Showing papers by "George L. Mutter published in 2020"

Deciphering serous ovarian carcinoma histopathology and platinum response by convolutional neural networks.

Abstract: Ovarian cancer causes 151,900 deaths per year worldwide. Treatment and prognosis are primarily determined by the histopathologic interpretation in combination with molecular diagnosis. However, the relationship between histopathology patterns and molecular alterations is not fully understood, and it is difficult to predict patients’ chemotherapy response using the known clinical and histological variables. We analyzed the whole-slide histopathology images, RNA-Seq, and proteomics data from 587 primary serous ovarian adenocarcinoma patients and developed a systematic algorithm to integrate histopathology and functional omics findings and to predict patients’ response to platinum-based chemotherapy. Our convolutional neural networks identified the cancerous regions with areas under the receiver operating characteristic curve (AUCs) > 0.95 and classified tumor grade with AUCs > 0.80. Functional omics analysis revealed that expression levels of proteins participated in innate immune responses and catabolic pathways are associated with tumor grade. Quantitative histopathology analysis successfully stratified patients with different response to platinum-based chemotherapy (P = 0.003). These results indicated the potential clinical utility of quantitative histopathology evaluation in tumor cell detection and chemotherapy response prediction. The developed algorithm is easily extensible to other tumor types and treatment modalities.

A New Classification of Benign, Premalignant, and Malignant Endometrial Tissues Using Machine Learning Applied to 1413 Candidate Variables.

Abstract: Benign normal (NL), premalignant (endometrial intraepithelial neoplasia, EIN) and malignant (cancer, EMCA) endometria must be precisely distinguished for optimal management. EIN was objectively defined previously as a regression model incorporating manually traced histologic variables to predict clonal growth and cancer outcomes. Results from this early computational study were used to revise subjective endometrial precancer diagnostic criteria currently in use. We here use automated feature segmentation and updated machine learning algorithms to develop a new classification algorithm. Endometrial tissue from 148 patients was randomly separated into 72-patient training and 76-patient validation cohorts encompassing all 3 diagnostic classes. We applied image analysis software to keratin stained endometrial tissues to automatically segment whole-slide digital images into epithelium, cells, and nuclei and extract corresponding variables. A total of 1413 variables were culled to 75 based on random forest classification performance in a 3-group (NL, EIN, EMCA) model. This algorithm correctly classifies cases with 3-class error rates of 0.04 (training set) and 0.058 (validation set); and 2-class (NL vs. EIN+EMCA) error rate of 0.016 (training set) and 0 (validation set). The 4 most heavily weighted variables are surrogates of those previously identified in manual-segmentation machine learning studies (stromal and epithelial area percentages, and normalized epithelial surface lengths). Lesser weighted predictors include gland and lumen axis lengths and ratios, and individual cell measures. Automated image analysis and random forest classification algorithms can classify normal, premalignant, and malignant endometrial tissues. Highest predictive variables overlap with those discovered independently in early models based on manual segmentation.

Augmented digital microscopy for lesion analysis

Abstract: Systems and methods are provided for augmenting digital analysis of lesions. An image of tissue having a glandular epithelial component is generated. The image represents a plurality of medium-scale epithelial components. For each of a plurality of cells within the image, a representative point is identified to provide a plurality of representative points for each of the plurality of medium-scale epithelial components. For each of a subset of the plurality of medium-scale epithelial components, a graph connecting the plurality of representative points is constructed. A plurality of classification features is extracted for each of the subset of medium-scale epithelial components from the graph constructed for the medium-scale epithelial component. A clinical parameter is assigned to each medium-scale epithelial component according to the extracted plurality of classification features.