Neurite Orientation Dispersion and Density Imaging (NODDI) in RRMS (P4.159)

Background: Neurite orientation dispersion and density imaging (NODDI) is a novel diffusion magnetic resonance imaging (MRI) technique that provides more specific markers of brain tissue microstructure than standard diffusion tensor imaging (DTI). Objectives: We aim to (i) compare NODDI metrics between relapsing remitting multiple sclerosis (RRMS) patients and controls, and (ii) determine if these indices are associated with disability. Methods: 22 RRMS patients (mean age 38.7yrs (±6.4), mean disease duration 8.4yrs (±5.6), median expanded disability scale (EDSS) 3.0 (range 1.0-6.5), 18 female) and 19 healthy controls (mean age 36.8yrs (±12.8), 12 female) were recruited. MRI data was obtained on a 3T clinical scanner. Standard clinical disability measures, cognitive, mood, fatigue and pain assessments were performed. Paired t-tests compared mean NODDI parameters (neurite density, orientation dispersion and free water) in white matter, cortical grey matter and deep grey matter between groups. Pearsons correlations tested the relationship between NODDI parameters and clinical scores. Correlations were corrected for age, gender, white matter fraction and grey matter fraction in multivariate linear regression models. Results: Neurite density in the white matter was lower in patients than controls. Free water in the cortical grey matter was higher in patients than controls. In patients, both lower neurite density and higher orientation dispersion in the white matter correlated with worse scores on the PASAT test; higher orientation dispersion in the deep grey matter correlated with higher disability, measured by EDSS, ASIA light touch and vibration threshold. Conclusions: NODDI metrics differ between RRMS patients and controls. Greater disability is correlated with lower neurite density and higher orientation dispersion. These microstructure changes are more specific than standard DTI imaging parameters and may be underlying mechanisms for disability. Recruitment is ongoing. The next steps are to check the role of lesions on NODDI changes, and compare NODDI with standard DTI values. Disclosure: Dr. Kipp has nothing to disclose. Dr. Cawley has nothing to disclose. Dr. Prados has nothing to disclose. Dr. Schneider has nothing to disclose. Dr. Ourselin has nothing to disclose. Dr. Wheeler-Kingshott has received personal compensation for activities with Biogen Idec as a consultant. Dr. Wheeler-Kingshott has received research support from the UK MS Society, UCL/UCLH, NIHR, BRC, EPSRC, ISRT, Wings for Life, and New Zealand Brain R Dr. Miller has received personal compensation for activities with UCL Institute of Neurology and Biogen Idec as a consultant. Dr. Thompson has nothing to disclose. Dr. Ciccarelli has received personal compensation for activities with Novartis, Biogen and GE as a consultant.