Date of Award
Doctor of Philosophy (PhD)
ABSTRACT OF THE DISSERTATION
PET/MR Imaging of Hypoxic Atherosclerotic Plaque Using 64Cu-ATSM
Doctor of Philosophy in Biomedical Engineering
Washington University in St. Louis, 2017
Professor Pamela K. Woodard, Chair
Professor Suzanne Lapi, Co-Chair
It is important to accurately identify the factors involved in the progression of atherosclerosis because advanced atherosclerotic lesions are prone to rupture, leading to disability or death. Hypoxic areas have been known to be present in human atherosclerotic lesions, and lesion progression is associated with the formation of lipid-loaded macrophages and increased local inflammation which are potential major factors in the formation of vulnerable plaque. This dissertation work represents a comprehensive investigation of non-invasive identification of hypoxic atherosclerotic plaque in animal models and human subjects using the PET hypoxia imaging agent 64Cu-ATSM.
We first demonstrated the feasibility of 64Cu-ATSM for the identification of hypoxic atherosclerotic plaque and evaluated the relative effects of diet and genetics on hypoxia progression in atherosclerotic plaque in a genetically-altered mouse model. We then fully validated the feasibility of using 64Cu-ATSM to image the extent of hypoxia in a rabbit model with atherosclerotic-like plaque using a simultaneous PET-MR system. We also proceeded with a pilot clinical trial to determine whether 64Cu-ATSM MR/PET scanning is capable of detecting hypoxic carotid atherosclerosis in human subjects.
In order to improve the 64Cu-ATSM PET image quality, we investigated the Siemens HD (high-definition) PET software and 4 partial volume correction methods to correct for partial volume effects. In addition, we incorporated the attenuation effect of the carotid surface coil into the MR attenuation correction _-map to correct for photon attention.
In the long term, this imaging strategy has the potential to help identify patients at risk for cardiovascular events, guide therapy, and add to the understanding of plaque biology in human patients.
Pamela K. Woodard & Suzanne Lapi
Mark Anastasio, Rudy Yoram, Richard Laforest, Jie Zheng,