Selective inversion recovery quantitative magnetization transfer (SIR-qMT)-derived macromolecular to free water pool size ratio (PSR) and diffusion tensor imaging (DTI)-derived radial diffusivity (RD) are potential metrics for assessing myelin integrity in multiple sclerosis (MS). However, establishing their accuracy in identifying tissue injury is essential for clinical translation. To compare the accuracy and Cohen's effect size (ES) of PSR and RD in detecting and quantifying tissue injury in early MS. Cross-sectional prospective study. Fourty-three subjects with newly diagnosed MS (mean age 38 ± 11 years, 70% females) and 18 age- and sex-matched healthy controls (HCs; age 38 ± 12 years, 62.5% females). 3-T MRI using T1-weighted (T1-w) turbo spin echo, T2-w fluid-attenuated inversion recovery (FLAIR), DTI, and SIR-qMT sequences. T2-lesions were identified as hyperintense on T2-w-FLAIR, and chronic black holes (cBHs) by simultaneous T2-w-FLAIR hyperintensity and T1-w hypointensity. Regions of interest (ROIs) in normal-appearing white matter (NAWM) were classified as proximal (p) or distant (d) to lesions, while normal white matter (NWM) was identified in HCs. PSR and RD values of T2-lesions and cBHs were compared to their matched p/dNAWM and NWM in HCs. Comparisons were also made between T2-lesions and cBHs. Receiver operating characteristic curves evaluated metric accuracy, and paired t tests compared ES values of PSR and RD, with significance set at P < 0.050. We identified 823 T2-lesions, 392 cBHs, 426 p-, and 213 d-NAWM ROIs in patients, and 162 NWM ROIs in HCs. PSR differed significantly in all comparisons, while RD was differed in all except cBHs vs. T2-lesions (P = 0.051). PSR had significantly higher accuracy in differentiating T2-lesions from p/dNAWM and NWM, with a larger ES when comparing T2-lesions to p/dNAWM and NWM and cBHs to pNAWM and NWM. PSR offers superior accuracy and ES over RD in detecting tissue injury in MS. 1 TECHNICAL EFFICACY: Stage 2.
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