Diffusion Tensor Imaging of Dystrophic Skeletal Muscle : Comparison of Two Segmentation Methods Adapted to Chemical-shift-encoded Water-fat MRI.

PURPOSE: To compare the influence of two different regions of interest (ROIs) on diffusion tensor metrics in dystrophic thigh muscles using a custom-made (whole muscle) ROI including and a selective ROI excluding areas of fatty replacement. METHODS: Diffusion tensor imaging (DTI) and chemical-shift-encoded water-fat magnetic resonance imaging (MRI) of the thigh was conducted on a 3-Tesla system in 15 cases with muscular dystrophy and controls. The ROIs were chosen according to patterns of fatty replacement on co-registered axial DTI and gradient echo sequence (GRE) images. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), fiber track length (FTL), and muscle fat fractions (MFF) were compared between both ROI segmentations. These comparisons, muscle-specific correlation coefficients, and the influence of ROI localization on tensor metrics were derived based on linear mixed effects regression models. RESULTS: In the cases a high correlation was observed for ADC and FA with MFF using a custom ROI. The correlation was weaker but still significant with a selective ROI method. Using the custom ROI, FTL correlated significantly with MFF in 3 out of 4 muscles (r ≤ -0.51). A correlation was not found for the selective ROI method. Interaction analysis revealed that the association of ADC and FA with MFF was not significantly influenced by the ROI localization. For FTL the ROI localization significantly reduced the negative association with MFF. CONCLUSION: The DTI metrics and FTL of custom ROI segmentation are significantly influenced by MFF. Contrary to ADC and FA, the effect of MFF on FTL is significantly reduced when applying selective ROI segmentation, which could therefore be a better option for MR tractography.

The mutation p.D313Y is associated with organ manifestation in Fabry disease.

Fabry disease (FD) is a multisystem lysosomal storage disorder caused by mutations in the GLA gene. The clinical significance of the mutation p.D313Y is still under debate. Retrospective chart analysis of clinical (neurological, cardiac, renal, and ophthalmological), genetic, and biochemical (lyso-globotriaosylsphingosine, lyso-Gb3; enzyme activity) data was performed in all our patients carrying the p.D313Y mutation. Fourteen patients from 5 families (10 female, 4 male; age range 10-51) were included. Symptoms and organ manifestations compatible with FD could be identified in 10 patients. Cerebrovascular events occurred in 4 females. Seven patients reported pain or acroparaesthesia. Cornea verticillata was found in 1 patient, mild retinal vascular tortuosity in 5 patients. Lyso-Gb3 was elevated in 2 females with cerebrovascular involvement. Classical cardiac, renal or skin manifestations could not be identified. The mutation p.D313Y in the GLA gene may lead to organ manifestations and elevation of the Fabry-specific biomarker lyso-Gb3. Neurological symptoms (stroke and pain) and ocular manifestations seem to be the leading findings. Annual routine visits are recommended for patients carrying the p.D313Y mutation. Enzyme replacement therapy might be considered in symptomatic patients.