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@ARTICLE{Arpin:281371,
author = {Arpin, David J and Subramony, S. H. and Vaillancourt, David
E and Ashizawa, Tetsuo and Durr, Alexandra and Mareci,
Thomas and Klockgether, Thomas and Faber, Jennifer and
Paulson, Henry L and Öz, Gülin and Burns, Matthew R},
collaboration = {Consortium, READISCA},
title = {{F}ixel-{B}ased {A}nalysis of {D}iffusion {I}maging as a
{Q}uantitative {M}arker of {D}isease {S}tate in
{S}pinocerebellar {A}taxia.},
journal = {Annals of Clinical and Translational Neurology},
volume = {12},
number = {9},
issn = {2328-9503},
address = {Chichester [u.a.]},
publisher = {Wiley},
reportid = {DZNE-2025-01118},
pages = {1846 - 1857},
year = {2025},
abstract = {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.},
keywords = {early‐stage SCA (Other) / neurodegeneration (Other) /
white matter (Other)},
cin = {Patient Studies (Bonn) / Clinical Research (Bonn)},
ddc = {610},
cid = {I:(DE-2719)1011101 / I:(DE-2719)1011001},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40665587},
doi = {10.1002/acn3.70116},
url = {https://pub.dzne.de/record/281371},
}