Grant: Discovery Grants Program - Individual

The overall goal of this research program is to develop novel magnetic resonance imaging (MRI) methods to map tissue pH in living organisms. Tissue pH regulates many cellular processes and is tightly controlled under normal conditions. Therefore, pH is a sensitive indicator of cellular dysfunction and distress, particularly when there is insufficient oxygen for normal function. Currently, there are no methods to map pH in living organisms with high resolution and sensitivity. Recently, it was discovered that MRI contrast agents could be designed to generate image contrast that is dependent on tissue pH. These agents perform pH measurement well in solution, but don't work as effectively in living organisms because detection sensitivity is reduced. We have recently developed two different methods of measuring tissue pH. One utilizes a new aspect of the contrast agent signal, the other uses signals found naturally in tissue. However, both methods require further refinement and optimization to realize their full potential. We will focus efforts in three areas designed to improve image quality. First, we will characterize pH response, temperature response, and detection sensitivity, as well as the physical properties of new agents designed and synthesized to improve pH mapping. Using these properties, we will mathematically model the response of the agent to determine whether we can predict how well it will work in tissue. Second, we will continue to develop more efficient MRI acquisition methods and optimize acquisition parameters to maximize contrast in tissue. We will develop a model system of tissue using vesicles. The vesicle system will allow us to control the space inside the vesicle separately from the outside, mimicking the intracellular and extracellular space in tissue. Finally, we will examine how well our methods work at different magnetic field strengths (9.4 Tesla, 7 Tesla, and 3 Tesla) using MRI scanners that are available at Western. In-vivo high-resolution tissue pH mapping will provide new information about evolving biological processes in living organisms, paving the way for applications in medicine and the pharmaceutical industry.