Multi-modal imaging mouse models of human epilepsy
Category: Current
Published Date
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How does a gene mutation, representing dysfunction at the molecular level, lead to altered whole brain function such as epilepsy? To begin to tackle this question we are utilizing mouse models of inherited epilepsy syndromes, combined with multi-modal imaging. Our research goal is to identify macroscopic and microscopic structural changes in the brain which may result in the generation of seizures. Our methodology consists of three parts: 1) MRI; 2) Histology and 3) High resolution 3D brain reconstruction. Part 1 includes analysis of gross anatomical structure of whole mouse brain using magnetic resonance imaging (MRI). Evidence from human MRI studies of patients who carry the ion channel mutation linked to generalized epilepsy with febrile seizures plus (GEFS+), show decreased brain volume in the corpus callosum. Our preliminary results from T2 weighted images of mice which carry the same gene mutation identified in GEFS+ suggest altered brain volume compared to control animals. Parts 2 and 3 of the project involve collection of histological stained serial sections of the same brain used to obtain MR imaging. The 30µm thick sections, imaged at x4 magnification have been used to produce high resolution histological data. All animals will have co-registration of MRI and histological sections as a 3D volume data set (collaboration with Prof David Reutens). The purpose of this is twofold: first, co-registration of MRI and 3D volume data set provide important in vivo information about changes in brain volume in the epilepsy model. Second: comparisons of MRI and histology of the brain identify structural alterations that are a consequence of histological processing. In addition; mapping high resolution information from sub structures in the brain back into a 3D space will identify specific regions which are altered in gene mutant animals, for example changes in brain nuclei and white matter tracts. Overall, this multi-modal imaging approach will provide valuable anatomical structural information and lead the way for future analysis.
