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

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.

Multiparametric quantitative MRI (qMRI) of peripheral nerves can differentiate demyelination from axonal loss.

Retrospective.

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).

3 T; 3D gradient-echo and spin-echo echo-planar-imaging-based diffusion tensor imaging.

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).

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.

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).

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.

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