Diffusion Basis Spectrum and Diffusion Tensor Imaging Detect Hippocampal Inflammation and Dendritic Injury in a Virus-Induced Mouse Model of Epilepsy

Jie Zhan, Tsen-Hsuan Lin, Jane E. Libbey, Peng Sun, Zezhong Ye, Chunyu Song, Michael Wallendorf, Honghan Gong, Robert S. Fujinami, Sheng-Kwei Song

Hippocampal CA1 inflammation and dendritic loss are common in epilepsy. Quantitative detection of coexisting brain inflammation and injury could be beneficial in monitoring disease progression and assessing therapeutic efficacy. In this work, we used conventional diffusion tensor imaging (DTI, known to detect axonal injury and demyelination) and a novel diffusion basis spectrum imaging (DBSI, known to detect axonal injury, demyelination, and inflammation) to detect hippocampal CA1 lesions resulting from neuronal dendritic injury/loss and concomitant inflammation in Theiler's murine encephalomyelitis virus (TMEV)-induced seizure mice. Following the cross-sectionalex vivodiffusion magnetic resonance imaging measurements, immunohistochemistry was performed to validate DTI and DBSI findings. Both DTI and DBSI detected immunohistochemistry-confirmed dendritic injury in the hippocampal CA1 region. Additionally, DBSI-derived restricted isotropic diffusion tensor fraction correlated with 4',6-diamidine-2'-phenylindole dihydrochloride (DAPI)-positive nucleus counts, and DBSI-derived fiber fraction correlated with dendrite density assessed by microtubule-associated protein 2 staining. DTI-derived fractional anisotropy (FA) correlated with dendrite density and negatively correlated with DAPI-positive nucleus counts. Although both DTI and DBSI detected hippocampal injury/inflammation, DTI-FA was less specific than DBSI-derived pathological metrics for hippocampal CA1 dendritic injury and inflammation in TMEV-induced seizure mice.