Comparison of Neurite Density Measured by MRI and Histology after TBI

BACKGROUND Functional recovery after brain injury in animals is improved by marrow stromal cells (MSC) which stimulate neurite reorganization. However, MRI measurement of neurite density changes after injury has not been performed. In this study, we investigate the feasibility of MRI measurement of neurite density in an animal model of traumatic brain injury (TBI) with and without MSC treatment. METHODS Fifteen male Wistar rats, were treated with saline (n = 6) or MSCs (n = 9) and were sacrificed at 6 weeks after controlled cortical impact (CCI). Healthy non-CCI rats (n = 5), were also employed. Ex-vivo MRI scans were performed two days after the rats were sacrificed. Multiple-shell hybrid diffusion imaging encoding scheme and spherical harmonic expansion of a two-compartment water diffusion displacement model were used to extract neurite related parameters. Bielshowski and Luxol Fast blue was used for staining axons and myelin, respectively. Modified Morris water maze and neurological severity score (mNSS) test were performed for functional evaluation. The treatment effects, the correlations between neurite densities measured by MRI and histology, and the correlations between MRI and functional variables were calculated by repeated measures analysis of variance, the regression correlation analysis tests, and spearman correlation coefficients. RESULTS Neurite densities exhibited a significant correlation (R(2)>0.80, p<1E-20) between MRI and immuno-histochemistry measurements with 95% lower bound of the intra-correlation coefficient (ICC) as 0.86. The conventional fractional anisotropy (FA) correlated moderately with histological neurite density (R(2) = 0.59, P<1E-5) with 95% lower bound of ICC as 0.76. MRI data revealed increased neurite reorganization with MSC treatment compared with saline treatment, confirmed by histological data from the same animals. mNSS were significantly correlated with MRI neurite density in the hippocampus region. CONCLUSIONS The present studies demonstrated that neurite density can be estimated by MRI after TBI and MRI measurement of neurite density is a sensitive marker to MSC treatment response.