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Control problem in a biological system is the problem of finding an interventional policy for changing the state of the biological system from an undesirable state, e.g. disease, into a desirable healthy state. Boolean networks are utilized as a mathematical model for gene regulatory networks. This paper provides an algorithm to solve the control problem in Boolean networks. The proposed algorithm is implemented and applied on two biological systems: T-cell receptor network and Drosophila melanogaster network. Results show that the proposed algorithm works faster in solving the control problem over these networks, while having similar accuracy, in comparison to previous exact methods. Source code and a simple web service of the proposed algorithm is available at http://goliaei.ir/net-control/www/., Competing Interests: The authors have declared that no competing interests exist.

We present a Riemannian formalism for effective diffusion of biomolecules in collective variable spaces that provides a robust framework for conformational free energy calculation methods. Unlike their Euclidean counterparts, the Riemannian potential of mean force (PMF) and minimum free energy path (MFEP) are invariant under coordinate transformations. The presented formalism can be readily employed to modify the collective variable based enhanced sampling techniques, such as umbrella sampling (US) commonly used in biomolecular simulations, to take into account the role of intrinsic geometry of collective variable space. Although our model is mathematically equivalent to a Euclidean diffusion with a position-dependent diffusion tensor, the Riemannian formulation provides a more convenient framework for free energy calculation methods and path-finding algorithms aimed at characterizing the effective conformational dynamics of biomolecules. A simple three-dimensional toy model and a pentapeptide (met-enkephalin) simulated in an explicit solvent environment are used to illustrate the workings of the formalism and its implementation.

Incomplete and inconsistent datasets often pose difficulties in multimodal studies. We introduce the concept of scandent decision trees to tackle these difficulties. Scandent trees are decision trees that optimally mimic the partitioning of the data determined by another decision tree, and crucially, use only a subset of the feature set. We show how scandent trees can be used to enhance the performance of decision forests trained on a small number of multimodal samples when we have access to larger datasets with vastly incomplete feature sets. Additionally, we introduce the concept of tree-based feature transforms in the decision forest paradigm. When combined with scandent trees, the tree-based feature transforms enable us to train a classifier on a rich multimodal dataset, and use it to classify samples with only a subset of features of the training data. Using this methodology, we build a model trained on MRI and PET images of the ADNI dataset, and then test it on cases with only MRI data. We show that this is significantly more effective in staging of cognitive impairments compared to a similar decision forest model trained and tested on MRI only, or one that uses other kinds of feature transform applied to the MRI data., (Copyright © 2016. Published by Elsevier B.V.)

Magnetic resonance imaging (MRI), particularly dynamic contrast enhanced (DCE) imaging, has shown great potential in prostate cancer diagnosis and staging. In the current practice of DCE-MRI, diagnosis is based on quantitative parameters extracted from the series of T1-weighted images acquired after the injection of a contrast agent. To calculate these parameters, a pharmacokinetic model is fitted to the T1-weighted intensities. Most models make simplistic assumptions about the perfusion process. Moreover, these models require accurate estimation of the arterial input function, which is challenging. In this work we propose a data-driven approach to characterization of the prostate tissue that uses the time series of DCE T1-weighted images without pharmacokinetic modeling. This approach uses a number of model-free empirical parameters and also the principal component analysis (PCA) of the normalized T1-weighted intensities, as features for cancer detection from DCE MRI. The optimal set of principal components is extracted with sparse regularized regression through least absolute shrinkage and selection operator (LASSO). A support vector machine classifier was used with leave-one-patient-out cross validation to determine the ability of this set of features in cancer detection. Our data is obtained from patients prior to radical prostatectomy and the results are validated based on histological evaluation of the extracted specimens. Our results, obtained on 449 tissue regions from 16 patients, show that the proposed data-driven features outperform the traditional pharmacokinetic parameters with an area under ROC of 0.86 for LASSO-isolated PCA parameters, compared to 0.78 for pharmacokinetic parameters. This shows that our novel approach to the analysis of DCE data has the potential to improve the multiparametric MRI protocol for prostate cancer detection., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

In this article, we describe a system for detecting dominant prostate tumors, based on a combination of features extracted from a novel multi-parametric quantitative ultrasound elastography technique. The performance of the system was validated on a data-set acquired from n = 10 patients undergoing radical prostatectomy. Multi-frequency steady-state mechanical excitations were applied to each patient's prostate through the perineum and prostate tissue displacements were captured by a transrectal ultrasound system. 3D volumetric data including absolute value of tissue elasticity, strain and frequency-response were computed for each patient. Based on the combination of all extracted features, a random forest classification algorithm was used to separate cancerous regions from normal tissue, and to compute a measure of cancer probability. Registered whole mount histopathology images of the excised prostate gland were used as a ground truth of cancer distribution for classifier training. An area under receiver operating characteristic curve of 0.82 +/- 0.01 was achieved in a leave-one-patient-out cross validation. Our results show the potential of multi-parametric quantitative elastography for prostate cancer detection for the first time in a clinical setting, and justify further studies to establish whether the approach can have clinical use.

Purpose: To develop an image-based technique capable of detection and grading of prostate cancer, which combines features extracted from multiparametric MRI into a single parameter map of cancer probability., Materials and Methods: A combination of features extracted from diffusion tensor MRI and dynamic contrast enhanced MRI was used to characterize biopsy samples from 29 patients. Support vector machines were used to separate the cancerous samples from normal biopsy samples and to compute a measure of cancer probability, presented in the form of a cancer colormap. The classification results were compared with the biopsy results and the classifier was tuned to provide the largest area under the receiver operating characteristic (ROC) curve. Based solely on the tuning of the classifier on the biopsy data, cancer colormaps were also created for whole-mount histopathology slices from four radical prostatectomy patients., Results: An area under ROC curve of 0.96 was obtained on the biopsy dataset and was validated by a "leave-one-patient-out" procedure. The proposed measure of cancer probability shows a positive correlation with Gleason score. The cancer colormaps created for the histopathology patients do display the dominant tumors. The colormap accuracy increases with measured tumor area and Gleason score., Conclusion: Dynamic contrast enhanced imaging and diffusion tensor imaging, when used within the framework of supervised classification, can play a role in characterizing prostate cancer., (Copyright © 2012 Wiley Periodicals, Inc.)

C-arm fluoroscopy images are frequently used for qualitative assessment of prostate brachytherapy. Three-dimensional seed reconstruction from C-arm images is necessary for intraoperative dosimetry and quantitative assessment. Seed reconstruction requires accurately known C-arm poses. We propose to measure the C-arm rotation angles and computationally compensate for inevitable C-arm motion to compute the pose. We compensate the translational motions of a C-arm, such as oscillation, sagging and wheel motion using a three-level optimization algorithm and obviate the need for full pose tracking using external trackers or fiducials. We validated our approach on simulated and 100 clinical data sets from 10 patients and gained on average, a seed matching rate of 98.5%, projection error of 0.33 mm (STD=0.21 mm) and computation time of 19.8s per patient, which must be considered as clinically excellent results. We also show that without motion compensation the reconstruction is likely to fail., (Copyright © 2011 Elsevier B.V. All rights reserved.)

In this paper we present a high-throughput system for detecting regions of carcinoma of the prostate (CaP) in HSs from radical prostatectomies (RPs) using probabilistic pairwise Markov models (PPMMs), a novel type of Markov random field (MRF). At diagnostic resolution a digitized HS can contain 80Kx70K pixels - far too many for current automated Gleason grading algorithms to process. However, grading can be separated into two distinct steps: (1) detecting cancerous regions and (2) then grading these regions. The detection step does not require diagnostic resolution and can be performed much more quickly. Thus, we introduce a CaP detection system capable of analyzing an entire digitized whole-mount HS (2x1.75cm(2)) in under three minutes (on a desktop computer) while achieving a CaP detection sensitivity and specificity of 0.87 and 0.90, respectively. We obtain this high-throughput by tailoring the system to analyze the HSs at low resolution (8microm per pixel). This motivates the following algorithm: (Step 1) glands are segmented, (Step 2) the segmented glands are classified as malignant or benign, and (Step 3) the malignant glands are consolidated into continuous regions. The classification of individual glands leverages two features: gland size and the tendency for proximate glands to share the same class. The latter feature describes a spatial dependency which we model using a Markov prior. Typically, Markov priors are expressed as the product of potential functions. Unfortunately, potential functions are mathematical abstractions, and constructing priors through their selection becomes an ad hoc procedure, resulting in simplistic models such as the Potts. Addressing this problem, we introduce PPMMs which formulate priors in terms of probability density functions, allowing the creation of more sophisticated models. To demonstrate the efficacy of our CaP detection system and assess the advantages of using a PPMM prior instead of the Potts, we alternately incorporate both priors into our algorithm and rigorously evaluate system performance, extracting statistics from over 6000 simulations run across 40 RP specimens. Perhaps the most indicative result is as follows: at a CaP sensitivity of 0.87 the accompanying false positive rates of the system when alternately employing the PPMM and Potts priors are 0.10 and 0.20, respectively., (Copyright 2010 Elsevier B.V. All rights reserved.)

Purpose: This article provides experimental evidence to show that the time series of radiofrequency (RF) ultrasound data can be used for tissue typing. It also explores the tissue typing information in RF time series. Clinical and high-frequency ultrasound are studied., Methods: Bovine liver, pig liver, bovine muscle, and chicken breast were used in the experiments as the animal tissue types. In the proposed approach, the authors record RF echo signals backscattered from tissue, while the imaging probe and the tissue are stationary. This sequence of recorded RF data generates a time series of RF echoes for each spatial sample of the RF signal. The authors use spectral and fractal features of ultrasound RF time series averaged over a region of interest, along with feedforward neural networks for tissue typing. The experiments are repeated at ultrasound frequency of 6.6 and also 55 MHz. The effects of increasing power and frame rate are studied., Results: The methodology yielded an average two-class classification accuracy of 95.1% when ultrasound data were acquired at 6.6 MHz and 98.1% when data were collected with a high-frequency probe operating at 55 MHz. In four-class classification experiments, the recorded accuracies were 78.6% and 86.5% for low and high-frequency ultrasound data, respectively. A set of 12 texture features extracted from the B-mode image equivalents of the RF data yields an accuracy of only 77.5% in typing the analyzed tissues. An increase in acoustic power and the frame rate of ultrasound results in an improvement in classification results., Conclusions: The results of this study demonstrate that RF time series can be used for ultrasound-based tissue typing. Further investigation of the underlying physical mechanisms is necessary.

During prostate brachytherapy, C-arm flouroscopy images are used for a qualitative assessment of the procedure. Three dimensional reconstruction of the implanted seeds can be used for intraoperative dosimetry and quantitative assessment. Accurate C-arm pose estimation is necessary for 3D localization of the seeds. We propose to measure the C-arm rotation angles and computationally compensate the inevitable C-arm translational motion to estimate the pose. We compensate the oscillation, sagging and wheel motion of the C-arm using a three-level optimization algorithm, without which the reconstruction can fail. We validated our approach on simulated and 10 data sets from 5 patients and gained on average 99.1% success rate, 0.33 mm projection error and computation time of less than one minute per patient, which are clinically excellent results.

In this paper we propose a fully automatic 2D prostate segmentation algorithm using fused ultrasound (US) and elastography images. We show that the addition of information from mechanical tissue properties acquired from elastography to acoustic information from B-mode ultrasound, can improve segmentation results. Gray level edge similarity and edge continuity in both US and elastography images deform an Active Shape Model. Comparison of automatic and manual contours on 107 transverse images of the prostate show a mean absolute error of 2.6 +/- 0.9 mm and a running time of 17.9 +/- 12.2 s. These results show that the combination of the high contrast elastography images with the more detailed but low contrast US images can lead to very promising results for developing an automatic 3D segmentation algorithm.

In this study, the local and global left ventricular function are estimated by fitting three-dimensional active mesh model (3D-AMM) to the initial sparse displacement which is measured from an establishing point correspondence procedure. To evaluate the performance of the algorithm, eight image sequences were used and the results were compared with those reported by other researchers. The findings were consistent with previously published values and the clinical evidence as well. The results demonstrated the superiority of the novel strategy with respect to formerly presented algorithm reported by author et al. Furthermore, the results are comparable to the current state-of-the-art methods.

We show that vibro-elastography, an ultrasound-based method that creates images of tissue viscoelasticity contrast, can be used for visualization and segmentation of the prostate. We use MRI as the gold standard and show that VE images yield more accurate 3D volumes of the prostate gland than conventional B-mode imaging. Furthermore, we propose two novel measures characterizing the strength and continuity of edges in noisy images. These measures, as well as contrast to noise ratio, demonstrate the utility of VE as a prostate imaging modality. The results of our study show that in addition to mapping the visco-elastic properties of tissue, VE can play a central role in improving the anatomic visualization of the prostate region and become an integral component of interventional procedures such as brachytherapy.

We describe a very efficient method based on ultrasound RF time series analysis and support vector machine classification for generating probabilistic prostate cancer colormaps to augment the biopsy process. To form the RF time series, we continuously record ultrasound RF echoes backscattered from tissue while the imaging probe and the tissue are stationary in position. In an in-vitro study involving 30 prostate specimens, we show that the features extracted from RF time series are significantly more accurate and sensitive compared to two other established categories of ultrasound-based tissue typing methods. The method results in an area under ROC curve of 0.95 in 10-fold cross-validation.

This paper is the first report on the analysis of ultrasound RF echo time series acquired using high frequency ultrasound. We show that variations in the intensity of one sample of RF echo over time is correlated with tissue microstructure. To form the RF time series, a high frequency probe and a tissue sample were fixed in position and RF signals backscattered from the tissue were continuously recorded. The fractal dimension of RF time series was used as a feature for tissue classification. Feature values acquired from different areas of one tissue type were statistically similar. For animal tissues with different cellular microstructure, we successfully used the fractal dimension of RF time series to distinguish segments as small as 20 microns with accuracies as high as 98%. The results of this study demonstrate that the analysis of RF time series is a promising approach for distinguishing tissue types with different cellular microstructure.

In this paper, we demonstrate that a set of six features extracted from the discrete Fourier transform of ultrasound Radio-Frequency (RF) time series can be used to detect prostate cancer with high sensitivity and specificity. Ultrasound RF time series refer to a series of echoes received from one spatial location of tissue while the imaging probe and the tissue are fixed in position. Our previous investigations have shown that at least one feature, fractal dimension, of these signals demonstrates strong correlation with the tissue microstructure. In the current paper, six new features that represent the frequency spectrum of the RF time series have been used, in conjunction with a neural network classification approach, to detect prostate cancer in regions of tissue as small as 0.03 cm2. Based on pathology results used as gold standard, we have acquired mean accuracy of 91%, mean sensitivity of 92% and mean specificity of 90% on seven human prostates.

Abstract: Simultaneous spatial and time variations of the volume fractions of the martensite and austenite phases of the SMA elements of the hybrid composite plates due to local and instantaneous variations of the stresses have not been completely or accurately considered in the available researches. Moreover, the constitutive models proposed to date for the SMAs are mainly suitable for the global loading and unloading events and have to be modified for the local loading and unloading, and especially, the reverse loading events. In the present research, nonlinear impact analysis of laminated composite plates with embedded SMA wires is accomplished imposing some modifications to Brinson’s model to enable tracing local loading and unloading and reverse loading events and presenting a solution procedure for treating the simultaneous kinematic (strain–displacement), analysis (contact), and constitutive laws nonlinearities of the plate. The governing equations are derived based on an energy method and a finite element discretization. The local and instantaneous variations of the volume fraction of the martensite phase are considered to update the stiffness matrix of the entire plate. Different contact laws are considered for the loading and unloading phases. A comprehensive parametric study is performed to extract more practical and new conclusions. [Copyright &y& Elsevier]

Abstract: This paper presents a modification on the stair-shaped volume of fluid (VOF) advection algorithm called defined donating and accepting region (DDAR) scheme which shows the importance of the more accurate definition of donating and accepting region. The algorithm which is suitable for uniform Cartesian grids uses multi-dimensional method of cell boundary flux integration. The performance of the modified scheme presented here has been compared with the performance of a number of alternative schemes taking into account translation, rotation and shear advection tests. In some aspects, the DDAR scheme is shown to be more accurate than linear constant and flux limited schemes, and in some way comparable with the linear piecewise schemes (PLIC). Without using any geometrical information, DDAR scheme predicts flux correctly using information of cell volume fraction and its face velocities and consequently improves the performance the first order DDR schemes. [Copyright &y& Elsevier]