This grant proposal addresses the non-invasive evaluation of coronary stenoses using Nuclear Magnetic Resonance imaging techniques. We will evaluate and improve several imaging methods to both directly measure and discern the effects of coronary stenoses. These methods include: standard spin-echo NMR imaging and viewing angle correction to image large portions of the coronary anatomy; flow velocity multi-dimensional imaging limited slice-selective 3D NMR angiography; slice- selective 2D projected NMR angiography; time-of-flight NMR imaging. Besides examination of the coronary vessel to determine the patent lumen, we will also be detecting and quantitating the atheroma in the coronary wall. We will evaluate these techniques in the following systems: a) a phantom 2-5 mm polyvinyl chloride tubing model of coronary stenosis with pulsatile flow and associated with a model of respiratory related motion, b) a porcine model of coronary atherogenesis allowing the longitudinal examination of coronary anatomy by cardiac catheterization and NMR non-invasive techniques as well as the single time point comparison of these methods with pathologic corroboration, c) the examination of human subjects who have undergone x-ray coronary angiography to compare results with this standard clinical x-ray modality, as well as the examination of human subjects who are scheduled to undergo cardiac transplantation for direct comparison of NMR determined coronary stenoses with pathologic specimens. We address the major limitations of NMR imaging for the observation of coronary anatomy which include limitations of resolution and signal-to-noise. We will be implementing variations of standard NMR sequences to reduce these limitations and will utilize methods of post-processing resolution enhancement to bring out the detail of coronary atheromata. As part of our atheroma detection protocol, we will use NMR microscopic techniques to improve the specifically and sensitivity of our measurements. We will also examine the utility of NMR as a measure of the flow limiting character of coronary stenoses by performing measurements before and after the administration of dipyridamole to our porcine model. Changes in flow in this system will be monitored with the radioactive microsphere blood flow method.
