Self-supervised learning has greatly facilitated medical image analysis by suppressing the training data requirement for real-world applications. Current paradigms predominantly rely on self-supervision within uni-modal image data, thereby neglecting the inter-modal correlations essential for effective learning of cross-modal image representations. This limitation is particularly significant for naturally grouped multi-modal data, e.g., multi-parametric MRI scans for a patient undergoing various functional imaging protocols in the same study. To bridge this gap, we conduct a novel multi-modal image pre-training with three proxy tasks to facilitate the learning of cross-modality representations and correlations using multi-modal brain MRI scans (over 2.4 million images in 16,022 scans of 3,755 patients), i.e., cross-modal image reconstruction, modality-aware contrastive learning, and modality template distillation. To demonstrate the generalizability of our pre-trained model, we conduct extensive experiments on various benchmarks with ten downstream tasks. The superior performance of our method is reported in comparison to state-of-the-art pre-training methods, with Dice Score improvement of 0.28%-14.47% across six segmentation benchmarks and a consistent accuracy boost of 0.65%-18.07% in four individual image classification tasks.

Multimodal large language models (MLLMs) have begun to demonstrate robust reasoning capabilities on general tasks, yet their application in the medical domain remains in its early stages. Constructing chain-of-thought (CoT) training data is essential for bolstering the reasoning abilities of medical MLLMs. However, existing approaches exhibit a deficiency in offering a comprehensive framework for searching and evaluating effective reasoning paths towards critical diagnosis. To address this challenge, we propose Mentor-Intern Collaborative Search (MICS), a novel reasoning-path searching scheme to generate rigorous and effective medical CoT data. MICS first leverages mentor models to initialize the reasoning, one step at a time, then prompts each intern model to continue the thinking along those initiated paths, and finally selects the optimal reasoning path according to the overall reasoning performance of multiple intern models. The reasoning performance is determined by an MICS-Score, which assesses the quality of generated reasoning paths. Eventually, we construct MMRP, a multi-task medical reasoning dataset with ranked difficulty, and Chiron-o1, a new medical MLLM devised via a curriculum learning strategy, with robust visual question-answering and generalizable reasoning capabilities. Extensive experiments demonstrate that Chiron-o1, trained on our CoT dataset constructed using MICS, achieves state-of-the-art performance across a list of medical visual question answering and reasoning benchmarks. Codes are available at https://github.com/Yankai96/Chiron-o1

Amyloid- positron emission tomography can reflect the Amyloid- protein deposition in the brain and thus serves as one of the golden standards for Alzheimer's disease (AD) diagnosis. However, its practical cost and high radioactivity hinder its application in large-scale early AD screening. Recent neuroscience studies suggest a strong association between changes in functional connectivity network (FCN) derived from functional MRI (fMRI), and deposition patterns of Amyloid- protein in the brain. This enables an FCN-based approach to assess the Amyloid- protein deposition with less expense and radioactivity. However, an effective FCN-based Amyloid- assessment remains lacking for practice. In this paper, we introduce a novel deep learning framework tailored for this task. Our framework comprises three innovative components: 1) a pre-trained Large Language Model Nodal Embedding Encoder, designed to extract task-related features from fMRI signals; 2) a task-oriented Hierarchical-order FCN Learning module, used to enhance the representation of complex correlations among different brain regions for improved prediction of Amyloid- deposition; and 3) task-feature consistency losses for promoting similarity between predicted and real Amyloid- values and ensuring effectiveness of predicted Amyloid- in downstream classification task. Experimental results show superiority of our method over several state-of-the-art FCN-based methods. Additionally, we identify crucial functional sub-networks for predicting Amyloid- depositions. The proposed method is anticipated to contribute valuable insights into the understanding of mechanisms of AD and its prevention.

Depression is a serious mental disorder with complex etiology, exhibiting strong heterogeneity in clinical manifestations such as various subtypes. Research on depression subtypes may deepen the understanding of the disease, contributing to the diagnosis and prognosis. While brain functional network and graph neural networks (GNNs) provide such a means, the task is still challenged by limited feature encoding from the informative fMRI data, ineffective information fusion of brain functional network, and small size of the recruited subjects. Therefore, we propose a hierarchical encoding and fusion framework of brain functions. First, we pre-train a model to extract the features from individual brain regions, which signify nodes in the brain functional network. Then, distinct graphs are constructed to link the nodes within each subject, resulting in multi-view graphs of the brain functional network. We further develop a graph fusion strategy to integrate the multi-view information, by referring to the local encoding of the nodes and their interactions across multiple graph instances. Finally, we attain the classification of depression subtypes based on the fused graph representation. The experimental results demonstrate that our method can superiorly distinguish major depression subtypes and outperform the state-of-the-art methods.

Image registration of liver dynamic contrast-enhanced computed tomography (DCE-CT) is crucial for diagnosis and image-guided surgical planning of liver cancer. However, intensity variations due to the flow of contrast agents combined with complex spatial motion induced by respiration brings great challenge to existing intensity-based registration methods. To address these problems, we propose a novel structure-aware registration method by incorporating structural information of related organs with segmentation-guided deep registration network. Existing segmentation-guided registration methods only focus on volumetric registration inside the paired organ segmentations, ignoring the inherent attributes of their anatomical structures. In addition, such paired organ segmentations are not always available in DCE-CT images due to the flow of contrast agents. Different from existing segmentation-guided registration methods, our proposed method extracts structural information in hierarchical geometric perspectives of line and surface. Then, according to the extracted structural information, structure-aware constraints are constructed and imposed on the forward and backward deformation field simultaneously. In this way, all available organ segmentations, including unpaired ones, can be fully utilized to avoid the side effect of contrast agent and preserve the topology of organs during registration. Extensive experiments on an in-house liver DCE-CT dataset and a public LiTS dataset show that our proposed method can achieve higher registration accuracy and preserve anatomical structure more effectively than state-of-the-art methods.

Resting-state fMRI (rs-fMRI) is an effective tool for quantifying functional connectivity (FC), which plays a crucial role in exploring various brain diseases. Due to the high dimensionality of fMRI data, FC is typically computed based on the region of interest (ROI), whose parcellation relies on a pre-defined atlas. However, utilizing the brain atlas poses several challenges including 1) subjective selection bias in choosing from various brain atlases, 2) parcellation of each subject's brain with the same atlas yet disregarding individual specificity; 3) lack of interaction between brain region parcellation and downstream ROI-based FC analysis. To address these limitations, we propose a novel randomizing strategy for generating brain function representation to facilitate neural disease diagnosis. Specifically, we randomly sample brain patches, thus avoiding ROI parcellations of the brain atlas. Then, we introduce a new brain function representation framework for the sampled patches. Each patch has its function description by referring to anchor patches, as well as the position description. Furthermore, we design an adaptive-selection-assisted Transformer network to optimize and integrate the function representations of all sampled patches within each brain for neural disease diagnosis. To validate our framework, we conduct extensive evaluations on three datasets, and the experimental results establish the effectiveness and generality of our proposed method, offering a promising avenue for advancing neural disease diagnosis beyond the confines of traditional atlas-based methods. Our code is available at https://github.com/mjliu2020/RandomFR.

Functional connectivity network (FCN) data from functional magnetic resonance imaging (fMRI) is increasingly used for the diagnosis of brain disorders. However, state-of-the-art studies used to build the FCN using a single brain parcellation atlas at a certain spatial scale, which largely neglected functional interactions across different spatial scales in hierarchical manners. In this study, we propose a novel framework to perform multiscale FCN analysis for brain disorder diagnosis. We first use a set of well-defined multiscale atlases to compute multiscale FCNs. Then, we utilize biologically meaningful brain hierarchical relationships among the regions in multiscale atlases to perform nodal pooling across multiple spatial scales, namely "Atlas-guided Pooling (AP)." Accordingly, we propose a multiscale-atlases-based hierarchical graph convolutional network (MAHGCN), built on the stacked layers of graph convolution and the AP, for a comprehensive extraction of diagnostic information from multiscale FCNs. Experiments on neuroimaging data from 1792 subjects demonstrate the effectiveness of our proposed method in the diagnoses of Alzheimer's disease (AD), the prodromal stage of AD [i.e., mild cognitive impairment (MCI)], as well as autism spectrum disorder (ASD), with the accuracy of 88.9%, 78.6%, and 72.7%, respectively. All results show significant advantages of our proposed method over other competing methods. This study not only demonstrates the feasibility of brain disorder diagnosis using resting-state fMRI empowered by deep learning but also highlights that the functional interactions in the multiscale brain hierarchy are worth being explored and integrated into deep learning network architectures for a better understanding of the neuropathology of brain disorders. The codes for MAHGCN are publicly available at "https://github.com/MianxinLiu/MAHGCN-code."

PET-based Alzheimer's disease (AD) assessment has many limitations in large-scale screening. Non-invasive techniques such as resting-state functional magnetic resonance imaging (rs-fMRI) have been proven valuable in early AD diagnosis. This study investigated feasibility of using rs-fMRI, especially functional connectivity (FC), for individualized assessment of brain amyloid-β deposition derived from PET. We designed a graph convolutional networks (GCNs) and random forest (RF) based integrated framework for using rs-fMRI-derived multi-level FC networks to predict amyloid-β PET patterns with the OASIS-3 (N = 258) and ADNI-2 (N = 291) datasets. Our method achieved satisfactory accuracy not only in Aβ-PET grade classification (for negative, intermediate, and positive grades, with accuracy in the three-class classification as 62.8% and 64.3% on two datasets, respectively), but also in prediction of whole-brain region-level Aβ-PET standard uptake value ratios (SUVRs) (with the mean square errors as 0.039 and 0.074 for two datasets, respectively). Model interpretability examination also revealed the contributive role of the limbic network. This study demonstrated high feasibility and reproducibility of using low-cost, more accessible magnetic resonance imaging (MRI) to approximate PET-based diagnosis.

In clinical practice, it is desirable for medical image segmentation models to be able to continually learn on a sequential data stream from multiple sites, rather than a consolidated dataset, due to storage cost and privacy restrictions. However, when learning on a new site, existing methods struggle with a weak memorizability for previous sites with complex shape and semantic information, and a poor explainability for the memory consolidation process. In this work, we propose a novel Shape and Semantics-based Selective Regularization ( [Formula: see text]) method for explainable cross-site continual segmentation to maintain both shape and semantic knowledge of previously learned sites. Specifically, [Formula: see text] method adopts a selective regularization scheme to penalize changes of parameters with high Joint Shape and Semantics-based Importance (JSSI) weights, which are estimated based on the parameter sensitivity to shape properties and reliable semantics of the segmentation object. This helps to prevent the related shape and semantic knowledge from being forgotten. Moreover, we propose an Importance Activation Mapping (IAM) method for memory interpretation, which indicates the spatial support for important parameters to visualize the memorized content. We have extensively evaluated our method on prostate segmentation and optic cup and disc segmentation tasks. Our method outperforms other comparison methods in reducing model forgetting and increasing explainability. Our code is available at https://github.com/jingyzhang/S3R.