Improving the assessment of axonal injury in early multiple sclerosis.

Rationale and Objectives: Several quantitative magnetic resonance imaging (MRI) methods are available to measure tissue injury in multiple sclerosis (MS), but their pathological specificity remains limited. The multi-compartment diffusion imaging using the spherical mean technique (SMT) overcomes several technical limitations of the diffusion-weighted image signal, thus delivering metrics with increased pathological specificity. Given these premises, here we assess whether the SMT-derived apparent axonal volume (V _ax ) provides a better tissue classifier than the diffusion tensor imaging (DTI)-derived axial diffusivity (AD) in the white matter (WM) of MS brains.
Methods: Forty-three treatment-naïve people with newly diagnosed MS, clinically isolated syndrome, or radiologically isolated syndrome and 18 healthy controls (HCs) underwent a 3.0 Tesla MRI inclusive of T ₁ -weighted (T ₁ -w) and T ₂ -w fluid-attenuated inversion recovery (FLAIR) sequences, and multi-b shell diffusion-weighted imaging. In patients only, pre- and post-gadolinium diethylenetriamine penta-acetic acid T ₁ -w sequences were obtained for the evaluation of contrast-active lesions (CELs). V _ax and AD were calculated in T ₂ -lesions, chronic black holes (cBHs), and normal appearing (NAWM) in patients and normal WM (NWM) in HCs. V _ax and AD values were compared across all the possible combinations of these regions. CELs were excluded from the analyses.
Results: V _ax differed in all comparisons (p ≤ 0.047 by paired t-test); AD differed in most comparisons (p < 0.001) except between NAWM and NWM, and between cBHs and T ₂ -lesions. V _ax had higher accuracy (p ≤ 0.029 by DeLong test) and larger effect size (p ≤ 0.038 by paired t-test) than AD in differentiating areas with even minimal tissue injury.
Conclusions: V _ax provides a better radiological quantitative discriminator of different degrees of axonal-mediated tissue injury even between areas with expected minimal pathology. Our data support further studies to assess the readiness of V _ax as a measure of outcome for clinical trials on neuroprotection in MS.
Competing Interests: Declaration of Competing Interest The authors declare no financial interests/personal relationships which may be considered as potential competing interests.
(Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)