obtained using magnetic resonance imaging. The Program Project Grant Application includes four research projects in dis- tinct areas all of which utilize positron tomography. The three areas are: a) synthesis and evaluation of new radiopharmaceu- ticals, b) neurological studies, c) cardiovascular studies; and d) pulmonary. Synergism exists between the three projects: they all share the 3 Core functions; they are all aimed at mea- suring metabolism and other physiological parameters in hu- mans and image manipulation is important in all projects. The 4 Projects share the 3 Cores which provide administration, ra- dionuclides, radiopharmaceuticals and state-of-the-art imaging devices. The Departments involved in this Program Project in- cludes the Department of Radiology, the Department of Inter- nal Medicine, the Department of Neurology and Neurosurgery and the Institute of Biomedical Computing.

Thesaurus Terms:part icle accelerator, positron emission tomography, radionuclide diagnosis, radiopharmacology bio- imaging/biomedical imaging

Institution:

Fiscal Year: Department: Project Start: Project End: ICD:

IRG:

Washington University Lindell and Skinker BIvd St. Louis, MO 63130 1999 Radiology 01-Jun-76 30-Jun-03 National Heart, Lung, And Blood

Institute HLBP

~ROJECT TITLE

IMAGING MYOCARDIAL PERFUSION WITH NMR

Grant Number: 5R01HL57409-03 PI Name: Weisskoff, Robert M.

Abstract: DESCRIPTION (Adapted from Applicant' s Ab- stract): 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 con- trast media. We propose theoretical models and experimental protocols to detect, characterize and exploit changes in the in- trinsic NMR signals caused by changes in the underlying physi- ology 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 ex- ample, the observed longitudinal relaxation time (T1) can be sensitized to changes in myocardial perfusion, and thus appro- priately Tl-weighted images can be made into quantitative per- fusion maps. In addition, due to the underlying magnetic prop- erties 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 opti- mization of image quality at 1.5 T, they seek to exploit these changes to produce quantitative maps of the results of vaso- dilatory (adenosine) stress, in an intact porcine model that includes flow limitation via coronary artery stenosis. They hypothesize that they can measure local myocardial flow re- serve using either T1 or T2/T2* effects under vasodilatory chal- lenge: 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 ar- tery disease.

Thesaurus Terms: blood flow measurement, diagnosis design /evaluation, heart circulation, heart scanning, myocardium, nuclear magnetic resonance spectroscopy artery stenosis, bio- mechanics, blood volume, computer simulation, dipyridamole, disease model, heart function, hemodynamics, image enhance- ment, model design/development, oxygen consumption, va- sodilation bioimaging/biomedical imaging, clinical research, dog, human subject, magnetic resonance imaging, outcomes research, swine

Institution:

Fiscal Year: Department: Project Start: Project End: ICD:

Massachusetts General Hospital 55 Fruit St Boston, MA 02114 1999

01-Aug-97 31 -Jul-00 National Heart, Lung, And Blood

Institute

IRG: RNM

)ROJECT TITLE

QUANTITATIVE MAGNETIC RESONANCE ASSESSMENTmMICROVASCULAR DYSFUNCTION

Grant Number: 5R01HL58876-03 PI Name: Wilke, Norbert

Abstract: DESCRIPTION (Adapted from Applicant's Ab- stract): With the advent of coronary angiography a unique group of patients was identified with classic symptoms of

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angina, positive exercise tests, and normal epicardial coronary arteries. The majority of these patients demonstrate a reduced coronary flow reserve. With the development of intracoronary Doppler catheters, these patients with microvascular angina are becoming increasingly recognized. The identification of myo- cardial ischemia in these patients has potential importance for their management and long-term treatment but this requires adequate, preferably non-invasive, diagnostic tools for the routine clinical assessment. Novel magnetic resonance (MR) techniques for the quantification of myocardial blood flow and blood flow reserve, and MR 31P spectroscopy are pro- posed here to elucidate the effects of low flow reserve on transmural flow and myocardial metabolism in patients with microvascular angina. The MR methods for determination of myocardial blood flow are proposed here as an alterna- tive to the "gold standard" of quantitative PET imaging with the advantages of superior spatial and temporal resolution. It is hypothesized that the source of the flow limitation re- sides at the pre-arteriolar level, but the presence of myocar- dial ischemia is controversial. The MR first pass imaging technique combined with kinetic modeling for determina- tion of absolute transmural blood flow and blood flow re- serve offers unique advantages to elucidate the extent of the microvascular flow impairment and the presence and degree of ischemia, even if limited to the subendocardium.

Thesaurus Terms: cardiovascular disorder diagnosis, diag- nosis design/evaluation, electromagnetic blood flow mea- surement, myocardial ischemia/hypoxia, nuclear magnetic resonance spectroscopy angina pectoris, cardiovascular visu- alization, heart circulation, microangiography, microcircula- tion, noninvasive diagnosis, patient monitoring device, reac- tive hyperemia clinical research, human subject, magnetic resonance imaging, positron emission tomography, ultra- sound blood flow measurement

Institution: University Of Minnesota Twin Cities

Twin Cities Minneapolis, MN 55455

Fiscal Year: 1999 Department: Radiology Project Start: 30-Sep-97 Project End: 31-Aug-00 ICD: National Heart, Lung, And Blood

Institute IRG: RNM

~ROJECT TITLE

MRI IDENTIFICATION--HIGH RISK ATHEROSCLEROTIC PLAQUES

Grant Number: 1R01HL60213-01 PI Name: Yuan, Chun

Abstract: Cardiovascular disease due to atherosclerosis re- mains the leading cause of death in the United States. Clini- cal symptoms and morbidity that result from atherosclerotic disease are due to plaque instability and are manifested as ul- ceration, thrombosis and/or intraplaque hemorrhage. Much research has been directed at understanding the atherogenesis, the progression of the disease and the final events that lead to heart attack or stroke. However, relatively little is known about how to identify high risk lesions in vivo noninvasively and to monitor the lesion progression longitudinally. This proposal presents a plan to measure the atherosclerotic plaque volume in MR images and to assess the power of MRI in detecting plaque characteristics that are associated with clinical symptoms. We focus our study on advanced lesions at the carotid bifurcation due to 1) their close association to stroke, 2) their accessibility by high resolution MRI techniques, and 3) the accessibility of carotid samples due to carotid endarterectomy that provides us with excellent opportunity to verify the MRI results by exam- ining the samples histologically. The long term goal of this project is to use high resolution MRI in patients with hemody- namically significant (greater than 70 percent diameter reduc- tion) carotid stenoses to differentiate those plaques that will lead to the development of thrombosis/embolization and stroke. At present there are no reliable means to either measure the plaque volume in vivo or to assess the characteristics of plaques in vivo. The specific aims are: 1) to test whether in vivo MRI can be used to measure the atherosclerotic volume, and 2) to test whether in vivo MRI can identify lesions with thin fibrous cap and a necrotic core. We propose to determine the accuracy of MRI plaque volume measurement and the sen- sitivity and specificity of MRI in the detection of different types of lesions. Accurate diagnosis of different plaque types has particular clinical relevance, as a weakened fibrous cap covering a necrotic core is thought to be structually weak, and may precede the events of plaque rupture and thromboembolic occlusion, which in the carotid artery may result in stroke. The ability to accurately measure plaque volumes and to distin- guish the structural characteristics of advanced lesions of ath- erosclerosis in vivo may provide a noninvasive mechanism to follow the evolution of plaque progression and to detect le- sions that may put individuals at greater risk of clinical events.

Thesaurus Terms: atherosclerotic plaque, cardiovascular dis- order diagnosis, diagnosis design/evaluation, disease/disorder proneness/risk, magnetic resonance imaging, prognosis artery stenosis, atherosclerosis, carotid artery, coronary occlusion / thrombosis, disease classification, sign/symptom, stroke clini- cal research, computer assisted diagnosis, endarterectomy, his- topathology, human subject

Institution: University Of Washington 3935 University Way NE Seattle, WA 98195

Fiscal Year: 1998 Department: Radiology Project Start: 01-Jul-98

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