Abstract

ObjectsThe diffusion‐based spherical mean technique (SMT) provides a novel model to relate multi‐b‐value diffusion magnetic resonance imaging (MRI) data to features of tissue microstructure. We propose the first clinical application of SMT to image the brain of patients with multiple sclerosis (MS) and investigate clinical feasibility and translation.MethodsEighteen MS patients and nine age‐ and sex‐matched healthy controls (HCs) underwent a 3.0 Tesla scan inclusive of clinical sequences and SMT images (isotropic resolution of 2 mm). Axial diffusivity (AD), apparent axonal volume fraction (V ax), and effective neural diffusivity (D ax) parametric maps were fitted. Differences in AD, V ax, and D ax between anatomically matched regions reflecting different tissues types were estimated using generalized linear mixed models for binary outcomes.ResultsDifferences were seen in all SMT‐derived parameters between chronic black holes (cBHs) and T2‐lesions (P ≤ 0.0016), in V ax and AD between T2‐lesions and normal appearing white matter (NAWM) (P < 0.0001), but not between the NAWM and normal WM in HCs. Inverse correlations were seen between V ax and AD in cBHs (r = −0.750, P = 0.02); in T2‐lesions D ax values were associated with V ax (r = 0.824, P < 0.0001) and AD (r = 0.570, P = 0.014).Interpretations SMT‐derived metrics are sensitive to pathological changes and hold potential for clinical application in MS patients.

Highlights

  • Axonal injury is a key element in the pathology of multiple sclerosis (MS) and a major determinant of patients’ disability.[1]

  • Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association

  • Vax [P < 0.0001, Akaike information criterion (AIC) = 446.5, odds ratios (OR) = 6.25, 95% confidence interval (CI) = (4.28, 9.52)] values were consistently lower in chronic black holes (cBHs) compared with T2-lesions

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Summary

Introduction

Axonal injury is a key element in the pathology of multiple sclerosis (MS) and a major determinant of patients’ disability.[1] Because capturing and characterizing axonal damage in MS patients in vivo is challenging,[2] there remains a pressing need to identify a magnetic resonance imaging (MRI) biometric indicative of axonal quantity. This biomarker would allow for the detection of microscopic damage before symptoms and irreversible tissue a 2019 The Authors. Lack of this biomarker is an impediment to a responsible design and conduct of phase II and phase III clinical trials on neuroprotection,[3] making MS an incurable disease

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