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Non-invasive quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR) provides incremental benefit to relative myocardial perfusion imaging (MPI) to diagnose and manage heart disease. MBF can be measured with single-photon emission computed tomography (SPECT) but the uncertainty in the measured values is high. Standardization and optimization of protocols for SPECT MBF measurements will improve the consistency of this technique. One element of the processing protocol is the choice of kinetic model used to analyze the dynamic image series.This study evaluates if a net tracer retention model (RET) will provide a better fit to the acquired data and greater test-retest precision than a one-compartment model (1CM) for SPECT MBF, with (+MC) and without (-MC) manual motion correction.Data from previously acquired rest-stress MBF studies (31 SPECT-PET and 30 SPECT-SPECT) were reprocessed ±MC. Rate constants (K1) were extracted using 1CM and RET, +/-MC, and compared pairwise with standard PET MBF measurements using cross-validation to obtain calibration parameters for converting SPECT rate constants to MBF and to assess the goodness-of-fit of the calibration curves. Precision (coefficient of variation of test re-test relative differences, COV) of flow measurements was computed for 1CM and RET ±MC using data from the repeated SPECT MBF studies.Both the RET model and MC improved the goodness-of-fit of the SPECT MBF calibration curves to PET. All models produced minimal bias compared with PET (mean bias0.6%). The SPECT-SPECT MBF COV significantly improved from 34% (1CM+MC) to 28% (RET+MC, p = 0.008).The RET+MC model provides a better calibration of SPECT to PET and blood flow measurements with better precision than the 1CM, without loss of accuracy. This article is protected by copyright. All rights reserved.

Background 82Rb PET is commonly performed using the same injected activity in all patients, resulting in lower image quality in larger patients. This study compared 82Rb dosing with exponential vs proportional functions of body weight on the standardization of myocardial perfusion image (MPI) quality. Methods Two sequential cohorts of N = 60 patients were matched by patient weight. Rest and dipyridamole stress 82Rb PET was performed using 0.1 MBq·kg−2 exponential and 9 MBq·kg−1 proportional dosing. MPI scans were compared qualitatively with visual image quality scoring (IQS) and quantitatively using the myocardium-to-blood contrast-to-noise ratio (CNR) and blood background signal-to-noise ratio (SNR) as a function of body weight. Results Average (min–max) patient body weight was 81 ± 18 kg (46–137 kg). Proportional dosing resulted in decreasing CNR, SNR, and visual IQS with increasing body weight (P Conclusion 82Rb PET dosing as an exponential (squared) function of body weight produced consistent stress perfusion image quality over a wide range of patient weights. Dramatically lower doses can be used in lighter patients, with the equivalent population dose shifted toward the heavier patients to standardize diagnostic image quality.

Aim The aim of the study was to evaluate the changes in central vascular inflammation measured by FDG PET and myocardial blood flow reserve (MFR) determined by 82Rb PET following therapy with biologic agents for 6 months in patients with psoriatic arthritis (PsA) and/or cutaneous psoriasis (PsO) (group 1) and compare with PsO subjects receiving non-biologic therapy (group 2) and controls (group 3). Methods and Results Target-to-background ratio (TBR) by FDG PET in the most diseased segment of the ascending aorta (TBRmax) was measured to assess vascular inflammation. 82Rb PET studies were used to assess changes in left ventricular MFR. A total of 34 participants were enrolled in the study (11 in group 1, 13 in group 2, and 10 controls). A significant drop in the thoracic aorta uptake was observed in the biologic-treated group (ΔTBRmax: − .46 ± .55) compared to the PsO group treated with non-biologic therapy (ΔTBRmax: .23 ± .67). Those showing response to biologic agents maintained MFR compared to who showed no response. Conclusion In a cohort of psoriasis patients treated with biologics, FDG uptake in the thoracic aorta decreased over the study period. Patients who demonstrated a significant anti-inflammatory response on FDG PET imaging maintained their MFR compared to non-responders.

In ischemic cardiomyopathy patients, cardiac sympathetic nervous system dysfunction is a predictor of sudden cardiac arrest (SCA). This study compared abnormal innervation and perfusion measured by [11C]meta-hydroxyephedrine (HED) vs [13N]ammonia (NH3), conventional uptake vs parametric tracer analysis, and their SCA risk discrimination. This is a sub-study analysis of the prospective PAREPET trial, which followed ischemic cardiomyopathy patients with reduced left ventricular ejection fraction (LVEF ≤ 35%) for events of SCA. Using n = 174 paired dynamic HED and NH3 positron emission tomography (PET) scans, regional defect scores (%LV extent × severity) were calculated using HED and NH3 uptake, as well as HED distribution volume and NH3 myocardial blood flow by kinetic modeling. During 4.1 years follow-up, there were 27 SCA events. HED defects were larger than NH3, especially in the lowest tertile of perfusion abnormality (P < .001). Parametric defects were larger than their respective tracer uptake defects (P < .001). SCA risk discrimination was not significantly improved with parametric or uptake mismatch (AUC = 0.73 or 0.70) compared to HED uptake defect scores (AUC = 0.67). Quantification of HED distribution volume and NH3 myocardial blood flow produced larger defects than their respective measures of tracer uptake, but did not lead to improved SCA risk stratification vs HED uptake alone.

Background Survivors of community-acquired pneumonia (CAP) are at increased risk of cardiovascular disease, cognitive and functional decline, and death, but the mechanisms remain unknown. Research Question Do CAP survivors have evidence of increased inflammatory activity in their lung parenchyma on 2-deoxy-2-[18F]fluoro- d -glucose (18FDG)-PET/CT imaging after clinical resolution of infection? Study Design and Methods We obtained 18FDG-PET/CT scans from 22 CAP survivors during their hospitalization with pneumonia (acute CAP) and 30 to 45 days after hospital discharge (post-CAP). In each set of scans, we assessed the lungs for foci of increased 18FDG uptake by visual interpretation and by total pulmonary glycolytic activity (tPGA), a background-corrected measure of total metabolic activity (as measured by 18FDG uptake). We also measured, post-CAP, the glycolytic activity of CAP survivor lung areas with volumes similar to the areas in 28 matched historical control subjects without pneumonia. Results Overall, 68% of CAP survivors (95% CI, 45%-85%) had distinct residual areas of increased 18FDG uptake in their post-CAP studies. tPGA decreased from 821.5 (SD, 1,140.2) in the acute CAP period to 80.0 (SD, 81.4) in the post-CAP period (P = .006). The tPGA post-CAP was significantly higher than that in lung areas of similar volume in control subjects (80.0 [SD, 81.4] vs –19.4 [SD, 5.9]; P Interpretation An important proportion of CAP survivors have persistent pulmonary foci of increased inflammatory activity beyond resolution of their infection. As inflammation contributes to cardiovascular disease, cognitive decline, functional waning, and mortality risk in the general population, this finding provides a plausible mechanism for the increased morbidity and mortality that have been observed post-CAP.

Objectives The aim of this study was to investigate the regional distribution of novel 18F-labeled positron emission tomographic (PET) tracer flubrobenguane (FBBG) (whose longer half-life could enable more widespread use) to assess myocardial presynaptic sympathetic nerve function in humans in comparison to [11C]meta-hydroxyephedrine (HED). Background The sympathetic nervous system (SNS) is vitally linked to cardiovascular regulation and disease. SNS imaging has shown prognostic value. HED is the most commonly used PET tracer for evaluation of sympathetic function in humans, but widespread clinical use is limited because of the short half-life of 11C. Methods A total of 25 participants (n = 6 healthy; n = 14 ischemic cardiomyopathy, left ventricular [LV] ejection fraction [EF] = 34 ± 5%; and n = 5 nonischemic cardiomyopathy, EF = 33 ± 3%) underwent 2 separate PET imaging visits 8.7 ± 7.6 days apart. On 1 visit, participants underwent dynamic HED PET imaging. On a different visit, participants underwent dynamic FBBG PET imaging. The order of testing was random. HED and FBBG global innervation (retention index [RI] and distribution volume [DV]) and regional denervation (% nonuniformity) were quantified to assess regional presynaptic sympathetic innervations. Results FBBG RI (r2 = 0.72; ICC = 0.79; p Conclusions FBBG and HED yield equivalent global and regional distributions in both patients with and without ischemic cardiomyopathy. 18F-labeled PET tracers, such as FBBG, are critical for widespread distribution necessary for multicenter clinical trials and to maximize patient impact.

Little is known about the sequelae of chronic sympathetic nervous system (SNS) activation in patients with pulmonary arterial hypertension (PAH) and right heart failure (RHF). We aimed to, (1) validate the use of [11C]-meta-hydroxyephedrine (HED) for assessing right ventricular (RV) SNS integrity, and (2) determine the effects of β-receptor blockade on ventricular function and myocardial SNS activity in a PAH rat model. PAH was induced in male Sprague-Dawley rats (N = 36) using the Sugen+chronic hypoxia model. At week 5 post-injection, PAH rats were randomized to carvedilol (15 mg·kg−1·day−1 oral; N = 16) or vehicle (N = 16) for 4 weeks. Myocardial SNS function was assessed with HED positron emission tomography(PET). With increasing PAH disease severity, immunohistochemistry confirmed selective sympathetic denervation within the RV and sparing of parasympathetic nerves. These findings were confirmed on PET with a significant negative relationship between HED volume of distribution(DV) and right ventricular systolic pressure (RVSP) in the RV (r = −0.90, p = 0.0003). Carvedilol did not reduce hemodynamic severity compared to vehicle. RV ejection fraction (EF) was lower in both PAH groups compared to control (p

Myocardial flow reserve (MFR) measurement provides incremental diagnostic and prognostic information. The objective of the current study was to investigate the application of a simplified model for the estimation of MFR using only the stress/rest myocardial activity ratio (MAR) in patients undergoing rest–stress cardiac PET MPI. Rest and dipyridamole stress dynamic PET imaging was performed in consecutive patients using 82Rb or 13NH3 (n = 250 each). Reference standard MFR was quantified using a standard one-tissue compartment model. Stress/rest myocardial activity ratio (MAR) was calculated using the LV-mean activity from 2 to 6 minutes post-injection. Simplified estimates of MFR (MFREST) were then calculated using an inverse power function. For 13NH3, there was good correlation between MFR and MFREST values (R = 0.63), with similar results for 82Rb (R = 0.73). There was no bias in the MFREST values with either tracer. The overall diagnostic performance of MFREST for detection of MFR

Background: Sarcoidosis is a condition of unknown etiology. A number of occupational, recreational, and environmental exposures have been associated with the development of extra-cardiac sarcoidosis. Patients with clinically manifest cardiac sarcoidosis (CS) have a distinct clinical phenotype. We sought to explore the exposures associated with clinically manifest CS. Methods: Two groups of patients were recruited in a prospective registry: cases (patients with clinically manifest CS) and controls (patients without sarcoidosis and who had similar cardiac presentations to cases). A validated survey, previously used in other sarcoidosis phenotypes, was sent to all patients. Results: A total of 113 patients met the inclusion criteria and were sent the survey, of whom 79 of 113 (69.9%) completed the survey. We found 3 environmental associations. First, we found a negative association of CS with smoking, with 8 of 43 (18.6%) CS patients being current or ex-smokers compared to 17 of 36 (47.2%) of the controls. Second, we found a positive association with mold exposure, with 21 of 43 (48.8%) CS patients having a prior history of mold exposure compared to 9 of 36 (25.0%) of the controls. After multivariable analysis, there remained significant associations between CS and smoking (odds ratio 0.14 [95% confidence interval 0.04-0.51], P = 0.002) and mold exposure (odds ratio 5.69 [95% confidence interval 1.68-19.25], P = 0.005). Finally, patients with CS and self-reported acne had a significantly longer duration of active acne (7.82 ± 3.97 years) than did control patients 2.67 ± 1.03 years (P = 0.006). Conclusions: We found a negative association between smoking history and the diagnosis of CS. We also found a significant 5-fold increase in mold exposure and a positive association with duration of acne in patients with CS compared to controls. Résumé: Contexte: Les causes de la sarcoïdose demeurent inconnues. Un certain nombre de facteurs de risque professionnels, récréatifs et environnementaux ont toutefois été associés à la survenue de la sarcoïdose extracardiaque. Les patients qui sont atteints d’une sarcoïdose cardiaque cliniquement manifeste ont un phénotype clinique particulier. Nous nous sommes penchés sur les facteurs de risque associés à cette maladie. Méthodologie: Nous avons recruté deux groupes de patients à partir d’un registre de données prospectives : des cas de sarcoïdose cardiaque (présentant les manifestations cliniques de la sarcoïdose cardiaque) et des cas témoins (patients sans sarcoïdose, mais qui présentaient des signes et des symptômes cardiaques similaires à ceux des patients atteints de sarcoïdose cardiaque). Nous avons envoyé à l’ensemble des participants un questionnaire validé et déjà utilisé auprès de patients présentant d’autres phénotypes de sarcoïdose. Résultats: Au total, 113 patients répondaient aux critères d’inclusion. Nous avons envoyé le questionnaire à ces 113 patients, et 79 d’entre eux (69,9 %) y ont répondu. Nous avons détecté trois facteurs environnementaux. Nous avons d’abord noté une association négative entre la sarcoïdose cardiaque et le tabagisme : 8 patients atteints de sarcoïdose cardiaque sur 43 (18,6 %) fumaient ou avaient déjà fumé, comparativement à 17 témoins sur 36 (47,2 %). Nous avons ensuite observé une association positive avec l’exposition aux moisissures : 21 patients atteints de sarcoïdose cardiaque sur 43 (48,8 %) avaient des antécédents d’une telle exposition, comparativement à 9 des 36 témoins (25,0 %). Les associations entre la sarcoïdose cardiaque et le tabagisme et l’exposition aux moisissures sont demeurées significatives après une analyse multivariée (risque relatif approché [RRA] pour le tabagisme : 0,14 [intervalle de confiance {IC} à 95 % : 0,04-0,51], p = 0,002; RRA pour l’exposition aux moisissures : 5,69 [IC à 95 % : 1,68-19,25], p = 0,005). Finalement, chez les patients atteints de sarcoïdose cardiaque et d’acné autodéclarée, la durée de l’acné était significativement plus longue (7,82 ± 3,97) que celle relevée chez les témoins (2,67 ± 1,03; p = 0,006). Conclusions: Nous avons détecté une association négative entre les antécédents de tabagisme et le diagnostic de sarcoïdose cardiaque. Nous avons également observé que l’exposition aux moisissures était 5 fois plus élevée et que l’acné est présente plus longtemps chez les patients atteints de sarcoïdose cardiaque que chez les témoins.

Myocardial blood flow (MBF) quantification by Rubidium-82 positron emission tomography (PET) has shown promise for cardiac allograft vasculopathy (CAV) surveillance and risk stratification post heart transplantation. The objective was to determine the prognostic value of serial PET performed early post transplantation. Heart transplant (HT) recipients at the University of Ottawa Heart Institute with 2 PET examinations (PET1 = baseline, PET2 = follow-up) within 6 years of transplant were included in the study. Evaluation of PET flow quantification included stress MBF, coronary vascular resistance (CVR), and myocardial flow reserve (MFR). The primary composite outcome was all-cause death, re-transplant, myocardial infarction, revascularization, allograft dysfunction, cardiac allograft vasculopathy (CAV), or heart failure hospitalization. A total of 121 patients were evaluated (79% male, mean age 56 ± 11 years) with consecutive scans performed at mean 1.4 ± 0.7 and 2.6 ± 1.0 years post HT for PET1 and PET2, respectively. Over a mean follow-up of 3.0 (IQR 1.8, 4.6) years, 26 (22%) patients developed the primary outcome: 1 death, 11 new or progressive angiographic CAV, 2 percutaneous coronary interventions, 12 allograft dysfunction. Unadjusted Cox analysis showed a significant reduction in event-free survival in patients with PET1 stress MBF 76 (HR: 2.19, 95% CI 0.87-5.51 P = 0.045). There was no association between MFR and outcomes. Low-stress MBF and persistent increased CVR on serial PET imaging early post HT are associated with adverse cardiovascular outcomes. Early post-transplant and longitudinal assessment by PET may identify at-risk patients for increased surveillance post HT.

In contrast to cardiac sympathetic activity which can be assessed with established PET tracers, there are currently no suitable radioligands to measure cardiac parasympathetic (cholinergic) activity. A radioligand able to measure cardiac cholinergic activity would be an invaluable clinical and research tool since cholinergic dysfunction has been associated with a wide array of pathologies (e.g., chronic heart failure, myocardial infarction, arrythmias). [18F]Fluoroethoxybenzovesamicol (FEOBV) is a cholinergic radiotracer that has been extensively validated in the brain. Whether FEOBV PET can be used to assess cholinergic activity in the heart is not known. Hence, this study aimed to evaluate the properties of FEOBV for cardiac PET imaging and cholinergic activity mapping. PET data were collected for 40 minutes after injection of 230 ± 50 MBq of FEOBV in four healthy participants (1 female; Age: 37 ± 10; BMI: 25 ± 2). Dynamic LV time activity curves were fitted with Logan graphical, 1-tissue compartment, and 2-tissue compartment models, yielding similar distribution volume estimates for each participant. Our initial data show that FEOBV PET has favorable tracer kinetics for quantification of cholinergic activity and is a promising new method for assessing parasympathetic function in the heart.

Cardiac sarcoidosis (CS) is an increasingly recognized condition, but cardiac magnetic resonance (CMR) image interpretation in these patients may be challenging as findings are often non-specific. The main objective of this study was to investigate the inter-reader agreement for the overall interpretation of CMR for the diagnosis of CS in an experienced reference center and investigate factors that may lead to discrepancies between readers. Consecutive patients undergoing CMR imaging to investigate for CS were included. CMR images were independently reviewed by two readers, blinded to all clinical, imaging and demographic information. The readers classified each scan as "consistent with cardiac sarcoidosis", "not consistent with cardiac sarcoidosis" or "indeterminate". Inter-reader agreement was assessed using κ-statistics. When there was disagreement on the overall interpretation, a third reader reviewed the images. Also, two readers independently commented on the presence of edema, presence of LGE (both ventricles) and quantified the extent of left ventricular LGE. 87 patients (43 women, mean age 54.3 ± 12.2 years) were included in the study. There was agreement regarding the overall interpretation in 72 of 87 (83%) CMR scans. The κ value was 0.64, indicating moderate agreement. There was similar moderate agreement in the interpretation of LGE parameters. In an experienced referral center, we found moderate agreement between readers in the interpretation of CMR in patients with suspected CS. Physicians should be aware of this inter-observer variability in interpretation of CMR studies in patients with suspected CS.

Molecular imaging with positron emission tomography (PET) and single-photon emission computed tomography (SPECT) serves numerous applications in clinical cardiology and research. Similar to other medical imaging technologies, this area has undergone and continues to experience rapid changes resulting from technological and medical advances. These have immediate impacts on diagnosis, treatment planning, and patient care, as well as supplying innovative tools for fundamental and translational research. A broad shift toward hybrid PET systems and incorporation of advanced computational tools has been accompanied by mechanism-specific, targeted radiopharmaceuticals that seek to address long-standing limitations in cardiac imaging. While this review addresses some of the still-emerging clinical uses of established radiopharmaceuticals, it too highlights newer imaging probes, applications, and imaging techniques and instrumentation on the horizon. We highlight molecular imaging advances in inflammatory and infiltrative myocardial conditions, heart metabolism, vascular and valvular diseases, neurohormonal dysregulation, and transformational technical advances such as the rise of artificial intelligence and theranostic approaches to cardiovascular disease.

INTRODUCTION Three-dimensional (3D) data acquisition is now standard on PET/computed tomography scanners. The aim of this study was to evaluate the repeatability of myocardial blood flow (MBF) estimation with rubidium-82 (Rb) 3D PET and to validate regional MBF measurements by comparison with two-dimensional (2D) PET. PATIENTS AND METHODS Fifteen healthy individuals (31.6 ± 11.4 years old) were enrolled for the evaluation of the short-term repeatability of rest 3D MBF quantification. Another 19 healthy individuals (35.3 ± 12.6 years old) underwent rest and pharmacological stress PET using 2D and 3D data acquisition within a 1-month interval. The injected dose was 1500 MBq for 2D and 555 MBq for 3D PET acquisition. RESULTS MBF at rest showed good repeatability [whole left ventricular MBF; 0.54 ± 0.13 vs. 0.52 ± 0.13 mL/min/g, P = 0.98]. Rest MBF, stress MBF, and myocardial flow reserve (MFR) were not significantly different between 3D and 2D data acquisition. 3D MBF correlated well with 2D MBF over a wide flow range for both whole left ventricular (r = 0.97, P

The objective of this study was to compare the hyperemic myocardial blood flow (MBF) and myocardial flow reserve (MFR) obtained with dobutamine to those of dipyridamole in patients referred for myocardial perfusion imaging (MPI) using 82Rb positron emission tomography. One hundred and fifty-six patients who underwent a 82Rb PET MPI study with dobutamine stress were included. A matching cohort of patients who underwent a 82Rb PET MPI study with dipyridamole stress was created, accounting for sex, age, history of coronary artery disease (CAD), prior revascularization, CAD risk factors, body mass index, and MPI interpretation. Global rest MBF (median [interquartile range] 0.84 [0.64-1.00] vs 0.69 [0.59-0.85]), stress MBF (2.36 [1.73-3.08] vs 1.66 [1.25-2.06]), MFR (2.75 [2.19-3.64] vs 2.29 [1.78-2.84]), and corrected MFR (2.85 [2.14-3.64] vs 2.20 [1.65-2.75]) were all significantly higher (P

Coronary artery disease has been the leading cause of death since the 1960s, which has motivated the research and development of myocardial perfusion imaging (MPI) agents for early diagnosis and to guide treatment. MPI with SPECT has been the clinical workhorse for MPI, but over the past two decades PET MPI is experiencing growth due to enhanced image quality that results in superior diagnostic accuracy over SPECT. Furthermore, dynamic PET imaging of the tracer distribution process from time of tracer administration to tracer accumulation in the myocardium has enabled routine quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR) in absolute units. MBF and MFR incrementally improve diagnostic and prognostic accuracy over MPI alone. In some cases (eg, rubidium PET imaging with pharmacologic stress) MPI, MBF, and MFR can be acquired simultaneously without incremental cost, radiation exposure, or significant processing time. Nuclear cardiology clinics have been looking to incorporate MBF quantification into clinical routine, but traditional SPECT and MPI tracers are inadequate for this challenge. Cardiac dedicated SPECT scanners can also perform dynamic imaging and have stimulated research into MBF quantification using SPECT tracers. New perfusion tracers must be tailored for emerging clinical needs (including MBF quantification), technical capabilities of imaging instrumentation, market constraints, and supply chain feasibility. Because these conditions have been evolving, tracers previously considered inferior may be reconsidered for future applications and some recently developed tracers may be suboptimal. This article reviews current, clinically-available tracers and those under development showing greatest potential. It discusses for each tracer the rationale for development, physiological mechanism of uptake by the myocardium, published evaluation results and development state. Finally, it gauges the suitability of each tracer for clinical application. The article demonstrates an acceleration in the pace of perfusion radiotracer development due to better understanding of the relevant physiology, better chemistry tools and small animal imaging. Consequently, bad tracers may fail faster and with less wasted investment, and good tracers may translate more efficiently from bench to bedside.

Introduction: Three-dimensional (3D) data acquisition is now standard on PET/computed tomography scanners. The aim of this study was to evaluate the repeatability of myocardial blood flow (MBF) estimation with rubidium-82 (Rb) 3D PET and to validate regional MBF measurements by comparison with two-dimensional (2D) PET. Patients and methods: Fifteen healthy individuals (31.6 ± 11.4 years old) were enrolled for the evaluation of the short-term repeatability of rest 3D MBF quantification. Another 19 healthy individuals (35.3 ± 12.6 years old) underwent rest and pharmacological stress PET using 2D and 3D data acquisition within a 1-month interval. The injected dose was 1500 MBq for 2D and 555 MBq for 3D PET acquisition. Results: MBF at rest showed good repeatability [whole left ventricular MBF; 0.54 ± 0.13 vs. 0.52 ± 0.13 mL/min/g, P = 0.98]. Rest MBF, stress MBF, and myocardial flow reserve (MFR) were not significantly different between 3D and 2D data acquisition. 3D MBF correlated well with 2D MBF over a wide flow range for both whole left ventricular (r = 0.97, P < 0.0001) and regional values (r = 0.61, P < 0.0001). Conclusion: MBF measured with 3D PET showed very good test-retest repeatability. Whole left ventricular and regional MBF measurements obtained using lower Rb-dose 3D PET were highly correlated over a wide range with those from 2D PET. Therefore, MBF with 3D PET can be applied using a lower Rb dosage in clinical settings with reduced radiation exposure.

Regional cardiac sympathetic denervation is predictive of sudden cardiac arrest in patients with ischemic cardiomyopathy. The reproducibility of denervation scores between automated software programs has not been evaluated. This study seeks to (1) compare the inter-rater reliability of regional denervation measurements using two analysis programs: FlowQuant® and Corridor4DM®; (2) evaluate test–retest repeatability of regional denervation scores. N = 190 dynamic [11C]meta-hydroxyephedrine (HED) PET scans were reviewed from the PAREPET trial in ischemic cardiomyopathy patients with reduced left ventricular ejection fraction(LVEF ≤ 35%). N = 12 scans were excluded due to non-diagnostic quality. N = 178 scans were analyzed using FlowQuant and Corridor4DM software, each by two observers. Test–retest scans from N = 20 patients with stable heart failure were utilized for test–retest analysis. Denervation scores were defined as extent × severity of relative uptake defects in LV regions with

Abnormalities in the cardiac sympathetic nervous system have been documented in various heart diseases and have been directly implicated in their pathogenesis and disease progression. Noninvasive techniques using single-photon-emitting radiotracers for planar scintigraphy and single-photon emission computed tomography, and positron-emitting tracers for positron emissions tomography, have been used to characterize the cardiac sympathetic nervous system with norepinephrine analogs [123I]meta-iodobenzylguanidine for planar and single-photon emission computed tomography imaging and [11C]meta-hydroxyephedrine for positron emissions tomography. Their usefulness in prognostication and risk stratification for cardiac events has been demonstrated. This review bridges basic and clinical research and focuses on applying an understanding of tracer kinetics and neuronal biology, to aid in the interpretation of nuclear imaging of cardiac sympathetic innervation.

Qualification and interpretation standards are essential for establishing 99mTc-SPECT MPI accuracy vs. alternative modalities. Rest–stress 99mTc-SPECT phantom scans were acquired on 35 cameras. LV defects were quantified with summed stress (SSS) and difference scores (SDS) at 2 core labs. SDS ≥ 2 in the right coronary artery (RCA) was the qualifying standard. Twenty rest (R)–stress (S) patient images were acquired on qualified cameras and interpreted by core labs. Global scoring differences > 3 between labs or discordant clinical interpretations underwent review. Scoring, interpretation, image quality, and diagnostic parameter agreement were assessed. Phantom scans: visual scoring confirmed RCA-ischemia on all cameras. Regional SSS, SDS agreement was moderate to very good: ICC-r = 0.57, 0.84. Patient scans: 90% of global SSS, 85% of SDS differences were ≤ 3. Regional SSS, SDS agreement: ICC-r = 0.87, 0.86, and global abnormal (SSS ≥ 4) and ischemic (SDS ≥ 2) interpretation: ICC-r = 0.90 were excellent. Clinical interpretation agreement was 100% following review. Image quality agreement was 70%. Automated metrics also agreed: ischemic total perfusion deficit ICC-r = 0.75, reversible perfusion defect, transient ischemic dilation, and S-R LV ejection fraction ICC-r ≥ 0.90. Quantitative scoring and interpretation of scans were highly repeatable with site qualification and clinical interpretation standardization, indicating that dual-core lab interpretation is appropriate to determine 99mTc-SPECT MPI accuracy.

Purpose: A data-driven motion tracking system was developed for respiratory gating in positron emission tomography (PET)/computed tomography (CT) studies. The positron emission tracking system (PeTrack) estimates the position of a low-activity fiducial marker placed on the patient during imaging. The aim of this study was to compare the performance of PeTrack against that of the real-time position management (RPM) system as applied to respiratory gating in cardiac PET/CT studies. Methods: The list-mode data of 35 patients that were referred for 82Rb myocardial perfusion studies were retrospectively processed with PeTrack to generate respiratory motion signals and triggers. Fifty acquisitions from the initial cohort, conducted under physiologic rest and stress, were considered for analysis. Respiratory-gated reconstructions were performed using reconstruction software provided by the vendor. The respiratory signals and triggers of the gating systems were compared using quantitative measurements of the respiratory signal correlation, median, and interquartiles range (IQR) of observed respiratory rates and the relative frequencies of respiratory cycle outliers. Quantitative measurements of left-ventricular wall thicknesses and motion due to respiration were also compared. Real-time position management signals were also retrospectively processed using the trigger detection method of PeTrack for a third comparator (“RPMretro”) that allowed direct comparison of the motion tracking quality independently of differences in the trigger detection methods. The comparison of PeTrack to the original RPM data represent a practical comparison of the two systems, whereas that of PeTrack and RPMretro represents an equal comparison of the two. Nongated images were also reconstructed to provide reference left-ventricular wall thicknesses. LV wall thickness and motion measurements were repeated for a subset of cases with motion ≥7 mm as image artifacts were expected to be more severe in these cases. Results: A significant correlation (P

Background Approximately 5% of patients with sarcoidosis have clinically manifest cardiac involvement. Clinical features of Cardiac Sarcoidosis are dependent on the location, extent, and activity of the disease. First line therapy is usually with prednisone and this is recommended based on clinician experience, expert opinion and small observational cohorts. There are no published clinical trials in cardiac sarcoidosis and multiple experts in the field have called for randomized clinical trials to answer important patient care questions. Corticosteroid are associated with multiple adverse effects including hypertension, diabetes, weight gain, osteoporosis, and increased risk of infections. In contrast Methotrexate is generally well tolerated and is increasingly used in other forms of sarcoidosis. Objectives The Cardiac Sarcoidosis Multi-Center Randomized Controlled Trial (CHASM CS-RCT; NCT03593759 ) is a multicenter randomized controlled trial designed to evaluate the optimal initial treatment strategy for patients with active cardiac sarcoidosis. We hypothesize that (1) a low dose prednisone/methotrexate combination will have non-inferior efficacy to standard dose prednisone and that (2) the low dose prednisone/ methotrexate combination will result in significantly better quality of life than standard dose prednisone, as a result of reduced burden of side effects. Methods/design Eligible study subjects will have active clinically manifest cardiac sarcoidosis presenting with one or more of the following clinical findings: advanced conduction system disease, significant sinus node dysfunction, non-sustained or sustained ventricular arrhythmia, left ventricular dysfunction or right ventricular dysfunction. Subjects will be randomized in a 1:1 ratio to prednisone 0.5 mg/kg/day for 6 months (maximum dose 30 mg daily) OR to prednisone 20 mg daily for 1 month, then 10 mg daily for 1 month, then 5 mg daily for one month then stop AND methotrexate 15–20 mg once weekly for 6 months. The primary endpoint is summed perfusion rest score on 6-month PET (blinded core-lab review). The summed perfusion rest score is measure of myocardial fibrosis/scar. The design is non-inferiority with a sample size of 97 per group. Discussion Given the multiorgan system potential adverse side effects of prednisone, proving noninferiority of an alternate regimen would be sufficient to make the alternative compare favorably to standard dose steroids. This is the first ever clinical trial in cardiac sarcoidosis and thus in addition to the listed goals of the trial, we will also establish a multi-center, multinational cardiac sarcoidosis clinical trials network. Such a collaborative infrastructure will enable a new era of high quality data to guide physicians when treating cardiac sarcoidosis patients.

We previously demonstrated high diagnostic accuracy of Rubidium-82 positron emission tomography (PET) myocardial blood flow (MBF) quantification for CAV. The purpose of this study was to validate multiparametric PET detection of CAV by combined rate-pressure-product-corrected myocardial flow reserve (cMFR), stress MBF, and coronary vascular resistance (CVR) assessment. Diagnostic CAV cut-offs of cMFR 55 determined in a previous study (derivation) were assessed in heart transplant recipients referred for coronary angiography and intravascular ultrasound (IVUS) (validation). CAV was defined as International Society of Heart and Lung Transplantation CAV1-3 on angiography; and maximal intimal thickness ≥ 0.5 mm on IVUS. Eighty patients (derivation n = 40, validation n = 40) were included: 80% male, mean age 54±14 years, 4.5±5.6 years post transplant. The prevalence of CAV was 44% on angiography and 78% on IVUS. Combined PET cMFR 55 CAV assessment yielded high 88% (specificity 75%) and 83% (specificity 40%) sensitivity for ≥ 1 abnormal parameter and high 88% (sensitivity 59%) and 90% (sensitivity 43%) specificity for 3 abnormal parameters, in the derivation and validation cohorts, respectively. We validate the diagnostic accuracy of multiparametric PET flow quantification by cMFR, stress MBF, and CVR for CAV.

1599 Introduction: The term “spinal cord injury” (SCI) refers to damage to the spinal cord due to trauma, disease, or degeneration. According to the World Health Organization, every year approximately 500,000 people suffer from SCI, with up to 90% of these SCI cases due to trauma. The symptoms of SCI depend upon the severity of the injury and its location in the spinal cord. These symptoms may include partial or complete loss of sensory or motor function. SCI can also affect the system that regulates bowel/bladder control, breathing, heart rate and blood pressure. In this study, we explored the long-term outcomes of a moderate severity SCI in a rat model on glucose uptake throughout the spinal cord. Methods: Adult male Sprague Dawley rats were randomly divided into 2 groups. The injured group received a laminectomy at vertebral level T9 and moderate contusion SCI (150 kdyne force) was induced with Infinite Horizon Impactor (Precision Systems Incorporated, Natick, MA). Sham animals received laminectomy but no impact. PET/CT images were acquired (Siemens Inveon preclinical scanner, Erlangen, Germany) at 4 time points - baseline (prior to injury), 6 hours, 1 month and 3 months post injury for both the groups of animals. FDG uptake was assessed by drawing regions of interest (ROI’s) in the cerebellum, cervical spinal cord (C2-C5, uninjured site) and thoracic spinal cord (injured site), using Siemens Inveon Workplace software (V4.2) [Figure 1]. The Basso-Beattie-Bresnahan (BBB) scale was used to assess neurological function in both the Sham and Injured group at 1, 7, 14, 21, 28 days and 2 and 3 months [Figure 2]. The statistical analysis was done using GraphPad Prism (v8.1), mixed effect model with Sidak’s multiple comparisons tests. Results: The Sham animals showed no significant changes in glucose uptake or motor function at any time point. The Injured group showed impaired functional performance at 1 day and 1-month post injury compared to Sham group. The injured group showed decreased FDG uptake at 1- month and 3- months post injury compared to baseline, not only at the lesion site (thoracic region) but also at the uninjured site (cervical region) [Figure 3 and 4]. Interestingly, the cerebellum also showed decreased FDG uptake at 3- months’ post injury compared to baseline in the injured group of animals but not the shams [Figure 5]. The acute time point (6 hours post injury) did not show any significant alterations. Conclusions: FDG PET can be used to assess moderate spinal cord contusion in rats and indicates decreased glucose uptake up to 3 months post injury at the lesion site and in distal locations possibly suggestive of axonal degeneration. Acknowledgements: This work was supported by the Defense Health Program, Congressionally Directed Medical Research Programs through the Spinal Cord Injury Research Program under Award No. SC170244. Disclaimer: The opinions and assertions expressed herein are those of the author(s) and do not necessarily reflect the official policy or position of the Uniformed Services University or the Department of Defense.

Purpose To estimate the interobserver agreement of the Carimas software package (SP) on global, regional, and segmental levels for the most widely used myocardial perfusion PET tracer—Rb-82. Materials and methods Rest and stress Rb-82 PET scans of 48 patients with suspected or known coronary artery disease (CAD) were analyzed in four centers using the Carimas SP. We considered values to agree if they simultaneously had an intraclass correlation coefficient (ICC) > 0.75 and a difference Results The median values on the segmental level were 1.08 mL/min/g for rest myocardial blood flow (MBF), 2.24 mL/min/g for stress MBF, and 2.17 for myocardial flow reserve (MFR). For the rest MBF and MFR, all the values at all the levels fulfilled were in excellent agreement. For stress MBF, at the global and regional levels, all the 24 comparisons showed excellent agreement. Only 1 out of 102 segmental comparisons (seg. 14) was over the adequate agreement limit—23.5% of the median value (ICC = 0.95). Conclusion Interobserver agreement for Rb-82 PET myocardial perfusion quantification analyzed with Carimas is good at any LV segmentation level—global, regional, and segmental. It is good for all the estimates—rest MBF, stress MBF, and MFR.