Deep Multi-modal Fusion of Image and Non-image Data in Disease Diagnosis and Prognosis: A Review

The rapid development of diagnostic technologies in healthcare is leading to higher requirements for physicians to handle and integrate the heterogeneous, yet complementary data that are produced during routine practice. For instance, the personalized diagnosis and treatment planning for a single cancer patient relies on the various images (e.g., radiological, pathological, and camera images) and non-image data (e.g., clinical data and genomic data). However, such decision-making procedures can be subjective, qualitative, and have large inter-subject variabilities. With the recent advances in multi-modal deep learning technologies, an increasingly large number of efforts have been devoted to a key question: how do we extract and aggregate multi-modal information to ultimately provide more objective, quantitative computer-aided clinical decision making? This paper reviews the recent studies on dealing with such a question. Briefly, this review will include the (1) overview of current multi-modal learning workflows, (2) summarization of multi-modal fusion methods, (3) discussion of the performance, (4) applications in disease diagnosis and prognosis, and (5) challenges and future directions.

Survival Prediction of Brain Cancer with Incomplete Radiology, Pathology, Genomics, and Demographic Data

Integrating cross-department multi-modal data (e.g., radiological, pathological, genomic, and clinical data) is ubiquitous in brain cancer diagnosis and survival prediction. To date, such an integration is typically conducted by human physicians (and panels of experts), which can be subjective and semi-quantitative. Recent advances in multi-modal deep learning, however, have opened a door to leverage such a process to a more objective and quantitative manner. Unfortunately, the prior arts of using four modalities on brain cancer survival prediction are limited by a "complete modalities" setting (i.e., with all modalities available). Thus, there are still open questions on how to effectively predict brain cancer survival from the incomplete radiological, pathological, genomic, and demographic data (e.g., one or more modalities might not be collected for a patient). For instance, should we use both complete and incomplete data, and more importantly, how to use those data? To answer the preceding questions, we generalize the multi-modal learning on cross-department multi-modal data to a missing data setting. Our contribution is three-fold: 1) We introduce optimal multi-modal learning with missing data (MMD) pipeline with optimized hardware consumption and computational efficiency; 2) We extend multi-modal learning on radiological, pathological, genomic, and demographic data into missing data scenarios; 3) a large-scale public dataset (with 962 patients) is collected to systematically evaluate glioma tumor survival prediction using four modalities. The proposed method improved the C-index of survival prediction from 0.7624 to 0.8053.

Characterizing Renal Structures with 3D Block Aggregate Transformers

Efficiently quantifying renal structures can provide distinct spatial context and facilitate biomarker discovery for kidney morphology. However, the development and evaluation of the transformer model to segment the renal cortex, medulla, and collecting system remains challenging due to data inefficiency. Inspired by the hierarchical structures in vision transformer, we propose a novel method using a 3D block aggregation transformer for segmenting kidney components on contrast-enhanced CT scans. We construct the first cohort of renal substructures segmentation dataset with 116 subjects under institutional review board (IRB) approval. Our method yields the state-of-the-art performance (Dice of 0.8467) against the baseline approach of 0.8308 with the data-efficient design. The Pearson R achieves 0.9891 between the proposed method and manual standards and indicates the strong correlation and reproducibility for volumetric analysis. We extend the proposed method to the public KiTS dataset, the method leads to improved accuracy compared to transformer-based approaches. We show that the 3D block aggregation transformer can achieve local communication between sequence representations without modifying self-attention, and it can serve as an accurate and efficient quantification tool for characterizing renal structures.

Holistic Fine-grained GGS Characterization: From Detection to Unbalanced Classification

Recent studies have demonstrated the diagnostic and prognostic values of global glomerulosclerosis (GGS) in IgA nephropathy, aging, and end-stage renal disease. However, the fine-grained quantitative analysis of multiple GGS subtypes (e.g., obsolescent, solidified, and disappearing glomerulosclerosis) is typically a resource extensive manual process. Very few automatic methods, if any, have been developed to bridge this gap for such analytics. In this paper, we present a holistic pipeline to quantify GGS (with both detection and classification) from a whole slide image in a fully automatic manner. In addition, we conduct the fine-grained classification for the sub-types of GGS. Our study releases the open-source quantitative analytical tool for fine-grained GGS characterization while tackling the technical challenges in unbalanced classification and integrating detection and classification.

Meta-optic Accelerators for Object Classifiers

Rapid advances in deep learning have led to paradigm shifts in a number of fields, from medical image analysis to autonomous systems. These advances, however, have resulted in digital neural networks with large computational requirements, resulting in high energy consumption and limitations in real-time decision making when computation resources are limited. Here, we demonstrate a meta-optic based neural network accelerator that can off-load computationally expensive convolution operations into high-speed and low-power optics. In this architecture, metasurfaces enable both spatial multiplexing and additional information channels, such as polarization, in object classification. End-to-end design is used to co-optimize the optical and digital systems resulting in a robust classifier that achieves 95% accurate classification of handwriting digits and 94% accuracy in classifying both the digit and its polarization state. This approach could enable compact, high-speed, and low-power image and information processing systems for a wide range of applications in machine-vision and artificial intelligence.

MAg: a simple learning-based patient-level aggregation method for detecting microsatellite instability from whole-slide images

The prediction of microsatellite instability (MSI) and microsatellite stability (MSS) is essential in predicting both the treatment response and prognosis of gastrointestinal cancer. In clinical practice, a universal MSI testing is recommended, but the accessibility of such a test is limited. Thus, a more cost-efficient and broadly accessible tool is desired to cover the traditionally untested patients. In the past few years, deep-learning-based algorithms have been proposed to predict MSI directly from haematoxylin and eosin (H&E)-stained whole-slide images (WSIs). Such algorithms can be summarized as (1) patch-level MSI/MSS prediction, and (2) patient-level aggregation. Compared with the advanced deep learning approaches that have been employed for the first stage, only the na\"ive first-order statistics (e.g., averaging and counting) were employed in the second stage. In this paper, we propose a simple yet broadly generalizable patient-level MSI aggregation (MAg) method to effectively integrate the precious patch-level information. Briefly, the entire probabilistic distribution in the first stage is modeled as histogram-based features to be fused as the final outcome with machine learning (e.g., SVM). The proposed MAg method can be easily used in a plug-and-play manner, which has been evaluated upon five broadly used deep neural networks: ResNet, MobileNetV2, EfficientNet, Dpn and ResNext. From the results, the proposed MAg method consistently improves the accuracy of patient-level aggregation for two publicly available datasets. It is our hope that the proposed method could potentially leverage the low-cost H&E based MSI detection method. The code of our work has been made publicly available at https://github.com/Calvin-Pang/MAg.

Omni-Seg: A Single Dynamic Network for Multi-label Renal Pathology Image Segmentation using Partially Labeled Data

Computer-assisted quantitative analysis on Giga-pixel pathology images has provided a new avenue in precision medicine. The innovations have been largely focused on cancer pathology (i.e., tumor segmentation and characterization). In non-cancer pathology, the learning algorithms can be asked to examine more comprehensive tissue types simultaneously, as a multi-label setting. The prior arts typically needed to train multiple segmentation networks in order to match the domain-specific knowledge for heterogeneous tissue types (e.g., glomerular tuft, glomerular unit, proximal tubular, distal tubular, peritubular capillaries, and arteries). In this paper, we propose a dynamic single segmentation network (Omni-Seg) that learns to segment multiple tissue types using partially labeled images (i.e., only one tissue type is labeled for each training image) for renal pathology. By learning from ~150,000 patch-wise pathological images from six tissue types, the proposed Omni-Seg network achieved superior segmentation accuracy and less resource consumption when compared to the previous the multiple-network and multi-head design. In the testing stage, the proposed method obtains "completely labeled" tissue segmentation results using only "partially labeled" training images. The source code is available at https://github.com/ddrrnn123/Omni-Seg.

Learn2Reg: comprehensive multi-task medical image registration challenge, dataset and evaluation in the era of deep learning

Image registration is a fundamental medical image analysis task, and a wide variety of approaches have been proposed. However, only a few studies have comprehensively compared medical image registration approaches on a wide range of clinically relevant tasks, in part because of the lack of availability of such diverse data. This limits the development of registration methods, the adoption of research advances into practice, and a fair benchmark across competing approaches. The Learn2Reg challenge addresses these limitations by providing a multi-task medical image registration benchmark for comprehensive characterisation of deformable registration algorithms. A continuous evaluation will be possible at https://learn2reg.grand-challenge.org. Learn2Reg covers a wide range of anatomies (brain, abdomen, and thorax), modalities (ultrasound, CT, MR), availability of annotations, as well as intra- and inter-patient registration evaluation. We established an easily accessible framework for training and validation of 3D registration methods, which enabled the compilation of results of over 65 individual method submissions from more than 20 unique teams. We used a complementary set of metrics, including robustness, accuracy, plausibility, and runtime, enabling unique insight into the current state-of-the-art of medical image registration. This paper describes datasets, tasks, evaluation methods and results of the challenge, and the results of further analysis of transferability to new datasets, the importance of label supervision, and resulting bias.

Semi-Supervised Contrastive Learning for Remote Sensing: Identifying Ancient Urbanization in the South Central Andes

The detection of ancient settlements is a key focus in landscape archaeology. Traditionally, settlements were identified through pedestrian survey, as researchers physically traversed the landscape and recorded settlement locations. Recently the manual identification and labeling of ancient remains in satellite imagery have increased the scale of archaeological data collection, but the process remains tremendously time-consuming and arduous. The development of self-supervised learning (e.g., contrastive learning) offers a scalable learning scheme in locating archaeological sites using unlabeled satellite and historical aerial images. However, archaeology sites are only present in a very small proportion of the whole landscape, while the modern contrastive-supervised learning approach typically yield inferior performance on the highly balanced dataset, such as identifying sparsely localized ancient urbanization on a large area using satellite images. In this work, we propose a framework to solve this long-tail problem. As opposed to the existing contrastive learning approaches that typically treat the labeled and unlabeled data separately, the proposed method reforms the learning paradigm under a semi-supervised setting to fully utilize the precious annotated data (<7% in our setting). Specifically, the highly unbalanced nature of the data is employed as the prior knowledge to form pseudo negative pairs by ranking the similarities between unannotated image patches and annotated anchor images. In this study, we used 95,358 unlabeled images and 5,830 labeled images to solve the problem of detecting ancient buildings from a long-tailed satellite image dataset. From the results, our semi-supervised contrastive learning model achieved a promising testing balanced accuracy of 79.0%, which is 3.8% improvement over state-of-the-art approaches.