Structural and diffusion imaging versus clinical assessment to monitor amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that affects upper and lower motor neurons. Observational and intervention studies can be tracked using clinical measures such as the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) but for a complete understanding of disease progression, objective in vivo biomarkers of both central and peripheral motor pathway pathology are highly desirable. The aim of this study was to determine the utility of structural and diffusion imaging as central nervous system biomarkers compared to the standard clinical measure, ALSFRS-R, to track longitudinal evolution using three time-point measurements. N = 34 patients with ALS were scanned and clinically assessed three times at a mean of three month time intervals. The MRI biomarkers were structural T1-weighted volumes for cortical thickness measurement as well as deep grey matter volumetry, voxel-based morphometry and diffusion tensor imaging (DTI). Cortical thickness focused specifically on the precentral gyrus while quantitative DTI biomarkers focused on the corticospinal tracts. The evolution of imaging biomarkers and ALSFRS-R scores over time were analysed using a mixed effects model that accounted for the scanning interval as a fixed effect variable, and, the initial measurements and time from onset as random variables. The mixed effects model showed a significant decrease in the ALSFRS-R score, (p < 0.0001, and an annual rate of change (AROC) of - 7.3 points). Similarly, fractional anisotropy of the corticospinal tract showed a significant decrease (p = 0.009, AROC = - 0.0066) that, in turn, was driven by a significant increase in radial diffusivity combined with a trend to decrease in axial diffusivity. No significant change in cortical thickness of the precentral gyrus was found (p > 0.5). In addition, deep grey matter volumetry and voxel-based morphometry also identified no significant changes. Furthermore, the availability of three time points was able to indicate that there was a linear progression in both clinical and fractional anisotropy measures adding to the validity of these results. The results indicate that DTI is clearly a superior imaging marker compared to atrophy for tracking the evolution of the disease and can act as a central nervous biomarker in longitudinal studies. It remains, however, less sensitive than the ALSFRS-R score for monitoring decline over time.
German Center for Neurodegenerative Diseases (DZNE), Leipziger Strasse 44, 39120 Magdeburg, Germany. Electronic address: Arturo.Cardenas@dzne.de.
Arturo
A
Cardenas-Blanco
German Center for Neurodegenerative Diseases (DZNE), Leipziger Strasse 44, 39120 Magdeburg, Germany. Electronic address: Judith.Machts@dzne.de.
Judith
J
Machts
German Center for Neurodegenerative Diseases (DZNE), Leipziger Strasse 44, 39120 Magdeburg, Germany. Electronic address: Julio.Acosta@dzne.de.
Julio
J
Acosta-Cabronero
Department of Neurology, Otto-von-Guericke University, Leipziger Strasse 44, 39120 Magdeburg, Germany. Electronic address: jkauf@neuro2.med.uni-magdeburg.de.
Joern
J
Kaufmann
German Center for Neurodegenerative Diseases (DZNE), Leipziger Strasse 44, 39120 Magdeburg, Germany; Department of Neurology, Otto-von-Guericke University, Leipziger Strasse 44, 39120 Magdeburg, Germany; Department of Neurology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. Electronic address: susanne.abdulla@med.ovgu.de.
Susanne
S
Abdulla
Department of Neurology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. Electronic address: Kollewe.Katja@mh-hannover.de.
Katja
K
Kollewe
Department of Neurology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. Electronic address: Petri.Susanne@mh-hannover.de.
Susanne
S
Petri
German Center for Neurodegenerative Diseases (DZNE), Leipziger Strasse 44, 39120 Magdeburg, Germany; Department of Neurology, Otto-von-Guericke University, Leipziger Strasse 44, 39120 Magdeburg, Germany. Electronic address: stefanie.schreiber@med.ovgu.de.
Stefanie
S
Schreiber
German Center for Neurodegenerative Diseases (DZNE), Leipziger Strasse 44, 39120 Magdeburg, Germany; Department of Neurology, Otto-von-Guericke University, Leipziger Strasse 44, 39120 Magdeburg, Germany; Leibniz Institute for Neurobiology, Brenneckestrasse 6, 39118 Magdeburg, Germany. Electronic address: Hans-Jochen.Heinze@med.ovgu.de.
Hans-Jochen
HJ
Heinze
Department of Neurology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. Electronic address: Dengler.Reinhard@mh-hannover.de.
Reinhard
R
Dengler
German Center for Neurodegenerative Diseases (DZNE), Leipziger Strasse 44, 39120 Magdeburg, Germany; Department of Neurology, Otto-von-Guericke University, Leipziger Strasse 44, 39120 Magdeburg, Germany. Electronic address: Stefan.Vielhaber@dzne.de.
Stefan
S
Vielhaber
German Center for Neurodegenerative Diseases (DZNE), Leipziger Strasse 44, 39120 Magdeburg, Germany. Electronic address: Peter.Nestor@dzne.de.
Peter J
PJ
Nestor
D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000000981:diagnostic imaging*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000473:pathology; D003430:Cross-Sectional Studies; D004185:Disability Evaluation; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D009483:Neuropsychological Tests; D018709:Statistics, Nonparametric
ALS; ALSFRS-R; Biomarker; Diffusion; Longitudinal; MRI