Deep Learning Predicts Biomarker Status and Discovers Related Histomorphology Characteristics for Low-Grade Glioma

Biomarker detection is an indispensable part in the diagnosis and treatment of low-grade glioma (LGG). However, current LGG biomarker detection methods rely on expensive and complex molecular genetic testing, for which professionals are required to analyze the results, and intra-rater variability is often reported. To overcome these challenges, we propose an interpretable deep learning pipeline, a Multi-Biomarker Histomorphology Discoverer (Multi-Beholder) model based on the multiple instance learning (MIL) framework, to predict the status of five biomarkers in LGG using only hematoxylin and eosin-stained whole slide images and slide-level biomarker status labels. Specifically, by incorporating the one-class classification into the MIL framework, accurate instance pseudo-labeling is realized for instance-level supervision, which greatly complements the slide-level labels and improves the biomarker prediction performance. Multi-Beholder demonstrates superior prediction performance and generalizability for five LGG biomarkers (AUROC=0.6469-0.9735) in two cohorts (n=607) with diverse races and scanning protocols. Moreover, the excellent interpretability of Multi-Beholder allows for discovering the quantitative and qualitative correlations between biomarker status and histomorphology characteristics. Our pipeline not only provides a novel approach for biomarker prediction, enhancing the applicability of molecular treatments for LGG patients but also facilitates the discovery of new mechanisms in molecular functionality and LGG progression.

Domain generalization across tumor types, laboratories, and species -- insights from the 2022 edition of the Mitosis Domain Generalization Challenge

Recognition of mitotic figures in histologic tumor specimens is highly relevant to patient outcome assessment. This task is challenging for algorithms and human experts alike, with deterioration of algorithmic performance under shifts in image representations. Considerable covariate shifts occur when assessment is performed on different tumor types, images are acquired using different digitization devices, or specimens are produced in different laboratories. This observation motivated the inception of the 2022 challenge on MItosis Domain Generalization (MIDOG 2022). The challenge provided annotated histologic tumor images from six different domains and evaluated the algorithmic approaches for mitotic figure detection provided by nine challenge participants on ten independent domains. Ground truth for mitotic figure detection was established in two ways: a three-expert consensus and an independent, immunohistochemistry-assisted set of labels. This work represents an overview of the challenge tasks, the algorithmic strategies employed by the participants, and potential factors contributing to their success. With an $F_1$ score of 0.764 for the top-performing team, we summarize that domain generalization across various tumor domains is possible with today's deep learning-based recognition pipelines. When assessed against the immunohistochemistry-assisted reference standard, all methods resulted in reduced recall scores, but with only minor changes in the order of participants in the ranking.

A Localization-to-Segmentation Framework for Automatic Tumor Segmentation in Whole-Body PET/CT Images

Fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with computed tomography (CT) is considered the primary solution for detecting some cancers, such as lung cancer and melanoma. Automatic segmentation of tumors in PET/CT images can help reduce doctors' workload, thereby improving diagnostic quality. However, precise tumor segmentation is challenging due to the small size of many tumors and the similarity of high-uptake normal areas to the tumor regions. To address these issues, this paper proposes a localization-to-segmentation framework (L2SNet) for precise tumor segmentation. L2SNet first localizes the possible lesions in the lesion localization phase and then uses the location cues to shape the segmentation results in the lesion segmentation phase. To further improve the segmentation performance of L2SNet, we design an adaptive threshold scheme that takes the segmentation results of the two phases into consideration. The experiments with the MICCAI 2023 Automated Lesion Segmentation in Whole-Body FDG-PET/CT challenge dataset show that our method achieved a competitive result and was ranked in the top 7 methods on the preliminary test set. Our work is available at: https://github.com/MedCAI/L2SNet.

Self-Supervised Scalable Deep Compressed Sensing

Compressed sensing (CS) is a promising tool for reducing sampling costs. Current deep neural network (NN)-based CS methods face challenges in collecting labeled measurement-ground truth (GT) data and generalizing to real applications. This paper proposes a novel $\mathbf{S}$elf-supervised s$\mathbf{C}$alable deep CS method, comprising a $\mathbf{L}$earning scheme called $\mathbf{SCL}$ and a family of $\mathbf{Net}$works named $\mathbf{SCNet}$, which does not require GT and can handle arbitrary sampling ratios and matrices once trained on a partial measurement set. Our SCL contains a dual-domain loss and a four-stage recovery strategy. The former encourages a cross-consistency on two measurement parts and a sampling-reconstruction cycle-consistency regarding arbitrary ratios and matrices to maximize data/information utilization. The latter can progressively leverage common signal prior in external measurements and internal characteristics of test samples and learned NNs to improve accuracy. SCNet combines the explicit guidance from optimization algorithms with implicit regularization from advanced NN blocks to learn a collaborative signal representation. Our theoretical analyses and experiments on simulated and real captured data, covering 1-/2-/3-D natural and scientific signals, demonstrate the effectiveness, superior performance, flexibility, and generalization ability of our method over existing self-supervised methods and its significant potential in competing against state-of-the-art supervised methods.

HVTSurv: Hierarchical Vision Transformer for Patient-Level Survival Prediction from Whole Slide Image

Survival prediction based on whole slide images (WSIs) is a challenging task for patient-level multiple instance learning (MIL). Due to the vast amount of data for a patient (one or multiple gigapixels WSIs) and the irregularly shaped property of WSI, it is difficult to fully explore spatial, contextual, and hierarchical interaction in the patient-level bag. Many studies adopt random sampling pre-processing strategy and WSI-level aggregation models, which inevitably lose critical prognostic information in the patient-level bag. In this work, we propose a hierarchical vision Transformer framework named HVTSurv, which can encode the local-level relative spatial information, strengthen WSI-level context-aware communication, and establish patient-level hierarchical interaction. Firstly, we design a feature pre-processing strategy, including feature rearrangement and random window masking. Then, we devise three layers to progressively obtain patient-level representation, including a local-level interaction layer adopting Manhattan distance, a WSI-level interaction layer employing spatial shuffle, and a patient-level interaction layer using attention pooling. Moreover, the design of hierarchical network helps the model become more computationally efficient. Finally, we validate HVTSurv with 3,104 patients and 3,752 WSIs across 6 cancer types from The Cancer Genome Atlas (TCGA). The average C-Index is 2.50-11.30% higher than all the prior weakly supervised methods over 6 TCGA datasets. Ablation study and attention visualization further verify the superiority of the proposed HVTSurv. Implementation is available at: https://github.com/szc19990412/HVTSurv.

Breast Cancer Immunohistochemical Image Generation: a Benchmark Dataset and Challenge Review

For invasive breast cancer, immunohistochemical (IHC) techniques are often used to detect the expression level of human epidermal growth factor receptor-2 (HER2) in breast tissue to formulate a precise treatment plan. From the perspective of saving manpower, material and time costs, directly generating IHC-stained images from hematoxylin and eosin (H&E) stained images is a valuable research direction. Therefore, we held the breast cancer immunohistochemical image generation challenge, aiming to explore novel ideas of deep learning technology in pathological image generation and promote research in this field. The challenge provided registered H&E and IHC-stained image pairs, and participants were required to use these images to train a model that can directly generate IHC-stained images from corresponding H&E-stained images. We selected and reviewed the five highest-ranking methods based on their PSNR and SSIM metrics, while also providing overviews of the corresponding pipelines and implementations. In this paper, we further analyze the current limitations in the field of breast cancer immunohistochemical image generation and forecast the future development of this field. We hope that the released dataset and the challenge will inspire more scholars to jointly study higher-quality IHC-stained image generation.

Progressive Content-aware Coded Hyperspectral Compressive Imaging

Hyperspectral imaging plays a pivotal role in a wide range of applications, like remote sensing, medicine, and cytology. By acquiring 3D hyperspectral images (HSIs) via 2D sensors, the coded aperture snapshot spectral imaging (CASSI) has achieved great success due to its hardware-friendly implementation and fast imaging speed. However, for some less spectrally sparse scenes, single snapshot and unreasonable coded aperture design tend to make HSI recovery more ill-posed and yield poor spatial and spectral fidelity. In this paper, we propose a novel Progressive Content-Aware CASSI framework, dubbed PCA-CASSI, which captures HSIs with multiple optimized content-aware coded apertures and fuses all the snapshots for reconstruction progressively. Simultaneously, by mapping the Range-Null space Decomposition (RND) into a deep network with several phases, an RND-HRNet is proposed for HSI recovery. Each recovery phase can fully exploit the hidden physical information in the coded apertures via explicit $\mathcal{R}$$-$$\mathcal{N}$ decomposition and explore the spatial-spectral correlation by dual transformer blocks. Our method is validated to surpass other state-of-the-art methods on both multiple- and single-shot HSI imaging tasks by large margins.

CoNIC Challenge: Pushing the Frontiers of Nuclear Detection, Segmentation, Classification and Counting

Nuclear detection, segmentation and morphometric profiling are essential in helping us further understand the relationship between histology and patient outcome. To drive innovation in this area, we setup a community-wide challenge using the largest available dataset of its kind to assess nuclear segmentation and cellular composition. Our challenge, named CoNIC, stimulated the development of reproducible algorithms for cellular recognition with real-time result inspection on public leaderboards. We conducted an extensive post-challenge analysis based on the top-performing models using 1,658 whole-slide images of colon tissue. With around 700 million detected nuclei per model, associated features were used for dysplasia grading and survival analysis, where we demonstrated that the challenge's improvement over the previous state-of-the-art led to significant boosts in downstream performance. Our findings also suggest that eosinophils and neutrophils play an important role in the tumour microevironment. We release challenge models and WSI-level results to foster the development of further methods for biomarker discovery.

AugDiff: Diffusion based Feature Augmentation for Multiple Instance Learning in Whole Slide Image

Multiple Instance Learning (MIL), a powerful strategy for weakly supervised learning, is able to perform various prediction tasks on gigapixel Whole Slide Images (WSIs). However, the tens of thousands of patches in WSIs usually incur a vast computational burden for image augmentation, limiting the MIL model's improvement in performance. Currently, the feature augmentation-based MIL framework is a promising solution, while existing methods such as Mixup often produce unrealistic features. To explore a more efficient and practical augmentation method, we introduce the Diffusion Model (DM) into MIL for the first time and propose a feature augmentation framework called AugDiff. Specifically, we employ the generation diversity of DM to improve the quality of feature augmentation and the step-by-step generation property to control the retention of semantic information. We conduct extensive experiments over three distinct cancer datasets, two different feature extractors, and three prevalent MIL algorithms to evaluate the performance of AugDiff. Ablation study and visualization further verify the effectiveness. Moreover, we highlight AugDiff's higher-quality augmented feature over image augmentation and its superiority over self-supervised learning. The generalization over external datasets indicates its broader applications.