Curvelet-Based Texture Classification in Computerized Critical Gleason Grading of Prostate Cancer Histological Images

Classical multi-resolution image processing using wavelets provides an efficient analysis of image characteristics represented in terms of pixel-based singularities such as connected edge pixels of objects and texture elements given by the pixel intensity statistics. Curvelet transform is a recently developed approach based on curved singularities that provides a more sparse representation for a variety of directional multi-resolution image processing tasks such as denoising and texture analysis. The objective of this research is to develop a multi-class classifier for the automated classification of Gleason patterns of prostate cancer histological images with the utilization of curvelet-based texture analysis. This problem of computer-aided recognition of four pattern classes between Gleason Score 6 (primary Gleason grade 3 plus secondary Gleason grade 3) and Gleason Score 8 (both primary and secondary grades 4) is of critical importance affecting treatment decision and patients’ quality of life. Multiple spatial sampling within each histological image is examined through the curvelet transform, the significant curvelet coefficient at each location of an image patch is obtained by maximization with respect to all curvelet orientations at a given location which represents the apparent curved-based singularity such as a short edge segment in the image structure. This sparser representation reduces greatly the redundancy in the original set of curvelet coefficients. The statistical textural features are extracted from these curvelet coefficients at multiple scales. We have designed a 2-level 4-class classification scheme, attempting to mimic the human expert’s decision process. It consists of two Gaussian kernel support vector machines, one support vector machine in each level and each is incorporated with a voting mechanism from classifications of multiple windowed patches in an image to reach the final decision for the image. At level 1, the support vector machine with voting is trained to ascertain the classification of Gleason grade 3 and grade 4, thus Gleason score 6 and score 8, by unanimous votes to one of the two classes, while the mixture voting inside the margin between decision boundaries will be assigned to the third class for consideration at level 2. The support vector machine in level 2 with supplemental features is trained to classify an image patch to Gleason grade 3+4 or 4+3 and the majority decision from multiple patches to consolidate the two-class discrimination of the image within Gleason score 7, or else, assign to an Indecision category. The developed tree classifier with voting from sampled image patches is distinct from the traditional voting by multiple machines. With a database of TMA prostate histological images from Urology/Pathology Laboratory of the Johns Hopkins Medical Center, the classifier using curvelet-based statistical texture features for recognition of 4-class critical Gleason scores was successfully trained and tested achieving a remarkable performance with 97.91% overall 4-class validation accuracy and 95.83% testing accuracy. This lends to an expectation of more testing and further improvement toward a plausible practical implementation

Making sense out of massive data by going beyond differential expression

With the rapid growth of publicly available high-throughput transcriptomic data, there is increasing recognition that large sets of such data can be mined to better understand disease states and mechanisms. Prior gene expression analyses, both large and small, have been dichotomous in nature, in which phenotypes are compared using clearly defined controls. Such approaches may require arbitrary decisions about what are considered “normal” phenotypes, and what each phenotype should be compared to. Instead, we adopt a holistic approach in which we characterize phenotypes in the context of a myriad of tissues and diseases. We introduce scalable methods that associate expression patterns to phenotypes in order both to assign phenotype labels to new expression samples and to select phenotypically meaningful gene signatures. By using a nonparametric statistical approach, we identify signatures that are more precise than those from existing approaches and accurately reveal biological processes that are hidden in case vs. control studies. Employing a comprehensive perspective on expression, we show how metastasized tumor samples localize in the vicinity of the primary site counterparts and are overenriched for those phenotype labels. We find that our approach provides insights into the biological processes that underlie differences between tissues and diseases beyond those identified by traditional differential expression analyses. Finally, we provide an online resource (http://concordia.csail.mit.edu) for mapping users’ gene expression samples onto the expression landscape of tissue and disease

Automated evaluation of radiodensities in a digitized mammogram database using local contrast estimation

Mammographic radiodensity is one of the strongest risk factors for developing breast cancer and there exists an urgent need to develop automated methods for predicting this marker. Previous attempts for automatically identifying and quantifying radiodense tissue in digitized mammograms have fallen short of the ideal. Many algorithms require significant heuristic parameters to be evaluated and set for predicting radiodensity. Many others have not demonstrated the efficacy of their techniques with a sufficient large and diverse patient database. This thesis has attempted to address both of these drawbacks in previous work. Novel automated digital image processing algorithms are proposed that have demonstrated the ability to rapidly sift through digitized mammogram databases for accurately estimating radiodensity. A judicious combination of point-processing, statistical, neural and contrast enhancement techniques have been employed for addressing this formidable problem. The algorithms have been developed and exercised using over 700 mammograms obtained from multiple age and ethnic groups and digitized using more than one type of X-ray digitizer. The automated algorithms developed in this thesis have been validated by comparing the estimation results using 40 of these mammograms with those predicted by a previously established manual segmentation technique. The automated algorithms developed in this thesis show considerable promise to be extremely useful in epidemiological studies when correlating other behavioral and genetic risk factors with mammographic radiodensity