Quantitative MRI analysis of deep gray matter aging: Volumetric, T1/T2 ratio, and blood perfusion alterations

BACKGROUND: The deep gray matter nuclei (DGMN)-including the thalamus, caudate, putamen, and pallidum-are essential for cognitive, motor, and affective functions and are highly susceptible to age-related degeneration. However, the combined effects of aging and sex on DGMN volume, microstructure, and perfusion remain incompletely characterized. METHODS: Using data from 652 healthy adults (36-89 years) from the Human Connectome Project-Aging cohort, we examined volumetric and perfusion changes across the DGMN. High-resolution T1- and T2-weighted MRI and multi-delay pseudo-continuous arterial spin labeling (pCASL) were used to quantify normalized volume, T1/T2 ratio, cerebral blood flow (CBF), and arterial transit time (ATT) in DGMN regions after perivascular spaces were removed. Age-related trajectories were modeled using linear and quadratic regression, and differences between sexes were examined, with false discovery rate correction applied. RESULTS: Advancing age was associated with significant volumetric decline in all DGMN regions (p < 0.001), prolonged ATT, and reduced CBF, particularly in the caudate and thalamus. The T1/T2 ratio exhibited region-specific nonlinear trajectories, peaking in mid-adulthood and declining thereafter, reflecting its underlying age-related processes of demyelination and iron accumulation. Sex-stratified analyses suggested modest differences in T1/T2, ATT, and CBF trajectories; however, no significant age × sex interactions were observed after correction for multiple comparisons. DGMN volumes correlated negatively with ATT, while T1/T2 ratio correlated inversely with CBF, indicating more complex interactions between structure, tissue properties, and perfusion. CONCLUSIONS: This large-scale quantitative MRI study delineates distinct age-related trajectories of DGMN over adult lifespan. Integrating volumetric, T1/T2 ratio, and multi-delay ASL metrics-while correcting for perivascular spaces-enhances sensitivity to subtle changes and provides normative benchmarks for detecting early neurodegenerative alterations.