PB 1 In vivo assessment of neurodegeneration in the brain by serial longitudinal diffusion tensor imaging – an application to amyotrophic lateral sclerosis

Abstract

Introduction The potential of magnetic resonance imaging (MRI) as a technical biomarker for cerebral alterations is under investigation in neurodegenerative diseases. In this study, a framework for the longitudinal analysis of diffusion tensor imaging (DTI)-based mapping with a series of follow-up scans was applied to longitudinal microstructure assessment of predefined white matter tracts in the course of amyotrophic lateral sclerosis (ALS), as an example for a rapidly progressive neurodegenerative disease. Methods Fifty-four longitudinal DTI datasets from 6 patients with ALS and 3 controls were recorded each 3 months (with up to 15 follow-up scans), yielding a total of 54 longitudinal DTI data sets. After individual alignment and stereotaxic normalization, an averaged DTI data set was created for fibertracking. Fractional anisotropy (FA) values of the tract structures were used to calculate progression rates based on DTI metrics. Results Patients with ALS showed an FA decline along the corticospinal tract (CST) which has been identified as the first affected tract structure in ALS and as the tract correlating with Braak‘s neuropathological stage 1 ( Kassubek et al., 2014 ). FA of controls remained stable in longitudinal DTI scans, whereas, FA decrease progression in the CST ranged from 0.5% to 6% per year in ALS-patients, i.e. four patients showed low progression rates between 0.5% and 2% per year and two patients showed fast progression rates between 3% and 6% per year. The ALS-FRS-R decline correlated significantly with FA decline over time. Conclusion On the basis of the longitudinal DTI data assessment with multiple follow-up measures, FA values were shown to be an in vivo marker for ALS-associated disease progression. That way, imaging-based progression rates at the individual patient level can be determined from DTI scans.