Early diagnosis of Alzheimer's Disease (AD), especially at the mild cognitive impairment (MCI) stage, is vital yet hindered by subjective assessments and the high cost of multimodal imaging modalities. Although deep learning methods offer automated alternatives, their energy inefficiency and computational demands limit real-world deployment, particularly in resource-constrained settings. As a brain-inspired paradigm, spiking neural networks (SNNs) are inherently well-suited for modeling the sparse, event-driven patterns of neural degeneration in AD, offering a promising foundation for interpretable and low-power medical diagnostics. However, existing SNNs often suffer from weak expressiveness and unstable training, which restrict their effectiveness in complex medical tasks. To address these limitations, we propose FasterSNN, a hybrid neural architecture that integrates biologically inspired LIF neurons with region-adaptive convolution and multi-scale spiking attention. This design enables sparse, efficient processing of 3D MRI while preserving diagnostic accuracy. Experiments on benchmark datasets demonstrate that FasterSNN achieves competitive performance with substantially improved efficiency and stability, supporting its potential for practical AD screening. Our source code is available at https://github.com/wuchangw/FasterSNN.

Magnetic resonance imaging of fetal and neonatal brains reveals rapid neurodevelopment marked by substantial anatomical changes unfolding within days. Studying this critical stage of the developing human brain, therefore, requires accurate brain models-referred to as atlases-of high spatial and temporal resolution. To meet these demands, established traditional atlases and recently proposed deep learning-based methods rely on large and comprehensive datasets. This poses a major challenge for studying brains in the presence of pathologies for which data remains scarce. We address this limitation with CINeMA (Conditional Implicit Neural Multi-Modal Atlas), a novel framework for creating high-resolution, spatio-temporal, multimodal brain atlases, suitable for low-data settings. Unlike established methods, CINeMA operates in latent space, avoiding compute-intensive image registration and reducing atlas construction times from days to minutes. Furthermore, it enables flexible conditioning on anatomical features including GA, birth age, and pathologies like ventriculomegaly (VM) and agenesis of the corpus callosum (ACC). CINeMA supports downstream tasks such as tissue segmentation and age prediction whereas its generative properties enable synthetic data creation and anatomically informed data augmentation. Surpassing state-of-the-art methods in accuracy, efficiency, and versatility, CINeMA represents a powerful tool for advancing brain research. We release the code and atlases at https://github.com/m-dannecker/CINeMA.

Supervised machine learning has enabled accurate pathology detection in brain MRI, but requires training data from diseased subjects that may not be readily available in some scenarios, for example, in the case of rare diseases. Reconstruction-based unsupervised anomaly detection, in particular using diffusion models, has gained popularity in the medical field as it allows for training on healthy images alone, eliminating the need for large disease-specific cohorts. These methods assume that a model trained on normal data cannot accurately represent or reconstruct anomalies. However, this assumption often fails with models failing to reconstruct healthy tissue or accurately reconstruct abnormal regions i.e., failing to remove anomalies. In this work, we introduce a novel conditional diffusion model framework for anomaly detection and healthy image reconstruction in brain MRI. Our weakly supervised approach integrates synthetically generated pseudo-pathology images into the modeling process to better guide the reconstruction of healthy images. To generate these pseudo-pathologies, we apply fluid-driven anomaly randomization to augment real pathology segmentation maps from an auxiliary dataset, ensuring that the synthetic anomalies are both realistic and anatomically coherent. We evaluate our model's ability to detect pathology, using both synthetic anomaly datasets and real pathology from the ATLAS dataset. In our extensive experiments, our model: (i) consistently outperforms variational autoencoders, and conditional and unconditional latent diffusion; and (ii) surpasses on most datasets, the performance of supervised inpainting methods with access to paired diseased/healthy images.

Using radio signals from a magnetic field, magnetic resonance imaging (MRI) represents a medical procedure that produces images to provide more information than typical scans. Diagnosing brain tumors from MRI is difficult because of the wide range of tumor shapes, areas, and visual features, thus universal and automated system to handle this task is required. Among the best deep learning methods, the U-Net architecture is the most widely used in diagnostic medical images. Therefore, U-Net-based attention is the most effective automated model in medical image segmentation dealing with various modalities. The self-attention structures that are used in the U-Net design allow for fast global preparation and better feature visualization. This research aims to study the progress of U-Net design and show how it improves the performance of brain tumor segmentation. We have investigated three U-Net designs (standard U-Net, Attention U-Net, and self-attention U-Net) for five epochs to find the last segmentation. An MRI image dataset that includes 3064 images from the Kaggle website is used to give a more comprehensive overview. Also, we offer a comparison with several studies that are based on U-Net structures to illustrate the evolution of this network from an accuracy standpoint. U-Net-based self-attention has demonstrated superior performance compared to other studies because self-attention can enhance segmentation quality, particularly for unclear structures, by concentrating on the most significant parts. Four main metrics are applied with a loss function of 5.03 %, a validation loss function of 4.82 %, a validation accuracy of 98.49 %, and an accuracy of 98.45 %.

Functional Magnetic Resonance Imaging (fMRI) is essential for studying brain function and diagnosing neurological disorders, but current analysis methods face reproducibility and transferability issues due to complex pre-processing and task-specific models. We introduce NeuroSTORM (Neuroimaging Foundation Model with Spatial-Temporal Optimized Representation Modeling), a generalizable framework that directly learns from 4D fMRI volumes and enables efficient knowledge transfer across diverse applications. NeuroSTORM is pre-trained on 28.65 million fMRI frames (>9,000 hours) from over 50,000 subjects across multiple centers and ages 5 to 100. Using a Mamba backbone and a shifted scanning strategy, it efficiently processes full 4D volumes. We also propose a spatial-temporal optimized pre-training approach and task-specific prompt tuning to improve transferability. NeuroSTORM outperforms existing methods across five tasks: age/gender prediction, phenotype prediction, disease diagnosis, fMRI-to-image retrieval, and task-based fMRI classification. It demonstrates strong clinical utility on datasets from hospitals in the U.S., South Korea, and Australia, achieving top performance in disease diagnosis and cognitive phenotype prediction. NeuroSTORM provides a standardized, open-source foundation model to improve reproducibility and transferability in fMRI-based clinical research.

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. Early and precise diagnosis of AD is crucial for timely intervention and treatment planning to alleviate the progressive neurodegeneration. However, most existing methods rely on single-modality data, which contrasts with the multifaceted approach used by medical experts. While some deep learning approaches process multi-modal data, they are limited to specific tasks with a small set of input modalities and cannot handle arbitrary combinations. This highlights the need for a system that can address diverse AD-related tasks, process multi-modal or missing input, and integrate multiple advanced methods for improved performance. In this paper, we propose ADAgent, the first specialized AI agent for AD analysis, built on a large language model (LLM) to address user queries and support decision-making. ADAgent integrates a reasoning engine, specialized medical tools, and a collaborative outcome coordinator to facilitate multi-modal diagnosis and prognosis tasks in AD. Extensive experiments demonstrate that ADAgent outperforms SOTA methods, achieving significant improvements in accuracy, including a 2.7% increase in multi-modal diagnosis, a 0.7% improvement in multi-modal prognosis, and enhancements in MRI and PET diagnosis tasks.

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. Early and precise diagnosis of AD is crucial for timely intervention and treatment planning to alleviate the progressive neurodegeneration. However, most existing methods rely on single-modality data, which contrasts with the multifaceted approach used by medical experts. While some deep learning approaches process multi-modal data, they are limited to specific tasks with a small set of input modalities and cannot handle arbitrary combinations. This highlights the need for a system that can address diverse AD-related tasks, process multi-modal or missing input, and integrate multiple advanced methods for improved performance. In this paper, we propose ADAgent, the first specialized AI agent for AD analysis, built on a large language model (LLM) to address user queries and support decision-making. ADAgent integrates a reasoning engine, specialized medical tools, and a collaborative outcome coordinator to facilitate multi-modal diagnosis and prognosis tasks in AD. Extensive experiments demonstrate that ADAgent outperforms SOTA methods, achieving significant improvements in accuracy, including a 2.7% increase in multi-modal diagnosis, a 0.7% improvement in multi-modal prognosis, and enhancements in MRI and PET diagnosis tasks.

IntroductionAccurately predicting Alzheimers Disease (AD) progression is useful for clinical care. The 2019 TADPOLE (The Alzheimers Disease Prediction Of Longitudinal Evolution) challenge evaluated 92 algorithms from 33 teams worldwide. Unlike typical clinical prediction studies, TADPOLE accommodates (1) variable number of observed timepoints across patients, (2) missing data across modalities and visits, and (3) prediction over an open-ended time horizon, which better reflects real-world data. However, TADPOLE only used the Alzheimers Disease Neuroimaging Initiative (ADNI) dataset, so how well top algorithms generalize to other cohorts remains unclear. MethodsWe tested five algorithms in three external datasets covering 2,312 participants and 13,200 timepoints. The algorithms included FROG, the overall TADPOLE winner, which utilized a unique Longitudinal-to-Cross-sectional (L2C) transformation to convert variable-length longitudinal histories into feature vectors of the same length across participants (i.e., same-length feature vectors). We also considered two FROG variants. One variant unified all XGBoost models from the original FROG with a single feedforward neural network (FNN), which we referred to as L2C-FNN. We also included minimal recurrent neural networks (MinimalRNN), which was ranked second at publication time, as well as AD Course Map (AD-Map), which outperformed MinimalRNN at publication time. All five models - three FROG variants, MinimalRNN and AD-Map - were trained on ADNI and tested on the external datasets. ResultsL2C-FNN performed the best overall. In the case of predicting cognition and ventricle volume, L2C-FNN and AD-Map were the best. For clinical diagnosis prediction, L2C-FNN was the best, while AD-Map was the worst. L2C-FNN also maintained its edge over other models, regardless of the number of observed timepoints, and regardless of the prediction horizon from 0 to 6 years into the future. ConclusionsL2C-FNN shows strong potential for both short-term and long-term dementia progression prediction. Pretrained ADNI models are available: https://github.com/ThomasYeoLab/CBIG/tree/master/stable_projects/predict_phenotypes/Zhang2025_L2CFNN.

Focal cortical dysplasia (FCD) is a common pathology for pharmacoresistant focal epilepsy, yet detection of FCD on clinical MRI is challenging. Magnetic resonance fingerprinting (MRF) is a novel quantitative imaging technique providing fast and reliable tissue property measurements. The aim of this study was to develop an MRF-based deep-learning (DL) framework for whole-brain FCD detection. We included patients with pharmacoresistant focal epilepsy and pathologically/radiologically diagnosed FCD, as well as age-matched and sex-matched healthy controls (HCs). All participants underwent 3D whole-brain MRF and clinical MRI scans. T1, T2, gray matter (GM), and white matter (WM) tissue fraction maps were reconstructed from a dictionary-matching algorithm based on the MRF acquisition. A 3D ROI was manually created for each lesion. All MRF maps and lesion labels were registered to the Montreal Neurological Institute space. Mean and SD T1 and T2 maps were calculated voxel-wise across using HC data. T1 and T2 <i>z</i>-score maps for each patient were generated by subtracting the mean HC map and dividing by the SD HC map. MRF-based morphometric maps were produced in the same manner as in the morphometric analysis program (MAP), based on MRF GM and WM maps. A no-new U-Net model was trained using various input combinations, with performance evaluated through leave-one-patient-out cross-validation. We compared model performance using various input combinations from clinical MRI and MRF to assess the impact of different input types on model effectiveness. We included 40 patients with FCD (mean age 28.1 years, 47.5% female; 11 with FCD IIa, 14 with IIb, 12 with mMCD, 3 with MOGHE) and 67 HCs. The DL model with optimal performance used all MRF-based inputs, including MRF-synthesized T1w, T1z, and T2z maps; tissue fraction maps; and morphometric maps. The patient-level sensitivity was 80% with an average of 1.7 false positives (FPs) per patient. Sensitivity was consistent across subtypes, lobar locations, and lesional/nonlesional clinical MRI. Models using clinical images showed lower sensitivity and higher FPs. The MRF-DL model also outperformed the established MAP18 pipeline in sensitivity, FPs, and lesion label overlap. The MRF-DL framework demonstrated efficacy for whole-brain FCD detection. Multiparametric MRF features from a single scan offer promising inputs for developing a deep-learning tool capable of detecting subtle epileptic lesions.

The four-repeat (4R) tauopathies are a group of neurodegenerative diseases, including progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and globular glial tauopathy (GGT). This study aimed to characterize spatiotemporal atrophy progression using structural magnetic resonance imaging (MRI) and to examine its relationship with clinical course and neuropathology in a cohort of autopsy-confirmed 4R tauopathies. The study included 85 autopsied patients (54 with PSP, 28 with CBD, and 3 with GGT) who underwent multiple 3T MRI scans, as well as neuropsychological, neurological, and speech/language examinations, and standardized postmortem neuropathological evaluations. An unsupervised machine-learning algorithm, Subtype and Stage Inference (SuStaIn), was applied to the cross-sectional brain volumes to estimate spatiotemporal atrophy patterns and data-driven subtypes and stages in each patient. The relationships among estimated subtypes, pathological diagnoses, and longitudinal changes in clinical testing were examined. The SuStaIn algorithm identified 2 distinct subtypes: (1) the subcortical subtype, in which atrophy progresses from the midbrain to the cortex, and (2) the cortical subtype, in which atrophy progresses from the frontal cortex to the subcortical regions. The subcortical subtype was more associated with typical PSP, whereas the cortical subtype was more associated with atypical PSP with a cortical distribution of pathology and CBD (p < 0.001). The cortical subtype had a faster rate of change on the PSP Rating Scale than the subcortical subtype (p < 0.05). SuStaIn analysis revealed 2 MRI-driven subtypes with distinct spatiotemporal atrophy patterns, clinical courses, and neuropathology. Our findings contribute to a comprehensive and improved understanding of disease progression and its relationship to tau pathology in 4R tauopathies. ANN NEUROL 2025.