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Updated: Aug 30, 2025
Advanced Diffusion Imaging in The Hippocampus of Rats with Mild Traumatic Brain Injury
Published on: August 14, 2019
Layer-specific microstructural patterns of anterior hippocampus in Alzheimer's disease with ex vivo diffusion MRI at
Zhiyong Zhao1, Lei Zhang2, Wanrong Luo1
1Key Laboratory for Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China.
Abstract:
High-resolution ex vivo diffusion MRI (dMRI) can provide exquisite mesoscopic details and microstructural information of the human brain. Microstructural pattern of the anterior part of human hippocampus, however, has not been well elucidated with ex vivo dMRI, either in normal or disease conditions. The present study collected high-resolution (0.1 mm isotropic) dMRI of post-mortem anterior hippocampal tissues from four Alzheimer's diseases (AD), three primary age-related tauopathy (PART), and three healthy control (HC) brains on a 14.1 T spectrometer. We evaluated how AD affected dMRI-based microstructural features in different layers and subfields of anterior hippocampus. In the HC samples, we found higher anisotropy, lower diffusivity, and more streamlines in the layers within cornu ammonis (CA) than those within dentate gyrus (DG). Comparisons between disease groups showed that (1) anisotropy measurements in the CA layers of AD, especially stratum lacunosum (SL) and stratum radiatum (SR), had higher regional variability than the other two groups; (2) streamline density in the DG layers showed a gradually increased variance from HC to PART to AD; (3) AD also showed the higher variability in terms of inter-layer connectivity than HC or PART. Moreover, voxelwise correlation analysis between the coregistered dMRI and histopathology images revealed significant correlations between dMRI measurements and the contents of amyloid beta (Aβ)/tau protein in specific layers of AD samples. These findings may reflect layer-specific microstructural characteristics in different hippocampal subfields at the mesoscopic resolution, which were associated with protein deposition in the anterior hippocampus of AD patients.
Insights
High-resolution diffusion MRI reveals distinct microstructural patterns in the anterior hippocampus. Alzheimer's disease shows increased variability in specific layers, correlating with amyloid beta and tau protein deposition.
Area of Science:
- Neuroimaging
- Neuroscience
- Biomedical Engineering
Background:
- Ex vivo diffusion MRI (dMRI) offers detailed microstructural insights into the human brain.
- The microstructural characteristics of the anterior hippocampus, particularly in disease states, remain underexplored using dMRI.
Purpose of the Study:
- To elucidate the microstructural patterns of the anterior hippocampus using high-resolution dMRI.
- To investigate the impact of Alzheimer's disease (AD) on anterior hippocampal microarchitecture.
- To correlate dMRI findings with histopathological markers of AD.
Main Methods:
- Acquired high-resolution (0.1 mm isotropic) ex vivo dMRI on post-mortem anterior hippocampal tissues from Alzheimer's disease (AD), primary age-related tauopathy (PART), and healthy control (HC) brains (14.1 T spectrometer).
- Evaluated dMRI-derived microstructural features (anisotropy, diffusivity, streamline density) across hippocampal layers and subfields.
- Performed voxelwise correlation analysis between dMRI metrics and coregistered histopathology (amyloid beta/tau).
Main Results:
- In healthy controls, cornu ammonis (CA) layers exhibited higher anisotropy, lower diffusivity, and more streamlines than dentate gyrus (DG) layers.
- Alzheimer's disease samples showed increased regional variability in CA layer anisotropy (stratum lacunosum, stratum radiatum) compared to PART and HC.
- Streamline density variance in DG layers increased progressively from HC to PART to AD.
- AD brains displayed higher inter-layer connectivity variability.
- Significant correlations were found between dMRI measurements and amyloid beta/tau protein content in specific AD hippocampal layers.
Conclusions:
- High-resolution dMRI can differentiate layer-specific microstructural characteristics in the anterior hippocampus.
- These microstructural alterations in AD are associated with the deposition of amyloid beta and tau proteins.
- The findings highlight the potential of ex vivo dMRI for understanding AD-related neuropathology at a mesoscopic level.
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