Abstract:Multimodal neuroimaging analysis often involves complex, modality-specific preprocessing workflows that require careful configuration, quality control, and coordination across heterogeneous toolchains. Beyond preprocessing, downstream statistical analysis and disease classification commonly require task-specific code, evaluation protocols, and data-format conventions, creating additional barriers between raw acquisitions and reproducible scientific analysis. We present NeuroAgent, an LLM-driven agentic framework that automates key preprocessing and analysis steps for heterogeneous neuroimaging data, including sMRI, fMRI, dMRI, and PET, and supports interactive downstream analysis through natural-language queries. NeuroAgent employs a hierarchical multi-agent architecture with a feedback-driven Generate-Execute-Validate engine: agents autonomously generate executable preprocessing code, detect and recover from runtime errors, and validate output integrity. We evaluate the system on 1,470 subjects pooled across all ADNI phases (CN=1,000, AD=470), where all subjects have sMRI and tabular data, with subsets also having Tau-PET (n=469), fMRI (n=278), and DTI ($n=620$). Pipeline ablation studies across multiple LLM backends show that capable models reach up to 100% intent-parsing accuracy, with the strongest backend (Qwen3.5-27B) reaching 84.8% end-to-end preprocessing step correctness. Automated recovery limits manual intervention to edge cases where human review is required via the Human-In-The-Loop interface. For Alzheimer's Disease classification using automatically preprocessed multimodal data, our agent ensemble achieves an AUC of 0.9518 with four modalities, outperforming all single-modality baselines. These results show that NeuroAgent can reduce the manual effort required for neuroimaging preprocessing and enable end-to-end automated analysis pipelines for neuroimaging research.




Abstract:The emergence of tau PET imaging over the last decade has enabled Alzheimer's disease (AD) researchers to examine tau pathology in vivo and more effectively characterize the disease trajectories of AD. Current tau PET analysis methods, however, typically perform inferences on large cortical ROIs and are limited in the detection of localized tau pathology that varies across subjects. Furthermore, a high-resolution MRI is required to carry out conventional tau PET analysis, which is not commonly acquired in clinical practices and may not be acquired for many elderly patients with dementia due to strong motion artifacts, claustrophobia, or certain metal implants. In this work, we propose a novel conditional diffusion model to perform MRI-free anomaly detection from tau PET imaging data. By including individualized conditions and two complementary loss maps from pseudo-healthy and pseudo-unhealthy reconstructions, our model computes an anomaly map across the entire brain area that allows simply training a support vector machine (SVM) for classifying disease severity. We train our model on ADNI subjects (n=534) and evaluate its performance on a separate dataset from the preclinical subjects of the A4 clinical trial (n=447). We demonstrate that our method outperforms baseline generative models and the conventional Z-score-based method in anomaly localization without mis-detecting off-target bindings in sub-cortical and out-of-brain areas. By classifying the A4 subjects according to their anomaly map using the SVM trained on ADNI data, we show that our method can successfully group preclinical subjects with significantly different cognitive functions, which further demonstrates the effectiveness of our method in capturing biologically relevant anomaly in tau PET imaging.