Multiparametric Quantitative MRI of Peripheral Nerves to Differentiate Demyelinating from Axonal Polyneuropathies
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Background
Differentiating demyelinating from axonal polyneuropathies is essential for accurate diagnosis and treatment. We hypothesized that multiparametric quantitative MRI (qMRI) of peripheral nerves can differentiate demyelination from axonal loss. This retrospective study leveraged genetically defined demyelinating and axonal polyneuropathies to test this concept.
Methods
Multiparametric qMRI data of proximal (sciatic) and distal (tibial) nerves were acquired on 3T MRI, including magnetization transfer ratio (MTR), MT saturation index (MTsat), T *, T, proton density (PD), fractional anisotropy (FA), mean/axial/radial diffusivities (MD, AD, RD), and fascicular volume (fVol). Data were analyzed from patients with Charcot-Marie-Tooth type 1 (CMT1, de-/dys-myelinating, n=19), CMT2 (axonal, n=12), hereditary neuropathy with liability to pressure palsies (HNPP, a cohort who often has intermediate changes between the two classifications, n=25), and health controls (HC, n=25). A composite qMRI score, as CMT Imaging Score (CMTIS), was developed to predict disease severity using the CMT Neuropathy Score version-2 (CMTNSv2) as a clinical reference. Receiver operating characteristic (ROC) analyses assessed diagnostic performance.
Results
CMT1 showed significantly increased fVol versus HCs, while CMT2 demonstrated reduced T 2 *. Both CMT1 and CMT2 exhibited reduced FA, MTsat, and AD, along with elevated T 1 and RD, with larger abnormalities in CMT1. ROC analyses demonstrated strong discrimination of CMT1 and CMT2 (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).
Conclusions
Multiparametric qMRI identifies distinct imaging signatures of demyelinating versus axonal hereditary polyneuropathies. The CMTIS shows strong potential as a biomarker for disease monitoring.
DATA AVAILABILITY
Anonymized data used in this study is available from the corresponding author upon request and subject to institutional approvals.
KEY MESSAGES
What is already known on this topic
Current electrophysiological tools are limited in their ability to differentiate demyelinating from axonal polyneuropathies when pathology occurs in proximal nerves. Quantitative MRI (qMRI) can assess proximal demyelination and axonal loss; however, individual qMRI metrics lack sufficient sensitivity for reliable differentiation.
What this study adds
This proof-of-concept study demonstrates the feasibility of using multiparametric qMRI for patient stratification and for distinguishing demyelinating from axonal inherited polyneuropathies. The proposed composite qMRI score shows a strong correlation with clinical disease severity.
How this study might affect research, practice, or policy
This study suggests that multiparametric qMRI of peripheral nerves can serve as a non-invasive adjunct to distal nerve conduction studies for improving diagnosis and treatment management of polyneuropathies. The composite qMRI score also shows potential as a monitoring biomarker for tracking disease progression.
