Findings observed in magnetic resonance imaging (MRI) could yield valuable insight for neurologic disorders, such as Friedreich ataxia (FA), according to a study recently published in Brain Communications.

“We show that fixel-based analysis of diffusion MRI data is particularly sensitive to longitudinal change in the cerebellar peduncles, as well as motor and sensory white matter tracts. In combination with other morphometric measures, they may therefore provide sensitive imaging biomarkers of disease progression for clinical trials,” the authors wrote.

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This study included 28 participants previously diagnosed with an early stage of FA, as well as 20 healthy controls. The researchers analyzed cross-sectional differences between MRI findings in patients with FA and controls and then investigated longitudinal changes in the patient group. The results provided a comprehensive picture of the nervous system in early-stage FA.

The authors focused on determining macrostructural and microstructural alterations in early-stage FA using fixel-based analysis (FBA). This method provides more detailed information on fiber density and cross-section, potentially more sensitive than traditional diffusion tensor imaging (DTI) measures.

Cross sectional brain morphometry revealed significant atrophy in the brainstem, cerebellar white matter, and deep gray matter structures, like the thalamus, in individuals with FA compared to controls. These structures are part of the ascending cerebello-thalamo-cortical pathway, suggesting the involvement of these regions in the disease.

Using FBA, widespread microstructural alterations were evident in several cerebral and cerebellar regions. Also, lower fiber density (intraaxonal volume fraction) and fiber bundle cross-section in multiple white matter tracts were present in individuals with FA. Notably, many of these affected tracts are also part of the ascending cerebello-thalamo-cortical pathway.

Longitudinal analysis revealed significant volume changes in the cerebellum, brain, brainstem, and fourth ventricle over time in patients with FA. Diffusion metrics, particularly in the superior cerebellar peduncles, posterior limb of the internal capsule, and superior corona radiata, showed significant longitudinal changes and strong correlations with clinical scores, indicating their potential as sensitive biomarkers of disease progression.

These findings offer valuable insights into the early-stage brain alterations in FS and highlight the potential of advanced neuroimaging techniques for clinical trials. The identified sensitive biomarkers may aid in monitoring disease progression and evaluating treatment efficacy in future trials.


Adanyeguh I, Joers J, Deelchand D, et al. Brain MRI detects early-stage alterations and disease progression in Friedreich ataxia. Brain Commun. Published online July 6, 2023. doi:10.1093/braincomms/fcad196