• Joseph Kuchling, Yael Backner, Frederike C Oertel, Noa Raz, Judith Bellmann-Strobl, Klemens Ruprecht, Friedemann Paul, Netta Levin, Alexander U Brandt, and Michael Scheel.
• Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Neurocure Cluster of Excellence, NeuroCure Clinical Research Center, NCRC Charité, Charitéplatz 1, 10117 Berlin, Germany; Department of Neurology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: joseph.kuchling@charite.de.
• Neuroimage Clin. 2018 Jan 1; 19: 538-550.

BackgroundDiffusion Tensor Imaging (DTI) can evaluate microstructural tissue damage in the optic radiation (OR) of patients with clinically isolated syndrome (CIS), early relapsing-remitting multiple sclerosis and neuromyelitis optica spectrum disorders (NMOSD). Different post-processing techniques, e.g. tract-based spatial statistics (TBSS) and probabilistic tractography, exist to quantify this damage.ObjectiveTo evaluate the capacity of TBSS-based atlas region-of-interest (ROI) combination with 1) posterior thalamic radiation ROIs from the Johns Hopkins University atlas (JHU-TBSS), 2) Juelich Probabilistic ROIs (JUEL-TBSS) and tractography methods using 3) ConTrack (CON-PROB) and 4) constrained spherical deconvolution tractography (CSD-PROB) to detect OR damage in patients with a) NMOSD with prior ON (NMOSD-ON), b) CIS and early RRMS patients with ON (CIS/RRMS-ON) and c) CIS and early RRMS patients without prior ON (CIS/RRMS-NON) against healthy controls (HCs).MethodsTwenty-three NMOSD-ON, 18 CIS/RRMS-ON, 21 CIS/RRMS-NON, and 26 HCs underwent 3 T MRI. DTI data analysis was carried out using JUEL-TBSS, JHU-TBSS, CON-PROB and CSD-PROB. Optical coherence tomography (OCT) and visual acuity testing was performed in the majority of patients and HCs.ResultsAbsolute OR fractional anisotropy (FA) values differed between all methods but showed good correlation and agreement in Bland-Altman analysis. OR FA values between NMOSD and HC differed throughout the methodologies (p-values ranging from p < 0.0001 to 0.0043). ROC-analysis and effect size estimation revealed higher AUCs and R2 for CSD-PROB (AUC = 0.812; R2 = 0.282) and JHU-TBSS (AUC = 0.756; R2 = 0.262), compared to CON-PROB (AUC = 0.742; R2 = 0.179) and JUEL-TBSS (AUC = 0.719; R2 = 0.161). Differences between CIS/RRMS-NON and HC were only observable in CSD-PROB (AUC = 0.796; R2 = 0.094). No significant differences between CIS/RRMS-ON and HC were detected by any of the methods.ConclusionsAll DTI post-processing techniques facilitated the detection of OR damage in patient groups with severe microstructural OR degradation. The comparison of distinct disease groups by use of different methods may lead to different - either false-positive or false-negative - results. Since different DTI post-processing approaches seem to provide complementary information on OR damage, application of distinct methods may depend on the relevant research question.

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