Grant: Discovery Grants Program - Individual

Research Program Vision: Advance molecular imaging through a) the development of cardiac hybrid PET/MRI methodologies and b) participate in their application to biological discovery, healthcare and commercialization. N.B. To be clear, hybrid PET/MRI is the simultaneous acquisition of PET and MRI data/images over the same anatomy (e.g. the heart). The Needed Infrastructure: I established a leading-edge hybrid PET/MRI program and state-of-the-art medical cyclotron and radiochemistry facility including the recruitment of eight PhD scientists (three radiochemists, two PET/MRI imaging biophysicists and three molecular biologists). Hypothesis: Hybrid PET/MRI has the potential to dramatically improve current understanding of the molecular biology of the heart. However, this requires a convergent incorporation of PET and MRI. Background: We will use this convergent approach to address two limitations of cardiac PET: a) restricted to distinguish only one PET probe as all PET probes are detected by the same signal (annihilation radiation) and b) dynamic PET acquisition to measure myocardial blood flow is collected without correction for bulk, cardiac and respiratory movement. We propose how the simultaneously collected MRI data could address these cardiac PET limitations. Specifically, we will focus on dynamic blood flow measurement of the myocardium using 13N-Ammonia (13NA). N.B. In my last NSERC/DG (ends June 2020) I a) completed my discovery work on biophysical mechanisms of magnetic field transduction (4 papers published; 77 citations) and b) for the development of an MRI reporter gene; (5 papers published, 2 submitted; 53 citations) this NSERC, if funded, would continue to support a PhD student who is completing this work. Specific New Objectives: 1.I will continue to investigate the use of cardiac functional MRI BOLD (cfBOLD) as an alternative to 13NA. Proof-of-principle has been established in dogs [Sci Transl Med, May 2019]. Implementation in humans would allow a PET/MRI evaluation of inflammation, that currently takes 200 min, to be done in 50 min. 2.I will develop a method to perform two measurements of blood flow (rest and stress using two injections of 13NA) that currently takes 70min to take only 20 min. This will use a subtraction technique dependent on detection and correction of bulk cardiac motion using simultaneously acquired MRI data. 3.I will develop a method using simultaneously acquired MRI data to correct for most of the cardiac and respiratory blurring of 13NA images. I will employ a low-rank tensor (LRT) formulation to generate the three-dimensional cardiac and respiratory motion fields from MRI data. These motion fields will be used to correct 13N-ammonia PET data. Impact: a) Reduce radiation dose (cfBOLD), b) Improved cardiac spatial resolution (cfBOLD, LRT approach), c) Reduce acquisition time (cfBOLD, rapid injections of 13NA), d) Increased information per examination, e) Allow accurate tracking of PET labeled cells.