TY  - JOUR
AU  - Arpin, David J
AU  - Subramony, S. H.
AU  - Vaillancourt, David E
AU  - Ashizawa, Tetsuo
AU  - Durr, Alexandra
AU  - Mareci, Thomas
AU  - Klockgether, Thomas
AU  - Faber, Jennifer
AU  - Paulson, Henry L
AU  - Öz, Gülin
AU  - Burns, Matthew R
TI  - Fixel-Based Analysis of Diffusion Imaging as a Quantitative Marker of Disease State in Spinocerebellar Ataxia.
JO  - Annals of Clinical and Translational Neurology
VL  - 12
IS  - 9
SN  - 2328-9503
CY  - Chichester [u.a.]
PB  - Wiley
M1  - DZNE-2025-01118
SP  - 1846 - 1857
PY  - 2025
AB  - 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.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.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.These results demonstrate that fixel metrics offer sensitive disease-specific measures of early SCA disease state that correlate with standard clinical measures.Clinical Trial Readiness for SCA1 and SCA3 (READISCA), NCT03487367. https://clinicaltrials.gov/ct2/show/NCT03487367.
KW  - early‐stage SCA (Other)
KW  - neurodegeneration (Other)
KW  - white matter (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40665587
DO  - DOI:10.1002/acn3.70116
UR  - https://pub.dzne.de/record/281371
ER  -