FV 1 In vivo staging in ALS – A mono-centric cross-sectional and longitudinal DTI-based study.

Introduction Neuropathological studies in amyotrophic lateral sclerosis (ALS) have shown that ALS may disseminate in a regional sequence in four disease-related patterns ( Braak et al., 2013 ). Recently, our group reported the diffusion tensor imaging (DTI)-based analysis of sequential spreading of disease in ALS ( Kassubek et al., 2014; Müller et al., 2016 ). The aim of this study was to show that longitudinal data support the pathological findings and to establish DTI as an in vivo tool to image pathological ALS stages by testing for longitudinal consistency of the categorization results. Methods The application of in vivo DTI analysis to fiber structures that are prone to be involved at each neuropathological pattern of ALS was performed in a large-scale monocentre sample of ALS patients. A total of 584DTI datasets from ALS patients ( N = 425) and controls ( N = 159) were analyzed by tract of interest (TOI)-based fiber tracking; 52 ALS patients and 22 controls obtained at least one follow-ups can with different time-intervals of 10 months ( ± 9 months) in average. Results At the individual level, a categorization into ALS staging patterns was possible. At the group level, longitudinal ALS data showed significant differences for the stage-related tract systems ( p < 0.05, corrected for multiple comparisons).Out of the 52 longitudinally scanned ALS patients, 13 ALS patients showed an increase in ALS-stage, while the other ALS patients remained stable. Conclusion In summary, in vivo imaging of the disease patterns in ALS has become feasible cross-sectionally and longitudinally and has potential to be used as a non-invasive readout in ALS trials. [ABSTRACT FROM AUTHOR]