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High-resolution In Vivo Manual Segmentation Protocol for Human Hippocampal Subfields Using 3T Magnetic Resonance Imaging
Published on: November 10, 2015
Pentad: A reproducible cytoarchitectonic protocol and its application to parcellation of the human hippocampus
Emily M Williams1, Emma W Rosenblum1, Nicole Pihlstrom1
1Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, United States.
Insights
A new pentad protocol for human hippocampus subfield segmentation was developed using five cellular traits. This histology-based method provides a detailed parcellation of 13 subfields across nine levels, advancing neuroimaging biomarkers.
Area of Science:
- Neuroscience
- Histology
- Neuroimaging
Background:
- The hippocampus is crucial for learning and memory, and its degeneration is linked to various diseases.
- Hippocampal subfield volumes are key neuroimaging biomarkers for neurodegeneration.
- Existing histologic parcellation studies have limitations, necessitating improved methods.
Purpose of the Study:
- To establish the first histology-based parcellation protocol for human hippocampal subfields.
- To advance the field of hippocampal subfield segmentation using a novel approach.
- To create a comprehensive and standardized method for analyzing hippocampal structure.
Main Methods:
- Developed the 'pentad protocol' focusing on five cellular traits: chromophilia, neuron size, packing density, clustering, and collinearity.
- Applied the protocol to 22 human hippocampal samples.
- Parcellated 13 subfields across nine anterior-posterior coronal levels, including medial subfields.
Main Results:
- Successfully parcellated 13 hippocampal subfields at nine distinct levels in 22 samples.
- Identified specific cytoarchitectural characteristics for subfields CA1, CA2, CA3, presubiculum, and subiculum.
- Provided evidence for CA4 and prosubiculum as distinct subfields based on cytoarchitecture.
Conclusions:
- The pentad protocol offers a comprehensive and standardized approach to human hippocampus subfield parcellation.
- This histology-based method serves as a gold standard for detailed hippocampal analysis.
- The protocol's detailed parcellation across multiple levels and samples enhances its utility in neuroimaging research.
Introduction:
The hippocampus is integral for learning and memory and is targeted by multiple diseases. Neuroimaging approaches frequently use hippocampal subfield volumes as a standard measure of neurodegeneration, thus making them an essential biomarker to study. Collectively, histologic parcellation studies contain various disagreements, discrepancies, and omissions. The present study aimed to advance the hippocampal subfield segmentation field by establishing the first histology based parcellation protocol, applied to n = 22 human hippocampal samples.
Methods:
The protocol focuses on five cellular traits observed in the pyramidal layer of the human hippocampus. We coin this approach the pentad protocol. The traits were: chromophilia, neuron size, packing density, clustering, and collinearity. Subfields included were CA1, CA2, CA3, CA4, prosubiculum, subiculum, presubiculum, parasubiculum, as well as the medial (uncal) subfields Subu, CA1u, CA2u, CA3u, and CA4u. We also establish nine distinct anterior-posterior levels of the hippocampus in the coronal plane to document rostrocaudal differences.
Results:
Applying the pentad protocol, we parcellated 13 subfields at nine levels in 22 samples. We found that CA1 had the smallest neurons, CA2 showed high neuronal clustering, and CA3 displayed the most collinear neurons of the CA fields. The border between presubiculum and subiculum was staircase shaped, and parasubiculum had larger neurons than presubiculum. We also demonstrate cytoarchitectural evidence that CA4 and prosubiculum exist as individual subfields.
Discussion:
This protocol is comprehensive, regimented and supplies a high number of samples, hippocampal subfields, and anterior-posterior coronal levels. The pentad protocol utilizes the gold standard approach for the human hippocampus subfield parcellation.
