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In recent years, deep learning has successfully been applied to automate a wide variety of tasks in diagnostic histopathology. However, fast and reliable localization of small-scale regions-of-interest (ROI) has remained a key challenge, as discriminative morphologic features often occupy only a small fraction of a gigapixel-scale whole-slide image (WSI). In this paper, we propose a sparse WSI analysis method for the rapid identification of high-power ROI for WSI-level classification. We develop an evaluation framework inspired by the early classification literature, in order to quantify the tradeoff between diagnostic performance and inference time for sparse analytic approaches. We test our method on a common but time-consuming task in pathology - that of diagnosing gastric intestinal metaplasia (GIM) on hematoxylin and eosin (H&E)-stained slides from endoscopic biopsy specimens. GIM is a well-known precursor lesion along the pathway to development of gastric cancer. We performed a thorough evaluation of the performance and inference time of our approach on a test set of GIM-positive and GIM-negative WSI, finding that our method successfully detects GIM in all positive WSI, with a WSI-level classification area under the receiver operating characteristic curve (AUC) of 0.98 and an average precision (AP) of 0.95. Furthermore, we show that our method can attain these metrics in under one minute on a standard CPU. Our results are applicable toward the goal of developing neural networks that can easily be deployed in clinical settings to support pathologists in quickly localizing and diagnosing small-scale morphologic features in WSI.

Suboptimal generalization of machine learning models on unseen data is a key challenge which hampers the clinical applicability of such models to medical imaging. Although various methods such as domain adaptation and domain generalization have evolved to combat this challenge, learning robust and generalizable representations is core to medical image understanding, and continues to be a problem. Here, we propose STRAP (Style TRansfer Augmentation for histoPathology), a form of data augmentation based on random style transfer from non-medical style source such as artistic paintings, for learning domain-agnostic visual representations in computational pathology. Style transfer replaces the low-level texture content of an image with the uninformative style of randomly selected style source image, while preserving the original high-level semantic content. This improves robustness to domain shift and can be used as a simple yet powerful tool for learning domain-agnostic representations. We demonstrate that STRAP leads to state-of-the-art performance, particularly in the presence of domain shifts, on two particular classification tasks in computational pathology.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Whole-slide imaging which is a method of scanning glass slides have been employed for diagnosis of HCC. Using high resolution Whole-slide images is infeasible for Convolutional Neural Network applications. Hence tiling the Whole-slide images is a common methodology for assigning Convolutional Neural Networks for classification and segmentation. Determination of the tile size affects the performance of the algorithms since small field of view can not capture the information on a larger scale and large field of view can not capture the information on a cellular scale. In this work, the effect of tile size on performance for classification problem is analysed. In addition, Multi Field of View CNN is assigned for taking advantage of the information provided by different tile sizes and Attention CNN is assigned for giving the capability of voting most contributing tile size. It is found that employing more than one tile size significantly increases the performance of the classification by 3.97% and both algorithms are found successful over the algorithm which uses only one tile size., Comment: This paper has been withdrawn by the authors due to need for heavy revise

While artificial intelligence (AI) algorithms continue to rival human performance on a variety of clinical tasks, the question of how best to incorporate these algorithms into clinical workflows remains relatively unexplored. We investigated how AI can affect pathologist performance on the task of differentiating between two subtypes of primary liver cancer, hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). We developed an AI diagnostic assistant using a deep learning model and evaluated its effect on the diagnostic performance of eleven pathologists with varying levels of expertise. Our deep learning model achieved an accuracy of 0.885 on an internal validation set of 26 slides and an accuracy of 0.842 on an independent test set of 80 slides. Despite having high accuracy on a hold out test set, the diagnostic assistant did not significantly improve performance across pathologists (p-value: 0.184, OR: 1.287 (95% CI 0.886, 1.871)). Model correctness was observed to significantly bias the pathologist decisions. When the model was correct, assistance significantly improved accuracy across all pathologist experience levels and for all case difficulty levels (p-value: < 0.001, OR: 4.289 (95% CI 2.360, 7.794)). When the model was incorrect, assistance significantly decreased accuracy across all 11 pathologists and for all case difficulty levels (p-value < 0.001, OR: 0.253 (95% CI 0.126, 0.507)). Our results highlight the challenges of translating AI models to the clinical setting, especially for difficult subspecialty tasks such as tumor classification. In particular, they suggest that incorrect model predictions could strongly bias an expert's diagnosis, an important factor to consider when designing medical AI-assistance systems., Comment: Machine Learning for Health (ML4H) at NeurIPS 2019 - Extended Abstract

Different convolutional neural network (CNN) models have been tested for their application in histological image analyses. However, these models are prone to overfitting due to their large parameter capacity, requiring more data or valuable computational resources for model training. Given these limitations, we introduced a novel architecture (termed PlexusNet). We utilized 310 Hematoxylin and Eosin stained (H&E) annotated histological images of prostate cancer cases from TCGA-PRAD and Stanford University and 398 H&E whole slides images from the Camelyon 2016 challenge. PlexusNet-architecture -derived models were compared to models derived from several existing "state of the art" architectures. We measured discrimination accuracy, calibration, and clinical utility. An ablation study was conducted to study the effect of each component of PlexusNet on model performance. A well-fitted PlexusNet-based model delivered comparable classification performance (AUC: 0.963) in distinguishing prostate cancer from healthy tissues, although it was at least 23 times smaller, had a better model calibration and clinical utility than the comparison models. A separate smaller PlexusNet model accurately detected slides with breast cancer metastases (AUC: 0.978); it helped reduce the slide number to examine by 43.8% without consequences, although its parameter capacity was 200 times smaller than ResNet18. We found that the partitioning of the development set influences the model calibration for all models. However, with PlexusNet architecture, we could achieve comparable well-calibrated models trained on different partitions. In conclusion, PlexusNet represents a novel model architecture for histological image analysis that achieves classification performance comparable to other models while providing orders-of-magnitude parameter reduction.