PROJECT SUMMARY Blood flow and cellular metabolism are two basic but vital physiological processes that are often dysregulated in major diseases. Imaging of flow-metabolism mismatch or coupling is of broad clinical and research significance in many diseases, for instance, in ischemic cardiomyopathy for assessing myocardial viability, in cancer for grading tumor aggressiveness, and in neurodegenerative diseases for studying brain function. A major challenge in PET imaging of flow-metabolism is that scanning for these two processes requires two different radiotracers–18F-fluorodeoxyglucose (FDG) for metabolism and a second flow radiotracer for perfusion imaging. While FDG is widely available in the clinic for metabolic imaging, perfusion imaging by PET is clinically limited, resulting in underutilization of flow-metabolism imaging in both research and clinics. The goal of this project is to develop a single-tracer multiparametric PET imaging solution for simultaneous flow- metabolism imaging using only 18F-FDG without the need for a second flow-specific radiotracer. Early attempts from others and our group have used FDG blood-to-tissue delivery rate (K1) as a proxy of blood flow. However, the accuracy of FDG K1 approximating blood flow largely depends on the FDG extraction fraction in tissues and is also compromised by the correlation between FDG K1 and blood glucose levels. Our preliminary work has tackled these problems specifically in the myocardium and demonstrated the feasibility of using FDG for measuring myocardial blood flow. The focus of this proposal is to extend the effort to a large study and to the whole body, and further develop the enabling techniques to improve FDG blood flow quantification. We will (1) develop glucose-normalized extraction fraction correction for FDG blood flow quantification in various organs using total-body dynamic PET; (2) develop high-temporal resolution kinetic modeling for improved FDG blood flow quantification; (3) improve FDG blood flow imaging on short PET scanners using advanced image reconstruction. Successful completion of this project will develop a new technical capability of 18F-FDG for simultaneous multiparametric imaging of blood flow and glucose metabolism with reduced radiation dose, imaging time and cost. This would also open up many new opportunities for clinical applications that require multiparametric imaging biomarkers but have been historically restricted by the accessibility of perfusion imaging, thus making a broad impact in multiple PET applications for patient clinical care and research.

PROJECT NARRATIVE Public Health Relevance Statement: Radiotracers for blood flow imaging suffer from limited clinical availability. This project develops a new technical capability of the classic metabolic radiotracer 18F-FDG for simultaneous multiparametric imaging of blood flow and glucose metabolism with reduced radiation dose, imaging time and cost. The enabled single-tracer multiparametric imaging would open up many new opportunities for clinical applications that require multiparametric imaging biomarkers but have been historically restricted by the accessibility of perfusion imaging.