Angelique Louie’s research is driven by the belief that imaging technologies offer unique testing grounds for probing the cellular and molecular basis of biological events. Her work employ a highly interdisciplinary approach to solve research problems, an amalgam of her fields of training, with the unifying theme being the applications of imaging techniques and the design of probes to characterize molecular phenomena. Specific interests are in the major health problems of retinal degeneration, cardiovascular disease and tumor formation. The unifying theme of this research is the application of imaging techniques and the design of probes to characterize molecular phenomena in diseased versus normal states. Much of the work involves the application of multiple imaging modalities. By using modalities in combination, one can exploit the strengths of each to maximize the information obtained by imaging. But the use of more than one imaging modality requires specialized probes with multiple modes of signal enhancement. Therefore, a primary component of her research is the development of novel imaging agents for molecular imaging, where molecular imaging is defined as the in vivo visualization of specific molecules or molecular function. Three main areas are under investigation:
1. Noninvasive Imaging of Vulnerable Plaques in Vivo
This research centers on the development of targeted, molecular imaging probes for multimodality imaging of atherosclerotic plaques. The high sensitivity of positron emission tomography (PET) is used to identify putative plaques, and high resolution, molecular imaging using magnetic resonance imaging (MRI) is then performed on these regions to obtain 3-dimensional images of the plaques and assess their vulnerability to rupture.
2. Multimodality Nanoparticles for Imaging: from Cancer to Health Effects of Air Pollution
This project aims to design and develop semiconductor-based probes (quantum dots) that incorporate magnetic resonance properties and luminescence in the same nanoparticle. Dr. Louie’s group is generating CdSe/ZnS core/shell nanoparticles where Mn2+, an MR agent, is incorporated into the shell. The ultimate goal is to apply these multifunctional quantum dots for imaging applications in heart disease and cancer. In addition, in collaboration with air pollution researchers at UCD, Dr. Louie’s group is employing quantum dots labeled with PET agents as model ultrafine particles to image the distribution of air pollutants in vivo. Inhalation of ultrafines is believed to be linked to cardiovascular disease and other developmental abnormalities. In these studies PET imaging is used to track the deposition and fate of inhaled model ultrafines over time, and optical methods are subsequently employed to identify subcellular localization in excised tissues.
3. Magnetic Resonance Imaging Probes for Mapping Retinal Activity
Although Age Related Macular Degeneration is the leading cause of blindness in people over 60, very little is known about the progression or cause of this disease. Visualization of the pattern of loss and type of cells involved can aid in elucidation of disease mechanisms. This project aims to facilitate such visualization through design and development of unique MRI agents that are responsive to membrane potential in order to generate 3-dimensional maps of retinal function. Dr. Louie’s group has developed an MRI agent that changes conformation in response to environmental inputs. The change in conformation results in intermolecular interactions that inhibit or promote contrast enhancement by the agent, thus the agent is “activatable” in response to outside cues.
