Oxygen is the most important nutrient for life and its deficiency can cause loss of cell viability and organ function. Additionally, oxygen is challenging to deliver in vivo due to its low solubility in water. Therefore, the opportunity to assess hypoxia non-invasively may be significant in understanding mechanisms of tissue function and in clinical prognosis of various diseases, such as cancer and stroke. The overall goal of this proposal is to develop and use quantitative methods employing Magnetic Resonance Imaging (MRI) to measure, non-invasively, oxygen levels in vivo. Besides advancing our fundamental understanding of tissue oxygenation under different physiologic conditions, this capability could also directly impact the development, screening and use of novel therapeutic agents that target hypoxia either for promoting it, as would be desirable with cancer, or for alleviating it, as would be the case in myocardial infarction and stroke. Findings could impact future patients by aiding the design and development of personalized therapy for cancer and by improving how radiotherapy is planned and delivered in the clinic. Educational activities integrate research with education at three different levels (high-school, undergraduate, and graduate), and multiple organizations (ASU, local high schools and foreign universities). A Hands-on Summer Program in Imaging Technology (HoSPIT) will increase awareness in the capabilities and limitations of Medical Imaging and will prepare students for the next steps in their educational paths and towards professional employment.
Two approaches will be investigated. The first is based on the binding of an MRI contrast agent in regions that are deficient in oxygen; and the second relies on the change in the MRI properties of a nanoprobe depending on the surrounding oxygen levels. In both cases, a comprehensive pharmacokinetic framework will be used to describe the delivery and distribution of the reporter probe and to relate the observed MRI parameters to tissue oxygenation. Three specific objectives will be pursued: the development of a theoretical model for systemic delivery of MRI-based oxygen imaging probes for dynamic measurement of tissue oxygenation and related parameters; the design and construction of an MRI-compatible tissue simulating phantom with tunable oxygenation and metabolic status for in vitro testing of the theoretical model; and the application of theoretical model for measurement of tissue oxygenation and related parameters to in vivo data. The proposed work is expected to advance the capability of developing three-dimensional images of tissue oxygenation in high resolution under both physiological and pathological conditions and under various pharmacological interventions.
