Tract-Specific Spinal Cord Diffusion Tensor Imaging in Friedreich's Ataxia

Spinal cord (SC) damage is a hallmark in Friedreich's ataxia (FRDA). Neuroimaging has been able to capture some SC macroscopic changes, but no study has evaluated microstructural SC white matter (WM) damage in vivo. This group designed a cross-sectional study to evaluate microstructural integrity in SC WM tracts of FRDA patients using diffusion tensor imaging (DTI) with an automated analysis pipeline. Thirty patients and 30 matched healthy controls underwent 3 Tesla (T) magnetic resonance imaging (MRI). Cervical SC T2 and diffusion-weighted imaging (DWI) acquisitions were obtained. Images were processed using the Spinal Cord Toolbox v.4.3.0. For levels C2-C5, cross-sectional area (CSA) and WM DTI parameters (axial diffusivity [AD], fractional anisotropy [FA], radial diffusivity [RD], and mean diffusivity [MD]) were measured. Age, duration, and FARS scores were also obtained. Mean age and disease duration of patients were 31 ± 10 and 11 ± 9 years, respectively. There was CSA reduction in FRDA amongst all levels. Between-group differences in FA, MD, and RD in total white matter (TWM), dorsal columns (DC), fasciculus gracilis (FG), fasciculus cuneatus (FC), and corticospinal tracts (CST) were present in all levels. FA and RD from TWM, DC, FC, and CST correlated with FARS scores, and in CST they also correlated with disease duration. DTI uncovered abnormalities in SC WM tracts, which correlated with clinical features in FRDA. CSA and CST FA in C2 correlated best with disease severity, whereas DC FA showed the largest effect size to differentiate patients and healthy controls. SC WM microstructure is a potential neuroimaging biomarker to be explored in the disease.

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