Age-dependent diffusion-relaxation coupling in the basal ganglia: Implications for iron deposition and...

This study investigates age-related changes in diffusion-relaxation coupling within basal ganglia nuclei using a novel single-scan multi-TE diffusion-weighted imaging (SMT-DWI) approach, with a focus on microstructural alterations associated with regional iron deposition patterns during normal brain aging. Fifty-seven healthy participants (10-73 years) underwent optimized SMT-DWI at 3T, simultaneously acquiring multi-b-value (0/500/1000 s/mm²) and multi-TE (53/71/89 ms) data in 7:58 minutes (1.5 × 1.5 × 4 mm³ resolution). Apparent diffusion coefficient (ADC) and R2 maps were generated through mono-exponential fitting, with coupling quantified via TE-dependent ADC (k_ADC/TE) and b-value-dependent R2 (k_R2/b) metrics. Iron-related tissue properties were assessed using R2 at b = 0 (R2_{b = 0}) as a surrogate. The SMT-DWI method achieved excellent image quality (e.g., SNR = 63.8 under the most unfavorable conditions of b = 1000 s/mm² and TE = 89 ms) with good anatomical delineation. Young subjects exhibited positive coupling (ADC increasing with TE, R2 rising with b-value) across basal ganglia, while older adults showed progressive inversion to negative coupling that correlated strongly with age after accounting for sex as a covariant (sex was not a significant predictor; all p > 0.05). This transition was the most pronounced in iron-rich putamen (p < 0.001, R2_{b = 0} = 0.0208 ± 0.0027 ms^-¹), globus pallidus (p < 0.001, R2_{b = 0} = 0.0276 ± 0.0030 ms^-¹), and substantia nigra (p < 0.001, R2_{b = 0} = 0.0241 ± 0.0023 ms^-¹), while the caudate maintained stable coupling (p > 0.05) with lower iron levels (R2_{b = 0} = 0.0169 ± 0.0012 ms^-¹). All four regions demonstrated significant negative correlations between coupling metrics and R2_{b = 0} (r = -0.38 to -0.75, all p < 0.01), consistent with a role for iron-mediated microstructural changes in driving the observed coupling shifts. The age-dependent inversion from positive to negative diffusion-relaxation coupling reflects regionally heterogeneous microstructural alterations in basal ganglia. Our method provides sensitive detection of compartment-sensitive microstructural alterations, offering new insights into normal brain aging and a potential biomarker for neurodegenerative risk assessment.