Myocardial Blood Flow Imaging Research Articles

Genotoxicity of Thallium-201 in Patients with Angina Pectoris Undergoing Myocardial Perfusion Study

Thallium-201 (201Tl) has been widely used as a nuclear reagent for myocardial blood flow imaging. The purpose of this study was to investigate genotoxic effects of 201Tl in patients with angina pectoris (n = 21), who had undergone myocardial perfusion imaging. Lymphocytes were isolated from each patient before, and 3, 30 and 90 days after 201Tl administration (111 MBq, 3 mCi) and were analyzed for chromosomal aberrations, sister chromatid exchanges, mitotic index and replicative index. There were significant increases in chromosomal aberrations and sister chromatid exchanges 3 days after 201Tl administration (p < 0.001), although no difference was noted in these values after 30 and 90 days (p > 0.05). Moreover, decreased mitotic index and replicative index were noted after 3 days of 201Tl administration (p < 0.001). These results suggest that the administration of 201Tl for myocardial blood flow imaging may induce genetic damage.

Real-time myocardial blood flow imaging in normal human beings with the use of myocardial contrast echocardiography

Triggered myocardial contrast echocardiography (MCE) has been used successfully to quantify myocardial blood flow and assess coronary stenosis in animal models, but practical considerations have limited its broad clinical use. Real-time MCE may have practical advantages to assess perfusion and real time myocardial blood flow in human beings. We compared real-time MCE with triggered imaging in 23 normal human volunteers by using an investigational ultrasound contrast agent (DMP-115) and a commercially available ultrasound platform (Acuson Sequoia). Peak myocardial opacification (reflecting myocardial blood volume) after contrast infusion was quantified digitally in gray scale units (GU). In 13 subjects, myocardial blood flow reserve was assessed during dipyridamole infusion with the use of intermittent destruction-replenishment techniques. Real-time MCE resulted in a 30- to 45-GU increase from baseline compared with a 20- to 70-GU increase with triggered imaging. Real-time MCE showed no statistical difference in opacification ( P = .131 by analysis of variance) among any of the myocardial regions of interest. Triggered imaging resulted in heterogeneous opacification among the regions of interest ( P < .05 by analysis of variance). Dipyridamole did not significantly change peak myocardial opacification (myocardial blood volume) for either technique. Quantification of flow reserve revealed that myocardial blood flow reserve for the dipyridamole group was 3.6 ± 0.4 (mean ± 1 standard error of the mean). Real-time MCE is feasible in normal human volunteers and provides homogenous opacification of the myocardium. Furthermore, quantification of myocardial blood flow with real-time MCE in normal human beings produces results that are consistent with the known physiology of the coronary microcirculation. (J Am Soc Echocardiogr 2001;14:698-705.)

Comparison of thallium-201 SPECT redistribution patterns and rubidium-82 PET rest-stress myocardial blood flow imaging

To compare regional thallium-201 SPECT redistribution patterns with rubidium-82 PET, we studied 81 patients with both imaging modalities. Sixty patients had significant coronary artery disease. All patients underwent PET imaging after dipyridamole infusion, while SPECT imaging was performed after exercise stress (38 patients) and dipyridamole (43 patients). Sixty-eight percent of patients with prior infarct had fixed defects on SPECT, compared to 39% with PET. Sixty-one percent of patients with prior infarct had PET perfusion defects which exhibited 'reflow' or normal rubidium-82 tracer uptake (p < 0.05 vs. SPECT). Similar results were seen in patients without prior infarct (26% fixed defects on SPECT vs. 12% for PET, p < 0.05). Regional analysis showed that 57% of fixed SPECT defects corresponded to PET defects with reflow or normal rubidium-82 uptake, while 78% of 'fixed' PET defects corresponded to fixed SPECT defects. PET reflow and normal rubidium-82 uptake in sites of fixed thallium-201 SPECT perfusion defects suggest that imaging modalities employing separate tracer injections at rest and after stress, such as rubidium-82 PET, may be more specific in the assessment of myocardial viability, especially in patients with prior myocardial infarction.

Noninvasive assessment of cardiac diabetic neuropathy by carbon-11 hydroxyephedrine and positron emission tomography

Objectives. The purpose of this investigation was to evaluate the sympathetic nervous system of the heart by positron emission tomographic (PET) imaging in patients with diabetes mellitus with and without diabetic autonomic neuropathy.Background. The clinical assessment of cardiac involvement in diabetic autonomic neuropathy has been limited to cardiovascular reflex testing. With the recent introduction of radiolabeled catecholamines such as carbon (C)-11 hydroxyephedrine, the sympathetic innervation of the heart can be specifically visualized with PET imaging.Methods. Positron emission tomographic imaging was performed with C-11 hydroxyephedrine and rest myocardial blood flow imaging with nitrogen-13 ammonia. Three patient groups were studied, including healthy volunteers as control subjects, diabetic patients with normal autonomic function testing and diabetic patients with varying severity of autonomic neuropathy. Homogeneity of cardiac tracer retention as well as absolute tracer retention was determined by relating myocardial tracer retention to an arterial C-11 activity input function.Results. Abnormal regional C-11 hydroxyephedrine retention was seen in seven of eight patients with autonomic neuropathy. Relative tracer retention was significantly reduced in apical, inferior and lateral segments. The extent of the abnormality correlated with the severity of conventional markers of autonomic dysfunction. Absolute myocardial tracer retention index measurements showed a 45 ± 21% decrease in distal compared with proximal myocardial segments in autonomic neuropathy (0.069 ± 0.037 min−1vs. 0.13 ± 0.052 min−1, p = 0.02).Conclusions. This study demonstrates a heterogeneous pattern of neuronal abnormalities in patients with diabetic cardiac neuropathy. The extent of this abnormality correlated with the severity of neuropathy assessed by conventional tests. Future studies in larger groups of patients are required to define the relative sensitivity of this imaging approach in detecting cardiac neuropathy and to determine the clinical significance of these scintigraphic findings in comparison with conventional markers of autonomic innervation.

Comparison of maximal myocardial blood flow during adenosine infusion with that of intravenous dipyridamole in normal men

Objective. This study compared quantitatively the efficacy of intravenous adenosine and dipyridamole for pharmacologic induction of myocardial hyperemia.Background. Pharmacologic vasodilation is used increasingly for induction of myocardial hyperemia in conjunction with radionuclide imaging of myocardial blood flow. Although both intravenous dipyridamole and adenosine have been used, the magnitude of hyperemia induced by these agents and the hyperemia to baseline blood flow ratios have not been quantified and compared.Methods. Twenty normal volunteers were studied with dynamic positron emission tomography (PET) and intravenous nitrogen-13 ammonia. Myocardial blood flow was quantified with a two-compartment tracer kinetic model.Results. Myocardial blood flow at rest averaged 1.1 ± 0.2 ml/min per g and increased significantly to 4.4 ± 0.9 ml/min per g during adenosine and 43 ± 1.3 ml/min per g after dipyridamole administration. Hyperemia to baseline flow ratios averaged 4.3 ± 1.6 for adenosine and 4.0 ± 1.3 for dipyridamole. The average flow ratios and the maximal flows achieved were similar for both agents, but there was considerable variation in the individual response to these agents, as indicated by the range of hyperemia to baseline flow ratios (from 2.0 to 8.4 for adenosine and from 1.5 to 5.8 for dipyridamole). in addition, the hyperemic responses to dipyridamole and to adenosine differed by > 1 ml/min per g in nine subjects.Conclusions. Despite these inter- and istraindividual differences, we conclude that both agents are equally effective in producing myocardial hyperemia.

Mechanisms of uptake of thallium-201 and two technetium-99m-labeled myocardial blood flow imaging agents: Study in cultured myocardial cells and in cardiac membranes

Mechanisms of uptake of thallium-201 and two technetium-99m-labeled myocardial blood flow imaging agents: Study in cultured myocardial cells and in cardiac membranes

Noninvasive Evaluation of Angina Pectoris

There is a sturdy body of evidence that exercise radionuclide studies are both more sensitive and more specific than the exercise ECG in the diagnosis of suspected coronary disease. The two major radionuclide diagnostic-prognostic techniques used for coronaiy disease—perfusion imaging of myocardial blood flow and cardiac blood-pool imaging—are reviewed.

A comparison between T1–201 and two new Tc-99m labeled myocardial blood flow imaging agents in cultures of cardiac cells: P. Gachon, N. Moins, M. Renoux, J. Maublant. INSERM U.195 and Centre Jean Perrin, University of Clermont-Ferrand, Clermont-Ferrand, France

A comparison between T1–201 and two new Tc-99m labeled myocardial blood flow imaging agents in cultures of cardiac cells: P. Gachon, N. Moins, M. Renoux, J. Maublant. INSERM U.195 and Centre Jean Perrin, University of Clermont-Ferrand, Clermont-Ferrand, France

N-13 ammonia as an indicator of myocardial blood flow.

SUMMARY We have characterized N-13 ammonia as a myocardial blood flow imaging agent suitable for positron-emission computed tomography. However, the mechanisms of uptake and retention of this agent in myocardium are not known, and effects of altered metabolism were not considered. Therefore, we studied the uptake and retention of N-13 ammonia in myocardium under various hemodynamic and metabolic conditions in open-chest dogs. N-13 ammonia was extracted nearly 100% during its initial capillary transit, followed by metabolic trapping that competed with flow-dependent back diffusion. At control flows, the first capillary transit extraction fraction (E) of N-13 ammonia averaged 0.82 ± 0.06. It fell with higher flows by E = 1 − 0.607 exp − 125/F. Myocardial N-13 tissue clearance half-times were similarly inversely related to blood flow, and ranged from 110–642 minutes. Cardiac work and changes in the myocardial inotropic state induced by isoproterenol and propranolol did not affect E or the tissue clearance half-times. Low plasma pH reduced E by an average of 20%, while elevated plasma pH had no effect. Decreases in flow below control also were associated with a fall in E. Inhibition of glutamine synthetase with L-methionine sulfoximine impaired metabolic trapping of N-13 ammonia and implicates the glutamic acid-glutamine reaction as the primary mechanism for ammonia fixation. The product of E times flow predicts the myocardial N-13 tissue concentrations, which increased by 70% when flow was doubled. Thus, blood flow and metabolic trapping are the primary determinants of myocardial uptake and retention of N-13 ammonia. The relative constancy of metabolic trapping over a wide range of hemodynamic and metabolic conditions demonstrates the value of N-13 ammonia as a myocardial blood flow imaging agent.