Neurite Orientation Dispersion and Density Imaging (NODDI) at the Onset of Clinically Isolated Syndrome (CIS): New Insights in the Early Microstructural Brain Tissue Changes (P4.157)

Background:Neurite orientation dispersion and density imaging (NODDI) is a new diffusion weighted (DW) magnetic resonance imaging (MRI) technique that provides specific indices of neuronal morphology. Objective:The aim of this study is to obtain NODDI neurite density index (NDI), orientation dispersion index (ODI, 0 for parallel neurites, 1 for dispersed neurites) and free water fraction (FWF) in normal appearing white matter (NAWM), cortical grey matter (CGM), deep grey matter (DGM) and T2 white matter (WM) lesions in patients presenting with a clinically isolated syndrome (CIS) compared to healthy controls (HC). Methods:We recruited 16 CIS subjects within 3 months from symptom onset (8 females[F]),(14 optic neuritis, 1 myelitis and 1 supratentorial syndrome)mean (standard deviation) age 34.25(8.57) years and 11 HC(7F),mean age 33.73(7.18) years. All subjects underwent a MRI protocol at 3T and 10/16 patients had abnormal MRI scan. We analysed DW scans with NODDI and derived voxel-wise ODI, NDI and FWF maps.Linear regression models were used to compare differences between groups adjusting for age, gender and brain volume fractions. Results:Orientation dispersion of neurites was higher in patients’ NAWM than in HC’s WM (0.270±0.081 vs. 0.222±0.007, p<0.033).Free water fraction in CGM was also higher in patients than in HC (0.192±0.098 versus 0.127±0.021, p<0.010).In patients, ODI in NAWM was higher than that in T2 lesions, accounting for 0.134±0.098, p<0.01. Conclusion: Despite the small size of the cohort (recruitment is ongoing), these findings suggest that in CIS patients fibre coherence is reduced in NAWM, possibly caused by microstructural changes affecting the myelinated axons. The increased free water in CGM may result from an early neurodegenerative process, which increases the chances of partial volume of cortical tissue with CSF. Therefore, NODDI parameters may be useful markers of early tissue changes, offering new insights into CIS pathogenesis. Disclosure: Dr. Collorone has nothing to disclose. Dr. Cawley has nothing to disclose. Dr. Prados has nothing to disclose. Dr. Ourselin has nothing to disclose. Dr. Tur Gomez has received personal compensation for activities with TEVA Pharmaceuticals, Ismar Healthcare, Serono Symposia International Foundation as a consultant. Dr. Grussu has nothing to disclose. Dr. Gandini Wheeler-Kingshott has nothing to disclose. Dr. Miller has nothing to disclose. Dr. Thompson has nothing to disclose. Dr. Toosy has received personal compensation for activities with Biogen Idec. Dr. Ciccarelli has received personal compensation for activities with Novartis, Biogen and GE as a consultant.