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

Overview

1. Changping Laboratory, Beijing, China
2. Center for Magnetic Resonance Research and Department of Radiology, University of Illinois Chicago, Chicago, IL, United States
3. Biomedical Pioneering Innovation Center, Peking University, Beijing, China

Abstract

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 (kADC/TE) and b-value-dependent R2 (kR2/b) metrics. Iron-related tissue properties were assessed using R2 at b = 0 (R2b = 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, R2b = 0 = 0.0208 ± 0.0027 ms−¹), globus pallidus (p < 0.001, R2b = 0 = 0.0276 ± 0.0030 ms−¹), and substantia nigra (p < 0.001, R2b = 0 = 0.0241 ± 0.0023 ms−¹), while the caudate maintained stable coupling (p > 0.05) with lower iron levels (R2b = 0 = 0.0169 ± 0.0012 ms−¹). All four regions demonstrated significant negative correlations between coupling metrics and R2b = 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.

Reproduced under the paper's license (CC BY), from the paper cited above.

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The sample data and analysis code that support the findings will be available upon reasonable request to the corresponding author.

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Version 2, 28 September 2026

• Funding: added Changping Laboratory: 2021B-01-01

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 6 authors, 4 keywords, 60 references.

Cite

This paper

Sun, K., Wang, Y., Sun, X., Zhang, Y., Zhou, X. J., & Liu, H. (2026). Age-dependent diffusion-relaxation coupling in the basal ganglia: Implications for iron deposition and microstructural dynamics. Imaging neuroscience (Cambridge, Mass.), 4, IMAG.a.1195. https://doi.org/10.1162/imag.a.1195

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