LAUSR

The article in this issue of JMRI by Cheah et al relates diffusion tensor and fat-water imaging of normal controls and patients with Charcot–Marie–Tooth (CMT) disease. CMT disease is a common, inherited neuromuscular disease with a prevalence of ~1 in 2,500 people. It is caused by mutations in the ~30 genes associated with myelin formation in peripheral nerves. Because of the large number of possible mutations, CMT can manifest in a panoply of forms. Decoding the precise CMT type is done with a combination of clinical observation, inheritance patterns, measuring nerve conduction velocity, and, ultimately, genetic testing. The most common form, CMT1, represents ~50% of the CMT cases. The most common mutation is a duplication of a 1.4 Mb section at 17p11.2, resulting in overexpression of a myelin protein, which leads to demyelination of peripheral nerves. The clinical phenotype of the disease is distal weakness, sensory loss, atrophying muscles, particularly in the lower legs, and later in the hands, joint deformities, and, frequently, aberrant nerve conduction. There is no accepted therapy for CMT but as our understanding of the molecular basis of the disease expands, targets for intervention will be identified and drugs developed. Because the disease is slowly progressing, noninvasive methods such as magnetic resonance imaging (MRI), which can reliably evaluate the effect of potential treatments, will become valuable to provide sensitive and objective quantification of changes indicative of the success or failure of a therapy. Efforts to characterize the relationship between MR methods and more accepted clinical measures will help establish MRI as a preferred method to evaluate therapeutic approaches. An additional value of MRI is that it can be applied both to animal models and patient populations. Investigators have demonstrated the reliability and reproducibility of diffusion tensor imaging (DTI) measurements of peripheral nerves in healthy controls. As well, they have demonstrated differences in diffusion tensor parameters between healthy patients and those with neuropathy. These investigators used DTI to assess the radial and axial diffusivity in the sciatic nerve of 18 patients, nine diagnosed with CMT and nine ageand gender-matched healthy controls. Imaging was performed on the hip and lower leg of the dominant lower limb to image the peroneal and sciatic nerves as well as muscle atrophy. Atrophy and fatty infiltration of the tibialis anterior muscle was assessed on a review of inand out-of-phase gradient echo imaging, which were rated subjectively using the Goutallier classification. The investigators demonstrated a significant reduction in fractional anisotropy (FA) and a significant increase in radial diffusivity (RD) in both the sciatic (P = 0.008) and peroneal (P = 0.008) nerves in the CMT group compared with healthy controls. Additionally, they showed a significantly higher muscle atrophy grade in the CMT group and a significant, negative correlation between muscle atrophy and FA values of sciatic (P < 0.001) and peroneal (P = 0.001) nerves. As noted by Jones et al, DTI measures a change in the MR signal amplitude as a result of changes in phase dispersion when we orient magnetic field gradients in specific directions. We interpret this as indicating changes in diffusivity relative to the nerve’s structure. We wish to interpret the MRI data in terms of changes in the microstructure of the nerve, but it is important to remember that our actual measurements are at least one step removed from direct observation. Consequently, it is valuable to have more studies that provide a consistent demonstration of how DTI correlates with expected or known changes in the anatomy of the nerve. In this work, the observed changes in FA and RD are consistent with the known deterioration of these peripheral nerves with CMT disease, and thus clarify the interpretation of the DTI results. The study has several limitations, notably the small number of patients and controls and the heterogeneity of the CMT type of the patients. As well, though the sciatic and peroneal nerves are relatively large, the challenge of outlining the nerve and segmenting it from the surrounding tissue is nontrivial. Nevertheless, the study is a valuable contribution to the growing literature about the anatomical correlation of DTI.