Ultra-high Resolution In-vivo 7.0T Structural Imaging of theHuman Hippocampus Reveals the Endfolial Pathway

摘要

The hippocampus is a very important structure in memory formation and retrieval, as well as in various neurological disorders such as Alzheimer’s disease, epilepsy and depression. It is composed of many intricate subregions making it difficult to study the anatomical changes that take place during disease. The hippocampal hilus may have unique neuroanatomy in humans compared to monkeys and rodents, with field CA3h greatly enlarged in humans compared to rodents, and a white-matter pathway, called the endfolial pathway, possibly only present in humans. In this study we have used newly developed 7.0T whole brain imaging, balanced steady-state free precession (bSSFP) that can achieve 0.4 mm isotropic images to study, in vivo, the anatomy of the hippocampal hilus. A detailed hippocampal subregional segmentation was performed according to anatomic atlases segmenting the following regions: CA4, CA3, CA2, CA1, SRLM (stratum radiatum lacunosum moleculare), alveus, fornix, and subiculum along with its molecular layer. We also segmented a hypointense structure centrally within the hilus that resembled the endfolial pathway. To validate that this hypointense signal represented the endfolial pathway, we acquired 0.1 mm isotropic 8-phase cycle bSSFP on an excised specimen, and then sectioned and stained the specimen for myelin using an anti-myelin basic protein antibody (SMI 94). A structure tensor analysis was calculated on the myelin-stained section to showdirectionality of the underlying fibers. The endfolial pathway was consistently visualizedwithin the hippocampal body in vivo in all subjects. It is a central pathway in thehippocampus, with unknown relevance in neurodegenerative disorders, but now that it can bevisualized noninvasively, we can study its function and alterations inneurodegeneration.