Cardiovascular metabolic imaging: physiologic and biochemical dynamics in vivo.

Fifty-eight investigators from the fields of biochemistry, physiology, cardiology, nuclear medicine, and physics met to discuss the development of metabolic imaging techniques for application to cardiovascular and pulmonary studies in health and disease. The workshop was sponsored by the Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute and was held on September 16 to 18 in Bethesda, Maryland, in facilities provided by the American College of Cardiology. This report summarizes the presentations and discussions and presents recommendations for future studies.

Retention and clearance of C-11 palmitic acid in ischemic and reperfused canine myocardium.

Free fatty acids are the major energy source for cardiac muscle. Oxidation of fatty acid decreases or even ceases during ischemia. Its recovery after transient ischemia remains largely unexplored.

Sustained regional abnormalities in cardiac metabolism after transient ischemia in the chronic dog model.

Positron emission tomography allows noninvasive assessment of myocardial blood flow and metabolism, and may aid in defining the extent and severity of an ischemic injury. This hypothesis was tested by studying, in chronically instrumented dogs, regional blood flow and metabolism during and after a 3 hour balloon occlusion of the left anterior descending coronary artery. The metabolic findings after ischemia were compared with the recovery of regional function over a 4 week period.

Quantitative measurement of myocardial blood flow with oxygen-15 water and positron computed tomography: an assessment of potential and problems.

An in vivo measurement technique using 15O water and positron CT for quantitation of myocardial blood flow (MBF) was investigated. A closed-chest dog model and NeuroECAT scanner were used in the study. The in vivo technique involves i.

Positron computed tomography and its applications in the young.

Positron computed tomography is a new method for the external quantification of regional myocardial blood flow, substrate fluxes and biochemical reaction rates. It takes advantage of positron emitting tracers, metabolically active tracers, tracer kinetic principles and the quantitative imaging capabilities of the tomograph. To date, the technique has been used primarily for the study of ischemic heart disease and cardiomyopathies in adults.

Measurement of regional myocardial blood flow with N-13 ammonia and positron-emission tomography in intact dogs.

N-13 ammonia mimics certain properties of microspheres. It rapidly clears from blood into myocardium where it becomes fixed in proportion to myocardial blood flow. Used with positron emission tomography as a means for quantifying in vivo myocardial indicator concentrations, N-13 ammonia may be useful for noninvasive determination of myocardial blood flow with the arterial reference sampling technique.

Cardiac emission computed tomography: underestimation of regional tracer concentrations due to wall motion abnormalities.

Possible effects of regional wall motion abnormalities on apparent regional myocardial tracer concentrations on emission tomographic images were evaluated in six open chest dogs. Each dog was studied twice: In Run 1, 13N ammonia and microspheres were injected during a 6 min coronary occlusion, and serial images acquired by positron emission tomography during occlusion and reperfusion. In Run 2, 1 h later, 13N ammonia and microspheres were reinjected at control, and serial images recorded at control, during a repeat 6 min coronary occlusion, and after reperfusion.

Limitations of quantitative phase analysis of radionuclide angiograms for detecting coronary artery disease in patients with impaired left ventricular function.

Phase analysis of radionuclide ventriculograms is used for identifying ischemic wall motion abnormalities. Myocardial segments with an abnormal phase, that is, delayed onset of wall motion, can be localized on a phase distribution image, and the synchronicity of left ventricular (LV) wall motion can be assessed from a histogram of LV phase distribution. The standard deviation of the LV peak on this histogram (SDP-LV) describes the width of the peak and is used as an index of the synchronicity of wall motion.

Left ventricular stroke volume determinations from radionuclide ventriculograms: the effects of photon attenuation.

To improve the accuracy of scintigraphic ventricular volume determination, which is limited by photon attenuation between the heart and the gamma camera, a method was developed for directly measuring the photon attenuation of radioactivity delivered as a bolus through a Swan-Ganz catheter into the right atrium. Comparison of the count rate recovered from this bolus with the total ex vivo measured activity determined by imaging an aliquot of the administered activity allowed calculation of the attenuation factor. Left ventricular stroke volumes determined scintigraphically by the count method in gated blood pool studies and then corrected with this attenuation factor correlated well with stroke volumes determined from thermodilution cardiac output and heart rate (r = 0.

Primary hemochromatosis: anatomic and physiologic characteristics of the cardiac ventricles and their response to phlebotomy.

M-mode and 2-dimensional echocardiography and gated equilibrium blood pool imaging (rest and exercise) were used in 10 patients with primary hemochromatosis to characterize the spectrum of pathophysiologic abnormalities of the cardiac ventricles and to determine the response to chronic therapeutic phlebotomy. Dilated and restrictive cardiomyopathic patterns were identified in 1 patient each, but our data do not permit conclusions on when in the natural history a given pattern becomes overt. On entry into study, 3 patients had normal ventricles and 7 had ventricular abnormalities on echocardiography and blood pool angiography.

Regional myocardial dysfunction in patients with angina at rest and response to isosorbide dinitrate assessed by phase analysis of radionuclide ventriculograms.

Left and right ventricular synchrony was assessed in 15 patients with angina at rest but no previous infarction by phase analysis of equilibrium radionuclide ventriculograms. Transient thallium-201 perfusion defects were noted in all during angina at rest and coronary vasospasm was documented in nine of the patients. Radionuclide ventriculograms were performed at control, during the ischemic episodes and after intravenous isosorbide dinitrate.

Alterations in regional myocardial metabolism, perfusion, and wall motion in Duchenne muscular dystrophy studied by radionuclide imaging.

Studies at necropsy have shown that the cardiomyopathy of Duchenne muscular dystrophy selects the posterobasal and contiguous lateral left ventricular (LV) walls as initial and primary sites of myocardial dystrophy in the absence of small-vessel coronary artery disease in these areas. The present investigation was designed chiefly to determine whether a myocardial metabolic abnormality could be identified in these same areas during a patient's life. Positron emission computed tomography was used to study regional LV metabolism with 18F 2-fluorodeoxyglucose, and metabolism and/or perfusion was studied with 13NH3.

Myocardial blood flow and metabolism in humans.

Segmental reductions in blood flow together with segmental shifts in substrate metabolism from oxidation of fatty acids to aerobic and anaerobic usage of glucose, commonly associated with regional myocardial ischemia in humans, can now be assessed noninvasively with position emission tomography (PET). Characterization of metabolic rather than blood flow changes is superior for assessing tissue viability. Persistence of metabolic activity, though abnormal, in myocardial segments with reduced blood flow and function as detected by PET is associated with greater morbidity in patients post myocardial infarction and identifies in chronic ischemic heart disease injured but viable myocardium that benefits from surgical revascularization.

Measurements of regional tissue and blood-pool radiotracer concentrations from serial tomographic images of the heart.

Quantification of myocardial tissue kinetics from serial tomographic images is limited because of bidirectional cross-contamination of recorded counts between myocardium and blood for metabolic tracers with relative slow blood clearance. We have developed and validated a new deconvolution technique that permits calculation of spillover fractions derived from geometric measurements of the imaged cross section (wall thickness, chamber diameter) and the intrinsic resolution of the tomograph. Serial gated positron-emission computerized imaging (PCT) and a-v blood sampling across the heart were performed in five dogs for 45 min after i.

Synthesis and myocardial kinetics of N-13 and C-11 labeled branched-chain L-amino acids.

Glutamate dehydrogenase (GDH), immobilized on CNBr-activated Sepharose supports, was used with N-13 ammonia to aminate alpha-ketoisocaproic acid (KIC), and alpha-ketoisovaleric acid (KIV) to produce N-13-labeled branched-chain L-amino acids with radiochemical yields ranging from 29% to 35%. From kinetic and practical considerations, pH 7.5-8.

[Positron computed tomography: a new method for quantitative determination of cardiac metabolism, blood circulation and function. I. Technical and experimental bases].

Positron computed tomography represents a new method which permits qualitative and quantitative assessment of physiologic processes in different organs on a molecular basis. Thus this 'physiologic imaging device' enables noninvasive detection of regional myocardial metabolism, perfusion and global as well as regional myocardial function. The unique capability of simultaneous measurement of the interdependent parameters perfusion, metabolism and function will provide new insights in physiologic and pathophysiologic processes of the heart and, hence, in the understanding of heart disease.

Positron emission tomography. The technique and its applications to the study of the cardiovascular system.

The technical features of positron computed tomography are reviewed, and the positron-emitting tracers of flow and metabolism and their relation to physiologic processes are described. The authors report some of their clinical experience with this new modality and emphasize areas of pediatric disorders of the heart that are likely to benefit from positron computed tomography.