NIH ImageJ and Slice-O-Matic computed tomography imaging software to quantify soft tissue

Objective: To compare reliability and limits of agreement of soft tissue cross‐sectional areas obtained using Slice‐O‐Matic and NIH ImageJ medical imaging software packages. Research Methods and Procedures: Abdominal and midthigh images were obtained using single‐slice computed tomography. Two trained investigators analyzed each computed tomography image in duplicate. Adipose tissue and skeletal muscle cross‐sectional areas (centimeters squared) were calculated using standard Hounsfield unit ranges (adipose tissue: ?190 to ?30 and skeletal muscle: ?29 to 150). Regions of interest included abdominal total area, total fat area, subcutaneous fat area, visceral fat area (AVF), and right and left thigh total area, fat area, and skeletal muscle area. Results: For all images, intra‐investigator coefficients of variation ranged from 0.2% to 3.4% and from 0.4% to 5.6% and inter‐investigator coefficients of variation ranged from 0.9% to 4.8% and 0.2% to 2.6% for Slice‐O‐Matic and NIH ImageJ, respectively, with intra‐ and inter‐investigator coefficients of reliability of R² = 0.99. Mean AVF values for investigators A and B ranged from 168 to 170 cm² using Slice‐O‐Matic and NIH ImageJ. Bland‐Altman analyses revealed that Slice‐O‐Matic and NIH ImageJ results were comparable. The mean differences (95% confidence intervals) between the AVF cross‐sectional areas obtained using the Slice‐O‐Matic and NIH ImageJ medical imaging software were +2.5 cm² (?5.7, +10.8 cm²) or +1.4% (?3.4%, +6.4%). Discussion: These findings show that both the Slice‐O‐Matic and NIH ImageJ medical imaging software systems provide reliable measurements of adipose tissue and skeletal muscle cross‐sectional areas.     

A statistical measure of tissue heterogeneity with application to 3D PET sarcoma data

In vivo measurement of local tissue characteristics by modern bioimaging techniques such as positron emission tomography (PET) provides the opportunity to analyze quantitatively the role that tissue heterogeneity may play in understanding biological function. This paper develops a statistical measure of the heterogeneity of a tissue characteristic that is based on the deviation of the distribution of the tissue characteristic from a unimodal elliptically contoured spatial pattern. An efficient algorithm is developed for computation of the measure based on volumetric region of interest data. The technique is illustrated by application to data from PET imaging studies of fluorodeoxyglucose utilization in human sarcomas. A set of 74 sarcoma patients (with five-year follow-up survival information) were evaluated for heterogeneity as well as a number of other potential prognostic indicators of survival. A Cox proportional hazards analysis of these data shows that the degree of heterogeneity of the sarcoma is the major risk factor associated with patient death. Some theory is developed to analyze the asymptotic statistical behavior of the heterogeneity estimator. In the context of data arising from Poisson deconvolution (PET being the prime example), the heterogeneity estimator, which is a non-linear functional of the PET image data, is consistent and converges at a rate that is parametric in the injected dose.     

An application of nanoindentation technique to measure bone tissue Lamellae properties

Measuring the microscopic mechanical properties of bone tissue is important in support of understanding the etiology and pathogenesis of many bone diseases. Knowledge about these properties provides a context for estimating the local mechanical environment of bone related cells thait coordinate the adaptation to loads experienced at the whole organ level. The objective of this study was to determine the effects of experimental testing parameters on nanoindentation measures of lamellar-level bone mechanical properties. Specifically, we examined the effect of specimen preparation condition, indentation depth, repetitive loading, time delay, and displacement rate. The nanoindentation experiments produced measures of lamellar elastic moduli for human cortical bone (average value of 17.7 +/- 4.0 GPa for osteons and 19.3 +/- 4.7 GPa for interstitial bone tissue). In addition, the hardness measurements produced results consistent with data in the literature (average 0.52 +/- 0.15 GPa for osteons and 0.59 +/- 0.20 GPa for interstitial bone tissue). Consistent modulus values can be obtained from a 500-nm-deep indent. The results also indicated that the moduli and hardnesses of the dry specimens are significantly greater (22.6% and 56.9%, respectively) than those of the wet and wet and embedded specimens. The latter two groups were not different. The moduli obtained at a 5-nm/s loading rate were significantly lower than the values at the 10- and 20-nm/s loading rates while the 10- and 20-nm/s rates were not significantly different. The hardness measurements showed similar rate-dependent results. The preliminary results indicated that interstitial bone tissue has significantly higher modulus and hardness than osteonal bone tissue. In addition, a significant correlation between hardness and elastic modulus was observed.     

Dystocia due to soft tissue

In dystocia caused by abnormal conditions of the soft parts, the etiologic changes may be either in the genital tissues or in adjacent soft structures. Broadly, the conditions causing the difficulty may be grouped as follows: (1) anomalies or congenital modifications; (2) tumors; (3) modifications due to age, accident or surgical operations; (4) modification of the expulsive forces; (5) abnormalities of the products of conception. Often in such circumstances cesarean section is necessary. Sometimes when tumor is present it can be removed before it interferes with delivery, but decision to excise the growth must be guided by such factors as the location of the lesion and the stage of gestation. This would determine to what extent the maintenance of pregnancy would be jeopardized by surgical intervention before term.     

A theoretical framework to analyze bend testing of soft tissue

It has been hypothesized that repetitive flexural stresses contribute to the fatigue-induced failure of bioprosthetic heart valves. Although experimental apparatuses capable of measuring the bending properties of biomaterials have been described, a theoretical framework to analyze the resulting data is lacking. Given the large displacements present in these bending experiments and the nonlinear constitutive behavior of most biomaterials, such a formulation must be based on finite elasticity theory. We present such a theory in this work, which is capable of fitting bending moment versus radius of curvature experimental data to an arbitrary strain energy function. A simple finite element model was constructed to study the validity of the proposed method. To demonstrate the application of the proposed approach, bend testing data from the literature for gluteraldehyde-fixed bovine pericardium were fit to a nonlinear strain energy function, which showed good agreement to the data. This method may be used to integrate bending behavior in constitutive models for soft tissue.     

Computational modeling of volumetric soft tissue growth: application to the cardiac left ventricle

As an initial step to investigate stimulus–response relations in growth and remodeling (G&R) of cardiac tissue, this study aims to develop a method to simulate 3D-inhomogeneous volumetric growth. Growth is regarded as a deformation that is decomposed into a plastic component which describes unconstrained growth and an elastic component to satisfy continuity of the tissue after growth. In current growth models, a single reference configuration is used that remains fixed throughout the entire growth process. However, considering continuous turnover to occur together with growth, such a fixed reference is unlikely to exist in reality. Therefore, we investigated the effect of tissue turnover on growth by incrementally updating the reference configuration. With both a fixed reference and an updated reference, strain-induced cardiac growth in magnitude of 30% could be simulated. However, with an updated reference, the amplitude of the stimulus for growth decreased over time, whereas with a fixed reference this amplitude increased. We conclude that, when modeling volumetric growth, the choice of the reference configuration is of great importance for the computed growth.     

Methods for quasi-linear viscoelastic modeling of soft tissue: application to incremental stress-relaxation experiments

The quasi-linear viscoelastic (QLV) model was applied to incremental stress-relaxation tests and an expression for the stress was derived for each step. This expression was used to compare two methods for normalizing stress data prior to estimating QLV parameters. The first and commonly used normalization method was shown to be strain-dependent. Thus, a second normalization method was proposed and shown to be strain-independent and more sensitive to QLV time constants. These analytical results agreed with representative tendon data. Therefore, this method for normalizing stress data was proposed for future studies of incremental stress-relaxation, or whenever comparing stress-relaxation at different strains.     

Rapid pre-screening: a validated quality assurance measure in cervical cytology

We present the results of 3 years' experience of rapid pre-screening in cervical cytology. In our laboratory we rapidly pre-screen all smears. The performance of each primary screener can be assessed. In addition, the relative sensitivity and specificity of each rapid pre-screener can itself be continuously monitored using the final report as a yardstick. In our laboratory individual sensitivity of rapid pre-screening for the detection of high-grade abnormalities was in the range of 44-90% with an overall laboratory sensitivity of 69%. Specificity was in the range of 94-99% with an overall laboratory specificity of 98%. Rapid pre-screening allows checking of the checkers and pathologists and tends to promote uniformity in the assessment of smear adequacy. This form of continuous quality assurance is practical, convenient and acceptable to staff.     

A method for measuring strains in soft tissue

A finite element based method has been developed for measuring strains in soft tissue. An array of markers is placed on the tissue surface and treated as nodes of a four node isoparametric element. The displacements of the marker centroids are directly measured using a high sensitivity television camera. Finite element method mathematics are then used to calculate the plane strain tensor at any point inside the element. The method has been implemented using non-rectangular elements that are approximately 2 mm on each side.     

Monochlorobimane fluorometric method to measure tissue glutathione

Glutathione (GSH) is the principal intracellular low-molecular-weight thiol and plays a critical role in the cellular defense against agents that impose oxidative stress. A common technique to measure GSH uses reversed-phase high-performance liquid chromatography (HPLC) following derivatization with 5, 5'-dithiobis(2-nitrobenzoic acid), a technique, although reliable and sensitive, that is time consuming and laborious. A common technique to measure GSH in cultured cells is to add monochlorobimane to the culture medium where it readily enters cells to form a fluorescent GSH-monochlorobimane adduct that can be measured fluorometrically. This reaction is catalyzed by glutathione S-transferase. We reasoned that adding glutathione S-transferase and monochlorobimane to tissue homogenates would allow a rapid reliable method to measure GSH. The accuracy of the new test was assessed in homogenates of rat livers. One-half of each homogenate was assayed for GSH using a HPLC approach while the other half was assayed using the monochlorobimane approach. The two methods were found to give identical results. We conclude that the monochlorobimane fluorescent method is sufficiently specific to reliably measure tissue GSH.     

利用数码相机和Photoshop软件非破坏性测定叶面积的简便方法

采用数码相机获取叶片的数字图像,用Photoshop图像处理软件计算叶面积,并与目前常用的剪纸法和叶面积仪测定法进行比较分析。结果表明,本方法和上述传统测定方法测定结果存在极显著线性相关;不同拍摄分辨率、单位叶面积存贮像素个数和拍摄角度对测定结果无显著影响。和其它方法相比,本方法具有准确、快速、成本低廉、适合非破坏性动态连续观测等优点,适用于植物生理生态学研究中叶面积的测定。     

A strategy to determine operating parameters in tissue engineering hollow fiber bioreactors

The development of tissue engineering hollow fiber bioreactors (HFB) requires the optimal design of the geometry and operation parameters of the system. This article provides a strategy for specifying operating conditions for the system based on mathematical models of oxygen delivery to the cell population. Analytical and numerical solutions of these models are developed based on Michaelis–Menten kinetics. Depending on the minimum oxygen concentration required to culture a functional cell population, together with the oxygen uptake kinetics, the strategy dictates the model needed to describe mass transport so that the operating conditions can be defined. If c_min ≫ K_m we capture oxygen uptake using zero‐order kinetics and proceed analytically. This enables operating equations to be developed that allow the user to choose the medium flow rate, lumen length, and ECS depth to provide a prescribed value of c_min. When , we use numerical techniques to solve full Michaelis–Menten kinetics and present operating data for the bioreactor. The strategy presented utilizes both analytical and numerical approaches and can be applied to any cell type with known oxygen transport properties and uptake kinetics. Biotechnol. Bioeng. 2011; 108:1450–1461. © 2011 Wiley Periodicals, Inc.     

A validated bioenergetics model for ruffe Gymnocephalus cernuus and its application to a northern lake

A bioenergetics model was constructed for ruffe Gymnocephalus cernuus , and the model was used to estimate the food consumption of a native G. cernuus stock in Pyhäjärvi, a large mesotrophic lake in south-west Finland. The parameters for the bioenergetics model were determined through laboratory experiments conducted at several temperatures between 5 and 22° C for different sized G. cernuus (from 6 to 27 g). The model was verified and validated with independent laboratory growth experiments. The validated model was applied to field data from Pyhäjärvi to estimate the food consumption of G. cernuus and its effects on the zoobenthos community during the years 2002–2004. The total annual food consumption of the G. cernuus stock ranged from 11·6 to 15·7 g m⁻² (wet mass). Chironomidae was the most abundant prey, 81% of the total consumption. The annual total production of zoobenthos in Pyhäjärvi was 15·2 g m⁻² (wet mass). Therefore, it can be concluded that G. cernuus stock is likely to exert a significant influence on the zoobenthos community in this lake, indicating a potential role of G. cernuus as an influential invasive species in many freshwater ecosystems in Europe and North America.     

爱贝芙在修复面部软组织凹陷中的应用

目的:探讨爱贝芙在修复面部凹陷中的疗效.方法:根据凹陷程度估计爱贝芙用量,然后在面部凹陷部位的真皮网状层或真皮与皮下脂肪交界平面注射爱贝芙,轻压、按摩平整,而后局部用胶布固定三天.结果:爱贝芙能明显修复眼睑沟、鼻梁、鼻翼塌陷及先天的软组织凹陷,患者满意,对凹陷瘢痕虽能矫正凹陷,但无法改变瘢痕已有的色素改变,对唇的效果较差.结论:爱贝芙可以用来修复面部大部分软组织凹陷,且痛苦小、恢复快.     

A method to measure antioxidant activity in organic media: application to lipophilic vitamins

The 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulphonic acid) radical (ABTS(.+)) can be generated by the enzymatic system formed by hydrogen peroxide and horseradish peroxidase in an organic medium. The ABTS radical is easily generated in acidified ethanol medium in about 100 s with a stability of 1.7 x 10(-3) (-deltaabs/min) monitored at 730 nm. Other organic solvents, such as methanol or acetone, have lower radical generation times but the radical is less stable. The addition of Trolox or a lipophilic antioxidant such as alpha-tocopherol or beta-carotene produces a decrease in absorbance that can be used to estimate antioxidant capacity. Using a spectrophotometric end-point method and microplate-reader equipment, we have developed a method that estimates the antioxidant activity of different lipophilic vitamins. The use of Trolox as an antioxidant standard led to a limit of detection of 0.08 nmoles and limit of quantitation of 0.28 nmoles, while similar values were obtained for alpha-tocopherol and beta-carotene. The relative antioxidant activity values obtained by different antioxidants showed that alpha-tocopherol has a similar antioxidant potential to Trolox and that beta-carotene has 2.6 times the antioxidant potential of Trolox. In our opinion, this method can be useful for estimating the antioxidant activity in lipophilic samples and as a complement to other methods that measure antioxidant activity in aqueous media.     

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

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.     

Anisotropic microsphere-based approach to damage in soft fibered tissue

An anisotropic damage model for soft fibered tissue is presented in this paper, using a multi-scale scheme and focusing on the directionally dependent behavior of these materials. For this purpose, a micro-structural or, more precisely, a microsphere-based approach is used to model the contribution of the fibers. The link between micro-structural contribution and macroscopic response is achieved by means of computational homogenization, involving numerical integration over the surface of the unit sphere. In order to deal with the distribution of the fibrils within the fiber, a von Mises probability function is incorporated, and the mechanical (phenomenological) behavior of the fibrils is defined by an exponential-type model. We will restrict ourselves to affine deformations of the network, neglecting any cross-link between fibrils and sliding between fibers and the surrounding ground matrix. Damage in the fiber bundles is introduced through a thermodynamic formulation, which is directly included in the hyperelastic model. When the fibers are stretched far from their natural state, they become damaged. The damage increases gradually due to the progressive failure of the fibrils that make up such a structure. This model has been implemented in a finite element code, and different boundary value problems are solved and discussed herein in order to test the model features. Finally, a clinical application with the material behavior obtained from actual experimental data is also presented.     

A heterogeneity measure for cluster identification with application to disease mapping

Mapping of disease incidence has long been of importance to epidemiology and public health. In this paper, we consider identification of clusters of spatial units with elevated disease rates and develop a new approach that estimates the relative disease risk in association with potential risk factors and simultaneously identifies clusters corresponding to elevated risks. A heterogeneity measure is proposed to enable the comparison of a candidate cluster and its complement under a pair of complementary models. A quasi-likelihood procedure is developed for estimating the model parameters and identifying the clusters. An advantage of our approach over traditional spatial clustering methods is the identification of clusters that can have arbitrary shapes due to abrupt or noncontiguous changes while accounting for risk factors and spatial correlation. Asymptotic properties of the proposed methodology are established and a simulation study shows empirically sound finite-sample properties. The mapping and clustering of enterovirus 71 infections in Taiwan are carried out for illustration.