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Updated: Dec 15, 2025
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
A prospective harmonized multicenter DTI study of cerebral white matter degeneration in ALS
Sanjay Kalra1, Hans-Peter Müller2, Abdullah Ishaque2
1From the Division of Neurology (S.K.), Department of Medicine, Neuroscience and Mental Health Institute (S.K., A.I.), and Department of Biomedical Engineering (C.B.), University of Alberta, Edmonton, Canada; Department of Neurology (H.-P.M., J.K.), University of Ulm, Germany; Sunnybrook Health Sciences Centre (L.Z., S.J.G.), University of Toronto, Ontario; Departments of Clinical Neurosciences (L.K., R.F.) and Radiology (R.F.), Hotchkiss Brain Institute, University of Calgary, Alberta; Montreal Neurological Institute and Hospital (A.G.), McGill University, Quebec; and Seaman Family MR Research Centre (R.F.), Foothills Medical Centre, Calgary, Alberta, Canada. sanjay.kalra@ualberta.ca.
Objective:
To evaluate progressive white matter (WM) degeneration in amyotrophic lateral sclerosis (ALS).
Methods:
Sixty-six patients with ALS and 43 healthy controls were enrolled in a prospective, longitudinal, multicenter study in the Canadian ALS Neuroimaging Consortium (CALSNIC). Participants underwent a harmonized neuroimaging protocol across 4 centers that included diffusion tensor imaging (DTI) for assessment of WM integrity. Three visits were accompanied by clinical assessments of disability (ALS Functional Rating Scale-Revised [ALSFRS-R]) and upper motor neuron (UMN) function. Voxel-wise whole-brain and quantitative tract-wise DTI assessments were done at baseline and longitudinally. Correction for site variance incorporated data from healthy controls and from healthy volunteers who underwent the DTI protocol at each center.
Results:
Patients with ALS had a mean progressive decline in fractional anisotropy (FA) of the corticospinal tract (CST) and frontal lobes. Tract-wise analysis revealed reduced FA in the CST, corticopontine/corticorubral tract, and corticostriatal tract. CST FA correlated with UMN function, and frontal lobe FA correlated with the ALSFRS-R score. A progressive decline in CST FA correlated with a decline in the ALSFRS-R score and worsening UMN signs. Patients with fast vs slow progression had a greater reduction in FA of the CST and upper frontal lobe.
Conclusions:
Progressive WM degeneration in ALS is most prominent in the CST and frontal lobes and, to a lesser degree, in the corticopontine/corticorubral tracts and corticostriatal pathways. With the use of a harmonized imaging protocol and incorporation of analytic methods to address site-related variances, this study is an important milestone toward developing DTI biomarkers for cerebral degeneration in ALS.
Clinicaltrialsgov Identifier:
NCT02405182.
