Neurite Orientation Dispersion and Density Imaging (NODDI) highlights axonal degeneration of the motor tracts as the core feature underlying Amyotrophic Lateral Sclerosis. (S53.008)

Objective: Compare neurite density in the white and gray matter in Amyotrophic Lateral Sclerosis (ALS) using NODDI, and ascertain how axonal degeneration relates to dendritic damage. Background: NODDI is a quantitative diffusion imaging technique which characterises microstructural features within the intra-neurite, extra-neurite, and cerebrospinal fluid compartments. NODDI yields indices of neurite density index (NDI), orientation dispersion index (ODI), and isotropic compartment (ISO). We used NODDI to investigate for abnormalities in neurite density accompanying ALS and assess how changes occurring within the corticospinal tracts (CST) correspond to alterations within cortical dendrites. Design/Methods: 23 ALS participants and 23 age-matched controls underwent diffusion-weighted MRI scans. Data were analysed using the NODDI toolbox obtaining indices of NDI, ODI, and ISO. The diffusion tensor was applied providing Fractional Anisotropy (FA) and Mean Diffusivity (MD) for comparison. Voxel-based analysis was performed using SPM12, including age as covariate, to evaluate for statistically significant group differences in imaging parameters. Results were accepted as significant for p Results: There was extensive reduction in NDI throughout the CST of the ALS group. ALS was also associated with significantly reduced NDI within the corpus callosum and primary motor cortex. FA was reduced and MD was increased within the CST, consistent with previous DTI findings in ALS. Conclusions: NODDI is an established MRI technique for estimating the density and organisation of axons and dendrites ‘in vivo’. We have shown that ALS is associated with extensive loss of axonal density within the CST, as well as the corpus callosum and primary motor cortex. These results highlight axonal loss as the main contributing factor to the altered diffusivity profile observed in ALS within the CST using DTI. Loss of motor neurone axonal density is demonstrated as the predominant degenerative process occurring in ALS using NODDI. Study Supported by: Motor Neurone Disease Association Disclosure: Dr. Broad has nothing to disclose. Dr. Gabel has nothing to disclose. Dr. Dowell has nothing to disclose. Dr. Zhang has nothing to disclose. Dr. Alexander has nothing to disclose. Dr. Cercignani has nothing to disclose. Dr. Leigh has received personal compensation for activities with Roche as a consultant. Dr. Leigh has received personal compensation in an editorial capacity. Dr. Leigh has received research support from Sanofi-Aventis UK, France and Germany.