William J. MacIntyre

Prognosis of patients with left ventricular dysfunction, with and without viable myocardium after myocardial infarction. Relative efficacy of medical therapy and revascularization.

BackgroundThe uptake of F-18 deoxyglucose into dysfunction segments after myocardial infarction identifies metabolically active (FDG+) or inactive (FDG−) myocardium. Although patients with FDG+ segments have been found to be at risk for adverse events, the prognostic significance of viable myocardium in relation to other influences on postinfarction prognosis, including revascularization, remain ill defined. The purpose of this study was to investigate the relative prognostic significance of FDG+ tissue and to establish whether myocardial revascularization in patients with viable tissue attenuates the risk of adverse outcome. Methods and ResultsOne hundred thirty-seven patients with left ventricular dysfunction and resting perfusion defects after myocardial infarction underwent positron emission tomography with both dipyridamole stress Rb-82 perfusion imaging and FDG imaging. After the exclusion of 4 patients proceeding to transplantation, 2 with uninterpretable scans and 2 lost to follow-up, 129 patients were followed clinically for 17 ± 9 months. Four groups were defined: patients with FDG+ dysfunctional myocardium who were revascularized (n = 49) or treated medically (n = 21) and those with FDG− segments who were revascularized (n = 19) or treated medically (n = 40). The groups of patients with FDG+ or FDG− findings, with and without revascularization, did not differ with respect to known determinants of postinfarction prognosis: age, left ventricular ejection fraction, or the prevalence of multivessel disease. Nonfatal ischemic events occurred in 48% of medically treated FDG+ patients compared with 8% of revascularized patients with FDG+ tissue (P < .001) and 5% of patients with FDG- myocardium (P < .001). Thirteen patients died from cardiac causes; 11 (85%) had a left ventricular ejection fraction of < 30%, and these patients were evenly distributed between FDG+ and FDG− groups. Using Coxs proportional hazards model, only the presence of FDG+ myocardium (odds ratio, 12.9; P < .001) and the absence of revascularization (odds ratio, 5.8; P = .002) independently predicted ischemic events, while only age (P = .02) and ejection fraction (P < .001) but not the presence of viable myocardium were predictive of death. ConclusionsResidual viable myocardium after myocardial infarction may act as an unstable substrate for further events unless it is revascularized. Despite this association, age and left ventricular dysfunction remained the strongest predictors of cardiac death after myocardial infarction in these patients with a spectrum of left ventricular dysfunction.

Metabolic responses of hibernating and infarcted myocardium to revascularization. A follow-up study of regional perfusion, function, and metabolism.

Background The presence of persistent myocardial uptake of 188F-deoxyglucose (FDG) within hypoperfused, dysfunctional segments has been shown to predict the recovery of regional contractile function after revascularization. The spectrum of metabolic responses of such hibernating tissue to revascularization is less clear. Methods and Results Sixteen patients with previous infarction were studied before and after revascularization by myocardial perfusion imaging using 82Rb positron emission tomography, digitized twodimensional echocardiography, and imaging of postexercise FDG uptake. Hibernation was identified in 35 of 85 segments showing perfusion and wall motion disturbances before intervention. At follow-up (4.9±2.6 months after revascularization), hibernating segments were characterized by reduction of wall motion score (p < 0.001), improvement of perfusion (p < 0.001), and reduction of FDG activity (p < 0.00l). Of the 35 hibernating segments, however, 10 still had abnormal elevation of FDG uptake (>2 SD above normal) without differing from other hibernating segments with respect to postoperative perfusion or wall motion score. Segments with persistently abnormal metabolism were characterized before intervention by more severe malperfusion (p < 0.0l) and greater FDG activity (p < 0.0l). Conclusions Although wall motion and perfusion improve with revascularization of hibernating tissue, myocardial metabolism remains abnormal in a significant proportion of segments. These segments are characterized by more extensive perfusion and metabolic changes before revascularization.

Computed tomography of the thorax and abdomen; a preliminary report

The utility of computed tomography (CT) in the study of the anatomy, physiology, and pathology of the human body has been the subject of considerable interest since the introduction of CT scanning. The advent of a new prototype scanning device has made it possible to examine a variety of abnormalities in the abdomen and thorax in a manner not previously possible. This development permits a remarkable insight into the study of human disease in vivo.

Prediction by postexercise fluoro-18 deoxyglucose positron emission tomography of improvement in exercise capacity after revascularization.

The extent of ischemic and hibernating myocardium, which may be detected by increased postexercise uptake of fluoro-18 deoxyglucose (FDG) using positron emission tomography, may determine the degree of functional benefit after revascularization. This study examined the influence of the amount of this FDG-avid myocardium on changes in left ventricular function and exercise parameters after revascularization. Echocardiography and exercise testing were performed before and after intervention in 23 patients who had undergone positron emission tomography for the evaluation of myocardial perfusion (using rubidium-82), and postexercise FDG imaging in the fasting state. Follow-up echocardiography (22 +/- 14 weeks after revascularization) was compared with preoperative FDG activity in 7 myocardial regions per patient. Systolic function improved after intervention in 19 of 26 malperfused, dysfunctional FDG-avid regions (73%), and did not improve in 35 of 47 dysfunctional regions without increased FDG uptake (74%). The influence of the amount of FDG-avid tissue on changes in functional state was examined by comparing 9 patients with multiple (greater than or equal to 2) FDG-avid regions with the remainder. Those with multiple FDG-avid regions demonstrated improvement in peak rate-pressure product (20 +/- 4 to 26 +/- 4 x 10(3), p less than 0.02), and percentage of maximal heart rate achieved at peak (84 +/- 10% to 93 +/- 6%, p = 0.04), neither of which changed significantly in the remaining patients. Exercise capacity increased from 5.6 +/- 2.7 to 7.5 +/- 1.7 METS in the group with multiple FDG-avid regions; this increase of 55 +/- 18% exceeded the increase of 13 +/- 10% in the remainder (p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Radiopharmaceuticals for Brain Imaging

Brain imaging is performed using radiopharmaceuticals by single photon emission computed tomography (SPECT) and positron emission tomography (PET). SPECT and PET radiopharmaceuticals are classified according to blood-brain-barrier permeability, cerebral perfusion and metabolism receptor-binding, and antigen-antibody binding. The blood-brain-barrier (BBB) SPECT agents, such as 99mTcO4-, [99mTc]DTPA, 201TI and [67Ga]citrate are excluded by normal brain cells, but enter into tumor cells because of altered BBB. These agents were used in the earlier period for the detection of brain tumors. SPECT perfusion agents such as [123I]IMP, [99mTc]HMPAO, [99mTc]ECD are lipophilic agents and therefore, diffuse into the normal brain. These tracers have been successfully used to detect various cerebrovascular diseases such as stroke, Parkinson disease, Huntingtons disease, epilepsy, dementia, and psychiatric disorders. Xenon-133 and radiolabeled microspheres have been used for the measurement of cerebral blood flow (CBF). Important receptor-binding SPECT radiopharmaceuticals include [123I]QNE, [123I]IBZM, and [123I]iomazenil. These tracers bind to specific receptors in the brain, thus displaying their distribution in various receptor-related cerebral diseases. Radioiodinated monoclonal antibodies were used for the detection of brain tumors. PET radiopharmaceuticals for brain imaging are commonly labeled with positron-emitters such as 11C, 13N, 15O, and 18F, although other radionuclides such as 82Rb, 62Cu and 68Ga also were used. The brain uptake of [13N]glutamate, [68Ga]EDTA and [82Rb]RbCl depends on the BBB permeability, but these are rarely used for brain imaging. Several cerebral perfusion agents have been introduced, of which [15O]water, [13N]ammonia, and [15O]butanol have been used more frequently. Regional CBF has been quantitated by using these tracers in normal and different cerebral disease states. Other perfusion agents include [15O]O2, [11C]CO, [11C]CO2, [18F]fluoromethane, [15O]O2, [11C]butanol, and [62Cu]PTSM. Among the PET cerebral metabolic agents, [18F]fluorodeoxyglucose (FDG) is most commonly used to detect metabolic abnormalities in the brain. Various brain tumors have been graded by [18F]FDG PET. This technique was used to detect epileptic foci by showing increased uptake in the foci during the ictal period and decreased uptake in the interictal period. Differentiation between recurrent tumors and radiation necrosis and the detection of Alzheimers disease have been made successfully by [18F]FDG PET. Other PET metabolic agents such as [11C]deoxyglucose, and [11C]methylmethionine have drawn attention in the detection of brain tumors. [18F]fluorodopa is a cerebral neurotransmitter agent, which has been found very useful in the detection of Parkinson disease that shows reduced uptake of the tracer in the striatum of the brain.(ABSTRACT TRUNCATED AT 400 WORDS)

The incidence of scintigraphically viable and nonviable tissue by rubidium-82 and fluorine-18-fluorodeoxyglucose positron emission tomographic imaging in patients with prior infarction and left ventricular dysfunction

BackgroundAlthough reversible perfusion defects, perfusion-metabolism mismatch and match patterns are important for differentiating viable from nonviable myocardium, the frequency of these scintigraphic patterns has not been reported. The study objective was to establish the incidence of these scintigraphic patterns to estimate the clinical need for metabolic positron emission tomography for evaluating tissue viability in patients with prior myocardial infarction (MI).Methods and Results82Rb perfusion images were interpreted to identify reversible or irreversible defects, followed by determination of their 18F-fluorodeoxyglucose (18F-FDG) uptake pattern. In 155 patients with prior MI, analysis of 613 abnormal segments showed reversible perfusion defects in 13%. The 87% irreversible defects, 18% showed perfusion-metabolism mismatch, whereas 69% showed the match pattern. Reversible perfusion defects and perfusion-metabolism mismatches were noted in 20% (31/155) and 29% (45/155) of patients, respectively, whereas the match pattern was noted in 51% (79/155) of patients.ConclusionIrreversible perfusion defects were common in our patients with prior MI, and distinction between viable and nonviable tissue was not possible by perfusion imaging alone. The identification of hibernating myocardium was possible only with the additional 18F-FDG imaging in about one third of patients. This indicates a significant clinical demand for 18F-FDG imaging that identifies patients who will benefit from revascularization.

RADIOISOTOPE SCANNING IN HEPATIC CIRRHOSIS.

The primary application of radioisotope scanning technics to the liver has involved the differentiation of non-functioning masses from the normal functioning liver parenchyma (1, 2, 4, 7). In most cases, therefore, this technic has been concerned with the identification of primary and metastatic tumors. In the present study, attention has been focused not on visualization as an end in itself, but rather on what information radioisotope scanning can contribute to all other data available in the cirrhotic patient. With this object in mind, consideration must be given to what information scanning can provide. In Figure 1 four factors are observed that may contribute useful information. First, the outline of the liver may be seen. In addition, when there is normal distribution the actual size of the liver may be estimated by reconstructing the effective dimensions through measurement of the areas of the scan at three successive cut-off levels (13). Second, the position of the body wall is illustrated on the s...

White and Gray Matter of the Brain Differentiated by Computed Tomography

The white and gray matter of the brain can be clearly differentiated by computed tomography (CT). The differentiation is enhanced by the administration of contrast material. Without contrast material, the mean attenuation number of the white matter was 29 units, of the gray matter, 35 units. The effective low contrast resolving power of CT scanners can be clinically evaluated by comparing their ability to differentiate the white and gray matter of the brain.

Cyclotrons and positron emission tomography radiopharmaceuticals for clinical imaging

Positron emission tomography (PET) requires positron-emitting radionuclides that emit 511-keV photons detectable by PET imagers. Positron-emitting radionuclides are commonly produced in charged particle accelerators, eg, linear accelerators or cyclotrons. The most widely available radiopharmaceuticals for PET imaging are carbon-11-, nitrogen-13-, and oxygen-15-labeled compounds, many of which, either in their normal state or incorporated in other compounds, serve as physiological tracers. Other useful PET radiopharmaceuticals include fluorine-18-, bromine-75-, gallium-68 (68Ga)-, rubidium-82 (82Rb)-, and copper-62 (62Cu)-labeled compounds. Many positron emitters have short half-lives and thus require on-site cyclotrons for application, and others (68Ga, 82Rb, and 62Cu) are available from radionuclides generators using relatively long-lived parent radionuclides. This review is divided into two sections: cyclotrons and PET radiopharmaceuticals for clinical imaging. In the cyclotron section, the principle of operation of the cyclotron, types of cyclotrons, medical cyclotrons, and production of radionuclides are discussed. In the section on PET radiopharmaceuticals, the synthesis and clinical use of PET radiopharmaceuticals are described.

Venous delay, a major source of error in isotopic cardiac output determination

Abstract The high correlation reported for cardiac output determinations by 99m Tc-HSA has not held for other unselected series. To investigate possible causes, cardiac output was determined simultaneously by two indicators: 99m Tc-HSA and indocyanine green both injected by rapid flush technique, the 99m Tc via antecubital vein and the dye (DD) via superior vena cava. Precordial counting rates were obtained by scintillation camera and dilution curves were derived by computer program from selected areas in right (RV) and left ventricles (LV). Thirty consecutive studies showed significant (p 99m Tc and DD output but a determination index of only 66 per cent. Varying degrees of persistence of counting rate were noted in the subclavian region in the absence of demonstrable venous obstruction. In seven studies (Group I) there was no isotope hang-up in the subclavian region; in 17 (Group II), counts in the subclavian region persisted only through RV visualization, and in six studies (Group III) counts persisted even when radioactivity was at its peak concentration over LV. Correlation coefficients ( 99m Tc output with DD output) varied inversely with delay; r was 0.90 for Group I and Group II, and 0.64 for Group III (determination indices 81 per cent, 81 per cent, and 41 per cent, respectively). Results suggest that unexpected delay in arrival of radioactive bolus into the heart results in erratic distortion of cardiac output values. Unless monitored, delay often remains unsuspected; in a consecutive series of 63 99m Tc studies severe delay occurred in 16 per cent. The reason for the delay is not clear. It did not seem related to the speed of circulation, to the presence of venous obstruction, or to anatomical variations. It could not be related to the speed of injection or to the physical characteristics of the injectate.