Potential Anti-Inflammatory Constituents from Aesculus wilsonii Seeds.

A chemical study of Aesculus wilsonii Rehd. (also called Suo Luo Zi) and the in vitro anti-inflammatory effects of the obtained compounds was conducted. Retrieving results through SciFinder showed that there were four unreported compounds, aeswilosides I-IV (1-4), along with fourteen known isolates (5-18). Their structures were elucidated by extensive spectroscopic methods such as UV, IR, NMR, [α]D, and MS spectra, as well as acid hydrolysis. Among the known ones, compounds 5, 6, 8-10, and 12-16 were obtained from the Aesculus genus for the first time; compounds 7, 11, 17, and 18 were first identified from this plant. The NMR data of 5 and 18 were reported first. The effects of 1-18 on the release of nitric oxide (NO) from lipopolysaccharide (LPS)-induced RAW264.7 cells were determined. The results showed that at concentrations of 10, 25, and 50 µM, the novel compounds, aeswilosides I (1) and IV (4), along with the known ones, 1-(2-methylbutyryl)phloroglucinyl-glucopyranoside (10) and pisuminic acid (15), displayed significant inhibitory effects on NO production in a concentration-dependent manner. It is worth mentioning that compound 10 showed the best NO inhibitory effect with a relative NO production of 88.1%, which was close to that of the positive drug dexamethasone. The Elisa experiment suggested that compounds 1, 4, 10, and 15 suppressed the release of TNF-α and IL-1ß as well. In conclusion, this study enriches the spectra of compounds with potential anti-inflammatory effects in A. wilsonii and provides new references for the discovery of anti-inflammatory lead compounds, but further mechanistic research is still needed.

VoxResNet: Deep voxelwise residual networks for brain segmentation from 3D MR images.

Segmentation of key brain tissues from 3D medical images is of great significance for brain disease diagnosis, progression assessment and monitoring of neurologic conditions. While manual segmentation is time-consuming, laborious, and subjective, automated segmentation is quite challenging due to the complicated anatomical environment of brain and the large variations of brain tissues. We propose a novel voxelwise residual network (VoxResNet) with a set of effective training schemes to cope with this challenging problem. The main merit of residual learning is that it can alleviate the degradation problem when training a deep network so that the performance gains achieved by increasing the network depth can be fully leveraged. With this technique, our VoxResNet is built with 25 layers, and hence can generate more representative features to deal with the large variations of brain tissues than its rivals using hand-crafted features or shallower networks. In order to effectively train such a deep network with limited training data for brain segmentation, we seamlessly integrate multi-modality and multi-level contextual information into our network, so that the complementary information of different modalities can be harnessed and features of different scales can be exploited. Furthermore, an auto-context version of the VoxResNet is proposed by combining the low-level image appearance features, implicit shape information, and high-level context together for further improving the segmentation performance. Extensive experiments on the well-known benchmark (i.e., MRBrainS) of brain segmentation from 3D magnetic resonance (MR) images corroborated the efficacy of the proposed VoxResNet. Our method achieved the first place in the challenge out of 37 competitors including several state-of-the-art brain segmentation methods. Our method is inherently general and can be readily applied as a powerful tool to many brain-related studies, where accurate segmentation of brain structures is critical.

RECIST-Induced Reliable Learning: Geometry-Driven Label Propagation for Universal Lesion Segmentation.

Automatic universal lesion segmentation (ULS) from Computed Tomography (CT) images can ease the burden of radiologists and provide a more accurate assessment than the current Response Evaluation Criteria In Solid Tumors (RECIST) guideline measurement. However, this task is underdeveloped due to the absence of large-scale pixel-wise labeled data. This paper presents a weakly-supervised learning framework to utilize the large-scale existing lesion databases in hospital Picture Archiving and Communication Systems (PACS) for ULS. Unlike previous methods to construct pseudo surrogate masks for fully supervised training through shallow interactive segmentation techniques, we propose to unearth the implicit information from RECIST annotations and thus design a unified RECIST-induced reliable learning (RiRL) framework. Particularly, we introduce a novel label generation procedure and an on-the-fly soft label propagation strategy to avoid noisy training and poor generalization problems. The former, named RECIST-induced geometric labeling, uses clinical characteristics of RECIST to preliminarily and reliably propagate the label. With the labeling process, a trimap divides the lesion slices into three regions, including certain foreground, background, and unclear regions, which consequently enables a strong and reliable supervision signal on a wide region. A topological knowledge-driven graph is built to conduct the on-the-fly label propagation for the optimal segmentation boundary to further optimize the segmentation boundary. Experimental results on a public benchmark dataset demonstrate that the proposed method surpasses the SOTA RECIST-based ULS methods by a large margin. Our approach surpasses SOTA approaches over 2.0%, 1.5%, 1.4%, and 1.6% Dice with ResNet101, ResNet50, HRNet, and ResNest50 backbones.

Multi-task heterogeneous graph learning on electronic health records.

Learning electronic health records (EHRs) has received emerging attention because of its capability to facilitate accurate medical diagnosis. Since the EHRs contain enriched information specifying complex interactions between entities, modeling EHRs with graphs is shown to be effective in practice. The EHRs, however, present a great degree of heterogeneity, sparsity, and complexity, which hamper the performance of most of the models applied to them. Moreover, existing approaches modeling EHRs often focus on learning the representations for a single task, overlooking the multi-task nature of EHR analysis problems and resulting in limited generalizability across different tasks. In view of these limitations, we propose a novel framework for EHR modeling, namely MulT-EHR (Multi-Task EHR), which leverages a heterogeneous graph to mine the complex relations and model the heterogeneity in the EHRs. To mitigate the large degree of noise, we introduce a denoising module based on the causal inference framework to adjust for severe confounding effects and reduce noise in the EHR data. Additionally, since our model adopts a single graph neural network for simultaneous multi-task prediction, we design a multi-task learning module to leverage the inter-task knowledge to regularize the training process. Extensive empirical studies on MIMIC-III and MIMIC-IV datasets validate that the proposed method consistently outperforms the state-of-the-art designs in four popular EHR analysis tasks - drug recommendation, and predictions of the length of stay, mortality, and readmission. Thorough ablation studies demonstrate the robustness of our method upon variations to key components and hyperparameters.

A Dual Enrichment Synergistic Strategy to Handle Data Heterogeneity for Domain Incremental Cardiac Segmentation.

Upon remarkable progress in cardiac image segmentation, contemporary studies dedicate to further upgrading model functionality toward perfection, through progressively exploring the sequentially delivered datasets over time by domain incremental learning. Existing works mainly concentrated on addressing the heterogeneous style variations, but overlooked the critical shape variations across domains hidden behind the sub-disease composition discrepancy. In case the updated model catastrophically forgets the sub-diseases that were learned in past domains but are no longer present in the subsequent domains, we proposed a dual enrichment synergistic strategy to incrementally broaden model competence for a growing number of sub-diseases. The data-enriched scheme aims to diversify the shape composition of current training data via displacement-aware shape encoding and decoding, to gradually build up the robustness against cross-domain shape variations. Meanwhile, the model-enriched scheme intends to strengthen model capabilities by progressively appending and consolidating the latest expertise into a dynamically-expanded multi-expert network, to gradually cultivate the generalization ability over style-variated domains. The above two schemes work in synergy to collaboratively upgrade model capabilities in two-pronged manners. We have extensively evaluated our network with the ACDC and M&Ms datasets in single-domain and compound-domain incremental learning settings. Our approach outperformed other competing methods and achieved comparable results to the upper bound.

Multi-sensor Learning Enables Information Transfer across Different Sensory Data and Augments Multi-modality Imaging.

Multi-modality imaging is widely used in clinical practice and biomedical research to gain a comprehensive understanding of an imaging subject. Currently, multi-modality imaging is accomplished by post hoc fusion of independently reconstructed images under the guidance of mutual information or spatially registered hardware, which limits the accuracy and utility of multi-modality imaging. Here, we investigate a data-driven multi-modality imaging (DMI) strategy for synergetic imaging of CT and MRI. We reveal two distinct types of features in multi-modality imaging, namely intra- and inter-modality features, and present a multi-sensor learning (MSL) framework to utilize the crossover inter-modality features for augmented multi-modality imaging. The MSL imaging approach breaks down the boundaries of traditional imaging modalities and allows for optimal hybridization of CT and MRI, which maximizes the use of sensory data. We showcase the effectiveness of our DMI strategy through synergetic CT-MRI brain imaging. The principle of DMI is quite general and holds enormous potential for various DMI applications across disciplines.

Unleash the Power of State Space Model for Whole Slide Image with Local Aware Scanning and Importance Resampling.

Whole slide image (WSI) analysis is gaining prominence within the medical imaging field. However, previous methods often fall short of efficiently processing entire WSIs due to their gigapixel size. Inspired by recent developments in state space models, this paper introduces a new Pathology Mamba (PAM) for more accurate and robust WSI analysis. PAM includes three carefully designed components to tackle the challenges of enormous image size, the utilization of local and hierarchical information, and the mismatch between the feature distributions of training and testing during WSI analysis. Specifically, we design a Bi-directional Mamba Encoder to process the extensive patches present in WSIs effectively and efficiently, which can handle large-scale pathological images while achieving high performance and accuracy. To further harness the local information and inherent hierarchical structure of WSI, we introduce a novel Local-aware Scanning module, which employs a local-aware mechanism alongside hierarchical scanning to adeptly capture both the local information and the overarching structure within WSIs. Moreover, to alleviate the patch feature distribution misalignment between training and testing, we propose a Test-time Importance Resampling module to conduct testing patch resampling to ensure consistency of feature distribution between the training and testing phases, and thus enhance model prediction. Extensive evaluation on nine WSI datasets with cancer subtyping and survival prediction tasks demonstrates that PAM outperforms current state-of-the-art methods and also its enhanced capability in modeling discriminative areas within WSIs. The source code is available at https://github.com/HKU-MedAI/PAM.

Hybrid Masked Image Modeling for 3D Medical Image Segmentation.

Masked image modeling (MIM) with transformer backbones has recently been exploited as a powerful self-supervised pre-training technique. The existing MIM methods adopt the strategy to mask random patches of the image and reconstruct the missing pixels, which only considers semantic information at a lower level, and causes a long pre-training time. This paper presents HybridMIM, a novel hybrid self-supervised learning method based on masked image modeling for 3D medical image segmentation. Specifically, we design a two-level masking hierarchy to specify which and how patches in sub-volumes are masked, effectively providing the constraints of higher level semantic information. Then we learn the semantic information of medical images at three levels, including: 1) partial region prediction to reconstruct key contents of the 3D image, which largely reduces the pre-training time burden (pixel-level); 2) patch-masking perception to learn the spatial relationship between the patches in each sub-volume (region-level); and 3) drop-out-based contrastive learning between samples within a mini-batch, which further improves the generalization ability of the framework (sample-level). The proposed framework is versatile to support both CNN and transformer as encoder backbones, and also enables to pre-train decoders for image segmentation. We conduct comprehensive experiments on five widely-used public medical image segmentation datasets, including BraTS2020, BTCV, MSD Liver, MSD Spleen, and BraTS2023. The experimental results show the clear superiority of HybridMIM against competing supervised methods, masked pre-training approaches, and other self-supervised methods, in terms of quantitative metrics, speed performance and qualitative observations.

Synthesizing Feature-Aligned and Category-aware Electronic Medical Records for Intracranial Aneurysm Rupture Prediction.

Rupture prediction is crucial for precise treatment and follow-up management of patients with intracranial aneurysms (IAs). Considerable machine learning (ML) methods have been proposed to improve rupture prediction by leveraging electronic medical records (EMRs), however, data scarcity and category imbalance strongly influence performance. Thus, we propose a novel data synthesis method i.e., Transformer-based conditional GAN (TransCGAN), to synthesize highly authentic and category-aware EMRs to address above challenges. Specifically, we first align feature-wise context relationship and distribution between synthetic and original data to enhance synthetic data quality. To achieve this, we first integrate the Transformer structure into GAN to match the contextual relationship by processing the long-range dependencies among clinical factors and introduce a statistical loss to maintain distributional consistency by constraining the mean and variance of the synthesis features. Additionally, a conditional module is designed to assign the category of the synthesis data, thereby addressing the challenge of category imbalance. Subsequently, the synthetic data are merged with the original data to form a large-scale and category-balanced training dataset for IAs rupture prediction. Experimental results show that using TransCGAN's synthetic data enhances classifier performance, achieving AUC of 0.89 and outperforming state-of-the-art resampling methods by 5 %-33 % in F1 score.

MPGAN: Multi Pareto Generative Adversarial Network for the denoising and quantitative analysis of low-dose PET images of human brain.

Positron emission tomography (PET) imaging is widely used in medical imaging for analyzing neurological disorders and related brain diseases. Usually, full-dose imaging for PET ensures image quality but raises concerns about potential health risks of radiation exposure. The contradiction between reducing radiation exposure and maintaining diagnostic performance can be effectively addressed by reconstructing low-dose PET (L-PET) images to the same high-quality as full-dose (F-PET). This paper introduces the Multi Pareto Generative Adversarial Network (MPGAN) to achieve 3D end-to-end denoising for the L-PET images of human brain. MPGAN consists of two key modules: the diffused multi-round cascade generator (GDmc) and the dynamic Pareto-efficient discriminator (DPed), both of which play a zero-sum game for n(n∈1,2,3) rounds to ensure the quality of synthesized F-PET images. The Pareto-efficient dynamic discrimination process is introduced in DPed to adaptively adjust the weights of sub-discriminators for improved discrimination output. We validated the performance of MPGAN using three datasets, including two independent datasets and one mixed dataset, and compared it with 12 recent competing models. Experimental results indicate that the proposed MPGAN provides an effective solution for 3D end-to-end denoising of L-PET images of the human brain, which meets clinical standards and achieves state-of-the-art performance on commonly used metrics.

Comprehensive assessment of immune context and immunotherapy response via noninvasive imaging in gastric cancer.

BACKGROUNDThe tumor immune microenvironment can provide prognostic and therapeutic information. We aimed to develop noninvasive imaging biomarkers from computed tomography (CT) for comprehensive evaluation of immune context and investigate their associations with prognosis and immunotherapy response in gastric cancer (GC).METHODSThis study involved 2,600 patients with GC from 9 independent cohorts. We developed and validated 2 CT imaging biomarkers (lymphoid radiomics score [LRS] and myeloid radiomics score [MRS]) for evaluating the IHC-derived lymphoid and myeloid immune context respectively, and integrated them into a combined imaging biomarker [LRS/MRS: low(-) or high(+)] with 4 radiomics immune subtypes: 1 (-/-), 2 (+/-), 3 (-/+), and 4 (+/+). We further evaluated the imaging biomarkers' predictive values on prognosis and immunotherapy response.RESULTSThe developed imaging biomarkers (LRS and MRS) had a high accuracy in predicting lymphoid (AUC range: 0.765-0.773) and myeloid (AUC range: 0.736-0.750) immune context. Further, similar to the IHC-derived immune context, 2 imaging biomarkers (HR range: 0.240-0.761 for LRS; 1.301-4.012 for MRS) and the combined biomarker were independent predictors for disease-free and overall survival in the training and all validation cohorts (all P < 0.05). Additionally, patients with high LRS or low MRS may benefit more from immunotherapy (P < 0.001). Further, a highly heterogeneous outcome on objective response ​rate was observed in 4 imaging subtypes: 1 (-/-) with 27.3%, 2 (+/-) with 53.3%, 3 (-/+) with 10.2%, and 4 (+/+) with 30.0% (P < 0.0001).CONCLUSIONThe noninvasive imaging biomarkers could accurately evaluate the immune context and provide information regarding prognosis and immunotherapy for GC.

Development and interpretation of a pathomics-driven ensemble model for predicting the response to immunotherapy in gastric cancer.

BACKGROUND: Only a subset of patients with gastric cancer experience long-term benefits from immune checkpoint inhibitors (ICIs). Currently, there is a deficiency in precise predictive biomarkers for ICI efficacy. The aim of this study was to develop and validate a pathomics-driven ensemble model for predicting the response to ICIs in gastric cancer, using H&E-stained whole slide images (WSI). METHODS: This multicenter study retrospectively collected and analyzed H&E-stained WSIs and clinical data from 584 patients with gastric cancer. An ensemble model, integrating four classifiers: least absolute shrinkage and selection operator, k-nearest neighbors, decision trees, and random forests, was developed and validated using pathomics features, with the objective of predicting the therapeutic efficacy of immune checkpoint inhibition. Model performance was evaluated using metrics including the area under the curve (AUC), sensitivity, and specificity. Additionally, SHAP (SHapley Additive exPlanations) analysis was used to explain the model's predicted values as the sum of the attribution values for each input feature. Pathogenomics analysis was employed to explain the molecular mechanisms underlying the model's predictions. RESULTS: Our pathomics-driven ensemble model effectively stratified the response to ICIs in training cohort (AUC 0.985 (95% CI 0.971 to 0.999)), which was further validated in internal validation cohort (AUC 0.921 (95% CI 0.839 to 0.999)), as well as in external validation cohort 1 (AUC 0.914 (95% CI 0.837 to 0.990)), and external validation cohort 2 (0.927 (95% CI 0.802 to 0.999)). The univariate Cox regression analysis revealed that the prediction signature of pathomics-driven ensemble model was a prognostic factor for progression-free survival in patients with gastric cancer who underwent immunotherapy (p<0.001, HR 0.35 (95% CI 0.24 to 0.50)), and remained an independent predictor after multivariable Cox regression adjusted for clinicopathological variables, (including sex, age, carcinoembryonic antigen, carbohydrate antigen 19-9, therapy regime, line of therapy, differentiation, location and programmed death ligand 1 (PD-L1) expression in all patients (p<0.001, HR 0.34 (95% CI 0.24 to 0.50)). Pathogenomics analysis suggested that the ensemble model is driven by molecular-level immune, cancer, metabolism-related pathways, and was correlated with the immune-related characteristics, including immune score, Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data score, and tumor purity. CONCLUSIONS: Our pathomics-driven ensemble model exhibited high accuracy and robustness in predicting the response to ICIs using WSIs. Therefore, it could serve as a novel and valuable tool to facilitate precision immunotherapy.

MCIBI++: Soft Mining Contextual Information Beyond Image for Semantic Segmentation.

Co-occurrent visual pattern makes context aggregation become an essential paradigm for semantic segmentation. The existing studies focus on modeling the contexts within image while neglecting the valuable semantics of the corresponding category beyond image. To this end, we propose a novel soft mining contextual information beyond image paradigm named MCIBI++ to further boost the pixel-level representations. Specifically, we first set up a dynamically updated memory module to store the dataset-level distribution information of various categories and then leverage the information to yield the dataset-level category representations during network forward. After that, we generate a class probability distribution for each pixel representation and conduct the dataset-level context aggregation with the class probability distribution as weights. Finally, the original pixel representations are augmented with the aggregated dataset-level and the conventional image-level contextual information. Moreover, in the inference phase, we additionally design a coarse-to-fine iterative inference strategy to further boost the segmentation results. MCIBI++ can be effortlessly incorporated into the existing segmentation frameworks and bring consistent performance improvements. Also, MCIBI++ can be extended into the video semantic segmentation framework with considerable improvements over the baseline. Equipped with MCIBI++, we achieved the state-of-the-art performance on seven challenging image or video semantic segmentation benchmarks.

Domain-Incremental Cardiac Image Segmentation With Style-Oriented Replay and Domain-Sensitive Feature Whitening.

Contemporary methods have shown promising results on cardiac image segmentation, but merely in static learning, i.e., optimizing the network once for all, ignoring potential needs for model updating. In real-world scenarios, new data continues to be gathered from multiple institutions over time and new demands keep growing to pursue more satisfying performance. The desired model should incrementally learn from each incoming dataset and progressively update with improved functionality as time goes by. As the datasets sequentially delivered from multiple sites are normally heterogenous with domain discrepancy, each updated model should not catastrophically forget previously learned domains while well generalizing to currently arrived domains or even unseen domains. In medical scenarios, this is particularly challenging as accessing or storing past data is commonly not allowed due to data privacy. To this end, we propose a novel domain-incremental learning framework to recover past domain inputs first and then regularly replay them during model optimization. Particularly, we first present a style-oriented replay module to enable structure-realistic and memory-efficient reproduction of past data, and then incorporate the replayed past data to jointly optimize the model with current data to alleviate catastrophic forgetting. During optimization, we additionally perform domain-sensitive feature whitening to suppress model's dependency on features that are sensitive to domain changes (e.g., domain-distinctive style features) to assist domain-invariant feature exploration and gradually improve the generalization performance of the network. We have extensively evaluated our approach with the M&Ms Dataset in single-domain and compound-domain incremental learning settings. Our approach outperforms other comparison methods with less forgetting on past domains and better generalization on current domains and unseen domains.

Shared-Specific Feature Learning With Bottleneck Fusion Transformer for Multi-Modal Whole Slide Image Analysis.

The fusion of multi-modal medical data is essential to assist medical experts to make treatment decisions for precision medicine. For example, combining the whole slide histopathological images (WSIs) and tabular clinical data can more accurately predict the lymph node metastasis (LNM) of papillary thyroid carcinoma before surgery to avoid unnecessary lymph node resection. However, the huge-sized WSI provides much more high-dimensional information than low-dimensional tabular clinical data, making the information alignment challenging in the multi-modal WSI analysis tasks. This paper presents a novel transformer-guided multi-modal multi-instance learning framework to predict lymph node metastasis from both WSIs and tabular clinical data. We first propose an effective multi-instance grouping scheme, named siamese attention-based feature grouping (SAG), to group high-dimensional WSIs into representative low-dimensional feature embeddings for fusion. We then design a novel bottleneck shared-specific feature transfer module (BSFT) to explore the shared and specific features between different modalities, where a few learnable bottleneck tokens are utilized for knowledge transfer between modalities. Moreover, a modal adaptation and orthogonal projection scheme were incorporated to further encourage BSFT to learn shared and specific features from multi-modal data. Finally, the shared and specific features are dynamically aggregated via an attention mechanism for slide-level prediction. Experimental results on our collected lymph node metastasis dataset demonstrate the efficiency of our proposed components and our framework achieves the best performance with AUC (area under the curve) of 97.34%, outperforming the state-of-the-art methods by over 1.27%.

Hybrid Graph Convolutional Network With Online Masked Autoencoder for Robust Multimodal Cancer Survival Prediction.

Cancer survival prediction requires exploiting related multimodal information (e.g., pathological, clinical and genomic features, etc.) and it is even more challenging in clinical practices due to the incompleteness of patient's multimodal data. Furthermore, existing methods lack sufficient intra- and inter-modal interactions, and suffer from significant performance degradation caused by missing modalities. This manuscript proposes a novel hybrid graph convolutional network, entitled HGCN, which is equipped with an online masked autoencoder paradigm for robust multimodal cancer survival prediction. Particularly, we pioneer modeling the patient's multimodal data into flexible and interpretable multimodal graphs with modality-specific preprocessing. HGCN integrates the advantages of graph convolutional networks (GCNs) and a hypergraph convolutional network (HCN) through node message passing and a hyperedge mixing mechanism to facilitate intra-modal and inter-modal interactions between multimodal graphs. With HGCN, the potential for multimodal data to create more reliable predictions of patient's survival risk is dramatically increased compared to prior methods. Most importantly, to compensate for missing patient modalities in clinical scenarios, we incorporated an online masked autoencoder paradigm into HGCN, which can effectively capture intrinsic dependence between modalities and seamlessly generate missing hyperedges for model inference. Extensive experiments and analysis on six cancer cohorts from TCGA show that our method significantly outperforms the state-of-the-arts in both complete and missing modal settings. Our codes are made available at https://github.com/lin-lcx/HGCN.

MuRCL: Multi-Instance Reinforcement Contrastive Learning for Whole Slide Image Classification.

Multi-instance learning (MIL) is widely adop- ted for automatic whole slide image (WSI) analysis and it usually consists of two stages, i.e., instance feature extraction and feature aggregation. However, due to the "weak supervision" of slide-level labels, the feature aggregation stage would suffer from severe over-fitting in training an effective MIL model. In this case, mining more information from limited slide-level data is pivotal to WSI analysis. Different from previous works on improving instance feature extraction, this paper investigates how to exploit the latent relationship of different instances (patches) to combat overfitting in MIL for more generalizable WSI classification. In particular, we propose a novel Multi-instance Rein- forcement Contrastive Learning framework (MuRCL) to deeply mine the inherent semantic relationships of different patches to advance WSI classification. Specifically, the proposed framework is first trained in a self-supervised manner and then finetuned with WSI slide-level labels. We formulate the first stage as a contrastive learning (CL) process, where positive/negative discriminative feature sets are constructed from the same patch-level feature bags of WSIs. To facilitate the CL training, we design a novel reinforcement learning-based agent to progressively update the selection of discriminative feature sets according to an online reward for slide-level feature aggregation. Then, we further update the model with labeled WSI data to regularize the learned features for the final WSI classification. Experimental results on three public WSI classification datasets (Camelyon16, TCGA-Lung and TCGA-Kidney) demonstrate that the proposed MuRCL outperforms state-of-the-art MIL models. In addition, MuRCL can achieve comparable performance to other state-of-the-art MIL models on TCGA-Esca dataset.

Data Discernment for Affordable Training in Medical Image Segmentation.

Collecting sufficient high-quality training data for deep neural networks is often expensive or even unaffordable in medical image segmentation tasks. We thus propose to train the network by using external data that can be collected in a cheaper way, e.g., crowd-sourcing. We show that by data discernment, the network is able to mine valuable knowledge from external data, even though the data distribution is very different from that of the original (internal) data. We discern the external data by learning an importance weight for each of them, with the goal to enhance the contribution of informative external data to network updating, while suppressing the data that are 'useless' or even 'harmful'. An iterative algorithm that alternatively estimates the importance weight and updates the network is developed by formulating the data discernment as a constrained nonlinear programming problem. It estimates the importance weight according to the distribution discrepancy between the external data and the internal dataset, and imposes a constraint to drive the network to learn more effectively, compared with the network without using the external data. We evaluate the proposed algorithm on two tasks: abdominal CT image and cervical smear image segmentation, using totally 6 publicly available datasets. The effectiveness of the algorithm is demonstrated by extensive experiments. Source codes are available at: https://github.com/YouyiSong/Data-Discernment.

4D-CT deformable image registration using unsupervised recursive cascaded full-resolution residual networks.

A novel recursive cascaded full-resolution residual network (RCFRR-Net) for abdominal four-dimensional computed tomography (4D-CT) image registration was proposed. The entire network was end-to-end and trained in the unsupervised approach, which meant that the deformation vector field, which presented the ground truth, was not needed during training. The network was designed by cascading three full-resolution residual subnetworks with different architectures. The training loss consisted of the image similarity loss and the deformation vector field regularization loss, which were calculated based on the final warped image and the fixed image, allowing all cascades to be trained jointly and perform the progressive registration cooperatively. Extensive network testing was conducted using diverse datasets, including an internal 4D-CT dataset, a public DIRLAB 4D-CT dataset, and a 4D cone-beam CT (4D-CBCT) dataset. Compared with the iteration-based demon method and two deep learning-based methods (VoxelMorph and recursive cascaded network), the RCFRR-Net achieved consistent and significant gains, which demonstrated that the proposed method had superior performance and generalization capability in medical image registration. The proposed RCFRR-Net was a promising tool for various clinical applications.

nnFormer: Volumetric Medical Image Segmentation via a 3D Transformer.

Transformer, the model of choice for natural language processing, has drawn scant attention from the medical imaging community. Given the ability to exploit long-term dependencies, transformers are promising to help atypical convolutional neural networks to learn more contextualized visual representations. However, most of recently proposed transformer-based segmentation approaches simply treated transformers as assisted modules to help encode global context into convolutional representations. To address this issue, we introduce nnFormer (i.e., not-another transFormer), a 3D transformer for volumetric medical image segmentation. nnFormer not only exploits the combination of interleaved convolution and self-attention operations, but also introduces local and global volume-based self-attention mechanism to learn volume representations. Moreover, nnFormer proposes to use skip attention to replace the traditional concatenation/summation operations in skip connections in U-Net like architecture. Experiments show that nnFormer significantly outperforms previous transformer-based counterparts by large margins on three public datasets. Compared to nnUNet, the most widely recognized convnet-based 3D medical segmentation model, nnFormer produces significantly lower HD95 and is much more computationally efficient. Furthermore, we show that nnFormer and nnUNet are highly complementary to each other in model ensembling. Codes and models of nnFormer are available at https://git.io/JSf3i.