A Comparison of Magnetic Resonance Imaging Methods to Assess Multiple Sclerosis Lesions: Implications for Patient Characterization and Clinical Trial Design

Abstract

Magnetic resonance imaging (MRI) is a sensitive imaging modality for identifying inflammatory and/or demyelinating lesions, which is critical for a clinical diagnosis of MS and evaluating drug responses. There are many unique means of probing brain tissue status, including conventional T1 and T2 weighted imaging (T1WI, T2WI), T2 fluid attenuated inversion recovery (FLAIR), magnetization transfer, myelin water fraction, diffusion tensor imaging (DTI), phase-sensitive inversion recovery and susceptibility weighted imaging (SWI), but no study has combined all of these modalities into a single well-controlled investigation. The goals of this study were to: compare different MRI measures for lesion visualization and quantification; evaluate the repeatability of various imaging methods in healthy controls; compare quantitative susceptibility mapping (QSM) with myelin water fraction; measure short-term longitudinal changes in the white matter of MS patients and map out the tissue properties of the white matter hyperintensities using STAGE (strategically acquired gradient echo imaging). Additionally, the outcomes of this study were anticipated to aid in the choice of an efficient imaging protocol reducing redundancy of information and alleviating patient burden. Of all the sequences used, T2 FLAIR and T2WI showed the most lesions. To differentiate the putative demyelinating lesions from inflammatory lesions, the fusion of SWI and T2 FLAIR was used. Our study suggests that a practical and efficient imaging protocol combining T2 FLAIR, T1WI and STAGE (with SWI and QSM) can be used to rapidly image MS patients to both find lesions and study the demyelinating and inflammatory characteristics of the lesions.

Quantitative susceptibility mapping in multiple sclerosis: A systematic review and meta-analysis

“…The number of hyperintense QSM lesions in reference to total lesion count on conventional scans (e.g., T2, FLAIR) was most frequently documented. Seventeen studies provided data on the percentages of hyperintense QSM lesions, showing varying proportions that ranged from 13 % to 88 % ( Guo et al, 2021 , Liao et al, 2023 ; Haacke et al, 2021; Castellaro et al, 2017 , Chawla et al, 2016 , Chawla et al, 2018 , Chen et al, 2014 , Cronin et al, 2016 , Gillen et al, 2021 , Harrison et al, 2016 , Kakeda et al, 2015 , Li et al, 2016 , Pelizzari et al, 2020 , Rahmanzadeh et al, 2022 , Tolaymat et al, 2020 , Zhang et al, 2016a , Zhang et al, 2016c ). Additionally, rim lesion counts on QSM were recorded in 12 studies, reporting proportions that ranged from 4 % to 44 % ( Chawla et al, 2018 , Cronin et al, 2016 , Guo et al, 2021 , Gillen et al, 2021 , Li et al, 2016 , Harrison et al, 2016 , Kaunzner et al, 2019 , Huang et al, 2022 , Rahmanzadeh et al, 2022 , Yao et al, 2018 , Zhang et al, 2022 ).…”

Multiparametric Quantitative MRI of Peripheral Nerves in the Leg: A Reliability Study

“…In compact neural tissues like cerebral white matter, these various qMRI parameters are partially associated with each other and may provide redundant information in the brain. 35 In contrast, the peripheral nerve is comprised of myelinated axons and bundles of unmyelinated axons within a fascicle, along with lipid-rich connective tissues between fascicles. 1 The size of the nerve fascicle is relatively small with respect to the clinical qMRI resolution; thus, it is often partial volume averaged.…”

“…These different quantitative measures of relaxometry, diffusivity, MT, and morphological features of the neural tissue potentially have different specificities to the pathological changes of tissue water, myelin, and iron contents. In compact neural tissues like cerebral white matter, these various qMRI parameters are partially associated with each other and may provide redundant information in the brain 35 . In contrast, the peripheral nerve is comprised of myelinated axons and bundles of unmyelinated axons within a fascicle, along with lipid‐rich connective tissues between fascicles 1 .…”

Reduced Oxygen Extraction Fraction in Deep Cerebral Veins Associated with Cognitive Impairment in Multiple Sclerosis

“…The inclusion and exclusion criteria were described in a previous publication using the quantitative MRI data acquired from the same cohorts. 40 A neurologist performed clinical assessment for MS patients, including the Expanded Disability Status Scale (EDSS) for disease severity 41 and the Paced Auditory Serial Addition Test (PASAT) for cognitive function. 42…”