BrainRotViT: Transformer-ResNet Hybrid for Explainable Modeling of Brain Aging from 3D sMRI

The human brain undergoes continuous transformations across the lifespan, representing a natural component of aging that does not inherently signal pathological conditions [1]. Neurodegenerative disorders such as dementia can compromise the brain structure and accelerate aging processes. Understanding and characterizing healthy brain aging patterns therefore becomes essential for distinguishing normal aging from pathological neurodegeneration, potentially enabling earlier detection of neurodegenerative diseases. The Brain Age-Gap (BAG), i.e. the discrepancy between predicted brain age and chronological age, has emerged as a robust biomarker that captures pathological brain processes and offers insights into the rate at which an individual's brain ages in comparison to others in the population [2, 3]. It is not only associated with various neurological disorders, such as Alzheimer's disease, cognitive impairment, and Autism Spectrum Disorder, but also serves as an indicator of all-cause mortality [4, 5, 6, 7, 8] Brain age estimation has been approached through both conventional and machine learning techniques, analyzing either the whole brain, specific regions, or localized patches [9, 10, 11]. One particular study presented a method using T1-weighted MRI to predict age through region-level and voxel-level metrics [12]. Regression-based machine learning has shown promise for the brain age prediction, with kernel regression applied to whole-brain MRI across diverse age ranges [13]. Various algorithms including Support Vector Regression and Binary Decision Trees have been compared for their brain age prediction capabilities [14]. Additional regression techniques such as Relevance Vector Regression, Twin Support Vector Regression, and Gaussian Process Regression have been explored across different imaging modalities for age estimation and mortality prediction [11, 15, 16, 17].