The goal of the cardiovascular MRI project is the technical and clinical development of cardiovascular MRI methodologies. The current year demonstrated a major increase in the utilization of MRI in clinical populations. This is a major step in the process toward moving technical developments into the clinical testing phase. Fundamental imaging development continued in several areas. A major emphasis was the application of the multi-slice perfusion imaging sequence to human subjects and more recently patients with coronary artery disease. This stage of clinical testing required the performance of full dose dipyridamole stress tests in the MR scanner. To date, approximately 20 normal volunteers and about 20 patients with coronary artery disease have been scanned. Several important findings have come from this evaluation process. A dosing study demonstrated the benefits of high contrast doses in the qualitative assessment of myocardial perfusion. The phase 1 safety considerations regarding stress testing in the magnet have been passed without clinically significant complications. Despite suggestions in the literature, the upslope of myocardial tissue enhancement during the first passage of contrast through the myocardium has difficulty discriminating normal from abnormal subjects. However, images obtained near and slightly after peak myocardial enhancement allow the detection of coronary artery disease. Visual assessment of images routinely demonstrates the perfusion defects as predominantly an endocardial phenomenon. This appears to be the first test that has the resolution to interrogate the whole heart at such a fine level. Final summary of the perfusion trial for patients with coronary artery disease is in progress. Four patients with hypertrophic cardiomyopathy have been studied. While still a small sample, these studies have revealed perfusion defects that correlate well with stress thallium. It is interesting that the perfusion defects do not appear in the thickest segments of the left ventricular myocardium. The transition to clinical validation of cardiovascular MRI methodologies took several other important steps in the past 12 months. A project was completed in comparing left ventricular volumes by MRI and real-time 3-D echocardiography. This led to a careful validation of the myocardial volumes derived on this ?cardiovascular scanner? since performance characteristics of the gradients had compromised their linearity. These studies reveal that even the largest human hearts remain within the 98% to 100% accurate volume portion of the MR scanner. These findings and the high image quality result in high reproducibility of myocardial volumes and mass measurements. We are ready to unblind the MRI study of the effects of losarten on myocardial mass in patients with hypertrophic cardiomyopathy. A follow up study comparing MRI with contrast enhanced real-time 3-D echocardiograms is in progress. Developments in coronary artery imaging were significant this year. The laboratory pursued 3 distinct approaches to the acquisition of coronary artery images. The lead project involved the development and testing of a 3-D coronary angiogram where data is collected while the heart is in the correct diaphragm position based on a navigator echo. The navigator echo is a 1-dimensional imaging experiment that can be analyzed in real-time by the scanner. This technology forms the basis of the NIH contribution to a multicenter clinical trial studying a novel intravascular contrast agent (MS-325). To date, 6 patients have been enrolled. Other approaches to coronary artery imaging have used variants of rapid 2-D acquisitions during short breathholds. One method allows cardiac motion to move the coronary artery through the imaging plane. An alternative method adjusts the imaging plane to try and ?track? the motion of the coronary artery across the cardiac cycle. Thus, coronary artery imaging has seen substantial technical developments this year and the start of clinical testing. Rapid functional imaging has been an important derivative project from the perfusion sequence development. The fundamental approach of the perfusion sequence marries the speed benefits of echoplanar imaging techniques with the minimal distortion of segmented and interleaved acquistions. This translates to a sequence that can image many locations in the heart each heart beat (perfusion mode) or many images across the cardiac cycle in a functional mode. This rapid functional imaging was a major development this year. We now have the capability to acquire high quality cardiac images with a much wider range of temporal resolutions than previously. For example images were acquired in 16 seconds that display cardiac motion with about 10 ms temporal resolution. This approaches the capabilities of high end digital echocardiography systems. At the other extreme, this fast imaging technique was modified to run in real-time. Myocardial global and regional function can be acquired without need for ECG gating. These studies of myocardial volumes or mass result in high concordance with more traditional MRI techniques. This methodology was validated in a range of patients with coronary artery disease and valvular heart disease. Finally, basic science projects have been utilizing MRI to evaluate LV function, myocardial perfusion, and myocardial edema at 1 day and 7 days after myocardial infarction in dogs undergoing therapy with fibroblast growth factor. This project is helping us validate state-of-the-art MRI methods of detecting and characterizing the myocardium near myocardial infarctions with histology as the gold standard. A new development in quantitative assessment of regional cardiac functionis also being evaluated in dogs before and after myocardial infarction. The displacement of myocardial tissue can now be measured on a pixel-by-pixel basis with high accuracy.
