Development and Validation of Multi-Parameter Mapping for the NISCI Multi-Center Clinical Trial

Embedded as a sub-study within the clinical trial NISCI (Nogo inhibition in spinal cord injury:, we employ whole brain quantitative imaging at 3 Tesla as a new biomarker for de- and regeneration. The quantitative MRI technique of multi-parameter mapping (MPM; Weiskopf et al., 2013, Frontiers in Neuroscience, 7, 1-11) was adapted to the possibilities at clinical sites with vendor sequences as well as reduced resolution (1 mm isotropic resolution) and scanning time to fit in a session <25 min. To evaluate the protocol setup for consistency between and within sites (test-retest) we performed a traveling heads study with five healthy subjects across six sites, involving different scanner hard- and software (see map). For processing the data we used the hMRI-toolbox ( for quantitative MRI data, which is developed by the MPI-CBS and an international consortium (Tabelow et al., 2019, NeuroImage, 194, 191-210).

For quantitative maps (Magnetization Transfer saturation [MT], Proton Density [PD], longitudinal [R1] and effective transverse relaxation times [R2*]) the intra-site coefficient of variation (CoV) was between 4% and 10% for maps of MT, R1, and PD, whereas it was higher for R2* with up to 16% (see below figure). The inter-site CoV varied between 3% and 9% for maps of MT, R1, and PD, whereas it was higher for R2* with up to 15% (see below figure). The inter-site bias varied between 1% and 4% for MT, R1, and PD, whereas it was higher for R2* (up to 6%, see below figure). However, longitudinal studies of spinal cord injury showed that effect sizes are in the range of 17-20% for R1, and 14% for MT (Grabher et al., 2015, Ann Neurol, 78, 751-761)1 year after injury compared to healthy controls. Thus, we expect to reliably detect injury related changes and potential significant treatment effects in the NISCI trial, using the optimized and validated MRI protocols and post-processing methods.

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