OBJECTIVES:The purpose of this study was to determine if combined intense lifestyle and pharmacologic lipid treatment reduce myocardial perfusion abnormalities and coronary events in comparison to usual-care cholesterol-lowering drugs and whether perfusion changes predict outcomes. BACKGROUND:Lifestyle and lipid drugs separately benefit patients with coronary artery disease (CAD). METHODS:A total of 409 patients with CAD, who underwent myocardial perfusion imaging by dipyridamole positron emission tomography at baseline and after 2.6 years, had quantitative size/severity of perfusion defects measured objectively by automated software with follow-up for five additional years for coronary artery bypass graft, percutaneous coronary intervention, myocardial infarction, or cardiac death. Patients were categorized blindly according to prospective, predefined criteria as "poor" treatment without diet or lipid drugs, or smoking; "moderate" treatment on American Heart Association diet and lipid-lowering drugs or on strict low-fat diet (<10% of calories) without lipid drugs; and "maximal" treatment with diet <10% of calories as fat, regular exercise, and lipid active drugs dosed to target goals of low-density lipoproteins <2.3 mmol/l (90 mg/dl), high-density lipoproteins >1.2 mmol/l (45 mg/dl), and triglycerides <1.1 mmol/l (100 mg/dl). RESULTS:Over five years, coronary events occurred in 6.6%, 20.3%, and 30.6% of patients on maximal, moderate, and poor treatment, respectively (p = 0.001). Size/severity of perfusion abnormalities significantly decreased for patients receiving maximal treatment and increased for patients undergoing moderate and poor treatment (p = 0.003 and 0.0001, respectively). Combined intense lifestyle change plus lipid active drugs and severity/change of perfusion abnormalities independently predicted cardiac events. CONCLUSIONS:Intense lifestyle and pharmacologic lipid treatment reduce size/severity of myocardial perfusion abnormalities and cardiac events compared with usual-care cholesterol-lowering drugs. Perfusion changes parallel treatment intensity and predict outcomes.

To map precise myocardial perfusion anatomy, we correlated detailed coronary arteriographic anatomy for every coronary artery and all secondary branches in the heart that had flow-limiting stenosis with corresponding specific, circumscribed, myocardial perfusion defects by positron emission tomography. Eight hundred ninety-five patients with abnormal coronary arteriograms showing any visible coronary artery narrowing of greater than 10% diameter stenosis underwent positron emission tomography perfusion imaging at rest and after dipyridamole stress; the data obtained were processed automatically into 3-dimensional topographic displays of relative radionuclide uptake in anterior, septal, left lateral, and inferior quadrant views, without attenuation artifacts, depth-dependent resolution, or spatial distortion of polar displays. The selection criterion for detailed anatomic analysis was the presence of a discrete, localized, moderate to severe, dipyridamole-induced perfusion defect, defined by automated algorithms as 1 quadrant view outside 2 SDs of healthy control subjects with which a specific stenotic coronary artery and/or its secondary branches could be correlated unequivocally on the coronary arteriogram for mapping precise perfusion anatomy, not for determining sensitivity or specificity.Because the anatomy of myocardial perfusion is inherently not statistical data, the results are presented as a summary atlas and series of individual cases that illustrate myocardial perfusion anatomy. Because the patterns of myocardial perfusion anatomy were derived from a large number of subjects, the atlas provides generalized information, not previously published, that correlates detailed arteriographic anatomy with perfusion anatomy including secondary diagonal, marginal, and posterior descending branches of the coronary arteries.

BACKGROUNDDiffuse coronary atherosclerosis is the substrate for plaque rupture and coronary events. Therefore, in patients with mild arteriographic coronary artery disease without significant segmental dipyridamole-induced myocardial perfusion defects, we tested the hypothesis that fluid dynamically significant diffuse coronary artery narrowing is frequently manifest as a graded, longitudinal, base-to-apex myocardial perfusion abnormality by noninvasive PET.METHODS AND RESULTSIn this study, 1001 patients with documented coronary artery disease by coronary arteriography showing any visible coronary artery narrowing underwent rest-dipyridamole PET perfusion imaging. Quantitative severity of dipyridamole-induced, circumscribed, segmental PET perfusion defects was objectively measured by automated software as the minimum quadrant average relative activity indicating localized flow limiting stenoses. Quantitative severity of the graded, longitudinal, base-to-apex myocardial perfusion gradient indicating fluid dynamic effects of diffuse coronary artery narrowing was objectively measured by automated software as the spatial slope of relative activity along the cardiac longitudinal axis.CONCLUSIONSIn patients with mild arteriographic disease without statistically significant dipyridamole-induced segmental myocardial perfusion defects caused by flow-limiting stenoses compared with normal control subjects, there was a graded, longitudinal, base-to-apex myocardial perfusion gradient significantly different from normal control subjects (P=0. 001) that was also observed for moderate to severe dipyridamole-induced segmental perfusion defects (P=0.0001), indicating diffuse disease underlying segmental perfusion defects; 43% of patients with or without segmental perfusion defects demonstrated graded, longitudinal, base-to-apex perfusion abnormalities beyond +/-2 SD of normal control subjects, indicating diffuse coronary arterial narrowing by noninvasive PET perfusion imaging.

UNLABELLED:The Simple and Patlak models for estimating myocardial blood flow with 13N-ammonia have become attractive for clinical applications with PET because of their simplicity and ease of implementation. However, these models are sensitive to factors such as the data acquisition times and data integration times, which can cause errors in the estimation of myocardial blood flow, as demonstrated in this study. Limiting the application of these models to specific conditions can minimize the errors.METHODS:Dynamic PET images of the uptake of 13N-ammonia in the heart were obtained in seven humans under rest and dipyridamole stress. Myocardial blood flow was estimated using the Simple and Patlak models for different data acquisition times and data integration times. Blood flow values were compared to flow values computed with the two-compartment model as a reference.RESULTS:Blood flow values calculated with the Simple and Patlak models during the first 2 min of data acquisition were closely correlated to the two-compartment model values. Longer acquisition times resulted in significant underestimation of blood flow for the Simple model. Long integration times of greater than 60 sec also resulted in significant underestimation of blood flow for both models.CONCLUSION:The Simple and Patlak models produce estimates of myocardial blood flow that are well correlated with the two-compartment model estimated blood flows for the integration time of 60 sec from 60 to 120 sec postinjection. Because of the errors associated with longer data acquisition times and longer integration times, use of these models should be limited to a well-documented data acquisition paradigm.

UNLABELLEDTo validate routine, noninvasive determination of absolute myocardial perfusion and coronary flow reserve (CFR), cardiac PET was performed in animals using a simplified imaging protocol, high-dose dipyridamole and a simplified quantitative algorithm specific for 82Rb and 13N-ammonia.METHODSOne hundred thirty-five PET scans were obtained in eight dogs after intravenous 13N-ammonia or 82Rb using serial dynamic PET or a simple two-image dataset. A simple flow model using the two-image dataset was developed for each radionuclide to account for varying arterial input function, flow-dependent myocardial extraction and increased permeability surface area (PS) product due to capillary recruitment at high flows not incorporated into previous models. Myocardial perfusion by the simple model was compared to standard, complete, two-compartment kinetic models validated by comparison to electromagnetic flow meter.RESULTSFor 13N-ammonia, myocardial perfusion by the simple PET model correlated with that by complete compartmental analysis of multiple serial PET images with r = 0.94, slope = 0.96; CFR by compartmental analysis correlated with CFR by electromagnetic flow meter with r = 0.94, slope = 0.97. For 82Rb, myocardial perfusion determined by the simple model correlated with that determined by complete compartmental analysis of multiple serial PET images with r = 0.98, slope = 1.06; CFR determined by compartmental analysis correlated with CFR by electromagnetic flow meter with r = 0.88, slope = 1.13.CONCLUSIONA simplified PET protocol using 13N-ammonia or 82Rb and simple flow models provide noninvasive measurement of CFR up to six times baseline flow throughout the heart and diagnostic image quality for routine clinical application.

Despite the widespread abuse of marijuana, knowledge about its effects in the human brain is limited. Brain glucose metabolism with and without delta 9 tetrahydrocannabinol (THC) (main psychoactive component of marijuana) was evaluated in eight normal subjects and eight chronic marijuana abusers with positron emission tomography. At baseline, marijuana abusers showed lower relative cerebellar metabolism than normal subjects. THC increased relative cerebellar metabolism in all subjects, but only abusers showed increases in orbitofrontal cortex, prefrontal cortex, and basal ganglia. Cerebellar metabolism during THC intoxication was significantly correlated with the subjective sense of intoxication. The decreased cerebellar metabolism in marijuana abusers at baseline could account for the motor deficits previously reported in these subjects. The activation of orbitofrontal cortex and basal ganglia by THC in the abusers but not in the normal subjects could underlie one of the mechanisms leading to the drive and the compulsion to self-administer the drug observed in addicted individuals.

OBJECTIVE:To quantify changes in size and severity of myocardial perfusion abnormalities by positron emission tomography (PET) in patients with coronary artery disease after 5 years of risk factor modification.DESIGN:Randomized controlled trial.SETTING:Outpatient community setting.INTERVENTION:Randomization of patients to risk factor modification consisting of very low-fat vegetarian diet, mild to moderate exercise, stress management, and group support (experimental group, n = 20) or to usual care by their own physicians, consisting principally of antianginal therapy (control group, n = 15).MAIN OUTCOME MEASURES:Quantitative coronary arteriography and PET at baseline and 5 years after randomization. Automated, objective measures of size and severity of perfusion abnormalities on rest-dipyridamole PET images and of stenosis severity on arteriograms were made by computer algorithms.RESULTS:Size and severity of perfusion abnormalities on dipyridamole PET images decreased (improved) after risk factor modification in the experimental group compared with an increase (worsening) of size and severity in controls. The percentage of left ventricle perfusion abnormalities outside 2.5 SDs of those of normal persons (based on 20 disease-free individuals) on the dipyridamole PET image of normalized counts worsened in controls (mean +/- SE, + 10.3% +/- 5.6%) and improved in the experimental group (mean +/- SE, -5.1% +/- 4.8%) (P = .02); the percentage of left ventricle with activity less than 60% of the maximum activity on the dipyridamole PET image of normalized counts worsened in controls (+13.5% +/- 3.8%) and improved in the experimental group (-4.2% +/- 3.8%) (P = .002); and the myocardial quadrant on the PET image with the lowest average activity expressed as a percentage of maximum activity worsened in controls (-8.8% +/- 2.3%) and improved in the experimental group (+4.9% +/- 3.3%) (P = .001). The size and severity of perfusion abnormalities on resting PET images were also significantly improved in the experimental group as compared with controls. The relative magnitude of changes in size and severity of PET perfusion abnormalities was comparable to or greater than the magnitude of changes in percent diameter stenosis, absolute stenosis lumen area, or stenosis flow reserve documented by quantitative coronary arteriography.CONCLUSIONS:Modest regression of coronary artery stenoses after risk factor modification is associated with decreased size and severity of perfusion abnormalities on rest-dipyridamole PET images. Progression or regression of coronary artery disease can be followed noninvasively by dipyridamole PET reflecting the integrated flow capacity of the entire coronary arterial circulation.

Positron emission tomography with 18F-deoxyglucose was used to evaluate regional brain glucose metabolism in eight normal subjects and eight psychiatric patients with a history of repetitive violent behavior. Seven of the patients showed widespread areas of low brain metabolism. Although the location of the abnormal regions varied among patients, they showed significantly lower relative metabolic values in medial temporal and prefrontal cortices than did normal comparison subjects. These regions have been implicated as substrates for aggression and impulsivity, and their dysfunction may have contributed to the patients' violent behavior.

Stereotactic localization using PET and SPECT has been used together with the Leksell stereotactic frame and the other imaging tools routinely provided to Gamma Knife radiosurgery sites. The accuracy of the measurements has been confirmed with CT and MR using a Radiation Analog Dosimetry phantom. The activity of the radionuclide solution placed in the tubes of Elekta Radiosurgery's MR imaging box is somewhat critical because the window levels chosen for the scan will affect the apparent size of the lesion. A technique is presented to resolve areas of activity more than about 12-14 mm apart, and it may prove useful in targeting epileptogenic sites in patients with medically intractable epilepsy.

Potassium loss from damaged myocardial cells is linearly related to CPK enzyme loss reflecting extent of necrosis. The potassium analog, rubidium-82 (82Rb), is extracted after i.v. injection and retained in viable myocardium but is not trapped or washed out of necrotic regions. To compare myocardial cell metabolism with membrane dysfunction as indicators of necrosis/viability, 43 patients with evolving myocardial infarction and coronary arteriography had positron emission tomography using fluorodeoxyglucose (FDG) and the potassium analog 82Rb. Percent of heart showing FDG defects and 82Rb washout on sequential images indicating failure to retain the potassium analogue were visually assessed and quantified by automated software. Infarct size based on rubidium kinetics correlated closely with size and location on FDG images (visual r = 0.93, automated r = 0.82), suggesting that loss of cell membrane integrity for trapping the potassium analog 82Rb parallels loss of intracellular glucose metabolism, both comparable quantitative markers of myocardial necrosis/viability.

Measurement of oxygen-15- (15O) water uptake with positron emission tomography (PET) is a sensitive technique to monitor regional brain activation secondary to stimulation paradigms. In order to investigate data acquisition times that show maximal changes in regional activation and to assess the optimal time for stimulus presentation, we investigated 10 controls with 15O-water and PET during baseline and stroboscopic light stimulation. Sequential scans were done varying the time of stimulus presentation. The images were reconstructed using three different periods of data acquisition: uptake phase (initial 30-35 sec), washout phase (40 sec following peak activity in brain), and total activity (3 min). The images reconstructed during the uptake phase showed the largest changes in occipital cortex from stimulation. Maximal changes in occipital cortex were obtained when the visual stimulus was maintained during the uptake phase only.