Multiparametric Quantitative MRI of Peripheral Nerves to Differentiate Demyelinating From Axonal Polyneuropathies

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), T₂*, T₁, 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 < 0.05. Results: CMT1 showed significantly increased fVol versus HCs (3733.7 ± 1426.9 mm³ vs. 1614.4 ± 286.32 mm³), while CMT2 demonstrated reduced T₂* (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 μm²/s and 1972.5 ± 197.4 μm²/s vs. 2183.6 ± 178.7 μm²/s), along with elevated T₁ (1689.1 ± 196.9 ms and 1435.1 ± 171.7 ms vs. 1305.4 ± 120.7 ms) and RD (1177.2 ± 192.9 μm²/s and 1065.9 ± 196.6 μm²/s vs. 843.3 ± 101.1 μm²/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.