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Background: We developed an explainable deep-learning (DL)-based classifier to identify flow-limiting coronary artery disease (CAD) by O-15 H 2 O perfusion positron emission tomography computed tomography (PET/CT) and coronary CT angiography (CTA) imaging. The classifier uses polar map images with numerical data and visualizes data findings., Methods: A DLmodel was implemented and evaluated on 138 individuals, consisting of a combined image-and data-based classifier considering 35 clinical, CTA, and PET variables. Data from invasive coronary angiography were used as reference. Performance was evaluated with clinical classification using accuracy (ACC), area under the receiver operating characteristic curve (AUC), F1 score (F1S), sensitivity (SEN), specificity (SPE), precision (PRE), net benefit, and Cohen's Kappa. Statistical testing was conducted using McNemar's test., Results: The DL model had a median ACC = 0.8478, AUC = 0.8481, F1S = 0.8293, SEN = 0.8500, SPE = 0.8846, and PRE = 0.8500. Improved detection of true-positive and false-negative cases, increased net benefit in thresholds up to 34%, and comparable Cohen's kappa was seen, reaching similar performance to clinical reading. Statistical testing revealed no significant differences between DL model and clinical reading., Conclusions: The combined DL model is a feasible and an effective method in detection of CAD, allowing to highlight important data findings individually in interpretable manner., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Vascular adhesion protein-1 (VAP-1) is an adhesion molecule and primary amine oxidase, and Gallium-68-labeled 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetra-acetic acid conjugated sialic acid-binding immunoglobulin-like lectin 9 motif containing peptide ([ 68 Ga]Ga-DOTA-Siglec-9) is a positron emission tomography (PET) tracer targeting VAP-1. We evaluated the feasibility of PET imaging with [ 68 Ga]Ga-DOTA-Siglec-9 for the detection of myocardial lesions in rats with autoimmune myocarditis., Methods: Rats (n = 9) were immunized twice with porcine cardiac myosin in complete Freund's adjuvant. Control rats (n = 6) were injected with Freund's adjuvant alone. On day 21, in vivo PET/computed tomography (CT) imaging with [ 68 Ga]Ga-DOTA-Siglec-9 was performed, followed by ex vivo autoradiography, histology, and immunohistochemistry of tissue sections. In addition, myocardial samples from three patients with cardiac sarcoidosis were studied., Results: [ 68 Ga]Ga-DOTA-Siglec-9 PET/CT images of immunized rats showed higher uptake in myocardial lesions than in myocardium outside lesions (SUV mean , 0.5 ± 0.1 vs 0.3 ± 0.1; P = .003) or control rats (SUV mean , 0.2 ± 0.03; P < .0001), which was confirmed by ex vivo autoradiography of tissue sections. Immunohistochemistry showed VAP-1-positive staining in lesions of rats with myocarditis and in patients with cardiac sarcoidosis., Conclusion: VAP-1-targeted [ 68 Ga]Ga-DOTA-Siglec-9 PET is a potential novel technique for the detection of myocardial lesions., (© 2023. The Author(s).)

Background: Machine Learning (ML) allows integration of the numerous variables delivered by cardiac PET/CT, while traditional survival analysis can provide explainable prognostic estimates from a restricted number of input variables. We implemented a hybrid ML-and-survival analysis of multimodal PET/CT data to identify patients who developed myocardial infarction (MI) or death in long-term follow up., Methods: Data from 739 intermediate risk patients who underwent coronary CT and selectively stress 15 O-water-PET perfusion were analyzed for the occurrence of MI and all-cause mortality. Images were evaluated segmentally for atherosclerosis and absolute myocardial perfusion through 75 variables that were integrated through ML into an ML-CCTA and an ML-PET score. These scores were then modeled along with clinical variables through Cox regression. This hybridized model was compared against an expert interpretation-based and a calcium score-based model., Results: Compared with expert- and calcium score-based models, the hybridized ML-survival model showed the highest performance (CI .81 vs .71 and .64). The strongest predictor for outcomes was the ML-CCTA score., Conclusion: Prognostic modeling of PET/CT data for the long-term occurrence of adverse events may be improved through ML imaging score integration and subsequent traditional survival analysis with clinical variables. This hybridization of methods offers an alternative to traditional survival modeling of conventional expert image scoring and interpretation., (© 2023. The Author(s).)

Background: New Block-Sequential-Regularized-Expectation-Maximization (BSREM) image reconstruction technique has been introduced for clinical use mainly for oncologic use. Accurate and quantitative image reconstruction is essential in myocardial perfusion imaging with positron emission tomography (PET) as it utilizes absolute quantitation of myocardial blood flow (MBF). The aim of the study was to evaluate BSREM reconstruction for quantitation in patients with suspected coronary artery disease (CAD)., Methods and Results: We analyzed cardiac [ 15 O]H 2 O PET studies of 177 patients evaluated for CAD. Differences between BSREM and Ordered-Subset-Expectation-Maximization with Time-Of-Flight (TOF) and Point-Spread-Function (PSF) modeling (OSEM-TOF-PSF) in terms of MBF, perfusable tissue fraction, and vascular volume fraction were measured. Classification of ischemia was assessed between the algorithms. OSEM-TOF-PSF and BSREM provided similar global stress MBF in patients with ischemia (1.84 ± 0.21 g⋅ml -1 ⋅min -1 vs 1.86 ± 0.21 g⋅ml -1 ⋅min -1 ) and no ischemia (3.26 ± 0.34 g⋅ml -1 ⋅min -1 vs 3.28 ± 0.34 g⋅ml -1 ⋅min -1 ). Global resting MBF was also similar (0.97 ± 0.12 g⋅ml -1 ⋅min -1 and 1.12 ± 0.06 g⋅ml -1 ⋅min -1 ). The largest mean relative difference in MBF values was 7%. Presence of myocardial ischemia was classified concordantly in 99% of patients using OSEM-TOF-PSF and BSREM reconstructions CONCLUSION: OSEM-TOF-PSF and BSREM image reconstructions produce similar MBF values and diagnosis of myocardial ischemia in patients undergoing [ 15 O]H 2 O PET due to suspected obstructive coronary artery disease., (© 2023. The Author(s).)

Background: Additional strategies are needed to refine the referral for diagnostic testing of symptomatic patients with suspected coronary artery disease (CAD). We aimed to compare various models to predict hemodynamically obstructive CAD., Methods and Results: Symptomatic patients with suspected CAD who underwent coronary artery calcium scoring (CACS) and sequential coronary computed tomography angiography (CCTA) and [ 15 O]H 2 O positron emission tomography (PET) myocardial perfusion imaging were analyzed. Obstructive CAD was defined as a suspected coronary artery stenosis on CCTA with myocardial ischemia on PET (absolute stress myocardial perfusion ≤ 2.4 mL/g/min in ≥ 1 segment). Three models were developed to predict obstructive CAD-induced myocardial ischemia using logistic regression analysis: (1) basic model: including age, sex and cardiac symptoms, (2) risk factor model: adding number of risk factors to the basic model, and (3) CACS model: adding CACS to the risk factor model. Model performance was evaluated using discriminatory ability with area under the receiver-operating characteristic curves (AUC). A total of 647 patients (mean age 62 ± 9 years, 45% men) underwent CACS and sequential CCTA and PET myocardial perfusion imaging. Obstructive CAD with myocardial ischemia on PET was present in 151 (23%) patients. CACS was independently associated with myocardial ischemia (P < .001). AUC for the discrimination of ischemia for the CACS model was superior over the basic model and risk factor model (P < .001)., Conclusions: Adding CACS to the model including age, sex, cardiac symptoms and number of risk factors increases the accuracy to predict obstructive CAD with myocardial ischemia on PET in symptomatic patients with suspected CAD., (© 2022. The Author(s).)

Introduction: The purpose of this study was to evaluate subjects with high-risk alcohol cardiotoxicity and patients with alcoholic cardiomyopathy (ACM) via dynamic 11 C-Acetate positron emission tomography (PET) imaging as a myocardial oxidative metabolic probe., Methods and Results: We recruited 37 subjects with chronic alcohol consumption [18 with moderate consumption (MC), 19 with heavy consumption (HC)], 5 ACM patients, and 12 healthy controls to receive dynamic 11 C-Acetate PET scans. PET imaging data were analyzed to calculate kinetic parameters (e.g., K mono , K 1 and k 2 ) based on the mono-exponential and one-tissue compartmental models. Myocardial oxygen consumption (MVO 2 ) and myocardial external efficiency (MEE) were then derived from these kinetic parameters. MVO 2 was significantly lowered in the HC group and in ACM patients (0.121± 0.018 and 0.111 ± 0.017 mL·g -1 ·min -1 , respectively) compared with those in healthy controls and MC subjects (0.144 ± 0.023 and 0.146 ± 0.027 mL·g -1 ·min -1 , respectively; P < .01). MEE was significantly reduced in ACM patients (13.0% ± 4.3%) compared with those of healthy controls (22.4% ± 4.6%, P < .01), MC subjects (20.1% ± 4.5%, P < .05), and HC subjects (22.3% ± 4.5%, P < .001)., Conclusion: Functional assessment via dynamic 11 C-Acetate PET imaging may represent a clinically feasible probe for identifying cohorts with high-risk cardiotoxicity due to addictive alcohol consumption and ACM., (© 2020. American Society of Nuclear Cardiology.)

Background: The aim of the present study was to compare the quantitative flow responses of regadenoson against adenosine using cardiac 15 O-water PET imaging in patients with suspected or known coronary artery disease (CAD)., Methods: Hyperemic myocardial blood flow (MBF) after adenosine and regadenoson was compared using correlation and Bland-Altman analysis in 21 patients who underwent rest and adenosine 15 O-water PET scans followed by rest and regadenoson 15 O-water PET scans., Results: Global mean (± SD) MBF values at rest and stress were 0.92 ± 0.27 and 2.68 ± 0.80 mL·g·min for the adenosine study and 0.95 ± 0.29 and 2.76 ± 0.79 mL·g·min for the regadenoson study (P = 0.55 and P = 0.49). The correlations between global and regional adenosine- and regadenoson-based stress MBF were strong (r = 0.80 and r = 0.77). The biases were small for both global and regional MBF comparisons (0.08 and 0.09 mL·min·g), but the limits of agreement were wide for stress MBF., Conclusion: The correlation between regadenoson- and adenosine-induced hyperemic MBF was strong but the agreement was only moderate indicating that established cut-off values for 15 0-water PET should be used cautiously if using regadenoson as vasodilator., (© 2021. The Author(s).)

Background: The diagnosis of cardiac implantable electronic device (CIED) infection is challenging because of its variable presentations. We studied the value of 2-[ 18 F]fluoro-2-deoxy-D-glucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) in the detection of CIED infection., Methods and Results: Thirty patients with suspected CIED infection underwent 18 F-FDG-PET/CT. The control group was ten patients with asymptomatic CIED who underwent cancer-related 18 F-FDG-PET/CT. 18 F-FDG-PET/CT was evaluated visually, semiquantitatively as maximum standardized uptake value (SUV max ) and target-to-background ratio (TBR). Final diagnosis of CIED infection was based on clinical and bacteriological data. 18 F-FDG-PET/CT was visually positive in all 9 patients with recent (≤ 8 weeks) implantation of CIED, but only 4 had confirmed CIED infection. 18 F-FDG-PET/CT was true positive in 9 out of 21 cases with remote implantation of CIED and false positive in 3 (14.3%) cases. 18 F-FDG-PET/CT was also false positive in 3 (30%) cases of control group. The SUV max of the pocket area was significantly higher in patients with CIED infection than in the control group (4.8 ± 2.4 vs 2.0 ± .8, P < .001). By using the cut-off value of TBR ≥ 1.8, sensitivity of 18 F-FDG-PET/CT for the diagnosis of CIED infection in patients with remote implantation was 90% and specificity 73%, PPV 75%, and NPV 89%., Conclusions: 18 F-FDG-PET/CT is a sensitive but nonspecific method in the diagnosis of CIED infection., (© 2020. The Author(s).)

Background: Assessment of myocardial viability is often needed in patients with chest pain and reduced ejection fraction. We evaluated the performance of reduced resting MBF, perfusable tissue fraction (PTF), and perfusable tissue index (PTI) in the assessment of myocardial viability in a pig model of myocardial infarction (MI)., Methods and Results: Pigs underwent resting [ 15 O]water PET perfusion study 12 weeks after surgical (n = 16) or 2 weeks after catheter-based (n = 4) occlusion of the proximal left anterior descending coronary artery. MBF, PTF, and PTI were compared with volume fraction of MI in matched segments as assessed by triphenyl tetrazolium chloride staining of LV slices. MBF and PTF were lower in infarcted than non-infarcted segments. Segmental analysis of MBF showed similar area under the curve (AUC) of 0.85, 0.86, and 0.90 with relative MBF, PTF, and PTI for the detection of viable myocardium defined as infarct volume fraction of < 75%. Cut-off values of relative MBF of ≥ 67% and PTF of ≥ 66% resulted in accuracies of 90% and 81%, respectively., Conclusions: Our results indicate that resting MBF, PTF, and PTI based on [ 15 O]water PET perfusion imaging are useful for the assessment of myocardial viability., (© 2019. The Author(s).)

Background: Positron emission tomography (PET) myocardial perfusion imaging (MPI) with the novel radiopharmaceutical Fluorine-18 Flurpiridaz has been shown in Phase 1, 2, and first Phase 3 clinical studies to be safe and effective in diagnosing coronary artery disease (CAD). We describe the methodology of the second FDA-mandated phase 3 prospective, open-label, international, multi-center trial of F-18 Flurpiridaz PET MPI., Methods: The primary study end point is to assess the diagnostic efficacy of F-18 Flurpiridaz PET MPI in the detection of significant CAD [≥ 50% by quantitative invasive coronary angiography (ICA)] in patients with suspected CAD. The secondary endpoints are to evaluate the diagnostic efficacy of F-18 Flurpiridaz PET MPI compared to Tc-99 m-labeled SPECT MPI in the detection of CAD in all patients and in the following subgroups: (1) females; (2) patients with body mass index ≥ 30 kg/m 2 ; and (3) diabetic patients. This trial's design differs from the first phase 3 trial in that (1) comparison to SPECT is now a secondary end point; (2) patients with known CAD are excluded; and (3) both SPECT and PET MPI are performed before ICA., Conclusions: This second phase 3 study will provide additional evidence on the diagnostic efficacy of F-18 Flurpiridaz PET MPI in the detection of significant CAD., Trial Registration Number: NCT03354273.

Background: Activation of glucagon-like peptide-1 receptor (GLP-1R) signaling protects against cardiac dysfunction and remodeling after myocardial infarction (MI). The aim of the study was to evaluate 68 Ga-NODAGA-exendin-4 positron emission tomography (PET) for assessment of GLP-1R expression after MI in rats., Methods and Results: Rats were studied at 3 days, 1 and 12 weeks after permanent coronary ligation or a sham-operation. Rats were injected with 68 Ga-NODAGA-exendin-4 and scanned with PET and contrast-enhanced computed tomography (CT) followed by digital autoradiography and histology of left ventricle tissue sections. 68 Ga-NODAGA-exendin-4 PET/CT showed focally increased tracer uptake in the infarcted regions peaking at 3 days and continuing at 1 week after MI. Pre-treatment with an unlabeled exendin-4 peptide significantly reduced 68 Ga-NODAGA-exendin-4 uptake. By autoradiography, 68 Ga-NODAGA-exendin-4 uptake was 8.6-fold higher in the infarcted region and slightly increased also in the remote, non-infarcted myocardium at 1 week and 12 weeks post-MI compared with sham. Uptake of 68 Ga-NODAGA-exendin-4 correlated with the amount of CD68-positive macrophages in the infarcted area and alpha-smooth muscle actin staining in the remote myocardium., Conclusions: 68 Ga-NODAGA-exendin-4 PET detects up-regulation of cardiac GLP-1R expression during healing of MI in rats and may provide information on the activated repair mechanisms after ischemic myocardial injury.

Background: We explored agreement in the quantification of myocardial perfusion by cross-comparison of implemented software packages (SPs) in three distinguishable patient profile populations., Methods: We studied 91 scans of patients divided into 3 subgroups based on their semi-quantitative perfusion findings: patients with normal perfusion, with reversible perfusion defects, and with fixed perfusion defects. Rest myocardial blood flow (MBF), stress MBF, and myocardial flow reserve (MFR) were obtained with QPET, SyngoMBF, and Carimas. Agreement between SPs was considered adequate when a pairwise standardized difference was found to be < 0.20 and its corresponding intraclass correlation coefficient was ≥ 0.75., Results: In patients with normal perfusion, two out of three comparisons of global stress MBF quantifications were outside the limits of agreement. In ischemic patients, all comparisons of global stress MBF and MFR were outside the limits of established agreement. In patients with fixed perfusion defects, all SP comparisons of perfusion quantifications were within the limit of agreement. Regionally, agreement of these perfusion estimates was mostly found for the left anterior descending artery vascular territory., Conclusion: Reversible defects demonstrated the worst agreement in global stress MBF and MFR and discrepancies showed to be regional dependent. Reproducibility between SPs should not be assumed.

Background: Magnetic resonance imaging (MRI) with Gadolinium 1,4,7,10-tetraazacyclododecane-N',N″,N''',N″″-tetraacetic acid (Gd-DOTA) enables assessment of myocardial perfusion during first-pass of the contrast agent, while increased retention can signify areas of myocardial infarction (MI). We studied whether Gallium-68-labeled analog, 68 Ga-DOTA, can be used to assess myocardial perfusion on positron emission tomography/computed tomography (PET/CT) in rats, comparing it with 11 C-acetate., Methods: Rats were studied with 11 C-acetate and 68 Ga-DOTA at 24 hours after permanent ligation of the left coronary artery or sham operation. One-tissue compartmental models were used to estimate myocardial perfusion in normal and infarcted myocardium. After the PET scan, hearts were sectioned for autoradiographic detection of 68 Ga-DOTA distribution., Results: 11 C-acetate PET showed perfusion defects and histology showed myocardial necrosis in all animals after coronary ligation. Kinetic modeling of 68 Ga-DOTA showed significantly higher k 1 values in normal myocardium than in infarcted areas. There was a significant correlation (r = 0.82, P = 0.001) between k 1 values obtained with 68 Ga-DOTA and 11 C-acetate. After 10 minutes of tracer distribution, the 68 Ga-DOTA concentration was significantly higher in the infarcted than normal myocardium on PET imaging and autoradiography., Conclusions: Our results indicate that acute MI can be detected as reduced perfusion, as well as increased late retention of 68 Ga-DOTA.

Background: A significant number of variables are obtained when characterizing patients suspected with myocardial ischemia or at risk of MACE. Guidelines typically use a handful of them to support further workup or therapeutic decisions. However, it is likely that the numerous available predictors maintain intrinsic complex interrelations. Machine learning (ML) offers the possibility to elucidate complex patterns within data to optimize individual patient classification. We evaluated the feasibility and performance of ML in utilizing simple accessible clinical and functional variables for the identification of patients with ischemia or an elevated risk of MACE as determined through quantitative PET myocardial perfusion reserve (MPR)., Methods: 1,234 patients referred to Nitrogen-13 ammonia PET were analyzed. Demographic (4), clinical (8), and functional variables (9) were retrieved and input into a cross-validated ML workflow consisting of feature selection and modeling. Two PET-defined outcome variables were operationalized: (1) any myocardial ischemia (regional MPR < 2.0) and (2) an elevated risk of MACE (global MPR < 2.0). ROC curves were used to evaluate ML performance., Results: 16 features were included for boosted ensemble ML. ML achieved an AUC of 0.72 and 0.71 in identifying patients with myocardial ischemia and with an elevated risk of MACE, respectively. ML performance was superior to logistic regression when the latter used the ESC guidelines risk models variables for both PET-defined labels (P < .001 and P = .01, respectively)., Conclusions: ML is feasible and applicable in the evaluation and utilization of simple and accessible predictors for the identification of patients who will present myocardial ischemia and an elevated risk of MACE in quantitative PET imaging.

Noninvasive imaging modalities offer the possibility to dynamically evaluate cardiac motion during the cardiac cycle by means of ECG-gated acquisitions. Such motion characterization along with orientation, segmentation preprocessing, and ultimately, phase analysis, can provide quantitative estimates of ventricular mechanical synchrony. Current evidence on the role of mechanical synchrony evaluation is mainly available for echocardiography and gated single-photon emission computed tomography, but less is known about the utilization of gated positron emission tomography (PET). Although data available are sparse, there is indication that mechanical synchrony evaluation can be of diagnostic and prognostic values in patients with known or suspected coronary artery disease-related myocardial ischemia, prediction of response to cardiac resynchronization therapy, and estimation of risk for adverse cardiac events in patients' heart failure. As such, the evaluation of mechanical ventricular synchrony through phase analysis of gated acquisitions represents a value addition to modern cardiac PET imaging modality, which warrants further research and development in the evaluation of patients with cardiovascular disease.

Background: Matrix metalloproteinases 2 and 9 (MMP-2/9) play a role in extracellular matrix remodeling after an ischemic myocardial injury. We evaluated 68 Ga-DOTA-peptide targeting MMP-2/9 for the detection of gelatinase expression after myocardial infarction (MI) in rat., Methods: Rats were injected with 43 ± 7.7 MBq of 68 Ga-DOTA-peptide targeting MMP-2/9 at 7 days (n = 7) or 4 weeks (n = 8) after permanent coronary ligation or sham operation (n = 5 at both time points) followed by positron emission tomography (PET). The left ventricle was cut in frozen sections for autoradiography and immunohistochemistry 30 minutes after tracer injection., Results: Immunohistochemical staining showed MMP-2 and MMP-9 expressing cells, CD31-positive endothelial cells, and CD68-positive macrophages in the infarcted myocardium. Autoradiography showed increased tracer uptake in the infarcted area both at 7 days and 4 weeks after MI (MI-to-remote area ratio 2.5 ± 0.46 and 3.1 ± 1.0, respectively). Tracer uptake in damaged tissue correlated with the amount of CD68-positive macrophages at 7 days after MI, and CD31-positive endothelial cells at 7 days and 4 weeks after MI. The tracer was rapidly metabolized, radioactivity in the blood exceeded that of the myocardium, and tracer accumulation in the heart was not detectable by in vivo PET., Conclusions: 68 Ga-DOTA-peptide targeting MMP-2/9 accumulates in the damaged rat myocardium after an ischemic injury, but tracer instability and slow clearance in vivo make it unsuitable for further evaluation.

Background: Radioligands of 18-kDa translocator protein (TSPO) expressed on activated macrophages are a potential approach for imaging of inflammation in atherosclerosis. We evaluated a novel TSPO-targeted tracer 18 F-FEMPA for the detection of atherosclerotic plaque inflammation in mice., Methods and Results: The distribution kinetics of 18 F-FEMPA was evaluated by in vivo PET/CT imaging. 18 F-FEMPA uptake was compared in atherosclerotic (LDLR -/- ApoB 100/100 , n = 10) and healthy mice (C57BL/6 N, n = 7) ex vivo at twenty minutes post-injection. Biodistribution was analyzed from harvested tissue samples, and aortas were sectioned for autoradiography. Aortas of LDLR -/- ApoB 100/100 mice showed large, macrophage-rich atherosclerotic plaques. In vivo, 18 F-FEMPA showed rapid blood clearance but no difference in aortic uptake between atherosclerotic and healthy mice. In the mice studied ex vivo at 20 minutes post-injection, quantification of radioactivity in the whole aorta showed 1.3-fold higher 18 F-FEMPA accumulation in atherosclerotic than healthy mice (P = .028). Autoradiography showed higher tracer uptake in plaque areas with high macrophage content as compared with areas of no macrophages (count densities 190 ± 54 vs 40 ± 13 PSL/mm 2 , P < .001), but the uptake in the plaques was not higher than in the normal vessel wall (230 ± 78 PSL/mm 2 ). In vitro blocking showed specific accumulation in mouse and human atherosclerotic plaques. Immunohistochemistry confirmed co-localization of TSPO and macrophages., Conclusions: 18 F-FEMPA shows rapid blood clearance and uptake in the mouse aorta. Uptake in atherosclerotic plaques correlated with the amount of macrophages, but did not exceed that in the normal vessel wall.

Background: The diagnosis of infective endocarditis (IE), especially the diagnosis of prosthetic valve endocarditis (PVE) is challenging since echocardiographic findings are often scarce in the early phase of the disease. We studied the use of 2-[ 18 F]fluoro-2-deoxy-D-glucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) in IE., Methods: Sixteen patients with suspected PVE and 7 patients with NVE underwent visual evaluation of 18 F-FDG-PET/CT. 18 F-FDG uptake was measured also semiquantitatively as maximum standardized uptake value (SUV max ) and target-to-background ratio (TBR). The modified Duke criteria were used as a reference., Results: There was strong, focal 18 F-FDG uptake in the area of the affected valve in all 6 cases of definite PVE, in 3 of 5 possible PVE cases, and in 2 of 5 rejected cases. In all patients with definite PVE, SUV max of the affected valve was higher than 4 and TBR higher than 1.8. In contrast to PVE, only 1 of 7 patients with NVE had uptake of 18 F-FDG by PET/CT in the valve area. Embolic infectious foci were detected in 58% of the patients with definite IE., Conclusions: 18 F-FDG-PET/CT appears to be a sensitive method for the detection of paravalvular infection associated with PVE. Instead, the sensitivity of PET/CT is limited in NVE.

Sudden cardiac death (SCD) represents a significant portion of all cardiac deaths. Current guidelines focus mainly on left ventricular ejection fraction (LVEF) as the main criterion for SCD risk stratification and management. However, LVEF alone lacks both sensitivity and specificity in stratifying patients. Recent research has provided interesting data which supports a greater role for advanced cardiac imaging in risk stratification and patient management. In this article, we will focus on nuclear cardiac imaging, including left ventricular function assessment, myocardial perfusion imaging, myocardial blood flow quantification, metabolic imaging, and neurohormonal imaging. We will discuss how these can be used to better understand SCD and better stratify patient with both ischemic and non-ischemic cardiomyopathy.

Background: In cardiac PET, CT, and MRI respiration is major reason for impaired image quality of small targets such as coronary arteries. Strong correlations between heart motion and respiratory signals have been detected but quantitative relation between signals and motion of cardiac structures in MRI or PET is not reported ., Methods: Relation between spirometric lung volume or pressure belt signal and motion of coronary vessels in MRI was studied on nine healthy volunteers. Spirometry was further applied to (18)F-FDG cardiac PET study to determine quantitative relation between volume change and motion of center of myocardium activity (CMA) on nine CAD patients., Results: Correlation coefficients (CC) between vessel motions and volume or pressure changes were 0.90-0.92 or 0.86-0.84, respectively. The linear equations based on volume or pressure changes derived 2.0-2.6 or 2.9-3.3 mm mean estimation error for vessel motions. In PET CC value of 0.93 was determined between volume changes and CMA motions. The linear equation based on volume change derived maximum estimation error of 2.5 mm for CMA motion., Conclusion: The spirometric volume change linearly estimates motion of myocardium in PET with good accuracy and have potential to guide selection of optimal number of respiratory gates in cardiac PET.

Aims: Large animal models are needed to study disease mechanisms in heart failure (HF). In the present study we characterized the functional, metabolic, and structural changes of myocardium in a novel pig model of chronic myocardial infarction (MI) by using multimodality imaging and histology., Methods and Results: Male farm pigs underwent a two-step occlusion of the left anterior descending coronary artery with concurrent distal ligation and implantation of a proximal ameroid constrictor (HF group), or sham operation (control group). Three months after the operation, cardiac output and wall stress were measured by echocardiography. Left ventricle (LV) volumes and mass were measured by computed tomography (CT). Myocardial perfusion was evaluated by [(15)O]water and oxygen consumption using [(11)C]acetate positron emission tomography, and the efficiency of myocardial work was calculated. Histological examinations were conducted to detect MI, hypertrophy, and fibrosis. Animals in the HF group had a large anterior MI scar. CT showed larger LV diastolic volume and lower ejection fraction in HF pigs than in controls. Perfusion and oxygen consumption in the remote non-infarcted myocardium were preserved in HF pigs as compared to controls. Global LV work and efficiency were significantly lower in HF than control pigs and was associated with increased wall stress. Histology showed myocyte hypertrophy but not increased interstitial fibrosis in the remote segments in HF pigs., Conclusions: The chronic post-infarction model of HF is suitable for studies aimed to evaluate LV remodeling and changes in oxidative metabolism and can be useful for testing new therapies for HF.

Positron emission tomography (PET) enables quantitative measurements of myocardial blood flow (MBF) and myocardial flow reserve (MFR). Recent developments and improved availability of PET technology have resulted in growing interest in translation of quantitative flow analysis from mainly a research tool to routine clinical practice. Quantitative PET measurements of absolute MBF and MFR have potential to improve accuracy of myocardial perfusion imaging in diagnosis of multivessel coronary artery disease as well as definition of the extent and functional importance of stenoses. This article reviews recent advances and experience in the quantitative myocardial perfusion imaging together with issues that need to be resolved for quantitative analysis to become clinical reality.

Background: Expression of α(v)β(3) integrin has been proposed as a marker for atherosclerotic lesion inflammation. We studied whether diet intervention reduces uptake of α(v)β(3) integrin-targeted positron emission tomography tracer (18)F-galacto-RGD in mouse atherosclerotic plaques., Methods and Results: Hypercholesterolemic LDLR(-/-) ApoB(100/100) mice on high-fat diet for 4 months were randomized to further 3 months on high-fat diet (high-fat group, n = 8) or regular mouse chow (intervention group, n = 7). Intima-media ratio describing plaque burden was comparable between intervention and high-fat groups (2.0 ± 0.5 vs 2.3 ± 0.8, P = .5). Uptake of (18)F-galacto-RGD in the aorta was lower in the intervention than high-fat group (%ID/g 0.16 vs 0.23, P < .01). Autoradiography showed 35% lower uptake of (18)F-galacto-RGD in the atherosclerotic plaques in the intervention than high-fat group (P = .007). Uptake of (18)F-galacto-RGD in plaques correlated with uptake of (3)H-deoxyglucose and nuclear density, which was lower in the intervention than high-fat group (P = .01). Flow cytometry demonstrated macrophages expressing α(v) and β(3) integrins in the aorta., Conclusions: Uptake of (18)F-galacto-RGD in mouse atherosclerotic lesions was reduced by lipid-lowering diet intervention. Expression of α(v)β(3) integrin is a potential target for evaluation of therapy response in atherosclerosis.

Background: In PET imaging respiratory and cardiac contraction motions interfere the imaging of heart. The aim was to develop and evaluate dual gating method for improving the detection of small targets of the heart., Methods: The method utilizes two independent triggers which are sent periodically into list mode data based on respiratory and ECG cycles. An algorithm for generating dual gated segments from list mode data was developed., Results: The test measurements showed that rotational and axial movements of point source can be separated spatially to different segments with well-defined borders. The effect of dual gating on detection of small moving targets was tested with a moving heart phantom. Dual gated images showed 51% elimination (3.6 mm out of 7.0 mm) of contraction motion of hot spot (diameter 3 mm) and 70% elimination (14 mm out of 20 mm) of respiratory motion. Averaged activity value of hot spot increases by 89% when comparing to non-gated images. Patient study of suspected cardiac sarcoidosis shows sharper spatial myocardial uptake profile and improved detection of small myocardial structures such as papillary muscles., Conclusions: The dual gating method improves detection of small moving targets in a phantom and it is feasible in clinical situations.

Background: The relationship between myocardial metabolic changes and the severity of left ventricular (LV) hypertrophy in patients with hypertrophic cardiomyopathy (HCM) is largely unknown. We characterized metabolic abnormalities in patients with a genetically identical cause for HCM but with variable LV hypertrophy., Methods and Results: Eight patients with HCM attributable to the Asp175Asn mutation in the alpha-tropomyosin gene underwent myocardial perfusion, oxidative, and free fatty acid (FFA) metabolism measurements via positron emission tomography and oxygen 15-labeled water, carbon 11 acetate, and fluorine 14(R,S)-[18F] Fluoro-6-thia-heptadecanoic acid (18 FTHA). LV mass, work, and efficiency were assessed by echocardiography. Thirty-six healthy volunteers served as control subjects. Compared with control subjects, HCM patients had increased myocardial oxidative metabolism and FFA uptake (P < .05). However, in patients, LV mass was inversely related to global myocardial perfusion, oxidative metabolism, and FFA uptake (all P < .03), and regional wall thickness was inversely related to regional perfusion (P < .01), oxidative metabolism (P < .001), and FFA uptake (P < .01). Therefore patients with mild (LV mass less than median of 177 g) but not advanced LV hypertrophy were characterized by increased perfusion, oxidative metabolism, and LV efficiency as compared with control subjects (P < .05)., Conclusions: In HCM attributable to the Asp175Asn mutation in the alpha-tropomyosin gene, myocardial oxidative metabolism and FFA metabolism are increased and inversely related to LV hypertrophy at both the whole heart and regional level. Increased metabolism and efficiency characterize patients with mild myocardial hypertrophy. These hypermetabolic alterations regress with advanced hypertrophy.

Background: The aim of this study was to develop a method to correct the heart position between two oxygen 15-labeled water cardiac positron emission tomography (PET) image sets to be able to use the equivalent regions of interest for the quantification of the perfusion values in the same myocardial segments., Methods and Results: Independent component analysis was applied to the dynamic image sets (simulated phantom and 6 rest-pharmacologic stress and 10 rest-rest image sets of healthy female volunteers) acquired at different time points to separate the cardiac structures (ventricles and myocardium). The separated component images from independent component analysis from the 2 studies of the same individual were aligned with a normalized mutual information-based registration method. The alignment parameters were applied to position the regions of interest in the floating image sets for calculation of the myocardial blood flow values. In the rest case the mean myocardial blood flow value was 0.76 +/- 0.12 mL x g(-1) x min(-1) for the manual method and 0.79 +/- 0.10 mL x g(-1) x min(-1) for the proposed method (by use of the right ventricle component in the alignment), and in the stress case these values were 3.39 +/- 0.70 mL x g(-1) x min(-1) and 4.01 +/- 0.71 mL x g(-1) x min(-1), respectively. No statistically significant difference was found between the methods., Conclusion: In the tests with the phantom and patient images the alignment of cardiac structures was shown to be successful. The alignment could be done without the use of information from the myocardial compartment.

Background: The effects of exercise training on myocardial substrate utilization have not previously been studied in patients with idiopathic dilated cardiomyopathy and mild heart failure., Methods and Results: Myocardial glucose uptake was studied in 15 clinically stable patients with dilated cardiomyopathy (New York Heart Association class I-II, ejection fraction 34% +/- 8%) with the use of 2-[fluorine 18]fluoro-2-deoxy-d-glucose ([F-18]FDG) and positron emission tomography under euglycemic hyperinsulinemia. Eight of these patients participated in a 5-month endurance and strength training program, whereas seven patients served as nontrained subjects. Left ventricular function was assessed by 2-dimensional echocardiography before and after the intervention. After the training period, insulin-stimulated myocardial fractional [F-18]FDG uptake and glucose uptake rates were significantly increased in the anterior, lateral, and septal walls (P <.01) in the trained subjects but remained unchanged in the nontrained subjects. In the trained patients, whole-body insulin-stimulated glucose uptake was enhanced and serum free fatty acid levels were suppressed during hyperinsulinemia compared with the baseline study (P <.05). No changes were observed in the nontrained group., Conclusions: These results indicate that exercise training in patients with dilated cardiomyopathy improves insulin-stimulated myocardial glucose uptake. This improvement in glucose uptake may be indicative of a switch in myocardial preference to a more energy-efficient substrate.