Background: 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.

Objective: To compare the accuracy and Cohen's effect size (ES) of PSR and RD in detecting and quantifying tissue injury in early MS.

Methods: Cross-sectional prospective study. Methods: 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.

Results: 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. Methods: 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. Results: 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.

Conclusions: PSR offers superior accuracy and ES over RD in detecting tissue injury in MS. Methods: 1 TECHNICAL EFFICACY: Stage 2.