Voxelwise Analysis of Diffusion Tensor Imaging and Structural MR Imaging in Patients with the m.3243A > G Mutation in Mitochondrial DNA

BACKGROUND AND PURPOSE: The m.3243A>G mutation is the most common pathogenic mutation in mtDNA; tissues with high dependence on aerobic energy metabolism, such as the brain, heart, and skeletal muscle, are most affected by the ensuing mitochondria! dysfunction. We hypothesized that the m.3243A>G mutation manifests as disturbances in white matter microstructural integrity and volumetric changes in the brain.

MATERIALS AND METHODS: DTI and structural MR imaging were performed on 15 adult patients with the m.3243A>G mutation and 14 healthy age-matched controls. Voxelwise analysis of the DTI data was performed to reveal possible differences in FA and MD values. Additionally, normalized brain tissue volumes of the subjects were measured, and voxelwise analysis of gray matter was performed to assess volumetric changes in the brain.

RESULTS: Among patients with m.3243A>G mutation, voxelwise analysis of the DTI data revealed significantly reduced FA in several areas located mainly in the occipital lobes, thalami, external and internal capsules, brain stem, cerebellar peduncles, and cerebellar white matter. There were no differences in MD values between the patients and the controls. Analysis of the structural MR imaging data revealed reduced total volume of gray and white matter in patients with m.3243A>G mutation, and VBM analysis identified areas of significant gray matter loss mainly in the occipital lobes and cerebellum.

CONCLUSIONS: Our findings show that patients with m.3243A>G mutation have mild microstructural damage leading to loss of directional organization of white matter and reduced brain volumes.