THE DEVELOPMENT OF A HARMONIZED SEGMENTATION PROTOCOL FOR HIPPOCAMPAL SUBFIELDS: AN UPDATE

Alzheimer's disease (AD), aging and vascular pathology are proposed to differentially affect hippocampal subfields. Characterizing these differences may provide more insight in disease processes and better biomarkers. However, substantial differences in subfield definitions across groups hinder the ability to compare results and draw conclusions across studies. The Hippocampal Subfields Group (HSG), an international working group formed in 2013, seeks to remedy this problem and provide an avenue for standardization of this research by creating a valid and reliable harmonized segmentation protocol for high-resolution T2-weighted 3T MRI (http://www.hippocampalsubfields.com). Our workflow consists of four steps: 1) collecting histology samples labeled by multiple expert neuroanatomists to form a novel reference dataset to guide the development of the MRI segmentation protocol, 2) developing boundary definitions for each segment of the hippocampus, i.e., hippocampal head, body, and tail, 3) assessing HSG community agreement with boundary rules via online questionnaires and revising boundary rules based on questionnaire responses, and 4) testing reliability of the protocol definitions on multiple MRI data sets. Given substantial differences in the anatomy of the hippocampal head and body, we have approached these regions separately. For both the hippocampal body and head, we have developed a preliminary subfield segmentation protocol, i.e., completed steps 1 and 2. With respect to the outer boundaries of the body (i.e., the anterior/posterior, medial/lateral, and superior/inferior boundaries), step 3 has been completed as well. An online questionnaire describing each of the outer boundary rules was sent to HSG members, with a total of 29 labs participating. Consensus agreement was reached for all rules, but several rules were updated to improve comprehension and clarity. We are now creating and administering additional questionnaires for assessing agreement of the inner boundary rules for the hippocampal body (e.g., between the cornu ammonis fields) as well as the boundary rules for the hippocampal head. Upon completion of the assessment/revision process for each set of rules, the final phase – reliability testing of the protocol – will begin. Once completed, the harmonized protocol will significantly facilitate cross-study comparisons thus advancing insight in the role of hippocampal subfields in aging and dementia.