The role of nuclear imaging in pulmonary hypertension.

Pulmonary hypertension (PH) is a disease characterized by a chronic elevation of pulmonary artery pressure from various causes. Pulmonary artery hypertension (PAH) is one of subtype which results in premature death often as a result of right ventricular (RV) dysfunction. In spite of the recent progress in novel cardiac imaging techniques and new drugs for PAH, there remain significant unresolved issues including a need for earlier diagnosis, refinement of risk stratification, and monitoring the effects of treatment. Cardiac and pulmonary imaging with transthoracic echocardiography (TTE) with Doppler, magnetic resonance imaging (MRI), and computed tomography (CT) are done routinely in many clinical centers. However, routine and emerging nuclear techniques may have a pivotal role of assessment of the patient with PH, and is currently the subject of significant research. Potential Roles for Nuclear Imaging in the Evaluation of the PH Patient: (1) Evaluation of cardiac structure and function (RNA) (non-nuclear techniques would include TTE, CT, and MRI). (2) Functional imaging. This includes the use of ventilation-perfusion scintigraphy (V/Q scan) to diagnose chronic thromboembolic pulmonary hypertension (CTEPH), 123l-metaiodobenzylguanidine (MIBG) imaging to evaluate the cardiac sympathetic nervous system (non-nuclear techniques include invasive right heart catheterization and TTE). (3) Measurement of RV perfusion (with gated SPECT studies). (4) Evaluation of cardiac and pulmonary metabolism (PET scans). This review article will summarize the pathophysiology, classification, natural history, and diagnostic approach of PH. Current and emerging nuclear techniques will be discussed under the four themes of evaluation of structure, functional imaging, flow, and metabolism. These will be compared to current and emerging nuclear and non-nuclear diagnostic tests in the evaluation and management of patients with PH. We will also discuss research applications exploring new insights into flow and metabolism in the right heart and lung and the application of new radioligands.

The role of F(18)-fluorodeoxyglucose positron emission tomography in guiding diagnosis and management in patients with known or suspected cardiac sarcoidosis.

Cardiac sarcoidosis (CS) has gained significant interest in recent years with the emergence of advanced imaging modalities such as MRI and F(18)-fluorodeoxyglucose-positron emission tomography (FDG-PET) as modalities to aid in the diagnosis of this condition. CS remains a difficult condition to diagnose, particularly in cases of isolated cardiac involvement and it can present with a broad spectrum of clinical syndromes. Furthermore, the appropriate management of these patients remains controversial. FDG-PET has a potential role not only in diagnosis of CS but also in directing further therapies, facilitating the decision to start immunosuppression and monitoring the response to it. In this article, we discuss when to consider FDG-PET, outline the current optimal patient preparation and scanning protocols and then, using case examples, discuss the use of FDG-PET in follow-up of patients with known or suspected CS. We also outline how PET can influence management decisions in these patients.

Kinetic model-based factor analysis of dynamic sequences for 82-rubidium cardiac positron emission tomography.

PURPOSE: Factor analysis has been pursued as a means to decompose dynamic cardiac PET images into different tissue types based on their unique temporal signatures to improve quantification of physiological function. In this work, the authors present a novel kinetic model-based (MB) method that includes physiological models of factor relationships within the decomposition process. The physiological accuracy of MB decomposed (82)Rb cardiac PET images is evaluated using simulated and experimental data. Precision of myocardial blood flow (MBF) measurement is also evaluated. METHODS: A gamma-variate model was used to describe the transport of (82)Rb in arterial blood from the right to left ventricle, and a one-compartment model to describe the exchange between blood and myocardium. Simulations of canine and rat heart imaging were performed to evaluate parameter estimation errors. Arterial blood sampling in rats and (11)CO blood pool imaging in dogs were used to evaluate factor and structure accuracy. Variable infusion duration studies in canine were used to evaluate MB structure and global MBF reproducibility. All results were compared to a previously published minimal structure overlap (MSO) method. RESULTS: Canine heart simulations demonstrated that MB has lower root-mean-square error (RMSE) than MSO for both factor (0.2% vs 0.5%, p < 0.001 MB vs MSO, respectively) and structure (3.0% vs 4.7%, p < 0.001) estimations, as with rat heart simulations (factors: 0.2% vs 0.9%, p < 0.001 and structures: 3.0% vs 6.7%, p < 0.001). MB blood factors compared to arterial blood samples in rats had lower RMSE than MSO (1.6% vs 2.2%, p =0.025). There was no difference in the RMSE of blood structures compared to a (11)CO blood pool image in dogs (8.5% vs 8.8%, p =0.23). Myocardial structures were more reproducible with MB than with MSO (RMSE=3.9% vs 6.2%, p < 0.001), as were blood structures (RMSE=4.9% vs 5.6%, p =0.006). Finally, MBF values tended to be more reproducible with MB compared to MSO (CV= 10% vs 18%, p =0.16). The execution time of MB was, on average, 2.4 times shorter than MSO (p < 0.001) due to fewer free parameters. CONCLUSIONS: Kinetic model-based factor analysis can be used to provide physiologically accurate decomposition of (82)Rb dynamic PET images, and may improve the precision of MBF quantification.

Naturally occurring R225W mutation of the gene encoding AMP-activated protein kinase (AMPK)gamma(3) results in increased oxidative capacity and glucose uptake in human primary myotubes.

AIMS/HYPOTHESIS: AMP-activated protein kinase (AMPK) has a broad role in the regulation of glucose and lipid metabolism making it a promising target in the treatment of type 2 diabetes mellitus. We therefore sought to characterise for the first time the effects of chronic AMPK activation on skeletal muscle carbohydrate metabolism in carriers of the rare gain-of-function mutation of the gene encoding AMPKgamma(3) subunit, PRKAG3 R225W. METHODS: Aspects of fuel metabolism were studied in vitro in myocytes isolated from vastus lateralis of PRKAG3 R225W carriers and matched control participants. In vivo, muscular strength and fatigue were evaluated by isokinetic dynamometer and surface electromyography, respectively. Glucose uptake in exercising quadriceps was determined using [(18)F]fluorodeoxyglucose and positron emission tomography. RESULTS: Myotubes from PRKAG3 R225W carriers had threefold higher mitochondrial content (p < 0.01) and oxidative capacity, higher leak-dependent respiration (1.6-fold, p < 0.05), higher basal glucose uptake (twofold, p < 0.01) and higher glycogen synthesis rates (twofold, p < 0.05) than control myotubes. They also had higher levels of intracellular glycogen (p < 0.01) and a trend for lower intramuscular triacylglycerol stores. R225W carriers showed remarkable resistance to muscular fatigue and a trend for increased glucose uptake in exercising muscle in vivo. CONCLUSIONS/INTERPRETATION: Through the enhancement of skeletal muscle glucose uptake and increased mitochondrial content, the R225W mutation may significantly enhance exercise performance. These findings are also consistent with the hypothesis that the gamma(3) subunit of AMPK is a promising tissue-specific target for the treatment of type 2 diabetes mellitus, a condition in which glucose uptake and mitochondrial function are impaired.

Myocardial blood flow in patients with low-flow, low-gradient aortic stenosis: differences between true and pseudo-severe aortic stenosis. Results from the multicentre TOPAS (Truly or Pseudo-Severe Aortic Stenosis) study.

BACKGROUND: Impairment of myocardial flow reserve (MFR) in aortic stenosis (AS) with normal left ventricular function relates to the haemodynamic severity. OBJECTIVES: To investigate whether myocardial blood flow (MBF) and MFR differ in low-flow, low-gradient AS depending on whether there is underlying true-severe AS (TSAS) or pseudo-severe AS (PSAS). METHODS: In 36 patients with low-flow, low-gradient AS, dynamic [13N]ammonia PET perfusion imaging was performed at rest (n = 36) and during dipyridamole stress (n = 20) to quantify MBF and MFR. Dobutamine echocardiography was used to classify patients as TSAS (n = 18) or PSAS (n = 18) based on the indexed projected effective orifice area (EOA) at a normal flow rate of 250 ml/s (EOAI(proj )0.55 cm(2)/m(2)). RESULTS: Compared with healthy controls (n = 14), patients with low-flow, low-gradient AS had higher resting mean (SD) MBF (0.83 (0.21) vs 0.69 (0.09) ml/min/g, p = 0.001), reduced hyperaemic MBF (1.16 (0.31) vs 2.71 (0.50) ml/min/g, p<0.001) and impaired MFR (1.44 (0.44) vs 4.00 (0.91), p<0.001). Resting MBF and MFR correlated with indices of AS severity in low-flow, low-gradient AS with the strongest relationship observed for EOAI(proj) (r(s) = -0.50, p = 0.002 and r(s) = 0.61, p = 0.004, respectively). Compared with PSAS, TSAS had a trend to a higher resting MBF (0.90 (0.19) vs 0.77 (0.21) ml/min/g, p = 0.06), similar hyperaemic MBF (1.16 (0.31) vs 1.17 (0.32) ml/min/g, p = NS), but a significantly smaller MFR (1.19 (0.26) vs 1.76 (0.41), p = 0.003). An MFR <1.8 had an accuracy of 85% for distinguishing TSAS from PSAS. CONCLUSIONS: Low-flow, low-gradient AS is characterised by higher resting MBF and reduced MFR that relates to the AS severity. The degree of MFR impairment differs between TSAS and PSAS and may be of value for distinguishing these entities.

CCS/CAR/CANM/CNCS/CanSCMR joint position statement on advanced noninvasive cardiac imaging using positron emission tomography, magnetic resonance imaging and multidetector computed tomographic angiography in the diagnosis and evaluation of ischemic heart disease--executive summary.

BACKGROUND: Over the past few decades, advanced imaging modalities with excellent diagnostic capabilities have emerged. The aim of the present position statement was to systematically review existing literature to define Canadian recommendations for their clinical use. METHODS: A systematic literature review to 2005 was conducted for positron emission tomography (PET), multidetector computed tomographic angiography and magnetic resonance imaging (MRI) in ischemic heart disease. Papers that met the criteria were reviewed for accuracy, prognosis data and study quality. Recommendations were presented to primary and secondary panels of experts, and consensus was achieved. RESULTS: Indications for PET include detection of coronary artery disease (CAD) with perfusion imaging, and defining viability using fluorodeoxyglucose to determine left ventricular function recovery and/or prognosis after revascularization (class I). Detection of CAD in patients, vessel segments and grafts using computed tomographic angiography was considered class IIa at the time of the literature review. Dobutamine MRI is class I for CAD detection and, along with late gadolinium enhancement MRI, class I for viability detection to predict left ventricular function recovery. Imaging must be performed at institutions and interpreted by physicians with adequate experience and training. CONCLUSIONS: Cardiac imaging using advanced modalities (PET, multidetector computed tomographic angiography and MRI) is useful for CAD detection, viability definition and, in some cases, prognosis. These modalities complement the more widespread single photon emission computed tomography and echocardiography. Given the rapid evolution of technology, initial guidelines for clinical use will require regular updates. Evaluation of their integration in clinical practice should be ongoing; optimal use will require proper training. A joint effort among specialties is recommended to achieve these goals.

Precision-controlled elution of a 82Sr/82Rb generator for cardiac perfusion imaging with positron emission tomography.

A rubidium-82 ((82)Rb) elution system is described for use with positron emission tomography. Due to the short half-life of (82)Rb (76 s), the system physics must be modelled precisely to account for transport delay and the associated activity decay and dispersion. Saline flow is switched between a (82)Sr/(82)Rb generator and a bypass line to achieve a constant-activity elution of (82)Rb. Pulse width modulation (PWM) of a solenoid valve is compared to simple threshold control as a means to simulate a proportional valve. A predictive-corrective control (PCC) algorithm is developed which produces a constant-activity elution within the constraints of long feedback delay and short elution time. The system model parameters are adjusted through a self-tuning algorithm to minimize error versus the requested time-activity profile. The system is self-calibrating with 2.5% repeatability, independent of generator activity and elution flow rate. Accurate 30 s constant-activity elutions of 10-70% of the total generator activity are achieved using both control methods. The combined PWM-PCC method provides significant improvement in precision and accuracy of the requested elution profiles. The (82)Rb elution system produces accurate and reproducible constant-activity elution profiles of (82)Rb activity, independent of parent (82)Sr activity in the generator. More reproducible elution profiles may improve the quality of clinical and research PET perfusion studies using (82)Rb.

Diagnostic and clinical perspectives of fusion imaging in cardiology: is the total greater than the sum of its parts?

Positron emission tomography, cardiovascular magnetic resonance and multislice computed tomography have contributed to changing our pathophysiological understanding of many conditions. Clinically, they have provided new tools for the identification of preclinical disease and a better understanding of how disease progresses. The application of these imaging modalities to preclinical disease and the use of these techniques in patients with overt cardiovascular disease are reviewed.

Treating the right patient at the right time: access to cardiovascular nuclear imaging.

Cardiovascular nuclear medicine uses agents labelled with radioisotopes that can be imaged with cameras (single-photon emission tomography [SPECT] or positron emission tomography [PET]) capable of detecting gamma photons to show physiological parameters such as myocardial perfusion, myocardial viability or ventricular function. There is a growing body of literature providing guidelines for the appropriate use of these techniques, but there are little data regarding the appropriate timeframe during which the procedures should be accessed. An expert working group composed of cardiologists and nuclear medicine specialists conducted an Internet search to identify current wait times and recommendations for wait times for a number of cardiac diagnostic tools and procedures, including cardiac catheterization and angioplasty, bypass grafting and vascular surgery. These data were used to estimate appropriate wait times for cardiovascular nuclear medicine procedures. The estimated times were compared with current wait times in each province. Wait time benchmarks were developed for the following: myocardial perfusion with either exercise or pharmacological stress and SPECT or PET imaging; myocardial viability assessment with either fluorodeoxyglucose SPECT or PET imaging, or thallium-201 SPECT imaging; and radionuclide angiography. Emergent, urgent and nonurgent indications were defined for each clinical examination. In each case, appropriate wait time benchmarks were defined as within 24 h for emergent indications, within three days for urgent indications and within 14 days for nonurgent indications. Substantial variability was noted from province to province with respect to access for these procedures. For myocardial perfusion imaging, mean emergent/urgent wait times varied from four to 24 days, and mean nonurgent wait times varied from 15 to 158 days. Only Ontario provided limited access to viability assessment, with fluorodeoxyglucose available in one centre. Mean emergent/urgent wait times for access to viability assessment with thallium-201 SPECT imaging varied from three to eight days, with the exception of Newfoundland, where an emergent/urgent assessment was not available; mean nonurgent wait times varied from seven to 85 days. Finally, for radionuclide angiography, mean emergent/urgent wait times varied from two to 20 days, and nonurgent wait times varied from eight to 36 days. Again, Newfoundland centres were unable to provide emergent/urgent access. The publication of these data and proposed wait times as national targets is a step toward the validation of these recommendations through consultation with clinicians caring for cardiac patients across Canada.

Potential utility of rubidium 82 PET quantification in patients with 3-vessel coronary artery disease.

BACKGROUND: Standard perfusion imaging may underestimate the extent of disease in 3-vessel coronary atherosclerosis. This study determined whether positron emission tomography quantification of perfusion reserve by use of rubidium 82 net retention defined a greater extent of disease than the standard approach in patients with 3-vessel disease. METHODS AND RESULTS: Rb-82 net retention was quantified as an estimation of absolute perfusion at rest and with dipyridamole stress by use of dynamic positron emission tomography imaging. The percent of abnormal myocardial sectors, as compared with a normal database, for a standard and quantification approach was determined. Twenty-three patients were evaluated. Defect sizes were larger in patients with 3-vessel disease (n = 13) by use of quantification methods: 44% +/- 18% of the myocardial sectors were abnormal by use of the standard approach versus 69% +/- 24% of sectors when measured by quantification of the stress-rest perfusion difference (P =.008). In patients with single-vessel disease (n = 10), defect sizes were smaller with quantification methods. CONCLUSIONS: Quantification of Rb-82 net retention to measure the stress-rest perfusion difference in the myocardium defined a greater extent of disease than the standard approach in this group of patients with triple-vessel disease. More accurate measurement of the extent of coronary artery disease could facilitate better risk stratification and identify more high-risk patients in whom aggressive intervention is required.

Precision control of eluted activity from a Sr/Rb generator for cardiac positron emission tomography.

A rubidium-82 (/sup 82/Rb) elution system is described for use with clinical positron emission tomography. The system is self-calibrating with 1.4% repeatability, independent of generator activity and elution flow rate. Saline flow is switched between a /sup 82/Sr//sup 82/Rb generator and a bypass line to achieve a constant activity elution of /sup 82/Rb. In the present study, pulse width modulation (PWM) of a solenoid valve is compared to simple threshold control as a means to simulate a proportional valve. A predictive-corrective control algorithm is developed which produces a constant activity elution within the constraints of long feedback delay and short elution time. Accurate constant-activity elutions of 10-70% of the total generator activity were demonstrated using the threshold comparison control. The adaptive-corrective control of the PWM valve provided a substantial improvement in precision of the steady-state output.

Myocardial glucose utilization and optimization of (18)F-FDG PET imaging in patients with non-insulin-dependent diabetes mellitus, coronary artery disease, and left ventricular dysfunction.

UNLABELLED: In patients with non-insulin-dependent diabetes mellitus (NIDDM), FDG PET imaging is often problematic because of poor uptake of FDG. Different protocols have been used; however, these have not been directly compared in patients with NIDDM who have both coronary artery disease (CAD) and severe left ventricular (LV) dysfunction, for which defining viability is most relevant. The aim of this study was to better define the optimal means of FDG PET imaging, assessed by image quality and myocardial glucose utilization rate (rMGU), among 3 imaging protocols in patients with NIDDM, CAD, and severe LV dysfunction. METHODS: Ten patients with NIDDM, CAD, and severe LV dysfunction (mean ejection fraction, 29.8% +/- 7.1%) underwent dynamic FDG PET scanning using 3 different protocols: the standard protocol, consisting of oral glucose loading or a supplemental insulin bolus based on fasting glucose; the niacin protocol, consisting of pretreatment with niacin to lower free fatty acids; and the insulin clamp protocol, consisting of hyperinsulinemic euglycemic clamp. Image quality was satisfactory with at least 1 approach in 8 patients, who formed the primary analysis group. RESULTS: Myocardium-to-blood-pool ratios were significantly higher with the insulin clamp (standard, 1.7 +/- 1.2; niacin, 1.6 +/- 1.0; insulin clamp, 3.4 +/- 2.5 [P < 0.05 vs. standard and niacin]). Values for rMGU were higher with the insulin clamp (standard, 0.11 +/- 0.07 micromol/g/min; niacin, 0.12 +/- 0.11 micromol/g/min; insulin clamping, 0.22 +/- 0.12 micromol/g/min [P = 0.004 vs. standard and 0.07 vs. niacin]). CONCLUSION: The hyperinsulinemic euglycemic clamp yielded the highest FDG PET image quality and the highest rMGU in a comparison with the standard and niacin protocols in this difficult group of patients with NIDDM, CAD, and severe LV dysfunction. The hyperinsulinemic euglycemic clamp may be the preferred method for FDG PET viability imaging in this population. Larger clinical trials are needed to assess whether accuracy is greater with this approach.

Stenting versus thrombolysis in acute myocardial infarction trial (STAT).

OBJECTIVES: We sought to directly compare primary stenting with accelerated tissue plasminogen activator (t-PA) in patients presenting with acute ST-elevation myocardial infarction (AMI). BACKGROUND: Thrombolysis remains the standard therapy for AMI. However, at some institutions primary angioplasty is favored. Randomized trials have shown that primary angioplasty is equal or superior to thrombolysis, while recent studies demonstrate that stent implantation improves the results of primary angioplasty. METHODS: Patients presenting with AMI were randomly assigned to primary stenting (n = 62) or accelerated t-PA (n = 61). The primary end point was the composite of death, reinfarction, stroke or repeat target vessel revascularization (TVR) for ischemia at six months. RESULTS: The primary end point was significantly reduced in the stent group compared with the accelerated t-PA group, 24.2% versus 55.7% (p < 0.001). The event rates for other outcomes in the stent group versus the t-PA group were as follows: mortality: 4.8% versus 3.3% (p = 1.00); reinfarction: 6.5% versus 16.4% (p = 0.096); stroke: 1.6% versus 4.9% (p = 0.36); recurrent unstable ischemia: 9.7% versus 26.2% (p = 0.03) and repeat TVR for ischemia: 14.5% versus 49.2% (p < 0.001). The median length of the initial hospitalization was four days in the stent group and seven days in the t-PA group (p < 0.001). CONCLUSIONS: Compared with accelerated t-PA, primary stenting reduces death, reinfarction, stroke or repeat TVR for ischemia. In centers where facilities and experienced interventionists are available, primary stenting offers an attractive alternative to thrombolysis.

The effects of beta(1)-blockade on oxidative metabolism and the metabolic cost of ventricular work in patients with left ventricular dysfunction: A double-blind, placebo-controlled, positron-emission tomography study.

BACKGROUND: The mechanism for the beneficial effect of beta-blocker therapy in patients with left ventricular (LV) dysfunction is unclear, but it may relate to an energy-sparing effect that results in improved cardiac efficiency. C-11 acetate kinetics, measured using positron-emission tomography (PET), are a proven noninvasive marker of oxidative metabolism and myocardial oxygen consumption (MVO(2)). This approach can be used to measure the work-metabolic index, which is a noninvasive estimate of cardiac efficiency. METHODS AND RESULTS: The aim of this study was to determine the effect of metoprolol on oxidative metabolism and the work-metabolic index in patients with LV dysfunction. Forty patients (29 with ischemic and 11 with nonischemic heart disease; LV ejection fraction <40%) were randomized to receive metoprolol or placebo in a treatment protocol of titration plus 3 months of stable therapy. Seven patients were not included in analysis because of withdrawal from the study, incomplete follow-up, or nonanalyzable PET data. The rate of oxidative metabolism (k) was measured using C-11-acetate PET, and stoke volume index (SVI) was measured using echocardiography. The work-metabolic index was calculated as follows: (systolic blood pressure x SVI x heart rate)/k. No significant change in oxidative metabolism occurred with placebo (k=0.061+/-0.022 to 0.054+/-0.012 per minute). Metoprolol reduced oxidative metabolism (k=0.062+/-0. 024 to 0.045+/-0.015 per minute; P:=0.002). The work-metabolic index did not change with placebo (from 5.29+/-2.46 x 10(6) to 5.14+/-2. 06 x 10(6) mm Hg. mL/m(2)), but it increased with metoprolol (from 5. 31+/-2.15 x 10(6) to 7.08+/-2.36 x 10(6) mm Hg. mL/m(2); P:<0.001). CONCLUSIONS: Selective beta-blocker therapy with metoprolol leads to a reduction in oxidative metabolism and an improvement in cardiac efficiency in patients with LV dysfunction. It is likely that this energy-sparing effect contributes to the clinical benefits observed with beta-blocker therapy in this patient population.

Detection of serial changes in absolute myocardial perfusion with 82Rb PET.

UNLABELLED: Serial changes in myocardial perfusion may represent an important marker of disease progression or regression or the effects of therapy for patients with coronary artery disease (CAD). Quantitative methods have not been developed for the assessment of serial changes in perfusion. The objective of this study was to use receiver operator characteristic (ROC) analysis to determine the sensitivity and specificity of direct paired comparisons (DPCs) to detect changes in absolute myocardial perfusion measured with 82Rb PET. METHODS: Repeated dynamic 82Rb PET scans were obtained on 8 dogs at rest and during hyperemia induced with dobutamine (n = 4) or atrial pacing (n = 4). Radiolabeled microspheres were used to verify perfusion changes. Polar maps of absolute 82Rb retention and associated SD were estimated from the dynamic images. Paired comparisons were then performed using a t test on each of the 532 polar map sectors. Rest-rest and stress-stress differences were used to assess specificity and reproducibility, and stress-rest differences were used to assess sensitivity. RESULTS: 82Rb retention differences of 20% over baseline were detected with 85%-90% sensitivity and specificity, using the optimal DPC probability value and image smoothness. The average 82Rb retention differences correlated well with microspheres (r = 0.74; P = 0.001). Reproducibility of the mean retention values was 4.7% +/- 2.1%. As reproducibility varies, the DPC probability value can be adjusted to maintain specificity. These ROC results are directly applicable to other image modalities that produce measurements with similar SEs (3.7% +/- 0.9%). CONCLUSION: The developed method of DPCs is sensitive and specific for the detection of changes in absolute myocardial perfusion measured with 82Rb PET.

Stress perfusion/metabolism imaging: a pilot study for a potential new approach to the diagnosis of coronary disease in women.

BACKGROUND: The diagnosis of coronary artery disease (CAD) in women continues to be a challenge. F-18 deoxyglucose (FDG) positron emission tomography (PET) has been used for detection of myocardial ischemia at rest. Little has been reported about FDG stress imaging. The aim of this pilot study was to assess stress FDG PET imaging for defining CAD in a group of women referred for chest pain. METHODS: Stress FDG imaging was performed in 19 women (mean age 59 +/- 10 years). All had abnormal stress testing before entering the study. FDG and 2-methoxy-2-methylpropyl isonitrile were injected at peak stress (treadmill n = 8, dipyridamole n = 11) followed by PET and single photon emission computed tomography image acquisitions. Myocardial ischemia was defined by regions that demonstrated both a defect on perfusion imaging and increased FDG uptake relative to uptake in normal perfusion zones. Defect/normal zone FDG ratios were also determined. Coronary angiography was performed on all patients. RESULTS: Average, or mean, body mass index was high at 29.2 +/- 5 kg/m2. Nine of 19 patients had significant CAD. Eight of 9 with CAD had FDG-defined ischemia. Nine of the 10 without CAD had negative FDG images (sensitivity 89%, specificity 90%). The average defect/normal zone FDG ratio was greater in patients with CAD than in those without (2.4 +/- 1.9 vs 0.9 +/- 0.4, P < .05). CONCLUSIONS: Regional FDG uptake in areas of perfusion defects with stress increased in this group with CAD. These pilot data suggest that stress FDG PET may be diagnostically helpful in obese female patients. This novel approach may complement current methods of CAD detection in women and warrants further study.