Hippocampal Subfields Group progress update: Consensus protocol to segment subfields within the hippocampal body on high-resolution in vivo MRI

Hippocampal subfields are differentially sensitive in development, aging, and neurodegenerative disease. High-resolution imaging techniques have accelerated clinical research of hippocampal subfields; however, substantial differences in protocols impede comparisons in the literature across laboratories. The Hippocampal Subfields Group (HSG) is an international organization seeking to address this issue by developing a histologically-valid, reliable, and freely available segmentation protocol for high-resolution T2-weighted 3T MRI (http://www.hippocampalsubfields.com). This progress update presents the consensus draft protocol for segmenting subfields within the hippocampal body. The segmentation protocol is based on a novel histological reference data set labeled by multiple expert neuroanatomists. Two naïve raters demonstrated feasibility on an MRI dataset including brains from children and adults, and all subfield volume measurements had good reliability. Twenty-six labs with reported 4 years or more experience segmenting hippocampal subfields in healthy lifespan and patient populations participated in an online survey, which included detailed protocol information, feasibility testing, demonstration videos, example segmentations, and labeled histology. Due to the complexity of the internal anatomy, two approaches for segmenting the boundary between cornu ammonis (CA) 3 and dentate gyrus subfields were presented, and the majority approved a geometric heuristic-based protocol over one that referenced the endfolial pathway anatomy: 58% geometric, 23% endfolial, and with 19% expressing no opinion. Labs rated each internal boundary definition for clarity and agreement with the protocol on a scale 1 (low) to 9 (high). All definitions were rated with high clarity (M = 8.42 – 8.65) and reached consensus agreement (binomial ps < 0.01). The geometric heuristic protocol includes labels for the internal boundaries between subiculum, each CA field, and dentate gyrus, which when combined with the external boundaries that previously reached consensus, labels subfield volumes throughout the hippocampal body. We are now conducting a formal reliability test of the hippocampal body protocol with a group of expert and novice raters who are naïve to the protocol. With confirmation of reliability, we will disseminate the validated harmonized segmentation protocol and resources for automated segmentation. The harmonized protocol will significantly facilitate cross-study comparisons and provide increased insight into the structure and function of hippocampal subfields across the lifespan and in disease