Interpretable classification of Alzheimer’s disease pathologies with a convolutional neural network pipeline

Neuropathologists assess vast brain areas to identify diverse and subtly-differentiated morphologies. Standard semi-quantitative scoring approaches, however, are coarse-grained and lack precise neuroanatomic localization. We report a proof-of-concept deep learning pipeline identifying specific neuropathologies—amyloid plaques and cerebral amyloid angiopathy—in immunohistochemically-stained archival slides. Using automated segmentation of stained objects and a cloud-based interface, we annotated >70,000 plaque candidates from 43 whole slide images (WSIs) to train and evaluate convolutional neural networks. Networks achieved strong plaque classification on a 10-WSI hold-out set (0.993 and 0.743 areas under the receiver operating characteristic and precision recall curve, respectively). Prediction confidence maps visualized morphology distributions for WSIs at high resolution. Resulting plaque-burden scores correlated well with established semi-quantitative scores on a 30-WSI blinded hold-out. Finally, saliency mapping demonstrated that networks learned patterns agreeing with accepted pathologic features. This scalable means to augment a neuropathologist’s ability may suggest a route to neuropathologic deep phenotyping.

Automated Volumetric Intravascular Plaque Classification Using Optical Coherence Tomography

An estimated 17.5 million people died from a cardiovascular disease in 2012, representing 31 percent of all global deaths. Most acute coronary events result from rupture of the protective fibrous cap overlying an atherosclerotic plaque. The task of early identification of plaque types that can potentially rupture is, therefore, of great importance. The state-of-the-art approach to imaging blood vessels is intravascular optical coherence tomography (IVOCT). However, currently, this is an offline approach where the images are first collected and then manually analyzed an image at a time to identify regions at risk of thrombosis. This process is extremely laborious, time consuming and prone to human error. We are building a system that, when complete, will provide interactive 3D visualization of a blood vessel as an IVOCT is in progress. The visualization will highlight different plaque types and enable quick identification of regions at risk for thrombosis. In this paper, we describe our approach, focusing on machine learning methods that are a key enabling technology. Our empirical results using real OCT data show that our approach can identify different plaque types efficiently with high accuracy across multiple patients.