The goal of this research is to develop and validate novel MR imaging approaches to quantify changes in local myocardial perfusion without the use of exogenous MR contrast media. We propose theoretical models and experimental protocols to detect, characterize and exploit changes in the intrinsic NMR signals caused by changes in the underlying physiology of the myocardium. These signals, which arise from the interaction of physical, chemical, biological and physiological variables, are subtly altered when the heart is perturbed. For example, the observed longitudinal relaxation time (T1) can be sensitized to changes in myocardial perfusion, and thus appropriately T1-weighted images can be made into quantitative perfusion maps. In addition, due to the underlying magnetic properties of oxy- and deoxyhemoglobin, the transverse relaxation times (T2*, T2) are inherently sensitive to changes in blood oxygenation. Preliminary results suggest that intrinsic NMR imaging approaches can measure myocardial flow reserve in animals and in man. In the proposed research, the investigators seek first to demonstrate that the amplitude of these changes can be predicted in a blood-perfused, ex vivo, canine heart model at 4.7 T, in which the important underlying physiological parameters (blood flow and volume, blood oxygenation, and hematocrit) can be controlled or measured. Following optimization of image quality at 1.5 T, they seek to exploit these changes to produce quantitative maps of the results of vasodilatory (adenosine) stress, in an intact porcine model that includes flow limitation via coronary artery stenosis. They hypothesize that they can measure local myocardial flow reserve using either T1 or T2/T2* effects under vasodilatory challenge: T1 changes can be directly interpreted as flow changes, whereas the T2 changes are the result of an increase in blood oxygenation due to the increased flow with minimal increased oxygen consumption. The applicants will optimize the imaging methodologies, determine which method more robustly detects deficits in perfusion reserve in animal models of coronary artery disease and demonstrate its feasibility in normal human subjects for subsequent studies in patients with suspected coronary artery disease.
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| Poncelet, B P; Koelling, T M; Schmidt, C J et al. (1999) Measurement of human myocardial perfusion by double-gated flow alternating inversion recovery EPI. Magn Reson Med 41:510-9 |
