Brain Magnetic Resonance Imaging

To be useful for downstream applications, vision decoding models that are trained to reconstruct seen images from human brain activity must be able to generalize to internally generated visual representations, i.e., mental images. In an analysis of the recently released NSD-Imagery dataset, we demonstrated that while some modern vision decoders can perform quite well on mental image reconstruction, some fail, and that state-of-the-art (SOTA) performance on seen image reconstruction is no guarantee of SOTA performance on mental image reconstruction. Motivated by these findings, we developed MIRAGE, a method explicitly designed to train on vision datasets and cross-decode mental images from brain activity. MIRAGE employs a linear backbone and multi-modal text and image features as input to a diffusion model. Feature metrics and human raters establish MIRAGE as SOTA for mental image reconstruction on the NSD-Imagery benchmark. With ablation analysis we show that mental image reconstruction works best when decoders use image features with relatively few dimensions and include guidance from text-based and both high- and low-level image-based features. Our work indicates that--given the right architecture--existing large-scale datasets using external stimuli are viable training data for decoding mental images, and warrant optimism about the future success and utility of mental image reconstruction.

Self-supervised learning (SSL) has advanced medical image analysis be enabling learning form large unlabelled data. However, in brain magnetic resonance imaging (MRI), most 3D models remain specialized for either segmentation of classification, limiting their ability to generalize across datasets, imaging protocols,, and downstream tasks. This lack of transferability constrains the clinical utility of 3D MRI models, despite the availability of unlabeled volumetric data. We present Volta-3D, a self-supervised 3D Vision Transformer framework designed to learn transferable volumetric representations. Volta-3D jointly aligns global class-style tokens and local patch tokens within a student-teacher paradigm and enforces fine-grained structural reconstruction. This combined global-local alignment addresses the limited semantic diversity and subtle anatomical characteristics of brain MRI, which challenges existing SSL approaches. We evaluate Volta-3D on multiple out-of-distribution downstream tasks, including hippocampal segmentation and classification of sex and Alzheimer's disease versus healthy controls. Across all tasks, representations learned by Volta-3D outperform randomly initialized baselines, demonstrating improved transferability and robustness under domain shift. Hence jointly enforcing global semantic consistency and local structural learning during pretraining enables broader concept learning from unlabeled brain MRI data. Overall VolTA-3D supports effective multi-task downstream performance with task-specific pertaining, a step towards generalizable and clinically viable 3D models.

Learning meaningful latent representations from nonlinear fMRI data remains a fundamental challenge in neuroimaging analysis. Traditional independent component analysis, widely used due to its ability to estimate interpretable functional brain networks, relies on a linear mixing assumption for latent sources, limiting its ability to capture the inherently nonlinear and complex organization of brain dynamics. More recently, deep representation learning methods have emerged as promising alternatives for modeling nonlinear latent structure. However, many of these approaches have been evaluated primarily on simulated datasets or natural image benchmarks, with comparatively limited validation on real-world neuroimaging data such as fMRI. In this work, we are motivated by the $β$-TCVAE (Total Correlation Variational Autoencoder), a refinement of the $β$-VAE framework for learning latent representations without introducing additional hyperparameters during training. We adapt and modify this model to fMRI data for nonlinear source disentanglement, aiming to separate mixed spatial and temporal brain signals into interpretable components. We show that the $β$-TCVAE framework can recover meaningful nonlinear spatial components with biological relevance, including well-established intrinsic connectivity networks such as the default mode network. Furthermore, we evaluate the learned representations using functional network connectivity, showing that the latent structure captures coherent and interpretable brain organization patterns. This study provides a pilot investigation that bridges nonlinear representation learning and fMRI analysis.

Clinical application of high-resolution diffusion MRI is hindered by hardware limitations and prohibitive scan times, motivating computational super-resolution. This study investigates the efficacy of a feature-based loss function in preserving diffusion signal consistency in deep learning super-resolution. Using 7T data from the human connectome project to generate pairs of low- and high-resolution diffusion weighted images (DWI), we trained UNets for 2D super-resolution. Ablation and isolation studies evaluated different VGG16-layers for feature-based losses against an image-based L1 baseline. Deeper layers and combinations thereof resulted in grid-like artifacts in super-resolution DWIs, which persisted in diffusion parameters like quantitative and fractional anisotropy. No such artifacts were present when using the shallowest layer. Downstream analysis for this layer showed great consistency with the ground truth, even for 9-fold super-resolution. Image SNR and used VGG16-layer depths modulated artifact appearance and severity, mandating careful selection of contributing layers for application in and beyond diffusion MRI.

Reconstructing dynamic visual experiences as videos from functional magnetic resonance imaging (fMRI) is pivotal for advancing the understanding of neural processes. However, current fMRI-to-video reconstruction methods are hindered by a semantic gap between noisy fMRI signals and the rich content of videos, stemming from a reliance on incomplete semantic embeddings that neither capture video-specific cues (e.g., actions) nor integrate prior knowledge. To this end, we draw inspiration from the dual-pathway processing mechanism in human brain and introduce CineNeuron, a novel hierarchical framework for semantically enhanced video reconstruction from fMRI signals with two synergistic stages. First, a bottom-up semantic enrichment stage maps fMRI signals to a rich embedding space that comprehensively captures textual semantics, image contents, action concepts, and object categories. Second, a top-down memory integration stage utilizes the proposed Mixture-of-Memories method to dynamically select relevant "memories" from previously seen data and fuse them with the fMRI embedding to refine the video reconstruction. Extensive experimental results on two fMRI-to-video benchmarks demonstrate that CineNeuron surpasses state-of-the-art methods across various metrics.

Spatio-temporal fetal brain atlases are important for characterizing normative neurodevelopment and identifying congenital anomalies. However, existing atlas construction pipelines necessitate days for slice-to-volume reconstruction (SVR) to generate high-resolution 3D brain volumes and several additional days for iterative volume registration, thereby rendering atlas construction from large-scale cohorts prohibitively impractical. We address these limitations with INFANiTE, an Implicit Neural Representation (INR) framework for high-resolution Fetal brain spatio-temporal Atlas learNing from clinical Thick-slicE MRI scans, bypassing both the costly SVR and the iterative non-rigid registration steps entirely, thereby substantially accelerating atlas construction. Extensive experiments demonstrate that INFANiTE outperforms existing baselines in subject consistency, reference fidelity, intrinsic quality and biological plausibility, even under challenging sparse-data settings. Additionally, INFANiTE reduces the end-to-end processing time (i.e., from raw scans to the final atlas) from days to hours compared to the traditional 3D volume-based pipeline (e.g., SyGN), facilitating large-scale population-level fetal brain analysis. Code: https://github.com/hu2274898/INFANiTE

Prenatal germinal matrix-intraventricular hemorrhage (GMH-IVH) is a leading cause of infant mortality and neurodevelopmental impairment, yet its manual diagnosis and lesion segmentation on fetal brain MRI are labor-intensive and error-prone. Although supervised deep learning offers potential for automation, it typically requires large amounts of annotated GMH-IVH data, which are challenging to obtain for such a rare condition (0.5-0.9 per 1000 pregnancies). To address these problems, an annotation-free deep learning framework, FreeHemoSeg, was developed for automated detection and segmentation of GMH-IVH without any real patient annotations. Instead of learning from expert labels, FreeHemoSeg was trained on pseudo GMH-IVH images synthesized from normal fetal data guided by medical priors. The framework was evaluated in a retrospective multicentre study of 1,674 stacks of 2D T2-weighted MRI from 558 pregnant women, using data from one hospital for internal training and validation and two hospitals for external validation. FreeHemoSeg achieved the highest diagnostic and segmentation performance in both internal validation (AUROC: 0.959; AUPR: 0.928; sensitivity: 0.914; specificity: 0.966; DSC: 0.559) and external validation (AUROC: 0.930; AUPR: 0.884; sensitivity: 0.824; specificity: 0.943; DSC: 0.512), outperforming a supervised model trained on limited empirical data and unsupervised anomaly detection methods. Moreover, FreeHemoSeg assistance improved radiologists' sensitivity (from 0.882 to 0.941-1.000) and diagnostic confidence, while reducing interpretation time by 16.0-52.7%. We anticipate its immediate utility in supporting earlier diagnosis, prognostic counselling, and perinatal planning for fetal GMH-IVH. Code: https://github.com/Arktis2022/FreeHemoSeg.

Existing cross-subject fMRI decoding methods typically train a model on multiple scanned subjects and then adapt it to a new subject using substantial paired fMRI-image data. However, in realistic scenarios, new-subject fMRI data are often limited due to costly data acquisition, and raw data from previous subjects may be inaccessible, leading existing methods to suffer performance degradation during new-subject adaptation. In this paper, we identify that this degradation stems from two key issues: brain-side instability caused by large subject differences in fMRI responses, and image-side supervision unreliability caused by fine-grained visual details that are not reliably supported by limited fMRI signals. To address these challenges, we propose StableMind, a regularized adaptation framework designed to improve brain-side representation stability and image-side supervision reliability. (1) To stabilize brain representations, StableMind reuses ridge projections from the pretrained model as adaptation priors to constrain limited-data new-subject adaptation, and applies Fourier-based feature-level brain augmentation to improve robustness to individual variability. (2) To improve image supervision reliability, StableMind introduces difficulty-aware image blur for brain-image alignment, reducing the influence of fine-grained visual details that are weakly supported by limited fMRI signals while preserving stable visual structure. Experiments on the Natural Scenes Dataset under a unified 1-hour adaptation protocol demonstrate that StableMind achieves 84.02% image retrieval accuracy and 81.66% brain retrieval accuracy averaged over four subjects, surpassing the state-of-the-art method by 5.71% brain retrieval accuracy with fewer trainable adaptation parameters. Our code is available at https://github.com/lingeringlight/StableMind.

Self-supervised pretraining is promising for large-scale neuroimaging, yet the impact of region-aware masking and hybrid sequence modeling remains underexplored. In this work, we introduce Rhamba, a region-aware pretraining framework that integrates anatomically guided masking with hybrid Attention-Mamba architectures for resting state functional magnetic resonance imaging (fMRI) analysis. Models were pretrained on the ABIDE dataset using region-aligned patch embeddings and three masking strategies (Any, Majority, and Pure) with increasing spatial specificity. We evaluated four architectural variants: a Mamba only model, an Alternate architecture with interleaved Mamba and Attention blocks, and two hybrid encoder-decoder configurations (Attention-Mamba (AM) and Mamba-Attention (MA)). The pretrained models were fine-tuned on downstream classification tasks using the COBRE and ADHD-200 datasets for schizophrenia and attention-deficit/hyperactivity disorder discrimination. We employed Integrated Gradients, an explainable AI method, to identify the brain regions contributing to model predictions. Masking strategy strongly influenced reconstruction behavior, with reconstruction loss following a consistent ordering (Any > Majority > Pure). However, this trend did not directly translate into downstream performance, where differences were modest and dataset-dependent. The hybrid architecture with the MA configuration achieved the highest average AUROC across both datasets, and Rhamba outperformed state-of-the-art methods in comparative evaluation. Region-wise analysis showed that peak performance depends on the interaction between masking strategy and architecture rather than a single dominant configuration. Overall, Rhamba offers a flexible framework for balancing interpretability, scalability, and performance in large-scale fMRI representation learning.

Brain MRI underpins a wide range of neuroscientific and clinical applications, yet most learning-based methods remain task-specific and require substantial labeled data. Here we show that a single self-supervised representation can generalize across heterogeneous brain MRI endpoints. We trained BrainDINO, a self-distilled foundation model, on approximately 6.6 million unlabeled axial slices from 20 datasets encompassing broad variation in population, disease, and acquisition setting. Using a frozen encoder with lightweight task heads, BrainDINO supported transfer across tumor segmentation, neurodegenerative and neurodevelopmental conditions classification, brain age estimation, post-stroke temporal prediction, molecular status prediction, MRI sequence classification, and survival modeling. Across tasks and supervision regimes, BrainDINO consistently equaled or exceeded natural-image and MRI-specific self-supervised baselines, with particularly strong advantages under label scarcity. Representation analyses further showed anatomically organized and pathology-sensitive feature structure in the absence of task-specific supervision. Our findings indicate that large-scale slice-wise self-supervised learning can yield a unified brain MRI representation that supports diverse neuroimaging tasks without volumetric pretraining or full-network fine-tuning, establishing a scalable foundation for robust and data-efficient brain imaging analysis. Code is available at https://github.com/mclwu22/BrainDINO

Encoding models provide a powerful framework for linking continuous stimulus features to neural activity; however, traditional voxelwise approaches are limited by measurement noise, inter-subject variability, and redundancy arising from spatially correlated voxels encoding overlapping neural signals. Here, we propose an independent component (IC)-based encoding framework that dissociates stimulus-driven and noise-driven signals in fMRI data. We decompose continuous fMRI data from naturalistic story listening into ICs using one subset of the data, and train encoding models on independent data to predict IC time series from large language model representations of linguistic input. Across subjects, a subset of ICs exhibited consistently high predictivity. These ICs were spatially and temporally consistent across subjects and included cognitive networks known to respond during story listening (auditory and language). Auditory component time series were strongly correlated with acoustic stimulus features, highlighting the interpretability of identified component time series. Components identified as noise or motion-related artifacts by ICA-AROMA showed uniformly poor predictive performance, confirming that highly predicted components reflect genuine stimulus-related neural signals rather than confounds. Overall, IC-based encoding models enable analyses at the level of functional networks, accommodating the variability in network locations across individuals and providing interpretable results that are easy to compare across subjects. Code provided at: https://github.com/kamyahari/IC-Encoding-Models.git

Resting-state functional magnetic resonance imaging (fMRI) has emerged as a cornerstone for psychiatric diagnosis, yet most approaches rely on pairwise brain cortical or sub-cortical connectivities that overlooks higher-order interactions (HOIs) central to complex brain dynamics. While hypergraph methods encode HOIs through predefined hyperedges, their construction typically relies on heuristic similarity metrics and does not explicitly characterize whether interactions are synergy- or redundancy-dominated. In this paper, we introduce $O$-information, a signed measure that characterizes the informational nature of HOIs, and integrate third- and fourth-order $O$-information into a unified multi-view information bottleneck framework for fMRI-based psychiatric diagnosis. To enable scalable $O$-information estimation, we further develop two independent acceleration strategies: a Gaussian analytical approximation and a randomized matrix-based Rényi entropy estimator, achieving over a 30-fold computational speedup compared with conventional estimators. Our tri-view architecture systematically fuses pairwise, triadic, and tetradic brain interactions, capturing comprehensive brain connectivity while explicitly penalizing redundancy. Extensive evaluation across four benchmark datasets (REST-meta-MDD, ABIDE, UCLA, ADNI) demonstrates consistent improvements, outperforming 11 baseline methods including state-of-the-art graph neural network (GNN) and hypergraph based approaches. Moreover, our method reveals interpretable region-level synergy-redundancy patterns which are not explicitly characterized by conventional hypergraph formulations.

How much data is enough to make a scientific discovery? As biomedical datasets scale to millions of samples and AI models grow in capacity, progress increasingly depends on predicting when additional data will substantially improve performance. In practice, model development often relies on empirical scaling curves measured across architectures, modalities, and dataset sizes, with limited theoretical guidance on when performance should improve, saturate, or exhibit cross-over behavior. We propose a scaling-law framework for cross-modal discoverability based on spectral structure of data covariance operators, task-aligned signal projections, and learned representations. Many performance metrics, including AUC, can be expressed in terms of cumulative signal-to-noise energy accumulated across identifiable spectral modes of an encoder and cross-modal operator. Under mild assumptions, this accumulation follows a zeta-like scaling law governed by power-law decay of covariance spectra and aligned signal energy, leading naturally to the appearance of the Riemann zeta function. Representation learning methods such as sparse models, low-rank embeddings, and multimodal contrastive objectives improve sample efficiency by concentrating useful signal into earlier stable modes, effectively steepening spectral decay and shifting scaling curves. The framework predicts cross-over regimes in which simpler models perform best at small sample sizes, while higher-capacity or multimodal encoders outperform them once sufficient data stabilizes additional degrees of freedom. Applications include multimodal disease classification, imaging genetics, functional MRI, and topological data analysis. The resulting zeta law provides a principled way to anticipate when scaling data, improving representations, or adding modalities is most likely to accelerate discovery.

Recent progress in visual brain decoding from fMRI has been enabled by large-scale datasets such as the Natural Scenes Dataset (NSD) and powerful diffusion-based generative models. While current pipelines are primarily optimized for perception, their performance under mental-imagery remains less well understood. In this work, we study how a state-of-the-art (SOTA) perception decoder (DynaDiff) can be adapted to reconstruct imagined content from the NSD-Imagery benchmark. We propose a latent functional alignment (LFA) approach that maps imagery-evoked activity to the pretrained model's semantic content-enriched conditioning space, by adding a simple alignment module, while keeping the original remaining components frozen. To mitigate the limited amount of matched imagery-perception supervision, we further introduce a neural retrieval-based augmentation strategy that selects semantically related NSD perception trials from the same participants. Across four subjects, LFA consistently improves high-level semantic reconstruction metrics relative to the frozen pretrained baseline and a voxel-space ridge alignment baseline, and enables above-chance decoding from multiple cortical regions. These results suggest that semantic structure learned from perception can be leveraged to stabilize and improve visual imagery decoding under out-of-distribution conditions.

Image registration is an ill-posed dense vision task, where multiple solutions achieve similar loss values, motivating probabilistic inference. Variational inference has previously been employed to capture these distributions, however restrictive assumptions about the posterior form can lead to poor characterisation, overconfidence and low-quality samples. More flexible posteriors are typically bottlenecked by the complexity of high-dimensional covariance matrices required for dense 3D image registration. In this work, we present a memory and computationally efficient inference method, Structured SIR, that enables expressive, multi-modal, characterisation of uncertainty with high quality samples. We propose the use of a Sampled Importance Resampling (SIR) algorithm with a novel memory-efficient high-dimensional covariance parameterisation as the sum of a low-rank covariance and a sparse, spatially structured Cholesky precision factor. This structure enables capturing complex spatial correlations while remaining computationally tractable. We evaluate the efficacy of this approach in 3D dense image registration of brain MRI data, which is a very high-dimensional problem. We demonstrate that our proposed method produces uncertainty estimates that are significantly better calibrated than those produced by variational methods, achieving equivalent or better accuracy. Crucially, we show that the model yields highly structured multi-modal posterior distributions, enable effective and efficient uncertainty quantification.

Accurate longitudinal analysis of brain MRI is often hindered by evolving lesions, which bias automated neuroimaging pipelines. While deep generative models have shown promise in inpainting these lesions, most existing methods operate cross-sectionally or lack 3D anatomical continuity. We present a novel pseudo-3D longitudinal inpainting framework based on Denoising Diffusion Probabilistic Models (DDPM). Our approach utilizes multi-channel conditioning to incorporate longitudinal context from distinct visits (t_1, t_2) and extends Region-Aware Diffusion (RAD) to the medical domain, focusing the generative process on pathological regions without altering surrounding healthy tissue. We evaluated our model against state-of-the-art baselines on longitudinal brain MRI from 93 patients. Our model significantly outperforms the leading baseline (FastSurfer-LIT) in terms of perceptual fidelity, reducing the Learned Perceptual Image Patch Similarity (LPIPS) distance from 0.07 to 0.03 while effectively eliminating inter-slice discontinuities. Furthermore, our model demonstrates high longitudinal stability with a Temporal Fidelity Index of 1.024, closely approaching the ideal value of 1.0 and substantially narrowing the gap compared to LIT's TFI of 1.22. Notably, the RAD mechanism provides a substantial gain in efficiency; our framework achieves an average processing time of 2.53 min per volume, representing approximately 10x speedup over the 24.30 min required by LIT. By leveraging longitudinal priors and region-specific denoising, our framework provides a highly reliable and efficient preprocessing step for the study of progressive neurodegenerative diseases. A derivative dataset consisting of 93 pre-processed scans used for testing will be available upon request after acceptance. Code will be released upon acceptance.

Demographic attributes can be predicted from medical images, raising concerns about bias in clinical AI systems. In X-ray imaging, acquisition characteristics have been shown to contribute substantially to this predictability. Whether the same holds in brain MRI remains unclear, as anatomical variation and acquisition-dependent contrast are deeply entangled in the image formation process, obscuring the origins of demographic signal. To address this, we propose a controlled framework based on disentangled representation learning, decomposing brain MRI into anatomy-focused representations that suppress acquisition influence and contrast embeddings that capture acquisition-dependent characteristics. Training predictive models for age, sex, and race on full images, anatomical representations, and contrast embeddings allows us to quantify the relative contributions of structure and acquisition to the demographic signal. Across three datasets and multiple MRI sequences, demographic predictability is found to be driven primarily by anatomical variation, with anatomy-focused representations largely preserving the performance of models trained on raw images. Contrast embeddings retain a weaker signal that is dataset-specific and does not generalise across sites. These findings suggest that effective mitigation must explicitly account for the primarily anatomical and secondarily acquisition-dependent origins of demographic signal, ensuring that any bias reduction generalizes robustly across domains.

Reconstructing natural images from fMRI requires bridging neural activity with both the structural and semantic representations used by modern generative models. Existing diffusion-based decoders often condition on a single global fMRI embedding, which limits their ability to exploit the hierarchical organization of the visual cortex and makes the contribution of different visual areas difficult to inspect. We propose Hi-DREAM, a brain-inspired hierarchical diffusion framework that structures fMRI conditioning according to early, middle, and late visual Regions of Interest (ROI) streams. A ROI adapter converts these streams into a multi-scale cortical pyramid, and a lightweight ROI-conditioned ControlNet injects the resulting anatomy-aware priors into matched U-Net depths during denoising. Experiments on the Natural Scenes Dataset (NSD) show that Hi-DREAM achieves state-of-the-art high-level semantic reconstruction while retaining strong low-level structure. Further ablation and attribution analyses show that the proposed hierarchy-aware conditioning is effective, and that different ROI streams provide complementary, inspectable contributions to reconstruction.

Acute ischemic stroke (AIS) requires time-critical decision-making, where inaccurate interpretation of neuroimaging findings can lead to irreversible disability. Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps from magnetic resonance imaging (MRI) are central to detecting acute infarction, yet generating factually reliable radiology reports directly from 3D MRI remains challenging due to the difficulty of learning robust cross-modal alignments between volumetric images and clinical text. We propose paired image-domain retrieval and text-domain augmentation (PIRTA), a retrieval-augmented generation framework that improves report factuality by avoiding explicit image-text alignment. PIRTA retrieves clinically similar 3D DWI/ADC volumes using a pretrained 3D vision encoder and leverages their paired clinician-authored reports to ground large language model (LLM)-based report generation. Experiments on multi-institutional in-house data, a held-out external privacy-preserving cohort, and the public ISLES benchmark demonstrate that PIRTA achieves strong image-domain retrieval performance and consistently improves ischemic-territory accuracy, a clinically grounded surrogate for report factuality, compared to direct image-to-text baselines. These results indicate that retrieval-grounded generation provides a scalable and reliable paradigm for producing factually consistent radiology reports from complex 3D brain MRI. Source code is available at https://github.com/jhlee0619/PIRTA.

Subcortical segmentation in neuroimages plays an important role in understanding brain anatomy and facilitating computer-aided diagnosis of traumatic brain injuries and neurodegenerative disorders. However, training accurate automatic models requires large amounts of labelled data. Despite the availability of publicly available subcortical segmentation datasets for Magnetic Resonance Imaging (MRI), a significant gap exists for Computed Tomography (CT). This paper proposes an automatic ensemble framework to generate high-quality subcortical segmentation labels for CT scans by leveraging existing MRI-based models. We introduce a robust ensembling pipeline to integrate them and apply it to unannotated paired MRI-CT data, resulting in a comprehensive CT subcortical segmentation dataset. Extensive experiments on multiple public datasets demonstrate the superior performance of our proposed framework. Furthermore, using our generated CT dataset, we train segmentation models that achieve improved performance on related segmentation tasks. To facilitate future research, we make our source code, generated dataset, and trained models publicly available at https://github.com/alxw0671/CT_Subcortical_Segmentation, marking the first open-source release for CT subcortical segmentation to the best of our knowledge.