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

Abstract

BackgroundPatients with polyneuropathies typically have demyelination and/or axonal degeneration in peripheral nerves. Currently, there is a lack of imaging biomarkers to track the changes in these pathologies.PurposeTo develop and evaluate the reliability of a multiparametric quantitative magnetic resonance imaging (qMRI) method of peripheral nerves in the leg.Study TypeProspective.SubjectsSeventeen healthy volunteers (36.2 ± 13.8 years old, 9 males) with 10 of them scanned twice for test–retest.Field Strength/Sequence3 T, three‐dimensional gradient echo and diffusion tensor imaging.AssessmentA qMRI protocol and processing pipeline was established for quantifying the following nerve parameters that are sensitive to myelin and axonal pathologies: magnetization transfer (MT) ratio (MTR), MT saturation index (MTsat), T2*, T1, proton density (PD), fractional anisotropy (FA), and mean/axial/radial diffusivities (MD, AD, and RD). The qMRI protocol also measures the volume of nerve fascicles (fVOL) and the fat fraction (FF) of muscles.Statistical TestsThe intersession reproducibility and inter‐rater reliability of each qMRI parameter were assessed by Bland–Altman analysis and intraclass correlation coefficient (ICC). Pairwise Pearson correlation analyses were performed to investigate the intrinsic association between qMRI parameters. Distal‐to‐proximal variations were evaluated by paired t‐tests with Bonferroni‐Holm multiple comparison corrections. P < 0.05 was considered statistically significant.ResultsThe MTR, MTsat, T2*, T1, PD, FA, AD, and fVOL of the sciatic and tibial nerves, and the FF of leg muscles, had an overall good‐to‐excellent test–retest agreement (ICC varying from 0.78 to 0.99). All the qMRI parameters had good‐to‐excellent inter‐rater reliability (ICC > 0.80). The data demonstrated a pattern of distal‐to‐proximal changes of an increased nerve MTsat and FA, and a decreased nerve T1, PD, MD, and RD, as well as a significantly increased muscle FF.Data ConclusionThe proposed multiparametric qMRI method of the peripheral nerves is highly reproducible and provided healthy control data which will be used in developing monitoring biomarkers in patients with polyneuropathies.Level of Evidence1Technical EfficacyStage 2

Response to “Validity of Quantitative, Multi‐Parametric MRI in the Diagnosis of Polyneuropathies”

“…Indeed, the research article does not conclude that qMRI is sensitive to myelin and axonal pathologies. 2 Instead, our main conclusion was that the proposed metrics were repeatable and may be viable monitoring biomarkers. Furthermore, none of the limitations mentioned in the commentary 1 are associated with the research article.…”

“…In this note, we respond to the commentary, 1 which concluded that imaging methods such as quantitative MRI (qMRI) can only be supplementary to the conventional diagnostic methods such as history, clinical exam, nerve conduction studies, electromyography, and nerve biopsies. More specifically, the commentary stated the following related to our recent publication 2 : 1) the "conclusion" that qMRI is sensitive to myelin and axonal pathologies is not supported by the healthy subject data presented by Chen et al 2 ; 2) the diagnosis of polyneuropathies should rely on the conventional electrophysiological methods rather than imaging procedures in polyneuropathies that only have functional abnormalities; 3) qMRI may not be used as a diagnostic biomarker because demyelination and axonal loss are often present simultaneously in polyneuropathies; 4) imaging biomarkers cannot differentiate information from motor, sensory, or autonomic fiber impairment; and 5) imaging methods cannot provide information of the involvement of large fibers, small fibers, or both.…”

“…Furthermore, none of the limitations mentioned in the commentary 1 are associated with the research article. 2 Instead, the long-term goal of this project is to develop monitoring biomarkers for evaluating the progression of polyneuropathies, rather than diagnostic biomarkers. This is based on previous studies that have demonstrated that qMRI readouts such as magnetization transfer ratio, longitudinal relaxation time (T 1 ), transverse relaxation time (T 2 ), and diffusivities, are sensitive to changes of myelin and axonal pathologies in the central 3 and peripheral nervous system.…”

“…5 Toward this end, the present study evaluated the test-rest and inter-rater reliability of the multiparametric qMRI method in healthy volunteers to understand natural sources of variation and the minimal detectable change over time for these future longitudinal studies. 2 The multiparametric qMRI method will be used in longitudinal studies in patients with various types of polyneuropathies to develop monitoring biomarkers.…”

Validity of Quantitative, Multi‐Parametric MRI in the Diagnosis of Polyneuropathies

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We read with interest the article by Chen et al about a study on the reliability of multiparametric, quantitative magnetic resonance imaging (qMRI) of lower limb peripheral nerves in 17 healthy volunteers. 1 It was found that the qMRI parameters magnetization transfer (MT) ratio, MT saturation index (MTsat), T2*, T1, proton density (PD), fractional anisotropy (FA), and mean/axial/radial diffusivities (MD, AD, and RD) had a good-to-excellent test-retest agreement and demonstrated a pattern of distal-to-proximal changes of an increased nerve MTsat and FA, and a decreased nerve T1, PD, MD, and RD, as well as a significantly increased muscle fat fraction. 1 It was concluded that multiparametric qMRI of peripheral nerves is highly reproducible and sensitive to myelin and axonal pathologies.

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