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May 20

Percept-Aware Surgical Planning for Visual Cortical Prostheses with Vascular Avoidance

Cortical visual prostheses aim to restore sight by electrically stimulating neurons in early visual cortex (V1). With the emergence of high-density and flexible neural interfaces, electrode placement within three-dimensional cortex has become a critical surgical planning problem. Existing strategies emphasize visual field coverage and anatomical heuristics but do not directly optimize predicted perceptual outcomes under safety constraints. We present a percept-aware framework for surgical planning of cortical visual prostheses that formulates electrode placement as a constrained optimization problem in anatomical space. Electrode coordinates are treated as learnable parameters and optimized end-to-end using a differentiable forward model of prosthetic vision. The objective minimizes task-level perceptual error while incorporating vascular avoidance and gray matter feasibility constraints. Evaluated on simulated reading and natural image tasks using realistic folded cortical geometry (FreeSurfer fsaverage), percept-aware optimization consistently improves reconstruction fidelity relative to coverage-based placement strategies. Importantly, vascular safety constraints eliminate margin violations while preserving perceptual performance. The framework further enables co-optimization of multi-electrode thread configurations under fixed insertion budgets. These results demonstrate how differentiable percept models can inform anatomically grounded, safety-aware computer-assisted planning for cortical neural interfaces and provide a foundation for optimizing next-generation visual prostheses.

  • 4 authors
·
Feb 27

Diffusion-Driven Generation of Minimally Preprocessed Brain MRI

The purpose of this study is to present and compare three denoising diffusion probabilistic models (DDPMs) that generate 3D T_1-weighted MRI human brain images. Three DDPMs were trained using 80,675 image volumes from 42,406 subjects spanning 38 publicly available brain MRI datasets. These images had approximately 1 mm isotropic resolution and were manually inspected by three human experts to exclude those with poor quality, field-of-view issues, and excessive pathology. The images were minimally preprocessed to preserve the visual variability of the data. Furthermore, to enable the DDPMs to produce images with natural orientation variations and inhomogeneity, the images were neither registered to a common coordinate system nor bias field corrected. Evaluations included segmentation, Frechet Inception Distance (FID), and qualitative inspection. Regarding results, all three DDPMs generated coherent MR brain volumes. The velocity and flow prediction models achieved lower FIDs than the sample prediction model. However, all three models had higher FIDs compared to real images across multiple cohorts. In a permutation experiment, the generated brain regional volume distributions differed statistically from real data. However, the velocity and flow prediction models had fewer statistically different volume distributions in the thalamus and putamen. In conclusion this work presents and releases the first 3D non-latent diffusion model for brain data without skullstripping or registration. Despite the negative results in statistical testing, the presented DDPMs are capable of generating high-resolution 3D T_1-weighted brain images. All model weights and corresponding inference code are publicly available at https://github.com/piksl-research/medforj .

  • 4 authors
·
Oct 29, 2025

Brain-IT: Image Reconstruction from fMRI via Brain-Interaction Transformer

Reconstructing images seen by people from their fMRI brain recordings provides a non-invasive window into the human brain. Despite recent progress enabled by diffusion models, current methods often lack faithfulness to the actual seen images. We present "Brain-IT", a brain-inspired approach that addresses this challenge through a Brain Interaction Transformer (BIT), allowing effective interactions between clusters of functionally-similar brain-voxels. These functional-clusters are shared by all subjects, serving as building blocks for integrating information both within and across brains. All model components are shared by all clusters & subjects, allowing efficient training with a limited amount of data. To guide the image reconstruction, BIT predicts two complementary localized patch-level image features: (i)high-level semantic features which steer the diffusion model toward the correct semantic content of the image; and (ii)low-level structural features which help to initialize the diffusion process with the correct coarse layout of the image. BIT's design enables direct flow of information from brain-voxel clusters to localized image features. Through these principles, our method achieves image reconstructions from fMRI that faithfully reconstruct the seen images, and surpass current SotA approaches both visually and by standard objective metrics. Moreover, with only 1-hour of fMRI data from a new subject, we achieve results comparable to current methods trained on full 40-hour recordings.

Improving visual image reconstruction from human brain activity using latent diffusion models via multiple decoded inputs

The integration of deep learning and neuroscience has been advancing rapidly, which has led to improvements in the analysis of brain activity and the understanding of deep learning models from a neuroscientific perspective. The reconstruction of visual experience from human brain activity is an area that has particularly benefited: the use of deep learning models trained on large amounts of natural images has greatly improved its quality, and approaches that combine the diverse information contained in visual experiences have proliferated rapidly in recent years. In this technical paper, by taking advantage of the simple and generic framework that we proposed (Takagi and Nishimoto, CVPR 2023), we examine the extent to which various additional decoding techniques affect the performance of visual experience reconstruction. Specifically, we combined our earlier work with the following three techniques: using decoded text from brain activity, nonlinear optimization for structural image reconstruction, and using decoded depth information from brain activity. We confirmed that these techniques contributed to improving accuracy over the baseline. We also discuss what researchers should consider when performing visual reconstruction using deep generative models trained on large datasets. Please check our webpage at https://sites.google.com/view/stablediffusion-with-brain/. Code is also available at https://github.com/yu-takagi/StableDiffusionReconstruction.

  • 2 authors
·
Jun 20, 2023

NeuroBOLT: Resting-state EEG-to-fMRI Synthesis with Multi-dimensional Feature Mapping

Functional magnetic resonance imaging (fMRI) is an indispensable tool in modern neuroscience, providing a non-invasive window into whole-brain dynamics at millimeter-scale spatial resolution. However, fMRI is constrained by issues such as high operation costs and immobility. With the rapid advancements in cross-modality synthesis and brain decoding, the use of deep neural networks has emerged as a promising solution for inferring whole-brain, high-resolution fMRI features directly from electroencephalography (EEG), a more widely accessible and portable neuroimaging modality. Nonetheless, the complex projection from neural activity to fMRI hemodynamic responses and the spatial ambiguity of EEG pose substantial challenges both in modeling and interpretability. Relatively few studies to date have developed approaches for EEG-fMRI translation, and although they have made significant strides, the inference of fMRI signals in a given study has been limited to a small set of brain areas and to a single condition (i.e., either resting-state or a specific task). The capability to predict fMRI signals in other brain areas, as well as to generalize across conditions, remain critical gaps in the field. To tackle these challenges, we introduce a novel and generalizable framework: NeuroBOLT, i.e., Neuro-to-BOLD Transformer, which leverages multi-dimensional representation learning from temporal, spatial, and spectral domains to translate raw EEG data to the corresponding fMRI activity signals across the brain. Our experiments demonstrate that NeuroBOLT effectively reconstructs unseen resting-state fMRI signals from primary sensory, high-level cognitive areas, and deep subcortical brain regions, achieving state-of-the-art accuracy with the potential to generalize across varying conditions and sites, which significantly advances the integration of these two modalities.

  • 10 authors
·
Oct 6, 2024

Explainable AI for Accelerated Microstructure Imaging: A SHAP-Guided Protocol on the Connectome 2.0 scanner

The diffusion MRI Neurite Exchange Imaging model offers a promising framework for probing gray matter microstructure by estimating parameters such as compartment sizes, diffusivities, and inter-compartmental water exchange time. However, existing protocols require long scan times. This study proposes a reduced acquisition scheme for the Connectome 2.0 scanner that preserves model accuracy while substantially shortening scan duration. We developed a data-driven framework using explainable artificial intelligence with a guided recursive feature elimination strategy to identify an optimal 8-feature subset from a 15-feature protocol. The performance of this optimized protocol was validated in vivo and benchmarked against the full acquisition and alternative reduction strategies. Parameter accuracy, preservation of anatomical contrast, and test-retest reproducibility were assessed. The reduced protocol yielded parameter estimates and cortical maps comparable to the full protocol, with low estimation errors in synthetic data and minimal impact on test-retest variability. Compared to theory-driven and heuristic reduction schemes, the optimized protocol demonstrated superior robustness, reducing the deviation in water exchange time estimates by over two-fold. In conclusion, this hybrid optimization framework enables viable imaging of neurite exchange in 14 minutes without loss of parameter fidelity. This approach supports the broader application of exchange-sensitive diffusion magnetic resonance imaging in neuroscience and clinical research, and offers a generalizable method for designing efficient acquisition protocols in biophysical parameter mapping.

  • 13 authors
·
Sep 11, 2025

The whole brain architecture approach: Accelerating the development of artificial general intelligence by referring to the brain

The vastness of the design space created by the combination of a large number of computational mechanisms, including machine learning, is an obstacle to creating an artificial general intelligence (AGI). Brain-inspired AGI development, in other words, cutting down the design space to look more like a biological brain, which is an existing model of a general intelligence, is a promising plan for solving this problem. However, it is difficult for an individual to design a software program that corresponds to the entire brain because the neuroscientific data required to understand the architecture of the brain are extensive and complicated. The whole-brain architecture approach divides the brain-inspired AGI development process into the task of designing the brain reference architecture (BRA) -- the flow of information and the diagram of corresponding components -- and the task of developing each component using the BRA. This is called BRA-driven development. Another difficulty lies in the extraction of the operating principles necessary for reproducing the cognitive-behavioral function of the brain from neuroscience data. Therefore, this study proposes the Structure-constrained Interface Decomposition (SCID) method, which is a hypothesis-building method for creating a hypothetical component diagram consistent with neuroscientific findings. The application of this approach has begun for building various regions of the brain. Moving forward, we will examine methods of evaluating the biological plausibility of brain-inspired software. This evaluation will also be used to prioritize different computational mechanisms, which should be merged, associated with the same regions of the brain.

  • 1 authors
·
Mar 5, 2021

HA-HI: Synergising fMRI and DTI through Hierarchical Alignments and Hierarchical Interactions for Mild Cognitive Impairment Diagnosis

Early diagnosis of mild cognitive impairment (MCI) and subjective cognitive decline (SCD) utilizing multi-modal magnetic resonance imaging (MRI) is a pivotal area of research. While various regional and connectivity features from functional MRI (fMRI) and diffusion tensor imaging (DTI) have been employed to develop diagnosis models, most studies integrate these features without adequately addressing their alignment and interactions. This limits the potential to fully exploit the synergistic contributions of combined features and modalities. To solve this gap, our study introduces a novel Hierarchical Alignments and Hierarchical Interactions (HA-HI) method for MCI and SCD classification, leveraging the combined strengths of fMRI and DTI. HA-HI efficiently learns significant MCI- or SCD- related regional and connectivity features by aligning various feature types and hierarchically maximizing their interactions. Furthermore, to enhance the interpretability of our approach, we have developed the Synergistic Activation Map (SAM) technique, revealing the critical brain regions and connections that are indicative of MCI/SCD. Comprehensive evaluations on the ADNI dataset and our self-collected data demonstrate that HA-HI outperforms other existing methods in diagnosing MCI and SCD, making it a potentially vital and interpretable tool for early detection. The implementation of this method is publicly accessible at https://github.com/ICI-BCI/Dual-MRI-HA-HI.git.

  • 7 authors
·
Jan 2, 2024

Individualizing Glioma Radiotherapy Planning by Optimization of Data and Physics-Informed Discrete Loss

Brain tumor growth is unique to each glioma patient and extends beyond what is visible in imaging scans, infiltrating surrounding brain tissue. Understanding these hidden patient-specific progressions is essential for effective therapies. Current treatment plans for brain tumors, such as radiotherapy, typically involve delineating a uniform margin around the visible tumor on pre-treatment scans to target this invisible tumor growth. This "one size fits all" approach is derived from population studies and often fails to account for the nuances of individual patient conditions. We present the GliODIL framework, which infers the full spatial distribution of tumor cell concentration from available multi-modal imaging, leveraging a Fisher-Kolmogorov type physics model to describe tumor growth. This is achieved through the newly introduced method of Optimizing the Discrete Loss (ODIL), where both data and physics-based constraints are softly assimilated into the solution. Our test dataset comprises 152 glioblastoma patients with pre-treatment imaging and post-treatment follow-ups for tumor recurrence monitoring. By blending data-driven techniques with physics-based constraints, GliODIL enhances recurrence prediction in radiotherapy planning, challenging traditional uniform margins and strict adherence to the Fisher-Kolmogorov partial differential equation (PDE) model, which is adapted for complex cases.

  • 10 authors
·
Dec 8, 2023

Brain Diffusion for Visual Exploration: Cortical Discovery using Large Scale Generative Models

A long standing goal in neuroscience has been to elucidate the functional organization of the brain. Within higher visual cortex, functional accounts have remained relatively coarse, focusing on regions of interest (ROIs) and taking the form of selectivity for broad categories such as faces, places, bodies, food, or words. Because the identification of such ROIs has typically relied on manually assembled stimulus sets consisting of isolated objects in non-ecological contexts, exploring functional organization without robust a priori hypotheses has been challenging. To overcome these limitations, we introduce a data-driven approach in which we synthesize images predicted to activate a given brain region using paired natural images and fMRI recordings, bypassing the need for category-specific stimuli. Our approach -- Brain Diffusion for Visual Exploration ("BrainDiVE") -- builds on recent generative methods by combining large-scale diffusion models with brain-guided image synthesis. Validating our method, we demonstrate the ability to synthesize preferred images with appropriate semantic specificity for well-characterized category-selective ROIs. We then show that BrainDiVE can characterize differences between ROIs selective for the same high-level category. Finally we identify novel functional subdivisions within these ROIs, validated with behavioral data. These results advance our understanding of the fine-grained functional organization of human visual cortex, and provide well-specified constraints for further examination of cortical organization using hypothesis-driven methods.

  • 4 authors
·
Jun 5, 2023

Brain decoding: toward real-time reconstruction of visual perception

In the past five years, the use of generative and foundational AI systems has greatly improved the decoding of brain activity. Visual perception, in particular, can now be decoded from functional Magnetic Resonance Imaging (fMRI) with remarkable fidelity. This neuroimaging technique, however, suffers from a limited temporal resolution (approx0.5 Hz) and thus fundamentally constrains its real-time usage. Here, we propose an alternative approach based on magnetoencephalography (MEG), a neuroimaging device capable of measuring brain activity with high temporal resolution (approx5,000 Hz). For this, we develop an MEG decoding model trained with both contrastive and regression objectives and consisting of three modules: i) pretrained embeddings obtained from the image, ii) an MEG module trained end-to-end and iii) a pretrained image generator. Our results are threefold: Firstly, our MEG decoder shows a 7X improvement of image-retrieval over classic linear decoders. Second, late brain responses to images are best decoded with DINOv2, a recent foundational image model. Third, image retrievals and generations both suggest that high-level visual features can be decoded from MEG signals, although the same approach applied to 7T fMRI also recovers better low-level features. Overall, these results, while preliminary, provide an important step towards the decoding -- in real-time -- of the visual processes continuously unfolding within the human brain.

  • 3 authors
·
Oct 18, 2023

GOUHFI 2.0: A Next-Generation Toolbox for Brain Segmentation and Cortex Parcellation at Ultra-High Field MRI

Ultra-High Field MRI (UHF-MRI) is increasingly used in large-scale neuroimaging studies, yet automatic brain segmentation and cortical parcellation remain challenging due to signal inhomogeneities, heterogeneous contrasts and resolutions, and the limited availability of tools optimized for UHF data. Standard software packages such as FastSurferVINN and SynthSeg+ often yield suboptimal results when applied directly to UHF images, thereby restricting region-based quantitative analyses. To address this need, we introduce GOUHFI 2.0, an updated implementation of GOUHFI that incorporates increased training data variability and additional functionalities, including cortical parcellation and volumetry. GOUHFI 2.0 preserves the contrast- and resolution-agnostic design of the original toolbox while introducing two independently trained 3D U-Net segmentation tasks. The first performs whole-brain segmentation into 35 labels across contrasts, resolutions, field strengths and populations, using a domain-randomization strategy and a training dataset of 238 subjects. Using the same training data, the second network performs cortical parcellation into 62 labels following the Desikan-Killiany-Tourville (DKT) protocol. Across multiple datasets, GOUHFI 2.0 demonstrated improved segmentation accuracy relative to the original toolbox, particularly in heterogeneous cohorts, and produced reliable cortical parcellations. In addition, the integrated volumetry pipeline yielded results consistent with standard volumetric workflows. Overall, GOUHFI 2.0 provides a comprehensive solution for brain segmentation, parcellation and volumetry across field strengths, and constitutes the first deep-learning toolbox enabling robust cortical parcellation at UHF-MRI.

  • 3 authors
·
Mar 9

Brain3D: Generating 3D Objects from fMRI

Understanding the hidden mechanisms behind human's visual perception is a fundamental question in neuroscience. To that end, investigating into the neural responses of human mind activities, such as functional Magnetic Resonance Imaging (fMRI), has been a significant research vehicle. However, analyzing fMRI signals is challenging, costly, daunting, and demanding for professional training. Despite remarkable progress in fMRI analysis, existing approaches are limited to generating 2D images and far away from being biologically meaningful and practically useful. Under this insight, we propose to generate visually plausible and functionally more comprehensive 3D outputs decoded from brain signals, enabling more sophisticated modeling of fMRI data. Conceptually, we reformulate this task as a {\em fMRI conditioned 3D object generation} problem. We design a novel 3D object representation learning method, Brain3D, that takes as input the fMRI data of a subject who was presented with a 2D image, and yields as output the corresponding 3D object images. The key capabilities of this model include tackling the noises with high-level semantic signals and a two-stage architecture design for progressive high-level information integration. Extensive experiments validate the superior capability of our model over previous state-of-the-art 3D object generation methods. Importantly, we show that our model captures the distinct functionalities of each region of human vision system as well as their intricate interplay relationships, aligning remarkably with the established discoveries in neuroscience. Further, preliminary evaluations indicate that Brain3D can successfully identify the disordered brain regions in simulated scenarios, such as V1, V2, V3, V4, and the medial temporal lobe (MTL) within the human visual system. Our data and code will be available at https://brain-3d.github.io/.

  • 7 authors
·
May 24, 2024

A Demographic-Conditioned Variational Autoencoder for fMRI Distribution Sampling and Removal of Confounds

Objective: fMRI and derived measures such as functional connectivity (FC) have been used to predict brain age, general fluid intelligence, psychiatric disease status, and preclinical neurodegenerative disease. However, it is not always clear that all demographic confounds, such as age, sex, and race, have been removed from fMRI data. Additionally, many fMRI datasets are restricted to authorized researchers, making dissemination of these valuable data sources challenging. Methods: We create a variational autoencoder (VAE)-based model, DemoVAE, to decorrelate fMRI features from demographics and generate high-quality synthetic fMRI data based on user-supplied demographics. We train and validate our model using two large, widely used datasets, the Philadelphia Neurodevelopmental Cohort (PNC) and Bipolar and Schizophrenia Network for Intermediate Phenotypes (BSNIP). Results: We find that DemoVAE recapitulates group differences in fMRI data while capturing the full breadth of individual variations. Significantly, we also find that most clinical and computerized battery fields that are correlated with fMRI data are not correlated with DemoVAE latents. An exception are several fields related to schizophrenia medication and symptom severity. Conclusion: Our model generates fMRI data that captures the full distribution of FC better than traditional VAE or GAN models. We also find that most prediction using fMRI data is dependent on correlation with, and prediction of, demographics. Significance: Our DemoVAE model allows for generation of high quality synthetic data conditioned on subject demographics as well as the removal of the confounding effects of demographics. We identify that FC-based prediction tasks are highly influenced by demographic confounds.

  • 10 authors
·
May 13, 2024

SIAM: Head and Brain MRI Segmentation from Few High-Quality Templates via Synthetic Training

Synthetic training has recently advanced brain MRI segmentation by enabling contrast-agnostic models trained entirely on generated data. However, most existing approaches rely on hundreds of automatically labeled templates, introducing systematic biases and limiting their flexibility to incorporate new anatomical structures. We present the Segment It All Model (SIAM), a 3D whole-head segmentation framework for 16 anatomical structures, trained using only six high-quality, manually annotated templates. SIAM extends domain randomization to both intensity and shape domains: synthetic image generation ensures contrast variability, while high-resolution spatial transformations model anatomical differences in cortical thickness and deep nuclei morphology. Unlike prior synthetic models, SIAM simultaneously segments brain as well as extra-cerebral tissues, including cerebrospinal fluid, vessels, dura mater, skull, and skin, enabling fully automated, preprocessing-free analysis. Evaluation across eight heterogeneous datasets (N=301), that include multiple contrasts (T1-weighted, T2-weighted, CT) and span a wide range of ages, demonstrates that SIAM matches or outperforms state-of-the-art methods for brain structures, in addition to extending automated segmentation to non-brain structures. The model also exhibits superior consistency across contrasts and repeated acquisitions, together with improved sensitivity to subtle gray matter atrophy. We openly release the model and the label templates at https://github.com/romainVala/SIAM.

  • 6 authors
·
May 3

StRegA: Unsupervised Anomaly Detection in Brain MRIs using a Compact Context-encoding Variational Autoencoder

Expert interpretation of anatomical images of the human brain is the central part of neuro-radiology. Several machine learning-based techniques have been proposed to assist in the analysis process. However, the ML models typically need to be trained to perform a specific task, e.g., brain tumour segmentation or classification. Not only do the corresponding training data require laborious manual annotations, but a wide variety of abnormalities can be present in a human brain MRI - even more than one simultaneously, which renders representation of all possible anomalies very challenging. Hence, a possible solution is an unsupervised anomaly detection (UAD) system that can learn a data distribution from an unlabelled dataset of healthy subjects and then be applied to detect out of distribution samples. Such a technique can then be used to detect anomalies - lesions or abnormalities, for example, brain tumours, without explicitly training the model for that specific pathology. Several Variational Autoencoder (VAE) based techniques have been proposed in the past for this task. Even though they perform very well on controlled artificially simulated anomalies, many of them perform poorly while detecting anomalies in clinical data. This research proposes a compact version of the "context-encoding" VAE (ceVAE) model, combined with pre and post-processing steps, creating a UAD pipeline (StRegA), which is more robust on clinical data, and shows its applicability in detecting anomalies such as tumours in brain MRIs. The proposed pipeline achieved a Dice score of 0.642pm0.101 while detecting tumours in T2w images of the BraTS dataset and 0.859pm0.112 while detecting artificially induced anomalies, while the best performing baseline achieved 0.522pm0.135 and 0.783pm0.111, respectively.

  • 10 authors
·
Jan 31, 2022

Surface-based parcellation and vertex-wise analysis of ultra high-resolution ex vivo 7 tesla MRI in Alzheimer's disease and related dementias

Magnetic resonance imaging (MRI) is the standard modality to understand human brain structure and function in vivo (antemortem). Decades of research in human neuroimaging has led to the widespread development of methods and tools to provide automated volume-based segmentations and surface-based parcellations which help localize brain functions to specialized anatomical regions. Recently ex vivo (postmortem) imaging of the brain has opened-up avenues to study brain structure at sub-millimeter ultra high-resolution revealing details not possible to observe with in vivo MRI. Unfortunately, there has been limited methodological development in ex vivo MRI primarily due to lack of datasets and limited centers with such imaging resources. Therefore, in this work, we present one-of-its-kind dataset of 82 ex vivo T2w whole brain hemispheres MRI at 0.3 mm isotropic resolution spanning Alzheimer's disease and related dementias. We adapted and developed a fast and easy-to-use automated surface-based pipeline to parcellate, for the first time, ultra high-resolution ex vivo brain tissue at the native subject space resolution using the Desikan-Killiany-Tourville (DKT) brain atlas. This allows us to perform vertex-wise analysis in the template space and thereby link morphometry measures with pathology measurements derived from histology. We will open-source our dataset docker container, Jupyter notebooks for ready-to-use out-of-the-box set of tools and command line options to advance ex vivo MRI clinical brain imaging research on the project webpage.

  • 23 authors
·
Mar 28, 2024

Brain Harmony: A Multimodal Foundation Model Unifying Morphology and Function into 1D Tokens

We present Brain Harmony (BrainHarmonix), the first multimodal brain foundation model that unifies structural morphology and functional dynamics into compact 1D token representations. The model was pretrained on two of the largest neuroimaging datasets to date, encompassing 64,594 T1-weighted structural MRI 3D volumes (~ 14 million images) and 70,933 functional MRI (fMRI) time series. BrainHarmonix is grounded in two foundational neuroscience principles: structure complements function - structural and functional modalities offer distinct yet synergistic insights into brain organization; function follows structure - brain functional dynamics are shaped by cortical morphology. The modular pretraining process involves single-modality training with geometric pre-alignment followed by modality fusion through shared brain hub tokens. Notably, our dynamics encoder uniquely handles fMRI time series with heterogeneous repetition times (TRs), addressing a major limitation in existing models. BrainHarmonix is also the first to deeply compress high-dimensional neuroimaging signals into unified, continuous 1D tokens, forming a compact latent space of the human brain. BrainHarmonix achieves strong generalization across diverse downstream tasks, including neurodevelopmental and neurodegenerative disorder classification and cognition prediction - consistently outperforming previous approaches. Our models - pretrained on 8 H100 GPUs - aim to catalyze a new era of AI-driven neuroscience powered by large-scale multimodal neuroimaging.

  • 12 authors
·
Sep 29, 2025

cWDM: Conditional Wavelet Diffusion Models for Cross-Modality 3D Medical Image Synthesis

This paper contributes to the "BraTS 2024 Brain MR Image Synthesis Challenge" and presents a conditional Wavelet Diffusion Model (cWDM) for directly solving a paired image-to-image translation task on high-resolution volumes. While deep learning-based brain tumor segmentation models have demonstrated clear clinical utility, they typically require MR scans from various modalities (T1, T1ce, T2, FLAIR) as input. However, due to time constraints or imaging artifacts, some of these modalities may be missing, hindering the application of well-performing segmentation algorithms in clinical routine. To address this issue, we propose a method that synthesizes one missing modality image conditioned on three available images, enabling the application of downstream segmentation models. We treat this paired image-to-image translation task as a conditional generation problem and solve it by combining a Wavelet Diffusion Model for high-resolution 3D image synthesis with a simple conditioning strategy. This approach allows us to directly apply our model to full-resolution volumes, avoiding artifacts caused by slice- or patch-wise data processing. While this work focuses on a specific application, the presented method can be applied to all kinds of paired image-to-image translation problems, such as CT leftrightarrow MR and MR leftrightarrow PET translation, or mask-conditioned anatomically guided image generation.

  • 4 authors
·
Nov 26, 2024

Digital Twin Brain: a simulation and assimilation platform for whole human brain

In this work, we present a computing platform named digital twin brain (DTB) that can simulate spiking neuronal networks of the whole human brain scale and more importantly, a personalized biological brain structure. In comparison to most brain simulations with a homogeneous global structure, we highlight that the sparseness, couplingness and heterogeneity in the sMRI, DTI and PET data of the brain has an essential impact on the efficiency of brain simulation, which is proved from the scaling experiments that the DTB of human brain simulation is communication-intensive and memory-access intensive computing systems rather than computation-intensive. We utilize a number of optimization techniques to balance and integrate the computation loads and communication traffics from the heterogeneous biological structure to the general GPU-based HPC and achieve leading simulation performance for the whole human brain-scaled spiking neuronal networks. On the other hand, the biological structure, equipped with a mesoscopic data assimilation, enables the DTB to investigate brain cognitive function by a reverse-engineering method, which is demonstrated by a digital experiment of visual evaluation on the DTB. Furthermore, we believe that the developing DTB will be a promising powerful platform for a large of research orients including brain-inspiredintelligence, rain disease medicine and brain-machine interface.

  • 15 authors
·
Aug 2, 2023

Brain-Streams: fMRI-to-Image Reconstruction with Multi-modal Guidance

Understanding how humans process visual information is one of the crucial steps for unraveling the underlying mechanism of brain activity. Recently, this curiosity has motivated the fMRI-to-image reconstruction task; given the fMRI data from visual stimuli, it aims to reconstruct the corresponding visual stimuli. Surprisingly, leveraging powerful generative models such as the Latent Diffusion Model (LDM) has shown promising results in reconstructing complex visual stimuli such as high-resolution natural images from vision datasets. Despite the impressive structural fidelity of these reconstructions, they often lack details of small objects, ambiguous shapes, and semantic nuances. Consequently, the incorporation of additional semantic knowledge, beyond mere visuals, becomes imperative. In light of this, we exploit how modern LDMs effectively incorporate multi-modal guidance (text guidance, visual guidance, and image layout) for structurally and semantically plausible image generations. Specifically, inspired by the two-streams hypothesis suggesting that perceptual and semantic information are processed in different brain regions, our framework, Brain-Streams, maps fMRI signals from these brain regions to appropriate embeddings. That is, by extracting textual guidance from semantic information regions and visual guidance from perceptual information regions, Brain-Streams provides accurate multi-modal guidance to LDMs. We validate the reconstruction ability of Brain-Streams both quantitatively and qualitatively on a real fMRI dataset comprising natural image stimuli and fMRI data.

  • 3 authors
·
Sep 18, 2024

Brain Captioning: Decoding human brain activity into images and text

Every day, the human brain processes an immense volume of visual information, relying on intricate neural mechanisms to perceive and interpret these stimuli. Recent breakthroughs in functional magnetic resonance imaging (fMRI) have enabled scientists to extract visual information from human brain activity patterns. In this study, we present an innovative method for decoding brain activity into meaningful images and captions, with a specific focus on brain captioning due to its enhanced flexibility as compared to brain decoding into images. Our approach takes advantage of cutting-edge image captioning models and incorporates a unique image reconstruction pipeline that utilizes latent diffusion models and depth estimation. We utilized the Natural Scenes Dataset, a comprehensive fMRI dataset from eight subjects who viewed images from the COCO dataset. We employed the Generative Image-to-text Transformer (GIT) as our backbone for captioning and propose a new image reconstruction pipeline based on latent diffusion models. The method involves training regularized linear regression models between brain activity and extracted features. Additionally, we incorporated depth maps from the ControlNet model to further guide the reconstruction process. We evaluate our methods using quantitative metrics for both generated captions and images. Our brain captioning approach outperforms existing methods, while our image reconstruction pipeline generates plausible images with improved spatial relationships. In conclusion, we demonstrate significant progress in brain decoding, showcasing the enormous potential of integrating vision and language to better understand human cognition. Our approach provides a flexible platform for future research, with potential applications in various fields, including neural art, style transfer, and portable devices.

  • 5 authors
·
May 19, 2023

BrainFLORA: Uncovering Brain Concept Representation via Multimodal Neural Embeddings

Understanding how the brain represents visual information is a fundamental challenge in neuroscience and artificial intelligence. While AI-driven decoding of neural data has provided insights into the human visual system, integrating multimodal neuroimaging signals, such as EEG, MEG, and fMRI, remains a critical hurdle due to their inherent spatiotemporal misalignment. Current approaches often analyze these modalities in isolation, limiting a holistic view of neural representation. In this study, we introduce BrainFLORA, a unified framework for integrating cross-modal neuroimaging data to construct a shared neural representation. Our approach leverages multimodal large language models (MLLMs) augmented with modality-specific adapters and task decoders, achieving state-of-the-art performance in joint-subject visual retrieval task and has the potential to extend multitasking. Combining neuroimaging analysis methods, we further reveal how visual concept representations align across neural modalities and with real world object perception. We demonstrate that the brain's structured visual concept representations exhibit an implicit mapping to physical-world stimuli, bridging neuroscience and machine learning from different modalities of neural imaging. Beyond methodological advancements, BrainFLORA offers novel implications for cognitive neuroscience and brain-computer interfaces (BCIs). Our code is available at https://github.com/ncclab-sustech/BrainFLORA.

  • 5 authors
·
Jul 13, 2025

Solving 3D Inverse Problems using Pre-trained 2D Diffusion Models

Diffusion models have emerged as the new state-of-the-art generative model with high quality samples, with intriguing properties such as mode coverage and high flexibility. They have also been shown to be effective inverse problem solvers, acting as the prior of the distribution, while the information of the forward model can be granted at the sampling stage. Nonetheless, as the generative process remains in the same high dimensional (i.e. identical to data dimension) space, the models have not been extended to 3D inverse problems due to the extremely high memory and computational cost. In this paper, we combine the ideas from the conventional model-based iterative reconstruction with the modern diffusion models, which leads to a highly effective method for solving 3D medical image reconstruction tasks such as sparse-view tomography, limited angle tomography, compressed sensing MRI from pre-trained 2D diffusion models. In essence, we propose to augment the 2D diffusion prior with a model-based prior in the remaining direction at test time, such that one can achieve coherent reconstructions across all dimensions. Our method can be run in a single commodity GPU, and establishes the new state-of-the-art, showing that the proposed method can perform reconstructions of high fidelity and accuracy even in the most extreme cases (e.g. 2-view 3D tomography). We further reveal that the generalization capacity of the proposed method is surprisingly high, and can be used to reconstruct volumes that are entirely different from the training dataset.

  • 5 authors
·
Nov 19, 2022

Geometric Machine Learning on EEG Signals

Brain-computer interfaces (BCIs) offer transformative potential, but decoding neural signals presents significant challenges. The core premise of this paper is built around demonstrating methods to elucidate the underlying low-dimensional geometric structure present in high-dimensional brainwave data in order to assist in downstream BCI-related neural classification tasks. We demonstrate two pipelines related to electroencephalography (EEG) signal processing: (1) a preliminary pipeline removing noise from individual EEG channels, and (2) a downstream manifold learning pipeline uncovering geometric structure across networks of EEG channels. We conduct preliminary validation using two EEG datasets and situate our demonstration in the context of the BCI-relevant imagined digit decoding problem. Our preliminary pipeline uses an attention-based EEG filtration network to extract clean signal from individual EEG channels. Our primary pipeline uses a fast Fourier transform, a Laplacian eigenmap, a discrete analog of Ricci flow via Ollivier's notion of Ricci curvature, and a graph convolutional network to perform dimensionality reduction on high-dimensional multi-channel EEG data in order to enable regularizable downstream classification. Our system achieves competitive performance with existing signal processing and classification benchmarks; we demonstrate a mean test correlation coefficient of >0.95 at 2 dB on semi-synthetic neural denoising and a downstream EEG-based classification accuracy of 0.97 on distinguishing digit- versus non-digit- thoughts. Results are preliminary and our geometric machine learning pipeline should be validated by more extensive follow-up studies; generalizing these results to larger inter-subject sample sizes, different hardware systems, and broader use cases will be crucial.

  • 1 authors
·
Feb 7, 2025

MindBridge: A Cross-Subject Brain Decoding Framework

Brain decoding, a pivotal field in neuroscience, aims to reconstruct stimuli from acquired brain signals, primarily utilizing functional magnetic resonance imaging (fMRI). Currently, brain decoding is confined to a per-subject-per-model paradigm, limiting its applicability to the same individual for whom the decoding model is trained. This constraint stems from three key challenges: 1) the inherent variability in input dimensions across subjects due to differences in brain size; 2) the unique intrinsic neural patterns, influencing how different individuals perceive and process sensory information; 3) limited data availability for new subjects in real-world scenarios hampers the performance of decoding models. In this paper, we present a novel approach, MindBridge, that achieves cross-subject brain decoding by employing only one model. Our proposed framework establishes a generic paradigm capable of addressing these challenges by introducing biological-inspired aggregation function and novel cyclic fMRI reconstruction mechanism for subject-invariant representation learning. Notably, by cycle reconstruction of fMRI, MindBridge can enable novel fMRI synthesis, which also can serve as pseudo data augmentation. Within the framework, we also devise a novel reset-tuning method for adapting a pretrained model to a new subject. Experimental results demonstrate MindBridge's ability to reconstruct images for multiple subjects, which is competitive with dedicated subject-specific models. Furthermore, with limited data for a new subject, we achieve a high level of decoding accuracy, surpassing that of subject-specific models. This advancement in cross-subject brain decoding suggests promising directions for wider applications in neuroscience and indicates potential for more efficient utilization of limited fMRI data in real-world scenarios. Project page: https://littlepure2333.github.io/MindBridge

  • 4 authors
·
Apr 11, 2024

Health system learning achieves generalist neuroimaging models

Frontier artificial intelligence (AI) models, such as OpenAI's GPT-5 and Meta's DINOv3, have advanced rapidly through training on internet-scale public data, yet such systems lack access to private clinical data. Neuroimaging, in particular, is underrepresented in the public domain due to identifiable facial features within MRI and CT scans, fundamentally restricting model performance in clinical medicine. Here, we show that frontier models underperform on neuroimaging tasks and that learning directly from uncurated data generated during routine clinical care at health systems, a paradigm we call health system learning, yields high-performance, generalist neuroimaging models. We introduce NeuroVFM, a visual foundation model trained on 5.24 million clinical MRI and CT volumes using a scalable volumetric joint-embedding predictive architecture. NeuroVFM learns comprehensive representations of brain anatomy and pathology, achieving state-of-the-art performance across multiple clinical tasks, including radiologic diagnosis and report generation. The model exhibits emergent neuroanatomic understanding and interpretable visual grounding of diagnostic findings. When paired with open-source language models through lightweight visual instruction tuning, NeuroVFM generates radiology reports that surpass frontier models in accuracy, clinical triage, and expert preference. Through clinically grounded visual understanding, NeuroVFM reduces hallucinated findings and critical errors, offering safer clinical decision support. These results establish health system learning as a paradigm for building generalist medical AI and provide a scalable framework for clinical foundation models.

NeuroClaw Technical Report

Agentic artificial intelligence systems promise to accelerate scientific workflows, but neuroimaging poses unique challenges: heterogeneous modalities (sMRI, fMRI, dMRI, EEG), long multi-stage pipelines, and persistent reproducibility risks. To address this gap, we present NeuroClaw, a domain-specialized multi-agent research assistant for executable and reproducible neuroimaging research. NeuroClaw operates directly on raw neuroimaging data across formats and modalities, grounding decisions in dataset semantics and BIDS metadata so users need not prepare curated inputs or bespoke model code. The platform combines harness engineering with end-to-end environment management, including pinned Python environments, Docker support, automated installers for common neuroimaging tools, and GPU configuration. In practice, this layer emphasizes checkpointing, post-execution verification, structured audit traces, and controlled runtime setup, making toolchains more transparent while improving reproducibility and auditability. A three-tier skill/agent hierarchy separates user-facing interaction, high-level orchestration, and low-level tool skills to decompose complex workflows into safe, reusable units. Alongside the NeuroClaw framework, we introduce NeuroBench, a system-level benchmark for executability, artifact validity, and reproducibility readiness. Across multiple multimodal LLMs, NeuroClaw-enabled runs yield consistent and substantial score improvements compared with direct agent invocation. Project homepage: https://cuhk-aim-group.github.io/NeuroClaw/index.html

  • 8 authors
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Apr 26

Multi-Coil MRI Reconstruction Challenge -- Assessing Brain MRI Reconstruction Models and their Generalizability to Varying Coil Configurations

Deep-learning-based brain magnetic resonance imaging (MRI) reconstruction methods have the potential to accelerate the MRI acquisition process. Nevertheless, the scientific community lacks appropriate benchmarks to assess MRI reconstruction quality of high-resolution brain images, and evaluate how these proposed algorithms will behave in the presence of small, but expected data distribution shifts. The Multi-Coil Magnetic Resonance Image (MC-MRI) Reconstruction Challenge provides a benchmark that aims at addressing these issues, using a large dataset of high-resolution, three-dimensional, T1-weighted MRI scans. The challenge has two primary goals: 1) to compare different MRI reconstruction models on this dataset and 2) to assess the generalizability of these models to data acquired with a different number of receiver coils. In this paper, we describe the challenge experimental design, and summarize the results of a set of baseline and state of the art brain MRI reconstruction models. We provide relevant comparative information on the current MRI reconstruction state-of-the-art and highlight the challenges of obtaining generalizable models that are required prior to broader clinical adoption. The MC-MRI benchmark data, evaluation code and current challenge leaderboard are publicly available. They provide an objective performance assessment for future developments in the field of brain MRI reconstruction.

  • 23 authors
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Nov 9, 2020

NeuroVLM-Bench: Evaluation of Vision-Enabled Large Language Models for Clinical Reasoning in Neurological Disorders

Recent advances in multimodal large language models enable new possibilities for image-based decision support. However, their reliability and operational trade-offs in neuroimaging remain insufficiently understood. We present a comprehensive benchmarking study of vision-enabled large language models for 2D neuroimaging using curated MRI and CT datasets covering multiple sclerosis, stroke, brain tumors, other abnormalities, and normal controls. Models are required to generate multiple outputs simultaneously, including diagnosis, diagnosis subtype, imaging modality, specialized sequence, and anatomical plane. Performance is evaluated across four directions: discriminative classification with abstention, calibration, structured-output validity, and computational efficiency. A multi-phase framework ensures fair comparison while controlling for selection bias. Across twenty frontier multimodal models, the results show that technical imaging attributes such as modality and plane are nearly solved, whereas diagnostic reasoning, especially subtype prediction, remains challenging. Tumor classification emerges as the most reliable task, stroke is moderately solvable, while multiple sclerosis and rare abnormalities remain difficult. Few-shot prompting improves performance for several models but increases token usage, latency, and cost. Gemini-2.5-Pro and GPT-5-Chat achieve the strongest overall diagnostic performance, while Gemini-2.5-Flash offers the best efficiency-performance trade-off. Among open-weight architectures, MedGemma-1.5-4B demonstrates the most promising results, as under few-shot prompting, it approaches the zero-shot performance of several proprietary models, while maintaining perfect structured output. These findings provide practical insights into performance, reliability, and efficiency trade-offs, supporting standardized evaluation of multimodal LLMs in neuroimaging.

  • 8 authors
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Mar 24

A Self-supervised Multimodal Deep Learning Approach to Differentiate Post-radiotherapy Progression from Pseudoprogression in Glioblastoma

Accurate differentiation of pseudoprogression (PsP) from True Progression (TP) following radiotherapy (RT) in glioblastoma (GBM) patients is crucial for optimal treatment planning. However, this task remains challenging due to the overlapping imaging characteristics of PsP and TP. This study therefore proposes a multimodal deep-learning approach utilizing complementary information from routine anatomical MR images, clinical parameters, and RT treatment planning information for improved predictive accuracy. The approach utilizes a self-supervised Vision Transformer (ViT) to encode multi-sequence MR brain volumes to effectively capture both global and local context from the high dimensional input. The encoder is trained in a self-supervised upstream task on unlabeled glioma MRI datasets from the open BraTS2021, UPenn-GBM, and UCSF-PDGM datasets to generate compact, clinically relevant representations from FLAIR and T1 post-contrast sequences. These encoded MR inputs are then integrated with clinical data and RT treatment planning information through guided cross-modal attention, improving progression classification accuracy. This work was developed using two datasets from different centers: the Burdenko Glioblastoma Progression Dataset (n = 59) for training and validation, and the GlioCMV progression dataset from the University Hospital Erlangen (UKER) (n = 20) for testing. The proposed method achieved an AUC of 75.3%, outperforming the current state-of-the-art data-driven approaches. Importantly, the proposed approach relies on readily available anatomical MRI sequences, clinical data, and RT treatment planning information, enhancing its clinical feasibility. The proposed approach addresses the challenge of limited data availability for PsP and TP differentiation and could allow for improved clinical decision-making and optimized treatment plans for GBM patients.

  • 22 authors
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Feb 5, 2025

Brain-ID: Learning Contrast-agnostic Anatomical Representations for Brain Imaging

Recent learning-based approaches have made astonishing advances in calibrated medical imaging like computerized tomography (CT), yet they struggle to generalize in uncalibrated modalities -- notably magnetic resonance (MR) imaging, where performance is highly sensitive to the differences in MR contrast, resolution, and orientation. This prevents broad applicability to diverse real-world clinical protocols. We introduce Brain-ID, an anatomical representation learning model for brain imaging. With the proposed "mild-to-severe" intra-subject generation, Brain-ID is robust to the subject-specific brain anatomy regardless of the appearance of acquired images (e.g., contrast, deformation, resolution, artifacts). Trained entirely on synthetic data, Brain-ID readily adapts to various downstream tasks through only one layer. We present new metrics to validate the intra- and inter-subject robustness of Brain-ID features, and evaluate their performance on four downstream applications, covering contrast-independent (anatomy reconstruction/contrast synthesis, brain segmentation), and contrast-dependent (super-resolution, bias field estimation) tasks. Extensive experiments on six public datasets demonstrate that Brain-ID achieves state-of-the-art performance in all tasks on different MRI modalities and CT, and more importantly, preserves its performance on low-resolution and small datasets. Code is available at https://github.com/peirong26/Brain-ID.

  • 5 authors
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Nov 28, 2023

Canonical Cortical Field Theories

We characterise the dynamics of neuronal activity, in terms of field theory, using neural units placed on a 2D-lattice modelling the cortical surface. The electrical activity of neuronal units was analysed with the aim of deriving a neural field model with a simple functional form that still able to predict or reproduce empirical findings. Each neural unit was modelled using a neural mass and the accompanying field theory was derived in the continuum limit. The field theory comprised coupled (real) Klein-Gordon fields, where predictions of the model fall within the range of experimental findings. These predictions included the frequency spectrum of electric activity measured from the cortex, which was derived using an equipartition of energy over eigenfunctions of the neural fields. Moreover, the neural field model was invariant, within a set of parameters, to the dynamical system used to model each neuronal mass. Specifically, topologically equivalent dynamical systems resulted in the same neural field model when connected in a lattice; indicating that the fields derived could be read as a canonical cortical field theory. We specifically investigated non-dispersive fields that provide a structure for the coding (or representation) of afferent information. Further elaboration of the ensuing neural field theory, including the effect of dispersive forces, could be of importance in the understanding of the cortical processing of information.

  • 3 authors
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Aug 20, 2023

The Alzheimer's Disease Prediction Of Longitudinal Evolution (TADPOLE) Challenge: Results after 1 Year Follow-up

We present the findings of "The Alzheimer's Disease Prediction Of Longitudinal Evolution" (TADPOLE) Challenge, which compared the performance of 92 algorithms from 33 international teams at predicting the future trajectory of 219 individuals at risk of Alzheimer's disease. Challenge participants were required to make a prediction, for each month of a 5-year future time period, of three key outcomes: clinical diagnosis, Alzheimer's Disease Assessment Scale Cognitive Subdomain (ADAS-Cog13), and total volume of the ventricles. The methods used by challenge participants included multivariate linear regression, machine learning methods such as support vector machines and deep neural networks, as well as disease progression models. No single submission was best at predicting all three outcomes. For clinical diagnosis and ventricle volume prediction, the best algorithms strongly outperform simple baselines in predictive ability. However, for ADAS-Cog13 no single submitted prediction method was significantly better than random guesswork. Two ensemble methods based on taking the mean and median over all predictions, obtained top scores on almost all tasks. Better than average performance at diagnosis prediction was generally associated with the additional inclusion of features from cerebrospinal fluid (CSF) samples and diffusion tensor imaging (DTI). On the other hand, better performance at ventricle volume prediction was associated with inclusion of summary statistics, such as the slope or maxima/minima of biomarkers. TADPOLE's unique results suggest that current prediction algorithms provide sufficient accuracy to exploit biomarkers related to clinical diagnosis and ventricle volume, for cohort refinement in clinical trials for Alzheimer's disease. However, results call into question the usage of cognitive test scores for patient selection and as a primary endpoint in clinical trials.

  • 96 authors
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Feb 9, 2020

GOUHFI: a novel contrast- and resolution-agnostic segmentation tool for Ultra-High Field MRI

Recently, Ultra-High Field MRI (UHF-MRI) has become more available and one of the best tools to study the brain. One common step in quantitative neuroimaging is to segment the brain into several regions, which has been done using software packages like FreeSurfer , FastSurferVINN or SynthSeg. However, the differences between UHF-MRI and 1.5T or 3T images are such that the automatic segmentation techniques optimized at these field strengths usually produce unsatisfactory segmentation results for UHF images. Thus, it has been particularly challenging to perform region-based quantitative analyses as typically done with 1.5-3T data, underscoring the crucial need for developing new automatic segmentation techniques designed to handle UHF images. Hence, we propose a novel Deep Learning (DL)-based segmentation technique called GOUHFI: Generalized and Optimized segmentation tool for Ultra-High Field Images, designed to segment UHF images of various contrasts and resolutions. For training, we used a total of 206 label maps from datasets acquired at 3T, 7T and 9.4T. In contrast to most DL strategies, we used a domain randomization approach, where synthetic images were used to train a 3D U-Net. GOUHFI was tested on seven different datasets and compared to existing techniques like FastSurferVINN,SynthSeg and CEREBRUM-7T. GOUHFI was able to segment the six contrasts and seven resolutions tested at 3T, 7T and 9.4T. Average Dice scores of 0.90, 0.90 and 0.93 were computed against the ground truth segmentations at 3T, 7T and 9.4T, respectively. Ultimately, GOUHFI is a promising new segmentation tool, being the first of its kind proposing a contrast- and resolution-agnostic alternative for UHF-MRI without requiring fine-tuning or retraining, making it the forthcoming alternative for neuroscientists working with UHF-MRI or even lower field strengths.

  • 6 authors
·
Sep 29, 2025

NeuroPictor: Refining fMRI-to-Image Reconstruction via Multi-individual Pretraining and Multi-level Modulation

Recent fMRI-to-image approaches mainly focused on associating fMRI signals with specific conditions of pre-trained diffusion models. These approaches, while producing high-quality images, capture only a limited aspect of the complex information in fMRI signals and offer little detailed control over image creation. In contrast, this paper proposes to directly modulate the generation process of diffusion models using fMRI signals. Our approach, NeuroPictor, divides the fMRI-to-image process into three steps: i) fMRI calibrated-encoding, to tackle multi-individual pre-training for a shared latent space to minimize individual difference and enable the subsequent cross-subject training; ii) fMRI-to-image cross-subject pre-training, perceptually learning to guide diffusion model with high- and low-level conditions across different individuals; iii) fMRI-to-image single-subject refining, similar with step ii but focus on adapting to particular individual. NeuroPictor extracts high-level semantic features from fMRI signals that characterizing the visual stimulus and incrementally fine-tunes the diffusion model with a low-level manipulation network to provide precise structural instructions. By training with over 60,000 fMRI-image pairs from various individuals, our model enjoys superior fMRI-to-image decoding capacity, particularly in the within-subject setting, as evidenced in benchmark datasets. Project page: https://jingyanghuo.github.io/neuropictor/.

  • 7 authors
·
Mar 26, 2024

Natural scene reconstruction from fMRI signals using generative latent diffusion

In neural decoding research, one of the most intriguing topics is the reconstruction of perceived natural images based on fMRI signals. Previous studies have succeeded in re-creating different aspects of the visuals, such as low-level properties (shape, texture, layout) or high-level features (category of objects, descriptive semantics of scenes) but have typically failed to reconstruct these properties together for complex scene images. Generative AI has recently made a leap forward with latent diffusion models capable of generating high-complexity images. Here, we investigate how to take advantage of this innovative technology for brain decoding. We present a two-stage scene reconstruction framework called ``Brain-Diffuser''. In the first stage, starting from fMRI signals, we reconstruct images that capture low-level properties and overall layout using a VDVAE (Very Deep Variational Autoencoder) model. In the second stage, we use the image-to-image framework of a latent diffusion model (Versatile Diffusion) conditioned on predicted multimodal (text and visual) features, to generate final reconstructed images. On the publicly available Natural Scenes Dataset benchmark, our method outperforms previous models both qualitatively and quantitatively. When applied to synthetic fMRI patterns generated from individual ROI (region-of-interest) masks, our trained model creates compelling ``ROI-optimal'' scenes consistent with neuroscientific knowledge. Thus, the proposed methodology can have an impact on both applied (e.g. brain-computer interface) and fundamental neuroscience.

  • 2 authors
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Mar 9, 2023

Progress and Prospects in 3D Generative AI: A Technical Overview including 3D human

While AI-generated text and 2D images continue to expand its territory, 3D generation has gradually emerged as a trend that cannot be ignored. Since the year 2023 an abundant amount of research papers has emerged in the domain of 3D generation. This growth encompasses not just the creation of 3D objects, but also the rapid development of 3D character and motion generation. Several key factors contribute to this progress. The enhanced fidelity in stable diffusion, coupled with control methods that ensure multi-view consistency, and realistic human models like SMPL-X, contribute synergistically to the production of 3D models with remarkable consistency and near-realistic appearances. The advancements in neural network-based 3D storing and rendering models, such as Neural Radiance Fields (NeRF) and 3D Gaussian Splatting (3DGS), have accelerated the efficiency and realism of neural rendered models. Furthermore, the multimodality capabilities of large language models have enabled language inputs to transcend into human motion outputs. This paper aims to provide a comprehensive overview and summary of the relevant papers published mostly during the latter half year of 2023. It will begin by discussing the AI generated object models in 3D, followed by the generated 3D human models, and finally, the generated 3D human motions, culminating in a conclusive summary and a vision for the future.

  • 2 authors
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Jan 4, 2024

Comparison Against Task Driven Artificial Neural Networks Reveals Functional Organization of Mouse Visual Cortex

Partially inspired by features of computation in visual cortex, deep neural networks compute hierarchical representations of their inputs. While these networks have been highly successful in machine learning, it remains unclear to what extent they can aid our understanding of cortical function. Several groups have developed metrics that provide a quantitative comparison between representations computed by networks and representations measured in cortex. At the same time, neuroscience is well into an unprecedented phase of large-scale data collection, as evidenced by projects such as the Allen Brain Observatory. Despite the magnitude of these efforts, in a given experiment only a fraction of units are recorded, limiting the information available about the cortical representation. Moreover, only a finite number of stimuli can be shown to an animal over the course of a realistic experiment. These limitations raise the question of how and whether metrics that compare representations of deep networks are meaningful on these datasets. Here, we empirically quantify the capabilities and limitations of these metrics due to limited image presentations and neuron samples. We find that the comparison procedure is robust to different choices of stimuli set and the level of subsampling that one might expect in a large-scale brain survey with thousands of neurons. Using these results, we compare the representations measured in the Allen Brain Observatory in response to natural image presentations to deep neural network. We show that the visual cortical areas are relatively high order representations (in that they map to deeper layers of convolutional neural networks). Furthermore, we see evidence of a broad, more parallel organization rather than a sequential hierarchy, with the primary area VISp(V1) being lower order relative to the other areas.

  • 3 authors
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Nov 18, 2019

Reconstructing the Mind's Eye: fMRI-to-Image with Contrastive Learning and Diffusion Priors

We present MindEye, a novel fMRI-to-image approach to retrieve and reconstruct viewed images from brain activity. Our model comprises two parallel submodules that are specialized for retrieval (using contrastive learning) and reconstruction (using a diffusion prior). MindEye can map fMRI brain activity to any high dimensional multimodal latent space, like CLIP image space, enabling image reconstruction using generative models that accept embeddings from this latent space. We comprehensively compare our approach with other existing methods, using both qualitative side-by-side comparisons and quantitative evaluations, and show that MindEye achieves state-of-the-art performance in both reconstruction and retrieval tasks. In particular, MindEye can retrieve the exact original image even among highly similar candidates indicating that its brain embeddings retain fine-grained image-specific information. This allows us to accurately retrieve images even from large-scale databases like LAION-5B. We demonstrate through ablations that MindEye's performance improvements over previous methods result from specialized submodules for retrieval and reconstruction, improved training techniques, and training models with orders of magnitude more parameters. Furthermore, we show that MindEye can better preserve low-level image features in the reconstructions by using img2img, with outputs from a separate autoencoder. All code is available on GitHub.

  • 12 authors
·
May 29, 2023 1

Geometric Stability: The Missing Axis of Representations

Analysis of learned representations has a blind spot: it focuses on similarity, measuring how closely embeddings align with external references, but similarity reveals only what is represented, not whether that structure is robust. We introduce geometric stability, a distinct dimension that quantifies how reliably representational geometry holds under perturbation, and present Shesha, a framework for measuring it. Across 2,463 configurations in seven domains, we show that stability and similarity are empirically uncorrelated (ρapprox 0.01) and mechanistically distinct: similarity metrics collapse after removing the top principal components, while stability retains sensitivity to fine-grained manifold structure. This distinction yields actionable insights: for safety monitoring, stability acts as a functional geometric canary, detecting structural drift nearly 2times more sensitively than CKA while filtering out the non-functional noise that triggers false alarms in rigid distance metrics; for controllability, supervised stability predicts linear steerability (ρ= 0.89-0.96); for model selection, stability dissociates from transferability, revealing a geometric tax that transfer optimization incurs. Beyond machine learning, stability predicts CRISPR perturbation coherence and neural-behavioral coupling. By quantifying how reliably systems maintain structure, geometric stability provides a necessary complement to similarity for auditing representations across biological and computational systems.

  • 1 authors
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Jan 14 2

A Tutorial on MRI Reconstruction: From Modern Methods to Clinical Implications

MRI is an indispensable clinical tool, offering a rich variety of tissue contrasts to support broad diagnostic and research applications. Clinical exams routinely acquire multiple structural sequences that provide complementary information for differential diagnosis, while research protocols often incorporate advanced functional, diffusion, spectroscopic, and relaxometry sequences to capture multidimensional insights into tissue structure and composition. However, these capabilities come at the cost of prolonged scan times, which reduce patient throughput, increase susceptibility to motion artifacts, and may require trade-offs in image quality or diagnostic scope. Over the last two decades, advances in image reconstruction algorithms--alongside improvements in hardware and pulse sequence design--have made it possible to accelerate acquisitions while preserving diagnostic quality. Central to this progress is the ability to incorporate prior information to regularize the solutions to the reconstruction problem. In this tutorial, we overview the basics of MRI reconstruction and highlight state-of-the-art approaches, beginning with classical methods that rely on explicit hand-crafted priors, and then turning to deep learning methods that leverage a combination of learned and crafted priors to further push the performance envelope. We also explore the translational aspects and eventual clinical implications of these methods. We conclude by discussing future directions to address remaining challenges in MRI reconstruction. The tutorial is accompanied by a Python toolbox (https://github.com/tutorial-MRI-recon/tutorial) to demonstrate select methods discussed in the article.

  • 7 authors
·
Jul 22, 2025

GeoDream: Disentangling 2D and Geometric Priors for High-Fidelity and Consistent 3D Generation

Text-to-3D generation by distilling pretrained large-scale text-to-image diffusion models has shown great promise but still suffers from inconsistent 3D geometric structures (Janus problems) and severe artifacts. The aforementioned problems mainly stem from 2D diffusion models lacking 3D awareness during the lifting. In this work, we present GeoDream, a novel method that incorporates explicit generalized 3D priors with 2D diffusion priors to enhance the capability of obtaining unambiguous 3D consistent geometric structures without sacrificing diversity or fidelity. Specifically, we first utilize a multi-view diffusion model to generate posed images and then construct cost volume from the predicted image, which serves as native 3D geometric priors, ensuring spatial consistency in 3D space. Subsequently, we further propose to harness 3D geometric priors to unlock the great potential of 3D awareness in 2D diffusion priors via a disentangled design. Notably, disentangling 2D and 3D priors allows us to refine 3D geometric priors further. We justify that the refined 3D geometric priors aid in the 3D-aware capability of 2D diffusion priors, which in turn provides superior guidance for the refinement of 3D geometric priors. Our numerical and visual comparisons demonstrate that GeoDream generates more 3D consistent textured meshes with high-resolution realistic renderings (i.e., 1024 times 1024) and adheres more closely to semantic coherence.

  • 6 authors
·
Nov 29, 2023 1

Optimizing Brain Tumor Segmentation with MedNeXt: BraTS 2024 SSA and Pediatrics

Identifying key pathological features in brain MRIs is crucial for the long-term survival of glioma patients. However, manual segmentation is time-consuming, requiring expert intervention and is susceptible to human error. Therefore, significant research has been devoted to developing machine learning methods that can accurately segment tumors in 3D multimodal brain MRI scans. Despite their progress, state-of-the-art models are often limited by the data they are trained on, raising concerns about their reliability when applied to diverse populations that may introduce distribution shifts. Such shifts can stem from lower quality MRI technology (e.g., in sub-Saharan Africa) or variations in patient demographics (e.g., children). The BraTS-2024 challenge provides a platform to address these issues. This study presents our methodology for segmenting tumors in the BraTS-2024 SSA and Pediatric Tumors tasks using MedNeXt, comprehensive model ensembling, and thorough postprocessing. Our approach demonstrated strong performance on the unseen validation set, achieving an average Dice Similarity Coefficient (DSC) of 0.896 on the BraTS-2024 SSA dataset and an average DSC of 0.830 on the BraTS Pediatric Tumor dataset. Additionally, our method achieved an average Hausdorff Distance (HD95) of 14.682 on the BraTS-2024 SSA dataset and an average HD95 of 37.508 on the BraTS Pediatric dataset. Our GitHub repository can be accessed here: Project Repository : https://github.com/python-arch/BioMbz-Optimizing-Brain-Tumor-Segmentation-with-MedNeXt-BraTS-2024-SSA-and-Pediatrics

  • 9 authors
·
Nov 24, 2024 2

Physics Steering: Causal Control of Cross-Domain Concepts in a Physics Foundation Model

Recent advances in mechanistic interpretability have revealed that large language models (LLMs) develop internal representations corresponding not only to concrete entities but also distinct, human-understandable abstract concepts and behaviour. Moreover, these hidden features can be directly manipulated to steer model behaviour. However, it remains an open question whether this phenomenon is unique to models trained on inherently structured data (ie. language, images) or if it is a general property of foundation models. In this work, we investigate the internal representations of a large physics-focused foundation model. Inspired by recent work identifying single directions in activation space for complex behaviours in LLMs, we extract activation vectors from the model during forward passes over simulation datasets for different physical regimes. We then compute "delta" representations between the two regimes. These delta tensors act as concept directions in activation space, encoding specific physical features. By injecting these concept directions back into the model during inference, we can steer its predictions, demonstrating causal control over physical behaviours, such as inducing or removing some particular physical feature from a simulation. These results suggest that scientific foundation models learn generalised representations of physical principles. They do not merely rely on superficial correlations and patterns in the simulations. Our findings open new avenues for understanding and controlling scientific foundation models and has implications for AI-enabled scientific discovery.

  • 5 authors
·
Nov 25, 2025

The Topology and Geometry of Neural Representations

A central question for neuroscience is how to characterize brain representations of perceptual and cognitive content. An ideal characterization should distinguish different functional regions with robustness to noise and idiosyncrasies of individual brains that do not correspond to computational differences. Previous studies have characterized brain representations by their representational geometry, which is defined by the representational dissimilarity matrix (RDM), a summary statistic that abstracts from the roles of individual neurons (or responses channels) and characterizes the discriminability of stimuli. Here we explore a further step of abstraction: from the geometry to the topology of brain representations. We propose topological representational similarity analysis (tRSA), an extension of representational similarity analysis (RSA) that uses a family of geo-topological summary statistics that generalizes the RDM to characterize the topology while de-emphasizing the geometry. We evaluate this new family of statistics in terms of the sensitivity and specificity for model selection using both simulations and functional MRI (fMRI) data. In the simulations, the ground truth is a data-generating layer representation in a neural network model and the models are the same and other layers in different model instances (trained from different random seeds). In fMRI, the ground truth is a visual area and the models are the same and other areas measured in different subjects. Results show that topology-sensitive characterizations of population codes are robust to noise and interindividual variability and maintain excellent sensitivity to the unique representational signatures of different neural network layers and brain regions.

  • 2 authors
·
Sep 19, 2023

EEG Foundation Models: Progresses, Benchmarking, and Open Problems

Electroencephalography (EEG) foundation models have recently emerged as a promising paradigm for brain-computer interfaces (BCIs), aiming to learn transferable neural representations from large-scale heterogeneous recordings. Despite rapid progresses, there lacks fair and comprehensive comparisons of existing EEG foundation models, due to inconsistent pre-training objectives, preprocessing choices, and downstream evaluation protocols. This paper fills this gap. We first review 50 representative models and organize their design choices into a unified taxonomic framework including data standardization, model architectures, and self-supervised pre-training strategies. We then evaluate 12 open-source foundation models and competitive specialist baselines across 13 EEG datasets spanning nine BCI paradigms. Emphasizing real-world deployments, we consider both cross-subject generalization under a leave-one-subject-out protocol and rapid calibration under a within-subject few-shot setting. We further compare full-parameter fine-tuning with linear probing to assess the transferability of pre-trained representations, and examine the relationship between model scale and downstream performance. Our results indicate that: 1) linear probing is frequently insufficient; 2) specialist models trained from scratch remain competitive across many tasks; and, 3) larger foundation models do not necessarily yield better generalization performance under current data regimes and training practices.

DeeperBrain: A Neuro-Grounded EEG Foundation Model Towards Universal BCI

Electroencephalography (EEG) foundation models hold significant promise for universal Brain-Computer Interfaces (BCIs). However, existing approaches often rely on end-to-end fine-tuning and exhibit limited efficacy under frozen-probing protocols, lacking the intrinsic universality required for broad generalization. This limitation stems from adapting general-purpose sequence architectures that overlook the biophysical and dynamical principles of neural activity. To bridge this gap, we propose DeeperBrain, a neuro-grounded foundation model integrating domain-specific inductive biases into its model design and learning objectives. Architecturally, DeeperBrain incorporates a volume conduction-aware channel encoding to model spatial mixing via 3D geometry, and a neurodynamics-aware temporal encoding capturing slow adaptations using oscillatory and exponential bases. For pretraining, we introduce a dual-objective strategy combining Masked EEG Reconstruction (MER) for local fidelity and Neurodynamics Statistics Prediction (NSP). NSP enforces alignment with macroscopic brain states by predicting interpretable order parameters, including spectral power, functional connectivity, cross-frequency coupling, and dynamic complexity. Extensive experiments demonstrate that DeeperBrain achieves state-of-the-art or highly competitive performance under end-to-end fine-tuning. Crucially, it maintains superior efficacy under a rigorous frozen-probing protocol, verifying that embedding neuroscientific first principles endows learned representations with the intrinsic universality essential for universal BCI. The code will be publicly available.

  • 6 authors
·
Jan 5

Deep Generative Modeling with Spatial and Network Images: An Explainable AI (XAI) Approach

This article addresses the challenge of modeling the amplitude of spatially indexed low frequency fluctuations (ALFF) in resting state functional MRI as a function of cortical structural features and a multi-task coactivation network in the Adolescent Brain Cognitive Development (ABCD) Study. It proposes a generative model that integrates effects of spatially-varying inputs and a network-valued input using deep neural networks to capture complex non-linear and spatial associations with the output. The method models spatial smoothness, accounts for subject heterogeneity and complex associations between network and spatial images at different scales, enables accurate inference of each images effect on the output image, and allows prediction with uncertainty quantification via Monte Carlo dropout, contributing to one of the first Explainable AI (XAI) frameworks for heterogeneous imaging data. The model is highly scalable to high-resolution data without the heavy pre-processing or summarization often required by Bayesian methods. Empirical results demonstrate its strong performance compared to existing statistical and deep learning methods. We applied the XAI model to the ABCD data which revealed associations between cortical features and ALFF throughout the entire brain. Our model performed comparably to existing methods in predictive accuracy but provided superior uncertainty quantification and faster computation, demonstrating its effectiveness for large-scale neuroimaging analysis. Open-source software in Python for XAI is available.

  • 3 authors
·
May 19, 2025

Neural Representations of Dynamic Visual Stimuli

Humans experience the world through constantly changing visual stimuli, where scenes can shift and move, change in appearance, and vary in distance. The dynamic nature of visual perception is a fundamental aspect of our daily lives, yet the large majority of research on object and scene processing, particularly using fMRI, has focused on static stimuli. While studies of static image perception are attractive due to their computational simplicity, they impose a strong non-naturalistic constraint on our investigation of human vision. In contrast, dynamic visual stimuli offer a more ecologically-valid approach but present new challenges due to the interplay between spatial and temporal information, making it difficult to disentangle the representations of stable image features and motion. To overcome this limitation -- given dynamic inputs, we explicitly decouple the modeling of static image representations and motion representations in the human brain. Three results demonstrate the feasibility of this approach. First, we show that visual motion information as optical flow can be predicted (or decoded) from brain activity as measured by fMRI. Second, we show that this predicted motion can be used to realistically animate static images using a motion-conditioned video diffusion model (where the motion is driven by fMRI brain activity). Third, we show prediction in the reverse direction: existing video encoders can be fine-tuned to predict fMRI brain activity from video imagery, and can do so more effectively than image encoders. This foundational work offers a novel, extensible framework for interpreting how the human brain processes dynamic visual information.

  • 6 authors
·
Jun 4, 2024

Unveiling and Bridging the Functional Perception Gap in MLLMs: Atomic Visual Alignment and Hierarchical Evaluation via PET-Bench

While Multimodal Large Language Models (MLLMs) have demonstrated remarkable proficiency in tasks such as abnormality detection and report generation for anatomical modalities, their capability in functional imaging remains largely unexplored. In this work, we identify and quantify a fundamental functional perception gap: the inability of current vision encoders to decode functional tracer biodistribution independent of morphological priors. Identifying Positron Emission Tomography (PET) as the quintessential modality to investigate this disconnect, we introduce PET-Bench, the first large-scale functional imaging benchmark comprising 52,308 hierarchical QA pairs from 9,732 multi-site, multi-tracer PET studies. Extensive evaluation of 19 state-of-the-art MLLMs reveals a critical safety hazard termed the Chain-of-Thought (CoT) hallucination trap. We observe that standard CoT prompting, widely considered to enhance reasoning, paradoxically decouples linguistic generation from visual evidence in PET, producing clinically fluent but factually ungrounded diagnoses. To resolve this, we propose Atomic Visual Alignment (AVA), a simple fine-tuning strategy that enforces the mastery of low-level functional perception prior to high-level diagnostic reasoning. Our results demonstrate that AVA effectively bridges the perception gap, transforming CoT from a source of hallucination into a robust inference tool and improving diagnostic accuracy by up to 14.83%. Code and data are available at https://github.com/yezanting/PET-Bench.

  • 17 authors
·
Jan 6

BrainDINO: A Brain MRI Foundation Model for Generalizable Clinical 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.

  • 8 authors
·
Apr 29

SridBench: Benchmark of Scientific Research Illustration Drawing of Image Generation Model

Recent years have seen rapid advances in AI-driven image generation. Early diffusion models emphasized perceptual quality, while newer multimodal models like GPT-4o-image integrate high-level reasoning, improving semantic understanding and structural composition. Scientific illustration generation exemplifies this evolution: unlike general image synthesis, it demands accurate interpretation of technical content and transformation of abstract ideas into clear, standardized visuals. This task is significantly more knowledge-intensive and laborious, often requiring hours of manual work and specialized tools. Automating it in a controllable, intelligent manner would provide substantial practical value. Yet, no benchmark currently exists to evaluate AI on this front. To fill this gap, we introduce SridBench, the first benchmark for scientific figure generation. It comprises 1,120 instances curated from leading scientific papers across 13 natural and computer science disciplines, collected via human experts and MLLMs. Each sample is evaluated along six dimensions, including semantic fidelity and structural accuracy. Experimental results reveal that even top-tier models like GPT-4o-image lag behind human performance, with common issues in text/visual clarity and scientific correctness. These findings highlight the need for more advanced reasoning-driven visual generation capabilities.

  • 7 authors
·
May 28, 2025 2

BrainAnytime: Anatomy-Aware Cross-Modal Pretraining for Brain Image Analysis with Arbitrary Modality Availability

Clinical diagnostic workups typically follow a modality escalation pathway: after initial clinical evaluation, clinicians begin with routine structural imaging (e.g., MRI), selectively add sequences such as FLAIR or T2 to refine the differential, and reserve molecular imaging (e.g., amyloid-PET) for cases that remain uncertain after standard evaluation. Consequently, patients are observed with heterogeneous and often incomplete modality subsets. However, most current AI models assume fixed data modalities as the model inputs. In this paper, we present BrainAnytime, a unified pretraining framework pretrained on 34,899 3D brain scans from five datasets that support brain image analysis under arbitrary modality availability spanning multi-sequence MRI and amyloid-PET. A single model accepts whatever imaging is available, from a lone T1 scan to a full multimodal workup. Pretraining learns structural-molecular correspondences between MRI and PET via cross-modal distillation (RCMD) and prioritizes disease-vulnerable anatomy via atlas-guided curriculum masking (PACM), all within a shared 3D masked autoencoder (Multi-MAE3D). Across four downstream tasks and five clinically motivated modality settings, BrainAnytime largely outperforms modality-specific models, missing-modality baselines, and large-scale brain MRI pretrained foundation models on most modality settings. Notably, it surpasses the strongest missing-modality baselines with relative improvements of 6.2% and 7.0% in average accuracy on CN vs. AD and CN vs. MCI classification, respectively. Code is available at https://github.com/SDH-Lab/BrainAnytime.

  • 7 authors
·
May 12

Explainable AI Methods for Neuroimaging: Systematic Failures of Common Tools, the Need for Domain-Specific Validation, and a Proposal for Safe Application

Trustworthy interpretation of deep learning models is critical for neuroimaging applications, yet commonly used Explainable AI (XAI) methods lack rigorous validation, risking misinterpretation. We performed the first large-scale, systematic comparison of XAI methods on ~45,000 structural brain MRIs using a novel XAI validation framework. This framework establishes verifiable ground truth by constructing prediction tasks with known signal sources - from localized anatomical features to subject-specific clinical lesions - without artificially altering input images. Our analysis reveals systematic failures in two of the most widely used methods: GradCAM consistently failed to localize predictive features, while Layer-wise Relevance Propagation generated extensive, artifactual explanations that suggest incompatibility with neuroimaging data characteristics. Our results indicate that these failures stem from a domain mismatch, where methods with design principles tailored to natural images require substantial adaptation for neuroimaging data. In contrast, the simpler, gradient-based method SmoothGrad, which makes fewer assumptions about data structure, proved consistently accurate, suggesting its conceptual simplicity makes it more robust to this domain shift. These findings highlight the need for domain-specific adaptation and validation of XAI methods, suggest that interpretations from prior neuroimaging studies using standard XAI methodology warrant re-evaluation, and provide urgent guidance for practical application of XAI in neuroimaging.

  • 6 authors
·
Aug 4, 2025