Age-related changes in myelin and myelin water quantified with short-TR adiabatic inversion-recovery (STAIR) sequences

Abstract

Myelin proton density fraction (MPDF) and myelin water fraction (MWF) measured with short-TR adiabatic inversion-recovery (STAIR) sequences are potential biomarkers of aging and neurodegeneration, but the effects of aging on MPDF/MWF remain unknown. This study aims to assess relationships between age and MPDF/MWF using the 3D STAIR ultrashort echo time (STAIR-UTE) and STAIR short echo time (STAIR-STE) sequences, respectively. 42 volunteers (29 young (<55y), 13 old (>55y)), were recruited for MPDF and MWF mapping for white matter (WM) and gray matter (GM) on a 3 T scanner. Excellent inter-reader reliability was demonstrated for MPDF and MWF measurements with ICC values of 0.97 and 0.98, respectively, between two readers. In the young group, WM MPDF and MWF range from 8-13 % and 6-13 %, respectively, while GM MPDF and MWF range from 5-7 % and 3-5 %, respectively. In the old group, WM MPDF and MWF range from 6-12 % and 5-13 %, and GM MPDF and MWF range from 3-6 % and 2-5 %, respectively. The young group's MPDF/MWF values were significantly higher than those of the old group. Altogether, the 42 volunteers display linear and quadratic associations of MPDF/MWF with age. MPDF demonstrated significant correlations with MWF in the majority of brain regions. This study demonstrates the capability of two myelin imaging biomarkers, STAIR-UTE measured MPDF and STAIR-STE measured MWF to map brain myelin and MW. These biomarkers hold the potential to differentiate normal aging from neuroinflammatory/neurodegenerative diseases.

Keywords: Aging; Biomarker; Brain; Myelin content; Myelin water.

Fig. 1

Representative MPDF (left column) and MWF (right column) maps comparing a 24-year-old volunteer (young group(<55y)) (top row) with an 87-year-old volunteer (old group (>55y)) (bottom row). WM regions display higher MPDF and MWF than GM regions, consistent with WM being more myelin-rich than GM. The young volunteer displays noticeably higher MPDF and MWF than the old volunteer.

Fig. 2

Bar plots (top row) comparing the averaged WM and GM (left column) MPDF and (right column) MWF of the young (<55y, n = 29) group and the old (>55y, n = 13) group. Mann-Whitney U test analysis was performed on WM and GM ROI values averaged by subject to investigate statistical difference between the young and old groups (“*” indicates p < 0.05, “**” indicates p < 0.01). MPDF and MWF measurements in the WM and GM of the young group are significantly higher than those of the old group. Corresponding violin plots (bottom row) of ROI values for the MPDF (left column) and MWF (right column) to visualize group distributions. WM and GM from the young group are depicted in dotted white. WM and GM from the old group are depicted in grey.

Fig. 3

Scatterplots for all MPDF (top two rows) and MWF (bottom two rows) ROI measurements for each region (LCS/RCS = left/right centrum semiovale; LV/RV = left/right periventricular region; LS/RS = left/right subcortical WM; G = genu; S = splenium; P = putamen; T = thalamus) with age across all 42 young and old group volunteers. Each plot displays fitted regression lines: red for the linear model and blue for the quadratic model, with their corresponding coefficients of determination R² and p-values when compared to the null model (p < 0.05, denoted by a “*”, and p < 0.01, denoted by a “**”). Black brackets indicate comparisons between the quadratic and linear models. (p > 0.05, denoted by a “▲”, p < 0.05, denoted by a “*”).

Fig. 4

Linear regression lines and scatterplots for MPDF and MWF measurements for each region (LCS/RCS = left/right centrum semiovale; LV/RV = left/right periventricular region; LS/RS = left/right subcortical WM; G = genu; S = splenium; P = putamen; T = thalamus) across all 37 young and old group volunteers. All Pearson’s correlation R values are displayed in the bottom right of each graph and exhibit positive correlations between MPDF and MWF. All correlations except that of S MWF vs. MPDF are significant (p < 0.05, denoted by a “*” and p < 0.01, denoted by a “**”).