Hippocampal subfields perform specific roles in normal cognitive functioning and have distinct vulnerabilities in neurological disorders. However, measurement of subfields with MRI is technically difficult in the head and tail of the hippocampus. Recent studies have utilized curved multiplanar reconstruction (CMPR) to improve subfield visualization in the head and tail, but this method has not yet been applied to histological data.
We utilized BigBrain data, an open-source database of serially sectioned histological data for our analyses. The left hippocampus was segmented according to histological criteria by two raters in order to evaluate intra- and inter-rater reliability of histology-based segmentation throughout the long axis. Segmentation according to our previous protocol for the hippocampal body was then compared to these histological measurements to evaluate for histological validity. Agreement between segmentations was evaluated using Dice similarity coefficients (DSCs).
Intra-rater reliability (DSCs) of histological segmentation was excellent for all subfields: CA1 (0.8599), CA2 (0.7586), CA3/CA4/DG (0.8907), SLM (0.9123), subiculum (0.8149). Similarly, inter-rater reliability analysis demonstrated excellent agreement (DSCs) for all subfield locations: CA1 (0.8203), CA2 (0.7253), CA3/CA4/DG (0.8439), SLM (0.8700), subiculum (0.7794). Finally, histological accuracy (DSCs) for our previous protocol was excellent for all subfields: CA1 (0.8821), CA2 (0.8810), CA3/CA4/DG (0.9802), SLM (0.9879), subiculum (0.8774). When subfields in the hippocampus head, body, and tail were analyzed independently, DSCs also showed excellent agreement.
CMPR allows reliable subfield segmentation based on histological criteria throughout the hippocampal head, body, and tail. Our previous protocol for the hippocampal body can be applied to provide histologically valid subfield measurements throughout the entire hippocampal long axis.