Autosomal dominant cerebellar ataxias: Imaging biomarkers with high effect sizes

Isaac M. Adanyeguh, Vincent Perlbarg, Pierre Gilles Henry, Daisy Rinaldi, Elodie Petit, Romain Valabregue, Alexis Brice, Alexandra Durr, Fanny Mochel

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Objective: As gene-based therapies may soon arise for patients with spinocerebellar ataxia (SCA), there is a critical need to identify biomarkers of disease progression with effect sizes greater than clinical scores, enabling trials with smaller sample sizes. Methods: We enrolled a unique cohort of patients with SCA1 (n = 15), SCA2 (n = 12), SCA3 (n = 20) and SCA7 (n = 10) and 24 healthy controls of similar age, sex and body mass index. We collected longitudinal clinical and imaging data at baseline and follow-up (mean interval of 24 months). We performed both manual and automated volumetric analyses. Diffusion tensor imaging (DTI) and a novel tractography method, called fixel-based analysis (FBA), were assessed at follow-up. Effect sizes were calculated for clinical scores and imaging parameters. Results: Clinical scores worsened as atrophy increased over time (p < 0.05). However, atrophy of cerebellum and pons showed very large effect sizes (>1.2) compared to clinical scores (<0.8). FBA, applied for the first time to SCA, was sensitive to microstructural cross-sectional differences that were not captured by conventional DTI metrics, especially in the less studied SCA7 group. FBA also showed larger effect sizes than DTI metrics. Conclusion: This study showed that volumetry outperformed clinical scores to measure disease progression in SCA1, SCA2, SCA3 and SCA7. Therefore, we advocate the use of volumetric biomarkers in therapeutic trials of autosomal dominant ataxias. In addition, FBA showed larger effect size than DTI to detect cross-sectional microstructural alterations in patients relative to controls.

Original languageEnglish (US)
Pages (from-to)858-867
Number of pages10
JournalNeuroImage: Clinical
Volume19
DOIs
StatePublished - Jan 1 2018

Fingerprint

Spinocerebellar Ataxias
Cerebellar Ataxia
Diffusion Tensor Imaging
Biomarkers
Disease Progression
Ataxia
Genetic Therapy
Sample Size
Atrophy
Body Mass Index

Keywords

  • Apparent fiber density
  • Diffusion imaging.
  • Fixel analysis
  • Imaging biomarkers
  • Spinocerebellar ataxia

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Adanyeguh, I. M., Perlbarg, V., Henry, P. G., Rinaldi, D., Petit, E., Valabregue, R., ... Mochel, F. (2018). Autosomal dominant cerebellar ataxias: Imaging biomarkers with high effect sizes. NeuroImage: Clinical, 19, 858-867. https://doi.org/10.1016/j.nicl.2018.06.011

Autosomal dominant cerebellar ataxias : Imaging biomarkers with high effect sizes. / Adanyeguh, Isaac M.; Perlbarg, Vincent; Henry, Pierre Gilles; Rinaldi, Daisy; Petit, Elodie; Valabregue, Romain; Brice, Alexis; Durr, Alexandra; Mochel, Fanny.

In: NeuroImage: Clinical, Vol. 19, 01.01.2018, p. 858-867.

Research output: Contribution to journalArticle

Adanyeguh, IM, Perlbarg, V, Henry, PG, Rinaldi, D, Petit, E, Valabregue, R, Brice, A, Durr, A & Mochel, F 2018, 'Autosomal dominant cerebellar ataxias: Imaging biomarkers with high effect sizes', NeuroImage: Clinical, vol. 19, pp. 858-867. https://doi.org/10.1016/j.nicl.2018.06.011
Adanyeguh, Isaac M. ; Perlbarg, Vincent ; Henry, Pierre Gilles ; Rinaldi, Daisy ; Petit, Elodie ; Valabregue, Romain ; Brice, Alexis ; Durr, Alexandra ; Mochel, Fanny. / Autosomal dominant cerebellar ataxias : Imaging biomarkers with high effect sizes. In: NeuroImage: Clinical. 2018 ; Vol. 19. pp. 858-867.
@article{42a081f9145a493c86aa50d6ccde99c5,
title = "Autosomal dominant cerebellar ataxias: Imaging biomarkers with high effect sizes",
abstract = "Objective: As gene-based therapies may soon arise for patients with spinocerebellar ataxia (SCA), there is a critical need to identify biomarkers of disease progression with effect sizes greater than clinical scores, enabling trials with smaller sample sizes. Methods: We enrolled a unique cohort of patients with SCA1 (n = 15), SCA2 (n = 12), SCA3 (n = 20) and SCA7 (n = 10) and 24 healthy controls of similar age, sex and body mass index. We collected longitudinal clinical and imaging data at baseline and follow-up (mean interval of 24 months). We performed both manual and automated volumetric analyses. Diffusion tensor imaging (DTI) and a novel tractography method, called fixel-based analysis (FBA), were assessed at follow-up. Effect sizes were calculated for clinical scores and imaging parameters. Results: Clinical scores worsened as atrophy increased over time (p < 0.05). However, atrophy of cerebellum and pons showed very large effect sizes (>1.2) compared to clinical scores (<0.8). FBA, applied for the first time to SCA, was sensitive to microstructural cross-sectional differences that were not captured by conventional DTI metrics, especially in the less studied SCA7 group. FBA also showed larger effect sizes than DTI metrics. Conclusion: This study showed that volumetry outperformed clinical scores to measure disease progression in SCA1, SCA2, SCA3 and SCA7. Therefore, we advocate the use of volumetric biomarkers in therapeutic trials of autosomal dominant ataxias. In addition, FBA showed larger effect size than DTI to detect cross-sectional microstructural alterations in patients relative to controls.",
keywords = "Apparent fiber density, Diffusion imaging., Fixel analysis, Imaging biomarkers, Spinocerebellar ataxia",
author = "Adanyeguh, {Isaac M.} and Vincent Perlbarg and Henry, {Pierre Gilles} and Daisy Rinaldi and Elodie Petit and Romain Valabregue and Alexis Brice and Alexandra Durr and Fanny Mochel",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.nicl.2018.06.011",
language = "English (US)",
volume = "19",
pages = "858--867",
journal = "NeuroImage: Clinical",
issn = "2213-1582",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Autosomal dominant cerebellar ataxias

T2 - Imaging biomarkers with high effect sizes

AU - Adanyeguh, Isaac M.

AU - Perlbarg, Vincent

AU - Henry, Pierre Gilles

AU - Rinaldi, Daisy

AU - Petit, Elodie

AU - Valabregue, Romain

AU - Brice, Alexis

AU - Durr, Alexandra

AU - Mochel, Fanny

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Objective: As gene-based therapies may soon arise for patients with spinocerebellar ataxia (SCA), there is a critical need to identify biomarkers of disease progression with effect sizes greater than clinical scores, enabling trials with smaller sample sizes. Methods: We enrolled a unique cohort of patients with SCA1 (n = 15), SCA2 (n = 12), SCA3 (n = 20) and SCA7 (n = 10) and 24 healthy controls of similar age, sex and body mass index. We collected longitudinal clinical and imaging data at baseline and follow-up (mean interval of 24 months). We performed both manual and automated volumetric analyses. Diffusion tensor imaging (DTI) and a novel tractography method, called fixel-based analysis (FBA), were assessed at follow-up. Effect sizes were calculated for clinical scores and imaging parameters. Results: Clinical scores worsened as atrophy increased over time (p < 0.05). However, atrophy of cerebellum and pons showed very large effect sizes (>1.2) compared to clinical scores (<0.8). FBA, applied for the first time to SCA, was sensitive to microstructural cross-sectional differences that were not captured by conventional DTI metrics, especially in the less studied SCA7 group. FBA also showed larger effect sizes than DTI metrics. Conclusion: This study showed that volumetry outperformed clinical scores to measure disease progression in SCA1, SCA2, SCA3 and SCA7. Therefore, we advocate the use of volumetric biomarkers in therapeutic trials of autosomal dominant ataxias. In addition, FBA showed larger effect size than DTI to detect cross-sectional microstructural alterations in patients relative to controls.

AB - Objective: As gene-based therapies may soon arise for patients with spinocerebellar ataxia (SCA), there is a critical need to identify biomarkers of disease progression with effect sizes greater than clinical scores, enabling trials with smaller sample sizes. Methods: We enrolled a unique cohort of patients with SCA1 (n = 15), SCA2 (n = 12), SCA3 (n = 20) and SCA7 (n = 10) and 24 healthy controls of similar age, sex and body mass index. We collected longitudinal clinical and imaging data at baseline and follow-up (mean interval of 24 months). We performed both manual and automated volumetric analyses. Diffusion tensor imaging (DTI) and a novel tractography method, called fixel-based analysis (FBA), were assessed at follow-up. Effect sizes were calculated for clinical scores and imaging parameters. Results: Clinical scores worsened as atrophy increased over time (p < 0.05). However, atrophy of cerebellum and pons showed very large effect sizes (>1.2) compared to clinical scores (<0.8). FBA, applied for the first time to SCA, was sensitive to microstructural cross-sectional differences that were not captured by conventional DTI metrics, especially in the less studied SCA7 group. FBA also showed larger effect sizes than DTI metrics. Conclusion: This study showed that volumetry outperformed clinical scores to measure disease progression in SCA1, SCA2, SCA3 and SCA7. Therefore, we advocate the use of volumetric biomarkers in therapeutic trials of autosomal dominant ataxias. In addition, FBA showed larger effect size than DTI to detect cross-sectional microstructural alterations in patients relative to controls.

KW - Apparent fiber density

KW - Diffusion imaging.

KW - Fixel analysis

KW - Imaging biomarkers

KW - Spinocerebellar ataxia

UR - http://www.scopus.com/inward/record.url?scp=85048390079&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048390079&partnerID=8YFLogxK

U2 - 10.1016/j.nicl.2018.06.011

DO - 10.1016/j.nicl.2018.06.011

M3 - Article

C2 - 29922574

AN - SCOPUS:85048390079

VL - 19

SP - 858

EP - 867

JO - NeuroImage: Clinical

JF - NeuroImage: Clinical

SN - 2213-1582

ER -