Prediction of Heart Transplant Rejection Using Histopathological Whole-Slide Imaging.

Abstract

Endomyocardial biopsies are the current gold standard for monitoring heart transplant patients for signs of cardiac allograft rejection. Manually analyzing the acquired tissue samples can be costly, time-consuming, and subjective. Computer-aided diagnosis, using digitized whole-slide images, has been used to classify the presence and grading of diseases such as brain tumors and breast cancer, and we expect it can be used for prediction of cardiac allograft rejection. In this paper, we first create a pipeline to normalize and extract pixel-level and object-level features from histopathological whole-slide images of endomyocardial biopsies. Then, we develop a two-stage classification algorithm, where we first cluster individual tiles and then use the frequency of tiles in each cluster for classification of each whole-slide image. Our results show that the addition of an unsupervised clustering step leads to higher classification accuracy, as well as the importance of object-level features based on the pathophysiology of rejection. Future expansion of this study includes the development of a multiclass classification pipeline for subtypes and grades of cardiac allograft rejection.