Magnetic resonance electrical impedance tomography (MREIT) is a new medical imaging modality visualizing static conductivity images of electrically conducting subjects. Recently, MREIT has rapidly progressed in its theory, algorithm, and experiment technique and now reached to the stage of in vivo animal experiments. In this paper, we present a software, named CoReHA 2.0 standing for the second version of conductivity reconstructor using harmonic algorithms, to facilitate in vivo MREIT reconstruction of conductivity image. This software offers various computational tools including preprocessing of MREIT data, identification of 2D geometry of the imaging domain and electrode positions, and reconstruction of cross-sectional scaled conductivity images from MREIT data. In particular, in the new version, we added several tools including ramp-preserving denoising, harmonic inpainting, and local harmonic Bz algorithm to deal with data from in vivo experiments. The presented software will be useful to researchers in the field of MREIT for simulation, validation, and further technical development.

The total number of influenza cases with medical attendance has been estimated from sentinel surveillance data in Japan under a random sampling assumption of sentinel medical institutions among the total medical institutions. The 2009 pandemic offered a research opportunity to validate the sentinel-based estimation method using the estimated proportion of infections measured by the population-wide seroepidemiological survey employing hemagglutinin inhibition (HI) assay. For the entire population, we estimated the age-standardized proportion of infections at 28.5% and 23.5% using cut-off values of HI titer at 1 : 20 and 1 : 40, respectively. Investigating the age profiles, we show that the estimated influenza-like illness (ILI) cases with medical attendance exceeded the estimated infections among those aged from 0 to 19 years, indicating an overestimation of the magnitude by sentinel-based estimation method. The ratio of estimated cases to estimated infections decreased as a function of age. Examining the geographic distributions, no positive correlation was identified between the estimated cases and infections. Our findings indicate a serious technical limitation of the so-called multiplier method in appropriately quantifying the risk of influenza due to limited specificity of ILI and reporting bias. A seroepidemiological study should be planned in advance of a pandemic.

Dentin is a hierarchically structured biomineralized composite material, and dentin's tubules are difficult to study in situ. Nano-CT provides the requisite resolution, but the field of view typically contains only a few tubules. Using a plate-like specimen allows reconstruction of a volume containing specific tubules from a number of truncated projections typically collected over an angular range of about 140°, which is practically accessible. Classical computed tomography (CT) theory cannot exactly reconstruct an object only from truncated projections, needless to say a limited angular range. Recently, interior tomography was developed to reconstruct a region-of-interest (ROI) from truncated data in a theoretically exact fashion via the total variation (TV) minimization under the condition that the ROI is piecewise constant. In this paper, we employ a TV minimization interior tomography algorithm to reconstruct interior microstructures in dentin from truncated projections over a limited angular range. Compared to the filtered backprojection (FBP) reconstruction, our reconstruction method reduces noise and suppresses artifacts. Volume rendering confirms the merits of our method in terms of preserving the interior microstructure of the dentin specimen.

The bidomain model describes the electrical properties of cardiac tissue and is often used to simulate the response of the heart to an electric shock. The strength-interval curve summarizes how refractory tissue is excited. This paper analyzes calculations of the strength-interval curve when a stimulus is applied through a unipolar electrode. In particular, the bidomain model is used to clarify why the cathodal and anodal strength-interval curves are different, and what the mechanism of the “dip” in the anodal strength-interval curve is.

Although previous studies have shown the successful use of pressure-induced reactive hyperemia as a tool for the assessment of endothelial function, its sensitivity remains questionable. This study aims to investigate the feasibility and sensitivity of a novel multiscale entropy index (MEI) in detecting subtle vascular abnormalities in healthy and diabetic subjects. Basic anthropometric and hemodynamic parameters, serum lipid profiles, and glycosylated hemoglobin levels were recorded. Arterial pulse wave signals were acquired from the wrist with an air pressure sensing system (APSS), followed by MEI and dilatation index (DI) analyses. MEI succeeded in detecting significant differences among the four groups of subjects: healthy young individuals, healthy middle-aged or elderly individuals, well-controlled diabetic individuals, and poorly controlled diabetic individuals. A reduction in multiscale entropy reflected age- and diabetes-related vascular changes and may serve as a more sensitive indicator of subtle vascular abnormalities compared with DI in the setting of diabetes.

Geometric assumption and verification with RANSAC has become a crucial step for corresponding to local features due to its wide applications in biomedical feature analysis and vision computing. However, conventional RANSAC is very time-consuming due to redundant sampling times, especially dealing with the case of numerous matching pairs. This paper presents a novel preprocessing model to explore a reduced set with reliable correspondences from initial matching dataset. Both geometric model generation and verification are carried out on this reduced set, which leads to considerable speedups. Afterwards, this paper proposes a reliable RANSAC framework using preprocessing model, which was implemented and verified using Harris and SIFT features, respectively. Compared with traditional RANSAC, experimental results show that our method is more efficient.

Computational mechanics has been advanced in every area of orthopedic biomechanics. The objective of this paper is to provide a general review of the computational models used in the analysis of the mechanical function of the knee joint in different loading and pathological conditions. Major review articles published in related areas are summarized first. The constitutive models for soft tissues of the knee are briefly discussed to facilitate understanding the joint modeling. A detailed review of the tibiofemoral joint models is presented thereafter. The geometry reconstruction procedures as well as some critical issues in finite element modeling are also discussed. Computational modeling can be a reliable and effective method for the study of mechanical behavior of the knee joint, if the model is constructed correctly. Single-phase material models have been used to predict the instantaneous load response for the healthy knees and repaired joints, such as total and partial meniscectomies, ACL and PCL reconstructions, and joint replacements. Recently, poromechanical models accounting for fluid pressurization in soft tissues have been proposed to study the viscoelastic response of the healthy and impaired knee joints. While the constitutive modeling has been considerably advanced at the tissue level, many challenges still exist in applying a good material model to three-dimensional joint simulations. A complete model validation at the joint level seems impossible presently, because only simple data can be obtained experimentally. Therefore, model validation may be concentrated on the constitutive laws using multiple mechanical tests of the tissues. Extensive model verifications at the joint level are still crucial for the accuracy of the modeling.

Physicians in the Intensive Care Unit (ICU) are specially trained to deal constantly with very large and complex quantities of clinical data and make quick decisions as they face complications. However, the amount of information generated and the way the data are presented may overload the cognitive skills of even experienced professionals and lead to inaccurate or erroneous actions that put patients' lives at risk. In this paper, we present the design, development, and validation of iOSC3, an ontology-based system for intelligent supervision and treatment of critical patients with acute cardiac disorders. The system analyzes the patient's condition and provides a recommendation about the treatment that should be administered to achieve the fastest possible recovery. If the recommendation is accepted by the doctor, the system automatically modifies the quantity of drugs that are being delivered to the patient. The knowledge base is constituted by an OWL ontology and a set of SWRL rules that represent the expert's knowledge. iOSC3 has been developed in collaboration with experts from the Cardiac Intensive Care Unit (CICU) of the Meixoeiro Hospital, one of the most significant hospitals in the northwest region of Spain.

A hybrid multiscale and multilevel image fusion algorithm for green fluorescent protein (GFP) image and phase contrast image of Arabidopsis cell is proposed in this paper. Combining intensity-hue-saturation (IHS) transform and sharp frequency localization Contourlet transform (SFL-CT), this algorithm uses different fusion strategies for different detailed subbands, which include neighborhood consistency measurement (NCM) that can adaptively find balance between color background and gray structure. Also two kinds of neighborhood classes based on empirical model are taken into consideration. Visual information fidelity (VIF) as an objective criterion is introduced to evaluate the fusion image. The experimental results of 117 groups of Arabidopsis cell image from John Innes Center show that the new algorithm cannot only make the details of original images well preserved but also improve the visibility of the fusion image, which shows the superiority of the novel method to traditional ones.

Medical imaging is a relevant field of application of image processing algorithms. In particular, the analysis of white blood cell (WBC) images has engaged researchers from fields of medicine and computer vision alike. Since WBCs can be approximated by a quasicircular form, a circular detector algorithm may be successfully applied. This paper presents an algorithm for the automatic detection of white blood cells embedded into complicated and cluttered smear images that considers the complete process as a circle detection problem. The approach is based on a nature-inspired technique called the electromagnetism-like optimization (EMO) algorithm which is a heuristic method that follows electromagnetism principles for solving complex optimization problems. The proposed approach uses an objective function which measures the resemblance of a candidate circle to an actual WBC. Guided by the values of such objective function, the set of encoded candidate circles are evolved by using EMO, so that they can fit into the actual blood cells contained in the edge map of the image. Experimental results from blood cell images with a varying range of complexity are included to validate the efficiency of the proposed technique regarding detection, robustness, and stability.

Objectives. Stressors have a serious role in precipitating mental and somatic disorders and are an interesting subject for many clinical and community-based studies. Hence, the proper and accurate measurement of them is very important. We revised the stressful life event (SLE) questionnaire by adding weights to the events in order to measure and determine a cut point. Methods. A total of 4569 adults aged between 18 and 85 years completed the SLE questionnaire and the general health questionnaire-12 (GHQ-12). A hybrid model of genetic algorithm (GA) and artificial neural networks (ANNs) was applied to extract the relation between the stressful life events (evaluated by a 6-point Likert scale) and the GHQ score as a response variable. In this model, GA is used in order to set some parameter of ANN for achieving more accurate results. Results. For each stressful life event, the number is defined as weight. Among all stressful life events, death of parents, spouse, or siblings is the most important and impactful stressor in the studied population. Sensitivity of 83% and specificity of 81% were obtained for the cut point 100. Conclusion. The SLE-revised (SLE-R) questionnaire despite simplicity is a high-performance screening tool for investigating the stress level of life events and its management in both community and primary care settings. The SLE-R questionnaire is user-friendly and easy to be self-administered. This questionnaire allows the individuals to be aware of their own health status.

Regularizing the deformation field is an important aspect in nonrigid medical image registration. By covering the template image with a triangular mesh, this paper proposes a new regularization constraint in terms of connections between mesh vertices. The connection relationship is preserved by the spring analogy method. The method is evaluated by registering cerebral magnetic resonance imaging (MRI) image data obtained from different individuals. Experimental results show that the proposed method has good deformation ability and topology-preserving ability, providing a new way to the nonrigid medical image registration.

The progression of osteoarthritis can be accompanied by depth-dependent changes in the properties of articular cartilage. The objective of the present study was to determine the subsequent alteration in the fluid pressurization in the human knee using a three-dimensional computer model. Only a small compression in the femur-tibia direction was applied to avoid numerical difficulties. The material model for articular cartilages and menisci included fluid, fibrillar and nonfibrillar matrices as distinct constituents. The knee model consisted of distal femur, femoral cartilage, menisci, tibial cartilage, and proximal tibia. Cartilage degeneration was modeled in the high load-bearing region of the medial condyle of the femur with reduced fibrillar and nonfibrillar elastic properties and increased hydraulic permeability. Three case studies were implemented to simulate (1) the onset of cartilage degeneration from the superficial zone, (2) the progression of cartilage degeneration to the middle zone, and (3) the progression of cartilage degeneration to the deep zone. As compared with a normal knee of the same compression, reduced fluid pressurization was observed in the degenerated knee. Furthermore, faster reduction in fluid pressure was observed with the onset of cartilage degeneration in the superficial zone and progression to the middle zone, as compared to progression to the deep zone. On the other hand, cartilage degeneration in any zone would reduce the fluid pressure in all three zones. The shear strains at the cartilage-bone interface were increased when cartilage degeneration was eventually advanced to the deep zone. The present study revealed, at the joint level, altered fluid pressurization and strains with the depth-wise cartilage degeneration. The results also indicated redistribution of stresses within the tissue and relocation of the loading between the tissue matrix and fluid pressure. These results may only be qualitatively interesting due to the small compression considered.

Colorectal cancer is a leading cause of cancer mortality in both developed and developing countries. Transforming basic research results into clinical practice is one of the key tasks of translational research, which will greatly improve the diagnosis and treatments of colorectal cancer. In this paper, a translational research platform for colorectal cancer, named crcTRP, is introduced. crcTRP serves the colorectal cancer translational research by providing various types of biomedical information related with colorectal cancer to the community. The information, including clinical data, epidemiology data, individual omics data, and public omics data, was collected through a multisource biomedical information collection solution and then integrated in a clinic-omics database, which was constructed with EAV-ER model for flexibility and efficiency. A preliminary exploration of conducting translational research on crcTRP was implemented and worked out a set of clinic-genomic relations, linking clinical data with genomic data. These relations have also been applied to crcTRP to make it more conductive for cancer translational research.

There are several statistical methods for time-to-event analysis, among which is the Cox proportional hazards model that is most commonly used. However, when the absolute change in risk, instead of the risk ratio, is of primary interest or when the proportional hazard assumption for the Cox proportional hazards model is violated, an additive hazard regression model may be more appropriate. In this paper, we give an overview of this approach and then apply a semiparametric as well as a nonparametric additive model to a data set from a study of the natural history of human papillomavirus (HPV) in HIV-positive and HIV-negative women. The results from the semiparametric model indicated on average an additional 14 oncogenic HPV infections per 100 woman-years related to CD4 count < 200 relative to HIV-negative women, and those from the nonparametric additive model showed an additional 40 oncogenic HPV infections per 100 women over 5 years of followup, while the estimated hazard ratio in the Cox model was 3.82. Although the Cox model can provide a better understanding of the exposure disease association, the additive model is often more useful for public health planning and intervention.

Cell morphology is the research foundation in many applications related to the estimation of cell status, drug response, and toxicity screening. In biomedical field, the quantitative phase detection is an inevitable trend for living cells. In this paper, the morphological change of HeLa cells treated with methanol of different concentrations is detected using digital holographic microscopy. The compact image-plane digital holographic system is designed based on fiber elements. The quantitative phase image of living cells is obtained in combination with numerical analysis. The statistical analysis shows that the area and average optical thickness of HeLa cells treated with 12.5% or 25% methanol reduce significantly, which indicates that the methanol with lower concentration could cause cellular shrinkage. The area of HeLa cells treated with 50% methanol is similar to that of normal cells (P > 0.05), which reveals the fixative effect of methanol with higher concentration. The maximum optical thickness of the cells treated with 12.5%, 25%, and 50% methanol is greater than that of untreated cells, which implies the pyknosis of HeLa cells under the effect of methanol. All of the results demonstrate that digital holographic microscopy has supplied a noninvasive imaging alternative to measure the morphological change of label-free living cells.

Bioluminescence tomography (BLT) has a great potential to provide a powerful tool for tumor detection, monitoring tumor therapy progress, and drug development; developing new reconstruction algorithms will advance the technique to practical applications. In the paper, we propose a BLT reconstruction algorithm by combining SP3 equations and Bregman iteration method to improve the quality of reconstructed sources. The numerical results for homogeneous and heterogeneous phantoms are very encouraging and give significant improvement over the algorithms without the use of SP3 equations and Bregman iteration method.

This paper proposes a plane-based sampling method to improve the traditional Ray Casting Algorithm (RCA) for the fast reconstruction of a three-dimensional biomedical model from sequential images. In the novel method, the optical properties of all sampling points depend on the intersection points when a ray travels through an equidistant parallel plan cluster of the volume dataset. The results show that the method improves the rendering speed at over three times compared with the conventional algorithm and the image quality is well guaranteed.

Results of epidemiological and public health surveys are often presented in the form of cross-classification tables. It is sometimes difficult to analyze data described in this way and to understand relations between variables. Graphical methods such as correspondence analysis are more convenient and useful. Our paper describes an application of correspondence analysis to epidemiological research. We apply the basic concepts of correspondence analysis like profiles, chi-square distance to medical data concerning prevalence of asthma. We aim at describing the relationship between asthma, region, and age. The data presented in this paper come from Epidemiology of Allergy in Poland (ECAP) survey in years 2006–2008. Correspondence analysis shows that there is a fundamental difference in the structure of age groups for people with symptoms compared to those who have declared asthma (regardless of the level of symptoms of asthma and the level of declaration). The variable which best differentiates declared asthma in all regions is “wheezing and whistling.” Correspondence analysis also shows significant differences between locations. Our analyses are performed in the R package “ca”.

With recent advances in microarray technology, there has been a flourish in genome-scale identification of molecular signatures for cancer. However, the differentially expressed genes obtained by different laboratories are highly divergent. The present discrepancy at gene level indicates a need for a novel strategy to obtain more robust signatures for cancer. In this paper we hypothesize that (1) the expression signatures of different cancer microarray datasets are more similar at pathway level than at gene level; (2) the comparability of the cancer molecular mechanisms of different individuals is related to their genetic similarities. In support of the hypotheses, we summarized theoretical and experimental evidences, and conducted case studies on colorectal and prostate cancer microarray datasets. Based on the above assumption, we propose that reliable cancer signatures should be investigated in the context of biological pathways, within a cohort of genetically homogeneous population. It is hoped that the hypotheses can guide future research in cancer mechanism and signature discovery.

Oxygenation is an important component of the tumour microenvironment, having a significant impact on the progression and management of cancer. Theoretical determination of tissue oxygenation through simulations of the oxygen transport process is a powerful tool to characterise the spatial distribution of oxygen on the microscopic scale and its dynamics and to study its impact on the response to radiation. Accurate modelling of tumour oxygenation must take into account important aspects that are specific to tumours, making the quantitative characterisation of oxygenation rather difficult. This paper aims to discuss the important aspects of modelling tumour oxygenation, reoxygenation, and implications for treatment.

Interval-censored data consist of adjacent inspection times that surround an unknown failure time. We have in this paper reviewed the classical approach which is maximum likelihood in estimating the Weibull parameters with interval-censored data. We have also considered the Bayesian approach in estimating the Weibull parameters with interval-censored data under three loss functions. This study became necessary because of the limited discussion in the literature, if at all, with regard to estimating the Weibull parameters with interval-censored data using Bayesian. A simulation study is carried out to compare the performances of the methods. A real data application is also illustrated. It has been observed from the study that the Bayesian estimator is preferred to the classical maximum likelihood estimator for both the scale and shape parameters.

Identifying transcription factor binding sites with experimental methods is often expensive and time consuming. Although many computational approaches and tools have been developed for this problem, the prediction accuracy is not satisfactory. In this paper, we develop a new computational approach that can model the relationships among all short sequence segments in the promoter regions with a graph theoretic model. Based on this model, finding the locations of transcription factor binding site is reduced to computing maximum weighted cliques in a graph with weighted edges. We have implemented this approach and used it to predict the binding sites in two organisms, Caenorhabditis elegans and mus musculus. We compared the prediction accuracy with that of the Gibbs Motif Sampler. We found that the accuracy of our approach is higher than or comparable with that of the Gibbs Motif Sampler for most of tested data and can accurately identify binding sites in cases where the Gibbs Motif Sampler has difficulty to predict their locations.

For a more detailed description of the interaction between residues, this paper proposes an amino acid network model, which contains two types of weight—similar weight and dissimilar weight. The weight of the link is based on a self-consistent statistical contact potential between different types of amino acids. In this model, we can get a more reasonable representation of the distance between residues. Furthermore, with the network parameter, average shortest path length, we can get a more accurate reflection of the molecular size. This amino acid network is a “small-world” network, and the network parameter is sensitive to the conformation change of protein. For some disease-related proteins, the highly central residues of the amino acid network are highly correlated with the hot spots. In the compound with the related drug, these residues either interacted directly with the drug or with the residue which is in contact with the drug.