82Rb Positron Emission Tomography Research Articles

Incremental diagnostic benefit of resolution recovery software in patients with equivocal myocardial perfusion single-photon emission computed tomography (SPECT)

BackgroundThough myocardial perfusion imaging (MPI) with single-photon emission computed tomography (SPECT) is an established diagnostic method, equivocal studies are commonly encountered. New software has been introduced that incorporates resolution recovery (RR) and noise regulation into the reconstruction algorithm and has been used to facilitate “half-dose” and “half-time” studies. Its utility with “full-time, full-dose” acquisition has not been well studied. ObjectiveWe sought to understand the potential benefit of incorporating RR software in equivocal SPECT studies. MethodsPatients with full-time, full-dose SPECT MPI were reviewed and those with equivocal results, who subsequently underwent cardiac Rb-82 positron emission tomography (PET) scan were identified. Image reconstruction was performed with iterative reconstruction (IR), attenuation correction (IR + AC), and RR software (IR + AC + RR). Images were anonymized and read blindly by consensus of two experienced readers. All images were qualitatively assessed and semi-quantitatively graded using summed stress and summed rest scores. Results45 patients were included (28 males, age = 59.6 ± 9.9 years) and the diagnostic accuracy of each of the reconstruction algorithms (IR, IR + AC, IR + AC + RR) was compared to Rb-82 PET. Agreement of clinical diagnosis of each SPECT reconstruction with Rb-PET showed incremental improvement. The agreement with PET for IR + AC + RR (κ = 0.66, CI 0.454-0.875) is significantly better than for IR (κ = 0.22, CI 0.0-0.450, P = .005) and for IR + AC (κ = 0.32, CI 0.077-0.563, P = .03). Also, IR + AC + RR improved the clinical diagnosis in 14 cases and with overall improvement of reclassification proportion of 23.5% compared to IR (P = .01). Using PET as a reference standard, ROC curves were created for IR + AC + RR, IR + AC, and IR which showed incremental value of the area under the curve of IR + AC + RR (AUC: 0.87; CI 0.76-0.98) over IR + AC (AUC: 0.75; CI 0.61-0.89, P = .078), and over IR (AUC 0.68; CI 0.52-0.84, P = .025). ConclusionThe addition of RR may help in the diagnosis of patients with equivocal SPECT MPI without the need for additional testing. Further prospective studies are needed to define the role of this new software.

Influence of Sex on Risk Stratification With Stress Myocardial Perfusion Rb-82 Positron Emission Tomography: Results From the PET (Positron Emission Tomography) Prognosis Multicenter Registry

The aim of the current analysis was to compare sex differences in the prognostic accuracy of stress myocardial perfusion rubidum-82 (Rb-82) positron emission tomography (PET).The diagnostic evaluation of women presenting with suspected cardiac symptoms is challenging with reported reduced accuracy, attenuation artifact, and more recent concerns regarding radiation safety. Stress myocardial perfusion Rb-82 PET is a diagnostic alternative with improved image quality and radiation dosimetry. Currently, the prognostic accuracy of stress Rb-82 PET in women has not been established.A total of 6,037 women and men were enrolled in the PET Prognosis Multicenter Registry. Patients were followed for the occurrence of coronary artery disease (CAD) mortality, with a median follow-up of 2.2 years. Cox proportional hazards modeling was used to estimate CAD mortality. The net re-classification improvement index (NRI) was calculated.The 5-year CAD mortality was 3.7% for women and 6.0% for men (p < 0.0001). Unadjusted CAD mortality ranged from 0.9% to 12.9% for women (p < 0.0001) and from 1.5% to 17.4% for men (p < 0.0001) for 0% to ≥15% abnormal myocardium at stress. In multivariable models, the percentage of abnormal stress myocardium was independently predictive of CAD mortality in women and men. An interaction term of sex by the percentage of abnormal stress myocardium was nonsignificant (p = 0.39). The categorical NRI when Rb-82 PET data was added to a clinical risk model was 0.12 for women and 0.17 for men. Only 2 cardiac deaths were reported in women <55 years of age; accordingly the percentage of abnormal myocardium at stress was of borderline significance (p = 0.063), but it was highly significant for women ≥55 years of age (p < 0.0001), with an increased NRI of 0.21 (95% confidence interval: 0.09 to 0.34), including 17% of CAD deaths and 3.9% of CAD survivors that were correctly re-classified in this older female subset.Stress Rb-82 PET provides significant and clinically meaningful effective risk stratification of women and men, supporting this modality as an alternative to comparative imaging modalities. Rb-82 PET findings were particularly helpful at identifying high-risk, older women.

Initial human experience with Rubidium‐82 renal PET/CT imaging

Preclinical data have shown that Rubidium-82 chloride ((82)Rb) is a radiotracer with high first pass extraction and slow washout in the kidneys. The goal of this study was to investigate the feasibility of human kidney imaging with (82)Rb positron emission tomography (PET) and obtain quantitative data of its uptake non-invasively. Eight healthy volunteers underwent dynamic PET/CT imaging with (82)Rb. A preprogrammed pump was used to insure reproducible injections. Tissue time activity curves were generated from the renal cortex. An input function was derived from the left ventricular blood pool (LVBP), the descending thoracic aorta and the abdominal aorta. Renal blood flow was estimated by applying a two-compartment kinetic model. Results obtained with different input functions were compared. Radiotracer accumulation was rapid and reached a plateau within 15-30 s after the bolus entered the kidneys. The derived K1 and k2 parameters were reproducible using input functions obtained from diverse vascular locations. K1 averaged 1.98 ± 0.14 mL/min/g. The average k2 was 0.35 ± 0.11/min. Correlation between K1 values obtained from the LVBP from different bed positions when the kidneys and abdominal aorta were in the same field of view was excellent (R = 0.95). Non-invasive quantitative human kidney imaging with (82)Rb PET is feasible. Advantages of renal PET with (82)Rb include excellent image quality with high image resolution and contrast. (82)Rb has potential as a clinical renal imaging agent in humans.

Added prognostic value of myocardial blood flow quantitation in rubidium-82 positron emission tomography imaging

We studied the respective added value of the quantitative myocardial blood flow (MBF) and the myocardial flow reserve (MFR) as assessed with (82)Rb positron emission tomography (PET)/CT in predicting major adverse cardiovascular events (MACEs) in patients with suspected myocardial ischaemia. Myocardial perfusion images were analysed semi-quantitatively (SDS, summed difference score) and quantitatively (MBF, MFR) in 351 patients. Follow-up was completed in 335 patients and annualized MACE (cardiac death, myocardial infarction, revascularization, or hospitalization for congestive heart failure or de novo stable angor) rates were analysed with the Kaplan-Meier method in 318 patients after excluding 17 patients with early revascularizations (<60 days). Independent predictors of MACEs were identified by multivariate analysis. During a median follow-up of 624 days (inter-quartile range 540-697), 35 MACEs occurred. An annualized MACE rate was higher in patients with ischaemia (SDS >2) (n = 105) than those without [14% (95% CI = 9.1-22%) vs. 4.5% (2.7-7.4%), P < 0.0001]. The lowest MFR tertile group (MFR <1.8) had the highest MACE rate [16% (11-25%) vs. 2.9% (1.2-7.0%) and 4.3% (2.1-9.0%), P < 0.0001]. Similarly, the lowest stress MBF tertile group (MBF <1.8 mL/min/g) had the highest MACE rate [14% (9.2-22%) vs. 7.3% (4.2-13%) and 1.8% (0.6-5.5%), P = 0.0005]. Quantitation with stress MBF or MFR had a significant independent prognostic power in addition to semi-quantitative findings. The largest added value was conferred by combining stress MBF to SDS. This holds true even for patients without ischaemia. Perfusion findings in (82)Rb PET/CT are strong MACE outcome predictors. MBF quantification has an added value allowing further risk stratification in patients with normal and abnormal perfusion images.

Respiratory phase alignment improves blood-flow quantification in Rb82 PET myocardial perfusion imaging

Positron emission tomography (PET) is considered the gold standard for measuring myocardial blood flow in vivo but it is known that respiratory motion can lead to misalignment of the PET and computed tomography (CT) data sets and introduce artifacts in the CT-based attenuation correction (AC) of images. In addition, respiratory motion blurs the PET image and degrades spatial resolution. The purpose of this study is to evaluate the combined effect of respiratory motion compensation (MC) and accurate attenuation correction on relative and absolute blood flow imaging of the heart. Dynamic (82)Rb-PET acquisitions were generated for a homogeneous tracer distribution in the heart using an anthropomorphic computer phantom and a Monte Carlo simulator. Attenuation correction was done using three different approaches in which the PET data were corrected by: (1) a respiratory-gated CT map with each respiratory phase of the PET scan corrected by its corresponding CT phase (matched); (2) a time-averaged attenuation map (avg); or (3) an attenuation map generated from the maximum CT-number of every voxel over the respiratory cycle (max). Motion compensated was done using an automated rigid-body registration algorithm that aligned all of the phases of the respiratory-gated PET data after AC. The corrected dynamic PET data were then processed by inhouse kinetic analysis software to generate 3D maps of blood flow. Polar maps of the blood-flow for each CT-AC method with and without MC were compared to the truth using a 17-segment model. The same comparison was performed on data from a pig study. Motion compensation significantly reduced the segmental mean percentage error (sMPE) in all cases (p < 0.01 for matched CTAC and avg CTAC and p = 0.03 for max CTAC). MC significantly increased image uniformity in the case of matched and avg CTAC (p < 0.01, p = 0.04, respectively) with the best improvement coming for matched CTAC. Without MC, there were no significant differences between the three CTAC approaches. With MC, matched CTAC had significantly smaller mean absolute sMPE (p < 0.01 vs avg CTAC; p < 0.01 vs max CTAC) and improved uniformity (p = 0.05 vs avg CTAC; p < 0.01 vs max CTAC). The results were supported with a pig study. Without MC, there was no significant difference between the three CTAC methods for measuring blood flow. With MC, the matched CTAC approach was significantly better, reducing the mean difference from truth by 6% in the simulated data and improving uniformity by 5%.

Assessment of a protocol for routine simultaneous myocardial blood flow measurement and standard myocardial perfusion imaging with rubidium-82 on a high count rate positron emission tomography system

High count rate positron emission tomography (PET) systems offer the potential for accurate myocardial blood flow (MBF) quantification during first-pass dynamic imaging in conjunction with standard rubidium-82 (Rb-82) PET myocardial perfusion imaging (MPI). We investigate the feasibility of this using a Siemens Biograph mCT. Current routine clinical PET MPI is performed with 1480 MBq (40 mCi) Rb-82. Dynamic first-pass images from 217 consecutive patients were reviewed for evidence of detector saturation, indicating that count rate limits had been exceeded. Phantom acquisitions in the presence of high count rates were performed to assess the effect of detector saturation on quantitative accuracy. Accurate MBF quantification and perfusion imaging using current protocols was successful in 85% of clinical cases. Detector block saturation was observed in 15% of cases, and phantom acquisitions indicate that saturation may have an adverse effect on quantitative accuracy. Visualization of transit or pooling of Rb-82 in the vessels in the axilla was the most consistent feature when saturation occurred. Reduction of administered activity to 1110 MBq (30 mCi) and subsequent evaluation of 159 patients ensured successful MBF quantification while maintaining good diagnostic quality perfusion imaging in 99% of cases. MBF quantification and good-quality standard perfusion imaging can be performed on a high count rate PET system using a single-acquisition protocol. The administered activity requires optimization and we recommend 1110 MBq for PET MPI with a Biograph mCT.

Does Rubidium-82 PET Have Superior Accuracy to SPECT Perfusion Imaging for the Diagnosis of Obstructive Coronary Disease?: A Systematic Review and Meta-Analysis

The purpose of this study was to evaluate the accuracy of rubidium (Rb)-82 positron emission tomography (PET) for the diagnosis of obstructive coronary artery disease (CAD) in comparison to single-photon emission tomography (SPECT). Myocardial perfusion imaging is widely used in the assessment of patients with known or suspected CAD. PET using Rb-82 has potential advantages over SPECT that may make it more accurate and that reduce radiation exposure compared with SPECT but has increased costs. Comparisons of these technologies are highly relevant for policy makers and practice guidelines. However, studies directly comparing Rb-82 PET with contemporary SPECT have been limited. The authors therefore undertook a systematic review of studies where either Rb-82 PET or technetium-99m SPECT with both attenuation correction and electrocardiography-gating were used as a diagnostic test for obstructive CAD with invasive coronary angiogram as a reference standard. These technologies were then compared. Fifteen PET and 8 SPECT studies (1,344 and 1,755 patients, respectively) met inclusion criteria and pooled accuracy using weighted averages according to the size of the patient population was determined for PET and SPECT with sensitivities of 90% (confidence interval [CI]: 0.88 to 0.92) and 85% (CI: 0.82 to 0.87) and specificities of 88% (CI: 0.85 to 0.91) and 85% (CI: 0.82 to 0.87), respectively. Summary receiver-operating characteristic curves were computed: area under the curve was 0.95 and 0.90 for PET and SPECT, respectively (p < 0.0001). There was heterogeneity among study populations and some studies were limited by referral bias. Rb-82 PET is accurate for the detection of obstructive CAD and, despite advances in SPECT technology, remains superior. More widespread use of Rb-82 PET may be beneficial to improve CAD detection.

Quantification of regional myocardial blood flow estimation with three-dimensional dynamic rubidium-82 PET and modified spillover correction model

PurposeMyocardial blood flow (MBF) estimation with 82Rubidium (82Rb) positron emission tomography (PET) is technically difficult because of the high spillover between regions of interest, especially due to the long positron range. We sought to develop a new algorithm to reduce the spillover in image-derived blood activity curves, using non-uniform weighted least-squares fitting. MethodsFourteen volunteers underwent imaging with both 3-dimensional (3D) 82Rb and 15O-water PET at rest and during pharmacological stress. Whole left ventricular (LV) 82Rb MBF was estimated using a one-compartment model, including a myocardium-to-blood spillover correction to estimate the corresponding blood input function Ca(t)whole. Regional K1 values were calculated using this uniform global input function, which simplifies equations and enables robust estimation of MBF. To assess the robustness of the modified algorithm, inter-operator repeatability of 3D 82Rb MBF was compared with a previously established method. ResultsWhole LV correlation of 82Rb MBF with 15O-water MBF was better (P < .01) with the modified spillover correction method (r = 0.92 vs r = 0.60). The modified method also yielded significantly improved inter-operator repeatability of regional MBF quantification (r = 0.89) versus the established method (r = 0.82) (P < .01). ConclusionA uniform global input function can suppress LV spillover into the image-derived blood input function, resulting in improved precision for MBF quantification with 3D 82Rb PET.

Does quantification of myocardial flow reserve using rubidium-82 positron emission tomography facilitate detection of multivessel coronary artery disease?

BackgroundRelative myocardial perfusion imaging (MPI) is the standard imaging approach for the diagnosis and prognostic work-up of coronary artery disease (CAD). However, this technique may underestimate the extent of disease in patients with 3-vessel CAD. Positron emission tomography (PET) is also able to quantify myocardial blood flow. Rubidium-82 (82Rb) is a valid PET tracer alternative in centers that lack a cyclotron. The aim of this study was to assess whether assessment of myocardial flow reserve (MFR) measured with 82Rb PET is an independent predictor of severe obstructive 3-vessel CAD. MethodsWe enrolled a cohort of 120 consecutive patients referred to a dipyridamole 82Rb PET MPI for evaluation of ischemia neither with prior coronary artery bypass graft nor with recent percutaneous coronary intervention that also underwent coronary angiogram within 6 months of the PET study. Patients with and without 3-vessel CAD were compared. ResultsAmong patients with severe 3-vessel CAD, MFR was globally reduced (<2) in 88% (22/25). On the adjusted logistic Cox model, MFR was an independent predictor of 3-vessel CAD [.5 unit decrease, HR: 2.1, 95% CI (1.2-3.8); P = .015]. The incremental value of 82Rb MFR over the SSS was also shown by comparing the adjusted SSS models with and without 82Rb MFR (P = .005). Conclusion82Rb MFR is an independent predictor of 3-vessel CAD and provided added value to relative MPI. Clinical integration of this approach should be considered to enhance detection and risk assessment of patients with known or suspected CAD.

Quantification of myocardial blood flow with 82Rb positron emission tomography: clinical validation with 15O-water

PurposeQuantification of myocardial blood flow (MBF) with generator-produced 82Rb is an attractive alternative for centres without an on-site cyclotron. Our aim was to validate 82Rb-measured MBF in relation to that measured using 15O-water, as a tracer 100% of which can be extracted from the circulation even at high flow rates, in healthy control subject and patients with mild coronary artery disease (CAD).MethodsMBF was measured at rest and during adenosine-induced hyperaemia with 82Rb and 15O-water PET in 33 participants (22 control subjects, aged 30 ± 13 years; 11 CAD patients without transmural infarction, aged 60 ± 13 years). A one-tissue compartment 82Rb model with ventricular spillover correction was used. The 82Rb flow-dependent extraction rate was derived from 15O-water measurements in a subset of 11 control subjects. Myocardial flow reserve (MFR) was defined as the hyperaemic/rest MBF. Pearson’s correlation r, Bland-Altman 95% limits of agreement (LoA), and Lin’s concordance correlation ρ c (measuring both precision and accuracy) were used.ResultsOver the entire MBF range (0.66–4.7 ml/min/g), concordance was excellent for MBF (r = 0.90, [82Rb–15O-water] mean difference ± SD = 0.04 ± 0.66 ml/min/g, LoA = −1.26 to 1.33 ml/min/g, ρ c = 0.88) and MFR (range 1.79–5.81, r = 0.83, mean difference = 0.14 ± 0.58, LoA = −0.99 to 1.28, ρ c = 0.82). Hyperaemic MBF was reduced in CAD patients compared with the subset of 11 control subjects (2.53 ± 0.74 vs. 3.62 ± 0.68 ml/min/g, p = 0.002, for 15O-water; 2.53 ± 1.01 vs. 3.82 ± 1.21 ml/min/g, p = 0.013, for 82Rb) and this was paralleled by a lower MFR (2.65 ± 0.62 vs. 3.79 ± 0.98, p = 0.004, for 15O-water; 2.85 ± 0.91 vs. 3.88 ± 0.91, p = 0.012, for 82Rb). Myocardial perfusion was homogeneous in 1,114 of 1,122 segments (99.3%) and there were no differences in MBF among the coronary artery territories (p > 0.31).ConclusionQuantification of MBF with 82Rb with a newly derived correction for the nonlinear extraction function was validated against MBF measured using 15O-water in control subjects and patients with mild CAD, where it was found to be accurate at high flow rates. 82Rb-derived MBF estimates seem robust for clinical research, advancing a step further towards its implementation in clinical routine.

Impaired Myocardial Flow Reserve on Rubidium-82 Positron Emission Tomography Imaging Predicts Adverse Outcomes in Patients Assessed for Myocardial Ischemia

We evaluated the prognostic value of myocardial flow reserve (MFR) using rubidium-82 ((82)Rb) positron emission tomography (PET) in patients assessed for ischemia. The clinical value of MFR quantification using (82)Rb PET beyond relative myocardial perfusion imaging remains uncertain. We prospectively enrolled 704 consecutive patients; 677 (96%) completed follow-up (median 387 days [interquartile range: 375 to 416 days]). Patients were divided into 4 groups: I, normal summed stress score (SSS) (<4) and normal myocardial flow reserve (MFR) (>2); II, normal SSS and MFR <2; III, SSS ≥4 and MFR ≥2; IV, SSS ≥4 and MFR <2. For patients with a normal SSS and those with an abnormal SSS, there were significant differences in outcomes for hard events (cardiac death and myocardial infarction) between patients with MFR ≥2 and those with MFR <2 (I: 1.3% vs. II: 2% [p = 0.029]; III: 1.1% vs. IV: 11.4% [p = 0.05]) and for major adverse cardiac events (MACE) (p = 0.003 and p < 0.001, respectively). In the adjusted Cox model, MFR was an independent predictor of hard events (hazard ratio: 3.3; 95% confidence interval: 1.1 to 9.5; p = 0.029) and MACE (hazard ratio: 2.4, 95% confidence interval: 1.4 to 4.4, p = 0.003). The incremental prognostic value of the MFR over the SSS was demonstrated by comparing the adjusted SSS model with and without the MFR for hard events (p = 0.0197) and MACE (p = 0.002). MFR quantified using (82)Rb PET predicts hard cardiac events and MACE independent of the SSS and other parameters. Routine assessment of (82)Rb PET-quantified MFR could improve risk stratification for patients being investigated for ischemia.

Prognosis of a Normal Positron Emission Tomography 82Rb Myocardial Perfusion Imaging Study in Women with No History of Coronary Disease

Objectives: Myocardial perfusion imaging (MPI) with positron emission tomography (PET) has advantages over single-photon emission computerized tomography, particularly for women. This investigation was undertaken to define the prognosis of a normal stress PET MPI study in women. Methods:The cohort comprised 457 women evaluated for suspected coronary artery disease (CAD) who had normal pharmacologic stress ⁸²Rb PET MPI. No patient had clinically evident CAD. Kaplan-Meier estimates were used to determine death and initial nonfatal cardiac event rates over 7 years. Log rank tests were used to assess the relationship between baseline cardiac risk and events during follow-up, and to contrast survival in the cohort with age- and gender-matched US census comparators. Results: During follow-up, there were 11 deaths (all nonischemic), 3 nonfatal myocardial infarctions, 3 percutaneous coronary interventions and 1 coronary artery bypass operation. Average risks of death and initial nonfatal cardiac events were 0.72 and 0.47% per year, respectively. Cardiac events were associated with a history of diabetes (p < 0.0003) and a family history of CAD (p < 0.05). Conclusion: A normal cardiac PET study is associated with a very low rate of future cardiac events. Women with diabetes and a strong family history of CAD are more likely to sustain events and require close surveillance for the development of coronary disease.

Incremental Diagnostic Value of Regional Myocardial Blood Flow Quantification Over Relative Perfusion Imaging With Generator-Produced Rubidium-82 PET

Myocardial blood flow (MBF) can be measured with positron emission tomography (PET) and its quantification should provide diagnostic information beyond that obtained through standard visual analysis. However, this possibility has not been fully studied with PET and generator-produced rubidium-82 (⁸²Rb). We evaluated regional MBF in segments with and without ischemia using ⁸²Rb PET in patients with coronary artery disease (CAD). Rest and stress ⁸²Rb PET and coronary angiography were performed for 12 patients with CAD. Based on angiography and relative ⁸²Rb perfusion images, segments were classified into 4 groups (Group A: myocardial ischemia with >70% diameter stenosis; Group B: no ischemia with stenosis; Group C: no ischemia without stenosis; Group D: ischemia without stenosis). Rest MBF was similar among the 4 groups. Groups A and B showed reduced hyperemic MBF compared with Group C (P < 0.05 vs. Group C) [Group A (n=16) 1.28 ± 0.58 ml·min⁻¹·g⁻¹; Group B (n=11) 1.72 ± 0.64 ml·min⁻¹·g⁻¹; Group C (n=9) 2.60 ± 1.09 ml·min⁻¹·g⁻¹; Group D (n=2) 2.33 ml·min⁻¹·g⁻¹]. Coronary flow reserves were inversely correlated with percent diameter stenosis (r=0.76, P < 0.0001). Segments with ischemia and coronary stenosis had reduced hyperemic MBF. Segments with coronary stenosis without ischemia also had reduced hyperemic MBF compared with non-stenotic segments. MBF quantification using ⁸²Rb PET may provide additional diagnostic information.

Coronary endothelial function: a clinical role for PET?

Coronary endothelial dysfunction is the earliest abnormality in the development of coronary atherosclerosis and is also independently associated with future cardiac events. Quantification of myocardial blood flow (MBF) can assist in the diagnosis of diffuse coronary artery disease (CAD), heart failure and microvascular disease [1, 2]. In the absence of coronary stenoses, a reduced coronary flow reserve (CFR) reflects dysfunction of the coronary microcirculation. Positron emission tomography (PET) plays an important role in the assessment of MBF due to four major characteristics: (1) high sensitivity, (2) excellent temporal resolution, (3) the possibility to label molecules without altering their chemical properties and (4) the short half-life of isotopes. The most common method of quantifying MBF involves the acquisition of dynamic images with the cyclotron-produced radiopharmaceuticals 13N-ammonia and 15O-water. An alternative method is the generator-produced 82Rb. In this issue of the European Journal of Nuclear Medicine and Molecular Imaging, Yoshinaga and colleagues present some interesting data comparing the quantitative analysis of coronary endothelial function with 82Rb and 15O-water PET [3]. MBF was assessed at rest and during a cold pressor test (CPT) with 82Rb and 15O-water PET in controls and smokers. They found a reduced CPT to rest ratio in smokers compared with controls for both radiopharmaceuticals. They concluded that 82Rb is a reliable method in comparison to 15O-water PET and that 82Rb may be applicable for risk assessment in subjects with coronary risk factors. The usefulness of 82Rb is proven in this study; however, the study included in total 19 subjects, and there will be a need for studies with larger sample sizes. A wide pallet of pathological disorders like hyperlipidaemia, hypertension, diabetes and smoking attenuate the vasomotor response to NO and reveals the widespread distribution of underlying causes that can result in endothelial dysfunction. In other words, MBF assessment provides a way to document how risk factors translate into measurable damage to the coronary circulation. In my opinion, it is time to get MBF PET ready for the future, because of the open access to 82Rb now in Europe. The use of 82Rb would give advantages compared to 13N-ammonia and 15O-water PET: no need for a cyclotron, 24-h/day access, fast acquisition protocols allowing high throughput, evaluation of stunning by using rest and stress gating modality and a better visual quality compared to 15O-water. Also absolute quantification of MBF is possible with 82Rb and validated [4, 5] and the important parameter of CFR for prognosis can be calculated [6]. Due to the wide range of the 82Rb positron, the resolution is reduced. An important issue of concern is the cost-effectiveness of 82Rb, especially compared to the widely used SPECT technique. The 82Rb generator needs to be replaced every 4–6 weeks, rendering this technique relatively expensive, with a price in the region of 25,000 euros. Industry should put maximal effort into reducing the price of the generator, so that 82Rb may finally facilitate a breakthrough of cardiac PET myocardial perfusion imaging (MPI) for routine clinical practice in Europe. The first studies on the clinical utility of 82Rb MPI were reported almost 25 years ago [7], and accurate data of 82Rb MPI are available in the literature linked to outcomes [8, 9]. Although 82Rb is now widely available in the USA, this tracer is moderately available in Europe; however, a dawn is coming. Industrial 82Rb supply for Europe is growing and may lead to a wider implementation of 82Rb. Nevertheless, and although the use of 82Rb has been already described in a number of reports in the literature, the merit of the present study is that it encourages us to benefit from the substantial superiority of the PET technique for instance over SPECT, resulting in good image quality even in obese patients. The superiority over SPECT can be expected regarding accuracy, study duration, staff radiation exposure, reduced patient dose, patient discomfort and potentially economic benefit. These are all important implications, which may not have been fully appreciated in Europe so far. A clinical role of MBF PET should be highlighted now, because of the easier access to 82Rb.

Quantitative analysis of coronary endothelial function with generator-produced 82Rb PET: comparison with 15O-labelled water PET

Endothelial dysfunction is the earliest abnormality in the development of coronary atherosclerosis. 82Rb is a generator-produced positron emission tomography (PET) myocardial perfusion tracer that is becoming more widely used. We aimed to (1) develop a method for quantitative assessment of coronary endothelial function using the myocardial blood flow (MBF) response during a cold pressor test (CPT) in smokers, measured using 82Rb PET, and (2) compare the results with those measured using 15O-water PET. MBF was assessed at rest and during the CPT with 82Rb and 15O-water in nine controls and ten smokers. A one-compartment model with tracer extraction correction was used to estimate MBF with both tracers. CPT response was calculated as the ratio of MBF during the CPT to MBF at rest. At rest, measurements of MBF for smokers vs controls were not different using 15O-water (0.86±0.18 vs 0.70±0.13, p=0.426) than they were using 82Rb (0.83±0.23 vs 0.62±0.20, p=0.051). Both methods showed a reduced CPT response in smokers vs controls (15O-water, 1.03±0.21 vs 1.42±0.29, p=0.006; 82Rb, 1.02±0.28 vs 1.70±0.52, p<0.001). There was high reliability [intraclass correlation coefficients: 0.48 (0.07, 0.75)] of MBF measurement between 82Rb and 15O-water during the CPT. Using a CPT, 82Rb MBF measurements detected coronary endothelial dysfunctions in smokers. 82Rb MBF measurements were comparable to those made using the 15O-water approach. Thus, 82Rb PET may be applicable for risk assessments or evaluation of risk factor modification in subjects with coronary risk factors.

Generator-produced rubidium-82 positron emission tomography myocardial perfusion imaging—From basic aspects to clinical applications

Cardiovascular disease is the leading cause of death in modern industrialized countries with an aging population. This fact has fueled the need for innovative diagnostic testing intended to improve coronary artery disease (CAD) patient care. Detection of myocardial ischemia using myocardial perfusion imaging (MPI) plays an important role for CAD diagnosis and the prediction of future risk of cardiovascular events. Positron emission tomography (PET) MPI has high diagnostic accuracy and can estimate regional myocardial blood flow (MBF) in patients with CAD. Rubidium-82 ((82)Rb) is a generator-produced PET myocardial perfusion tracer and has been widely used in North America in clinical practice. (82)Rb PET has recently become available in some cardiovascular centers in Europe and Japan. Clinical trials are expected in both regions. (82)Rb PET has high diagnostic accuracy and recent data have shown its prognostic value. Thus, (82)Rb PET would greatly contribute to CAD patients' care. (82)Rb PET can also be used to quantify MBF. This review describes the current status of (82)Rb MPI from basic principles to clinical implications. This paper also highlights the recent development of MBF quantification using (82)Rb PET.

3D versus 2D dynamic 82Rb myocardial blood flow imaging in a canine model of stunned and infarcted myocardium

Previous studies have shown the ability of rubidium-82 ((82)Rb) positron emission tomography (PET) imaging to quantitatively measure myocardial blood flow (MBF), many of which are performed using two-dimensional (2D) imaging. Three-dimensional (3D) imaging provides increased sensitivity and may result in decreased costs owing to a reduction in the required injected activity of radiotracer. This study compares 2D and 3D (82)Rb PET MBF results obtained in the same imaging session. Three-dimensional and 2D (82)Rb perfusion imaging was performed in canines on a GE Discovery LS PET/CT scanner at rest and during hyperemia in stunned and infarcted tissue. MBF (ml/min/g) was determined using a 1-compartment model and an extraction correction of the uptake rate and analyzed using a standard 17-segment model. A strong, significant correlation was present (rho = 0.95, P<0.0001). Average 3D MBF values were slightly lower at rest and higher during stress versus 2D. MBF results in normal, stunned, and infarcted tissue differed by 7% on average and significant increases in MBF from rest to hyperemia were noted with both the techniques. These results imply that MBF results obtained in 3D are comparable with traditional 2D imaging. Therefore, it may be possible to use 3D imaging with lower administered activity, helping to reduce costs and patient dose without compromising quantitative information.

Independent and incremental prognostic value of left ventricular ejection fraction determined by stress gated rubidium 82 PET imaging in patients with known or suspected coronary artery disease

Whether left ventricular ejection fraction (EF) obtained by gated rubidium 82 positron emission tomography (PET) myocardial imaging can identify patients at risk for future cardiac events is unclear. Consecutive patients with known or suspected coronary artery disease who underwent dipyridamole stress gated Rb-82 PET imaging were evaluated. Scoring of perfusion was accomplished by use of a 17-segment model. EF was automatically generated. Patients were stratified based on summed stress scores (SSSs) (0-3, 4-8, or >8) and stress EF (>50%, 40%-49%, or <40%). All-cause mortality was determined by use of the Social Security Death Index. Of 1,441 patients, 132 (9.2%) died during mean follow-up of 2.7 +/- 0.8 years. Annualized mortality rates across SSS groups were 2.4% for SSS of 0 to 3, 4.1% for SSS of 4 to 8, and 6.9% for SSS greater than 8 (P < .001). Similarly, annualized mortality rates were 2.4%, 6.2%, and 9.2% for the group with EF greater than 50%, group with EF of 40% to 49%, and group with EF lower than 40%, respectively (P < .001). On multivariate analysis, the addition of EF to clinical and perfusion variables significantly increased the global chi(2) (73.3 to 107.7, P < .001). Integration of EF with SSS significantly enhanced risk stratification. EF assessed by stress gated Rb-82 PET imaging provides independent and incremental prognostic information and, hence, should be routinely incorporated in risk assessment.

Quantitative relationship between coronary vasodilator reserve assessed by 82Rb PET imaging and coronary artery stenosis severity

The relationship between myocardial blood flow (MBF) and stenosis severity has been determined previously using cyclotron-produced radiotracers such as (15)O-H(2)O and (13)N-ammonia. An attractive alternative to overcome the limitations related to the use of cyclotron might be to use the generator-produced (82)Rb as a flow tracer. The current study was undertaken to investigate the relationship between MBF and coronary vasodilator reserve (CVR) as measured by (82)Rb positron emission tomography (PET) and the percent diameter stenosis as defined by quantitative coronary arteriography. We prospectively evaluated 22 individuals: 15 patients (60 +/- 11 years of age) with angiographically documented coronary artery disease (CAD) and seven age-matched (56 +/- 9 years) asymptomatic individuals without risk factors for CAD. Dynamic (82)Rb PET was performed at rest and after dipyridamole vasodilation. MBF, CVR and an index of 'minimal coronary resistance' (MCR) were assessed in each of the three main coronary territories. Rest and stress MBF in regions subtended by vessels with less than 50% diameter stenosis was similar to that of the individuals with no risk factors for CAD. As a result, CVR was also similar in the two groups (1.9, interquartile [IQ] range from 1.7 to 2.7 vs. 2.2, IQ range from 2 to 3.4 respectively, p = 0.09). CVR successfully differentiated coronary lesions with stenosis severity 70% to 89% from those with 50% to 69% stenosis (1, IQ range from 1 to 1.3 vs. 1.7, IQ range from 1.4 to 2), respectively, p = 0.001. In addition, hyperaemic MBF (r (2) = 0.74, p < 0.001), CVR (r (2) = 0.69, p < 0.001) and MCR (r (2) = 0.78, p < 0.001) measurements were inversely and non-linearly correlated to the percent diameter stenosis on angiography. MBF and CVR are inversely and non-linearly correlated to stenosis severity. Quantitative (82)Rb PET can be a clinically useful tool for an accurate functional assessment of CAD.

Advances in rubidium PET and integrated imaging with CT angiography

The role of rubidium-82 (Rb-82) positron emission tomography (PET) in the evaluation and care of patients with suspected coronary artery disease is evolving in conjunction with advances in PET instrumentation, data analysis, and clinical research. Instrumentation developments such as three-dimensional acquisition, new scintillator materials, and x-ray CT help to improve the quality of Rb-82 images. New approaches to kinetic modeling and software tools for analysis of clinical Rb-82 studies are being developed and evaluated, enabling quantification of absolute myocardial blood flow and flow reserve. Recent clinical research studies are providing new insights into the value of Rb-82 cardiac imaging compared with single photon emission CT myocardial perfusion imaging. Integrated x-ray CT angiography and Rb-82 PET perfusion imaging on hybrid PET/CT systems is an exciting new prospect. Complementary anatomical and functional information on atherosclerosis and ischemia can be provided in a single imaging session for better diagnosis and risk stratification of patients with coronary artery disease.