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

MULTIRIDGELETS FOR TEXTURE ANALYSIS

Directional wavelets have orientation selectivity and thus are able to efficiently represent highly anisotropic elements such as line segments and edges. Ridgelet transform is a kind of directional multi-resolution transform and has been successful in many image processing and texture analysis applications. The objective of this research is to develop multi-ridgelet transform by applying multiwavelet transform to the Radon transform so as to attain attractive improvements. By adapting the cardinal orthogonal multiwavelets to the ridgelet transform, it is shown that the proposed cardinal multiridgelet transform (CMRT) possesses cardinality, approximate translation invariance, and approximate rotation invariance simultaneously, whereas no single ridgelet transform can hold all these properties at the same time. These properties are beneficial to image texture analysis. This is demonstrated in three studies of texture analysis applications. Firstly a texture database retrieval study taking a portion of the Brodatz texture album as an example has demonstrated that the CMRT-based texture representation for database retrieval performed better than other directional wavelet methods. Secondly the study of the LCD mura defect detection was based upon the classification of simulated abnormalities with a linear support vector machine classifier, the CMRT-based analysis of defects were shown to provide efficient features for superior detection performance than other competitive methods. Lastly and the most importantly, a study on the prostate cancer tissue image classification was conducted. With the CMRT-based texture extraction, Gaussian kernel support vector machines have been developed to discriminate prostate cancer Gleason grade 3 versus grade 4. Based on a limited database of prostate specimens, one classifier was trained to have remarkable test performance. This approach is unquestionably promising and is worthy to be fully developed

Computer-Aided Cancer Diagnosis and Grading via Sparse Directional Image Representations

Prostate cancer and breast cancer are the second cause of death among cancers in males and females, respectively. If not diagnosed, prostate and breast cancers can spread and metastasize to other organs and bones and make it impossible for treatment. Hence, early diagnosis of cancer is vital for patient survival. Histopathological evaluation of the tissue is used for cancer diagnosis. The tissue is taken during biopsies and stained using hematoxylin and eosin (H&E) stain. Then a pathologist looks for abnormal changes in the tissue to diagnose and grade the cancer. This process can be time-consuming and subjective. A reliable and repetitive automatic cancer diagnosis method can greatly reduce the time while producing more reliable results. The scope of this dissertation is developing computer vision and machine learning algorithms for automatic cancer diagnosis and grading methods with accuracy acceptable by the expert pathologists. Automatic image classification relies on feature representation methods. In this dissertation we developed methods utilizing sparse directional multiscale transforms - specifically shearlet transform - for medical image analysis. We particularly designed theses computer visions-based algorithms and methods to work with H&E images and MRI images. Traditional signal processing methods (e.g. Fourier transform, wavelet transform, etc.) are not suitable for detecting carcinoma cells due to their lack of directional sensitivity. However, shearlet transform has inherent directional sensitivity and multiscale framework that enables it to detect different edges in the tissue images. We developed techniques for extracting holistic and local texture features from the histological and MRI images using histogram and co-occurrence of shearlet coefficients, respectively. Then we combined these features with the color and morphological features using multiple kernel learning (MKL) algorithm and employed support vector machines (SVM) with MKL to classify the medical images. We further investigated the impact of deep neural networks in representing the medical images for cancer detection. The aforementioned engineered features have a few limitations. They lack generalizability due to being tailored to the specific texture and structure of the tissues. They are time-consuming and expensive and need prepossessing and sometimes it is difficult to extract discriminative features from the images. On the other hand, feature learning techniques use multiple processing layers and learn feature representations directly from the data. To address these issues, we have developed a deep neural network containing multiple layers of convolution, max-pooling, and fully connected layers, trained on the Red, Green, and Blue (RGB) images along with the magnitude and phase of shearlet coefficients. Then we developed a weighted decision fusion deep neural network that assigns weights on the output probabilities and update those weights via backpropagation. The final decision was a weighted sum of the decisions from the RGB, and the magnitude and the phase of shearlet networks. We used the trained networks for classification of benign and malignant H&E images and Gleason grading. Our experimental results show that our proposed methods based on feature engineering and feature learning outperform the state-of-the-art and are even near perfect (100%) for some databases in terms of classification accuracy, sensitivity, specificity, F1 score, and area under the curve (AUC) and hence are promising computer-based methods for cancer diagnosis and grading using images

Image analysis discloses differences in nuclear parameters between ERG+ and ERG- prostatic carcinomas

Prostatic carcinoma (PC) is the most frequent urologic cancer and one of the most frequent cancers in males; it is a heterogeneous disease, in terms of molecular features, morphology and prognosis. About half of cases depends on TMPRSS2-ETS translocation which leads to a production of ERG transcription factor. ERG+ and ERG– cancers seem to differ in a number of features, which could lead to an altered nuclear structure; the aim of the study was to test this hypothesis. The material consisted of total 39 PC cases, representing ERG+ and ERG–, as well as Gleason pattern 3 and 4. Filtering by color deconvolution and automatic segmentation were used, and the properly detected nuclei were manually selected. From each case fifty nuclei were obtained; then geometric features and texture parameters were assessed. The analysis of the collected data showed differences both between ERG+/ERG– and Gleason pattern 3 and 4 cases in most of the features analyzed. Our results suggest that indeed the ERG status, thus likely TMPRSS2-ETS translocation, has an impact on morphology of nuclei in PC, and their differences are evident enough to be detectable by image analysis

Cascade of classifier ensembles for reliable medical image classification

Medical image analysis and recognition is one of the most important tools in modern medicine. Different types of imaging technologies such as X-ray, ultrasonography, biopsy, computed tomography and optical coherence tomography have been widely used in clinical diagnosis for various kinds of diseases. However, in clinical applications, it is usually time consuming to examine an image manually. Moreover, there is always a subjective element related to the pathological examination of an image. This produces the potential risk of a doctor to make a wrong decision. Therefore, an automated technique will provide valuable assistance for physicians. By utilizing techniques from machine learning and image analysis, this thesis aims to construct reliable diagnostic models for medical image data so as to reduce the problems faced by medical experts in image examination. Through supervised learning of the image data, the diagnostic model can be constructed automatically. The process of image examination by human experts is very difficult to simulate, as the knowledge of medical experts is often fuzzy and not easy to be quantified. Therefore, the problem of automatic diagnosis based on images is usually converted to the problem of image classification. For the image classification tasks, using a single classifier is often hard to capture all aspects of image data distributions. Therefore, in this thesis, a classifier ensemble based on random subspace method is proposed to classify microscopic images. The multi-layer perceptrons are used as the base classifiers in the ensemble. Three types of feature extraction methods are selected for microscopic image description. The proposed method was evaluated on two microscopic image sets and showed promising results compared with the state-of-art results. In order to address the classification reliability in biomedical image classification problems, a novel cascade classification system is designed. Two random subspace based classifier ensembles are serially connected in the proposed system. In the first stage of the cascade system, an ensemble of support vector machines are used as the base classifiers. The second stage consists of a neural network classifier ensemble. Using the reject option, the images whose classification results cannot achieve the predefined rejection threshold at the current stage will be passed to the next stage for further consideration. The proposed cascade system was evaluated on a breast cancer biopsy image set and two UCI machine learning datasets, the experimental results showed that the proposed method can achieve high classification reliability and accuracy with small rejection rate. Many computer aided diagnosis systems face the problem of imbalance data. The datasets used for diagnosis are often imbalanced as the number of normal cases is usually larger than the number of the disease cases. Classifiers that generalize over the data are not the most appropriate choice in such an imbalanced situation. To tackle this problem, a novel one-class classifier ensemble is proposed. The Kernel Principle Components are selected as the base classifiers in the ensemble; the base classifiers are trained by different types of image features respectively and then combined using a product combining rule. The proposed one-class classifier ensemble is also embedded into the cascade scheme to improve classification reliability and accuracy. The proposed method was evaluated on two medical image sets. Favorable results were obtained comparing with the state-of-art results