Blood flow-dependent uptake of indium-111 monoclonal antimyosin antibody in canine acute myocardial infarction.

OBJECTIVES: The relation of myocardial blood flow and indium-111 (111In) antimyosin antibody uptake was studied by inducing myocardial infarction in 18 dogs, 8 with closed chest left anterior descending artery balloon occlusion for 3 h followed by reperfusion (group A) and 10 dogs with open chest left anterior descending artery ligation (without reperfusion, group B). BACKGROUND: The relation of antimyosin uptake to myocardial injury has been documented. However, its relation to tracer delivery by myocardial blood flow has not been studied and has been assumed to be independent. METHODS: Indium-111 antimyosin antibody, 2 mCi, was injected 20 min after reperfusion and 3 h after coronary artery ligation in groups A and B, respectively. Regional blood flows were determined by radiolabeled microspheres during occlusion and 24 h later in both groups. On day 2, dogs were killed after risk zone delineation with gentian violet. The heart was excised and stained with triphenyltetrazolium chloride solution and graded for increasing severity of tissue injury based on extent of staining. Microsphere activity and 111In antimyosin activity were measured in control tissue (grade 1), noninfarct tissue at risk (grade 2), mixed tissue (grade 3), infarct tissue (grade 4) and hemorrhagic infarct tissue (grade 5, present only in group A dogs). Count activity was normalized to that of the mean value in control tissue (grade 1) and expressed as a ratio of activity. RESULTS: Indium-111 antimyosin activity was high in triphenyltetrazolium chloride grade 4 tissue in both groups but was attenuated in grade 4 tissue in group B dogs (10.6 +/- 5.1 vs. 5.0 +/- 4.5; p < 0.05 group A vs. group B), which had lower blood flow on day 2 (0.51 +/- 0.36 vs. 0.23 vs. 0.22; p < 0.01). Normalizing 111In antimyosin activity for blood flow on day 2 resulted in equivalent 111In antimyosin uptake for infarct tissue (32.6 +/- 21.6 vs. 36.6 +/- 29.8 for group A vs. group B; p = NS). CONCLUSIONS: Thus, 111In antimyosin uptake is a specific marker of necrotic tissue with a high signal ratio in reperfused tissue. However, its uptake is dependent on residual blood flow in the infarct territory. Indium-111 antimyosin could potentially serve as a suitable tracer for infarct sizing if myocardial blood flow in the same region were factored simultaneously.

Dipyridamole vasodilator response after human orthotopic heart transplantation: quantification by oxygen-15-labeled water and positron emission tomography.

To assess coronary vasodilator reserve after orthotopic heart transplantation, regional myocardial perfusion was measured with oxygen-15-labeled water and dynamic positron emission tomography in 14 cardiac allograft recipients who were not experiencing rejection and who had no angiographic evidence of epicardial coronary sclerosis 15 to 73 months (mean +/- SD 43 +/- 19) after transplantation (group I). Twelve normal men with an average age of 31 years (group II) served as a control group. Regional perfusion was measured at rest and after the intravenous administration of 0.6 mg/kg body weight of dipyridamole. Rest regional myocardial blood flow was homogeneously distributed throughout the left ventricle and was significantly higher in transplant recipients (mean 1.16 +/- 0.26 ml/g per min [range 0.8 to 1.73] than in normal subjects (mean 0.85 +/- 0.13 ml/g per min [range 0.57 to 0.99]; p = 0.001) as was rest heart rate-systolic blood pressure product (rate-pressure product 11,255 +/- 2,540 vs. 7,073 +/- 1,306; p less than 0.001). After dipyridamole, perfusion in the transplant recipients was homogeneous and slightly lower (2.73 +/- 1.03 vs. 3.40 +/- 1.09 ml/g per min; p = NS), whereas rate-pressure product was slightly higher (12,179 +/- 2,266 vs. 10,885 +/- 1,895; p = NS) than the value in normal subjects. Dipyridamole vasodilator response (dipyridamole/rest myocardial blood flow) ranged from 1.23 to 4.92 (mean 2.50 +/- 1.13) in group I and from 2.65 to 5.45 (3.97 +/- 0.89) in group II (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced myocardial 18F-2-fluoro-2-deoxyglucose uptake after orthotopic heart transplantation assessed by positron emission tomography.

OBJECTIVES: We sought to assess the relation between glucose metabolism, myocardial perfusion and cardiac work after orthotopic heart transplantation. BACKGROUND: The metabolic profile of the transplanted cardiac muscle is affected by the lack of sympathetic innervation, impaired inotropic function, chronic vasculopathy, allograft rejection and immunosuppressive therapy. In relation to myocardial perfusion and cardiac work, glucose metabolism has not previously been studied in heart transplant recipients. METHODS: Regional myocardial blood flow (ml.min-1.g-1) and 18F-2-fluoro-2-deoxyglucose (18FDG) uptake rate (ml.s-1.g-1) were measured after an overnight fast in 9 healthy male volunteers (mean age +/- SD 32 +/- 7 years) and in 10 male patients (mean age 50 +/- 10 years) who had a nonrejecting heart transplant, normal left ventricular function and no angiographic evidence of epicardial coronary sclerosis. Measurements were made by using dynamic positron emission tomography (PET) with 15O-labeled water and 18FDG, respectively. Heart rate and blood pressure were also measured for calculation of rate-pressure product. RESULTS: 18FDG uptake was similar in all heart regions in the patients and volunteers (intrasubject regional variably 12 +/- 8% and 16 +/- 12%, respectively, p = 0.51). Regional myocardial blood flow was similarly evenly distributed (intrasubject regional variability 14 +/- 10% and 12 +/- 8%, respectively, p = 0.67). Mean 18FDG uptake and myocardial blood flow values for the whole heart are given because no regional differences were identified. 18FDG uptake was on average 196% higher in the patients than in the volunteers (2.90 +/- 1.79 x 10(-4) vs. 0.98 +/- 0.38 x 10(-4) ml.s-1.g-1, p = 0.006). Regional myocardial blood flow and rate-pressure product were similarly increased in the patient group, but by only 41% (1.14 +/- 0.3 vs. 0.81 +/- 0.13 ml.min-1.g-1, p = 0.008) and 53% (11,740 +/- 2,830 vs. 7,689 +/- 1,488, p = 0.001), respectively. CONCLUSIONS: 18FDG uptake is homogeneously increased in normally functioning nonrejecting heart transplants. This finding suggests that glucose may be a preferred substrate in the transplanted heart. The magnitude of this observed increase is significantly greater than that observed for myocardial blood flow or cardiac work. In the patient group, the latter two variables were increased to a similar degree over values in control hearts, indicating a coupling between cardiac work load and myocardial blood flow. The disproportionate rise in 18FDG uptake may be accounted for by inefficient metabolic utilization of glucose by the transplanted myocardium or by the influence of circulating catecholamines, which may stimulate glucose uptake independently of changes in cardiac work load.

Improved uniformity in tomographic myocardial perfusion imaging with attenuation correction and enhanced acquisition and processing.

UNLABELLED: Tissue attenuation results in nonuniform myocardial perfusion images with significant sex differences. New SPECT imaging protocols to correct attenuation are currently under investigation. This study was performed to assess the effects of attenuation correction (AC) on overall image uniformity compared with more conventional imaging protocols in both men and women. METHODS: Thirty-nine patients (19 men, 20 women) with less than a 5% likelihood of coronary artery disease were studied. (99m)Tc-sestamibi studies were acquired with a triple-head scanner equipped with a simultaneous transmission and emission protocol. Four imaging protocols were compared: a 180 degrees acquisition and filtered backprojection reconstruction (FBP), a 360 degrees acquisition and FBP, a 360 degrees acquisition and iterative reconstruction (IT), and a 360 degrees acquisition with IT and AC. Quantitative analysis was performed to evaluate myocardial tracer uniformity for men and women. RESULTS: 180 degrees, 360 degrees FBP, and 360 degrees IT showed sex differences, with decreased tracer concentration in the anterior wall in women and decreased tracer concentration in the inferior wall in men. AC images showed the greatest uniformity (9.9% coefficient of variation for AC versus 12.5% for IT, P < 0.0001), and no statistically significant differences in uniformity were seen between male and female AC studies. CONCLUSION: More uniform myocardial perfusion images were obtained with AC, resulting in images with no differences in uniformity between men and women. These techniques are expected to improve specificity and overall diagnostic accuracy.

Hemodynamic indices of myocardial dysfunction correlate with dipyridamole thallium-201 SPECT.

UNLABELLED: Important differences in hemodynamics and tracer kinetics occur with dipyridamole compared to exercise scintigraphy. To better understand the clinical significance of dipyridamole SPECT 201Tl scintigraphy, we examined the relationships between scintigraphy and clinical, and angiographic and hemodynamic variables in patients with CAD. METHODS: Forty-nine subjects were divided into three study groups. Patients in Groups A (n = 11) and B (n = 20) had a low (<5%) likelihood of CAD. Group A underwent maximal exercise thallium stress testing. Group B underwent thallium dipyridamole scintigraphy. Group C (n = 18) consisted of patients with coronary artery disease who had dipyridamole thallium scintigraphy and cardiac catheterization within 2 wk. Thallium lung-to-myocardial ratio (L/M), left ventricular dilation and perfusion defect site were compared to hemodynamic, clinical and angiographic variables. RESULTS: The Group A L/M ratio of 0.23 +/- 0.05 (mean +/- 1 s.d.) was significantly lower (p < 0.001) compared to the Group B L/M ratio of 0.31 +/- 0.05. In Group C, the UM ratio showed correlation with indices of left ventricular dysfunction including lower resting ejection fraction (p = 0.02, r = 0.83), higher pulmonary capillary wedge pressure (p = 0.01, r = 0.58) and lower cardiac index (p = 0.03, r = 0.54). Left ventricular dilation was associated with hemodynamic changes of ventricular failure including lower resting ejection fraction (p = 0.008, r = 0.88) and higher pulmonary capillary wedge pressure (p = 0.02, r =0.54). Immediate and delayed perfusion defect size showed good correlation with lower resting left ventricular ejection fraction (p = 0.02, r = 0.83, and p = 0.004, r = 0.91, respectively). CONCLUSION: Lung uptake, left ventricular dilation and perfusion defect size show good correlation to hemodynamic indices of resting left ventricular dysfunction. A combination of these factors may be a better predictor of future cardiac events and prognosis.

Myocardial tissue fraction--correction for partial volume effects and measure of tissue viability.

We have compared two independent methods of correcting the systematic underestimation in measurements of myocardial radiotracer concentration due to wall motion and small transmural wall thickness in cardiac PET studies. The first technique was based on measurement of the tissue fraction by fitting 15O-labeled water dynamic PET data. The other technique involved the subtraction of the C15O-blood volume scan from the transmission data, producing an image of extravascular density. In normal myocardial regions, both values were observed to be about 60% of myocardial tissue density. The tissue fraction was approximately 10% larger than the extravascular density in normal tissue regions. The ratio of alpha/Dev indicates the proportion of the total extravascular tissue for a given ROI that is perfusable by water--independent of the partial volume effect. This ratio was confirmed to be the expected value in normal tissue regions but was reduced in regions of infarction. The use of 15O-water, C15O and transmission data may aid in the differentiation between perfusable and nonperfusable tissue in the infarcted myocardium.

Use of the left ventricular time-activity curve as a noninvasive input function in dynamic oxygen-15-water positron emission tomography.

Noninvasive recording of arterial input functions using regions of interest (ROIs) in the left ventricular (LV) chamber obviates the need for arterial cannulation in PET, but it is compromised by the limited recovery coefficient of the LV chamber and by statistical noise. In the present study, a new mathematical model has been developed, which corrects for the spillover of radioactivity both from the myocardium into the LV ROI and the blood into the myocardial ROI. The method requires the measurement of a time-activity curve in the LV chamber during the dynamic H2(15)O PET study and the measurement of the recovery coefficient of the LV ROI using a 15O-carbon monoxide (C15O) scan and venous blood sampling. This approach was successfully validated against direct measurements of the arterial input function using an on-line beta detector in five greyhounds undergoing dynamic H2(15)O PET imaging. This technique also yielded myocardial blood flow (MBF) values which were not significantly different from those obtained with the beta-probe analyses (maximum difference less than 2%), provided that the LV ROIs were sufficiently large to provide good counting statistics. When this model was not applied for large ROIs (small recovery in LV ROI), systematic overestimations in MBF compared with beta-probe analysis (e.g., a factor by 40% for a recovery coefficient of 0.7) were observed. Thus, this technique enabled the prediction of an accurate input function using the LV time-activity curve, and hence, noninvasive quantification of MBF without arterial cannulation.

Biodistribution and dosimetry of TRODAT-1: a technetium-99m tropane for imaging dopamine transporters.

UNLABELLED: Technetium-99m TRODAT-1 is an analog of cocaine that selectively binds the presynaptic dopamine transporters. The primary purpose of this study was to measure its whole-body biokinetics and radiation dosimetry in healthy human volunteers. The study was conducted within a regulatory framework that required its pharmacological safety to be assessed simultaneously. METHODS: The sample included 4 men and 6 women ranging in age from 22-54 yr. An average of 20 whole-body scans were acquired sequentially on a dual-head camera for up to 46 hr after the intravenous administration of 370+/-16 MBq (10.0+/-0.42 mCi) 99mTc TRODAT. The renal excretion fractions were measured from 12-24 discrete urine specimens. The fraction of the administered dose in 17 regions of interest and each urine specimen was quantified from the attenuation and background corrected geometric mean counts in conjugate views. Multiexponential functions were iteratively fit to each time-activity curve using a nonlinear, least squares regression algorithm. These curves were numerically integrated to yield source organ residence times. Gender-specific radiation doses were then estimated with the Medical Internal Radiation Dose technique for each subject individually before any results were averaged. RESULTS: There were no pharmacological effects of the radiotracer on any of the subjects. The early planar images showed differentially increased activity in the nose, pudendum and stomach. SPECT images demonstrated that the radiopharmaceutical localized in the basal ganglia in a distribution that was consistent with selective transporter binding. Image analysis showed that the kidneys excreted between 20% and 32% of the injected dose during the first 22-28 hr postadministration, after which no more activity could be recovered in the urine. The dose limiting organ in both men and women was the liver, which received an average of 0.046 mGy/MBq (0.17 rads/mCi, range 0.14-0.22 rad/mCi). In the worst case, which was clearly an over-estimation, it would have taken 22.7 mCi to deliver 5 rad to the liver. CONCLUSION: TRODAT may be a safe and effective radiotracer for imaging dopamine transporters in the brain and the body.

Beneficial effect of nitrates on myocardial glucose utilization in unstable angina pectoris.

Myocardial uptake of the glucose analog F-18-2-fluoro-2-deoxy-D-glucose (FDG) was assessed by positron emission tomography in 6 normal volunteers, 7 patients with chronic stable angina and 22 patients with unstable angina at rest in fasting conditions. Regional myocardial perfusion was assessed by rubidium-82. The study was repeated a few days later after intravenous infusion of isosorbide dinitrate. FDG uptake was similar in control subjects and patients with stable angina (0.023 +/- 0.032 vs 0.012 +/- 0.008 mol/ml/min, p less than 0.42) but was about 4-fold higher on the average in patients with unstable angina (0.084 +/- 0.047, p less than 0.01). The severity of coronary obstructions in stable and unstable angina patients was similar. The increased uptake involved the whole heart, including areas not distal to critically stenosed vessels; it was not associated with reduced myocardial perfusion and was not related to a recent episode of transient ischemia as assessed by symptoms and by Holter monitoring. After continuous infusion of nitrates, FDG uptake was consistently and significantly reduced toward normal levels both in areas perfused by critically stenosed coronary arteries and by noncritically stenosed vessels.

Comparison of regional myocardial blood flow in syndrome X and one-vessel coronary artery disease.

Myocardial blood flow (MBF) was measured using continuous inhalation of oxygen-15-labeled carbon dioxide, and positron emission tomography before and after intravenous dipyridamole in 13 patients with syndrome X (angina pectoris, angiographically normal coronary arteries, positive exercise test and negative ergonovine test), 7 healthy subjects and 8 patients with 1-vessel coronary artery disease (CAD). In patients with syndrome X, baseline MBF was greater than in healthy subjects and patients with CAD (1.24 +/- 0.27 vs 0.87 +/- 0.07 and 1.03 +/- 0.23 ml/g/min, respectively; p < 0.05), and more heterogeneous (34 +/- 7 vs 26 +/- 5 and 25 +/- 6, respectively; p < 0.05) as assessed by the coefficient of variation among myocardial regions < or = 2.3 cm3. After dipyridamole, MBF in patients with syndrome X was similar to that in healthy subjects (2.95 +/- 0.75 vs 3.40 +/- 0.82 ml/g/min; p = NS) and greater than in patients with CAD (1.78 +/- 0.76 ml/g/min; p < 0.05). However in patients with both syndrome X and CAD, MBF was more heterogeneous than in healthy subjects (48 +/- 12 and 48 +/- 11, respectively, vs 30 +/- 7; p < 0.01). Thus, in patients with syndrome X, MBF is abnormally heterogeneous both at baseline and after dipyridamole. These findings are compatible with the presence of dynamic alterations of small coronary arteries. Because these alterations appear to be very sparse within the myocardium, they can be undetected when myocardial perfusion, function and metabolism are assessed using conventional methods that are unable to detect small myocardial regions.

The hyperventilation test as a method for developing successful therapy in Prinzmetal's angina.

In 10 cases of Prinzmetal's angina in which episodes of myocardial ischemia were easily and reproducibly induced by hyperventilation, this test was performed 111 times, 41 times under control conditions and 70 times during treatment with one or more of the following drugs: phentolamine, isosorbide dinitrate, propranolol, verapamil, nifedipine and amiodarone. Seventeen of 18 negative tests performed under the influence of a long-acting drug coincided with total remission of the patient's anginal episodes when this drug was administered on a short- or long-term basis. No patient died or sustained infarction during a follow-up period of 10.9 months. A negative test was thus a good indication that the clinical response to the corresponding drug would be favorable. The electrocardiographic changes and chest pain provoked by hyperventilation occurred not when alkalosis was greatest (hydrogen ion [pH] change from 7.42 to 7.58, p less than 0.001), but when pH was approaching normal or control values. The onset of electrocardiographic changes occurred an average of 175 seconds after the end of hyperventilation and, in two cases, the time lag was as much as 480 and 705 seconds, respectively. This raises several questions regarding the true mechanism triggering coronary spasm under such conditions. The hyperventilation test appears to be a useful and safe procedure for selecting the best possible drug for long-term treatment of Prinzmetal's angina as well as for comparing the relative efficacy of different drugs.

Regional myocardial glucose metabolism in angina pectoris obtained from positron emission tomography.

This article presents a review of studies carried out with positron tomography on myocardial blood flow and glucose metabolism in patients with coronary artery disease and either stable (SA) or unstable angina (UA) pectoris. Regional blood flow was assessed with rubidium 82, an analogue of potassium, and glucose metabolism both with fluorine 18-labeled fluorodeoxyglucose (FDG) and carbon 11-labeled glucose (CG). There were no clear differences in regional myocardial blood flow between SA and UA patients and a group of normal volunteers. FDG uptake was low and homogeneous in both SA patients and normals. In contrast, all UA patients showed abnormally high FDG uptake in at least one left ventricular region at rest in the absence of symptoms or signs of acute ischemia. In the recovery from a period of exercise-induced angina, FDG uptake in SA patients was observed to be higher in previously ischemic regions than in nonischemic regions (as defined by 82Rb). It is postulated that higher FDG uptake in the postischemic myocardium of SA patients is due to repletion of glycogen stores. It remains unclear whether the high uptake in UA patients is due to a recent ischemic episode or is a reflection of a chronic adaptation to repeated stress.

F-18 FDG uptake in the large arteries: a new observation.

PURPOSE: The cellular components of the atherosclerotic plaque, such as macrophages, exhibits high glucose metabolic activity. The aim of this study was to show the frequency of vascular uptake and possibly to explain the significance of this finding on fluorodeoxyglucose (FDG) positron emission tomographic (PET) scans. METHODS: We evaluated the presence of FDG vascular uptake in 132 consecutive patients undergoing whole-body PET scans and 5 patients who had only lower extremity scans. The presence of vascular FDG uptake was assessed in the abdominal aorta, iliac, and proximal femoral arteries on the 132 whole-body scans, whereas only the femoral and the popliteal arteries were examined on the leg scans. The patients' ages ranged from 20 to 80 years, and they were divided into three age groups: 35 patients were younger than 40 years (group 1; mean age, 32.4 years), 48 patients were 41 to 60 years (group 2; mean age, 50.3 years), and 54 patients were older than 60 years (group 3; mean age, 70.3 years). RESULTS: Fifty percent (69 of 137) of the total population showed vascular FDG uptake in at least one vessel. Thirty-four percent (12 of 35) of group 1, 50% (24 of 48) of group 2, and 61% (33 of 54) of group 3 showed vascular wall uptake (P = 0.017 between groups 1 and 3). In addition, the correlation between the mean age of the age groups and the prevalence of FDG vascular uptake is strong (r = 0.99). CONCLUSIONS: Vascular FDG uptake is present in 50% of the patients examined for this study, with an increased prevalence in older patients. This vascular uptake might be explained by smooth muscle metabolism in the media, subendothelial smooth muscle proliferation from senescence, and the presence of macrophages within the atherosclerotic plaque. The relative contribution of these sources needs further investigation.

[Impact of the correction of the attenuation in myocardial perfusion image with SPECT]. / Impacto de la corrección de atenuación en la imagen de perfusión miocárdica con SPET.

BACKGROUND: The aim of this study was to assess the effect of attenuation correction on gender differences in normals and to evaluate its effect on the size and severity of lateral wall perfusion defects in patients with circumflex artery disease. MATERIAL AND METHODS: Tomographic myocardial perfusion imaging with and without attenuation correction was performed on 32 patients with circumflex artery stenosis and compared with patients with less than 5% likelihood of coronary disease. Images were acquired with a triple headed scanner and reconstructed using an iterative algorithm and re-sliced in the short axis plane. Regional count densities were measured on selected short axis slices from the base to the apex in both patients and normals. RESULTS: All attenuation corrected images were found to be more uniform than the non attenuation corrected images on the patients with less than 5% likelihood of coronary artery disease. The coefficient of variation was 12.5% for non attenuation corrected images versus 9.9% for attenuation corrected images (p < 0.0001). When female and male segmental count distributions were compared, significant differences were found which were resolved after attenuation correction. In patients with circumflex artery stenosis, the anterolateral and lateral count densities were lower at all levels with attenuation corrected images with an increasing difference from base to apex. CONCLUSIONS: The use of attenuation correction results in a greater uniformity in normals and an improved estimation of extent and severity of perfusion defects in the territory of the circumflex artery.

Whole heart distribution of myocardial perfusion, metabolism and myocardial viability by positron emission tomography.

The three dimensional evaluation of regional myocardial perfusion and metabolism of the whole left ventricular wall is now possible using the new generation of Positron Emission Tomography scanners (PET). We have used whole heart PET to study the metabolic consequences of transient myocardial ischaemia distal to critical coronary obstructions and to assess the viability of non contractile myocardium. At present whole heart PET should be considered a sophisticated technique for clinical research but its remarkable potential and further possible technical advances suggest its diagnostic application could be considered in the future, if justified on a cost benefit basis.

Physical aspects of cardiac scanning with a block detector positron tomograph.

Physical aspects relating to cardiac scanning are described for an eight ring (15 plane) positron tomograph consisting of BGO block detectors (CTI/Siemens 931-08/12). Performance parameters were derived from a cylindrical heart phantom having a "myocardial" wall of thickness varying from 3 mm to 27 mm. This phantom was inserted into a chest phantom consisting of simulated chest wall, lungs, and arms. Recovery coefficients for myocardial thicknesses of 10 mm and 15 mm were 0.75 and 0.9, respectively. Division by the transmission minus "blood pool" (extravascular density) image was found to give a variation of corrected myocardial counts within +/- 5% when transmission data were smoothed. The on-line dead time correction algorithm was found to be accurate to within 5% up to 20 mCi (740 MBq) in the axial field of view (FOV) (10.8 cm) in the central chamber of the heart phantom. However, the correction factor at this rate is approximately 3, which would imply poor use of administered dose. Counts in the image due to scatter are approximately 2% in the (cold) central cavity of the heart phantom relative to counts/pixel in the active myocardium. The presence of phantom arms in the FOV was found to have only a small effect on mean pixel counts and noise in the heart phantom image, as did movement of the arms within a reasonable range.

Measurement of regional myocardial blood flow using C15O2 and positron emission tomography: comparison of tracer models.

Eight different modifications of the same single tissue compartment model to measure myocardial blood flow, based on inhalation of 15O-labelled CO2 and positron emission tomography, were assessed in both dogs and human normal volunteers. Several models provided results with the same degree of accuracy in dogs. However, a number of these models gave poorer results in humans. It was established that the model containing components for blood flow, fraction of water exchanging tissue and spill-over arterial blood volume provided the most accurate and reproducible results. This model contains inherent corrections for the limited spatial resolution of positron emission tomographs. For ease of computation, linearisation of the operational (fitting) equation was tested, but found not to be satisfactory. The left atrium was slightly better than the left ventricle for determining the arterial input function. Inclusion of the blood volume term in the fitting procedure was significantly better than subtracting blood volume prior to analysis, both in terms of accuracy and precision.

Abnormalities in myocardial metabolism in patients with unstable angina as assessed by positron emission tomography.

Regional myocardial perfusion and glucose metabolism were assessed in six normal volunteers and 29 patients with coronary heart disease and stable or unstable angina using rubidium-82 (Rb-82) and F-18 fluoro 2-deoxy-D-glucose (FDG) with positron emission tomography. All normals and patients were studied following overnight fasting, at rest, with no angina or electrocardiographic signs of acute myocardial ischemia or necrosis. Rb-82 myocardial cross-sectional images were obtained employing the continuous infusion technique, while dynamic FDG imaging was employed after intravenous tracer bolus injection. Regional Rb-82 and FDG myocardial concentrations were then calculated by drawing regions of interest over the interventricular septum, anterior and lateral wall of the left ventricle. The mean Rb-82 uptake for each left ventricular region analyzed was found to be similar between both groups of patients and normal volunteers. The mean myocardial glucose utilization was found to be similar in normal volunteers and patients with stable angina (0.023 +/- 0.032 vs. 0.012 +/- 0.008 microns ml/min p less than 0.42). However, myocardial glucose utilization was found to be significantly higher in patients with unstable angina compared with both normals and patients with stable angina (0.048 +/- 0.047 microM/ml/min p less than 0.001 for both comparisons). Thus, in patients with severe coronary artery disease and unstable angina, myocardial glucose utilization was enhanced in spite of the absence of clinical, electrocardiographic, or detectable perfusion evidence of acute ischemia.