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Introduction: Despite the decades long use of [11C]palmitate positron emission tomography (PET)/computed tomography in basic metabolism studies, only personal communications regarding dosimetry and biodistribution data have been published. Methods: Dosimetry and biodistribution studies were performed in 2 pigs and 2 healthy volunteers by whole-body [11C]palmitate PET scans. Metabolite studies were performed in 40 participants (healthy and with type 2 diabetes) under basal and hyperinsulinemic conditions. Metabolites were estimated using 2 approaches and subsequently compared: Indirect [11C]CO2 release and parent [11C]palmitate measured by a solid-phase extraction (SPE) method. Finally, myocardial fatty acid uptake was calculated in a patient cohort using input functions derived from individual metabolite correction compared with population-based metabolite correction. Results: In humans, mean effective dose was 3.23 (0.02) µSv/MBq, with the liver and myocardium receiving the highest absorbed doses. Metabolite correction using only [11C]CO2 estimates underestimated the fraction of metabolites in studies lasting more than 20 minutes. Population-based metabolite correction showed excellent correlation with individual metabolite correction in the cardiac PET validation cohort. Conclusion: First, mean effective dose of [11C]palmitate is 3.23 (0.02) µSv/MBq in humans allowing multiple scans using ∼300 MBq [11C]palmitate, and secondly, population-based metabolite correction compares well with individual correction. [ABSTRACT FROM AUTHOR]

Background: Single photon emission computed tomography (SPECT) has limited ability to identify multivessel and microvascular coronary artery disease. Gamma cameras with cadmium zinc telluride detectors allow the quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR). However, evidence of its accuracy is limited, and of its reproducibility is lacking. We aimed to validate 99mTc-sestamibi SPECT MBF and MFR using standard and spline-fitted reconstruction algorithms compared with 13N-ammonia positron emission tomography in a cohort of patients with known or suspected coronary artery disease and to evaluate the reproducibility of this technique. Methods: Accuracy was assessed in 34 participants who underwent dynamic 99mTc-sestamibi SPECT and 13N-ammonia positron emission tomography and reproducibility in 14 participants who underwent 2 99mTc-sestamibi SPECT studies, all within 2 weeks. A rest/pharmacological stress single-day SPECT protocol was performed. SPECT images were reconstructed using a standard ordered subset expectation maximization (OSEM) algorithm with (N=21) and without (N=30) application of spline fitting. SPECT MBF was quantified using a net retention kinetic model‚ and MFR was derived as the stress/rest MBF ratio. Results: SPECT global MBF with splines showed good correlation with 13N-ammonia positron emission tomography (r=0.81, P <0.001) and MFR estimates (r=0.74, P <0.001). Correlations were substantially weaker for standard reconstruction without splines (r=0.61, P <0.001 and r=0.34, P =0.07, for MBF and MFR, respectively). Reproducibility of global MBF estimates with splines in paired SPECT scans was good (r=0.77, P <0.001), while ordered subset expectation maximization without splines led to decreased MBF (r=0.68, P <0.001) and MFR correlations (r=0.33, P =0.3). There were no significant differences in MBF or MFR between the 2 reproducibility scans independently of the reconstruction algorithm (P >0.05 for all). Conclusions: MBF and MFR quantification using 99mTc-sestamibi cadmium zinc telluride SPECT with spatiotemporal spline fitting improved the correlation with 13N-ammonia positron emission tomography flow estimates and test/retest reproducibility. The use of splines may represent an important step toward the standardization of SPECT flow estimation. [ABSTRACT FROM AUTHOR]

Purpose: Parametric imaging of absolute myocardial blood flow (MBF) using [O]HO enables determination of MBF with high spatial resolution. The aim of this study was to develop a method for generating reproducible, high-quality and quantitative parametric MBF images with minimal user intervention. Methods: Nineteen patients referred for evaluation of MBF underwent rest and adenosine stress [O]HO positron emission tomography (PET) scans. Ascending aorta and right ventricular (RV) cavity volumes of interest (VOIs) were used as input functions. Implementation of a basis function method (BFM) of the single-tissue model with an additional correction for RV spillover was used to generate parametric images. The average segmental MBF derived from parametric images was compared with MBF obtained using nonlinear least-squares regression (NLR) of VOI data. Four segmentation algorithms were evaluated for automatic extraction of input functions. Segmental MBF obtained using these input functions was compared with MBF obtained using manually defined input functions. Results: The average parametric MBF showed a high agreement with NLR-derived MBF [intraclass correlation coefficient (ICC) = 0.984]. For each segmentation algorithm there was at least one implementation that yielded high agreement (ICC > 0.9) with manually obtained input functions, although MBF calculated using each algorithm was at least 10% higher. Cluster analysis with six clusters yielded the highest agreement (ICC = 0.977), together with good segmentation reproducibility (coefficient of variation of MBF <5%). Conclusion: Parametric MBF images of diagnostic quality can be generated automatically using cluster analysis and a implementation of a BFM of the single-tissue model with additional RV spillover correction. [ABSTRACT FROM AUTHOR]

Background: Cardiac positron emission tomography (PET) offers non-invasive assessment of perfusion and left ventricular (LV) function from a single dynamic scan. However, no prior assessment of mitral regurgitation severity by PET has been presented. Application of indicator dilution techniques and gated image analyses to PET data enables calculation of forward stroke volume and total LV stroke volume. We aimed to evaluate a combination of these methods for measurement of regurgitant volume (RegVol) and fraction (RegF) using dynamic 15O-water and 11C-acetate PET in comparison to cardiovascular magnetic resonance (CMR). Results: Twenty-one patients with severe primary mitral valve regurgitation underwent same-day dynamic PET examinations (15O-water and 11C-acetate) and CMR. PET data were reconstructed into dynamic series with short time frames during the first pass, gated 15O-water blood pool images, and gated 11C-acetate myocardial uptake images. PET-based RegVol and RegF correlated strongly with CMR (RegVol: 15O-water r = 0.94, 11C-acetate r = 0.91 and RegF: 15O-water r = 0.88, 11C-acetate r = 0.84, p < 0.001). A systematic underestimation (bias) was found for PET (RegVol: 15O-water − 11 ± 13 mL, p = 0.002, 11C-acetate − 28 ± 16 mL, p < 0.001 and RegF: 15O-water − 4 ± 6%, p = 0.01, 11C-acetate − 10 ± 7%, p < 0.001). PET measurements in patients were compared to healthy volunteers (n = 18). Mean RegVol and RegF was significantly lower in healthy volunteers compared to patients for both tracers. The accuracy of diagnosing moderately elevated regurgitant volume (> 30mL) was 95% for 15O-water and 92% for 11C-acetate. Conclusions: LV regurgitation severity quantified using cardiac PET correlated with CMR and showed high accuracy for discriminating patients from healthy volunteers. [ABSTRACT FROM AUTHOR]

Background: The pathophysiology of symptoms and reduced exercise capacity from peripheral artery disease (PAD) remains unclear. Additionally, there is limited information, on blood flow and skeletal muscle energetics after walking exercise in patients with claudication in comparison to healthy individuals., Methods: We prospectively enrolled 19 patients with claudication from PAD and 12 healthy subjects. All participants underwent rest and post-exercise perfusion imaging of the lower leg muscles via PET/CT. Participants exercised on a treadmill following the Gardner-Skinner protocol. Skeletal muscle blood flow (SMBF) was quantified in each leg at rest and immediately after exercise. Phosphocreatine (PCr) recovery and NAD + /NADH concentrations were measured pre- and post-exercise by 31 P magnetic resonance spectroscopy (MRS) in a subset of participants. Comparisons were made between legs of healthy subjects and the asymptomatic and symptomatic legs of patients with PAD., Results: SMBF increased post-exercise in all participants. Among patients with PAD, the post-exercise/rest SMBF ratio, was higher in the symptomatic (n= 25) than asymptomatic (n=13) legs (8.03 ± 2.84 versus 6.03 ± 2.81, p=0.046) and higher than the post-exercise/rest SMBF ratio measured in the legs of healthy subjects (4.40 ± 1.47, p<0.001). The post-exercise/rest PCr and NAD + /NADH ratios were lower in the legs of patients with PAD (n=3) when compared with the legs of healthy subjects (n=6) (0.79 ± 0.06 versus 1.00 ± 0.07 (p=0.004) and 1.15 ± 0.43 versus 2.08 ± 0.30 (p=0.007), respectively)., Conclusions: SMBF increased post-exercise to the greatest degree in the symptomatic legs of patients with PAD and post-exercise skeletal muscle mitochondrial function was abnormal in patients with PAD. These data suggest that the causes of symptoms and reduced exercise capacity from PAD are not limited to abnormal perfusion pressure in the legs., Competing Interests: Declaration of Competing Interest ☒ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sanjay Divakaran reports financial support was provided by American Society of Nuclear Cardiology. Sanjay Divakaran reports financial support was provided by American Heart Association. Sanjay Divakaran reports financial support was provided by Brigham and Women’s Hospital. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 American Society of Nuclear Cardiology. Published by Elsevier Inc. All rights reserved.)

Various non-invasive images are used in clinical practice for the diagnosis and prognostication of chronic coronary syndromes. Notably, quantitative myocardial perfusion imaging (MPI) through positron emission tomography (PET) has seen significant technical advancements and a substantial increase in its use over the past two decades. This progress has generated an unprecedented wealth of clinical information, which, when properly applied, can diagnose and fine-tune the management of patients with different types of ischemic syndromes. This state-of-art review focuses on quantitative PET MPI, its integration into clinical practice, and how it holds up at the eyes of modern cardiac imaging and revascularization clinical trials, along with future perspectives., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: This study aimed to study the prognostic value of myocardial oxygen consumption (MVO 2 ) and myocardial external efficiency (MEE) from 11 C-acetate positron emission tomography (PET) in cardiac amyloidosis (CA) patients., Methods and Results: Forty-eight CA patients, both transthyretin (ATTR) and immunoglobulin light chain (AL) amyloidosis, and 20 controls were included. All subjects were examined with 11 C-acetate PET and echocardiography. MVO 2 , forward stroke volume (FSV), and left ventricular mass (LVM) were derived from 11 C-acetate PET and used to calculate MEE. CA patients were followed for survival and the prognostic impact of clinical, echocardiographic, and 11 C-acetate PET parameters was analysed. MVO 2 and MEE were reduced in CA compared with controls, but without significant difference between deceased and surviving CA patients. The ratio of 11 C-acetate PET-derived FSV and LVM was also reduced in CA and significantly lowered in deceased patients compared with survivors. In univariate analysis, New York Heart Association class, N-terminal pro-brain natriuretic peptide, and the 11 C-acetate PET parameters FSV/LVM and MEE were the strongest prognostic factors. Of the 11 C-acetate PET parameters, FSV/LVM was the strongest survival predictor with hazard ratio of 0.56 per 0.1 mL/g (95% confidence interval 0.39-0.81, P = 0.002) and independently prognostic in a multivariate model. MEE significantly separated deceased from surviving CA patients with the cut-off of 15.7% (P = 0.032). Survival was significantly shorter with FSV/LVM below 0.27 mL/g (P < 0.001), also when separating AL- and ATTR-CA., Conclusions: Reduced MEE was associated with shorter survival in CA patients, but FSV/LVM was the strongest survival predictor and the only independently prognostic 11 C-acetate PET parameter in multivariate analysis., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Cardiac amyloidosis (CA) is a restrictive and infiltrative cardiomyopathy, characterized by increased biventricular filling pressures and low output. Symptoms are predominantly of right heart origin. The role of right ventricular (RV) myocardial blood flow (MBF) in CA has not been studied., Objectives: This study aimed to first associate RV MBF measured by using positron emission tomography (PET) with reference standards of RV pressures and then to explore its prognostic value in CA., Methods: Cardiac PET was performed at rest in 52 patients with CA and 9 healthy control subjects. MBF was quantified from the right and left ventricles by using 11 C-acetate, 15 O-water, or both (n = 25). RV pressure was measured invasively or by echocardiography. Associations between biventricular MBF toward symptoms, RV function, and outcome (death or acute heart failure) were studied in patients with CA., Results: MBF of the right ventricle (MBF RV ) and the ratio of MBF RV and MBF of the left ventricle (MBF RV/LV ) for the 2 tracers were significantly correlated (r > 0.92). MBF RV was directly correlated with RV systolic pressures with both tracers (P ≤ 0.005). MBF LV was inversely correlated with wall thickness (P < 0.0001). MBF RV/LV was significantly associated with N-terminal pro-B-type natriuretic peptide levels, NYHA functional class, RV pressures, and RV systolic function (all; P < 0.001). Twenty-six cardiac events (25 deaths) occurred during follow-up (median 44 months). MBF RV/LV higher than 56% was associated with a diagnosis of pulmonary hypertension (AUC: 0.96 [95% CI: 0.91-1.00]; P < 0.0001); and predicted outcome with HR: 9.0 (95% CI: 4.2-14.5), P < 0.0001)., Conclusions: Measurements of MBF RV using PET are feasible, as confirmed with 2 different tracers. Imbalance between RV and LV myocardial perfusion is associated with increased RV load and adverse events in cardiac amyloidosis., Competing Interests: Funding Support and Author Disclosures This study was supported by grants from Lundbeck foundation (grant number R192-2015-966, awarded to Dr Harms) and Swedish Heart-Lung Foundation (grant numbers 20160746 and 20190593 awarded to Dr Sorensen). Drs Harms, Tolbod, and Sorensen are co-founders and co-owners of MedTrace Pharma A/S. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. All rights reserved.)

Background: 15 O-water PET is the gold standard for noninvasive quantification of myocardial blood flow. In addition to evaluation of ischemia, the assessment of cardiac function and remodeling is important in all cardiac diseases. However, since 15 O-water is freely diffusible and standard uptake images show little contrast between the myocardium and blood pool, the assessment of left-ventricular (LV) volumes and ejection fraction (EF) is challenging. Therefore, the aim of the present study was to investigate the feasibility of calculating LV volumes and EF from first-pass analysis of 15 O-water PET, by comparison with cardiac magnetic resonance imaging (CMR) using a hybrid PET/MR scanner., Methods: Twenty-four patients with known or suspected CAD underwent a simultaneous ECG-gated cardiac PET/MR scan. The 15 O-water first-pass images (0-50 seconds) were analyzed using the CarPET software and the CMR images were analyzed using the software Segment, for LV volumes and EF calculations. The LV volumes and EF were compared using correlation and Bland-Altman analysis. In addition, inter- and intra-observer variability of LV volumes and EF were assessed for both modalities., Results: The correlation between PET and CMR was strong for volumes (r > 0.84) and moderate for EF (r = 0.52), where the moderate correlation for EF was partly due to the small range of EF values. Agreement was high for all parameters, with a slight overestimation of PET values for end-diastolic volume but with no significant mean bias for other parameters. Inter- and intra-observer agreement of volumes was high and comparable between PET and CMR. For EF, inter-observer agreement was higher for PET and intra-observer agreement was higher for CMR., Conclusion: LV volumes and EF can be calculated by first-pass analysis of a 15 O-water PET scan with high accuracy and comparable precision as with CMR., (© 2022. The Author(s).)

Subjects with asymptomatic moderate-to-severe or severe primary mitral regurgitation are closely observed for signs of progression or symptoms requiring surgical intervention. The role of myocardial metabolic function in progression of mitral regurgitation is poorly understood. We used 11 C-acetate PET to noninvasively measure myocardial mechanical external efficiency (MEE), which is the energetic ratio of external cardiac work and left ventricular (LV) oxygen consumption. Methods: Forty-seven patients in surveillance with mitral regurgitation and no or minimal symptoms prospectively underwent PET, echocardiography, and cardiac MRI on the same day. PET was used to simultaneously measure cardiac output, LV mass, and oxygen consumption to establish MEE. PET findings were compared between patients and healthy volunteers ( n = 9). MEE and standard imaging indicators of regurgitation severity, LV volumes, and function were studied as predictors of time to surgical intervention. Patients were followed a median of 3.0 y (interquartile range, 2.0-3.8 y), and the endpoint was reached in 22 subjects (47%). Results: MEE in patients reaching the endpoint (23.8% ± 5.0%) was lower than in censored patients (28.5% ± 4.5%, P = 0.002) or healthy volunteers (30.1% ± 4.9%, P = 0.001). MEE with a cutoff lower than 25.7% was significantly associated with the outcome (hazard ratio, 7.5; 95% CI, 2.7-20.6; P < 0.0001) and retained independent significance when compared with standard imaging parameters. Conclusion: MEE independently predicted time to progression requiring valve surgery in patients with asymptomatic moderate-to-severe or severe primary mitral regurgitation. The study suggests that inefficient myocardial oxidative metabolism precedes clinically observed progression in mitral regurgitation., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

It was recently shown that high-risk prostate carcinoma (PCa) exhibited parasympathetic neurogenesis. The PET tracer 11 C-donepezil is a marker of parasympathetic innervation. Therefore, we studied if parasympathetic nerve density in PCa measured with 11 C-donepezil PET correlated with PCa aggressiveness and if metastases could be visualized. Twenty-six patients were included into three groups with varying tumor aggressiveness. Dynamic and static PET scans were performed. Maximal standardized uptake values (SUV max ) were determined in lesions within the prostate, lymph nodes, and bones. SUV max in primary PCa were compared between groups, and comparisons between SUV max and Gleason score and Prostate-specific antigen (PSA) were performed. Kinetic modelling was performed and time-activity curves of healthy tissue and tumor tissue fitted and compared. Tumor kinetic parameters were normalized to those of healthy tissue producing ratios of K1 and k2. Median SUV max in primary PCa was higher in high-grade compared to low-grade PCa (P = 0.052). No correlation was seen between Gleason score and SUV max (P = 0.28). A trend-level correlation was seen between PSA and SUV max (P = 0.078). Median SUV max was 7.7 (4.7-22.5) for suspected lymph node metastases and 8.2 (5.4-14.8) for suspected bone metastases. A significant difference was seen between time-activity tissue curves for low- and high-grade PCa (P = 0.012). Highly significant differences were seen in K1- and k2-ratios between low- and high-grade PCa (P = 0.0006 and P < 0.0001). We showed that 11 C-donepezil accumulates in primary PCa and metastases. Simple SUV max values of the cancer hot spots were higher in high-risk tumors compared to low-risk tumors. Further studies should elucidate the importance of cholinergic neurogenesis for prostate cancer biology., Competing Interests: None.

Tumor blood flow (TBF) measurements in prostate cancer (PCa) provide an integrative index of tumor growth, which could be important for primary diagnosis and therapy response evaluation. 15 O-water PET is the non-invasive gold standard but is technically demanding. The aim of this study was to compare the accuracy of three different non-invasive strategies with an invasively measured arterial input function (BSIF): Using image-derived input functions (IDIF) from either 1) a separate heart scan or 2) the pelvic scan or 3) a populations-based input function (PBIF). Nine patients with biopsy-verified PCa scheduled for prostatectomy were included. All patients were characterized with serum levels of PSA (s-PSA), multiparametric magnetic resonance imaging (mpMRI) and post-surgical histopathology Gleason Grade. Dynamic 15 O-water was performed of the heart and the pelvic area 15 minutes apart. TBF estimated from both wash-in (K 1 ) and wash-out (k 2 ) constants was calculated using a one-compartmental model. Results: Mean (range) s-PSA was 12 (3-27) ng/mL, Gleason Grade Group was 2.9 (1-5), k 2 was 0.44 (0.007-1.2), and K 1 was 0.24 (0.07-0.55) mL/mL/min. k 2 (BSIF) correlated with s-PSA (r=0.86, P<0.01) and Gleason Grade Group (rho=0.78, P=0.01). BSIF, heart-IDIF and PBIF provided near-identical k 2 and K 1 (r>0.95, P<0.001) with slopes near unity. The correlations of BSIF and pelvic-IDIF rate constants were good (r>0.95, P<0.001), but individual errors high. In conclusion, non-invasive protocols for 15 O-water PET with IDIF or PBIF accurately measures perfusion in prostate cancer and might be useful for evaluation of tumor aggressiveness and treatment response., Competing Interests: None.

Aims: The pathophysiology underlying aortic valve stenosis (AVS)-induced cardiac dysfunction and reduced exercise capacity is unclear. We hypothesize that improvement of myocardial external efficiency (MEE)--the ratio between external work and myocardial oxygen consumption (MVO2)--underlies functional improvement of AVS patients after aortic valve replacement (AVR). Therefore, the aim of this proof-of-concept study was to investigate whether myocardial efficiency is reduced in patients with cardiac hypertrophy caused by AVS and to assess the effect of AVR on myocardial efficiency in relation to exercise capacity., Methods and Results: Echocardiography, cardiopulmonary exercise test, [(11)C]-acetate positron emission tomography and cardiovascular magnetic resonance imaging were performed in 10 AVS patients prior to (pre-AVR) and 4 months after AVR (post-AVR). Fourteen healthy individuals served as control group. MEE was significantly lower in pre-AVR patients (32 ± 7%) than in controls (49 ± 6%). AVR significantly decreased left ventricle mass and MVO2. Also, external work significantly decreased post-AVR reaching similar values as in controls. AVR significantly improved MEE from 32 ± 7 to 37 ± 5% (P = 0.02). Moreover, significant correlations were present between the AVR-induced increase in MEE and changes in both exercise work (r = 0.74, P = 0.01) and peak VO2 (r = 0.67, P = 0.03). However, four AVS patients did not show improved MEE, which was associated with no or minimal improvement in exercise parameters., Conclusion: MEE is significantly reduced in patients with AVS-induced hypertrophy. Improved MEE is an important predictor of AVR-induced improvement of exercise capacity in AVS patients. Future investigation is needed to confirm our observations in a large prospective, multicenter clinical trial., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Aims: Sympathetic denervation typically occurs in the infarcted myocardium and is associated with sudden cardiac death. Impaired innervation was also demonstrated in non-infarcted myocardium in ischaemic and dilated cardiomyopathy (ICMP and DCMP). Factors affecting sympathetic nerve integrity in remote myocardium are unknown. Perfusion abnormalities, even in the absence of epicardial coronary artery disease, may relate to sympathetic dysfunction. This study was aimed to assess the interrelations of myocardial blood flow (MBF), contractile function, and sympathetic innervation in non-infarcted remote myocardium., Methods and Results: Seventy patients with ICMP or DCMP and LVEF ≤35% were included. [(15)O]H2O- and [(11)C]hydroxyephedrine (HED) PET was performed to quantify resting MBF, hyperaemic MBF, and sympathetic innervation. Cardiovascular magnetic resonance (CMR) imaging was performed to assess left ventricular function, mass, wall thickening, and scar size. Wall thickening, [(11)C]HED retention index (RI), and MBF were assessed in remote segments without scar, selected on CMR. [(11)C]HED RI was correlated with resting MBF (r = 0.41, P < 0.001) and hyperaemic MBF (r = 0.55, P < 0.001) in remote myocardium in both ICMP and DCMP. In addition, LV volumes (r = -0.40, P = 0.001), LV mass (r = -0.31, P = 0.008), and wall thickening (r = 0.45, P < 0.001) correlated with remote [(11)C]HED RI. Multivariable analysis revealed that hyperaemic MBF (B = 0.79, P < 0.001), wall thickening (B = 0.01, P = 0.03), and LVEDV (B = -0.03, P = 0.02) were independent predictors for remote [(11)C]HED RI., Conclusion: Hyperaemic MBF is independently associated with sympathetic innervation in non-infarcted remote myocardium in patients with ICMP and DCMP. This suggests that microvascular dysfunction might be an important factor related to sympathetic nerve integrity. Whether impaired hyperaemic MBF is the primary cause of this relation remains unclear., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Aims: Absolute quantification of myocardial blood flow (MBF) with (15)O-water cardiac positron emission tomography (PET)/CT has recently demonstrated to hold promising diagnostic value for the detection of coronary artery disease (CAD). However, methodological differences in utilized analysis software packages (SP) could affect generated MBF values, potentially prohibiting widespread clinical applicability of obtained normal thresholds. The aim of this study was to compare two validated non-commercial SP, Carimas and Cardiac VUer, for the quantification of MBF using (15)O-water PET., Methods and Results: One hundred patients with intermediate likelihood of CAD and scanned in academic centres in Amsterdam (n = 50) and Turku (n = 50) were included in the study. Patients underwent a (15)O-water PET/CT scan during rest and vasodilator stress based on clinical indications. A single observer, blinded from clinical results and with no prior experience in either SP, analysed all patients twice with both SP. Reproducibility of each SP was assessed using intraclass correlation coefficients (ICC). Intersoftware agreement was assessed using paired t-tests and linear regression. ICC was excellent for each SP for both global and regional MBF (ICC >0.90). Global MBF was comparable between Carimas and Cardiac VUer during rest (1.02 ± 0.28 vs. 0.99 ± 0.23 mL min(-1)g(-1), respectively, P = 0.07), and slightly higher for Carimas during stress (2.73 ± 0.82 vs. 2.63 ± 0.84 mL min(-1)g(-1), respectively, P = 0.01). At a regional level, for resting conditions small (<10%) but significant discrepancies were noted in each vascular territory while for stress MBF, a significant difference was only observed for the LAD region. Differences between SP for the LAD territory were abolished after exclusion of the distal apical segment, which is susceptible to spillover artefacts. An excellent correlation between MBF values was found for global (r = 0.96) and regional MBF (r > 0.94 for all)., Conclusion: For global and regional MBF, Carimas and Cardiac VUer showed excellent agreement and intra-observer reproducibility. These results confirm that, for patients with intermediate likelihood of CAD, these validated SP are interchangeable and can be utilized for routine clinical practice of (15)O-water cardiac PET.

Aims: This study evaluates the impact of hybrid imaging on referral for invasive coronary angiography (ICA) and revascularization rates., Methods and Results: A total of 375 patients underwent hybrid (15)O-water positron emission tomography (PET)/computed tomography (CT)-based coronary angiography (CTCA) imaging for the evaluation of coronary artery disease (CAD). Downstream treatment strategy within a 60-day period after hybrid PET/CTCA imaging for ICA referral and revascularization was assessed. CTCA examinations were classified as showing no (obstructive) CAD, equivocal (borderline test result), or obstructive CAD, while the PET perfusion images were classified into normal or abnormal. On the basis of CTCA imaging, 182 (49%) patients displayed no (obstructive) CAD. Only 10 (5%) patients who showed no (obstructive) CAD on CTCA were referred for ICA, which were all negative. An equivocal CT study was observed in 80 (21%) patients, among whom 56 (70%) showed normal myocardial perfusion imaging (MPI), resulting in referral rates for ICA of 18% for normal MPI and 71% for abnormal MPI, respectively. No revascularizations were performed in the presence of normal MPI, while 59% of those with abnormal MPI were revascularized. CTCA indentified obstructive CAD in 113 (30%) patients accompanied in 59 (52%) patients with abnormal MPI. Referral rate for ICA was 57% for normal MPI and 88% for those with abnormal MPI, resulting in revascularization rates of 26% and 72%, respectively., Conclusion: Hybrid (15)O-water PET/CTCA imaging impacts clinical decision-making with regard to referral for ICA and revascularization procedures. Particularly, in the presence of an equivocal or abnormal CTCA, MPI could guide in the decision to refer for ICA and revascularization.

Unlabelled: Hybrid imaging using PET in conjunction with CT-based coronary angiography (PET/CTCA) enables near-simultaneous quantification of myocardial blood flow (MBF) and anatomical evaluation of coronary arteries. CTCA is an excellent imaging modality to rule out obstructive coronary artery disease (CAD), but functional assessment is warranted in the presence of a CTCA-observed stenosis because the specificity of CTCA is relatively low. Quantitative H(2)(15)O PET/CTCA may yield complementary information and enhance diagnostic accuracy. The purpose of this study was to evaluate the diagnostic accuracy of quantitative H(2)(15)O PET/CTCA in a clinical cohort of patients with suspected CAD who underwent both cardiac H(2)(15)O PET/CTCA and invasive coronary angiography (ICA). In addition, this study aimed to evaluate and compare the accuracy of hyperemic MBF versus coronary flow reserve (CFR)., Methods: Patients (n = 120; mean age ± SD, 61 ± 10 y; 77 men and 43 women) with a predominantly intermediate pretest likelihood for CAD underwent both quantitative H(2)(15)O PET/CTCA and ICA. A ≥50% stenosis at ICA or a fractional flow reserve ≤ 0.80 was considered significant., Results: Obstructive CAD was diagnosed in 49 of 120 patients (41%). The diagnostic accuracy of hyperemic MBF was significantly higher than CFR (80% vs. 68%, respectively, P = 0.02), with optimal cutoff values of 1.86 mL/min/g and 2.30, respectively. On a per-patient basis, the sensitivity, specificity, negative predictive value, and positive predictive value of CTCA were 100%, 34%, 100%, and 51%, respectively, as compared with 76%, 83%, 83%, and 76%, respectively, for quantitative hyperemic MBF PET. Quantitative H(2)(15)O PET/CTCA reduced the number of false-positive CTCA studies from 47 to 6, although 12 of 49 true-positive CTCAs were incorrectly reclassified as false-negative hybrid scans on the basis of (presumably) sufficient hyperemic MBF. Compared with CTCA (61%) or H(2)(15)O PET (80%) alone (both P < 0.05), the hybrid approach significantly improved diagnostic accuracy (85%)., Conclusion: The diagnostic accuracy of quantitative H(2)(15)O PET/CTCA is superior to either H(2)(15)O PET or CTCA alone for the detection of clinically significant CAD. Hyperemic MBF was more accurate than CFR, implying that a single measurement of MBF in diagnostic protocols may suffice.

Aims: There is growing evidence that coronary artery disease (CAD) affects not only the conduit epicardial coronary arteries, but also the microvascular coronary bed. Moreover, coronary microvascular dysfunction (CMVD) often precedes the stage of clinically overt epicardial CAD. Coronary artery calcium (CAC) and carotid intima-media thickness (C-IMT) measured with computed tomography (CT) and ultrasound, respectively, are among the available techniques to non-invasively assess atherosclerotic burden. An increased CAC score and C-IMT have also been associated with CMVD. It is therefore of interest to explore and compare the potential of CAC against C-IMT to predict minimal coronary vascular resistance (CVR)., Methods and Results: We evaluated 120 patients (mean age 56 ± 9 years, 58 men) without a documented history of CAD in whom obstructive CAD was excluded. All patients underwent C-IMT measurements, CAC scoring, and vasodilator stress (15)O-water positron emission tomography (PET)/CT, during which the coronary flow reserve (CFR) and minimal CVR were analysed. Minimal CVR increased significantly with increasing tertiles of C-IMT (22 ± 6, 27 ± 11, and 28 ± 9 mmHg mL(-1)min(-1) g(-1), P < 0.01), whereas the CFR was comparable across all C-IMT groups (P = 0.50). Minimal CVR increased significantly with an increase in CAC score (23 ± 9, 27 ± 8, 32 ± 10, and 32 ± 7 mmHg mL(-1) min(-1) g(-1), P < 0.01), whereas the CFR did not show a significant decrease with higher CAC scores (P = 0.18). Multivariable regression analysis revealed that C-IMT (P = 0.03), but not CAC, was independently associated with minimal CVR., Conclusion: C-IMT, but not CAC score, independently predicts minimal CVR in patients with multiple cardiovascular risk factors and suspected of CAD.