Autosomal dominant cerebellar ataxias: Imaging biomarkers with high effect sizes
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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-01-01
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| Series: | NeuroImage: Clinical |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213158218301943 |
| _version_ | 1819120888536104960 |
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| author | Isaac M. Adanyeguh Vincent Perlbarg Pierre-Gilles Henry Daisy Rinaldi Elodie Petit Romain Valabregue Alexis Brice Alexandra Durr Fanny Mochel |
| author_facet | Isaac M. Adanyeguh Vincent Perlbarg Pierre-Gilles Henry Daisy Rinaldi Elodie Petit Romain Valabregue Alexis Brice Alexandra Durr Fanny Mochel |
| author_sort | Isaac M. Adanyeguh |
| collection | DOAJ |
| description | 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: Spinocerebellar ataxia, Imaging biomarkers, Apparent fiber density, Fixel analysis, Diffusion imaging. |
| first_indexed | 2024-12-22T06:27:49Z |
| format | Article |
| id | doaj.art-a98f9f436c4249948524b4f7c0ddd367 |
| institution | Directory Open Access Journal |
| issn | 2213-1582 |
| language | English |
| last_indexed | 2024-12-22T06:27:49Z |
| publishDate | 2018-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage: Clinical |
| spelling | doaj.art-a98f9f436c4249948524b4f7c0ddd3672022-12-21T18:35:47ZengElsevierNeuroImage: Clinical2213-15822018-01-0119858867Autosomal dominant cerebellar ataxias: Imaging biomarkers with high effect sizesIsaac M. Adanyeguh0Vincent Perlbarg1Pierre-Gilles Henry2Daisy Rinaldi3Elodie Petit4Romain Valabregue5Alexis Brice6Alexandra Durr7Fanny Mochel8INSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013 Paris, FranceINSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013 Paris, France; Bioinformatics and Biostatistics Core Facililty, iCONICS, Institut du Ceveau et de la Moelle épinière, ICM, F-75013 Paris, FranceCenter for Magnetic Resonance Research (CMRR), University of Minnesota, Minneapolis, MN, United StatesINSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013 Paris, FranceINSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013 Paris, FranceINSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013 Paris, France; Center for NeuroImaging Research (CENIR), Institut du Cerveau et de la Moelle épinière, 75013 Paris, FranceINSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013 Paris, FranceINSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013 Paris, France; AP-HP, Pitié-Salpêtrière University Hospital, Department of Genetics, Paris, FranceINSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013 Paris, France; AP-HP, Pitié-Salpêtrière University Hospital, Department of Genetics, Paris, France; University Pierre and Marie Curie, Neurometabolic Research Group, Paris, France; Corresponding author at: Reference Center for Neurometabolic Diseases, Department of Genetics, La Pitié-Salpêtrière University Hospital, 47 Boulevard de l'Hôpital, 75013 Paris, France.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: Spinocerebellar ataxia, Imaging biomarkers, Apparent fiber density, Fixel analysis, Diffusion imaging.http://www.sciencedirect.com/science/article/pii/S2213158218301943 |
| spellingShingle | Isaac M. Adanyeguh Vincent Perlbarg Pierre-Gilles Henry Daisy Rinaldi Elodie Petit Romain Valabregue Alexis Brice Alexandra Durr Fanny Mochel Autosomal dominant cerebellar ataxias: Imaging biomarkers with high effect sizes NeuroImage: Clinical |
| title | Autosomal dominant cerebellar ataxias: Imaging biomarkers with high effect sizes |
| title_full | Autosomal dominant cerebellar ataxias: Imaging biomarkers with high effect sizes |
| title_fullStr | Autosomal dominant cerebellar ataxias: Imaging biomarkers with high effect sizes |
| title_full_unstemmed | Autosomal dominant cerebellar ataxias: Imaging biomarkers with high effect sizes |
| title_short | Autosomal dominant cerebellar ataxias: Imaging biomarkers with high effect sizes |
| title_sort | autosomal dominant cerebellar ataxias imaging biomarkers with high effect sizes |
| url | http://www.sciencedirect.com/science/article/pii/S2213158218301943 |
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