Year: 2026
Type: preprint
Abstract: Brain age models can systematically mispredict age for specific demographic groups, risking biased estimates of neurological health. We present an approach to improve accuracy and reduce racial disparities using synthetic T1 images generated via style-transfer with SuperSynth, an open-source FreeSurfer tool that produces intensity harmonized isotropic images regardless of the input's contrast or resolution. We refer to the original scans as the real domain and their SuperSynth-derived counterparts as the synthetic domain. Because each synthetic image derives from the participant's own scan, comparisons between domains hold anatomy and demographic composition constant. We audited fairness by training a neural network across thirteen racial compositions on a diverse cohort (683 White, 605 Black, 431 Asian) in both domains. Our findings highlight three key insights. First, the synthetic domain enhanced both fairness and accuracy, and even models trained on a single demographic showed reduced racial disparity purely from switching domain. The same pattern appeared in two independently developed pretrained models. Second, models trained on synthetic data demonstrated superior out-of-distribution robustness in external clinical testing. Third, augmenting imbalanced datasets with synthetic minority images closed 61% of the fairness gap without requiring new data collection, and unlike explicitly supplying race labels, does not require race as a model input at deployment. Representational analyses indicated that appearance standardization changes which features drive age prediction rather than removing demographic information from the images. By utilizing synthetic data, our approach offers a robust pathway to more equitable and generalizable brain age models.
Language: English
Subfield: Health Informatics
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Foundation for the National Institutes of Health, Alzheimer's Association, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Biogen, F. Hoffmann-La Roche, Meso Scale Diagnostics, Alzheimer's Disease Neuroimaging Initiative, BioClinica, Novartis Pharmaceuticals Corporation, Northern California Institute for Research and Education, Eisai, Servier, H. Lundbeck A/S, National Institutes of Health, Genentech, Canadian Institutes of Health Research, National Institute on Aging, National Institute of Mental Health
Awards: G1880935189, Acquisition-independent machine learning for morphometric analysis of underrepresented aging populations with clinical and low-field brain MRI, G2534680557, G29951154, G3372319170, G3553156159, G3752451908, G3870774570, G3966393351, G4079001475, G5209990037, G5235017436, G5654639750, G5723525410, G5740349702, G6371410416, G6408183974, Measuring Brain Health Using Low-Field Portable MRI, G6899163935, G7414321945, G781725486, G839208290, G9000122335, Functionally guided adult whole brain cell atlas in human and NHP, Alzheimer's Disease Neuroimaging Initiative (ADNI4), Diagnosing the undiagnosable: studies of Alzheimer disease mimics and confounders via "neuropathometry" of dissection photos with 3D scanning, A multimodal brain cell atlas and community resource of Alzheimer's disease and comorbid dementias.
OpenAlex ID: W7214405407