Journal Article

DZNE-2025-01118

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Fixel-Based Analysis of Diffusion Imaging as a Quantitative Marker of Disease State in Spinocerebellar Ataxia.

Arpin, D. J. ; Subramony, S. H. ; Consortium, R. (Collaboration Author) ; Vaillancourt, D. E. ; Ashizawa, T. ; Durr, A. ; Mareci, T. ; Klockgether, T.DZNE* ; Faber, J.DZNE* ; Paulson, H. L. ; Öz, G. ; Burns, M. R.

2025
Wiley Chichester [u.a.]

This record in other databases:  

Please use a persistent id in citations: doi:10.1002/acn3.70116

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.

Keyword(s): early‐stage SCA ; neurodegeneration ; white matter

---

Contributing Institute(s):

1. Patient Studies (Bonn) (Patient Studies (Bonn))
2. Clinical Research Coordination (Clinical Research (Bonn))

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2025

---

Database coverage:
; ; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; DEAL Wiley ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---