Validation of MRC Centre MRI calf muscle fat fraction protocol as an outcome measure in CMT1A.

OBJECTIVE

To translate the quantitative MRC Centre MRI protocol in Charcot-Marie-Tooth disease type 1A (CMT1A) to a second site; validate its responsiveness in an independent cohort; and test the benefit of participant stratification to increase outcome measure responsiveness.

METHODS

Three healthy volunteers were scanned for intersite standardization. For the longitudinal patient study, 11 patients with CMT1A were recruited with 10 patients rescanned at a 12-month interval. Three-point Dixon MRI of leg muscles was performed to generate fat fraction (FF) maps, transferred to a central site for quality control and analysis. Clinical data collected included CMT Neuropathy Score.

RESULTS

Test-retest reliability of FF within individual healthy calf muscles at the remote site was excellent: intraclass correlation coefficient 0.79, limits of agreement -0.67 to +0.85 %FF. In patients, mean calf muscle FF was 21.0% and correlated strongly with disease severity and age. Calf muscle FF significantly increased over 12 months (+1.8 ± 1.7 %FF, = 0.009). Patients with baseline FF >10% showed a 12-month FF increase of 2.9% ± 1.3% (standardized response mean = 2.19).

CONCLUSIONS

We have validated calf muscle FF as an outcome measure in an independent cohort of patients with CMT1A. Responsiveness is significantly improved by enrolling a stratified patient cohort with baseline calf FF >10%.