Splenic switch-off in [15O]H2O-positron emission tomography myocardial perfusion imaging using parametric blood flow images.

BACKGROUND: Evaluation of sufficient adenosine response constitutes a significant challenge in myocardial perfusion imaging (MPI). Splenic switch-off in MPI studies denotes a visually (qualitatively) reduced splenic radiotracer signal during adenosine stress and is considered indicative of sufficient cardiac vasodilation. In this study, we examined semi-quantitative and quantitative approaches to splenic switch-off assessment using [15O]H2O-PET with either summed activity images or calculated parametric splenic blood flow images. METHODS: Cohort 1: 90 clinical patients undergoing [15O]H2O MPI in whom adenosine response was considered clinically adequate were identified to characterize the corresponding splenic switch-off. Spleen stress/rest-ratio (SSR-ratio) was calculated as spleen stress signal intensity/spleen rest signal intensity on both summed activity and parametric blood flow images. Cohort 2: Twenty-five patients with repeat MPI due to suspected insufficient adenosine response were identified to observe if splenic switch-off on the initial MPI could predict the outcome of the repeat MPI. Cohort 3: Fifty-four patients who were considered adenosine responders on MPI and who had a coronary angiogram (CAG) follow-up within 3 months after MPI served as a separate validation group. RESULTS: Splenic switch-off was present in most patients with a clinically sufficient adenosine response (Cohort 1), illustrated by both visual (74.4%-86.7%), semi-quantitative (summed activity images) (85.6%), and quantitative (parametric blood flow images) (92.2%) evaluation, which corresponds to the distribution in patients with sufficient adenosine response and follow-up CAG (Cohort 3). In patients suspected of insufficient adenosine response on the initial MPI (Cohort 2), the repeat MPI only yielded different myocardial blood flow (MBF) results if the initial SSR-ratio was >0.90 on splenic parametric blood flow images. CONCLUSION: quantitative splenic switch-off assessment on parametric blood flow images was superior to the semi-quantitative splenic switch-off approach. Patients with a suspected insufficient initial adenosine response and SSR-ratio >0.90 can benefit from a repeat MPI. Thus, the integration of quantitative splenic switch-off using parametric blood flow images in the evaluation of adenosine response may support future clinical decision-making.

Extracardiac findings with increased perfusion during clinical O-15-H2O PET/CT myocardial perfusion imaging: A case series.

BACKGROUND: Coincidental extracardiac findings with increased perfusion were reported during myocardial perfusion imaging (MPI) with various retention radiotracers. Clinical parametric O-15-H2O PET MPI yielding quantitative measures of myocardial blood flow (MBF) was recently implemented at our facility. We aim to explore whether similar extracardiac findings are observed using O-15-H2O. METHODS AND RESULTS: All patients (2963) were scanned with O-15-H2O PET MPI according to international guidelines and extracardiac findings were collected. In contrast to parametric O-15-H2O MBF images, extracardiac perfusion was assessed using summed images. Biopsy histopathology and other imaging modalities served as reference standards. Various malignant lesions with increased perfusion were detected, including lymphomas, large-celled neuroendocrine tumour, breast, and lung cancer plus metastases from colonic and renal cell carcinomas. Furthermore, inflammatory and hyperplastic benign conditions with increased perfusion were observed: rib fractures, gynecomastia, atelectasis, sarcoidosis, pneumonia, chronic lung inflammation and fibrosis, benign lung nodule, chronic diffuse lung infiltrates, pleural plaques and COVID-19 infiltrates. CONCLUSIONS: Malignant and benign extracardiac coincidental findings with increased perfusion are readily visible and frequently seen on O-15-H2O PET MPI. We recommend evaluating the summed O-15-H2O PET images in addition to the low-dose CT attenuation images.

Tumour blood flow for prediction of human prostate cancer aggressiveness: a study with Rubidium-82 PET, MRI and Na+/K+-ATPase-density.

PURPOSE: Tumour blood flow (TBF) is a crucial determinant of cancer growth. Recently, we validated Rubidium-82 (82Rb) positron emission tomography (PET) for TBF measurement in prostate cancer (PCa) and found TBF and cancer aggressiveness positively correlated. The aims of the present study were to determine the ability of TBF for separating significant from insignificant PCa and to examine the relation to underlying Na+/K+-ATPase density, which is relevant as 82Rb is transported intracellularly via the Na+/K+-ATPase. METHODS: One hundred and two patients were included for pelvic 82Rb PET scan prior to magnetic resonance imaging (MRI)-guided prostate biopsy. Findings constituted 100 PCa lesions (86 patients) and 25 benign lesions (16 patients). Tumours were defined on MRI and transferred to 82Rb PET for TBF measurement. Immunohistochemical Na+/K+-ATPase staining was subsequently performed on biopsies. RESULTS: TBF was the superior predictor (rho = 0.68, p < 0.0001, inflammatory lesions excluded) of MRI-guided biopsy grade group (GG) over lowest apparent diffusion coefficient (ADC) value (rho = -0.23, p = 0.01), independent of ADC value and tumour volume (p < 0.0001). PET could separate GG-2-5 from GG-1 and benign lesions with an area under the curve (AUC), sensitivity, and specificity of 0.79, 96%, and 59%, respectively. For separating GG-3-5 from GG-1-2 and benign lesions the AUC, sensitivity, and specificity were 0.82, 95%, and 63%, respectively. Na+/K+-ATPase density per PCa cell profile was 38% lower compared with that of the benign prostate cell profiles. Neither cell density nor Na+/K+-ATPase density determined tumour 82Rb uptake. CONCLUSION: TBF is an independent predictor of PCa aggressiveness and deserves more attention, as it may be valuable in separating clinically significant from insignificant PCa.

Cardiovascular Effects of Treatment With the Ketone Body 3-Hydroxybutyrate in Chronic Heart Failure Patients.

BACKGROUND: Myocardial utilization of 3-hydroxybutyrate (3-OHB) is increased in patients with heart failure and reduced ejection fraction (HFrEF). However, the cardiovascular effects of increased circulating plasma-3-OHB levels in these patients are unknown. Consequently, the authors' aim was to modulate circulating 3-OHB levels in HFrEF patients and evaluate: (1) changes in cardiac output (CO); (2) a potential dose-response relationship between 3-OHB levels and CO; (3) the impact on myocardial external energy efficiency (MEE) and oxygen consumption (MVO2); and (4) whether the cardiovascular response differed between HFrEF patients and age-matched volunteers. METHODS: Study 1: 16 chronic HFrEF patients (left ventricular ejection fraction: 37±3%) were randomized in a crossover design to 3-hour of 3-OHB or placebo infusion. Patients were monitored invasively with a Swan-Ganz catheter and with echocardiography. Study 2: In a dose-response study, 8 HFrEF patients were examined at increasing 3-OHB infusion rates. Study 3 to 4: 10 HFrEF patients and 10 age-matched volunteers were randomized in a crossover design to 3-hour 3-OHB or placebo infusion. MEE and MVO2 were evaluated using 11C-acetate positron emission tomography. RESULTS: 3-OHB infusion increased circulating levels of plasma 3-OHB from 0.4±0.3 to 3.3±0.4 mM ( P<0.001). CO rose by 2.0±0.2 L/min ( P<0.001) because of an increase in stroke volume of 20±2 mL ( P<0.001) and heart rate of 7±2 beats per minute (bpm) ( P<0.001). Left ventricular ejection fraction increased 8±1% ( P<0.001) numerically. There was a dose-response relationship with a significant CO increase of 0.3 L/min already at plasma-3-OHB levels of 0.7 mM ( P<0.001). 3-OHB increased MVO2 without altering MEE. The response to 3-OHB infusion in terms of MEE and CO did not differ between HFrEF patents and age-matched volunteers. CONCLUSIONS: 3-OHB has beneficial hemodynamic effects in HFrEF patients without impairing MEE. These beneficial effects are detectable in the physiological concentration range of circulating 3-OHB levels. The hemodynamic effects of 3-OHB were observed in both HFrEF patients and age-matched volunteers. 3-OHB may potentially constitute a novel treatment principle in HFrEF patients.

Effect of liraglutide on myocardial glucose uptake and blood flow in stable chronic heart failure patients: A double-blind, randomized, placebo-controlled LIVE sub-study.

BACKGROUND: The glucagon-like peptide-1 analog liraglutide increases heart rate and may be associated with more cardiac events in chronic heart failure (CHF) patients. We studied whether this could be ascribed to effects on myocardial glucose uptake (MGU), myocardial blood flow (MBF) and MBF reserve (MFR). METHODS AND RESULTS: CHF patients with left ventricular ejection fraction ≤45% and without type 2 diabetes were randomized to liraglutide (N = 18) 1.8 mg once daily or placebo (N = 18) for 24 weeks in a double-blinded design. Changes in MGU during an oral glucose tolerance test (OGTT) and changes in MBF and MFR from baseline to follow-up were measured quantitatively by 18F-FDG and 15O-H2O positron emission tomography. Compared with placebo, liraglutide reduced weight (P = 0.03), HbA1c (P = 0.03) and the 2-hour glucose value during the OGTT (P = 0.004). Despite this, changes in MGU (P = 0.98), MBF (P = 0.76) and MFR (P = 0.89) from baseline to follow-up did not differ between groups. Furthermore, there was no association between the level of insulin resistance at baseline and changes in MGU in patients treated with liraglutide. CONCLUSION: Liraglutide did not affect MGU, MBF, or MFR in non-diabetic CHF patients. Any potential increase in cardiac events in these patients seems not to involve changes in MGU, MBF, or MFR. TRIAL REGISTRATION: Trial registry: http://www.ClinicalTrials.org . Identifier: NCT01472640. Url: https://clinicaltrials.gov/ct2/show/NCT01472640?term=NCT01472640&rank=1.

Effect of remote ischemic conditioning on myocardial perfusion in patients with suspected ischemic coronary artery disease.

BACKGROUND: Remote ischemic conditioning (RIC) confers protection against myocardial ischemia-reperfusion injury and may modulate coronary blood flow. We investigated whether RIC affects resting myocardial perfusion (MP) in patients with suspected ischemic coronary artery disease by quantitative MP imaging. METHODS AND RESULTS: We included 49 patients with suspected ischemic coronary artery disease. Resting MP was quantified by 82Rubidium positron emission tomography/computed tomography (82Rb-PET/CT) imaging before and after RIC, performed as four cycles of 5 minutes upper arm ischemia and reperfusion. Subsequent adenosine 82Rb-PET/CT stress-imaging identified non-ischemic and reversibly ischemic myocardial segments. MicroRNA-144 plasma levels were measured before and after RIC. Normalized for rate pressure product, RIC did not affect MP globally (P = .64) or in non-ischemic myocardial segments (P = .58) but decreased MP in reversibly ischemic myocardial segments (-0.11 mL/min/g decrease in MP following RIC; 95% CI -0.17 to -0.06, P < .001). However, we found no effect of RIC when MP was normalized for cardiac work. MicroRNA-144 plasma levels increased following RIC (P = .006) but did not correlate with a change in global MP in response to RIC (P = .40). CONCLUSIONS: RIC did not substantially affect resting MP globally or in non-ischemic and reversibly ischemic myocardial territories in patients with suspected ischemic coronary artery disease.

Clinical features, exercise hemodynamics, and determinants of left ventricular elevated filling pressure in heart-transplanted patients.

This study aimed to assess clinical, functional, and hemodynamic characteristics of heart-transplanted (HTX) patients during exercise. We performed comprehensive echocardiographic graft function assessment during invasive hemodynamic semi-supine exercise test in 57 HTX patients. According to hemodynamics findings, patients were divided into Group A: normal left ventricular (LV) filling pressure (FP): pulmonary capillary wedge pressure (PCWP) <15 mmHg at rest and <25 mmHg at peak exercise, and Group B: elevated LV-FP: PCWP ≥15 mmHg at rest or ≥25 mmHg at peak exercise. Thirty-one patients (54%) had normal LV-FP and 26 patients (46%) had elevated LV-FP. The latter had higher cumulative rejection burden (P < 0.01) and were more symptomatic (NYHA class >1) (P < 0.05), and cardiac allograft vasculopathy (CAV) was more prevalent (P < 0.05). With exercise, the changes in both left- and right-sided filling pressures were significantly increased, whereas LV longitudinal myocardial deformation was lower (P < 0.05) in patients with elevated LV-FP than in patients with normal LV-FP. No between-group difference was observed for cardiac index or LV ejection fraction (LVEF) during exercise. In conclusion, elevated LV-FP can be demonstrated in approximately 50% of HTX patients. Patients with elevated LV-FP have impaired myocardial deformation capacity, higher prevalence of CAV, and higher rejection burden, and were more symptomatic. Exercise test with the assessment of longitudinal myocardial deformation should be considered in routine surveillance of HTX patients as a marker of restrictive filling (ClinicalTrials.gov Identifier: NCT02077764).

Repeatability of [15O]H2O PET imaging for lower extremity skeletal muscle perfusion: a test-retest study.

BACKGROUND: [15O]H2O PET/CT allows noninvasive quantification of tissue perfusion and can potentially play a future role in the diagnosis and treatment of peripheral artery disease. We aimed to evaluate the reliability of dynamic [15O]H2O PET imaging for measuring lower extremity skeletal muscle perfusion. Ten healthy participants underwent same-day test-retest study with six dynamic [15O]H2O PET scans of lower legs and feet. Manual volume-of-interests were drawn in skeletal muscles, and PET time activity curves were extracted. K1 values (mL/min/100 mL) were estimated using a single-tissue compartment model (1TCM), autoradiography (ARG), and parametric imaging with blood input functions obtained from separate heart scans. RESULTS: Resting perfusion values in the muscle groups of the lower legs ranged from 1.18 to 5.38 mL/min/100 mL (ARG method). In the muscle groups of the feet, perfusion values ranged from 0.41 to 3.41 mL/min/100 mL (ARG method). Test-retest scans demonstrated a strong correlation and good repeatability for skeletal muscle perfusion with an intraclass correlation coefficient (ICC) of 0.88 and 0.87 and a repeatability coefficient of 34% and 53% for lower legs and feet, respectively. An excellent correlation was demonstrated when comparing volume-of-interest-based methods (1TCM and ARG) (lower legs: ICC = 0.96, feet: ICC = 0.99). Parametric images were in excellent agreement with the volume-of-interest-based ARG method (lower legs: ICC = 0.97, feet: ICC = 0.98). CONCLUSION: Parametric images and volume-of-interest-based methods demonstrated comparable resting perfusion values in the lower legs and feet of healthy individuals. The largest variation was seen between individuals, whereas a smaller variation was seen between muscle groups. Repeated measurements of resting blood flow yielded a strong overall correlation for all methods.

Guiding early revascularization using [15O]H2O positron emission tomography myocardial perfusion imaging: impact of atrial fibrillation.

AIMS: Myocardial perfusion imaging (MPI) using [15O]H2O positron emission tomography (PET) is used to guide the selection of patients with angina for invasive angiography and possible revascularization. Our study evaluated (i) whether atrial fibrillation (AF) reduces global hyperaemic myocardial blood flow (MBF) and (ii) whether [15O]H2O PET MPI effectively guides revascularization procedures for patients with ongoing AF. METHODS AND RESULTS: We prospectively recruited 346 patients with angina and persistent or paroxysmal AF referred for baseline/hyperaemic [15O]H2O PET MPI. The primary outcome was revascularization within 3 months of MPI. In the analyses, patients were divided into four groups based on whether they had ongoing AF or sinus rhythm (SR) and whether they had previously documented coronary artery disease (CAD) or not. Thus, four groups were compared: SR-noCAD, AF-noCAD, SR-CAD, and AF-CAD. Hyperaemic MBF was affected by both ongoing AF and prior CAD [MBF (mL/min/g): 2.82 (SR-noCAD) vs. 2.12 (AF-noCAD) vs. 2.22 (SR-CAD) vs. 1.80 (AF-CAD), two-way analysis of variance P < 0.0001]. In multiple linear regression, ongoing AF was independently associated with reduced hyperaemic MBF. Every 0.1 mL/min/g decrease in hyperaemic MBF was associated with a 23% increase in odds of early revascularization. Receiver operating characteristic (ROC) analysis of vessel-specific hyperaemic MBF to predict early revascularization yielded the following areas under the ROC curve: SR-noCAD: 0.95 (P < 0.0001); AF-noCAD: 0.79 (P < 0.0001); SR-CAD: 0.78 (P < 0.0001); and AF-CAD: 0.88 (P < 0.0001). CONCLUSION: Ongoing AF is associated with 19-25% reduced global hyperaemic MBF as measured by [15O]H2O MPI PET. Regardless, vessel-specific hyperaemic MBF still predicts early revascularization in patients with AF.

A ketogenic diet lowers myocardial fatty acid oxidation but does not affect oxygen consumption: a study in overweight humans.

OBJECTIVE: A ketogenic diet (KD) characterized by very low carbohydrate intake and high fat consumption may simultaneously induce weight loss and be cardioprotective. The "thrifty substrate hypothesis" posits that ketone bodies are more energy efficient compared with other cardiac oxidative substrates such as fatty acids. This work aimed to study whether a KD with presumed increased myocardial ketone body utilization reduces cardiac fatty acid uptake and oxidation, resulting in decreased myocardial oxygen consumption (MVO2 ). METHODS: This randomized controlled crossover trial examined 11 individuals with overweight or obesity on two occasions: (1) after a KD and (2) after a standard diet. Myocardial free fatty acid (FFA) oxidation, uptake, and esterification rate were measured using dynamic [11 C]palmitate positron emission tomography (PET)/computed tomography, whereas MVO2 and myocardial external efficiency (MEE) were measured using dynamic [11 C]acetate PET. RESULTS: The KD increased plasma ß-hydroxybutyrate, reduced myocardial FFA oxidation (p < 0.01) and uptake (p = 0.03), and increased FFA esterification (p = 0.03). No changes were observed in MVO2 (p = 0.2) or MEE (p = 0.87). CONCLUSIONS: A KD significantly reduced myocardial FFA uptake and oxidation, presumably by increasing ketone body oxidation. However, this change in cardiac substrate utilization did not improve MVO2 , speaking against the thrifty substrate hypothesis.

Ex Vivo Simultaneous H215O Positron Emission Tomography and Magnetic Resonance Imaging of Porcine Kidneys-A Feasibility Study.

The aim was to establish combined H215O PET/MRI during ex vivo normothermic machine perfusion (NMP) of isolated porcine kidneys. We examined whether changes in renal arterial blood flow (RABF) are accompanied by changes of a similar magnitude in renal blood perfusion (RBP) as well as the relation between RBP and renal parenchymal oxygenation (RPO). METHODS: Pig kidneys (n = 7) were connected to a NMP circuit. PET/MRI was performed at two different pump flow levels: a blood-oxygenation-level-dependent (BOLD) MRI sequence performed simultaneously with a H215O PET sequence for determination of RBP. RESULTS: RBP was measured using H215O PET in all kidneys (flow 1: 0.42-0.76 mL/min/g, flow 2: 0.7-1.6 mL/min/g). We found a linear correlation between changes in delivered blood flow from the perfusion pump and changes in the measured RBP using PET imaging (r2 = 0.87). CONCLUSION: Our study demonstrated the feasibility of combined H215O PET/MRI during NMP of isolated porcine kidneys with tissue oxygenation being stable over time. The introduction of H215O PET/MRI in nephrological research could be highly relevant for future pre-transplant kidney evaluation and as a tool for studying renal physiology in healthy and diseased kidneys.

Pulmonary vascular adaptations to hypoxia in elite breath-hold divers.

Introduction: Elite breath-hold divers (BHD) possess several oxygen conserving adaptations to endure long dives similar to diving mammals. During dives, Bottlenose Dolphins may increase the alveolar ventilation (VA) to perfusion (Q) ratio to increase alveolar oxygen delivery. We hypothesized that BHD possess similar adaptive mechanisms during apnea. Methods and results: Pulmonary blood volume (PBV) was determined by echocardiography, 15O-H2O PET/CT, and cardiac MRi, (n = 6) during and after maximum apneas. Pulmonary function was determined by body box spirometry and compared to matched controls. After 2 min of apnea, the PBV determined by echocardiography and 15O-H2O-PET/CT decreased by 26% and 41%, respectively. After 4 min of apnea, the PBV assessed by echocardiography and cardiac MRi decreased by 48% and 67%, respectively (n = 6). Fractional saturation (F)O2Hb determined by arterial blood-gas-analyses collected after warm-up and a 5-minute pool-apnea (n = 9) decreased by 43%. Compared to matched controls (n = 8), spirometry revealed a higher total and alveolar-lung-capacity in BHD (n = 9), but a lower diffusion-constant. Conclusion: Our results contrast with previous studies, that demonstrated similar lung gas transfer in BHD and matched controls. We conclude that elite BHD 1) have a lower diffusion constant than matched controls, and 2) gradually decrease PBV during apnea and in turn increase VA/Q to increase alveolar oxygen delivery during maximum apnea. We suggest that BHD possess pulmonary adaptations similar to diving mammals to tolerate decreasing tissue oxygenation. New and noteworthy: This manuscript addresses novel knowledge on tolerance to hypoxia during diving, which is shared by elite breath-hold divers and adult diving mammals: Our study indicates that elite breath-hold divers gradually decrease pulmonary blood volume and in turn increase VA/Q, to increase alveolar oxygen delivery during maximum apnea to tolerate decreasing oxygen levels similar to the Bottlenose Dolphin.

[15O]H2O PET/MRI for Assessment of Complete Response to Neoadjuvant or Induction Chemotherapy in Patients with Muscle-Invasive Bladder Cancer: A Pilot Study.

Background: Accurate assessment of therapy response to chemotherapy could possibly offer a bladder-sparing approach in selected patients with localized muscle-invasive bladder cancer (MIBC). The aim of this study was to evaluate whether [15O]H2O PET/MRI can be used for assessment of complete local pathological response to preoperative chemotherapy in patients with MIBC. Methods: This prospective pilot study included 13 patients with MIBC treated with neoadjuvant or induction chemotherapy and subsequent radical cystectomy. Patients underwent a [15O]H2O PET/MRI scan before chemotherapy and another scan after chemotherapy before radical cystectomy. Volumes of interest were delineated on T2-weighted MRI and transferred to parametric images for dynamic analysis. Tumor blood flow (TBF) was estimated by [15O]H2O PET. Changes in TBF were compared with histopathology. The Wilcoxon matched-pairs signed-ranks test was used for comparing pre- and post-chemotherapy measurements. Results: Mean TBF decreased by 49%. Mean TBF in complete responders (ypT0N0/ypTis) was not significantly different from non-complete responders (≥ypT1) (p = 0.52). Conclusions: Despite a measurable decrease in TBF after chemotherapy treatment, we were not able to estimate a TBF threshold for identifying complete responders to chemotherapy for MIBC patients. Further studies are needed to elucidate the potential of [15O]H2O PET/MRI in assessing therapy response in MIBC.

Hemoglobin concentration and blood shift during dry static apnea in elite breath hold divers.

Introduction: Elite breath-hold divers (BHD) enduring apneas of more than 5 min are characterized by tolerance to arterial blood oxygen levels of 4.3 kPa and low oxygen-consumption in their hearts and skeletal muscles, similar to adult seals. Adult seals possess an adaptive higher hemoglobin-concentration and Bohr effect than pups, and when sedated, adult seals demonstrate a blood shift from the spleen towards the brain, lungs, and heart during apnea. We hypothesized these observations to be similar in human BHD. Therefore, we measured hemoglobin- and 2,3-biphosphoglycerate-concentrations in BHD (n = 11) and matched controls (n = 11) at rest, while myocardial mass, spleen and lower extremity volumes were assessed at rest and during apnea in BHD. Methods and results: After 4 min of apnea, left ventricular myocardial mass (LVMM) determined by 15O-H2O-PET/CT (n = 6) and cardiac MRI (n = 6), was unaltered compared to rest. During maximum apnea (∼6 min), lower extremity volume assessed by DXA-scan revealed a ∼268 mL decrease, and spleen volume, assessed by ultrasonography, decreased ∼102 mL. Compared to age, BMI and VO2max matched controls (n = 11), BHD had similar spleen sizes and 2,3- biphosphoglycerate-concentrations, but higher total hemoglobin-concentrations. Conclusion: Our results indicate: 1) Apnea training in BHD may increase hemoglobin concentration as an oxygen conserving adaptation similar to adult diving mammals. 2) The blood shift during dry apnea in BHD is 162% more from the lower extremities than from the spleen. 3) In contrast to the previous theory of the blood shift demonstrated in sedated adult seals, blood shift is not towards the heart during dry apnea in humans.

Complete somatostatin-induced insulin suppression combined with heparin loading does not significantly suppress myocardial 18F-FDG uptake in patients with suspected cardiac sarcoidosis.

BACKGROUND: Cardiac 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography preceded by extended fasting is used to demonstrate active cardiac sarcoidosis. However, physiological insulin-dependent myocardial 18F-FDG uptake often obscures 18F-FDG uptake in sarcoid lesions. We therefore aimed to completely suppress physiological myocardial 18F-FDG uptake by pharmaceutically blocking endogenous insulin secretion while elevating free fatty acids (FFAs). METHODS AND RESULTS: Six patients with suspected cardiac sarcoidosis were studied in a randomized cross-over design: (1) 12 hours fasting followed by 2 hours saline infusion (SALINE), and (2) 12 hours fasting followed by 2 hour infusions of somatostatin (300 µg/hour) and heparin (70 mIE/kg/minutes) (SOMA). 18F-FDG PET scans were performed post-infusion. Glucose, insulin, and FFA levels were measured and left ventricle SUV-values were recorded. During the SALINE infusion, insulin, glucose, and FFAs remained stable. By design, the SOMA infusions rapidly (<60 minutes) suppressed insulin completely, while FFA levels peaked at 1.13 ± 0.23 mM. However, SOMA infusions only suppressed cardiac 18F-FDG uptake insignificantly globally [SUVmean (g/mL): 4.0 ± 3.3 (SALINE) vs 2.4 ± 1.2 (SOMA), P = .15] and regionally. CONCLUSIONS: Complete insulin suppression combined with markedly increased circulating FFAs does not completely suppress physiological myocardial 18F-FDG uptake and thus conveys no extra diagnostic value compared with extended fasting.

A Persistent Left-Sided Superior Vena Cava Detected on a O-15-H 2 O PET/CT of the Heart.

ABSTRACT: A persistent left-sided superior vena cava (PLSVC) is an uncommon finding with a prevalence of up to 0.5% in the general population. The PLSVC appears when the left anterior cardinal vein fails to regress as the ligament of Marshall during embryologic development. It is usually asymptomatic and discovered incidentally; however, its recognition is important because it might complicate invasive cardiovascular procedures. In this case, we report an incidental finding of a PLSVC detected on the O-15-H 2 O PET/CT of a patient who was referred for myocardial perfusion imaging.

Intravenous and oral whole body ketone dosimetry, biodistribution, metabolite correction and kinetics studied by (R)-[1-11C]ß-hydroxybutyrate ([11C]OHB) PET in healthy humans.

BACKGROUND: Ketones are increasingly recognized as an important and possibly oxygen sparing source of energy in vital organs such as the heart, the brain and the kidneys. Drug treatments, dietary regimens and oral ketone drinks designed to deliver ketones for organ and tissue energy production have therefore gained popularity. However, whether ingested ketones are taken up by various extra-cerebral tissues and to what extent is still largely unexplored. It was therefore the aim of this study to use positron emission tomography (PET) to explore the whole body dosimetry, biodistribution and kinetics of the ketone tracer (R)-[1-11C]ß-hydroxybutyrate ([11C]OHB). Six healthy subjects (3 women and 3 men) underwent dynamic PET studies after both intravenous (90 min) and oral (120 min) administration of [11C]OHB. Dosimetry estimates of [11C]OHB was calculated using OLINDA/EXM software, biodistribution was assessed visually and [11C]OHB tissue kinetics were obtained using an arterial input function and tissue time-activity curves. RESULTS: Radiation dosimetry yielded effective doses of 3.28 [Formula: see text]Sv/MBq (intravenous administration) and 12.51 [Formula: see text]Sv/MBq (oral administration). Intravenous administration of [11C]OHB resulted in avid radiotracer uptake in the heart, liver, and kidneys, whereas lesser uptake was observed in the salivary glands, pancreas, skeletal muscle and red marrow. Only minimal uptake was noted in the brain. Oral ingestion of the tracer resulted in rapid radiotracer appearance in the blood and radiotracer uptake in the heart, liver and kidneys. In general, [11C]OHB tissue kinetics after intravenous administration were best described by a reversible 2-tissue compartmental model. CONCLUSION: The PET radiotracer [11C]OHB shows promising potential in providing imaging data on ketone uptake in various physiologically relevant tissues. As a result, it may serve as a safe and non-invasive imaging tool for exploring ketone metabolism in organs and tissues of both patients and healthy individuals. Trial registration Clinical trials, NCT0523812, Registered February 10th 2022, https://clinicaltrials.gov/ct2/show/NCT05232812?cond=NCT05232812&draw=2&rank=1 .

Myocardial perfusion imaging by 15O-H2O positron emission tomography predicts clinical revascularization procedures in symptomatic patients with previous coronary artery bypass graft.

Aims: We wanted to assess if 15O-H2O myocardial perfusion imaging (MPI) in a clinical setting can predict referral to coronary artery catheterization [coronary angiography (CAG)], execution of percutaneous coronary intervention (PCI), and post-PCI angina relief for patients with angina and previous coronary artery bypass graft (CABG). Methods and results: We analysed 172 symptomatic CABG patients referred for 15O-H2O positron emission tomography (PET) MPI at Aarhus University Hospital Department of Nuclear Medicine & PET Centre, of which five did not complete the scan. In total, 145 (87%) enrolled patients had an abnormal MPI. Of these, 86/145 (59%) underwent CAG within 3 months; however, no PET parameters predicted referral to CAG. During the CAG, 25/86 (29%) patients were revascularized by PCI. Relative flow reserve (RFR) (0.49 vs. 0.54 P = 0.03), vessel-specific myocardial blood flow (MBF) (1.53 vs. 1.88 mL/g/min, P < 0.01), and vessel-specific myocardial flow reserve (MFR) (1.73 vs. 2.13, P < 0.01) were significantly lower in patients revascularized by PCI. Receiver operating characteristic analysis of the vessel-specific parameters yielded optimal cutoffs of 1.36 mL/g/min (MBF) and 1.28 (MFR) to predict PCI. Angina relief was experienced by 18/24 (75%) of the patients who underwent PCI. Myocardial blood flow was an excellent predictor of angina relief on both a global [area under the curve (AUC) = 0.85, P < 0.01] and vessel-specific (AUC = 0.90, P < 0.01) level with optimal cutoff levels of 1.99 mL/g/min and 1.85 mL/g/min, respectively. Conclusion: For CABG patients, RFR, vessel-specific MBF, and vessel-specific MFR measured by 15O-H2O PET MPI predict whether subsequent CAG will result in PCI. Additionally, global and vessel-specific MBF values predict post-PCI angina relief.

Clinical use of cardiac 18 F-FDG viability PET: a retrospective study of 44 patients undergoing post-test revascularization.

The coupling between coronary artery disease and the development of ischemic heart failure is well-established. For these patients, assessment of potentially viable but dysfunctional myocardial tissue (hibernation) is considered critical to guide optimal surgical treatment. Assessment with positron emission tomography (PET) theoretically provides measurements of hibernating tissue and maximal myocardial glucose uptake (MGU) in all cardiac territories. However, the clinical benefits of these measures are not thoroughly studied. We therefore aimed to investigate whether cardiac viability testing with combined Rubidium-82 (82Rb) and 18F-fluorodeoxyglucose (18F-FDG) predicts post-intervention improvement in left ventricle ejection fraction (LVEF) and survival. This retrospective study consisted of 131 patients with ischemic heart failure referred for dynamic 82Rb/18F-FDG PET viability testing prior to revascularization. The FDG viability scan was done during a hyperinsulinemic-euglycemic clamp and included PET measures static FDG hibernation and absolute MGU as well as myocardial blood flow and coronary flow reserve. In total, 44/131 patients undergoing viability testing were subsequently revascularized. Following revascularization, 26 patients had LVEF improvement of at least 5% while 18 patients had no improvement. A poor correlation between areas of intervention and areas of hibernation was observed. Receiver operating characteristics for all PET metrics did not predict improvement in LVEF. Furthermore, hibernation failed to predict survival regardless of whether patients underwent subsequent revascularization. Dynamic viability PET metrics (hibernation and MGU) do not predict post-intervention improvement in LVEF or overall survival in ischemic heart failure patients undergoing revascularization. In a clinical setting, the value of these measurements may therefore be limited. Kindly check and confirm the Given names and Family names for all the authors.All names are correct!