Proximal nerve magnetization transfer MRI relates to disability in Charcot-Marie-Tooth diseases

Abstract

Objective: The objectives of this study were (1) to develop a novel magnetization transfer ratio (MTR) MRI assay of the proximal sciatic nerve (SN), which is inaccessible via current tools for assessing peripheral nerves, and (2) to evaluate the resulting MTR values as a potential biomarker of myelin content changes in patients with Charcot-Marie-Tooth (CMT) diseases.Methods: MTR was measured in the SN of patients with CMT type 1A (CMT1A, n 5 10), CMT type 2A (CMT2A, n 5 3), hereditary neuropathy with liability to pressure palsies (n 5 3), and healthy controls (n 5 21). Additional patients without a genetically confirmed subtype (n 5 4), but whose family histories and electrophysiologic tests were consistent with CMT, were also included. The relationship between MTR and clinical neuropathy scores was assessed, and the interscan and inter-rater reliability of MTR was estimated.Results: Mean volumetric MTR values were significantly decreased in the SN of patients with CMT1A (33.8 6 3.3 percent units) and CMT2A (31.5 6 1.9 percent units) relative to controls (37.2 6 2.3 percent units). A significant relationship between MTR and disability scores was also detected (p 5 0.01 for genetically confirmed patients only, p 5 0.04 for all patients). From interscan and inter-rater reliability analyses, proximal nerve MTR values were repeatable at the slicewise and mean volumetric levels. Charcot-Marie-Tooth (CMT) diseases are a group of inherited neuropathies that affect motor and sensory nerves. A majority of CMT phenotypes can be classified as primary demyelination/dysmyelinating (CMT1) or primary axonal (CMT2) neuropathies.1,2 CMT type 1A (CMT1A z 80% of CMT1 cases 3,4 ) arises from duplication of the peripheral myelin protein 22 (PMP22) gene 5,6 and results in dysmyelination and secondary axonal loss. 7 CMT type 2A (CMT2A z 35% of CMT2 cases 8 ) is caused by missense mutations in the gene that encodes for mitofusin 2 9 and leads to primary axonal degeneration. 8 Although the pathologic features of CMT1A/CMT2A are different, length-dependent axonal loss occurs in both and is predictive of outcomes.

A novel missense mutation in AIFM1 results in axonal polyneuropathy and misassembly of OXPHOS complexes

“…The sciatic nerve is labelled with the red oval. The sciatic nerve diameter of the patient (mean ± SEM = 4.3 ± 0.1 mm) was reduced relative to previously published values in controls (mean ± SD = 5.1 ± 0.6) . (b) Corresponding magnetic transfer ratio ( MTR ) map from the same slice.…”

“…(c) Mean MTR values versus age for controls and the patient with CMTX 4. Note that MTR values were not dependent on age in controls (•) (mean ± SD = 37.2 ± 2.3) and MTR values in the patient with CMTX 4 () (mean ± SEM = 33.4 ± 0.3 p.u.) were in the lower range of values observed in controls.…”

Chemical Shift magnetization transfer magnetic resonance imaging

“…First, the CSMT method was tested using oil/agar phantoms, though one animal model study was performed to demonstrate feasibility of the method. However, for in vivo applications, particularly in clinical settings, multiple confounding factors, including B 0 and B 1 inhomogeneity , T 1 effects , eddy current effects , and susceptibility‐induced fat‐resonance shifts , need to be considered. The effect of B 0 inhomogeneity, as one of the potential limitations of the current method, should be included in the model, particularly for potential applications to abdominal imaging of visceral organs.…”

Feasibility of 7T MRI for imaging fascicular structures of peripheral nerves

“…The fluid sensitivity of MRI provides detection of edema in nerves potentially caused by various pathologic mechanisms including inflammation, ischemia, and autoimmune disease . Quantitative mapping of diffusion, T2, and magnetization transfer demonstrated promising results in monitoring nerve degeneration …”

“…14,15 Quantitative mapping of diffusion, T2, and magnetization transfer demonstrated promising results in monitoring nerve degeneration. 9,16,17 MRI evaluation of nerve fascicular structures, however, has not been reliable because of the limited resolution on the widely used 1.5T or 3T MRI scanners. High-resolution ultrasound imaging showed that evaluation of nerve fascicles could improve preoperative planning 18 or identification of nerve pathology.…”