iMD4GC: Incomplete Multimodal Data Integration to Advance Precise Treatment Response Prediction and Survival Analysis for Gastric Cancer

Gastric cancer (GC) is a prevalent malignancy worldwide, ranking as the fifth most common cancer with over 1 million new cases and 700 thousand deaths in 2020. Locally advanced gastric cancer (LAGC) accounts for approximately two-thirds of GC diagnoses, and neoadjuvant chemotherapy (NACT) has emerged as the standard treatment for LAGC. However, the effectiveness of NACT varies significantly among patients, with a considerable subset displaying treatment resistance. Ineffective NACT not only leads to adverse effects but also misses the optimal therapeutic window, resulting in lower survival rate. However, existing multimodal learning methods assume the availability of all modalities for each patient, which does not align with the reality of clinical practice. The limited availability of modalities for each patient would cause information loss, adversely affecting predictive accuracy. In this study, we propose an incomplete multimodal data integration framework for GC (iMD4GC) to address the challenges posed by incomplete multimodal data, enabling precise response prediction and survival analysis. Specifically, iMD4GC incorporates unimodal attention layers for each modality to capture intra-modal information. Subsequently, the cross-modal interaction layers explore potential inter-modal interactions and capture complementary information across modalities, thereby enabling information compensation for missing modalities. To evaluate iMD4GC, we collected three multimodal datasets for GC study: GastricRes (698 cases) for response prediction, GastricSur (801 cases) for survival analysis, and TCGA-STAD (400 cases) for survival analysis. The scale of our datasets is significantly larger than previous studies. The iMD4GC achieved impressive performance with an 80.2% AUC on GastricRes, 71.4% C-index on GastricSur, and 66.1% C-index on TCGA-STAD, significantly surpassing other compared methods.

Histo-Genomic Knowledge Distillation For Cancer Prognosis From Histopathology Whole Slide Images

Histo-genomic multi-modal methods have recently emerged as a powerful paradigm, demonstrating significant potential for improving cancer prognosis. However, genome sequencing, unlike histopathology imaging, is still not widely accessible in underdeveloped regions, limiting the application of these multi-modal approaches in clinical settings. To address this, we propose a novel Genome-informed Hyper-Attention Network, termed G-HANet, which is capable of effectively distilling the histo-genomic knowledge during training to elevate uni-modal whole slide image (WSI)-based inference for the first time. Compared with traditional knowledge distillation methods (i.e., teacher-student architecture) in other tasks, our end-to-end model is superior in terms of training efficiency and learning cross-modal interactions. Specifically, the network comprises the cross-modal associating branch (CAB) and hyper-attention survival branch (HSB). Through the genomic data reconstruction from WSIs, CAB effectively distills the associations between functional genotypes and morphological phenotypes and offers insights into the gene expression profiles in the feature space. Subsequently, HSB leverages the distilled histo-genomic associations as well as the generated morphology-based weights to achieve the hyper-attention modeling of the patients from both histopathology and genomic perspectives to improve cancer prognosis. Extensive experiments are conducted on five TCGA benchmarking datasets and the results demonstrate that G-HANet significantly outperforms the state-of-the-art WSI-based methods and achieves competitive performance with genome-based and multi-modal methods. G-HANet is expected to be explored as a useful tool by the research community to address the current bottleneck of insufficient histo-genomic data pairing in the context of cancer prognosis and precision oncology.

HistGen: Histopathology Report Generation via Local-Global Feature Encoding and Cross-modal Context Interaction

Histopathology serves as the gold standard in cancer diagnosis, with clinical reports being vital in interpreting and understanding this process, guiding cancer treatment and patient care. The automation of histopathology report generation with deep learning stands to significantly enhance clinical efficiency and lessen the labor-intensive, time-consuming burden on pathologists in report writing. In pursuit of this advancement, we introduce HistGen, a multiple instance learning-empowered framework for histopathology report generation together with the first benchmark dataset for evaluation. Inspired by diagnostic and report-writing workflows, HistGen features two delicately designed modules, aiming to boost report generation by aligning whole slide images (WSIs) and diagnostic reports from local and global granularity. To achieve this, a local-global hierarchical encoder is developed for efficient visual feature aggregation from a region-to-slide perspective. Meanwhile, a cross-modal context module is proposed to explicitly facilitate alignment and interaction between distinct modalities, effectively bridging the gap between the extensive visual sequences of WSIs and corresponding highly summarized reports. Experimental results on WSI report generation show the proposed model outperforms state-of-the-art (SOTA) models by a large margin. Moreover, the results of fine-tuning our model on cancer subtyping and survival analysis tasks further demonstrate superior performance compared to SOTA methods, showcasing strong transfer learning capability. Dataset, model weights, and source code are available in https://github.com/dddavid4real/HistGen.

Prototypical Information Bottlenecking and Disentangling for Multimodal Cancer Survival Prediction

Multimodal learning significantly benefits cancer survival prediction, especially the integration of pathological images and genomic data. Despite advantages of multimodal learning for cancer survival prediction, massive redundancy in multimodal data prevents it from extracting discriminative and compact information: (1) An extensive amount of intra-modal task-unrelated information blurs discriminability, especially for gigapixel whole slide images (WSIs) with many patches in pathology and thousands of pathways in genomic data, leading to an ``intra-modal redundancy" issue. (2) Duplicated information among modalities dominates the representation of multimodal data, which makes modality-specific information prone to being ignored, resulting in an ``inter-modal redundancy" issue. To address these, we propose a new framework, Prototypical Information Bottlenecking and Disentangling (PIBD), consisting of Prototypical Information Bottleneck (PIB) module for intra-modal redundancy and Prototypical Information Disentanglement (PID) module for inter-modal redundancy. Specifically, a variant of information bottleneck, PIB, is proposed to model prototypes approximating a bunch of instances for different risk levels, which can be used for selection of discriminative instances within modality. PID module decouples entangled multimodal data into compact distinct components: modality-common and modality-specific knowledge, under the guidance of the joint prototypical distribution. Extensive experiments on five cancer benchmark datasets demonstrated our superiority over other methods.

Multimodal Optimal Transport-based Co-Attention Transformer with Global Structure Consistency for Survival Prediction

Survival prediction is a complicated ordinal regression task that aims to predict the ranking risk of death, which generally benefits from the integration of histology and genomic data. Despite the progress in joint learning from pathology and genomics, existing methods still suffer from challenging issues: 1) Due to the large size of pathological images, it is difficult to effectively represent the gigapixel whole slide images (WSIs). 2) Interactions within tumor microenvironment (TME) in histology are essential for survival analysis. Although current approaches attempt to model these interactions via co-attention between histology and genomic data, they focus on only dense local similarity across modalities, which fails to capture global consistency between potential structures, i.e. TME-related interactions of histology and co-expression of genomic data. To address these challenges, we propose a Multimodal Optimal Transport-based Co-Attention Transformer framework with global structure consistency, in which optimal transport (OT) is applied to match patches of a WSI and genes embeddings for selecting informative patches to represent the gigapixel WSI. More importantly, OT-based co-attention provides a global awareness to effectively capture structural interactions within TME for survival prediction. To overcome high computational complexity of OT, we propose a robust and efficient implementation over micro-batch of WSI patches by approximating the original OT with unbalanced mini-batch OT. Extensive experiments show the superiority of our method on five benchmark datasets compared to the state-of-the-art methods. The code is released.

Unsupervised Domain Adaptation via Deep Hierarchical Optimal Transport

Unsupervised domain adaptation is a challenging task that aims to estimate a transferable model for unlabeled target domain by exploiting source labeled data. Optimal Transport (OT) based methods recently have been proven to be a promising direction for domain adaptation due to their competitive performance. However, most of these methods coarsely aligned source and target distributions, leading to the over-aligned problem where the category-discriminative information is mixed up although domain-invariant representations can be learned. In this paper, we propose a Deep Hierarchical Optimal Transport method (DeepHOT) for unsupervised domain adaptation. The main idea is to use hierarchical optimal transport to learn both domain-invariant and category-discriminative representations by mining the rich structural correlations among domain data. The DeepHOT framework consists of a domain-level OT and an image-level OT, where the latter is used as the ground distance metric for the former. The image-level OT captures structural associations of local image regions that are beneficial to image classification, while the domain-level OT learns domain-invariant representations by leveraging the underlying geometry of domains. However, due to the high computational complexity, the optimal transport based models are limited in some scenarios. To this end, we propose a robust and efficient implementation of the DeepHOT framework by approximating origin OT with sliced Wasserstein distance in image-level OT and using a mini-batch unbalanced optimal transport for domain-level OT. Extensive experiments show that DeepHOT surpasses the state-of-the-art methods in four benchmark datasets. Code will be released on GitHub.

Semantic Graph-enhanced Visual Network for Zero-shot Learning

Zero-shot learning uses semantic attributes to connect the search space of unseen objects. In recent years, although the deep convolutional network brings powerful visual modeling capabilities to the ZSL task, its visual features have severe pattern inertia and lack of representation of semantic relationships, which leads to severe bias and ambiguity. In response to this, we propose the Graph-based Visual-Semantic Entanglement Network to conduct graph modeling of visual features, which is mapped to semantic attributes by using a knowledge graph, it contains several novel designs: 1. it establishes a multi-path entangled network with the convolutional neural network (CNN) and the graph convolutional network (GCN), which input the visual features from CNN to GCN to model the implicit semantic relations, then GCN feedback the graph modeled information to CNN features; 2. it uses attribute word vectors as the target for the graph semantic modeling of GCN, which forms a self-consistent regression for graph modeling and supervise GCN to learn more personalized attribute relations; 3. it fuses and supplements the hierarchical visual-semantic features refined by graph modeling into visual embedding. By promoting the semantic linkage modeling of visual features, our method outperforms state-of-the-art approaches on multiple representative ZSL datasets: AwA2, CUB, and SUN.

Multiple Attentional Pyramid Networks for Chinese Herbal Recognition

Chinese herbs play a critical role in Traditional Chinese Medicine. Due to different recognition granularity, they can be recognized accurately only by professionals with much experience. It is expected that they can be recognized automatically using new techniques like machine learning. However, there is no Chinese herbal image dataset available. Simultaneously, there is no machine learning method which can deal with Chinese herbal image recognition well. Therefore, this paper begins with building a new standard Chinese-Herbs dataset. Subsequently, a new Attentional Pyramid Networks (APN) for Chinese herbal recognition is proposed, where both novel competitive attention and spatial collaborative attention are proposed and then applied. APN can adaptively model Chinese herbal images with different feature scales. Finally, a new framework for Chinese herbal recognition is proposed as a new application of APN. Experiments are conducted on our constructed dataset and validate the effectiveness of our methods.

Stochastic Region Pooling: Make Attention More Expressive

Global Average Pooling (GAP) is used by default on the channel-wise attention mechanism to extract channel descriptors. However, the simple global aggregation method of GAP is easy to make the channel descriptors have homogeneity, which weakens the detail distinction between feature maps, thus affecting the performance of the attention mechanism. In this work, we propose a novel method for channel-wise attention network, called Stochastic Region Pooling (SRP), which makes the channel descriptors more representative and diversity by encouraging the feature map to have more or wider important feature responses. Also, SRP is the general method for the attention mechanisms without any additional parameters or computation. It can be widely applied to attention networks without modifying the network structure. Experimental results on image recognition datasets including CIAFR-10/100, ImageNet and three Fine-grained datasets (CUB-200-2011, Stanford Cars and Stanford Dogs) show that SRP brings the significant improvements of the performance over efficient CNNs and achieves the state-of-the-art results.