T₁ Over Squared Proton Density Ratio to Characterize Multiple Sclerosis Lesions

Differentiating remyelinated from demyelinated lesions in MS remains challenging without histological confirmation. This study introduces the T₁-to-PD² ratio (TPR) imaging approach and evaluates its ability to characterize MS lesions alongside other quantitative MRI (qMRI) metrics.

Thirty individuals with MS (mean age: 47.5 ± 11.5 years) underwent 3 T MRI using 3D gradient-echo qMRI sequences to generate quantitative maps of T₁, proton density (PD), T₂*, quantitative susceptibility mapping (QSM), magnetization transfer ratio (MTR), and MT saturation index (MTsat). TPR images were derived from B₁-corrected T₁ and PD maps. White matter hyperintense lesions on T₂-weighted FLAIR were classified as hyper-, hypo-, or iso-intense relative to normal-appearing white matter on TPR. Lesion-specific qMRI values were analyzed, and simulated signal intensities based on empirical T₁ and PD values were used to illustrate TPR contrast. Statistical analyses included Wilcoxon rank-sum tests and Spearman correlations (p < 0.05).

We found that hyperintense lesions on TPR exhibited significantly higher T₁ (1566 ms), PD (0.96 a.u.), and T₂* (92 ms) values but lower MTR (37.3%) and MTsat (1.57%) compared to hypointense lesions (1085 ms; 0.88 a.u.; 64 ms; 46%; 2.48%, respectively). QSM values varied across lesion types.

In summary, TPR imaging visually differentiates MS lesions into hyper-, hypo-, and iso-intense categories, whereas all lesions appear hyperintense on FLAIR. Hyperintense TPR lesions correspond to increased water and reduced myelin content, as confirmed by quantitative T₁, PD, and MT metrics, consistent with demyelination. In contrast, hypointense lesions may reflect tissue changes associated with repair processes such as remyelination.