Machine learning methods for histopathological image analysis

Abundant accumulation of digital histopathological images has led to the increased demand for their analysis, such as computer-aided diagnosis using machine learning techniques. However, digital pathological images and related tasks have some issues to be considered. In this mini-review, we introduce the application of digital pathological image analysis using machine learning algorithms, address some problems specific to such analysis, and propose possible solutions.Comment: 23 pages, 4 figure

Bi-directional Weakly Supervised Knowledge Distillation for Whole Slide Image Classification

Computer-aided pathology diagnosis based on the classification of Whole Slide Image (WSI) plays an important role in clinical practice, and it is often formulated as a weakly-supervised Multiple Instance Learning (MIL) problem. Existing methods solve this problem from either a bag classification or an instance classification perspective. In this paper, we propose an end-to-end weakly supervised knowledge distillation framework (WENO) for WSI classification, which integrates a bag classifier and an instance classifier in a knowledge distillation framework to mutually improve the performance of both classifiers. Specifically, an attention-based bag classifier is used as the teacher network, which is trained with weak bag labels, and an instance classifier is used as the student network, which is trained using the normalized attention scores obtained from the teacher network as soft pseudo labels for the instances in positive bags. An instance feature extractor is shared between the teacher and the student to further enhance the knowledge exchange between them. In addition, we propose a hard positive instance mining strategy based on the output of the student network to force the teacher network to keep mining hard positive instances. WENO is a plug-and-play framework that can be easily applied to any existing attention-based bag classification methods. Extensive experiments on five datasets demonstrate the efficiency of WENO. Code is available at https://github.com/miccaiif/WENO.Comment: Accepted by NeurIPS 202

Cross-scale Multi-instance Learning for Pathological Image Diagnosis

Analyzing high resolution whole slide images (WSIs) with regard to information across multiple scales poses a significant challenge in digital pathology. Multi-instance learning (MIL) is a common solution for working with high resolution images by classifying bags of objects (i.e. sets of smaller image patches). However, such processing is typically performed at a single scale (e.g., 20x magnification) of WSIs, disregarding the vital inter-scale information that is key to diagnoses by human pathologists. In this study, we propose a novel cross-scale MIL algorithm to explicitly aggregate inter-scale relationships into a single MIL network for pathological image diagnosis. The contribution of this paper is three-fold: (1) A novel cross-scale MIL (CS-MIL) algorithm that integrates the multi-scale information and the inter-scale relationships is proposed; (2) A toy dataset with scale-specific morphological features is created and released to examine and visualize differential cross-scale attention; (3) Superior performance on both in-house and public datasets is demonstrated by our simple cross-scale MIL strategy. The official implementation is publicly available at https://github.com/hrlblab/CS-MIL

Automatic Emphysema Detection using Weakly Labeled HRCT Lung Images

A method for automatically quantifying emphysema regions using High-Resolution Computed Tomography (HRCT) scans of patients with chronic obstructive pulmonary disease (COPD) that does not require manually annotated scans for training is presented. HRCT scans of controls and of COPD patients with diverse disease severity are acquired at two different centers. Textural features from co-occurrence matrices and Gaussian filter banks are used to characterize the lung parenchyma in the scans. Two robust versions of multiple instance learning (MIL) classifiers, miSVM and MILES, are investigated. The classifiers are trained with the weak labels extracted from the forced expiratory volume in one minute (FEV$_1$) and diffusing capacity of the lungs for carbon monoxide (DLCO). At test time, the classifiers output a patient label indicating overall COPD diagnosis and local labels indicating the presence of emphysema. The classifier performance is compared with manual annotations by two radiologists, a classical density based method, and pulmonary function tests (PFTs). The miSVM classifier performed better than MILES on both patient and emphysema classification. The classifier has a stronger correlation with PFT than the density based method, the percentage of emphysema in the intersection of annotations from both radiologists, and the percentage of emphysema annotated by one of the radiologists. The correlation between the classifier and the PFT is only outperformed by the second radiologist. The method is therefore promising for facilitating assessment of emphysema and reducing inter-observer variability.Comment: Accepted at PLoS ON

Contrastive Deep Encoding Enables Uncertainty-aware Machine-learning-assisted Histopathology

Deep neural network models can learn clinically relevant features from millions of histopathology images. However generating high-quality annotations to train such models for each hospital, each cancer type, and each diagnostic task is prohibitively laborious. On the other hand, terabytes of training data -- while lacking reliable annotations -- are readily available in the public domain in some cases. In this work, we explore how these large datasets can be consciously utilized to pre-train deep networks to encode informative representations. We then fine-tune our pre-trained models on a fraction of annotated training data to perform specific downstream tasks. We show that our approach can reach the state-of-the-art (SOTA) for patch-level classification with only 1-10% randomly selected annotations compared to other SOTA approaches. Moreover, we propose an uncertainty-aware loss function, to quantify the model confidence during inference. Quantified uncertainty helps experts select the best instances to label for further training. Our uncertainty-aware labeling reaches the SOTA with significantly fewer annotations compared to random labeling. Last, we demonstrate how our pre-trained encoders can surpass current SOTA for whole-slide image classification with weak supervision. Our work lays the foundation for data and task-agnostic pre-trained deep networks with quantified uncertainty.Comment: 18 pages, 8 figure