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., 20× 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.

Omni-Seg: A Scale-Aware Dynamic Network for Renal Pathological Image Segmentation.

Comprehensive semantic segmentation on renal pathological images is challenging due to the heterogeneous scales of the objects. For example, on a whole slide image (WSI), the cross-sectional areas of glomeruli can be 64 times larger than that of the peritubular capillaries, making it impractical to segment both objects on the same patch, at the same scale. To handle this scaling issue, prior studies have typically trained multiple segmentation networks in order to match the optimal pixel resolution of heterogeneous tissue types. This multi-network solution is resource-intensive and fails to model the spatial relationship between tissue types. In this article, we propose the Omni-Seg network, a scale-aware dynamic neural network that achieves multi-object (six tissue types) and multi-scale (5× to 40× scale) pathological image segmentation via a single neural network. The contribution of this article is three-fold: (1) a novel scale-aware controller is proposed to generalize the dynamic neural network from single-scale to multi-scale; (2) semi-supervised consistency regularization of pseudo-labels is introduced to model the inter-scale correlation of unannotated tissue types into a single end-to-end learning paradigm; and (3) superior scale-aware generalization is evidenced by directly applying a model trained on human kidney images to mouse kidney images, without retraining. By learning from 150,000 human pathological image patches from six tissue types at three different resolutions, our approach achieved superior segmentation performance according to human visual assessment and evaluation of image-omics (i.e., spatial transcriptomics).

An Accelerated Pipeline for Multi-label Renal Pathology Image Segmentation at the Whole Slide Image Level.

Deep-learning techniques have been used widely to alleviate the labour-intensive and time-consuming manual annotation required for pixel-level tissue characterization. Our previous study introduced an efficient single dynamic network - Omni-Seg - that achieved multi-class multi-scale pathological segmentation with less computational complexity. However, the patch-wise segmentation paradigm still applies to Omni-Seg, and the pipeline is time-consuming when providing segmentation for Whole Slide Images (WSIs). In this paper, we propose an enhanced version of the Omni-Seg pipeline in order to reduce the repetitive computing processes and utilize a GPU to accelerate the model's prediction for both better model performance and faster speed. Our proposed method's innovative contribution is two-fold: (1) a Docker is released for an end-to-end slide-wise multi-tissue segmentation for WSIs; and (2) the pipeline is deployed on a GPU to accelerate the prediction, achieving better segmentation quality in less time. The proposed accelerated implementation reduced the average processing time (at the testing stage) on a standard needle biopsy WSI from 2.3 hours to 22 minutes, using 35 WSIs from the Kidney Tissue Atlas (KPMP) Datasets. The source code and the Docker have been made publicly available at https://github.com/ddrrnn123/Omni-Seg.

Cross-scale Attention Guided Multi-instance Learning for Crohn's Disease Diagnosis with Pathological Images.

Multi-instance learning (MIL) is widely used in the computer-aided interpretation of pathological Whole Slide Images (WSIs) to solve the lack of pixel-wise or patch-wise annotations. Often, this approach directly applies "natural image driven" MIL algorithms which overlook the multi-scale (i.e. pyramidal) nature of WSIs. Off-the-shelf MIL algorithms are typically deployed on a single-scale of WSIs (e.g., 20× magnification), while human pathologists usually aggregate the global and local patterns in a multi-scale manner (e.g., by zooming in and out between different magnifications). In this study, we propose a novel cross-scale attention mechanism to explicitly aggregate inter-scale interactions into a single MIL network for Crohn's Disease (CD), which is a form of inflammatory bowel disease. The contribution of this paper is two-fold: (1) a cross-scale attention mechanism is proposed to aggregate features from different resolutions with multi-scale interaction; and (2) differential multi-scale attention visualizations are generated to localize explainable lesion patterns. By training ~250,000 H&E-stained Ascending Colon (AC) patches from 20 CD patient and 30 healthy control samples at different scales, our approach achieved a superior Area under the Curve (AUC) score of 0.8924 compared with baseline models. The official implementation is publicly available at https://github.com/hrlblab/CS-MIL.