Abstract
Numerous neuroimaging studies in amyotrophic lateral sclerosis (ALS) have reported links between structural changes and clinical data; however phenotypic and disease course heterogeneity have occluded robust associations. The present study used the novel D50 model, which distinguishes between disease accumulation and aggressiveness, to probe correlations with measures of diffusion tensor imaging (DTI). DTI scans of 145 ALS patients and 69 controls were analyzed using tract-based-spatial-statistics of fractional anisotropy (FA), mean- (MD), radial (RD), and axial diffusivity (AD) maps. Intergroup contrasts were calculated between patients and controls, and between ALS subgroups: based on (a) the individual disease covered (Phase I vs. II) or b) patients' disease aggressiveness (D50 value). Regression analyses were used to probe correlations with model-derived parameters. Case–control comparisons revealed widespread ALS-related white matter pathology with decreased FA and increased MD/RD. These affected pathways showed also correlations with the accumulated disease for increased MD/RD, driven by the subgroup of Phase I patients. No significant differences were noted between patients in Phase I and II for any of the contrasts. Patients with high disease aggressiveness (D50 < 30 months) displayed increased AD/MD in bifrontal and biparietal pathways, which was corroborated by significant voxel-wise regressions with D50. Application of the D50 model revealed associations between DTI measures and ALS pathology in Phase I, representing individual disease accumulation early in disease. Patients' overall disease aggressiveness correlated robustly with the extent of DTI changes. We recommend the D50 model for studies developing/validating neuroimaging or other biomarkers for ALS.
| Original language | English |
|---|---|
| Journal | Human Brain Mapping |
| Volume | 42 |
| Issue number | 3 |
| Pages (from-to) | 737-752 |
| Number of pages | 16 |
| ISSN | 1065-9471 |
| DOIs | |
| Publication status | Published - 15.02.2021 |
Funding
The authors are grateful to the community of ALS patients and their caregivers, without whom this work would not be possible. The authors extend their thanks to Mandy Arnold, Ann‐Kathrin Klose, and Cindy Hoepfner for continuous assessment and patient care. The authors further extend their thanks to Christian Baldauf, Isabel Baer, Hannes Bulski, Marie Dreger, Jana Droege, Theresa Ebersbach, Philipp Garrison, Annalena Goebel, Martha Hantsch, Linda Kloß, Tamar Kvartskhava, Carmen Lewa, Carolin Nikolaus, and Anna Schneider for patient assessments. The present study was supported by the German Bundesministerium für Bildung und Forschung (BMBF) grant SOPHIA (01ED1202B) and ONWebDUALS (01ED15511A) to J. G. under the aegis of the EU Joint Program Neurodegenerative Disease Research (JPND) and a BMBF grant PYRAMID (01GM1304) to J. G. in the framework of the ERANET E‐RARE program. T. P. was also supported by a Bun desministerium für Bildung und Forschung grant (01GY1804). Support was also received from the Motor Neurone Disease Association (MNDA) and Deutsche Gesellschaft fuer Muskelkranke (DGM). R. S. and A. R. are supported by the Deutsche Forschungsgemeinschaft (DFG) with a clinician scientist program (WI 830/12‐1). N. G. is supported by a doctoral scholarship (Landesgraduiertenstipendien) from the Graduate Academy of Friedrich Schiller University, Jena, Germany and the state of Thuringia. Open access funding enabled and organized by Projekt DEAL. The authors are grateful to the community of ALS patients and their caregivers, without whom this work would not be possible. The authors extend their thanks to Mandy Arnold, Ann-Kathrin Klose, and Cindy Hoepfner for continuous assessment and patient care. The authors further extend their thanks to Christian Baldauf, Isabel Baer, Hannes Bulski, Marie Dreger, Jana Droege, Theresa Ebersbach, Philipp Garrison, Annalena Goebel, Martha Hantsch, Linda Klo?, Tamar Kvartskhava, Carmen Lewa, Carolin Nikolaus, and Anna Schneider for patient assessments. The present study was supported by the German Bundesministerium f?r Bildung und Forschung (BMBF) grant SOPHIA (01ED1202B) and ONWebDUALS (01ED15511A) to J. G. under the aegis of the EU Joint Program Neurodegenerative Disease Research (JPND) and a BMBF grant PYRAMID (01GM1304) to J. G. in the framework of the ERANET E-RARE program. T. P. was also supported by a Bun desministerium f?r Bildung und Forschung grant (01GY1804). Support was also received from the Motor Neurone Disease Association (MNDA) and Deutsche Gesellschaft fuer Muskelkranke (DGM). R. S. and A. R. are supported by the Deutsche Forschungsgemeinschaft (DFG) with a clinician scientist program (WI 830/12-1). N. G. is supported by a doctoral scholarship (Landesgraduiertenstipendien) from the Graduate Academy of Friedrich Schiller University, Jena, Germany and the state of Thuringia. Open access funding enabled and organized by Projekt DEAL.
Research Areas and Centers
- Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)
- Centers: Center for Neuromuscular Diseases
