Rubidium-82 PET Research Articles

Entropy-based myocardial blood flow measurements using PET: a way to improve reproducibility

Abstract Funding Acknowledgements Type of funding sources: None. Background and purpose Myocardial blood flow (MBF) measurements using PET are increasingly used to guide the management of patients with (suspected) coronary artery disease (CAD). Day-to-day variability of these measurements is poor with a 21% standard deviation or 40% 95%-confidence interval [Reference: JACC Cardiovasc Imaging, 2017;10(5):565]. This limits clinical applicability in diagnosis, risk stratification and follow-up as these all depend on comparison of flow values with fixed cut-off values. We expect that reproducibility can be improved by combining flow measurements with the variation of flow values within the myocardium. As entropy is a measure of variability of the associated distribution, we compared the reproducibility of an entropy-based flow parameter with that of conventional myocardial flow reserve (MFR) measurements. Methods We performed a study using intra-individual comparison in 24 patients who underwent rest and regadenoson-induced stress myocardial perfusion imaging using Rubidium-82 on two different PET systems (PET1: Discovery 690, GE Healthcare, and PET2: Vereos, Philips Healthcare) within 3 weeks. MBF for both rest and stress was calculated using Lortie’s one-tissue compartment model (Corridor4DM, INVIA). MFR (ratio of MBF stress/rest) was determined for the myocardial as a whole (MFRglobal), for the three vascular territories: LAD, LCX and RCA (MFRregional) and for the 17 segments. Next, we calculated Shannon’s entropy to measure the variation of the 17 MFR segmental values. We multiplied Shannon’s entropy by the mean of the MFR segmental values resulting in an entropy-based MFR (MFRentropy). For each patient MFRglobal, MFRregional and MRFentropy were compared between both PET systems. For each of the three parameters the test-retest precision was calculated as the SD of the relative difference between measurements. Results The mean difference in MFR measurements between both cameras did not differ from zero (p > 0.05). Mean values for PET1 were MFRglobal = 2.4, MFRregional = 2.4 (LAD), 2.4 (LCX) and 2.5 (RCA), and MFRentropy = 2.4. For PET2 we found MFRglobal = 2.5, MFRregional = 2.5 (LAD), 2.4 (LCX) and 2.6 (RCA), and MFRentropy = 2.5. Test-retest precision was lower for MFRentropy with 11% compared to that of MFRglobal (21%), MFRregional LAD (22%), MFRregional LCX (23%) and MFRregional RCA (24%) (p < 0.01). Conclusion The reproducibility of myocardial flow reserve measurements using Rubidium-82 PET improved by a factor of 2 when an entropy-based flow parameter instead of global or regional MFR parameters is used. This entropy-based flow-parameter may be used to better discriminate ischemia from non-ischemia and may therefore improve CAD management.

Cardiac imaging of a patient with unusual presentation of granulomatosis with polyangiitis: A case report and review of the literature

BackgroundRecent evidence suggests that cardiac involvement in patients with granulomatosis with polyangiitis (GPA) occurs more frequently than previously reported. Multimodality cardiac imaging is gaining attention in the diagnosis, prognostication, and follow-up of such patients; however, the data remain scarce. Results2D-TTE was useful for initial screening; while both cardiac magnetic resonance imaging and 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) metabolic imaging with rubidium-82 PET perfusion imaging were useful for characterization of myocardial disease. 18FDG-PET/CT was very useful for the follow-up of cardiac disease activity following treatment. Conclusion18FDG-PET/CT is sensitive for the detection of cardiac involvement by GPA and is useful for the tissue characterization and follow-up of disease activity following treatment.

3D PET/CT 82Rb PET myocardial blood flow quantification: comparison of half-dose and full-dose protocols.

Quantification of myocardial blood flow (MBF) has become central in the clinical application of Rubidium-82 (82Rb) PET myocardial perfusion scans. Current recommendations suggest injections of 1100-1500MBq of 82Rb in bolus form, which poses a potential risk of PET system saturation on most 3D PET/CT systems currently being used. We aimed to evaluate the frequency and impact of PET system saturation and to test the potential use of a half-dose acquisition protocol. This study comprised 20 patients who underwent repeated rest scans in a single imaging session, one employing a full-dose (FD), and the other scan a half-dose (HfD) protocol. Datasets were evaluated for saturation based on visual assessments of input functions and sinograms. We compared FD and HfD MBF measurements using Bland-Altman plots, coefficients of variation (CV), and paired t tests. A correction factor permitting serial analyses using FD/HfD imaging protocols was obtained using only the datasets without saturation. A dose reduction of 47% was reported for the HfD protocol (FD, 1247 ± 196MBq; HfD, 662 ± 115MBq). Saturation effects were observed in 4/20 (20%) FD scans, with none observed in the 20 HfD scans. Assessment of MBFs for FD and HfD protocols revealed bias in the MBF assessments of 0.09ml/g/min (global MBF, FD = 1.03 ± 0.29 vs HfD = 0.94 ± 0.22ml/g/min (p = 0.001)). Exclusion of patients with visually identified saturation effects (N = 4) reduced the bias to 0.05ml/g/min (global MBF, FD = 0.97 ± 0.28 vs HfD = 0.92 ± 0.23ml/g/min (p = 0.02)). From the datasets without saturation effect, it was possible to generate a bias-correction: Corrected MBFHfD = 1.09*MBFHfD-0.03ml/g/min. MBFFD and MBFHfD did not differ following the bias correction (MBFFD = 0.97 ± 0.28, MBFHfD,corrected = 0.98 ± 0.25ml/g/min, p = 0.77). Saturation effects can be problematic in 82Rb MBF studies using the recommended FD protocols for 3D PET/CT scanners. The use of HfD protocol eliminates the risks of saturation and should be used instead of clinical protocols to avoid erroneous results.

RELATIVE PROGNOSTIC SIGNIFICANCE OF POSITRON EMISSION TOMOGRAPHY (PET) MYOCARDIAL PERFUSION IMAGING (MPI) MARKERS IN ISCHEMIC AND NON-ISCHEMIC CARDIOMYOPATHY

Rubidium-82 PET MPI measures of rest and peak stress perfusion, myocardial flow reserve (MFR), and changes in ejection fraction (LVEF). We compared the relative association of MFR, perfusion defects, and LVEF reserve with prognosis in ICM and NICM. Between 2010-2016, 1,679 consecutive patients with

P4157Coronary flow reserve but not ischemia is a strong predictor of mortality in 551 outpatients referred for stress myocardial perfusion by Rubidium-82 PET imaging

Abstract Background The assessment of myocardial ischemia in patients with suspected coronary artery disease (CAD) is encouraged by current guidelines. The ischemic burden is associated with impaired prognosis. Coronary flow reserve (CFR) is also an independent predictor of cardiovascular mortality but it is unclear which one of these two variables would be stronger to predict mortality. Purpose To evaluate the predictors of death in symptomatic stable patients with suspected CAD referred for stress myocardial perfusion (MP) Rubidium-82 PET imaging. Methods 551 consecutive patients (52% men, mean age 63 years) were enrolled in this study from February to October 2013. The primary endpoint was all-cause death. The event-free survival curves for the primary endpoint were obtained using the Kaplan-Meier method in four groups of patients based on whether ischemia was present and whether CRF was impaired (<2) (Figure). Univariate analysis was performed using Cox regression to identify the variables that were associated with mortality, and the Cox proportional-hazards regression model for the multivariate analysis adjustment. Results During a median follow-up period of 32 months there were 43 deaths giving an estimated cumulative event rate of 7.8%. Univariate predictors of death were: age, higher prevalence of DM and CKD, lower LVEF and BMI. Following a multivariate analysis, only CFR was independently associated with mortality (Table). Predictors of death Variable Univariate model Multivariate model HR (95% CI) P value HR (95% CI) P value Age 1.03 (1.00–1.06) 0.036 1.01 (0.99–1.04) 0.324 Male sex 1.41 (0.76–2.56) 0.277 0.96 (0.70–1.32) 0.809 History of DM 2.12 (1,13–3,97) 0.019 – – History of CKD 4.95 (2,66–9,20) <0.001 – – BMI <30 1.14 (1.05–1.22) <0.001 2.22 (0.93–5.26) 0.071 Rest LVEF, % 0.98 (0.96–0.99) 0.029 0.99 (0.98–1.01) 0.477 Ischemia, % 1.02 (0.97–1.06) 0.436 0.99 (0.91–1.10) 0.990 Ischemia ≥10% 1.33 (0.59–2.99) 0.488 0.90 (0.40–2.05) 0.806 CFR 0.26 (0.15–0.43) <0.001 0.27 (0.16–0.46) <0.001 LVEF = left ventricular ejection fraction. Survival curves for all-cause death. Conclusions In symptomatic outpatients with suspected CAD referred for stress MP Rubidium-82 PET imaging, CFR is the strongest predictor of mortality. Notably, neither the presence of ischemia nor the ischemic burden was associated with the outcome in question.

1. Prevalence and predictors of endothelial dysfunction measured by coronary flow reserve on rubidium-82 PET among symptomatic patients with diabetes mellitus

1. Prevalence and predictors of endothelial dysfunction measured by coronary flow reserve on rubidium-82 PET among symptomatic patients with diabetes mellitus

P394Feasibility of a digital PET system for myocardial blood flow quantification using Rubidium-82 PET

P394Feasibility of a digital PET system for myocardial blood flow quantification using Rubidium-82 PET

How to detect and correct myocardial creep in myocardial perfusion imaging using Rubidium-82 PET?

Reliability of myocardial blood flow (MBF) quantification in myocardial perfusion imaging (MPI) using PET can majorly be affected by the occurrence of myocardial creep when using pharmacologically induced stress. In this paper, we provide instructions on how to detect and correct for myocardial creep. For example, in each time frame of the PET images the myocardium contour and the observed activity have to be compared to check for misalignments. In addition, we provide an overview of the functionality of commonly used software packages to perform this quality control step as not all software packages currently provide this functionality. Furthermore, important clinical considerations to obtain accurate MBF measurements are given.

P396Assessment of motion correction on myocardial blood flow from dynamic rubidium-82 PET

P396Assessment of motion correction on myocardial blood flow from dynamic rubidium-82 PET

Rubidium-82 PET imaging is feasible in a rat myocardial infarction model

BackgroundSmall-animal myocardial infarct models are frequently used in the assessment of new cardioprotective strategies. A validated quantification of perfusion using a non-cyclotron-dependent PET tracer would be of importance in monitoring response to therapy. We tested whether myocardial PET perfusion imaging is feasible with Rubidium-82 (82Rb) in a small-animal scanner using a rat myocardial infarct model. Methods18 Sprague-Dawley rats underwent permanent coronary artery ligation (infarct group), and 11 rats underwent ischemia-reperfusion (reperfusion group) procedure. 82Rb-PET and magnetic resonance imaging (MRI) were conducted before and after the intervention. Perfusion was compared to both left ventricle ejection fraction (LVEF) and infarct size assessed by MRI. ResultsFollow-up global 82Rb-uptake correlated significantly with infarct size (infarct group: r = −0.81, P < 0.001 and reperfusion group: r = −0.61, P = 0.04). Only 82Rb-uptake in the infarct group correlated with LVEF. At follow-up, a higher segmental 82Rb-uptake in the infarct group was associated with better wall motion (β = 0.034, CI [0.028;0.039], P < 0.001, R2 = 0.30), and inversely associated with scar transmurality (β = −2.4 [−2.6; −2.2], P < 0.001, R2 = 0.59). The associations were similar for the reperfusion group. Conclusion82Rb-PET is feasible in small animal scanners despite the long positron range and enables fast and time-efficient myocardial perfusion imaging in rat models.

Relationship of non-invasive quantification of myocardial blood flow to arrhythmic events in patients with implantable cardiac defibrillators

BackgroundIschemia contributes to arrhythmogenesis though its role is incompletely understood. Abnormal myocardial perfusion measured by PET imaging may predict ventricular arrhythmias (VAs) in a high-risk population. MethodsPatients with implantable cardiac defibrillators who had undergone rubidium-82 cardiac PET imaging were identified. Patients were stratified by median MBF and MFR values for analysis. The Cox proportional hazards model was used to assess the impact of myocardial perfusion on survival free of VT independent of critical covariates. ResultsA total of 159 patients (124 (78%) males, median age 65.9 years, IQR [56.76-72.63]) were followed for 1.43 years IQR [0.83-2.21]. VA occurred in 29 patients (23.7%). After adjustment for ejection fraction, age, and sex, impaired stress MBF was associated with an increased risk of VA (adjusted HR per ml/min/g 1.52, 95% CI (1.01-2.31), P = 0.04). Summed rest and stress scores were not predictive of VA. Among patients with severe LV dysfunction, stress MBF remained an independent predictor of VA (adjusted HR per 1 ml/min/g HR 1.69, 95% CI (1.03-11.36), P = 0.03), while residual EF, summed rest, and summed stress scores were not (P > 0.05). ConclusionsImpaired stress myocardial blood flow was associated with less survival free of ventricular arrhythmias.

Impact of regadenoson-induced myocardial creep on dynamic Rubidium-82 PET myocardial blood flow quantification

BackgroundRepositioning of the heart during myocardial perfusion imaging (MPI) using Rubidium-82 (Rb-82) PET may occur when using regadenoson. Our aim was to determine the prevalence and the effect of correcting for this myocardial creep on myocardial blood flow (MBF) quantification. MethodsWe retrospectively included 119 consecutive patients who underwent dynamic rest- and regadenoson-induced stress MPI using Rb-82 PET. The presence of myocardial creep was visually assessed in the dynamic stress PET series by identifying differences between the automatically drawn myocardium contour and the activity. Uncorrected and corrected stress MBFs were compared for the three vascular territories (LAD, LCX, and RCA) and for the whole myocardium. ResultsMyocardial creep was observed in 52% of the patients during stress. Mean MBF values decreased after correction in the RCA from 4.0 to 2.7 mL/min/g (P < 0.001), in the whole myocardium from 2.7 to 2.6 mL/min/g (P = 0.01), and increased in the LAD from 2.5 to 2.6 mL/min/g (P = 0.03) and remained comparable in the LCX (P = 0.3). ConclusionsMyocardial creep is a frequent phenomenon when performing regadenoson-induced stress Rb-82 PET and has a significant impact on MBF values, especially in the RCA territory. As this may hamper diagnostic accuracy, myocardial creep correction seems necessary for reliable quantification.

Perfusion imaging using rubidium-82 (82Rb) PET in rats with myocardial infarction: First small animal cardiac 82Rb-PET

Perfusion imaging using rubidium-82 (82Rb) PET in rats with myocardial infarction: First small animal cardiac 82Rb-PET

Left ventricular function in response to dipyridamole stress: head-to-head comparison between 82Rubidium PET and 99mTc-sestamibi SPECT ECG-gated myocardial perfusion imaging

PurposeMyocardial perfusion imaging (MPI) with 99mTc-sestamibi (sestamibi) SPECT and rubidium-82 (82Rb) PET both allow for combined assessment of perfusion and left ventricular (LV) function. We sought to compare parameters of LV function obtained with both methods using a single dipyridamole stress dose.Materials and methodsA group of 221 consecutive patients (65.2 ± 10.4 years, 52.9% male) underwent consecutive sestamibi and 82Rb MPI after a single dipyridamole stress dose. Sestamibi and 82Rb summed rest (SRS), stress (SSS) and difference (SDS) scores, and LV end-diastolic (EDV) and end-systolic (ESV) volumes and left ventricular ejection fraction (LVEF) were compared.ResultsBland-Altman analysis showed that with increasing ESV and EDV the difference between the two perfusion tracers increased both at rest and post-stress. The mean difference in EDV and ESV between the two perfusion tracers at rest could both be independently explained by the 82Rb SDS and the sestamibi SRS. The combined models explained approximately 30% of the variation in these volumes between the two perfusion tracers (R2 = 0.261, p = 0.005; R2 = 0.296, p < 0.001, for EDV and ESV respectively). However, the mean difference in LVEF between sestamibi and 82Rb showed no significant trend post-stress (R2 = 0.001, p = 0.70) and only a modest linear increase with increasing LVEF values at rest (R2 = 0.032, p = 0.009).ConclusionsDifferences in left ventricular volumes between sestamibi and 82Rb MPI increase with increasing volumes. However, these differences did only marginally affect LVEF between sestamibi and 82Rb. In clinical practice these results should be taken into account when comparing functional derived parameters between sestamibi and 82Rb MPI.

Transthoracic Doppler echocardiography compared with positron emission tomography for assessment of coronary microvascular dysfunction: The iPOWER study

BackgroundCoronary microvascular function can be assessed by transthoracic Doppler echocardiography as a coronary flow velocity reserve (TTDE CFVR) and by positron emission tomography as a myocardial blood flow reserve (PET MBFR). PET MBFR is regarded the noninvasive reference standard for measuring coronary microvascular function but has limited availability. We compared TTDE CFVR with PET MBFR in women with angina pectoris and no obstructive coronary artery disease and assessed repeatability of TTDE CFVR. MethodsFrom a cohort of women with angina and no obstructive coronary artery stenosis at invasive coronary angiography, TTDE CFVR by dipyridamole induced stress and MBFR by rubidium-82 PET with adenosine was successfully measured in 107 subjects. Repeatability of TTDE CFVR was assessed in 10 symptomatic women and in 10 healthy individuals. ResultsMBFR was systematically higher than CFVR. Median MBFR (interquartile range, IQR) was 2.68 (2.29–3.10) and CFVR (IQR) was 2.31 (1.89–2.72). Pearson's correlation coefficient was 0.36 (p<0.01). Limits of agreement (2·standard deviation) assessed by the Bland–Altman (confidence interval, CI) method was 1.49 (1.29;1.69) and unaffected by time-interval between examinations. Results were similar when adjusting for rate pressure product or focusing on perfusion of the left anterior descending artery region. Limits of agreement (CI) for repeated CFVR in 10 healthy individuals and in 10 women with angina was 0.44 (0.21;0.68) and 0.48 (0.22; 0.74), respectively. ConclusionCFVR had a good repeatability, but the agreement between CFVR and MBFR was modest. Divergence could be due to methodology differences; TTDE estimates flow velocities whereas PET estimates myocardial blood flow.

Male breast uptake in rubidium-82 PET due to spironolactone-induced gynecomastia

Male breast uptake in rubidium-82 PET due to spironolactone-induced gynecomastia

Feasibility of stress only rubidium-82 PET myocardial perfusion imaging

BackgroundStress only SPECT myocardial perfusion imaging (MPI) is a validated strategy to streamline cardiac diagnostic imaging. The potential use of Rb82 PET stress only MPI has not been investigated. Methods and ResultsStress images from 200 Rb82 PET-MPI were reviewed by two blinded readers and categorized as not requiring additional rest images (normal) or requiring additional images (abnormal or equivocal). No additional images were deemed necessary for 95 (48%) and 99 (50%) by the two blinded readers. The stress only interpretation was compared to the previous read of the complete rest-stress study. The rate of detecting a normal result with stress only reading was 76%-79% with a negative predictive value of 94%-95%. Clinical predictors of a normal stress only PET-MPI included lower age, the absence of CAD, and female gender, but not body mass index. Blinded reads of 50 additional consecutive PET-MPI from patients with selected clinical predictors (age <65 years, no known CAD) were then performed. Of these, 40 (80%) were normal by previous rest-stress reading, and 34 (68%) were categorized as not requiring additional images after stress only reading. PET stress only imaging would have resulted in a mean reduction of radiation exposure of 2.4 mSv per study according to a published radiation estimate. ConclusionStress only Rb82 PET-MPI is a feasible strategy to reduce resource utilization and radiation exposure associated with MPI. This strategy would be most applicable to patients with a lower pretest likelihood.

Regadenoson pharmacologic rubidium-82 PET: A comparison of quantitative perfusion and function to dipyridamole

BackgroundDipyridamole is used for stress 82rubidium chloride (82RbCl) PET because of its long hyperemic duration. Regadenoson has advantages of a fixed dose and favorable symptom profile, but its mean maximal hyperemia is only 2.3 minutes. To determine its suitability for 82RbCl PET, we imaged subjects using a regadenoson protocol based on its hyperemic response and compared the images in the same subjects having dipyridamole PET. MethodsIn 32 subjects (23 M), we assessed visually by blinded interpretation and quantitatively compared summed stress and difference scores, total perfusion deficit (TPD), LVEF, LV volumes, and change in stress-rest function. Linear correlation and Bland-Altman analysis of the paired measurements were applied for evaluation of differences. Paired t test and Pearson’s correlation were applied for testing of significance. ResultsThe images were interpreted the same by visual assessment. Twenty-six (26) subjects had reversible defects; by quantitation the SSS was 12.9 ± 7.0 and 14.1 ± 6.4 (P = .23) and SDS was 7.0 ± 6.8 versus 7.6 ± 6.2 (P = .40) for dipyridamole and regadenoson, respectively. Six (6) subjects had <5% likelihood of CAD and were normal by both. All paired measurements showed a high positive correlation between regadenoson and dipyridamole; stress segmental perfusion Reg = 0.93Dip + 4.4, r = 0.88; TPD Reg = 0.94Dip + 0.41, r = 0.93; LVEF Reg = 0.92Dip + 4.7, r = 0.95; stress minus rest LVEF Reg = 0.87Dip − 0.99, r = 0.82. ConclusionRegadenoson stress 82RbCl PET perfusion defect and cardiac function measurements are visually and quantitatively equivalent to dipyridamole studies and can be obtained with the clinical advantages of regadenoson.

Short-term repeatability of resting myocardial blood flow measurements using rubidium-82 PET imaging

BackgroundRubidium-82 (82Rb) PET imaging has been proposed for routine myocardial blood flow (MBF) quantification. However, few studies have investigated the test-retest repeatability of this method. The aim of this study was to optimize same-day repeatability of rest MBF imaging with a highly automated analysis program (FlowQuant) using image-derived input functions and dual spillover corrections (SOC). MethodsTest-retest repeatability of resting left-ventricle (LV) MBF was measured in patients (n = 27) with suspected coronary artery disease (CAD) and healthy volunteers (n = 9). The effects of scan-time, reconstruction, and quantification methods were assessed with correlation and Bland-Altman repeatability coefficients. ResultsFactors affecting rest MBF included gender, suspected CAD, and SOC (P < .001). Significant test-retest correlations were found using all analysis methods tested (r > 0.79). The best repeatability coefficient for same-day MBF was 0.20 mL/minute/g using a 6-minute scan-time, iterative reconstruction, SOC, resting rate-pressure-product (RPP) adjustment, and left atrium input function. This protocol was significantly less variable than standard protocols using filtered back-projection reconstruction, longer scan-time, no SOC, or LV input function. ConclusionAbsolute MBF can be measured with good repeatability using FlowQuant analysis of 82Rb PET scans with a 6-minute scan time, iterative reconstruction, dual SOC, RPP-adjustment, and an image-derived input function in the left atrium cavity.

Evaluating the Prognostic Value of Positron‐Emission Tomography Myocardial Perfusion Imaging Using Automated Software to Calculate Perfusion Defect Size

Myocardial perfusion imaging by positron-emission tomography (PET MPI) is regarded as a valid technique for the diagnosis of coronary artery disease (CAD), but the incremental prognostic value of PET MPI among individuals with known or suspected CAD is not firmly established. Myocardial perfusion defect sizes as measured by PET MPI using automated software will provide incremental prognostic value for cardiac and all-cause mortality. This study included 3739 individuals who underwent rest-stress rubidium-82 PET MPI for the evaluation of known or suspected CAD. Rest, stress, and stress-induced myocardial perfusion defect sizes were determined objectively by automated computer software. Study participants were followed for a mean of 5.2 years for cardiac and all-cause mortality. Cox proportional hazards models were developed to evaluate the incremental prognostic value of PET MPI. A strong correlation was observed between perfusion defect sizes assessed visually and by automated software (r = 0.76). After adjusting for cardiac risk factors, known CAD, noncoronary vascular disease, and use of cardioprotective medications, stress perfusion defect size was strongly associated with cardiac death (P < 0.001). Rest perfusion defects demonstrated a stronger association with cardiac death (P < 0.001) than stress-induced perfusion defects (P = 0.01), yet both were highly significant. Similar patterns held for all-cause death. The current study is the largest to date demonstrating PET MPI provides incremental prognostic value among individuals with known or suspected CAD. Automated calculation of perfusion defect sizes may provide valuable supplementary information to visual assessment.