Mingxia Liu

Hao Guan, Mingxia Liu

Domain adaptation (DA) is an important technique for modern machine learning-based medical data analysis, which aims at reducing distribution differences between different medical datasets. A proper domain adaptation method can significantly enhance the statistical power by pooling data acquired from multiple sites/centers. To this end, we have developed the Domain Adaptation Toolbox for Medical data analysis (DomainATM) - an open-source software package designed for fast facilitation and easy customization of domain adaptation methods for medical data analysis. The DomainATM is implemented in MATLAB with a user-friendly graphical interface, and it consists of a collection of popular data adaptation algorithms that have been extensively applied to medical image analysis and computer vision. With DomainATM, researchers are able to facilitate fast feature-level and image-level adaptation, visualization and performance evaluation of different adaptation methods for medical data analysis. More importantly, the DomainATM enables the users to develop and test their own adaptation methods through scripting, greatly enhancing its utility and extensibility. An overview characteristic and usage of DomainATM is presented and illustrated with three example experiments, demonstrating its effectiveness, simplicity, and flexibility. The software, source code, and manual are available online.

Yuqi Fang, Pew-Thian Yap, Weili Lin et al.

Unsupervised domain adaptation (UDA) via deep learning has attracted appealing attention for tackling domain-shift problems caused by distribution discrepancy across different domains. Existing UDA approaches highly depend on the accessibility of source domain data, which is usually limited in practical scenarios due to privacy protection, data storage and transmission cost, and computation burden. To tackle this issue, many source-free unsupervised domain adaptation (SFUDA) methods have been proposed recently, which perform knowledge transfer from a pre-trained source model to unlabeled target domain with source data inaccessible. A comprehensive review of these works on SFUDA is of great significance. In this paper, we provide a timely and systematic literature review of existing SFUDA approaches from a technical perspective. Specifically, we categorize current SFUDA studies into two groups, i.e., white-box SFUDA and black-box SFUDA, and further divide them into finer subcategories based on different learning strategies they use. We also investigate the challenges of methods in each subcategory, discuss the advantages/disadvantages of white-box and black-box SFUDA methods, conclude the commonly used benchmark datasets, and summarize the popular techniques for improved generalizability of models learned without using source data. We finally discuss several promising future directions in this field.

Hao Guan, Pew-Thian Yap, Andrea Bozoki et al.

Machine learning in medical imaging often faces a fundamental dilemma, namely, the small sample size problem. Many recent studies suggest using multi-domain data pooled from different acquisition sites/centers to improve statistical power. However, medical images from different sites cannot be easily shared to build large datasets for model training due to privacy protection reasons. As a promising solution, federated learning, which enables collaborative training of machine learning models based on data from different sites without cross-site data sharing, has attracted considerable attention recently. In this paper, we conduct a comprehensive survey of the recent development of federated learning methods in medical image analysis. In this survey, we first introduce the background knowledge of federated learning for dealing with privacy protection and collaborative learning issues in medical imaging. We then present a comprehensive review of recent advances in federated learning methods for medical image analysis. Specifically, existing methods are categorized based on three critical aspects of a federated learning system, including client end, server end, and communication techniques. In each category, we summarize the existing federated learning methods according to specific research problems in medical image analysis and also provide insights into the motivations of different approaches. In addition, we provide a review of existing benchmark medical imaging datasets and software platforms for current federated learning research. We also conduct an experimental study to empirically evaluate typical federated learning methods for medical image analysis. This survey can help to better understand the current research status, challenges, and potential research opportunities in this promising research field.

Lintao Zhang, Lihong Wang, Minhui Yu et al.

Late-life depression (LLD) is a highly prevalent mood disorder occurring in older adults and is frequently accompanied by cognitive impairment (CI). Studies have shown that LLD may increase the risk of Alzheimer's disease (AD). However, the heterogeneity of presentation of geriatric depression suggests that multiple biological mechanisms may underlie it. Current biological research on LLD progression incorporates machine learning that combines neuroimaging data with clinical observations. There are few studies on incident cognitive diagnostic outcomes in LLD based on structural MRI (sMRI). In this paper, we describe the development of a hybrid representation learning (HRL) framework for predicting cognitive diagnosis over 5 years based on T1-weighted sMRI data. Specifically, we first extract prediction-oriented MRI features via a deep neural network, and then integrate them with handcrafted MRI features via a Transformer encoder for cognitive diagnosis prediction. Two tasks are investigated in this work, including (1) identifying cognitively normal subjects with LLD and never-depressed older healthy subjects, and (2) identifying LLD subjects who developed CI (or even AD) and those who stayed cognitively normal over five years. To the best of our knowledge, this is among the first attempts to study the complex heterogeneous progression of LLD based on task-oriented and handcrafted MRI features. We validate the proposed HRL on 294 subjects with T1-weighted MRIs from two clinically harmonized studies. Experimental results suggest that the HRL outperforms several classical machine learning and state-of-the-art deep learning methods in LLD identification and prediction tasks.

Qianqian Wang, Wei Wang, Yuqi Fang et al.

Resting-state functional magnetic resonance imaging (rs-fMRI) can reflect spontaneous neural activities in brain and is widely used for brain disorder analysis.Previous studies propose to extract fMRI representations through diverse machine/deep learning methods for subsequent analysis. But the learned features typically lack biological interpretability, which limits their clinical utility. From the view of graph theory, the brain exhibits a remarkable modular structure in spontaneous brain functional networks, with each module comprised of functionally interconnected brain regions-of-interest (ROIs). However, most existing learning-based methods for fMRI analysis fail to adequately utilize such brain modularity prior. In this paper, we propose a Brain Modularity-constrained dynamic Representation learning (BMR) framework for interpretable fMRI analysis, consisting of three major components: (1) dynamic graph construction, (2) dynamic graph learning via a novel modularity-constrained graph neural network(MGNN), (3) prediction and biomarker detection for interpretable fMRI analysis. Especially, three core neurocognitive modules (i.e., salience network, central executive network, and default mode network) are explicitly incorporated into the MGNN, encouraging the nodes/ROIs within the same module to share similar representations. To further enhance discriminative ability of learned features, we also encourage the MGNN to preserve the network topology of input graphs via a graph topology reconstruction constraint. Experimental results on 534 subjects with rs-fMRI scans from two datasets validate the effectiveness of the proposed method. The identified discriminative brain ROIs and functional connectivities can be regarded as potential fMRI biomarkers to aid in clinical diagnosis.

Lintao Zhang, Jinjian Wu, Lihong Wang et al.

Brain structural MRI has been widely used to assess the future progression of cognitive impairment (CI). Previous learning-based studies usually suffer from the issue of small-sized labeled training data, while there exist a huge amount of structural MRIs in large-scale public databases. Intuitively, brain anatomical structures derived from these public MRIs (even without task-specific label information) can be used to boost CI progression trajectory prediction. However, previous studies seldom take advantage of such brain anatomy prior. To this end, this paper proposes a brain anatomy prior modeling (BAPM) framework to forecast the clinical progression of cognitive impairment with small-sized target MRIs by exploring anatomical brain structures. Specifically, the BAPM consists of a pretext model and a downstream model, with a shared brain anatomy-guided encoder to model brain anatomy prior explicitly. Besides the encoder, the pretext model also contains two decoders for two auxiliary tasks (i.e., MRI reconstruction and brain tissue segmentation), while the downstream model relies on a predictor for classification. The brain anatomy-guided encoder is pre-trained with the pretext model on 9,344 auxiliary MRIs without diagnostic labels for anatomy prior modeling. With this encoder frozen, the downstream model is then fine-tuned on limited target MRIs for prediction. We validate the BAPM on two CI-related studies with T1-weighted MRIs from 448 subjects. Experimental results suggest the effectiveness of BAPM in (1) four CI progression prediction tasks, (2) MR image reconstruction, and (3) brain tissue segmentation, compared with several state-of-the-art methods.

Hao Guan, Ling Yue, Pew-Thian Yap et al.

Subjective cognitive decline (SCD) is a preclinical stage of Alzheimer's disease (AD) which occurs even before mild cognitive impairment (MCI). Progressive SCD will convert to MCI with the potential of further evolving to AD. Therefore, early identification of progressive SCD with neuroimaging techniques (e.g., structural MRI) is of great clinical value for early intervention of AD. However, existing MRI-based machine/deep learning methods usually suffer the small-sample-size problem which poses a great challenge to related neuroimaging analysis. The central question we aim to tackle in this paper is how to leverage related domains (e.g., AD/NC) to assist the progression prediction of SCD. Meanwhile, we are concerned about which brain areas are more closely linked to the identification of progressive SCD. To this end, we propose an attention-guided autoencoder model for efficient cross-domain adaptation which facilitates the knowledge transfer from AD to SCD. The proposed model is composed of four key components: 1) a feature encoding module for learning shared subspace representations of different domains, 2) an attention module for automatically locating discriminative brain regions of interest defined in brain atlases, 3) a decoding module for reconstructing the original input, 4) a classification module for identification of brain diseases. Through joint training of these four modules, domain invariant features can be learned. Meanwhile, the brain disease related regions can be highlighted by the attention mechanism. Extensive experiments on the publicly available ADNI dataset and a private CLAS dataset have demonstrated the effectiveness of the proposed method. The proposed model is straightforward to train and test with only 5-10 seconds on CPUs and is suitable for medical tasks with small datasets.

Yuqi Fang, Jinjian Wu, Qianqian Wang et al.

Resting-state functional MRI (rs-fMRI) is increasingly employed in multi-site research to aid neurological disorder analysis. Existing studies usually suffer from significant cross-site/domain data heterogeneity caused by site effects such as differences in scanners/protocols. Many methods have been proposed to reduce fMRI heterogeneity between source and target domains, heavily relying on the availability of source data. But acquiring source data is challenging due to privacy concerns and/or data storage burdens in multi-site studies. To this end, we design a source-free collaborative domain adaptation (SCDA) framework for fMRI analysis, where only a pretrained source model and unlabeled target data are accessible. Specifically, a multi-perspective feature enrichment method (MFE) is developed for target fMRI analysis, consisting of multiple collaborative branches to dynamically capture fMRI features of unlabeled target data from multiple views. Each branch has a data-feeding module, a spatiotemporal feature encoder, and a class predictor. A mutual-consistency constraint is designed to encourage pair-wise consistency of latent features of the same input generated from these branches for robust representation learning. To facilitate efficient cross-domain knowledge transfer without source data, we initialize MFE using parameters of a pretrained source model. We also introduce an unsupervised pretraining strategy using 3,806 unlabeled fMRIs from three large-scale auxiliary databases, aiming to obtain a general feature encoder. Experimental results on three public datasets and one private dataset demonstrate the efficacy of our method in cross-scanner and cross-study prediction tasks. The model pretrained on large-scale rs-fMRI data has been released to the public.

Junhao Zhang, Qianqian Wang, Xiaochuan Wang et al.

Resting-state functional magnetic resonance imaging (rs-fMRI) offers a non-invasive approach to examining abnormal brain connectivity associated with brain disorders. Graph neural network (GNN) gains popularity in fMRI representation learning and brain disorder analysis with powerful graph representation capabilities. Training a general GNN often necessitates a large-scale dataset from multiple imaging centers/sites, but centralizing multi-site data generally faces inherent challenges related to data privacy, security, and storage burden. Federated Learning (FL) enables collaborative model training without centralized multi-site fMRI data. Unfortunately, previous FL approaches for fMRI analysis often ignore site-specificity, including demographic factors such as age, gender, and education level. To this end, we propose a specificity-aware federated graph learning (SFGL) framework for rs-fMRI analysis and automated brain disorder identification, with a server and multiple clients/sites for federated model aggregation and prediction. At each client, our model consists of a shared and a personalized branch, where parameters of the shared branch are sent to the server while those of the personalized branch remain local. This can facilitate knowledge sharing among sites and also helps preserve site specificity. In the shared branch, we employ a spatio-temporal attention graph isomorphism network to learn dynamic fMRI representations. In the personalized branch, we integrate vectorized demographic information (i.e., age, gender, and education years) and functional connectivity networks to preserve site-specific characteristics. Representations generated by the two branches are then fused for classification. Experimental results on two fMRI datasets with a total of 1,218 subjects suggest that SFGL outperforms several state-of-the-art approaches.

Mengqi Wu, Minhui Yu, Shuaiming Jing et al.

Multi-site structural MRI is increasingly used in neuroimaging studies to diversify subject cohorts. However, combining MR images acquired from various sites/centers may introduce site-related non-biological variations. Retrospective image harmonization helps address this issue, but current methods usually perform harmonization on pre-extracted hand-crafted radiomic features, limiting downstream applicability. Several image-level approaches focus on 2D slices, disregarding inherent volumetric information, leading to suboptimal outcomes. To this end, we propose a novel 3D MRI Harmonization framework through Conditional Latent Diffusion (HCLD) by explicitly considering image style and brain anatomy. It comprises a generalizable 3D autoencoder that encodes and decodes MRIs through a 4D latent space, and a conditional latent diffusion model that learns the latent distribution and generates harmonized MRIs with anatomical information from source MRIs while conditioned on target image style. This enables efficient volume-level MRI harmonization through latent style translation, without requiring paired images from target and source domains during training. The HCLD is trained and evaluated on 4,158 T1-weighted brain MRIs from three datasets in three tasks, assessing its ability to remove site-related variations while retaining essential biological features. Qualitative and quantitative experiments suggest the effectiveness of HCLD over several state-of-the-arts

Minhui Yu, Yongheng Sun, David S. Lalush et al.

Multi-tracer positron emission tomography (PET) provides critical insights into diverse neuropathological processes such as tau accumulation, neuroinflammation, and $β$-amyloid deposition in the brain, making it indispensable for comprehensive neurological assessment. However, routine acquisition of multi-tracer PET is limited by high costs, radiation exposure, and restricted tracer availability. Recent efforts have explored deep learning approaches for synthesizing PET images from structural MRI. While some methods rely solely on T1-weighted MRI, others incorporate additional sequences such as T2-FLAIR to improve pathological sensitivity. However, existing methods often struggle to capture fine-grained anatomical and pathological details, resulting in artifacts and unrealistic outputs. To this end, we propose RelA-Diffusion, a Relativistic Adversarial Diffusion framework for multi-tracer PET synthesis from multi-sequence MRI. By leveraging both T1-weighted and T2-FLAIR scans as complementary inputs, RelA-Diffusion captures richer structural information to guide image generation. To improve synthesis fidelity, we introduce a gradient-penalized relativistic adversarial loss to the intermediate clean predictions of the diffusion model. This loss compares real and generated images in a relative manner, encouraging the synthesis of more realistic local structures. Both the relativistic formulation and the gradient penalty contribute to stabilizing the training, while adversarial feedback at each diffusion timestep enables consistent refinement throughout the generation process. Extensive experiments on two datasets demonstrate that RelA-Diffusion outperforms existing methods in both visual fidelity and quantitative metrics, highlighting its potential for accurate synthesis of multi-tracer PET.

Yuqi Fang, Junhao Zhang, Linmin Wang et al.

Functional magnetic resonance imaging (fMRI) has been increasingly employed to investigate functional brain activity. Many fMRI-related software/toolboxes have been developed, providing specialized algorithms for fMRI analysis. However, existing toolboxes seldom consider fMRI data augmentation, which is quite useful, especially in studies with limited or imbalanced data. Moreover, current studies usually focus on analyzing fMRI using conventional machine learning models that rely on human-engineered fMRI features, without investigating deep learning models that can automatically learn data-driven fMRI representations. In this work, we develop an open-source toolbox, called Augmentation and Computation Toolbox for braIn netwOrk aNalysis (ACTION), offering comprehensive functions to streamline fMRI analysis. The ACTION is a Python-based and cross-platform toolbox with graphical user-friendly interfaces. It enables automatic fMRI augmentation, covering blood-oxygen-level-dependent (BOLD) signal augmentation and brain network augmentation. Many popular methods for brain network construction and network feature extraction are included. In particular, it supports constructing deep learning models, which leverage large-scale auxiliary unlabeled data (3,800+ resting-state fMRI scans) for model pretraining to enhance model performance for downstream tasks. To facilitate multi-site fMRI studies, it is also equipped with several popular federated learning strategies. Furthermore, it enables users to design and test custom algorithms through scripting, greatly improving its utility and extensibility. We demonstrate the effectiveness and user-friendliness of ACTION on real fMRI data and present the experimental results. The software, along with its source code and manual, can be accessed online.

Mengqi Wu, Yongheng Sun, Qianqian Wang et al.

Aggregating multi-site brain MRI data can enhance deep learning model training, but also introduces non-biological heterogeneity caused by site-specific variations (e.g., differences in scanner vendors, acquisition parameters, and imaging protocols) that can undermine generalizability. Recent retrospective MRI harmonization seeks to reduce such site effects by standardizing image style (e.g., intensity, contrast, noise patterns) while preserving anatomical content. However, existing methods often rely on limited paired traveling-subject data or fail to effectively disentangle style from anatomy. Furthermore, most current approaches address only single-sequence harmonization, restricting their use in real-world settings where multi-sequence MRI is routinely acquired. To this end, we introduce MMH, a unified framework for multi-site multi-sequence brain MRI harmonization that leverages biomedical semantic priors for sequence-aware style alignment. MMH operates in two stages: (1) a diffusion-based global harmonizer that maps MR images to a sequence-specific unified domain using style-agnostic gradient conditioning, and (2) a target-specific fine-tuner that adapts globally aligned images to desired target domains. A tri-planar attention BiomedCLIP encoder aggregates multi-view embeddings to characterize volumetric style information, allowing explicit disentanglement of image styles from anatomy without requiring paired data. Evaluations on 4,163 T1- and T2-weighted MRIs demonstrate MMH's superior harmonization over state-of-the-art methods in image feature clustering, voxel-level comparison, tissue segmentation, and downstream age and site classification.

Yingkun Hou, Jun Xu, Mingxia Liu et al.

Non-local self similarity (NSS) is a powerful prior of natural images for image denoising. Most of existing denoising methods employ similar patches, which is a patch-level NSS prior. In this paper, we take one step forward by introducing a pixel-level NSS prior, i.e., searching similar pixels across a non-local region. This is motivated by the fact that finding closely similar pixels is more feasible than similar patches in natural images, which can be used to enhance image denoising performance. With the introduced pixel-level NSS prior, we propose an accurate noise level estimation method, and then develop a blind image denoising method based on the lifting Haar transform and Wiener filtering techniques. Experiments on benchmark datasets demonstrate that, the proposed method achieves much better performance than previous non-deep methods, and is still competitive with existing state-of-the-art deep learning based methods on real-world image denoising. The code is publicly available at https://github.com/njusthyk1972/NLH.

Yongheng Sun, Yueh Z. Lee, Genevieve A. Woodard et al.

Radiology report generation is crucial in medical imaging,but the manual annotation process by physicians is time-consuming and labor-intensive, necessitating the develop-ment of automatic report generation methods. Existingresearch predominantly utilizes Transformers to generateradiology reports, which can be computationally intensive,limiting their use in real applications. In this work, we presentR2Gen-Mamba, a novel automatic radiology report genera-tion method that leverages the efficient sequence processingof the Mamba with the contextual benefits of Transformerarchitectures. Due to lower computational complexity ofMamba, R2Gen-Mamba not only enhances training and in-ference efficiency but also produces high-quality reports.Experimental results on two benchmark datasets with morethan 210,000 X-ray image-report pairs demonstrate the ef-fectiveness of R2Gen-Mamba regarding report quality andcomputational efficiency compared with several state-of-the-art methods. The source code can be accessed online.

Yongheng Sun, Mingxia Liu, Chunfeng Lian

Brain tumor segmentation is crucial for accurate diagnosisand treatment planning, but the small size and irregular shapeof tumors pose significant challenges. Existing methods of-ten fail to effectively incorporate medical domain knowledgesuch as tumor grade, which correlates with tumor aggres-siveness and morphology, providing critical insights for moreaccurate detection of tumor subregions during segmentation.We propose an Automated and Editable Prompt Learning(AEPL) framework that integrates tumor grade into the seg-mentation process by combining multi-task learning andprompt learning with automatic and editable prompt gen-eration. Specifically, AEPL employs an encoder to extractimage features for both tumor-grade prediction and segmen-tation mask generation. The predicted tumor grades serveas auto-generated prompts, guiding the decoder to produceprecise segmentation masks. This eliminates the need formanual prompts while allowing clinicians to manually editthe auto-generated prompts to fine-tune the segmentation,enhancing both flexibility and precision. The proposed AEPLachieves state-of-the-art performance on the BraTS 2018dataset, demonstrating its effectiveness and clinical potential.The source code can be accessed online.

Mengqi Wu, Lintao Zhang, Pew-Thian Yap et al.

Brain magnetic resonance imaging (MRI) has been extensively employed across clinical and research fields, but often exhibits sensitivity to site effects arising from non-biological variations such as differences in field strength and scanner vendors. Numerous retrospective MRI harmonization techniques have demonstrated encouraging outcomes in reducing the site effects at the image level. However, existing methods generally suffer from high computational requirements and limited generalizability, restricting their applicability to unseen MRIs. In this paper, we design a novel disentangled latent energy-based style translation (DLEST) framework for unpaired image-level MRI harmonization, consisting of (a) site-invariant image generation (SIG), (b) site-specific style translation (SST), and (c) site-specific MRI synthesis (SMS). Specifically, the SIG employs a latent autoencoder to encode MRIs into a low-dimensional latent space and reconstruct MRIs from latent codes. The SST utilizes an energy-based model to comprehend the global latent distribution of a target domain and translate source latent codes toward the target domain, while SMS enables MRI synthesis with a target-specific style. By disentangling image generation and style translation in latent space, the DLEST can achieve efficient style translation. Our model was trained on T1-weighted MRIs from a public dataset (with 3,984 subjects across 58 acquisition sites/settings) and validated on an independent dataset (with 9 traveling subjects scanned in 11 sites/settings) in four tasks: histogram and feature visualization, site classification, brain tissue segmentation, and site-specific structural MRI synthesis. Qualitative and quantitative results demonstrate the superiority of our method over several state-of-the-arts.

Minhui Yu, Mengqi Wu, Ling Yue et al.

Magnetic resonance imaging (MRI) and positron emission tomography (PET) are increasingly used in multimodal analysis of neurodegenerative disorders. While MRI is broadly utilized in clinical settings, PET is less accessible. Many studies have attempted to use deep generative models to synthesize PET from MRI scans. However, they often suffer from unstable training and inadequately preserve brain functional information conveyed by PET. To this end, we propose a functional imaging constrained diffusion (FICD) framework for 3D brain PET image synthesis with paired structural MRI as input condition, through a new constrained diffusion model (CDM). The FICD introduces noise to PET and then progressively removes it with CDM, ensuring high output fidelity throughout a stable training phase. The CDM learns to predict denoised PET with a functional imaging constraint introduced to ensure voxel-wise alignment between each denoised PET and its ground truth. Quantitative and qualitative analyses conducted on 293 subjects with paired T1-weighted MRI and 18F-fluorodeoxyglucose (FDG)-PET scans suggest that FICD achieves superior performance in generating FDG-PET data compared to state-of-the-art methods. We further validate the effectiveness of the proposed FICD on data from a total of 1,262 subjects through three downstream tasks, with experimental results suggesting its utility and generalizability.

Lintao Zhang, Mengqi Wu, Lihong Wang et al.

Image noise and motion artifacts greatly affect the quality of brain MRI and negatively influence downstream medical image analysis. Previous studies often focus on 2D methods that process each volumetric MR image slice-by-slice, thus losing important 3D anatomical information. Additionally, these studies generally treat image denoising and artifact correction as two standalone tasks, without considering their potential relationship, especially on low-quality images where severe noise and motion artifacts occur simultaneously. To address these issues, we propose a Joint image Denoising and motion Artifact Correction (JDAC) framework via iterative learning to handle noisy MRIs with motion artifacts, consisting of an adaptive denoising model and an anti-artifact model. In the adaptive denoising model, we first design a novel noise level estimation strategy, and then adaptively reduce the noise through a U-Net backbone with feature normalization conditioning on the estimated noise variance. The anti-artifact model employs another U-Net for eliminating motion artifacts, incorporating a novel gradient-based loss function designed to maintain the integrity of brain anatomy during the motion correction process. These two models are iteratively employed for joint image denoising and artifact correction through an iterative learning framework. An early stopping strategy depending on noise level estimation is applied to accelerate the iteration process. The denoising model is trained with 9,544 T1-weighted MRIs with manually added Gaussian noise as supervision. The anti-artifact model is trained on 552 T1-weighted MRIs with motion artifacts and paired motion-free images. Experimental results on a public dataset and a clinical study suggest the effectiveness of JDAC in both tasks of denoising and motion artifact correction, compared with several state-of-the-art methods.

Yuzhen Gao, Qianqian Wang, Yongheng Sun et al.

Accurate identification of late-life depression (LLD) using structural brain MRI is essential for monitoring disease progression and facilitating timely intervention. However, existing learning-based approaches for LLD detection are often constrained by limited sample sizes (e.g., tens), which poses significant challenges for reliable model training and generalization. Although incorporating auxiliary datasets can expand the training set, substantial domain heterogeneity, such as differences in imaging protocols, scanner hardware, and population demographics, often undermines cross-domain transferability. To address this issue, we propose a Collaborative Domain Adaptation (CDA) framework for LLD detection using T1-weighted MRIs. The CDA leverages a Vision Transformer (ViT) to capture global anatomical context and a Convolutional Neural Network (CNN) to extract local structural features, with each branch comprising an encoder and a classifier. The CDA framework consists of three stages: (a) supervised training on labeled source data, (b) self-supervised target feature adaptation and (c) collaborative training on unlabeled target data. We first train ViT and CNN on source data, followed by self-supervised target feature adaptation by minimizing the discrepancy between classifier outputs from two branches to make the categorical boundary clearer. The collaborative training stage employs pseudo-labeled and augmented target-domain MRIs, enforcing prediction consistency under strong and weak augmentation to enhance domain robustness and generalization. Extensive experiments conducted on multi-site T1-weighted MRI data demonstrate that the CDA consistently outperforms state-of-the-art unsupervised domain adaptation methods.

Meimei Yang, Yongheng Sun, Qianqian Wang et al.

Multimodal neuroimages, such as diffusion tensor imaging (DTI) and resting-state functional MRI (fMRI), offer complementary perspectives on brain activities by capturing structural or functional interactions among brain regions. While existing studies suggest that fusing these multimodal data helps detect abnormal brain activity caused by neurocognitive decline, they are generally implemented in Euclidean space and can't effectively capture intrinsic hierarchical organization of structural/functional brain networks. This paper presents a hyperbolic kernel graph fusion (HKGF) framework for neurocognitive decline analysis with multimodal neuroimages. It consists of a multimodal graph construction module, a graph representation learning module that encodes brain graphs in hyperbolic space through a family of hyperbolic kernel graph neural networks (HKGNNs), a cross-modality coupling module that enables effective multimodal data fusion, and a hyperbolic neural network for downstream predictions. Notably, HKGNNs represent graphs in hyperbolic space to capture both local and global dependencies among brain regions while preserving the hierarchical structure of brain networks. Extensive experiments involving over 4,000 subjects with DTI and/or fMRI data suggest the superiority of HKGF over state-of-the-art methods in two neurocognitive decline prediction tasks. HKGF is a general framework for multimodal data analysis, facilitating objective quantification of structural/functional brain connectivity changes associated with neurocognitive decline.

Qianqian Wang, Wei Wang, Yuqi Fang et al.

Brain networks/graphs derived from resting-state functional MRI (fMRI) help study underlying pathophysiology of neurocognitive disorders by measuring neuronal activities in the brain. Some studies utilize learning-based methods for brain network analysis, but typically suffer from low model generalizability caused by scarce labeled fMRI data. As a notable self-supervised strategy, graph contrastive learning helps leverage auxiliary unlabeled data. But existing methods generally arbitrarily perturb graph nodes/edges to generate augmented graphs, without considering essential topology information of brain networks. To this end, we propose a topology-aware graph augmentation (TGA) framework, comprising a pretext model to train a generalizable encoder on large-scale unlabeled fMRI cohorts and a task-specific model to perform downstream tasks on a small target dataset. In the pretext model, we design two novel topology-aware graph augmentation strategies: (1) hub-preserving node dropping that prioritizes preserving brain hub regions according to node importance, and (2) weight-dependent edge removing that focuses on keeping important functional connectivities based on edge weights. Experiments on 1, 688 fMRI scans suggest that TGA outperforms several state-of-the-art methods.

Mengting Xu, Tao Zhang, Zhongnian Li et al.

Deep learning models (with neural networks) have been widely used in challenging tasks such as computer-aided disease diagnosis based on medical images. Recent studies have shown deep diagnostic models may not be robust in the inference process and may pose severe security concerns in clinical practice. Among all the factors that make the model not robust, the most serious one is adversarial examples. The so-called "adversarial example" is a well-designed perturbation that is not easily perceived by humans but results in a false output of deep diagnostic models with high confidence. In this paper, we evaluate the robustness of deep diagnostic models by adversarial attack. Specifically, we have performed two types of adversarial attacks to three deep diagnostic models in both single-label and multi-label classification tasks, and found that these models are not reliable when attacked by adversarial example. We have further explored how adversarial examples attack the models, by analyzing their quantitative classification results, intermediate features, discriminability of features and correlation of estimated labels for both original/clean images and those adversarial ones. We have also designed two new defense methods to handle adversarial examples in deep diagnostic models, i.e., Multi-Perturbations Adversarial Training (MPAdvT) and Misclassification-Aware Adversarial Training (MAAdvT). The experimental results have shown that the use of defense methods can significantly improve the robustness of deep diagnostic models against adversarial attacks.

Hao Guan, Mingxia Liu

Machine learning techniques used in computer-aided medical image analysis usually suffer from the domain shift problem caused by different distributions between source/reference data and target data. As a promising solution, domain adaptation has attracted considerable attention in recent years. The aim of this paper is to survey the recent advances of domain adaptation methods in medical image analysis. We first present the motivation of introducing domain adaptation techniques to tackle domain heterogeneity issues for medical image analysis. Then we provide a review of recent domain adaptation models in various medical image analysis tasks. We categorize the existing methods into shallow and deep models, and each of them is further divided into supervised, semi-supervised and unsupervised methods. We also provide a brief summary of the benchmark medical image datasets that support current domain adaptation research. This survey will enable researchers to gain a better understanding of the current status, challenges.

Li Zhang, Mingliang Wang, Mingxia Liu et al.

Deep learning has been recently used for the analysis of neuroimages, such as structural magnetic resonance imaging (MRI), functional MRI, and positron emission tomography (PET), and has achieved significant performance improvements over traditional machine learning in computer-aided diagnosis of brain disorders. This paper reviews the applications of deep learning methods for neuroimaging-based brain disorder analysis. We first provide a comprehensive overview of deep learning techniques and popular network architectures, by introducing various types of deep neural networks and recent developments. We then review deep learning methods for computer-aided analysis of four typical brain disorders, including Alzheimer's disease, Parkinson's disease, Autism spectrum disorder, and Schizophrenia, where the first two diseases are neurodegenerative disorders and the last two are neurodevelopmental and psychiatric disorders, respectively. More importantly, we discuss the limitations of existing studies and present possible future directions.

Kelei He, Wei Zhao, Xingzhi Xie et al.

Understanding chest CT imaging of the coronavirus disease 2019 (COVID-19) will help detect infections early and assess the disease progression. Especially, automated severity assessment of COVID-19 in CT images plays an essential role in identifying cases that are in great need of intensive clinical care. However, it is often challenging to accurately assess the severity of this disease in CT images, due to variable infection regions in the lungs, similar imaging biomarkers, and large inter-case variations. To this end, we propose a synergistic learning framework for automated severity assessment of COVID-19 in 3D CT images, by jointly performing lung lobe segmentation and multi-instance classification. Considering that only a few infection regions in a CT image are related to the severity assessment, we first represent each input image by a bag that contains a set of 2D image patches (with each cropped from a specific slice). A multi-task multi-instance deep network (called M$^2$UNet) is then developed to assess the severity of COVID-19 patients and also segment the lung lobe simultaneously. Our M$^2$UNet consists of a patch-level encoder, a segmentation sub-network for lung lobe segmentation, and a classification sub-network for severity assessment (with a unique hierarchical multi-instance learning strategy). Here, the context information provided by segmentation can be implicitly employed to improve the performance of severity assessment. Extensive experiments were performed on a real COVID-19 CT image dataset consisting of 666 chest CT images, with results suggesting the effectiveness of our proposed method compared to several state-of-the-art methods.

Weida Li, Mingxia Liu, Daoqiang Zhang

Recently, Nyström method has proved its prominence empirically and theoretically in speeding up the training of kernel machines while retaining satisfactory performances and accuracy. So far, there are several different approaches proposed to exploit Nyström method in scaling up kernel machines. However, there is no comparative study over these approaches, and they were individually analyzed for specific types of kernel machines. Therefore, it remains a question that the philosophy of which approach is more promising when it extends to other kernel machines. In this work, motivated by the column inclusion property of Gram matrices, we develop a new approach with a clear geometric interpretation for running Nyström-based kernel machines. We show that the other two well-studied approaches can be equivalently transformed to be our proposed one. Consequently, analysis established for the proposed approach also works for these two. Particularly, our proposed approach makes it possible to develop approximation errors in a general setting. Besides, our analysis also manifests the relations among the aforementioned two approaches and another naive one. First, the analytical forms of the corresponding approximate solutions are only at odds with one term. Second, the naive approach can be implemented efficiently by sharing the same training procedure with others. These analytical results lead to the conjecture that the naive approach can provide more accurate approximate solutions than the other two sophisticated approaches. Since our analysis also offers ways for computing the accuracy of these approximate solutions, we run experiments with classification tasks to confirm our conjecture.

Weida Li, Mingxia Liu, Fang Chen et al.

Aggregating multi-subject functional magnetic resonance imaging (fMRI) data is indispensable for generating valid and general inferences from patterns distributed across human brains. The disparities in anatomical structures and functional topographies of human brains warrant aligning fMRI data across subjects. However, the existing functional alignment methods cannot handle well various kinds of fMRI datasets today, especially when they are not temporally-aligned, i.e., some of the subjects probably lack the responses to some stimuli, or different subjects might follow different sequences of stimuli. In this paper, a cross-subject graph that depicts the (dis)similarities between samples across subjects is used as a priori for developing a more flexible framework that suits an assortment of fMRI datasets. However, the high dimension of fMRI data and the use of multiple subjects makes the crude framework time-consuming or unpractical. To address this issue, we further regularize the framework, so that a novel feasible kernel-based optimization, which permits nonlinear feature extraction, could be theoretically developed. Specifically, a low-dimension assumption is imposed on each new feature space to avoid overfitting caused by the highspatial-low-temporal resolution of fMRI data. Experimental results on five datasets suggest that the proposed method is not only superior to several state-of-the-art methods on temporally-aligned fMRI data, but also suitable for dealing `with temporally-unaligned fMRI data.