MTL Postmortem Imaging
High-Resolution Postmortem Imaging of the Human Medial Temporal Lobe
The PATCH lab has done extensive work in the field of ex vivo human brain imaging, including developing algorithms for postmortem MRI segmentation, reconstruction and registration of serial histology to MRI, pathology quantification, building probabilistic atlases from multiple MRI scans, and in vivo to ex vivo MRI registration. The hippocampus and the medial temporal lobe (MTL) have been the main areas on which this work has focused. These structures are of crucial importance in neurodegenerative diseases, since the earliest AD-related neurodegeneration occurs in the MTL. This project is a close collaboration with the Human Neuroanatomy Laboratory at the University of Castilla-La Mancha in Albacete, and renouned neuroanatomist Ricardo Insausti (1954-2024).
Using postmortem MRI and histology from increasingly large datasets, we built first-of-its-kind probabilistic atlases of the human hippocampus (Adler et al., 2018) and human medial temporal lobe (MTL) (Ravikumar et al., 2024). These atlases describe the average/characteristic shape of these structures, their composition into anatomical subregions, and provide a reference space for statistical analysis. More recently, we used serial immunohistochemistry (IHC) to describe the 3D distribution of tau neurofibrillary tangle pathology in the MTL and characterize the associations between tau load and MTL thinning, while accounting for co-pathologies such as TDP-43 (Yushkevich et al., 2021; Ravikumar et al., 2024).
This research direction remains active, funded by NIH grant R01AG056014. We are collecting a dataset of serial histology and 9.4T MRI in >100 brain donors on the Alzheimer’s disease continuum, characterizing variability in patterns of spread of tau pathology in the MTL and how tau spread is impacted by beta-amyloid pathology and co-pathologies. We are also embarking on 3D mapping of other histologically-derived markers, including neuronal density, calcium-binding interneurons, and beta-amyloid plaques.
