PROJECT SUMMARY Oxygen is the most important nutrient for life and its deficiency in can cause rapid loss of cell and organ function. Thus, 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. This proposal is aimed at extracting quantitative physiological properties of tissue from non-invasive imaging data. Specifically we will focus on assessment of tissue oxygenation and oxygen consumption from Magnetic Resonance Imaging (MRI) data obtained from two novel oximetry techniques developed in the PIs lab. One technique relies on the binding of a MRI contrast agent in regions that are deficient in oxygen. Another technique relies on the change in the MRI properties of a nanoprobe depending on the surrounding oxygen levels. In both cases a comprehensive pharmacokinetic frame work is needed that accounts for delivery and distribution of the reporter probe and relates the observed MRI parameters to tissue oxygenation. A secondary goal is to expand develop models that relate the intrinsic tissue MRI properties to tissue oxygenation and metabolism. We propose a rigorous research plan and integrate imaging research with education with a view to achieving local and global impact. The intellectual merits of the proposed research are many. The proposed work aims to improve the understanding of how MRI properties of reporter probes change with tissue oxygenation and how this can be exploited to obtain a three-dimensional picture of tissue oxygenation. The PI was first to develop these oximetry approaches and is uniquely positioned to take the next step towards assessment of tissue oxygenation in high resolution in three dimensions for the first time. This could directly impact the development, screening and use of novel hypoxia targeted therapeutics that, after good preclinical results, often perform equivocally in the clinic for want of hypoxia based stratification of a heterogeneous patient population. The proposed work could also be applied to improved radiotherapy planning by incorporation of hypoxia maps (i.e. regions that need a boost) along with anatomical images. The broader impacts of the proposed work fall under two related categories. At the research level, the proposed work will impact the scientific community by improving basic understanding of tissue oxygen dynamics in response to interventions. Findings could impact future patients by aiding the design and development of personalized therapy for cancer (e.g. patient stratification for novel hypoxia activated prodrugs) and by the potential to improve how radiotherapy is planned and delivered in the clinic. At the educational front, we want to impact young minds by demystifying Medical Imaging and demonstrating its potential to impact public health and as an exciting career option, at the high school and undergraduate level, both locally and globally. This will be accomplished using a Hands-on Summer Program in Imaging Technology (HoSPIT) that leverages the strong culture of student research and research outreach within the Fulton Schools of Engineering at Arizona State University (ASU). Importantly, the course will incorporate concepts and techniques relevant to engineering of Medical Imaging technology which are currently not emphasized at all in high school level curricula and underemphasized at the undergraduate level. The experience will impact Biomedical engineering graduate students, who will participate in developing and delivering various components of the course and thus learn to be educators themselves. An online version of the summer program will be made available to undergraduates from developing countries through expanding programmatic partnerships with institutions in those countries, thus impacting students and universities globally. The proposed activity integrates research and educational activities between three different educational levels (highschool, undergraduate, and graduate) and multiple organizations (ASU, local high schools and foreign universities). We hope to inspire and attract the participants to engineering careers in general and Medical Imaging in particular. The training received by the participants will provide the groundwork for a transition from high school to college to higher education or employment and thus impact them at a personal level. Last but not the least; the proposed work will impact the PI by providing him the opportunity and resources to be a better scientist and educator.
|Effective start/end date||4/15/14 → 3/31/19|
- National Science Foundation (NSF): $440,000.00