Diffusion MRI revealed altered inter-hippocampal projections in the mouse brain after intrauterine inflammation

Diffusion MRI (dMRI) is commonly used to map large axonal pathways in the white matter. Recent technical advances have also enabled dMRI to resolve the small and complex axonal and dendritic projections in the gray matter. This study investigated whether high-resolution dMRI can resolve the hippocampal neuronal projections and detect abnormal connections due to neurological injury. We performed 3D high spatial and angular resolution dMRI of the mouse brains of the offspring survivors from a model of intrauterine (UI) inflammation, who had known functional deficiency in the hippocampus. We used a novel hippocampal connection mapping method to quantify the intra- and inter-hippocampal projections among 34 automatically segmented hippocampal sub-regions. The results demonstrated wide-spread intra-hippocampal projections, but rather specific intra-hippocampal projections that primarily connected through the CA3 region. Compared with the control group (n = 9), UI-injured mice (n = 11) exhibited significantly reduced inter-hippocampal projection strength (p < 0.01), which correlated well with the neurobehavioral assessments (R² = 0.47). Furthermore, using a whole-brain fixel-based analysis, we identified reduced fiber-density in the CA3 and the ventral hippocampal commissure of the UI-injured mice, which may explain the reduced inter-hippocampal projections. Histological findings also indicated reduced commissural fibers due to the UI-injury. Our study suggested that the dMRI-based connectivity mapping technique can potentially characterize abnormal hippocampal projections in neurological disorders.