The use of myocardial perfusion 82 Rb PET/CT studies continues to increase but its accuracy using database quantification methods for the diagnosis of coronary artery disease (CAD) has not been established. Methods: A sex-independent normal database and criteria for abnormality for rest-stress 82 Rb PET/CT myocardial perfusion imaging were developed and validated by evaluation of 281 patients (136 females: mean age 6 SD, 63.3 6 13.3 y; 145 males: mean age 6 SD, 63.9 6 12.8 y) who underwent a rest-adenosine stress 82 Rb PET/CT study. These patients were divided into 3 groups: (a) healthy group: 30 patients, with ,5% likelihood of CAD (low likelihood [LLK]) based on sequential Bayesian analysis; these patients were used to generate the normal distribution; (b) pilot group: 174 patients; these patients were used to determine the optimal criteria for detecting and localizing the perfusion abnormality; and (c) validation group: 76 patients (23 with LLK of CAD and 53 who underwent coronary angiography; these patients were used for prospective validation. Results: Of the 53 patients who underwent coronary angiography, 8 had ,50% stenosis and 45 patients had at least one stenosis $50% in one major artery. Fifteen patients had single-vessel disease, 17 had double-vessel disease, and 13 had triple-vessel disease. The prospective validation shows a normalcy rate of 78% (18/23) for global CAD. The analyses by individual arteries show a normalcy rate of 96% (22/23) for the left anterior descending coronary artery, 96% for the left circumflex coronary artery (22/23), and 100% for the right coronary artery (23/23). The overall sensitivity for detection of CAD ($50% stenosis) was 93% (42/45). The overall specificity for detection of the absence of CAD (#50% stenosis) was 75% (6/8). Also, the positive predictive value for global CAD was 95% (42/44), the negative predictive value was 67% (6/9), and the accuracy was 91% (48/53). Conclusion: The quantitative 82 Rb PET/CT database created and validated in this study is highly accurate for the detection and localization of CAD. Physicians should consider using the quantitative output of these algorithms as decision support tools to aid with image interpretation. Rest -stress 82 Rb myocardial perfusion PET is widely regarded as a clinically accurate imaging modality for diagnosing and managing patients with coronary artery disease (CAD) (1,2). The reasons given for this high diagnostic performance are (a) the kinetic properties of 82 Rb, (b) the high sensitivity of a ring PET system, (c) the high-contrast resolution of PET scanners, and (d) the accurate attenuation correction used in PET (1-4). With the advent and wide dissemination of PET/CT scanners for cardiac imaging, high-quality transmission scans are generated by the CT scanner for attenuation correction.Although these PET/CT scanners yield high imaging performance, misregistration of the CT transmission and PET emission scans is often seen because of the different temporal resolution of the 2 modalities. Moreover, the transmi...