Yue Joseph Wang

Computerized radiographic mass detection. I. Lesion site selection by morphological enhancement and contextual segmentation

This paper presents a statistical model supported approach for enhanced segmentation and extraction of suspicious mass areas from mammographic images. With an appropriate statistical description of various discriminate characteristics of both true and false candidates from the localized areas, an improved mass detection may be achieved in computer-assisted diagnosis (CAD). In this study, one type of morphological operation is derived to enhance disease patterns of suspected masses by cleaning up unrelated background clutters, and a model-based image segmentation is performed to localize the suspected mass areas using a stochastic relaxation labeling scheme. We discuss the importance of model selection when a finite generalized Gaussian mixture is employed, and use the information theoretic criteria to determine the optimal model structure and parameters. Examples are presented to show the effectiveness of the proposed methods on mass lesion enhancement and segmentation when applied to mammographical images. Experimental results demonstrate that the proposed method achieves a very satisfactory performance as a preprocessing procedure for mass detection in CAD.

Quantification and segmentation of brain tissues from MR images: a probabilistic neural network approach

This paper presents a probabilistic neural network based technique for unsupervised quantification and segmentation of brain tissues from magnetic resonance images. It is shown that this problem can be solved by distribution learning and relaxation labeling, resulting in an efficient method that may be particularly useful in quantifying and segmenting abnormal brain tissues where the number of tissue types is unknown and the distributions of tissue types heavily overlap. The new technique uses suitable statistical models for both the pixel and context images and formulates the problem in terms of model-histogram fitting and global consistency labeling. The quantification is achieved by probabilistic self-organizing mixtures and the segmentation by a probabilistic constraint relaxation network. The experimental results show the efficient and robust performance of the new algorithm and that it outperforms the conventional classification based approaches.

Differential dependency network analysis to identify condition-specific topological changes in biological networks

MOTIVATION Significant efforts have been made to acquire data under different conditions and to construct static networks that can explain various gene regulation mechanisms. However, gene regulatory networks are dynamic and condition-specific; under different conditions, networks exhibit different regulation patterns accompanied by different transcriptional network topologies. Thus, an investigation on the topological changes in transcriptional networks can facilitate the understanding of cell development or provide novel insights into the pathophysiology of certain diseases, and help identify the key genetic players that could serve as biomarkers or drug targets. RESULTS Here, we report a differential dependency network (DDN) analysis to detect statistically significant topological changes in the transcriptional networks between two biological conditions. We propose a local dependency model to represent the local structures of a network by a set of conditional probabilities. We develop an efficient learning algorithm to learn the local dependency model using the Lasso technique. A permutation test is subsequently performed to estimate the statistical significance of each learned local structure. In testing on a simulation dataset, the proposed algorithm accurately detected all the genes with network topological changes. The method was then applied to the estrogen-dependent T-47D estrogen receptor-positive (ER+) breast cancer cell line datasets and human and mouse embryonic stem cell datasets. In both experiments using real microarray datasets, the proposed method produced biologically meaningful results. We expect DDN to emerge as an important bioinformatics tool in transcriptional network analyses. While we focus specifically on transcriptional networks, the DDN method we introduce here is generally applicable to other biological networks with similar characteristics. AVAILABILITY The DDN MATLAB toolbox and experiment data are available at http://www.cbil.ece.vt.edu/software.htm.

A Convex Analysis Framework for Blind Separation of Non-Negative Sources

This paper presents a new framework for blind source separation (BSS) of non-negative source signals. The proposed framework, referred herein to as convex analysis of mixtures of non-negative sources (CAMNS), is deterministic requiring no source independence assumption, the entrenched premise in many existing (usually statistical) BSS frameworks. The development is based on a special assumption called local dominance. It is a good assumption for source signals exhibiting sparsity or high contrast, and thus is considered realistic to many real-world problems such as multichannel biomedical imaging. Under local dominance and several standard assumptions, we apply convex analysis to establish a new BSS criterion, which states that the source signals can be perfectly identified (in a blind fashion) by finding the extreme points of an observation-constructed polyhedral set. Methods for fulfilling the CAMNS criterion are also derived, using either linear programming or simplex geometry. Simulation results on several data sets are presented to demonstrate the efficacy of the proposed method over several other reported BSS methods.

A multiple circular path convolution neural network system for detection of mammographic masses

A multiple circular path convolution neural network (MCPCNN) architecture specifically designed for the analysis of tumor and tumor-like structures has been constructed. We first divided each suspected tumor area into sectors and computed the defined mass features for each sector independently. These sector features were used on the input layer and were coordinated by convolution kernels of different sizes that propagated signals to the second layer in the neural network system. The convolution kernels were trained, as required, by presenting the training cases to the neural network. In this study, randomly selected mammograms were processed by a dual morphological enhancement technique. Radiodense areas were isolated and were delineated using a region growing algorithm. The boundary of each region of interest was then divided into 36 sectors using 36 equi-angular dividers radiated from the center of the region. A total of 144 Breast Imaging-Reporting and Data System-based features (i.e., four features per sector for 36 sectors) were computed as input values for the evaluation of this newly invented neural network system. The overall performance was 0.78-0.80 for the areas (A/sub z/) under the receiver operating characteristic curves using the conventional feed-forward neural network in the detection of mammographic masses. The performance was markedly improved with A/sub z/ values ranging from 0.84 to 0.89 using the MCPCNN. This paper does not intend to claim the best mass detection system. Instead it reports a potentially better neural network structure for analyzing a set of the mass features defined by an investigator.

Nonnegative Least-Correlated Component Analysis for Separation of Dependent Sources by Volume Maximization

Although significant efforts have been made in developing nonnegative blind source separation techniques, accurate separation of positive yet dependent sources remains a challenging task. In this paper, a joint correlation function of multiple signals is proposed to reveal and confirm that the observations after nonnegative mixing would have higher joint correlation than the original unknown sources. Accordingly, a new nonnegative least-correlated component analysis (nLCA) method is proposed to design the unmixing matrix by minimizing the joint correlation function among the estimated nonnegative sources. In addition to a closed-form solution for unmixing two mixtures of two sources, the general algorithm of nLCA for the multisource case is developed based on an iterative volume maximization (IVM) principle and linear programming. The source identifiability and required conditions are discussed and proven. The proposed nLCA algorithm, denoted by nLCA-IVM, is evaluated with both simulation data and real biomedical data to demonstrate its superior performance over several existing benchmark methods.

Probabilistic principal component subspaces: a hierarchical finite mixture model for data visualization

Visual exploration has proven to be a powerful tool for multivariate data mining and knowledge discovery. Most visualization algorithms aim to find a projection from the data space down to a visually perceivable rendering space. To reveal all of the interesting aspects of multimodal data sets living in a high-dimensional space, a hierarchical visualization algorithm is introduced which allows the complete data set to be visualized at the top level, with clusters and subclusters of data points visualized at deeper levels. The methods involve hierarchical use of standard finite normal mixtures and probabilistic principal component projections, whose parameters are estimated using the expectation-maximization and principal component neural networks under the information theoretic criteria.We demonstrate the principle of the approach on several multimodal numerical data sets, and we then apply the method to the visual explanation in computer-aided diagnosis for breast cancer detection from digital mammograms.

Iterative normalization of cDNA microarray data

Describes an approach to normalizing microarray expression data. The novel feature is to unify the tasks of estimating normalization coefficients and identifying the control gene set. Unification is realized by constructing a window function over the scatter plot defining the subset of constantly expressed genes and by affecting optimization using an iterative procedure. The structure of window function gates contributions to the control gene set used to estimate normalization coefficients. This window measures the consistency of the matched neighborhoods in the scatter plot and provides a means of rejecting control gene outliers. The recovery of normalizational regression and control gene selection are interleaved and are realized by applying coupled operations to the mean square error function. In this way, the two processes bootstrap one another. We evaluate the technique on real microarray data from breast cancer cell lines and complement the experiment with a data cluster visualization study.

Computerized radiographic mass detection. II. Decision support by featured database visualization and modular neural networks

For pt.I see ibid., vol.20, no.4, p.289-301 (2001). Based on the enhanced segmentation of suspicious mass areas, further development of computer-assisted mass detection may be decomposed into three distinctive machine learning tasks: (1) construction of the featured knowledge database; (2) mapping of the classified and/or unclassified data points in the datahase; and (3) development of an intelligent user interface. A decision support system may then be constructed as a complementary machine observer that should enhance the radiologists performance in mass detection, We adopt a mathematical feature extraction procedure to construct the featured knowledge database from all the suspicious mass sites localized by the enhanced segmentation. The optimal mapping of the data points is then obtained by learning the generalized normal mixtures and decision boundaries, where a probabilistic modular neural network (PMNN) is developed to carry out both soft and hard clustering. A visual explanation of the decision making is further invented as a decision support, based on an interactive visualization hierarchy through the probabilistic principal component projections of the knowledge database and the localized optimal displays of the retrieved raw data. A prototype system is developed and pilot tested to demonstrate the applicability of this framework to mammographic mass detection.

Tissue-Specific Compartmental Analysis for Dynamic Contrast-Enhanced MR Imaging of Complex Tumors

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provides a noninvasive method for evaluating tumor vasculature patterns based on contrast accumulation and washout. However, due to limited imaging resolution and tumor tissue heterogeneity, tracer concentrations at many pixels often represent a mixture of more than one distinct compartment. This pixel-wise partial volume effect (PVE) would have profound impact on the accuracy of pharmacokinetics studies using existing compartmental modeling (CM) methods. We, therefore, propose a convex analysis of mixtures (CAM) algorithm to explicitly mitigate PVE by expressing the kinetics in each pixel as a nonnegative combination of underlying compartments and subsequently identifying pure volume pixels at the corners of the clustered pixel time series scatter plot simplex. The algorithm is supported theoretically by a well-grounded mathematical framework and practically by plug-in noise filtering and normalization preprocessing. We demonstrate the principle and feasibility of the CAM-CM approach on realistic synthetic data involving two functional tissue compartments, and compare the accuracy of parameter estimates obtained with and without PVE elimination using CAM or other relevant techniques. Experimental results show that CAM-CM achieves a significant improvement in the accuracy of kinetic parameter estimation. We apply the algorithm to real DCE-MRI breast cancer data and observe improved pharmacokinetic parameter estimation, separating tumor tissue into regions with differential tracer kinetics on a pixel-by-pixel basis and revealing biologically plausible tumor tissue heterogeneity patterns. This method combines the advantages of multivariate clustering, convex geometry analysis, and compartmental modeling approaches. The open-source MATLAB software of CAM-CM is publicly available from the Web.