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This study investigates the use of denoising diffusion probabilistic models (DDPMs) to generate synthetic 3D T1-weighted brain MRI images in this context. Addressing the dual challenges of limited training data and structural fidelity, we propose a generative pipeline trained on a multicenter dataset of healthy subjects. The model suggests the potential to produce anatomically coherent synthetic scans with realistic variability. Quantitative evaluation based on Maximum Mean Discrepancy confirms the similarity between real and generated data distributions, while visual assessments highlight the preservation of global and local brain structures. Despite limitations in high-frequency detail reconstruction, the results suggest that DDPMs hold promise as a tool for augmenting neuroimaging datasets and supporting downstream tasks such as classification and segmentation. This work lays the foundation for future research aimed at improving resolution and adapting generative models to the specific challenges of rare disease imaging.<\/jats:p>","DOI":"10.1007\/s10916-025-02300-1","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T06:58:32Z","timestamp":1763362712000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Diffusion Models for Neuroimaging Data Augmentation: Assessing Realism and Clinical Relevance"],"prefix":"10.1007","volume":"49","author":[{"given":"Giulio","family":"Mallardi","sequence":"first","affiliation":[]},{"given":"Fabio","family":"Calefato","sequence":"additional","affiliation":[]},{"given":"Filippo","family":"Lanubile","sequence":"additional","affiliation":[]},{"given":"Giancarlo","family":"Logroscino","sequence":"additional","affiliation":[]},{"given":"Benedetta","family":"Tafuri","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"2300_CR1","doi-asserted-by":"publisher","unstructured":"Lai, M., Marzi, C., Mascalchi, M., Diciotti, S.: Brain mri synthesis using stylegan2-ada. 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