Deep learning for digitized histology image analysis

“Cervical cancer is the fourth most frequent cancer that affects women worldwide. Assessment of cervical intraepithelial neoplasia (CIN) through histopathology remains as the standard for absolute determination of cancer. The examination of tissue samples under a microscope requires considerable time and effort from expert pathologists. There is a need to design an automated tool to assist pathologists for digitized histology slide analysis. Pre-cervical cancer is generally determined by examining the CIN which is the growth of atypical cells from the basement membrane (bottom) to the top of the epithelium. It has four grades, including: Normal, CIN1, CIN2, and CIN3. In this research, different facets of an automated digitized histology epithelium assessment pipeline have been explored to mimic the pathologist diagnostic approach. The entire pipeline from slide to epithelium CIN grade has been designed and developed using deep learning models and imaging techniques to analyze the whole slide image (WSI). The process is as follows: 1) identification of epithelium by filtering the regions extracted from a low-resolution image with a binary classifier network; 2) epithelium segmentation; 3) deep regression for pixel-wise segmentation of epithelium by patch-based image analysis; 4) attention-based CIN classification with localized sequential feature modeling. Deep learning-based nuclei detection by superpixels was performed as an extension of our research. Results from this research indicate an improved performance of CIN assessment over state-of-the-art methods for nuclei segmentation, epithelium segmentation, and CIN classification, as well as the development of a prototype WSI-level tool”--Abstract, page iv

Data fusion techniques for biomedical informatics and clinical decision support

Data fusion can be used to combine multiple data sources or modalities to facilitate enhanced visualization, analysis, detection, estimation, or classification. Data fusion can be applied at the raw-data, feature-based, and decision-based levels. Data fusion applications of different sorts have been built up in areas such as statistics, computer vision and other machine learning aspects. It has been employed in a variety of realistic scenarios such as medical diagnosis, clinical decision support, and structural health monitoring. This dissertation includes investigation and development of methods to perform data fusion for cervical cancer intraepithelial neoplasia (CIN) and a clinical decision support system. The general framework for these applications includes image processing followed by feature development and classification of the detected region of interest (ROI). Image processing methods such as k-means clustering based on color information, dilation, erosion and centroid locating methods were used for ROI detection. The features extracted include texture, color, nuclei-based and triangle features. Analysis and classification was performed using feature- and decision-level data fusion techniques such as support vector machine, statistical methods such as logistic regression, linear discriminant analysis and voting algorithms --Abstract, page iv

Uterine cervical cancer histology image feature extraction and classification

The current study presents the investigation and development of image processing, computational intelligence, fuzzy logic, and statistical techniques for different types of data fusion for a varied range of applications. Raw data, decision level and feature level fusion techniques are explored for detection of pre Cervical cancer (CIN) grades from digital histology images of the cervical epithelium tissues. In previous research, an automated, localized, fusion-based approach was investigated for classifying squamous epithelium into Normal, CIN1, CIN2, and CIN3 grades of cervical intraepithelial neoplasia (CIN) based on image analysis. The approach included medial axis determination, vertical segment partitioning as medial axis orthogonal cuts, individual vertical segment feature extraction and classification, and image-based classification using a voting scheme to fuse the vertical segment CIN grades. This paper presents advances in medial axis determination, epithelium atypical cell concentration feature development and a particle swarm optimization neural network and receiver operating characteristic curve technique for individual vertical segment-based classification. Combining individual vertical segment classification confidence values using a weighted sum fusion approach for image-based classification, exact grade labeling accuracy was as high as 90% for a 62-image data set --Abstract, page iii