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

Abstract

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/mm2 and 2000 s/mm2). 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.