The medial temporal lobe (MTL) is an important brain region that subserves functions of episodic memory and learning. MTL contains the hippocampal formation, composed of histologically and functionally distinct sub- fields, and extra-hippocampal cortices. Subfield-specific memory functions have so far been investigated using high-resolution MRI at 3 Tesla. However, 7 Tesla MR scanners are capable of acquiring ultra-high resolution MR images that can potentially resolve functional activation at an even finer level within smaller subfields such as CA2 and CA3, and at the same time provide structural images with superior contrast properties for localiz- ing subfields. However, smaller voxels and greater magnetic field inhomogeneity pose challenges to acquiring functional MRI data with acceptable image quality at higher field strengths, particularly in the MTL. In this pilot project,we propose to develop and optimize MR acquisition sequences to obtain ultra-high resolution BOLD fMRI at a resolution of 1x1x1 mm3. We will implement state-of-the-art distortion-correction and SNR improve- ment techniques using a combination of image acquisition and post-processing methods to satisfy pre- specified signal-quality metrics in the MTL. We will then demonstrate the utility of ultra-high resolution fMRI in an experiment designed to dissoci- ate BOLD fMRI activation in CA3 and DG subfields. Subfields will be labeled in 7T structural MRI using ground truth histological labeling as reference. The experimental paradigm will operationalize pattern separation and pattern completion-based memory processes which have been shown to differentially activate CA3 and DG subfields under certain conditions in rodents, but similar effects have not been shown in humans. If successful, this project will enable testing of complex, MTL subregion-specific hypotheses regarding human episodic memory function in healthy brain. Additionally, it can provide a granular understanding of ef- fects of pathology on the episodic memory system, as involvement of MTL subregions often show a topo- graphic specificity in many neurological disorders, including Alzheimer's Disease. Finally, this work will provide a comprehensive image acquisition and analysis framework for future imaging-based investigations to more finely characterize normative function as well as the effects of pathology on MTL-supported cognitive proc- esses.

Public Health Relevance

This project will develop and optimize technologies for imaging the medial temporal lobe, a brain region responsible for learning and memory function, using MRI scanners operating at a high magnetic field strength of 7 Tesla. High-field imaging makes it possible to obtain images with very high spatial resolution, which will allow for detailed investigation of substructures in this brain area that play distinct functional roles in learning ad memory. We will use this technology in a functional imaging experiment studying specific aspects of human memory. Such studies can reveal finer levels of complexity of the role of these substructures in normal memory function, and how they are affected in neurological disorders.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Small Research Grants (R03)
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Special Emphasis Panel (NOIT)
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Liu, Guoying
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University of Pennsylvania
Schools of Medicine
United States
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