue. Our objective was to characterize the determinants of enhanced glucose utilization in adipose tissue during catch-up fat. RESEARCH DESIGN AND METHODS White adipose tissue morphometry, lipogenic capacity, fatty acid composition, insulin signaling, in vivo glucose homeostasis, and insulinemic response to glucose were assessed in a rat model of semistarvation-refeeding. This model is characterized by glucose redistribution from skeletal muscle to adipose tissue during catch-up fat that results solely from suppressed thermogenesis (i.e., without hyperphagia). RESULTS Adipose tissue recovery during the dynamic phase of catch-up fat is accompanied by increased adipocyte number with smaller diameter, increased expression of genes for adipogenesis and de novo lipogenesis, increased fatty acid synthase activity, increased proportion of saturated fatty acids in triglyceride (storage) fraction but not in phospholipid (membrane) fraction, and no impairment in insulin signaling. Furthermore, it is shown that hyperinsulinemia and enhanced adipose tissue de novo lipogenesis occur concomitantly and are very early events in catch-up fat. CONCLUSIONS These findings suggest that increased adipose tissue insulin stimulation and consequential increase in intracellular glucose flux play an important role in initiating catch-up fat. Once activated, the machinery for lipogenesis and adipogenesis contribute to sustain an increased insulin-stimulated glucose flux toward fat storage. Such adipose tissue plasticity could play an active role in the thrifty metabolism that underlies glucose redistribution from skeletal muscle to adipose tissue. PMID:19602538

Method for accurate registration of tissue autofluorescence imaging data with corresponding histology: a means for enhanced tumor margin assessment

NASA Astrophysics Data System (ADS)

Unger, Jakob; Sun, Tianchen; Chen, Yi-Ling; Phipps, Jennifer E.; Bold, Richard J.; Darrow, Morgan A.; Ma, Kwan-Liu; Marcu, Laura

2018-01-01

An important step in establishing the diagnostic potential for emerging optical imaging techniques is accurate registration between imaging data and the corresponding tissue histopathology typically used as gold standard in clinical diagnostics. We present a method to precisely register data acquired with a point-scanning spectroscopic imaging technique from fresh surgical tissue specimen blocks with corresponding histological sections. Using a visible aiming beam to augment point-scanning multispectral time-resolved fluorescence spectroscopy on video images, we evaluate two different markers for the registration with histology: fiducial markers using a 405-nm CW laser and the tissue block's outer shape characteristics. We compare the registration performance with benchmark methods using either the fiducial markers or the outer shape characteristics alone to a hybrid method using both feature types. The hybrid method was found to perform best reaching an average error of 0.78±0.67 mm. This method provides a profound framework to validate diagnostical abilities of optical fiber-based techniques and furthermore enables the application of supervised machine learning techniques to automate tissue characterization.

Actomyosin-based tissue folding requires a multicellular myosin gradient

PubMed Central

Miller, Pearson W.; Chanet, Soline; Stoop, Norbert; Dunkel, Jörn

2017-01-01

Tissue folding promotes three-dimensional (3D) form during development. In many cases, folding is associated with myosin accumulation at the apical surface of epithelial cells, as seen in the vertebrate neural tube and the Drosophila ventral furrow. This type of folding is characterized by constriction of apical cell surfaces, and the resulting cell shape change is thought to cause tissue folding. Here, we use quantitative microscopy to measure the pattern of transcription, signaling, myosin activation and cell shape in the Drosophila mesoderm. We found that cells within the ventral domain accumulate different amounts of active apical non-muscle myosin 2 depending on the distance from the ventral midline. This gradient in active myosin depends on a newly quantified gradient in upstream signaling proteins. A 3D continuum model of the embryo with induced contractility demonstrates that contractility gradients, but not contractility per se, promote changes to surface curvature and folding. As predicted by the model, experimental broadening of the myosin domain in vivo disrupts tissue curvature where myosin is uniform. Our data argue that apical contractility gradients are important for tissue folding. PMID:28432215

Current State-of-the-Art 3D Tissue Models and Their Compatibility with Live Cell Imaging.

PubMed

Bardsley, Katie; Deegan, Anthony J; El Haj, Alicia; Yang, Ying

2017-01-01

Mammalian cells grow within a complex three-dimensional (3D) microenvironment where multiple cells are organized and surrounded by extracellular matrix (ECM). The quantity and types of ECM components, alongside cell-to-cell and cell-to-matrix interactions dictate cellular differentiation, proliferation and function in vivo. To mimic natural cellular activities, various 3D tissue culture models have been established to replace conventional two dimensional (2D) culture environments. Allowing for both characterization and visualization of cellular activities within possibly bulky 3D tissue models presents considerable challenges due to the increased thickness and subsequent light scattering features of such 3D models. In this chapter, state-of-the-art methodologies used to establish 3D tissue models are discussed, first with a focus on both scaffold-free and scaffold-based 3D tissue model formation. Following on, multiple 3D live cell imaging systems, mainly optical imaging modalities, are introduced. Their advantages and disadvantages are discussed, with the aim of stimulating more research in this highly demanding research area.

Wavelet data processing of micro-Raman spectra of biological samples

NASA Astrophysics Data System (ADS)

Camerlingo, C.; Zenone, F.; Gaeta, G. M.; Riccio, R.; Lepore, M.

2006-02-01

A wavelet multi-component decomposition algorithm is proposed for processing data from micro-Raman spectroscopy (μ-RS) of biological tissue. The μ-RS has been recently recognized as a promising tool for the biopsy test and in vivo diagnosis of degenerative human tissue pathologies, due to the high chemical and structural information contents of this spectroscopic technique. However, measurements of biological tissues are usually hampered by typically low-level signals and by the presence of noise and background components caused by light diffusion or fluorescence processes. In order to overcome these problems, a numerical method based on discrete wavelet transform is used for the analysis of data from μ-RS measurements performed in vitro on animal (pig and chicken) tissue samples and, in a preliminary form, on human skin and oral tissue biopsy from normal subjects. Visible light μ-RS was performed using a He-Ne laser and a monochromator with a liquid nitrogen cooled charge coupled device equipped with a grating of 1800 grooves mm-1. The validity of the proposed data procedure has been tested on the well-characterized Raman spectra of reference acetylsalicylic acid samples.

Monitoring Cartilage Tissue Engineering Using Magnetic Resonance Spectroscopy, Imaging, and Elastography

PubMed Central

Klatt, Dieter; Magin, Richard L.

2013-01-01

A key technical challenge in cartilage tissue engineering is the development of a noninvasive method for monitoring the composition, structure, and function of the tissue at different growth stages. Due to its noninvasive, three-dimensional imaging capabilities and the breadth of available contrast mechanisms, magnetic resonance imaging (MRI) techniques can be expected to play a leading role in assessing engineered cartilage. In this review, we describe the new MR-based tools (spectroscopy, imaging, and elastography) that can provide quantitative biomarkers for cartilage tissue development both in vitro and in vivo. Magnetic resonance spectroscopy can identify the changing molecular structure and alternations in the conformation of major macromolecules (collagen and proteoglycans) using parameters such as chemical shift, relaxation rates, and magnetic spin couplings. MRI provides high-resolution images whose contrast reflects developing tissue microstructure and porosity through changes in local relaxation times and the apparent diffusion coefficient. Magnetic resonance elastography uses low-frequency mechanical vibrations in conjunction with MRI to measure soft tissue mechanical properties (shear modulus and viscosity). When combined, these three techniques provide a noninvasive, multiscale window for characterizing cartilage tissue growth at all stages of tissue development, from the initial cell seeding of scaffolds to the development of the extracellular matrix during construct incubation, and finally, to the postimplantation assessment of tissue integration in animals and patients. PMID:23574498

Attenuation measuring ultrasound shearwave elastography and in vivo application in post-transplant liver patients

NASA Astrophysics Data System (ADS)

Nenadic, Ivan Z.; Qiang, Bo; Urban, Matthew W.; Zhao, Heng; Sanchez, William; Greenleaf, James F.; Chen, Shigao

2017-01-01

Ultrasound and magnetic resonance elastography techniques are used to assess mechanical properties of soft tissues. Tissue stiffness is related to various pathologies such as fibrosis, loss of compliance, and cancer. One way to perform elastography is measuring shear wave velocity of propagating waves in tissue induced by intrinsic motion or an external source of vibration, and relating the shear wave velocity to tissue elasticity. All tissues are inherently viscoelastic and ignoring viscosity biases the velocity-based estimates of elasticity and ignores a potentially important parameter of tissue health. We present attenuation measuring ultrasound shearwave elastography (AMUSE), a technique that independently measures both shear wave velocity and attenuation in tissue and therefore allows characterization of viscoelasticity without using a rheological model. The theoretical basis for AMUSE is first derived and validated in finite element simulations. AMUSE is validated against the traditional methods for assessing shear wave velocity (phase gradient) and attenuation (amplitude decay) in tissue mimicking phantoms and excised tissue. The results agreed within one standard deviation. AMUSE was used to measure shear wave velocity and attenuation in 15 transplanted livers in patients with potential acute rejection, and the results were compared with the biopsy findings in a preliminary study. The comparison showed excellent agreement and suggests that AMUSE can be used to separate transplanted livers with acute rejection from livers with no rejection.

Comparative study of Hsp27, GSK3β, Wnt1 and PRDX3 in Hirschsprung's disease.

PubMed

Gao, Hong; Liu, Xiaomei; Chen, Dong; Lv, Liangying; Wu, Mei; Mi, Jie; Wang, Weilin

2014-06-01

Hirschsprung's disease (HSCR) is a developmental disorder of the enteric nervous system characterized by aganglionosis in distal gut. In this study, we used two-dimensional gel electrophoresis (2-DE) technology coupled with matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis to identify differentially expressed proteins in the aganglionic (stenotic) and ganglionic (normal) colon segment tissues from patients with HSCR. We identified 15 proteins with different expression levels between the stenotic and the normal colon segment tissues from patients with HSCR. Nine proteins were upregulated and six proteins downregulated in the stenotic colon segment tissues compared to the normal colon segment tissues. Based on the biological functions, we selected the Hsp27 upregulated proteins and the PRDX3 downregulated proteins to confirm their expression in 20 patients. The protein and mRNA expressions of Hsp27 were statistically higher in the stenotic colon segment tissues than in the normal colon segment tissues, whereas the protein and mRNA expressions of PRDX3 were statistically lower in the stenotic colon segment tissues than in the normal colon segment tissues. These findings of changes in mRNA and protein in tissues from patients with HSCR provide information which may be helpful in understanding the pathomechanism that is implicated in the disease. © 2014 The Authors. International Journal of Experimental Pathology © 2014 International Journal of Experimental Pathology.

An optical coherence tomography (OCT)-based air jet indentation system for measuring the mechanical properties of soft tissues

PubMed Central

Huang, Yan-Ping; Zheng, Yong-Ping; Wang, Shu-Zhe; Chen, Zhong-Ping; Huang, Qing-Hua; He, Yong-Hong

2010-01-01

A novel noncontact indentation system with the combination of an air jet and optical coherence tomography (OCT) was presented in this paper for the quantitative measurement of the mechanical properties of soft tissues. The key idea of this method is to use a pressure-controlled air jet as an indenter to compress the soft tissue in a noncontact way and utilize the OCT signals to extract the deformation induced. This indentation system provides measurement and mapping of tissue elasticity for small specimens with high scanning speed. Experiments were performed on 27 silicone tissue-mimicking phantoms with different Young’s moduli, which were also measured by uniaxial compression tests. The regression coefficient of the indentation force to the indentation depth (N mm−1) was used as an indicator of the stiffness of tissue under air jet indentation. Results showed that the stiffness coefficients measured by the current system correlated well with the corresponding Young’s moduli obtained by conventional mechanical testing (r = 0.89, p < 0.001). Preliminary in vivo tests also showed that the change of soft tissue stiffness with and without the contraction of the underlying muscles in the hand could be differentiated by the current measurement. This system may have broad applications in tissue assessment and characterization where alterations of mechanical properties are involved, in particular with the potential of noncontact micro-indentation for tissues. PMID:20463843

Boiling histotripsy lesion characterization on a clinical magnetic resonance imaging-guided high intensity focused ultrasound system

PubMed Central

Eranki, Avinash; Farr, Navid; Partanen, Ari; V. Sharma, Karun; Chen, Hong; Rossi, Christopher T.; Kothapalli, Satya V. V. N.; Oetgen, Matthew; Kim, AeRang; H. Negussie, Ayele; Woods, David; J. Wood, Bradford; C. W. Kim, Peter; S. Yarmolenko, Pavel

2017-01-01

Purpose High intensity focused ultrasound (HIFU) is a non-invasive therapeutic technique that can thermally ablate tumors. Boiling histotripsy (BH) is a HIFU approach that can emulsify tissue in a few milliseconds. Lesion volume and temperature effects for different BH sonication parameters are currently not well characterized. In this work, lesion volume, temperature distribution, and area of lethal thermal dose were characterized for varying BH sonication parameters in tissue-mimicking phantoms (TMP) and demonstrated in ex vivo tissues. Methods The following BH sonication parameters were varied using a clinical MR-HIFU system (Sonalleve V2, Philips, Vantaa, Finland): acoustic power, number of cycles/pulse, total sonication time, and pulse repetition frequency (PRF). A 3×3×3 pattern was sonicated inside TMP’s and ex vivo tissues. Post sonication, lesion volumes were quantified using 3D ultrasonography and temperature and thermal dose distributions were analyzed offline. Ex vivo tissues were sectioned and stained with H&E post sonication to assess tissue damage. Results Significant increase in lesion volume was observed while increasing the number of cycles/pulse and PRF. Other sonication parameters had no significant effect on lesion volume. Temperature full width at half maximum at the end of sonication increased significantly with all parameters except total sonication time. Positive correlation was also found between lethal thermal dose and lesion volume for all parameters except number of cycles/pulse. Gross pathology of ex vivo tissues post sonication displayed either completely or partially damaged tissue at the focal region. Surrounding tissues presented sharp boundaries, with little or no structural damage to adjacent critical structures such as bile duct and nerves. Conclusion Our characterization of effects of HIFU sonication parameters on the resulting lesion demonstrates the ability to control lesion morphologic and thermal characteristics with a clinical MR-HIFU system in TMP’s and ex vivo tissues. We demonstrate that this system can produce spatially precise lesions in both phantoms and ex vivo tissues. The results provide guidance on a preliminary set of BH sonication parameters for this system, with a potential to facilitate BH translation to the clinic. PMID:28301597

* Animal Models for Periodontal Tissue Engineering: A Knowledge-Generating Process.

PubMed

Fawzy El-Sayed, Karim M; Dörfer, Christof E

2017-12-01

The human periodontium is a uniquely complex vital structure, supporting and anchoring the teeth in their alveolar sockets, thereby playing a decisive role in tooth homeostasis and function. Chronic periodontitis is a highly prevalent immune-inflammatory disease of the periodontium, affecting 15% of adult individuals, and is characterized by progressive destruction of the periodontal tooth-investing tissues, culminating in their irreversible damage. Current periodontal evidence-based treatment strategies achieve periodontal healing via repair processes, mostly combating the inflammatory component of the disease, to halt or reduce prospective periodontal tissue loss. However, complete periodontal tissue regeneration remains a hard fought-for goal in the field of periodontology and multiple in vitro and in vivo studies have been conducted, in the conquest to achieve a functional periodontal tissue regeneration in humans. The present review evaluates the current status of periodontal regeneration attempted through tissue-engineering concepts, ideal requirements for experimental animal models under investigation, the methods of induction and classification of the experimentally created periodontal defects, types of experimental defects employed in the diverse animal studies, as well as the current state of knowledge obtained from in vivo animal experiments, with special emphasis on large animal models.

Predictive analysis of photodynamic therapy applied to esophagus cancer

NASA Astrophysics Data System (ADS)

Fanjul-Vélez, F.; del Campo-Gutiérrez, M.; Ortega-Quijano, N.; Arce-Diego, J. L.

2008-04-01

The use of optical techniques in medicine has revolutionized in many cases the medical praxis, providing new tools for practitioners or improving the existing ones in the fight against diseases. The application of this technology comprises mainly two branches, characterization and treatment of biological tissues. Photodynamic Therapy (PDT) provides a solution for malignant tissue destruction, by means of the inoculation of a photosensitizer and irradiation by an optical source. The key factor of the procedure is the localization of the damage to avoid collateral harmful effects. The volume of tissue destroyed depends on the type of photosensitizer inoculated, both on its reactive characteristics and its distribution inside the tissue, and also on the specific properties of the optical source, that is, the optical power, wavelength and exposition time. In this work, a model for PDT based on the one-dimensional diffusion equation, extensible to 3D, to estimate the optical distribution in tissue, and on photosensitizer parameters to take into account the photobleaching effect is proposed. The application to esophagus cancer allows the selection of the right optical source parameters, like irradiance, wavelength or exposition time, in order to predict the area of tissue destruction.

Biocompatibility of hydroxyapatite scaffolds processed by lithography-based additive manufacturing.

PubMed

Tesavibul, Passakorn; Chantaweroad, Surapol; Laohaprapanon, Apinya; Channasanon, Somruethai; Uppanan, Paweena; Tanodekaew, Siriporn; Chalermkarnnon, Prasert; Sitthiseripratip, Kriskrai

2015-01-01

The fabrication of hydroxyapatite scaffolds for bone tissue engineering applications by using lithography-based additive manufacturing techniques has been introduced due to the abilities to control porous structures with suitable resolutions. In this research, the use of hydroxyapatite cellular structures, which are processed by lithography-based additive manufacturing machine, as a bone tissue engineering scaffold was investigated. The utilization of digital light processing system for additive manufacturing machine in laboratory scale was performed in order to fabricate the hydroxyapatite scaffold, of which biocompatibilities were eventually evaluated by direct contact and cell-culturing tests. In addition, the density and compressive strength of the scaffolds were also characterized. The results show that the hydroxyapatite scaffold at 77% of porosity with 91% of theoretical density and 0.36 MPa of the compressive strength are able to be processed. In comparison with a conventionally sintered hydroxyapatite, the scaffold did not present any cytotoxic signs while the viability of cells at 95.1% was reported. After 14 days of cell-culturing tests, the scaffold was able to be attached by pre-osteoblasts (MC3T3-E1) leading to cell proliferation and differentiation. The hydroxyapatite scaffold for bone tissue engineering was able to be processed by the lithography-based additive manufacturing machine while the biocompatibilities were also confirmed.

Polymeric membranes for guided bone regeneration.

PubMed

Gentile, Piergiorgio; Chiono, Valeria; Tonda-Turo, Chiara; Ferreira, Ana M; Ciardelli, Gianluca

2011-10-01

In this review, different barrier membranes for guided bone regeneration (GBR) are described as a useful surgical technique to enhance bone regeneration in damaged alveolar sites before performing implants and fitting other dental appliances. The GBR procedure encourages bone regeneration through cellular exclusion and avoids the invasion of epithelial and connective tissues that grow at the defective site instead of bone tissue. The barrier membrane should satisfy various properties, such as biocompatibility, non-immunogenicity, non-toxicity, and a degradation rate that is long enough to permit mechanical support during bone formation. Other characteristics such as tissue integration, nutrient transfer, space maintenance and manageability are also of interest. In this review, various non-resorbable and resorbable commercially available membranes are described, based on expanded polytetrafluoroethylene, poly(lactic acid), poly(glycolic acid) and their copolymers. The polyester-based membranes are biodegradable, permit a single-stage procedure, and have higher manageability than non-resorbable membranes; however, they have shown poor biocompatibility. In contrast, membranes based on natural materials, such as collagen, are biocompatible but are characterized by poor mechanical properties and stability due to their early degradation. Moreover, new approaches are described, such as the use of multi-layered, graft-copolymer-based and composite membranes containing osteoconductive ceramic fillers as alternatives to conventional membranes. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multipulse technique exploiting the intermodulation of ultrasound waves in a nonlinear medium.

PubMed

Biagi, Elena; Breschi, Luca; Vannacci, Enrico; Masotti, Leonardo

2009-03-01

In recent years, the nonlinear properties of materials have attracted much interest in nondestructive testing and in ultrasound diagnostic applications. Acoustic nonlinear parameters represent an opportunity to improve the information that can be extracted from a medium such as structural organization and pathologic status of tissue. In this paper, a method called pulse subtraction intermodulation (PSI), based on a multipulse technique, is presented and investigated both theoretically and experimentally. This method allows separation of the intermodulation products, which arise when 2 separate frequencies are transmitted in a nonlinear medium, from fundamental and second harmonic components, making them available for improved imaging techniques or signal processing algorithms devoted to tissue characterization. The theory of intermodulation product generation was developed according the Khokhlov-Zabolotskaya-Kuznetsov (KZK) nonlinear propagation equation, which is consistent with experimental results. The description of the proposed method, characterization of the intermodulation spectral contents, and quantitative results coming from in vitro experimentation are reported and discussed in this paper.

Non-invasive characterization of structure and morphology of silk fibroin biomaterials using non-linear microscopy

PubMed Central

Rice, William L.; Firdous, Shamaraz; Gupta, Sharad; Hunter, Martin; Foo, Cheryl Wong Po; Wang, Yongzhong; Kim, Hyeon Joo; Kaplan, David L.; Georgakoudi, Irene

2009-01-01

Designing biomaterial scaffolds remains a major challenge in tissue engineering. Key to this challenge is improved understanding of the relationships between the scaffold properties and its degradation kinetics, as well as the cell interactions and the promotion of new matrix deposition. Here we present the use of non-linear spectroscopic imaging as a non-invasive method to characterize not only morphological, but also structural aspects of silkworm silk fibroin-based biomaterials, relying entirely on endogenous optical contrast. We demonstrate that two photon excited fluorescence and second harmonic generation are sensitive to the hydration, overall β sheet content and molecular orientation of the sample. Thus, the functional content and high resolution afforded by these non-invasive approaches offer promise for identifying important connections between biomaterial design and functional engineered tissue development. The strategies described also have broader implications for understanding and tracking the remodeling of degradable biomaterials under dynamic conditions both in vitro and in vivo. PMID:18291520

Maltose conjugation to PCL: Advanced structural characterization and preliminary biological properties

NASA Astrophysics Data System (ADS)

Secchi, Valeria; Guizzardi, Roberto; Russo, Laura; Pastori, Valentina; Lecchi, Marzia; Franchi, Stefano; Iucci, Giovanna; Battocchio, Chiara; Cipolla, Laura

2018-05-01

The emerging trends in regenerative medicine rely among others on biomaterial-based therapies, with the use of biomaterials as a central delivery system for biochemical and physical cues to manipulate transplanted or ingrowth cells and to orchestrate tissue regeneration. Cell adhesion properties of a biomaterial strongly depend on its surface characteristics. Among others poly(ε-caprolactone) (PCL) is a biocompatible and biodegradable material with low cytotoxicity that is widely adopted as synthetic polymer in several applications. However, it is hydrophobic, which limits its use in tissue engineering. In order to improve its hydrophilicity and cellular compatibility, PCL surface was grafted with maltose through a two-step procedure in which controlled aminolysis of PCL ester bonds by hexanediamine was followed by reductive amination with the carbohydrate reducing end. The modified PCL surface was then characterized in detail by x-ray Photoelectron Spectroscopy (XPS) and Near Edge x-ray Absorption Fine Structure (NEXAFS) spectroscopies. In addition, the biocompatibility of the proposed biomaterial was investigated in preliminary biological assays.

Mass-spectrometric analysis of hydroperoxy- and hydroxy-derivatives of cardiolipin and phosphatidylserine in cells and tissues induced by pro-apoptotic and pro-inflammatory stimuli

PubMed Central

Tyurin, Vladimir A.; Tyurina, Yulia Y.; Jung, Mi-Yeon; Tungekar, Muhammad A.; Wasserloos, Karla J.; Bayir, Hülya; Greenberger, Joel S.; Kochanek, Patrick M.; Shvedova, Anna A.; Pitt, Bruce; Kagan, Valerian E.

2009-01-01

Oxidation of two anionic phospholipids - cardiolipin (CL) in mitochondria and phosphatidylserine (PS) in extramitochondrial compartments - are important signaling events, particularly during the execution of programmed cell death and clearance of apoptotic cells. Quantitative analysis of CL and PS oxidation products is central to understanding their molecular mechanisms of action. We combined the identification of diverse phospholipid molecular species by ESI-MS with quantitative assessments of lipid hydroperoxides using a fluorescence HPLC-based protocol. We characterized CL and PS oxidation products formed in a model system (cyt c/H2O2), in apoptotic cells (neurons, pulmonary artery endothelial cells) and mouse lung under inflammatory/oxidative stress conditions (hyperoxia, inhalation of single walled carbon nanotubes). Our results demonstrate the usefulness of this approach for quantitative assessments, identification of individual molecular species and structural characterization of anionic phospholipids that are involved in oxidative modification in cells and tissues. PMID:19328050

Mechanical Properties of Single Collagen Fibrils Revealed by Force Spectroscopy

NASA Astrophysics Data System (ADS)

Graham, John; Phillips, Charlotte; Grandbois, Michel

2004-03-01

In the field of biomechanics, collagen fibrils are believed to be robust mechanical structures characterized by a low extensibility. Until very recently, information on the mechanical properties of collagen fibrils could only be derived from ensemble measurements performed on complete tissues such as bone, skin and tendon. Here we measure force-elongation/relaxation profiles of single collagen fibrils using atomic force microscopy-based force spectroscopy. The elongation profiles indicate that in vitro assembled heterotrimeric type I collagen fibrils are characterized by a large extensibility. Numerous discontinuities and a plateau in the force profile indicate major reorganization occurs within the fibrils in the 1.5 -- 4.5 nN range. Our study demonstrates that newly assembled collagen fibrils are robust structures with a significant reserve of elasticity that could play a determinant role in cellular motion in the context of tissue growth and morphogenesis. In contrast, homotrimeric collagen fibrils corresponding to osteogenesis imperfecta pathology exhibit a marked difference in their elasticity profile.

Design and characterization of a composite material based on Sr(II)-loaded clay nanotubes included within a biopolymer matrix.

PubMed

Del Buffa, Stefano; Bonini, Massimo; Ridi, Francesca; Severi, Mirko; Losi, Paola; Volpi, Silvia; Al Kayal, Tamer; Soldani, Giorgio; Baglioni, Piero

2015-06-15

This paper reports on the preparation, characterization, and cytotoxicity of a hybrid nanocomposite material made of Sr(II)-loaded Halloysite nanotubes included within a biopolymer (3-polyhydroxybutyrate-co-3-hydroxyvalerate) matrix. The Sr(II)-loaded inorganic scaffold is intended to provide mechanical resistance, multi-scale porosity, and to favor the in-situ regeneration of bone tissue thanks to its biocompatibility and bioactivity. The interaction of the hybrid system with the physiological environment is mediated by the biopolymer coating, which acts as a binder, as well as a diffusional barrier to the Sr(II) release. The degradation of the polymer progressively leads to the exposure of the Sr(II)-loaded Halloysite scaffold, tuning its interaction with osteogenic cells. The in vitro biocompatibility of the composite was demonstrated by cytotoxicity tests on L929 fibroblast cells. The results indicate that this composite material could be of interest for multiple strategies in the field of bone tissue engineering. Copyright © 2015 Elsevier Inc. All rights reserved.

Heating of tissues by microwaves: a model analysis.

PubMed

Foster, K R; Lozano-Nieto, A; Riu, P J; Ely, T S

1998-01-01

We consider the thermal response times for heating of tissue subject to nonionizing (microwave or infrared) radiation. The analysis is based on a dimensionless form of the bioheat equation. The thermal response is governed by two time constants: one (tau1) pertains to heat convection by blood flow, and is of the order of 20-30 min for physiologically normal perfusion rates; the second (tau2) characterizes heat conduction and varies as the square of a distance that characterizes the spatial extent of the heating. Two idealized cases are examined. The first is a tissue block with an insulated surface, subject to irradiation with an exponentially decreasing specific absorption rate, which models a large surface area of tissue exposed to microwaves. The second is a hemispherical region of tissue exposed at a spatially uniform specific absorption rate, which models localized exposure. In both cases, the steady-state temperature increase can be written as the product of the incident power density and an effective time constant tau(eff), which is defined for each geometry as an appropriate function of tau1 and tau2. In appropriate limits of the ratio of these time constants, the local temperature rise is dominated by conductive or convective heat transport. Predictions of the block model agree well with recent data for the thresholds for perception of warmth or pain from exposure to microwave energy. Using these concepts, we developed a thermal averaging time that might be used in standards for human exposure to microwave radiation, to limit the temperature rise in tissue from radiation by pulsed sources. We compare the ANSI exposure standards for microwaves and infrared laser radiation with respect to the maximal increase in tissue temperature that would be allowed at the maximal permissible exposures. A historical appendix presents the origin of the 6-min averaging time used in the microwave standard.

The connective tissue phenotype of glaucomatous cupping in the monkey eye - Clinical and research implications.

PubMed

Yang, Hongli; Reynaud, Juan; Lockwood, Howard; Williams, Galen; Hardin, Christy; Reyes, Luke; Stowell, Cheri; Gardiner, Stuart K; Burgoyne, Claude F

2017-07-01

In a series of previous publications we have proposed a framework for conceptualizing the optic nerve head (ONH) as a biomechanical structure. That framework proposes important roles for intraocular pressure (IOP), IOP-related stress and strain, cerebrospinal fluid pressure (CSFp), systemic and ocular determinants of blood flow, inflammation, auto-immunity, genetics, and other non-IOP related risk factors in the physiology of ONH aging and the pathophysiology of glaucomatous damage to the ONH. The present report summarizes 20 years of technique development and study results pertinent to the characterization of ONH connective tissue deformation and remodeling in the unilateral monkey experimental glaucoma (EG) model. In it we propose that the defining pathophysiology of a glaucomatous optic neuropathy involves deformation, remodeling, and mechanical failure of the ONH connective tissues. We view this as an active process, driven by astrocyte, microglial, fibroblast and oligodendrocyte mechanobiology. These cells, and the connective tissue phenomena they propagate, have primary and secondary effects on retinal ganglion cell (RGC) axon, laminar beam and retrolaminar capillary homeostasis that may initially be "protective" but eventually lead to RGC axonal injury, repair and/or cell death. The primary goal of this report is to summarize our 3D histomorphometric and optical coherence tomography (OCT)-based evidence for the early onset and progression of ONH connective tissue deformation and remodeling in monkey EG. A second goal is to explain the importance of including ONH connective tissue processes in characterizing the phenotype of a glaucomatous optic neuropathy in all species. A third goal is to summarize our current efforts to move from ONH morphology to the cell biology of connective tissue remodeling and axonal insult early in the disease. A final goal is to facilitate the translation of our findings and ideas into neuroprotective interventions that target these ONH phenomena for therapeutic effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

Generation of Functional Thyroid Tissue Using 3D-Based Culture of Embryonic Stem Cells.

PubMed

Antonica, Francesco; Kasprzyk, Dominika Figini; Schiavo, Andrea Alex; Romitti, Mírian; Costagliola, Sabine

2017-01-01

During the last decade three-dimensional (3D) cultures of pluripotent stem cells have been intensively used to understand morphogenesis and molecular signaling important for the embryonic development of many tissues. In addition, pluripotent stem cells have been shown to be a valid tool for the in vitro modeling of several congenital or chronic human diseases, opening new possibilities to study their physiopathology without using animal models. Even more interestingly, 3D culture has proved to be a powerful and versatile tool to successfully generate functional tissues ex vivo. Using similar approaches, we here describe a protocol for the generation of functional thyroid tissue using mouse embryonic stem cells and give all the details and references for its characterization and analysis both in vitro and in vivo. This model is a valid approach to study the expression and the function of genes involved in the correct morphogenesis of thyroid gland, to elucidate the mechanisms of production and secretion of thyroid hormones and to test anti-thyroid drugs.

Further insights into the characterization of equine adipose tissue-derived mesenchymal stem cells.

PubMed

Raabe, Oksana; Shell, Katja; Würtz, Antonia; Reich, Christine Maria; Wenisch, Sabine; Arnhold, Stefan

2011-08-01

Adipose tissue-derived stem cells (ADSCs) represent a promising subpopulation of adult stem cells for tissue engineering applications in veterinary medicine. In this study we focused on the morphological and molecular biological properties of the ADSCs. The expression of stem cell markers Oct4, Nanog and the surface markers CD90 and CD105 were detected using RT-PCR. ADSCs showed a proliferative potential and were capable of adipogenic and osteogenic differentiation. Expression of Alkaline phosphatase (AP), phosphoprotein (SPP1), Runx2 and osteocalcin (OC) mRNA were positive in osteogenic lineages and peroxisome proliferator activated receptor (Pparγ2) mRNA was positive in adipogenic lineages. ADSCs show stem cell and surface marker profiles and differentiation characteristics that are similar to but distinct from other adult stem cells, such as bone marrow-derived mesenchymal stem cells (BM-MSCs). The availability of an easily accessible and reproducible cell source may greatly facilitate the development of stem cell based tissue engineering and therapies for regenerative equine medicine.

Nanocellulose reinforced gellan-gum hydrogels as potential biological substitutes for annulus fibrosus tissue regeneration.

PubMed

Pereira, Diana R; Silva-Correia, Joana; Oliveira, Joaquim M; Reis, Rui L; Pandit, Abhay; Biggs, Manus J

2018-04-01

Intervertebral disc (IVD) degeneration is associated with both structural damage and aging related degeneration. Annulus fibrosus (AF) defects such as annular tears, herniation and discectomy require novel tissue engineering strategies to functionally repair AF tissue. An ideal construct will repair the AF by providing physical and biological support, facilitating regeneration. The presented strategy herein proposes a gellan gum-based construct reinforced with cellulose nanocrystals (nCell) as a biological self-gelling AF substitute. Nanocomposite hydrogels were fabricated and characterized with respect to hydrogel swelling capacity, degradation rate in vitro and mechanical properties. Rheological evaluation on the nanocomposites demonstrated the GGMA reinforcement with nCell promoted matrix entanglement with higher scaffold stiffness observed upon ionic crosslinking. Compressive mechanical tests demonstrated compressive modulus values close to those of the human AF tissue. Furthermore, cell culture studies with encapsulated bovine AF cells indicated that nanocomposite constructs promoted cell viability and a physiologically relevant cell morphology for up to fourteen days in vitro. Copyright © 2017 Elsevier Inc. All rights reserved.

Osteoconductive composite graft based on bacterial synthesized hydroxyapatite nanoparticles doped with different ions: From synthesis to in vivo studies.

PubMed

Ahmadzadeh, Elham; Talebnia, Farid; Tabatabaei, Meisam; Ahmadzadeh, Hossein; Mostaghaci, Babak

2016-07-01

To repair damaged bone tissues, osteoconductive bone graft substitutes are required for enhancement of the regenerative potential of osteoblast cells. Nanostructured hydroxyapatite is a bioactive ceramic used for bone tissue engineering purposes. In this study, carbonate hydroxyapatite (cHA) and zinc-magnesium substituted hydroxyapatite (Zn-Mg-HA) nanoparticles were synthesized via biomineralization method using Enterobacter aerogenes. The structural phase composition and the morphology of the samples were analyzed using appropriate powder characterization methods. Next, a composite graft was fabricated by using polyvinyl alcohol and both cHA and Zn-Mg-HA samples. In vivo osteogenic potential of the graft was then investigated in a rabbit tibial osteotomy model. Histological, radiological and morphological studies showed that the graft was mineralized by the newly formed bone tissue without signs of inflammation or infection after 4 weeks of implantation. These histomorphometric results suggest that the fabricated graft can function as a potent osteoconductive bone tissue substitute. Copyright © 2016 Elsevier Inc. All rights reserved.

Myositis Ossificans.

PubMed

Walczak, Brian E; Johnson, Christopher N; Howe, B Matthew

2015-10-01

Myositis ossificans is a self-limiting, benign ossifying lesion that can affect any type of soft tissue, including subcutaneous fat, tendons, and nerves. It is most commonly found in muscle as a solitary lesion. Ossifying soft-tissue lesions historically have been inconsistently classified. Fundamentally, myositis ossificans can be categorized into nonhereditary and hereditary types, with the latter being a distinct entity with a separate pathophysiology and treatment approach. The etiology of myositis ossificans is variable; however, clinical presentation generally is characterized by an ossifying soft-tissue mass. Advanced cross-sectional imaging alone can be nonspecific and may appear to be similar to more sinister etiologies. Therefore, the evaluation of a suspicious soft-tissue mass often necessitates multiple imaging modalities for accurate diagnosis. When imaging is indeterminate, biopsy may be required for a histologic diagnosis. However, histopathology varies based on stage of evolution. The treatment of myositis ossificans is complex and is often made in a multidisciplinary fashion because accurate diagnosis is fundamental to a successful outcome. Copyright 2015 by the American Academy of Orthopaedic Surgeons.

Importance of Multimodal MRI in Characterizing Brain Tissue and Its Potential Application for Individual Age Prediction.

PubMed

Cherubini, Andrea; Caligiuri, Maria Eugenia; Peran, Patrice; Sabatini, Umberto; Cosentino, Carlo; Amato, Francesco

2016-09-01

This study presents a voxel-based multiple regression analysis of different magnetic resonance image modalities, including anatomical T1-weighted, T2(*) relaxometry, and diffusion tensor imaging. Quantitative parameters sensitive to complementary brain tissue alterations, including morphometric atrophy, mineralization, microstructural damage, and anisotropy loss, were compared in a linear physiological aging model in 140 healthy subjects (range 20-74 years). The performance of different predictors and the identification of the best biomarker of age-induced structural variation were compared without a priori anatomical knowledge. The best quantitative predictors in several brain regions were iron deposition and microstructural damage, rather than macroscopic tissue atrophy. Age variations were best resolved with a combination of markers, suggesting that multiple predictors better capture age-induced tissue alterations. The results of the linear model were used to predict apparent age in different regions of individual brain. This approach pointed to a number of novel applications that could potentially help highlighting areas particularly vulnerable to disease.

Evaluation of an optical fiber probe for in vivo measurement of the photoacoustic response of tissues

NASA Astrophysics Data System (ADS)

Beard, Paul C.; Mills, Timothy N.

1995-05-01

A miniature (1 mm diameter) all-optical photoacoustic probe for generating and detecting ultrasonic thermoelastic waves in biological media at the tip of an optical fiber has been developed. The probe provides a compact and convenient means of performing pulsed photoacoustic spectroscopy for the characterization of biological tissue. The device is based upon a transparent Fabry Perot polymer film ultrasound sensor mounted directly over the end of a multimode optical fiber. The optical fiber is used to deliver nanosecond laser pulses to the tissue producing thermoelastic waves which are then detected by the sensor. Detection sensitivities of 53 mv/MPa and a 10 kPa acoustic noise floor have been demonstrated giving excellent signal to noise ratios in a strong liquid absorber. Lower, but clearly detectable, signals in post mortem human aorta have also been observed. The performance and small physical size of the device suggest that it has the potential to perform remote in situ photoacoustic measurements in tissue.

Protein profiling in potato (Solanum tuberosum L.) leaf tissues by differential centrifugation.

PubMed

Lim, Sanghyun; Chisholm, Kenneth; Coffin, Robert H; Peters, Rick D; Al-Mughrabi, Khalil I; Wang-Pruski, Gefu; Pinto, Devanand M

2012-04-06

Foliar diseases, such as late blight, result in serious threats to potato production. As such, potato leaf tissue becomes an important substrate to study biological processes, such as plant defense responses to infection. Nonetheless, the potato leaf proteome remains poorly characterized. Here, we report protein profiling of potato leaf tissues using a modified differential centrifugation approach to separate the leaf tissues into cell wall and cytoplasmic fractions. This method helps to increase the number of identified proteins, including targeted putative cell wall proteins. The method allowed for the identification of 1484 nonredundant potato leaf proteins, of which 364 and 447 were reproducibly identified proteins in the cell wall and cytoplasmic fractions, respectively. Reproducibly identified proteins corresponded to over 70% of proteins identified in each replicate. A diverse range of proteins was identified based on their theoretical pI values, molecular masses, functional classification, and biological processes. Such a protein extraction method is effective for the establishment of a highly qualified proteome profile.

A Phantom Study of Terahertz Spectroscopy and Imaging of Micro- and Nano-diamonds and Nano-onions as Contrast Agents for Breast Cancer.

PubMed

Bowman, Tyler; Walter, Alec; Shenderova, Olga; Nunn, Nicholas; McGuire, Gary; El-Shenawee, Magda

2017-10-01

THz imaging is effective in distinguishing between cancerous, healthy, and fatty tissues in breast tumors, but a challenge remains in the contrast between cancerous and fibroglandular (healthy) tissues. This work investigates carbon-based nanoparticles as potential contrast agents for terahertz imaging of breast cancer. Microdiamonds, nanodiamonds, and nanometer-scale onion-like carbon are characterized with terahertz transmission spectroscopy in low-absorption backgrounds of polydimethylsiloxane or polyethylene. The refractive index and absorption coefficients are calculated based on the measured electric fields. Nanodiamonds show little effect on the terahertz signal, microdiamonds express resonance-like, size-dependent absorption peaks, and onion-like carbon provides a uniform increase in the optical properties even at low concentration. Due to its strong interaction with terahertz frequencies and ability to be activated for selective binding to cancer cells, onion-like carbon is implemented into engineered three-dimensional breast tumor models composed of phantom tissue mimicking infiltrating ductal carcinoma surrounded by a phantom mimicking healthy fibroglandular tissue. This model is imaged using the terahertz reflection mode to examine the effectiveness of contrast agents for differentiation between the two tissue types. In both spectroscopy and imaging, a 10% concentration of onion-like carbon shows the strongest impact on the terahertz signal and holds promise as a terahertz contrast agent.

Acoustic radiation force impulse (ARFI) imaging: Characterizing the mechanical properties of tissues using their transient response to localized force

NASA Astrophysics Data System (ADS)

Nightingale, Kathryn R.; Palmeri, Mark L.; Congdon, Amy N.; Frinkely, Kristin D.; Trahey, Gregg E.

2004-05-01

Acoustic radiation force impulse (ARFI) imaging utilizes brief, high energy, focused acoustic pulses to generate radiation force in tissue, and conventional diagnostic ultrasound methods to detect the resulting tissue displacements in order to image the relative mechanical properties of tissue. The magnitude and spatial extent of the applied force is dependent upon the transmit beam parameters and the tissue attenuation. Forcing volumes are on the order of 5 mm3, pulse durations are less than 1 ms, and tissue displacements are typically several microns. Images of tissue displacement reflect local tissue stiffness, with softer tissues (e.g., fat) displacing farther than stiffer tissues (e.g., muscle). Parametric images of maximum displacement, time to peak displacement, and recovery time provide information about tissue material properties and structure. In both in vivo and ex vivo data, structures shown in matched B-mode images are in good agreement with those shown in ARFI images, with comparable resolution. Potential clinical applications under investigation include soft tissue lesion characterization, assessment of focal atherosclerosis, and imaging of thermal lesion formation during tissue ablation procedures. Results from ongoing studies will be presented. [Work supported by NIH Grant R01 EB002132-03, and the Whitaker Foundation. System support from Siemens Medical Solutions USA, Inc.

Characterization and Biomimcry of Avian Nanostructured Tissues

DTIC Science & Technology

2016-01-19

keratin cortex (Maia et al. 2011) at the outer edge of barbs from TEM images. Geometric morphometrics of barb shape Digitized images of the barb thin...morphological measurements (all P > 0.05; Figure 4C; Table S2). Gloss and Barb Geometric Morphometrics Matte and glossy barbs differed significantly in...barbs and lack of multiple, clear anatomically homologous features, traditional landmark based morphometric techniques (Bookstein, 1982) would be

Development, characterization, and applications of self-assembling, photocrosslinkable collagen-based hydrogels

NASA Astrophysics Data System (ADS)

Gaudet, Ian Daniel

Development of functional soft-tissue engineered constructs for use in regenerative medicine is currently limited by homogeneity within scaffolds that fails to recapitulate the complex architecture that supports normal function in healthy tissues. Additionally, recent breakthroughs in our understanding the biomechanical cell-matrix interface have provided insight into the role of substrate compliance during development and in the pathophysiological environment. This thesis is the result of investigation into using type-I collagen as a base material for creating dynamic, self-assembling, mechanically and biochemically tunable 3D hydrogel scaffolds into which instructive cellular cues can be imparted anisotropically via the directed application of light. This overarching goal was approached by (1) evaluating extant methods for photonically manipulating type I collagen mechanical properties, which led us to the conclusion that published methods were inadequate for our purposes. Following this realization, we (2) developed a novel process for derivatizing free amines on collagen amino acid residues to reactive methacrylamide moieties, allowing robust spatiotemporal control of mechanical properties through photocrosslinking with long-wave UV light and the water-soluble photoinitiator Irgacure 2959. Thorough characterization of this material, collagen methacrylamide (CMA), provided the basis for multiple applications in the field of soft tissue engineering. Additionally, (3) CMA was used in conjunction with synthetic photopolymers in an effort to create a hybrid natural/synthetic hydrogel material. CMA was also (4) employed as a dynamic hydrogel scaffold which we showed could be used to culture a number of neurogenic stem and progenitor cell types with a focus on using photomodulation to impart instructive heterogeneity to the mechanical and biochemical microenvironment. Finally, (5) we used a computational modeling approach to explain interesting yet poorly understood material phenomena exhibited by CMA observed during characterization. Using sequence and structure based models of an optimized triple helical segment of type-I collagen, we obtained valuable insight into the role of amino acid electrostatic interactions in CMA thermodynamic behavior as well as in the context of understanding the biophysical mechanisms of native type I collagen self-assembly and stability.

Differential Impacts of Land-Based Sources of Pollution on the Microbiota of Southeast Florida Coral Reefs

PubMed Central

Staley, Christopher; Kaiser, Thomas; Gidley, Maribeth L.; Enochs, Ian C.; Jones, Paul R.; Goodwin, Kelly D.; Sinigalliano, Christopher D.

2017-01-01

ABSTRACT Coral reefs are dynamic ecosystems known for decades to be endangered due, in large part, to anthropogenic impacts from land-based sources of pollution (LBSP). In this study, we utilized an Illumina-based next-generation sequencing approach to characterize prokaryotic and fungal communities from samples collected off the southeast coast of Florida. Water samples from coastal inlet discharges, oceanic outfalls of municipal wastewater treatment plants, treated wastewater effluent before discharge, open ocean samples, and coral tissue samples (mucus and polyps) were characterized to determine the relationships between microbial communities in these matrices and those in reef water and coral tissues. Significant differences in microbial communities were noted among all sample types but varied between sampling areas. Contamination from outfalls was found to be the greatest potential source of LBSP influencing native microbial community structure among all reef samples, although pollution from inlets was also noted. Notably, reef water and coral tissue communities were found to be more greatly impacted by LBSP at southern reefs, which also experienced the most degradation during the course of the study. The results of this study provide new insights into how microbial communities from LBSP can impact coral reefs in southeast Florida and suggest that wastewater outfalls may have a greater influence on the microbial diversity and structure of these reef communities than do contaminants carried in runoff, although the influences of runoff and coastal inlet discharge on coral reefs are still substantial. IMPORTANCE Coral reefs are known to be endangered due to sewage discharge and to runoff of nutrients, pesticides, and other substances associated with anthropogenic activity. Here, we used next-generation sequencing to characterize the microbial communities of potential contaminant sources in order to determine how environmental discharges of microbiota and their genetic material may influence the microbiomes of coral reef communities and coastal receiving waters. Runoff delivered through inlet discharges impacted coral microbial communities, but impacts from oceanic outfalls carrying treated wastewater were greater. Geographic differences in the degree of impact suggest that coral microbiomes may be influenced by the microbiological quality of treated wastewater. PMID:28341673

Differential Impacts of Land-Based Sources of Pollution on the Microbiota of Southeast Florida Coral Reefs.

PubMed

Staley, Christopher; Kaiser, Thomas; Gidley, Maribeth L; Enochs, Ian C; Jones, Paul R; Goodwin, Kelly D; Sinigalliano, Christopher D; Sadowsky, Michael J; Chun, Chan Lan

2017-05-15

Coral reefs are dynamic ecosystems known for decades to be endangered due, in large part, to anthropogenic impacts from land-based sources of pollution (LBSP). In this study, we utilized an Illumina-based next-generation sequencing approach to characterize prokaryotic and fungal communities from samples collected off the southeast coast of Florida. Water samples from coastal inlet discharges, oceanic outfalls of municipal wastewater treatment plants, treated wastewater effluent before discharge, open ocean samples, and coral tissue samples (mucus and polyps) were characterized to determine the relationships between microbial communities in these matrices and those in reef water and coral tissues. Significant differences in microbial communities were noted among all sample types but varied between sampling areas. Contamination from outfalls was found to be the greatest potential source of LBSP influencing native microbial community structure among all reef samples, although pollution from inlets was also noted. Notably, reef water and coral tissue communities were found to be more greatly impacted by LBSP at southern reefs, which also experienced the most degradation during the course of the study. The results of this study provide new insights into how microbial communities from LBSP can impact coral reefs in southeast Florida and suggest that wastewater outfalls may have a greater influence on the microbial diversity and structure of these reef communities than do contaminants carried in runoff, although the influences of runoff and coastal inlet discharge on coral reefs are still substantial. IMPORTANCE Coral reefs are known to be endangered due to sewage discharge and to runoff of nutrients, pesticides, and other substances associated with anthropogenic activity. Here, we used next-generation sequencing to characterize the microbial communities of potential contaminant sources in order to determine how environmental discharges of microbiota and their genetic material may influence the microbiomes of coral reef communities and coastal receiving waters. Runoff delivered through inlet discharges impacted coral microbial communities, but impacts from oceanic outfalls carrying treated wastewater were greater. Geographic differences in the degree of impact suggest that coral microbiomes may be influenced by the microbiological quality of treated wastewater. Copyright © 2017 Staley et al.

Contact inhibition of locomotion determines cell–cell and cell–substrate forces in tissues

PubMed Central

Zimmermann, Juliane; Camley, Brian A.; Rappel, Wouter-Jan; Levine, Herbert

2016-01-01

Cells organized in tissues exert forces on their neighbors and their environment. Those cellular forces determine tissue homeostasis as well as reorganization during embryonic development and wound healing. To understand how cellular forces are generated and how they can influence the tissue state, we develop a particle-based simulation model for adhesive cell clusters and monolayers. Cells are contractile, exert forces on their substrate and on each other, and interact through contact inhibition of locomotion (CIL), meaning that cell–cell contacts suppress force transduction to the substrate and propulsion forces align away from neighbors. Our model captures the traction force patterns of small clusters of nonmotile cells and larger sheets of motile Madin–Darby canine kidney (MDCK) cells. In agreement with observations in a spreading MDCK colony, the cell density in the center increases as cells divide and the tissue grows. A feedback between cell density, CIL, and cell–cell adhesion gives rise to a linear relationship between cell density and intercellular tensile stress and forces the tissue into a nonmotile state characterized by a broad distribution of traction forces. Our model also captures the experimentally observed tissue flow around circular obstacles, and CIL accounts for traction forces at the edge. PMID:26903658

Congruence of Imaging Estimators and Mechanical Measurements of Viscoelastic Properties of Soft Tissues

PubMed Central

Zhang, Man; Castaneda, Benjamin; Wu, Zhe; Nigwekar, Priya; Joseph, Jean V.; Rubens, Deborah J.; Parker, Kevin J.

2007-01-01

Biomechanical properties of soft tissues are important for a wide range of medical applications, such as surgical simulation and planning and detection of lesions by elasticity imaging modalities. Currently, the data in the literature is limited and conflicting. Furthermore, to assess the biomechanical properties of living tissue in vivo, reliable imaging-based estimators must be developed and verified. For these reasons we developed and compared two independent quantitative methods – crawling wave estimator (CRE) and mechanical measurement (MM) for soft tissue characterization. The CRE method images shear wave interference patterns from which the shear wave velocity can be determined and hence the Young’s modulus can be obtained. The MM method provides the complex Young’s modulus of the soft tissue from which both elastic and viscous behavior can be extracted. This article presents the systematic comparison between these two techniques on the measurement of gelatin phantom, veal liver, thermal-treated veal liver, and human prostate. It was observed that the Young’s moduli of liver and prostate tissues slightly increase with frequency. The experimental results of the two methods are highly congruent, suggesting CRE and MM methods can be reliably used to investigate viscoelastic properties of other soft tissues, with CRE having the advantages of operating in nearly real time and in situ. PMID:17604902

Cartilage Dysfunction in ALS Patients as Side Effect of Motion Loss: 3D Mechano-Electrochemical Computational Model

PubMed Central

Gaffney, Eamonn A.; Doblaré, Manuel

2014-01-01

Amyotrophic lateral sclerosis (ALS) is a debilitating motor neuron disease characterized by progressive weakness, muscle atrophy, and fasciculation. This fact results in a continuous degeneration and dysfunction of articular soft tissues. Specifically, cartilage is an avascular and nonneural connective tissue that allows smooth motion in diarthrodial joints. Due to the avascular nature of cartilage tissue, cells nutrition and by-product exchange are intermittently occurring during joint motions. Reduced mobility results in a change of proteoglycan density, osmotic pressure, and permeability of the tissue. This work aims to demonstrate the abnormal cartilage deformation in progressive immobilized articular cartilage for ALS patients. For this aim a novel 3D mechano-electrochemical model based on the triphasic theory for charged hydrated soft tissues is developed. ALS patient parameters such as tissue porosity, osmotic coefficient, and fixed anions were incorporated. Considering different mobility reduction of each phase of the disease, results predicted the degree of tissue degeneration and the reduction of its capacity for deformation. The present model can be a useful tool to predict the evolution of joints in ALS patients and the necessity of including specific cartilage protectors, drugs, or maintenance physical activities as part of the symptomatic treatment in amyotrophic lateral sclerosis. PMID:24991537

Temperature-dependent elastic properties of brain tissues measured with the shear wave elastography method.

PubMed

Liu, Yan-Lin; Li, Guo-Yang; He, Ping; Mao, Ze-Qi; Cao, Yanping

2017-01-01

Determining the mechanical properties of brain tissues is essential in such cases as the surgery planning and surgical training using virtual reality based simulators, trauma research and the diagnosis of some diseases that alter the elastic properties of brain tissues. Here, we suggest a protocol to measure the temperature-dependent elastic properties of brain tissues in physiological saline using the shear wave elastography method. Experiments have been conducted on six porcine brains. Our results show that the shear moduli of brain tissues decrease approximately linearly with a slope of -0.041±0.006kPa/°C when the temperature T increases from room temperature (~23°C) to body temperature (~37°C). A case study has been further conducted which shows that the shear moduli are insensitive to the temperature variation when T is in the range of 37 to 43°C and will increase when T is higher than 43°C. With the present experimental setup, temperature-dependent elastic properties of brain tissues can be measured in a simulated physiological environment and a non-destructive manner. Thus the method suggested here offers a unique tool for the mechanical characterization of brain tissues with potential applications in brain biomechanics research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Two-photon Microscopy and Polarimetry for Assessment of Myocardial Tissue Organization

NASA Astrophysics Data System (ADS)

Archambault-Wallenburg, Marika

Optical methods can provide useful tissue characterization tools. For this project, two-photon microscopy and polarized light examinations (polarimetry) were used to assess the organizational state of myocardium in healthy, infarcted, and stem-cell regenerated states. Two-photon microscopy visualizes collagen through second-harmonic generation and myocytes through two-photon excitation autofluorescence, providing information on the composition and structure/organization of the tissue. Polarimetry measurements yield a value of linear retardance that can serve as an indicator of tissue anisotropy, and with a dual-projection method, information about the anisotropy axis orientation can also be extracted. Two-photon microscopy results reveal that stem-cell treated tissue retains more myocytes and structure than infarcted myocardium, while polarimetry findings suggest that the injury caused by temporary ligation of a coronary artery is less severe and more diffuse that than caused by a permanent ligation. Both these methods show potential for tissue characterization.

Liver fat quantification using fast kVp-switching dual energy CT

NASA Astrophysics Data System (ADS)

Kriston, Andras; Mendonça, Paulo; Silva, Alvin; Paden, Robert G.; Pavlicek, William; Sahani, Dushyant; Janos Kis, Benedek; Rusko, Laszlo; Okerlund, Darin; Bhotika, Rahul

2011-03-01

Nonalcoholic steatohepatitis (NASH) is a liver disease that occurs in patients that lack a history of the well-proven association of alcohol use. A major symptom of NASH is increased fat deposition in the liver. Gemstone Spectral Imaging (GSI) with fast kVp-switching enables projection-based material decomposition, offering the opportunity to accurately characterize tissue types, e.g., fat and healthy liver tissue, based on their energy-sensitive material attenuation and density. We describe our pilot efforts to apply GSI to locate and quantify the amount of fat deposition in the liver. Two approaches are presented, one that computes percentage fat from the difference in HU values at high and low energies and the second based on directly computing fat volume fraction at each voxel using multi-material decomposition. Simulation software was used to create a phantom with a set of concentric rings, each composed of fat and soft tissue in different relative amounts with attenuation values obtained from the National Institute of Standards and Technology. Monte Carlo 80 and 140 kVp X-ray projections were acquired and CT images of the phantom were reconstructed. Results demonstrated the sensitivity of dual energy CT to the presence of fat and its ability to distinguish fat from soft tissue. Additionally, actual patient (liver) datasets were acquired using GSI and monochromatic images at 70 and 140 keV were reconstructed. Preliminary results demonstrate a tissue sensitivity that appears sufficient to quantify fat content with a degree of accuracy as may be needed for non-invasive clinical assessment of NASH.