Multiparametric Quantitative <scp>MRI</scp> of Peripheral Nerves to Differentiate Demyelinating From Axonal Polyneuropathies

ABSTRACT Background Differentiating demyelinating from axonal polyneuropathies helps for accurate diagnosis and treatment. However, the current clinical tools lack sensitivity to confirm demyelination in peripheral nerves, particularly for proximal nerves. Hypothesis Multiparametric quantitative MRI (qMRI) of peripheral nerves can differentiate demyelination from axonal loss. Study Type Retrospective. Subjects Twenty patients with Charcot–Marie‐Tooth type‐1 (CMT1, demyelinating, females = 12), 12 patients with CMT2 (axonal, females = 6), 25 patients with hereditary neuropathy with liability to pressure palsies (HNPP, a cohort who often has intermediate changes between the two classifications, females = 17), and 25 healthy controls (HC, females = 14). Field‐Strength/Sequences 3 T; 3D gradient‐echo and spin‐echo echo‐planar‐imaging‐based diffusion tensor imaging. Assessment Multiparametric qMRI maps were computed for magnetization transfer ratio (MTR), MT saturation index (MTsat), T 2 *, T 1 , proton density (PD), fractional anisotropy (FA), mean/axial/radial diffusivities (MD, AD, RD), and fascicular volume (fVol). Statistical Tests Descriptive statistics were performed for group comparisons for each qMRI parameter. Receiver operating characteristic (ROC) analysis with logistic regression was performed to stratify patients. A composite qMRI score, as the CMT Imaging Score (CMTIS), was developed to reflect disease severity using the CMT Neuropathy Score version‐2 (CMTNSv2) as a clinical reference. The statistical significance level was set at p &lt; 0.05. Results CMT1 showed significantly increased fVol versus HCs (3733.7 ± 1426.9 mm 3 vs. 1614.4 ± 286.32 mm 3 ), while CMT2 demonstrated reduced T 2 * (25.24 ± 3.27 ms vs. 29.97 ± 4.28 ms). Both CMT1 and CMT2 exhibited reduced FA (0.32 ± 0.08 and 0.39 ± 0.11 vs. 0.54 ± 0.06), MTsat (2.24% ± 0.35% and 2.66% ± 0.34% vs. 3.07% ± 0.39%), and AD (1925.2 ± 216.6 μm 2 /s and 1972.5 ± 197.4 μm 2 /s vs. 2183.6 ± 178.7 μm 2 /s), along with elevated T 1 (1689.1 ± 196.9 ms and 1435.1 ± 171.7 ms vs. 1305.4 ± 120.7 ms) and RD (1177.2 ± 192.9 μm 2 /s and 1065.9 ± 196.6 μm 2 /s vs. 843.3 ± 101.1 μm 2 /s), with larger abnormalities in CMT1. ROC analyses demonstrated strong discrimination of CMT1 and CMT2 (area under curves [AUCs]: 0.95 and 0.85 for sciatic; 0.89 and 0.73 for tibial nerves). CMTIS correlated strongly with CMTNSv2 ( r = 0.67 sciatic; r = 0.72 tibial; r = 0.79 combined). Data Conclusions Multiparametric qMRI identified distinct imaging signatures of inherited demyelinating (CMT1) versus axonal (CMT2) polyneuropathies. The CMTIS showed strong potential as a monitoring biomarker in patients with inherited polyneuropathy. Evidence Level 3. Stage of Technology Efficacy 3.