Reproducibility of Neurite Orientation Dispersion and Density Imaging (NODDI) in rats at 9.4 Tesla

PURPOSE: Neurite Orientation Dispersion and Density Imaging (NODDI) is a diffusion MRI (dMRI) technique used to characterize tissue microstructure by compartmental modelling of neural water fractions. Intra-neurite, extra-neurite, and cerebral spinal fluid volume fractions are measured. The purpose of this study was to determine the reproducibility of NODDI in the rat brain at 9.4 Tesla. METHODS: Eight data sets were successfully acquired on adult male Sprague Dawley rats. Each rat was scanned twice on a 9.4T Agilent MRI with a 7 ± 1 day separation between scans. A multi-shell diffusion protocol was implemented consisting of 108 total directions varied over two shells (b-values of 1000 s/mm(2) and 2000 s/mm(2)). Three techniques were used to analyze the NODDI scalar maps: mean region of interest (ROI) analysis, whole brain voxel-wise analysis, and targeted ROI analyses (voxel-wise within a given ROI). The coefficient of variation (CV) was used to assess the reproducibility of NODDI and provide insight into necessary sample sizes and minimum detectable effect size. RESULTS: CV maps for orientation dispersion index (ODI) and neurite density index (NDI) showed high reproducibility both between and within subjects. Furthermore, it was found that small biological changes (<5%) may be detected with feasible sample sizes (n < 6–10). In contrast, isotropic volume fraction (IsoVF) was found to have low reproducibility, requiring very large sample sizes (n > 50) for biological changes to be detected. CONCLUSIONS: The ODI and NDI measured by NODDI in the rat brain at 9.4T are highly reproducible and may be sensitive to subtle changes in tissue microstructure.