Myelin paucity of the superior cerebellar peduncle in individuals with Friedreich ataxia: an MRI magnetization transfer imaging study

• ¹ Murdoch Childrens Research Institute, Bruce Lefroy Centre, Australia
• ² Monash University, School of Psychological Sciences, Australia
• ³ Monash University, Monash Biomedical Imaging, Australia
• ⁴ Victoria University, School of Engineering and Science, Australia
• ⁵ Austin Health, Department of Clinical Genetics, Australia

Background: Friedreich ataxia (FRDA) is the most common of the hereditary ataxias. The dentate nucleus (DN), the major relay station for neural connection between the cerebellum and cortex via the thalamus, and is a major site of neurodegeneration in individuals with FRDA. We have shown that the size of the superior cerebellar peduncle (SCP), which links the DN to cortical and subcortical structures, is significantly reduced in individuals with FRDA compared to controls. Previous studies have demonstrated that specific cognitive impairment in individuals with FRDA are likely due to impairment in neural connectivity between the cerebellum and cortical structures. This study used magnetization transfer imaging (MTI) to examine the integrity of white matter in the SCP and the corpus callosum (CC) (control region). We hypothesized that individuals with FRDA would have reduced magnetization transfer ratio (MTR) in the SCP compared to control participants but that there would be no difference in the MTR value in the CC between groups. Methods: Ten individuals with FRDA and ten controls participated. T2 weighted magnetic resonance images (MRIs) were acquired with and without saturation, using a magnetization transfer pulse placed before each slice-selective excitation (3T Siemens Skyra, TE = 8.4ms, TR = 734ms). Results: Individuals with FRDA demonstrated a significant reduction in the MTR in the SCP compared to control participants (F(1,18)=53.58, p<0.001). However, there was no significant difference between groups in MTR in the CC. There was a significant reduction in MTR in the SCP compared to CC in participants with FRDA [t(9)=-9.18, p<0.001], but not in controls. Conclusion: We suggest that the reduction in MTR in the SCP may be indicative of lack of myelin secondary to axonal loss and oligodendroglial dysfunction in white matter tracts in individuals with FRDA and this may contribute to the cognitive impairment seen in FRDA.