Metabolite T₂ relaxation times decrease across the adult lifespan in a large multi-site cohort

Relaxation correction is crucial for accurately estimating metabolite concentrations measured using in vivo MRS. However, the majority of MRS quantification routines assume that relaxation values remain constant across the lifespan, despite prior evidence of T₂ changes with aging for multiple of the major metabolites. Here, we comprehensively investigate correlations between T₂ and age in a large, multi-site cohort.

We recruited approximately 10 male and 10 female participants from each decade of life: 18-29, 30-39, 40-49, 50-59, and 60+ y old (n = 101 total). We collected PRESS data at eight TEs (30, 50, 74, 101, 135, 179, 241, and 350 ms) from voxels placed in white-matter-rich centrum semiovale (CSO) and gray-matter-rich posterior cingulate cortex (PCC). We quantified metabolite amplitudes using Osprey and fit exponential decay curves to estimate T₂.

Older age was correlated with shorter T₂ for tNAA_2.0, tCr_3.0, tCr_3.9, tCho, and tissue water (CSO and PCC), as well as mI and Glx (PCC only); r_s = -0.22 to -0.63, all p < 0.05, false discovery rate (FDR)-corrected. These associations largely remained statistically significant when controlling for cortical atrophy. By region, T₂ values were longer in the CSO for tNAA_2.0, tCr_3.9, Glx, and tissue water and longer in the PCC for tCho and mI. T₂ did not differ by region for tCr_3.0.

These findings underscore the importance of considering metabolite T₂ differences with aging in MRS quantification. We suggest that future 3T work utilize the equations presented here to estimate age-specific T₂ values instead of relying on uniform default values.