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Biomedical subjects

H R Schelbert

Publications and source records attributed to H R Schelbert.

At least 163 records · Page 9Linked to original sources

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. We examined in this study the sensitivity of SDP-LV for identifying coronary artery disease (CAD) and its specificity in patients with normal and various degrees of LV impairment. A total of 84 patients were studied. Forty-five patients had CAD and 39 had congestive cardiomyopathy or valvular heart disease. Patients were grouped according to their LV ejection fraction (EF). In group I (37 patients) resting LVEF was equal to or greater than 50%, in group II (24 patients) it ranged from 35% to 50%, and in group III (23 patients) it was less than 25%. SDP-LV was highly specific in groups I and II for CAD with sensitivities of 48% and 89% at rest that increased with exercise to 88% and 100%. In group III patients, SDP-LV remained highly sensitive but was no longer specific for CAD. Therefore, in severe LV impairment, phase analysis does not aid in distinguishing CAD from other causes of ventricular dysfunction. By contrast, phase analysis is highly sensitive and specific for CAD in patients with normal or moderately depressed LV function.

Blood Pressure↗

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. Left and right ventricular phase histograms were quantified by the standard deviation from the mean of the peak (SD). Left ventricular ejection fraction averaged 65 +/- 11% (mean +/- standard deviation) at control, decreased in all patients during angina at rest to 49 +/- 14% (p less than 0.01) and increased in all patients after isosorbide dinitrate to 66 +/- 12%. However, ejection fraction during ischemia was abnormal in only nine patients and changed in two by less than 5% from the control value. Regional wall motion abnormalities were noted in all patients during the ischemic episodes but resolved after isosorbide dinitrate administration. Control left ventricular SD was 14.5 +/- 4 degrees, increased in all patients to 22.8 +/- 5 degrees during angina at rest (p less than 0.01) and returned to control values after isosorbide dinitrate administration (14.2 +/- 4 degrees). In contrast, right ventricular SD did not significantly change during ischemia as compared with control and isosorbide dinitrate. It is concluded that in angina at rest, a normal left ventricular ejection fraction does not exclude severe regional dysfunction; separate left and right ventricular SD is a sensitive index in detecting transient left ventricular dysfunction, and relief of ischemia is associated with rapid normalization of regional left ventricular function.

Adult↗

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 = 0.92; SEE, 6.1 ml). The agreement between the two measurements was markedly less when an average attenuation factor was employed for correction of scintigraphic volumes (r = 0.52; SEE, 14.8 ml). The results indicate that correction for photon attenuation is needed for accurate measurement of left ventricular volumes. Correction of left ventricular counts based on body weight or body surface area improves the accuracy of volume estimates.

Adult↗

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. In addition, all subjects had the following performed: thallium-201 scans, technetium-99m multiple-gated equilibrium blood pool imaging, electrocardiograms, vectorcardiograms, and M mode and two-dimensional echocardiograms. 18F 2-fluorodeoxyglucose activity was selectively increased in the posterobasal and posterolateral walls of the left ventricle in 11 of 12 patients with technically adequate images, indicating accelerated regional exogenous glucose utilization. 13NH3 activity was selectively decreased in the same areas in 13 of 15 patients, indicating either a regional metabolic alteration in uptake and trapping, a reduction in regional blood flow, or both. These data identify a myocardial metabolic abnormality concentrated in specific segments of the LV free wall in living patients with Duchenne dystrophy.

Adolescent↗

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. Segmental function was monitored with ultrasonic crystals, and 13N tissue concentrations determined in vivo from the tomographic images and postmortem by well counting. In Run 1, fractional shortening in ischemic segments fell by 89 +/- 16% SD from control. The ischemic versus control segment ratio for 13N activity concentrations averaged 0.29 +/- 0.08 and for microspheres 0.20 +/- 0.15. In Run 2 the ischemic versus control segment ratio was at control 0.77 +/- 0.12 for 13N tissue activity and 0.85 +/- 0.07 for microspheres. Fractional shortening fell during occlusion by 131 +/- 29% from control, returned to control early, and fell again by 11 +/- 16% late during reperfusion. These changes were paralleled by changes in apparent regional 13N tissue concentrations of the prelabeled myocardium. Compared with control, they were 37 +/- 9% lower during occlusion and rose to 94 +/- 20% early and to 89 +/- 16% at control late during reperfusion. In vitro determined tissue concentration ratios of ischemic to control myocardium were similar for 13N and microsphere activity (0.83 and 0.85), which ruled out loss of 13N ammonia from tissue during occlusion or reperfusion. Our results indicate that regional wall motion abnormalities cause artifactual segmental defects in tracer concentrations on emission tomographic images of the heart, which must be considered for qualitative and quantitative analysis of regional tracer tissue concentrations.

Ammonia↗

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. PET also detects persistent metabolic activity in acutely infarcted tissue and hence may guide interventions for salvaging injured myocardium.

Animals↗

Identification and differentiation of resting myocardial ischemia and infarction in man with positron computed tomography, 18F-labeled fluorodeoxyglucose and N-13 ammonia.

Studies have shown that the extraction of glucose per unit flow is increased in moderately ischemic myocardium primarily due to anaerobic glucose metabolism manifested as lactate production, whereas myocardial infarction is characterized by the loss of metabolically active myocardium. To determine the feasibility of demonstrating these metabolic abnormalities reflecting both ischemia and infarction, we used positron computed tomography (PCT) to evaluate relative regional myocardial exogenous glucose utilization and perfusion in 15 patients with recent myocardial infarction. The positron-emitting tracers of glucose metabolism and perfusion, 18F-2-fluoro-2-deoxyglucose (FDG) and N-13 ammonia, respectively, were used. Fourteen of 19 documented infarctions were demonstrated by PCT to have concordantly decreased glucose utilization and perfusion. However, in an additional 11 regions, glucose utilization was disproportionately increased relative to perfusion, consistent with ischemic glucose consumption. These findings correlated with the presence of postinfarction angina, the site of ischemic electrocardiographic changes during chest pain, and the presence of regional left ventricular dysfunction and severe coronary artery disease. Because three ECG infarct zones not detected by PCT demonstrated ischemic glucose utilization, only two of 19 electrocardiographically defined infarctions had no detectable metabolic abnormality. We conclude that the changes in regional FDG and N-13 ammonia concentrations detected with PCT in patients who had had a recent myocardial infarction are consistent with regional exogenous glucose utilization and perfusion in moderately ischemic and irreversibly infarcted myocardium. This approach has the potential to identify and differentiate resting myocardial ischemia from infarction and to assess tissue viability after an ischemic event.

Adult↗

Positron computed tomography for studies of myocardial and cerebral function.

Positron computed tomography is a noninvasive medical imaging technique. Biologically active, radiolabeled compounds are administered intravenously to patients and the distribution of the radioactivity is quantitatively measured. By using appropriate mathematical models and labeled compounds, quantitative measurements of local metabolism, blood flow and volume, protein synthesis, transport, receptor binding, drug kinetics, and concentrations can be obtained noninvasively. This technique goes beyond medical imaging; it allows local analytic assays of biochemical reactions. In the heart, the technique measures local blood flow as well as myocardial free fatty acid and glucose metabolism, and can clinically evaluate patients with ischemic heart disease or cardiomyopathies. In the brain, positron computed tomography can be used to examine alterations in blood flow and metabolism including ischemia and degenerative disorders (Huntington's disease and Alzheimer's disease), cerebral tumors, and epilepsy. In normal persons, positron computed tomography shows cerebral activations resulting from physiologic stimulation (auditory and visual).

Alzheimer 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.

Acetates↗

[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. Since a great number of cardiac disorders is related to disturbances at the cellular and metabolic level, this new method may contribute to the early detection and eventually to an early treatment of heart disease. With improvements in instrumentation as well as the development of new physiologic indicators and small generator-like cyclotrons, positron computed tomography will become clinically more widespread in various medical centers.

Amino Acids↗

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.v. C-11 palmitate (CPA) and in five dogs for 3 hr after i.v. F-18 deoxyglucose (FDG). Tracer concentrations in myocardial tissue and arterial blood were also measured in vitro. Uncorrected PCT tissue and blood concentrations correlated poorly with in vitro measurements. After correction for count crossover, the correlation for FDG in tissue was r = 0.99, for FDG in blood r = 0.97, and for CPA in blood r = 0.99. Deconvolution techniques applied to serial PCT images provide accurate noninvasive measurement of myocardial tracer concentrations and direct determination of the arterial input function required for measurements of myocardial metabolism.

Animals↗

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 7.5-8.0 was established to be optimal for the synthesis of N-13-labeled branched-chain-L-amino acids. Myocardial time-activity curves in dogs at control, during low-flow ischemia, reperfusion, and after transaminase inhibition following intracoronary bolus injection of the N-13-labeled amino acids were biexponential. Higher retention of N-13 activity was observed in ischemic segments both during low-flow ischemia (29.2%) and reperfusion (23.2%) when compared with controls (20.0%), (n = 4). On the other hand, transaminase inhibition decreased residue fractions from 21.0% at control to 13.9% (n = 4). The residual activity with L-[1-11C]leucine allows for the calculation of protein synthesis rates.

Amino Acids, Branched-Chain↗

Noninvasive assessment of coronary stenoses by myocardial imaging during pharmacologic coronary vasodilation. VI. Detection of coronary artery disease in human beings with intravenous N-13 ammonia and positron computed tomography.

The possibility of detecting mild coronary stenoses with positron computed tomography and nitrogen (N-13) ammonia administered during pharmacologic coronary vasodilation was previously demonstrated in chronically instrumented dogs. The feasibility of using this technique in human beings and its sensitivity in determining the degree and extent of coronary artery disease were examined in 13 young normal healthy volunteers and 32 patients with angiographically documented coronary artery disease. N-13 ammonia was administered intravenously and its distribution in the left ventricular myocardium recorded at rest and during dipyridamole-induced coronary hyperemia. In the 13 volunteers, N-13 activity was homogeneous at rest and during hyperemia, whereas 31 of the 32 patients had regional defects on the hyperemic images not present during rest. All six patients with double, all 10 with triple and 15 of 16 patients with single vessel disease (97 percent) were correctly identified with the technique. Two vessel involvement was correctly identified in five of the six patients with double vessel disease and three vessel disease in six of 10 patients. Of all 58 coronary stenoses, 52 (90 percent) were correctly identified. In a subgroup of 11 patients, the technique was compared with exercise thallium-201 planar images, which were abnormal in 10 (91 percent) whereas N-13 images were abnormal in all 11. Of the 19 stenosed coronary arteries in this subgroup, 11 (58 percent) were correctly identified with thallium-201 and 17 (89 percent) with tomography (p less than 0.01). It is concluded that cross-sectional imaging of the myocardial distribution of N-13 ammonia administered during pharmacologic coronary vasodilation is a highly sensitive and accurate means for noninvasive detection of coronary stenoses in human beings and for estimating the extent of coronary artery disease.

Adolescent↗