Positron Emission Tomography Myocardial Blood Flow Research Articles

PET-determined myocardial perfusion and flow in coronary artery disease characterization

Positron emission tomography (PET) myocardial perfusion imaging in conjunction with tracer-kinetic modeling enables the concurrent assessment of myocardial perfusion and regional myocardial blood flow (MBF) of the left ventricle in absolute terms in milliliters per gram per minute (mL/g/min). The non-invasive quantification of MBF during pharmacologically induced hyperemia, at rest, and corresponding myocardial flow reserve (MFR) opens a new avenue for the identification and characterization of classical or endogen type of coronary microvascular dysfunction (CMD) as functional substrate for microvascular angina in patients with non-obstructive coronary artery disease (CAD) and/or no CAD at all. Further, PET-MBF quantification expands the scope of conventional myocardial perfusion imaging from the identification of advanced, and flow-limiting, epicardial CAD to early stages of atherosclerosis and/or CMD. Adding MBF assessment to myocardial perfusion may also reliably unravel diffuse ischemia owing to significant left main stenosis and/or multivessel CAD, confirmed by peak stress transient ischemic cavity dilation of the left ventricle during maximal vasomotor stress on gated PET images. Owing to high spatial and contrast resolution in conjunction with photon-attenuation free myocardial perfusion PET images, PET is preferentially used for CAD in advanced obesity and women with pronounced breast habitus. With increasing clinical use of cardiac PET perfusion and MBF assessment, individualized, and image-guided cardiovascular treatment decisions in CAD patients is likely to ensue, while its translation into improved cardiovascular outcome remains to be investigated.

Validation of the resting full-cycle ratio and diastolic pressure ratio through myocardial perfusion imaging with [15O]H2O positron emission tomography

Abstract Background Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging techniques and clinical trials. However, new invasive pressure indices that do not require hyperemia have recently emerged, and it is essential to confirm their diagnostic efficacy. Purpose To validate the resting full-cycle ratio (RFR) and the diastolic pressure ratio (dPR), against [15O]H2O positron emission tomography (PET) imaging. Methods A total of 129 symptomatic patients with an intermediate risk of coronary artery disease (CAD) were included. All patients underwent cardiac [15O]H2O PET with quantitative assessment of myocardial perfusion, and within 2 weeks coronary angiography was performed. Intracoronary pressure measurements were obtained in 320 vessels and RFR, dPR, and FFR were computed. In the case of RFR and dPR, values ≤ 0.89, and for FFR, values ≤ 0.8 were classified as abnormal. PET myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) served as reference standards. The index tests and gold standard results were evaluated by blinded researchers. Results Figure 1 shows the diagnostic performance of each ratio in coronary arteries with stenoses (136 of 320 vessels, 38%). The overall diagnostic accuracies of RFR, dPR and FFR did not differ when PET MBF < 2.3 ml · min-1 and PET MPR < 2.5 were considered as the reference standard. No significant differences were observed in the areas under the receiver-operating-characteristic (ROC) curve among the indices (Figure 2). In addition, the indices demonstrated comparable performance when the analysis included all of the vessels. Conclusion The novel non-hyperemic pressure ratios, RFR and dPR, have a diagnostic performance that is comparable to FFR when using [15O]H2O PET to assess myocardial perfusion abnormalities. These findings suggest that RFR and dPR may be considered for clinical use in symptomatic patients with CAD.Figure 1Diagnostic performance;StenosisFigure 2ROC curve analysis;Stenosis

Advances in Digital PET Technology and Its Potential Impact on Myocardial Perfusion and Blood Flow Quantification.

In this review, we explore the development of digital PET scanners and describe the mechanism by which they work. We dive into some technical details on what differentiates a digital PET from a conventional PET scanner and how such differences lead to better imaging characteristics. Additionally, we summarize the available evidence on the improvements in the images acquired by digital PET as well as the remaining pitfalls. Finally, we report the comparative studies available on how digital PET compares to conventional PET, particularly in the quantification of coronary blood flow. The advent of digital PET offers high sensitivity and time-of-flight (TOF), which allow lower activity and scan times, with much less risk of detector saturation. This allows faster patient throughput, scanning more patients per generator, and acquiring more consistent image quality across patients. The higher sensitivity captures more of the potential artifacts, particularly motion-related ones, which presents a current challenge that still needs to be tackled. The digital silicon photomultiplier (SiPM) positron emission tomography (PET) machine has been an important development in the technological advancements of non-invasive nuclear cardiovascular imaging. It has enhanced the utility for PET myocardial perfusion imaging (MPI) and myocardial blood flow (MBF) quantification.

PET Myocardial Blood Flow for Post-transplant Surveillance and Cardiac Allograft Vasculopathy in Heart Transplant Recipients.

Cardiac allograft vasculopathy (CAV) is a late-occurring complication of heart transplantation significantly limiting overall graft survival. In the last few years, evidence has been growing about the use of positron emission tomography (PET) myocardial perfusion imaging with integrated myocardial blood flow (MBF) quantification in heart transplant recipients. Multiple studies have demonstrated that PET MBF assessment can be utilized to establish the diagnosis of CAV noninvasively and can be employed for prognostication. PET MBF quantification has also helped to define the link between transplant rejection and CAV. In addition, limited data suggests that PET MBF quantification can be used in heart transplant patients for serial monitoring of CAV. PET myocardial perfusion imaging integrating MBF quantification shows great promise for the evaluation of CAV with good diagnostic and prognostic performance.

Warranty period of normal CCTA and [15O]H2O PET in chest pain patients

Abstract Background Normal coronary computed tomography angiography (CTA) and positron emission tomography (PET) are associated with an excellent prognosis. Hitherto, data on the warranty period of normal coronary CTA and normal myocardial blood flow (MBF) by PET are scarce. Purpose To determine the event-free period after normal coronary CTA and PET results. In addition, to determine whether PET MBF imaging confers additional prognostic value beyond coronary anatomy in symptomatic patients. Methods Patients with suspected but not previously diagnosed coronary artery disease (CAD) who underwent coronary CTA or [15O]H2O PET were categorized based upon coronary CTA as no CAD, non-obstructive CAD or obstructive CAD. A hyperemic MBF <2.3 ml/min/g was considered abnormal and indicative for ischemia. A cumulative risk below 5% against death and myocardial infarction (MI) was used to define the warranty period. Results Of 2575 included patients (mean age 61.4±9.9 years, 41% male) 1319 (51.2%) underwent coronary CTA only, 1237 (48.0%) underwent both coronary CTA and PET and 19 (0.74%) patients underwent PET imaging only. During a median follow-up of 7.0 years 163 deaths and 68 MIs occurred. The warranty period for patients without any CAD was >10 years. Patients with non-obstructive CAD had a 5 year warranty period. In patients with no, non-obstructive or obstructive CAD on CTA, normal PET extended the warranty period with ≥2 years. The warranty period of patients with non-obstructive CAD or normal perfusion varied between 2.5 and >10 years for patients with or without clinical risk factors. Conclusions As standalone imaging, the warranty period for a normal coronary CTA is >10 years, whereas patients with non-obstructive CAD have a warranty period of 5 years. Independent of coronary anatomy normal perfusion imaging has additional prognostic value and extends the warranty period by ≥2 years. Funding Acknowledgement Type of funding sources: None.

A 7-year warranty period for chest pain patients with a non-ischaemic [15O]H2O positron emission tomography: a follow-up of 273 individuals

Abstract Funding Acknowledgements Type of funding sources: None. Background A normal perfusion scan is associated with a favourable outcome. The aim of the present study is to determine the warranty period of normal hyperemic myocardial blood flow (MBF) derived with quantitative [15O]H2O positron emission tomography (PET) in symptomatic individuals with cardiovascular risk factors. Methods A total of 539 patients referred for baseline adenosine [15O]H2O PET MBF imaging because of suspected coronary artery disease (CAD) were investigated. A PET scan was considered normal if the hyperemic MBF was > 2.3 ml/min/g. The warranty period was predefined as < 2% annual event rate. The primary endpoint was a composite of late revascularizations, myocardial infarction and all-cause mortality. Results In a total of 273 patients (mean age 57.2 ± 9.1; 34.4% male) with a normal PET scan, 19 events occurred during a median follow-up of 6.8 years (interquartile range 4.9-7.7). Events included 10 late revascularizations, 2 myocardial infarctions and 7 deaths. The annual event rate exceeded 2% in the 8th year of follow-up, resulting in a warranty period of 7 years (see Figure 1). Conclusion In patients referred for suspected CAD a normal hyperemic perfusion derived by [15O]H2O PET confers a 7-year warranty period against late revascularization, myocardial infarction and all-cause mortality.

Incremental prognostic value of hybrid [15O]H2O positron emission tomography–computed tomography: combining myocardial blood flow, coronary stenosis severity, and high-risk plaque morphology

Aims This study sought to determine the prognostic value of combined functional testing using positron emission tomography (PET) perfusion imaging and anatomical testing using coronary computed tomography angiography (CCTA)-derived stenosis severity and plaque morphology in patients with suspected coronary artery disease (CAD).Methods and results In this retrospective study, 539 patients referred for hybrid [15O]H2O PET-CT imaging because of suspected CAD were investigated. PET was used to determine myocardial blood flow (MBF), whereas CCTA images were evaluated for obstructive stenoses and high-risk plaque (HRP) morphology. Patients were followed up for the occurrence of all-cause death and non-fatal myocardial infarction (MI). During a median follow-up of 6.8 (interquartile range 4.8–7.8) years, 42 (7.8%) patients experienced events, including 23 (4.3%) deaths, and 19 (3.5%) MIs. Annualized event rates for normal vs. abnormal results of PET MBF, CCTA-derived stenosis, and HRP morphology were 0.6 vs. 2.1%, 0.4 vs. 2.1%, and 0.8 vs. 2.8%, respectively (P < 0.001 for all). Cox regression analysis demonstrated prognostic values of PET perfusion imaging [hazard ratio (HR) 3.75 (1.84–7.63), P < 0.001], CCTA-derived stenosis [HR 5.61 (2.36–13.34), P < 0.001], and HRPs [HR 3.37 (1.83–6.18), P < 0.001] for the occurrence of death or MI. However, only stenosis severity [HR 3.01 (1.06–8.54), P = 0.039] and HRPs [HR 1.93 (1.00–3.71), P = 0.049] remained independently associated.Conclusion PET-derived MBF, CCTA-derived stenosis severity, and HRP morphology were univariably associated with death and MI, whereas only stenosis severity and HRP morphology provided independent prognostic value.

Accuracy of Myocardial Blood Flow Estimation From Dynamic Contrast-Enhanced Cardiac CT Compared With PET

Background The accuracy of absolute myocardial blood flow (MBF) from dynamic contrast-enhanced cardiac computed tomography acquisitions has not been fully characterized. We evaluate computed tomography (CT) compared with rubidium-82 positron emission tomography (PET) MBF estimates in a high-risk population. Methods In a prospective trial, patients receiving clinically indicated rubidium-82 PET exams were recruited to receive a dynamic contrast-enhanced cardiac computed tomography exam. The CT protocol included a rest and stress dynamic portion each acquiring 12 to 18 cardiac-gated frames. The global MBF was estimated from the PET and CT exam. Results Thirty-four patients referred for cardiac rest-stress PET were recruited. Of the 68 dynamic contrast-enhanced cardiac computed tomography scans, 5 were excluded because of injection errors or mismatched hemodynamics. The CT-derived global MBF was highly correlated with the PET MBF (r=0.92; P<0.001) with a mean difference of 0.7±26.4%. The CT MBF estimates were within 20% of PET estimates ( P<0.02) with a mean of (1) MBF for resting flow of PET versus CT of 0.9±0.3 versus 1.0±0.2 mL/min per gram and (2) MBF for stress flow of 2.1±0.7 versus 2.0±0.8 mL/min per gram. Myocardial flow reserve was -14±28% underestimated with CT (PET versus CT myocardial flow reserve, 2.5±0.6 versus 2.2±0.6). The proposed rest+stress+computed tomography angiography protocol had a dose length product of 598±76 mGy×cm resulting in an approximate effective dose of 8.4±1.1 mSv. Conclusions In a high-risk clinical population, a clinically practical dynamic contrast-enhanced cardiac computed tomography provided unbiased MBF estimates within 20% of rubidium-82 PET. Although unbiased, the CT estimates contain substantial variance with an standard error of the estimate of 0.44 mL/min per gram. Myocardial flow reserve estimation was not as accurate as individual MBF estimates.

Impact of individualized segmentation on diagnostic performance of quantitative positron emission tomography for haemodynamically significant coronary artery disease.

Despite high variability in coronary anatomy, quantitative positron emission tomography (PET) perfusion in coronary territories is traditionally calculated according to the American Heart Association (AHA) 17-segments model. This study aimed to assess the impact of individualized segmentation of myocardial segments on the diagnostic accuracy of hyperaemic myocardial blood flow (MBF) values for haemodynamically significant coronary artery disease (CAD). Patients with suspected CAD (n = 204) underwent coronary computed tomography angiography (CCTA) and [15O]H2O PET followed by invasive coronary angiography with fractional flow reserve assessment of all major coronary arteries. Hyperaemic MBF per vascular territory was calculated using both standard segmentation according to the AHA model and individualized segmentation, in which CCTA was used to assign coronary arteries to PET perfusion territories. In 122 (59.8%) patients, one or more segments were redistributed after individualized segmentation. No differences in mean MBF values were seen between segmentation methods, except for a minor difference in hyperaemic MBF in the LCX territory (P = 0.001). These minor changes resulted in discordant PET-defined haemodynamically significant CAD between the two methods in only 5 (0.8%) vessels. The diagnostic value for detecting haemodynamically significant CAD did not differ between individualized and standard segmentation, with area under the curves of 0.79 and 0.78, respectively (P = 0.34). Individualized segmentation using CCTA-derived coronary anatomy led to redistribution of standard myocardial segments in 60% of patients. However, this had little impact on [15O]H2O PET MBF values and diagnostic value for detecting haemodynamically significant CAD did not change. Therefore, clinical impact of individualized segmentation seems limited.

Reduced Myocardial Flow Reserve by Positron Emission Tomography Predicts Cardiovascular Events After Cardiac Transplantation.

We evaluated the diagnostic and prognostic value of quantification of myocardial flow reserve (MFR) with positron emission tomography (PET) in orthotopic heart transplant patients. We retrospectively identified orthotopic heart transplant patients who underwent rubidium-82 cardiac PET imaging. The primary outcome was the composite of cardiovascular death, acute coronary syndrome, coronary revascularization, and heart failure hospitalization. Cox regression was used to evaluate the association of MFR with the primary outcome. The relationship of MFR and cardiac allograft vasculopathy severity in patients with angiography within 1 year of PET imaging was assessed using Spearman rank correlation and logistic regression. A total of 117 patients (median age, 60 years; 71% men) were identified. Twenty-one of 62 patients (34%) who underwent angiography before PET had cardiac allograft vasculopathy. The median time from orthotopic heart transplant to PET imaging was 6.4 years (median global MFR, 2.31). After a median of 1.4 years, 22 patients (19%) experienced the primary outcome. On an unadjusted basis, global MFR (hazard ratio, 0.22 per unit increase; 95% confidence interval, 0.09-0.50; P<0.001) and stress myocardial blood flow (hazard ratio, 0.48 per unit increase; 95% confidence interval, 0.29-0.79; P=0.004) were associated with the primary outcome. Decreased MFR independently predicted the primary outcome after adjustment for other variables. In 42 patients who underwent angiography within 12 months of PET, MFR and stress myocardial blood flow were associated with moderate-severe cardiac allograft vasculopathy (International Society of Heart and Lung Transplantation grade 2-3). MFR assessed by cardiac rubidium-82 PET imaging is a predictor of cardiovascular events after orthotopic heart transplant and is associated with cardiac allograft vasculopathy severity.

Multimodality quantitative assessments of myocardial perfusion using dynamic contrast enhanced magnetic resonance and 15O-labelled water positron emission tomography imaging.

Kinetic modelling of myocardial perfusion imaging data allows the absolute quantification of myocardial blood flow (MBF) and can improve the diagnosis and clinical assessment of coronary artery disease (CAD). Positron emission tomography (PET) imaging is considered the reference standard technique for absolute quantification, whilst oxygen-15 (15O)-water has been extensively implemented for MBF quantification. Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) has also been used for MBF quantification and showed comparable diagnostic performance against (15O)-water PET studies. We investigated for the first time the diagnostic performance of two different PET MBF analysis softwares PMOD and Carimas, for obstructive CAD detection against invasive clinical standard methods in 20 patients with known or suspected CAD. Fermi and distributed parameter modelling-derived MBF quantification from DCE-MRI was also compared against (15O)-water PET, in a subgroup of 6 patients. The sensitivity and specificity for PMOD was significantly superior for obstructive CAD detection in both per vessel (0.83, 0.90) and per patient (0.86, 0.75) analysis, against Carimas (0.75, 0.65), (0.81, 0.70), respectively. We showed strong, significant correlations between MR and PET MBF quantifications (r=0.83-0.92). However, DP and PMOD analysis demonstrated comparable and higher haemodynamic differences between obstructive versus (no, minor or non)-obstructive CAD, against Fermi and Carimas analysis. Our MR method assessments against the optimum PET reference standard technique for perfusion analysis showed promising results in per segment level and can support further multi-modality assessments in larger patient cohorts. Further MR against PET assessments may help to determine their comparative diagnostic performance for obstructive CAD detection.

Computed tomography myocardial perfusion vs 15O-water positron emission tomography and fractional flow reserve

ObjectivesComputed tomography (CT) can perform comprehensive cardiac imaging. We compared CT coronary angiography (CTCA) and CT myocardial perfusion (CTP) with 15O-water positron emission tomography (PET) and invasive coronary angiography (ICA) with fractional flow reserve (FFR).Methods51 patients (63 (61–65) years, 80 % male) with known/suspected coronary artery disease (CAD) underwent 320-multidetector CTCA followed by “snapshot” adenosine stress CTP. Of these 22 underwent PET and 47 ICA/FFR. Obstructive CAD was defined as CTCA stenosis >50 % and CTP hypoperfusion, ICA stenosis >70 % or FFR <0.80.ResultsPET hyperaemic myocardial blood flow (MBF) was lower in obstructive than non-obstructive territories defined by ICA/FFR (1.76 (1.32–2.20) vs 3.11 (2.44–3.79) mL/(g/min), P < 0.001) and CTCA/CTP (1.76 (1.32–2.20) vs 3.12 (2.44–3.79) mL/(g/min), P < 0.001). Baseline and hyperaemic CT attenuation density was lower in obstructive than non-obstructive territories (73 (71–76) vs 86 (84–88) HU, P < 0.001 and 101 (96–106) vs 111 (107–114) HU, P 0.001). PET hyperaemic MBF corrected for rate pressure product correlated with CT attenuation density (r = 0.579, P < 0.001). There was excellent per-patient sensitivity (96 %), specificity (85 %), negative predictive value (90 %) and positive predictive value (94 %) for CTCA/CTP vs ICA/FFR.ConclusionCT myocardial attenuation density correlates with 15O-water PET MBF. CTCA and CTP can accurately identify obstructive CAD.Key Points•CT myocardial perfusion can aid the assessment of suspected coronary artery disease.• CT attenuation density from “snapshot” imaging is a marker of myocardial perfusion.• CT myocardial attenuation density correlates with15O-water PET myocardial blood flow.• CT attenuation density is lower in obstructive territories defined by invasive angiography.• Diagnostic accuracy of CTCA+CTP is comparable to invasive angiography + fractional flow reserve.

Doppler-derived intracoronary physiology indices predict the occurrence of microvascular injury and microvascular perfusion deficits after angiographically successful primary percutaneous coronary intervention.

A total of 40% to 50% of patients with ST-segment-elevation myocardial infarction develop microvascular injury (MVI) despite angiographically successful primary percutaneous coronary intervention (PCI). We investigated whether hyperemic microvascular resistance (HMR) immediately after angiographically successful PCI predicts MVI at cardiovascular magnetic resonance and reduced myocardial blood flow at positron emission tomography (PET). Sixty patients with ST-segment-elevation myocardial infarction were included in this prospective study. Immediately after successful PCI, intracoronary pressure-flow measurements were performed and analyzed off-line to calculate HMR and indices derived from the pressure-velocity loops, including pressure at zero flow. Cardiovascular magnetic resonance and H2 (15)O PET imaging were performed 4 to 6 days after PCI. Using cardiovascular magnetic resonance, MVI was defined as a subendocardial recess of myocardium with low signal intensity within a gadolinium-enhanced area. Myocardial perfusion was quantified using H2 (15)O PET. Reference HMR values were obtained in 16 stable patients undergoing coronary angiography. Complete data sets were available in 48 patients of which 24 developed MVI. Adequate pressure-velocity loops were obtained in 29 patients. HMR in the culprit artery in patients with MVI was significantly higher than in patients without MVI (MVI, 3.33±1.50 mm Hg/cm per second versus no MVI, 2.41±1.26 mm Hg/cm per second; P=0.03). MVI was associated with higher pressure at zero flow (45.68±13.16 versus 32.01±14.98 mm Hg; P=0.015). Multivariable analysis showed HMR to independently predict MVI (P=0.04). The optimal cutoff value for HMR was 2.5 mm Hg/cm per second. High HMR was associated with decreased myocardial blood flow on PET (myocardial perfusion reserve <2.0, 3.18±1.42 mm Hg/cm per second versus myocardial perfusion reserve ≥2.0, 2.24±1.19 mm Hg/cm per second; P=0.04). Doppler-flow-derived physiological indices of coronary resistance (HMR) and extravascular compression (pressure at zero flow) obtained immediately after successful primary PCI predict MVI and decreased PET myocardial blood flow. http://www.trialregister.nl. Unique identifier: NTR3164.

β2-adrenergic stress evaluation of coronary endothelial-dependent vasodilator function in mice using (11)C-acetate micro-PET imaging of myocardial blood flow and oxidative metabolism.

BackgroundEndothelial dysfunction is associated with vascular risk factors such as dyslipidemia, hypertension, and diabetes, leading to coronary atherosclerosis. Sympathetic stress using cold-pressor testing (CPT) has been used to measure coronary endothelial function in humans with positron emission tomography (PET) myocardial blood flow (MBF) imaging, but is not practical in small animal models. This study characterized coronary vasomotor function in mice with [11C]acetate micro-PET measurements of nitric-oxide-mediated endothelial flow reserve (EFRNOM) (adrenergic-stress/rest MBF) and myocardial oxygen consumption (MVO2) using salbutamol β2-adrenergic-activation.Methods[11C]acetate PET MBF was performed at rest + salbutamol (SB 0.2, 1.0 μg/kg/min) and norepinephrine (NE 3.2 μg/kg/min) stress to measure an index of MBF response. β-adrenergic specificity of NE was evaluated by pretreatment with α-adrenergic-antagonist phentolamine (PHE), and β2-selectivity was assessed using SB.ResultsAdjusting for changes in heart rate × systolic blood pressure product (RPP), the same stress/rest MBF ratio of 1.4 was measured using low-dose SB and NE in normal mice (equivalent to human CPT response). The MBF response was correlated with changes in MVO2 (p = 0.02). Nitric oxide synthase (NOS)-inhibited mice (Ng-nitro-L-arginine methyl ester (L-NAME) pretreatment and endothelial nitric oxide synthase (eNOS) knockout) were used to assess the EFRNOM, in which the low-dose SB- and NE-stress MBF responses were completely blocked (p = 0.02). With high-dose SB-stress, the MBF ratio was reduced by 0.4 following NOS inhibition (p = 0.03).ConclusionsLow-dose salbutamol β2-adrenergic-stress [11C]acetate micro-PET imaging can be used to measure coronary-specific EFRNOM in mice and may be suitable for assessment of endothelial dysfunction in small animal models of disease and evaluation of new therapies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-014-0068-9) contains supplementary material, which is available to authorized users.

Inducibility of ventricular arrhythmias is related with impaired hyperaemic myocardial blood flow assessed with [15O]H2O PET in patients with ischaemic cardiomyopathy

Purpose: Prediction of ventricular arrhythmias (VA) is important to refine selection criteria for implantable cardioverter defibrillator (ICD) therapy in patients with ischaemic cardiomyopathy (ICMP). Cardiac positron emission tomography (PET) allows for absolute quantification of myocardial blood flow (MBF) and is increasingly available in clinical practice. Hyperaemic MBF has been demonstrated to predict cardiac death in ischaemic and non-ischaemic cardiomyopathy. However, data on the relationship with VA are lacking. The aim of this study was to assess whether hyperaemic MBF impairment is related with the inducibility of VA in patients with ICMP. Methods: Patients with ICM who were referred for ICD implantation for primary prevention based on current guidelines were included. They underwent [15O]H2O PET assessment of global MBF under both resting and hyperaemic conditions. After implantation, according to standard procedure, the ICD was used to perform an electrophysiological study (EPS) to test the inducibility of VA. EPS was considered positive in case of sustained VA. Results: Twenty-eight patients were included (24 men, age 67±9 years, LVEF 28±7%). Patients (n=10) with positive EPS had significantly reduced global hyperaemic MBF and coronary flow reserve (CFR) compared with EPS negative patients (1.19±0.28 vs. 1.58±0.35 ml/min/g, p<0.01 and 1.55±0.34 vs. 2.05±0.46, p<0.01, respectively). No significant differences were found in age, sex, LVEF, creatinine, NT-proBNP, NYHA class and resting MBF. ROC-curve analysis demonstrated that hyperaemic MBF (AUC 0.82, 95% CI 0.66-0.99, p<0.01) and CFR (AUC 0.80, 95% CI 0.63-0.97, p=0.01) were predictors for VA inducibility. Univariate analysis revealed that hyperaemic MBF (p=0.02) and CFR (p=0.02) were the only variables significantly associated with a positive EPS. Conclusion: Impaired global hyperaemic MBF and CFR predict inducibility of VA in patients with ICMP. These results suggest that impaired hyperaemic MBF might contribute to electrical instability. Risk stratification for VA might be enhanced by quantitative [15O]H2O PET MBF assessment in ICMP patients.

Myocardial Blood Flow Quantification Using Positron-Emission Tomography

Myocardial perfusion imaging (MPI) has played an important role in the diagnosis and risk assessment of coronary artery disease (CAD) since the early 1970s. Positron emission tomography (PET) MPI has high diagnostic accuracy and prognostic value. PET MPI can also be used to quantitatively evaluate regional myocardial blood flow (MBF) through a mathematical model. PET MBF measurements can be used in evaluating early-stage atherosclerosis with endothelial dysfunction right through to diagnosing CAD. PET/computed tomography scanners are now found in many facilities across North America, Europe, and Asia, and PET MBF quantification is expected to move from strictly research to more clinical applications. Nuclear cardiology has been a leader in quantification approaches that can be applied to other new imaging modalities. Therefore, it would be valuable to understand the basic aspects of quantification approaches. This review will address the basic aspects of MBF quantification and the additional value of quantification approaches in the clinical setting.

The frontiers of nuclear cardiology research

The frontiers of nuclear cardiology research

Assessment of coronary endothelial function using PET

Endothelial dysfunction is the earliest abnormality in the development of coronary atherosclerosis. Several coronary risk factors adversely affect endothelial function. Therefore, a finding of endothelial dysfunction may guide interventions for preventing the development of future cardiovascular events. The non-invasive aspects and coronary specificity of measurements of myocardial blood flow (MBF) using positron emission tomography (PET) with sympathetic stress make it widely applicable for the evaluation of endothelial function. PET MBF measurements with sympathetic stress have been applied to a variety of subjects with coronary risk factors and have been shown to have value for risk assessment in these subjects. Endothelial measurement using PET remains an ideal research tool for the study of the pathophysiology of several cardiac diseases. PET is also well suited for the acute and longitudinal evaluation of treatment. Thus, the continued development of this approach for the evaluation of new treatment effects should be expected.