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Updated: Sep 15, 2025
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Fixel-Based Analysis of Diffusion Imaging as a Quantitative Marker of Disease State in Spinocerebellar Ataxia
David J Arpin1, S H Subramony2,3,
1Department of Applied Physiology & Kinesiology, University of Florida, Gainesville, Florida, USA.
Objective:
Spinocerebellar ataxias (SCAs) are a group of genetically heterogeneous neurodegenerative diseases causing progressive deterioration and reduced quality of life. Therapeutic advances have been limited by a lack of sensitive anatomic, functional, or diffusion imaging-based biomarkers. This study aimed to identify white matter differences in the brains of preataxic and early-stage SCA1 and SCA3 mutation carriers using diffusion magnetic resonance imaging data from a multisite trial setting.
Methods:
Fixel-based analysis was used to estimate microscopic fiber density, macroscopic fiber-bundle cross-section, and a combined fiber density and fiber-bundle cross-section measure within 45 cerebral and cerebellar tracts. Multivariate ANOVAs compared controls (n = 16), pre-ataxic (n = 10 SCA1, n = 24 SCA3), and ataxic patients (n = 14 SCA1, n = 36 SCA3). Clinical variables were correlated with fixel metrics and receiver operating characteristic analyses identified white matter tracts sensitive to distinguishing controls from pre-ataxic SCA1 and SCA3.
Results:
We found widespread white matter deficits in pre-ataxic and ataxic patients compared to controls with regard to fiber density, fiber-bundle cross-section, and combined measures, all of which were associated with clinical measures of ataxia severity. We also found the combined fiber density and fiber-bundle cross-section measure from cerebellar tracts distinguished controls from pre-ataxia with high sensitivity and specificity for both SCA1 (receiver operating characteristic area under the curve = 0.96) and SCA3 (area under the curve = 0.97). The receiver operating characteristic analyses revealed that cerebellar tracts resulted in greater area under the curve than cortico-spinal and transcallosal tracts.
Interpretation:
These results demonstrate that fixel metrics offer sensitive disease-specific measures of early SCA disease state that correlate with standard clinical measures.
Trial Registration:
Clinical Trial Readiness for SCA1 and SCA3 (READISCA), NCT03487367. https://clinicaltrials.gov/ct2/show/NCT03487367.
