From mouse to human: cellular morphometric subtype learned from mouse mammary tumors provides prognostic value in human breast cancer

Mouse models of cancer provide a powerful tool for investigating all aspects of cancer biology. In this study, we used our recently developed machine learning approach to identify the cellular morphometric biomarkers (CMB) from digital images of hematoxylin and eosin (H&E) micrographs of orthotopic Trp53-null mammary tumors (n = 154) and to discover the corresponding cellular morphometric subtypes (CMS). Of the two CMS identified, CMS-2 was significantly associated with shorter survival (p = 0.0084). We then evaluated the learned CMB and corresponding CMS model in MMTV-Erbb2 transgenic mouse mammary tumors (n = 53) in which CMS-2 was significantly correlated with the presence of metastasis (p = 0.004). We next evaluated the mouse CMB and CMS model on The Cancer Genome Atlas breast cancer (TCGA-BRCA) cohort (n = 1017). Kaplan–Meier analysis showed significantly shorter overall survival (OS) of CMS-2 patients compared to CMS-1 patients (p = 0.024) and added significant prognostic value in multi-variable analysis of clinical and molecular factors, namely, age, pathological stage, and PAM50 molecular subtype. Thus, application of CMS to digital images of routine workflow H&E preparations can provide unbiased biological stratification to inform patient care.This work was supported by the Department of Defense (DoD)BCRP: BC190820 (J-HM); and the National Cancer Institute (NCI) at the National Institutes of Health (NIH): R01CA184476 (HC). Lawrence Berkeley National Laboratory (LBNL) is a multi-program national laboratory operated by the University of California for the DOE under contract DE AC02-05CH1123

Patch-based Convolutional Neural Network for Whole Slide Tissue Image Classification

Convolutional Neural Networks (CNN) are state-of-the-art models for many image classification tasks. However, to recognize cancer subtypes automatically, training a CNN on gigapixel resolution Whole Slide Tissue Images (WSI) is currently computationally impossible. The differentiation of cancer subtypes is based on cellular-level visual features observed on image patch scale. Therefore, we argue that in this situation, training a patch-level classifier on image patches will perform better than or similar to an image-level classifier. The challenge becomes how to intelligently combine patch-level classification results and model the fact that not all patches will be discriminative. We propose to train a decision fusion model to aggregate patch-level predictions given by patch-level CNNs, which to the best of our knowledge has not been shown before. Furthermore, we formulate a novel Expectation-Maximization (EM) based method that automatically locates discriminative patches robustly by utilizing the spatial relationships of patches. We apply our method to the classification of glioma and non-small-cell lung carcinoma cases into subtypes. The classification accuracy of our method is similar to the inter-observer agreement between pathologists. Although it is impossible to train CNNs on WSIs, we experimentally demonstrate using a comparable non-cancer dataset of smaller images that a patch-based CNN can outperform an image-based CNN

A Survey on Deep Learning in Medical Image Analysis

Deep learning algorithms, in particular convolutional networks, have rapidly become a methodology of choice for analyzing medical images. This paper reviews the major deep learning concepts pertinent to medical image analysis and summarizes over 300 contributions to the field, most of which appeared in the last year. We survey the use of deep learning for image classification, object detection, segmentation, registration, and other tasks and provide concise overviews of studies per application area. Open challenges and directions for future research are discussed.Comment: Revised survey includes expanded discussion section and reworked introductory section on common deep architectures. Added missed papers from before Feb 1st 201