Imaging microstructure with diffusion and susceptibility MR: neuronal density correlation in Disrupted-in-Schizophrenia-1 mutant mice

Purpose: To probe cerebral microstructural abnormalities and assess changes of neuronal density in Disrupted-in-Schizophrenia-1 (DISC1) mice using non-Gaussian diffusion and quantitative susceptibility mapping (QSM). Materials and Methods: Brain specimens of transgenic DISC1 mice (n = 8) and control mice (n = 7) were scanned. Metrics of neurite orientation dispersion and density imaging (NODDI) and diffusion kurtosis imaging (DKI), as well as QSM, were acquired. Cell counting was performed on Nissl-stained sections. Group differences of imaging metrics and cell density were assessed. Pearson correlations between imaging metrics and cell densities were also examined. Results: Significant increases of neuronal density were observed in the hippocampus of DISC1 mice. DKI metrics such as mean kurtosis exhibited significant group differences in the caudate putamen (P = 0.015), cerebral cortex (P = 0.021), and hippocampus (P = 0.011). However, DKI metrics did not correlate with cell density. In contrast, significant positive correlation between density of neurons and the neurite density index of NODDI in the hippocampus was observed (r = 0.783, P = 0.007). Significant correlation between density of neurons and susceptibility (r = 0.657, P = 0.039), as well as between density of neuroglia and susceptibility (r = 0.750, P = 0.013), was also observed in the hippocampus. Conclusion: The imaging metrics derived from DKI were not sensitive specifically to cell density, while NODDI could provide diffusion metrics sensitive to density of neurons. The magnetic susceptibility values derived from the QSM method can serve as a sensitive biomarker for quantifying neuronal density.