WP Leaders: Julian Grosskreutz & Martin Turner

WP3 extends the clinical data in WP1 with standardized quantification of brain (MRI; upper motor neuron) and spinal cord (MUNIX; lower motor neuron) motor neuron involvement, the hallmarks of ALS. It aims to develop both techniques as widely applicable surrogate markers of disease stage and progression and as markers of therapeutic response in future drug trials. Acquisition of longitudinal MRI and MUNIX data along with other biomarkers will help to understand critical stages of upper and lower motor neuron demise. Thus, WP3 will complement WP1 and WP2 by developing quantitative markers of ALS-related tissue damage. These markers will be included in standardized ALS patient datasets, and will be available for scientific interrogation within the wider neurodegeneration field.

Computational MRI analyses are inherently investigator-independent but contain numerous potential error sources (i.e. protocol, scanner type and analysis tool). Thus, to implement optimization and harmonization, MRI requires continuous multicenter comparative analyses feeding identified sources of quality loss back to ALS centres. The existing NISALS initiative and its recent delivery of broad consensus guidelines has laid the groundwork for WP3a to analyse existing MRI acquisition and analysis parameters for brain VBM and DTI datasets in ALS patients; to harmonise these parameters across EU centres and to link MRI datasets to biofluid (blood and CSF) samples in the same individual. This will in turn allow the later development of a multimodal biomarker profile. In the shorter term, WP3a will help to estimate of the range within which MRI biomarkers report disease severity and progression of ALS in a quantitatively reproducible manner in a multicenter setting; and will implement a quality control �round robin� feedback system for centres wishing to use MRI as biomarker in ALS and other motor neuron diseases.