A harmonized protocol for medial temporal lobe subfield segmentation: initial results of the 3-tesla protocol for the hippocampal body

Alzheimer’s disease (AD), aging and vascular pathology are proposed to differentially affect subregions of the medial temporal lobe (MTL). Characterizing these differences may provide more insight in disease processes and better biomarkers. However, the comparison of different studies is hampered by differences in how these subfields are segmented on in vivo MRIs by different research groups. The Hippocampal Subfields Group (HSG) was formed to create a harmonized protocol for MTL subregion segmentation. The group began developing a subfield segmentation protocol for the hippocampal body using high-resolution T2-weighted 3 tesla MRI. We present the initial results of this effort. Stage 1. Establish the anterior and posterior borders of the hippocampal body as a whole and the boundaries with surrounding structures, 2. Determine subfield boundaries on histological sections throughout the hippocampal body in three specimens, 3. Identify the corresponding boundaries between adjacent subfields on in vivo MRI, 4. Solicit feedback on the initial protocol from the HSG, and 5. Perform formal reliability analysis by six experts. The initial results are from stage 1. The anterior border was defined as one slice posterior to the last slice containing the uncal apex and the posterior border as the most posterior slice containing the colliculi. A reliability test yielded a Fleiss κ >0.75. An initial protocol for the boundaries with surrounding structures is also developed, with the dorsal and lateral border at the interface of the gray matter of the hippocampus and the white matter of the alveus/fimbria, the ventral border placed at the parahippocampal white matter and the medial border at the most medial point of the hippocampus. Additionally, the histological annotations are being finalized and an MRI protocol for the subfield boundaries is being prepared. The harmonized protocol, once completed, is expected to impact the field significantly by producing measurements that are comparable between labs and by making it easier to relate and pool results from different studies. Given the heterogeneity of AD, vascular and aging-related changes in the MTL, a reliable measure of subfield-specific effects may lead to more powerful biomarkers.