Cardiac Positron Emission Tomography Imaging Research Articles

A novel method in myocardial injury risk stratification using intravenous fat emulsion as sole rapid preparation for unfasted patients to suppress myocardial 18F-fluorodeoxyglucose uptake for optimal cardiac PET imaging: a proof-of-concept randomized-crossover trial.

Optimal imaging of ischemic or inflammed myocardium via 18F-FDG PET imaging requires suppression of background carbohydrate metabolism in normal myocardium. Sole administration of intravenous lipid emulsion has not previously been used to rapidly prepare unfasted patients, such as in emergent clinical situations. In this proof-of-concept pilot, we posited that intravenous fat emulsion suppresses physiological metabolic uptake of in non-ischemic, non-inflammatory myocardium in unprepared and unfasted setting for enhanced cardiac positron emission tomography (PET) imaging. We conducted an ethics-approved, single-blind, prospective randomized crossover trial of 10 healthy volunteers from January 2020 to June 2021. Participants were unfasted and rendered hyperglycemic before being administered either high dose intravenous lipid emulsion-1.5 ml kg of 20% lipid emulsion, followed by 15 ml/kg/hr for 30mins-or saline prior to 18F-FDG injection and subsequent cardiac PET imaging. Assessors undertook image analysis for maximum standard uptake value (SUVmax), minimum standard uptake value (SUVmin) and qualitative assessment, and groups were compared using univariate analysis. The study population age was 44.5 years [IQR 32.5-56.5], with 50% male and a median BMI of 22.75 [IQR 25.0-28.5] kg/m2. The study was feasible and there were no adverse side effects from the interventions. In these participants with normal myocardium, 18F-FDG uptake was reduced by intravenous lipid emulsion as assessed by SUVmax and qualitative assessment (p = 0.042, r = 0.454 and p = 0.009, r = -0.581, respectively). Intravenous lipid emulsion suppresses background metabolic uptake of 18F-FDG even in unprepared and unfasted patients. Our findings prove and expand the possible applications for cardiac 18F-FDG PET in various settings, including in emergent settings as a means of rapid preparation in place of current more time-consuming standard protocols, allowing time-critical management to be effected.

Risk Stratification in Cardiac Sarcoidosis With Cardiac Positron Emission Tomography: A Systematic Review and Meta-Analysis

BackgroundAlthough positron emission tomography (PET) imaging is well established for its diagnostic role in cardiac sarcoidosis, less is known about the prognostic value of PET and its use in risk stratification for major adverse cardiac events (MACE). ObjectivesThe goal of this study was to perform a systematic review and meta-analysis looking at the prognostic value of PET imaging in patients with cardiac sarcoidosis. MethodsStudy investigators systematically searched EMBASE (Excerpta Medica dataBASE), MEDLINE, PubMed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, CINAHL (Cumulative Index to Nursing and Allied Health Literature), ClinicalTrials.gov, and the European Union Clinical Trial Registry for cardiac sarcoidosis and PET imaging. The primary outcome of interest was MACE. ResultsThe search revealed 3,010 records, of which 55 studies were included. This represented 5,250 patients. Factors associated with MACE included the following: the combination of abnormal fluorodeoxyglucose (FDG) uptake and perfusion defect, which had an OR of 2.86 (95% CI: 1.74-4.71; P < 0.0001); abnormal perfusion or FDG uptake, which had an OR of 2.69 (95% CI: 1.67-4.33); abnormal FDG uptake, which had an OR of 2.61 (95% CI: 1.51-4.50); focal abnormal right ventricular uptake, which had an OR of 6.27 (95% CI: 3.19-12.32; P < 0.00001); and a lack of response to immunosuppression on serial PET, which had an OR of 8.43 (95% CI: 3.25-21.85; P < 0.0001). A QUIPS (Quality in Prognostic Studies) tool analysis found a low to moderate risk of bias, particularly given the small sample sizes in the individual studies. ConclusionsMultiple cardiac PET parameters provide risk stratification value in cardiac sarcoidosis. Focal right ventricular uptake and a lack of response to immunosuppressive therapy on serial PET imaging were particularly predictive of MACE.

Deep generative denoising networks enhance quality and accuracy of gated cardiac PET data.

Cardiac positron emission tomography (PET) can visualize and quantify the molecular and physiological pathways of cardiac function. However, cardiac and respiratory motion can introduce blurring that reduces PET image quality and quantitative accuracy. Dual cardiac- and respiratory-gated PET reconstruction can mitigate motion artifacts but increases noise as only a subset of data are used for each time frame of the cardiac cycle. The objective of this study is to create a zero-shot image denoising framework using a conditional generative adversarial networks (cGANs) for improving image quality and quantitative accuracy in non-gated and dual-gated cardiac PET images. Our study included retrospective list-mode data from 40 patients who underwent an 18F-fluorodeoxyglucose (18F-FDG) cardiac PET study. We initially trained and evaluated a 3D cGAN-known as Pix2Pix-on simulated non-gated low-count PET data paired with corresponding full-count target data, and then deployed the model on an unseen test set acquired on the same PET/CT system including both non-gated and dual-gated PET data. Quantitative analysis demonstrated that the 3D Pix2Pix network architecture achieved significantly (p value<0.05) enhanced image quality and accuracy in both non-gated and gated cardiac PET images. At 5%, 10%, and 15% preserved count statistics, the model increased peak signal-to-noise ratio (PSNR) by 33.7%, 21.2%, and 15.5%, structural similarity index (SSIM) by 7.1%, 3.3%, and 2.2%, and reduced mean absolute error (MAE) by 61.4%, 54.3%, and 49.7%, respectively. When tested on dual-gated PET data, the model consistently reduced noise, irrespective of cardiac/respiratory motion phases, while maintaining image resolution and accuracy. Significant improvements were observed across all gates, including a 34.7% increase in PSNR, a 7.8% improvement in SSIM, and a 60.3% reduction in MAE. The findings of this study indicate that dual-gated cardiac PET images, which often have post-reconstruction artifacts potentially affecting diagnostic performance, can be effectively improved using a generative pre-trained denoising network.

Cardiac PET Imaging of ATP Binding Cassette (ABC) Transporters: Opportunities and Challenges.

Adenosine triphosphate binding cassette (ABC) transporters are a broad family of membrane protein complexes that use energy to transport molecules across cells and/or intracellular organelle lipid membranes. Many drugs used to treat cardiac diseases have an affinity for these transporters. Among others, P-glycoprotein (P-gp) plays an essential role in regulating drug concentrations that reach cardiac tissue and therefore contribute to cardiotoxicity. As a molecular imaging modality, positron emission tomography (PET) has emerged as a viable technique to investigate the function of P-gp in organs and tissues. Using PET imaging to evaluate cardiac P-gp function provides new insights for drug development and improves the precise use of medications. Nevertheless, information in this field is limited. In this review, we aim to examine the current applications of ABC transporter PET imaging and its tracers in the heart, with a specific emphasis on P-gp. Furthermore, the opportunities and challenges in this novel field will be discussed.

Enhanced Extraction of Blood and Tissue Time-Activity Curves in Cardiac Mouse FDG PET Imaging by Means of Constrained Nonnegative Matrix Factorization.

We propose an enhanced method to accurately retrieve time-activity curves (TACs) of blood and tissue from dynamic 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) cardiac images of mice. The method is noninvasive and consists of using a constrained nonnegative matrix factorization algorithm (CNMF) applied to the matrix (A) containing the intensity values of the voxels of the left ventricle (LV) PET image. CNMF factorizes A into nonnegative matrices H and W, respectively, representing the physiological factors (blood and tissue) and their associated weights, by minimizing an extended cost function. We verified our method on 32 C57BL/6 mice, 14 of them with acute myocardial infarction (AMI). With CNMF, we could break down the mouse LV into myocardial and blood pool images. Their corresponding TACs were used in kinetic modeling to readily determine the [18F]FDG influx constant (Ki) required to compute the myocardial metabolic rate of glucose. The calculated Ki values using CNMF for the heart of control mice were in good agreement with those published in the literature. Significant differences in Ki values for the heart of control and AMI mice were found using CNMF. The values of the elements of W agreed well with the LV structural changes induced by ligation of the left coronary artery. CNMF was compared with the recently published method based on robust unmixing of dynamic sequences using regions of interest (RUDUR). A clear improvement of signal separation was observed with CNMF compared to the RUDUR method.

68Ga-FAPI PET visualize heart failure: from mechanism to clinic.

Heart failure (HF) is a chronic progressive clinical syndrome associated with structural and/or functional heart abnormalities. Active fibroblasts and ventricular remodelling play an essential role in HF progression. 68Ga-labelled fibroblast activation protein (FAP) inhibitor (68Ga-FAPI) binds to FAP. This study aimed to examine the feasibility of using 68Ga-FAPI positron emission tomography (PET)/computed tomography (CT) to visualize changes in cardiac fibrosis and function over time in the HF setting. After establishing an isoproterenol (ISO)-induced HF rat model (14 consecutive days of intraperitoneal ISO injections), echocardiography and 68Ga-FAPI PET/CT were performed weekly in experimental and control groups. Rat hearts were examined weekly for biodistribution analysis; autoradiography; and haematoxylin and eosin, FAP immunofluorescence and Masson's trichrome staining analysis. Rat blood was sampled weekly for enzyme-linked immunosorbent assay analysis of various plasma indicators. A preliminary clinical study was also performed in seven HF patients who underwent both 13N-amino (NH3) perfusion and 68Ga-FAPI cardiac PET imaging. In the animal experiments, myocardial 68Ga-FAPI uptake, expression of FAP and myocardial contractility peaked on day 7 after the initial ISO injection. Only slight fibrotic changes were observed on histopathological examination. 68Ga-FAPI uptake and ventricular wall motion decreased over time as cardiac fibrosis and degree of myocardial injury gradually increased. In the human HF patient study, 68Ga-FAPI PET imaging identified varying degrees of 68Ga-FAPI uptake in the myocardium that did not precisely match with 13N-NH3 myocardial perfusion. As HF progresses, 68Ga-FAPI uptake is high in the early stages and then gradually decreases. Although preliminary, our findings suggest that 68Ga-FAPI PET can be used to demonstrate active myocardial fibrosis. Active myocardial FAP expression is followed by myocardial remodelling and fibrosis. Detection of early active FAP expression may assist treatment decision making in HF patients. NCT04982458.

PET-based artificial intelligence applications in cardiac nuclear medicine.

In the recent years, artificial intelligence (AI) applications have gained interest in the field of cardiovascular medical imaging, including positron emission tomography (PET). The use of AI in cardiac PET imaging is to date limited, although first, important results have been shown, overcoming technical issues, improving diagnostic accuracy and providing prognostic information. In this review we aimed to summarize the state-of-the-art regarding AI applications in cardiovascular PET.

Epstein Barr Virus Infection Induced Suspected Acute Myocarditis in COVID-19 Pandemic

Background: Epstein Barr Virus infection (EBV) could be associated with cardiovascular disease, including myocarditis. We informed a case of EBV infection presenting initially as myocarditis, followed 5 days later by the typical symptoms of infectious mononucleosis. Case Presentation: A 19-year-old man with persistent retrosternal chest pain was admitted to the emergency department. On physical examination, the patient had sub-febrile fever (37.2°C) and palpable cervical lymphadenopathy, with no hepatosplenomegaly. Initial ECG has repolarization abnormalities in leads II, aVF and III. Laboratory testing revealed elevated cardiac enzymes and liver enzymes (high sensitive troponin I levels 3000 ng/mL, aspartate transaminase 158 U/L, alanine transaminase 100 U/L). Blood white cells were 10,500 μL, platelet level were low 98,000 (thrombocytopenia), and lenfo-monocytosis in complete blood count. We hospitalized the patients the intensive coronary unit (ICU) because of high troponin levels. We recognized hypokinesia of the posterolateral wall of the left ventricle with mild impaired systolic function and increased perimyocardial brightness by echocardiography. Antibody serology tests showed that the anti-EBV capsid antigen IgM (EBV-VCA) was positive, EBV-VCA) IgG was negative. Other etiologies were excluded. Therefore, the patient was referred to cardiac positron emission tomography due to technic problems of magnetic resonance imaging device. We documented in positron emission tomography imaging that increased 18F-FDG uptake on posterior and posterolateral walls of left ventricle (indicating a large jeopardized area). We diagnosed suspected diagnosis of myocarditis without associated pericarditis. We monitored the patient and gave beta blocker, and aldosterone antagonists. Complications in the intensive care unit not occurred. We discharged patients after one week. After three weeks, we re-evaluated the patient. We not observed wall segment motion abnormality on echocardiography and liver tests were near normal. Conclusion: In suspected EBV myocarditis, 18F-FDG PET-CT cardiac positron emission tomography imaging represents an interesting noninvasive imaging technique to identify inflammatory processes in acute myocarditis and can be considered in patients with contraindications/unavailable to cardiac magnetic resonance.

Incremental value of 18F-FDG cardiac PET imaging over dobutamine stress echocardiography in predicting myocardial ischemia in patients with suspected coronary artery disease

BackgroundTo assess the incremental value of 18F-fluorodeoxyglucose (FDG) cardiac positron emission tomography (PET) over dobutamine stress echocardiography (DSE) in predicting myocardial ischemia in patients with suspected coronary artery disease (CAD). MethodsForty-one patients with suspected CAD underwent within 7 days apart rest-stress cardiac PET with 82Rb and DSE followed by cardiac 18F-FDG PET imaging. 18F-FDG images were scored on a 0 (no discernible uptake) to 2 (intense uptake) scale. Logistic regression analysis was performed to identify predictors of stress-induced ischemia. The incremental value of 18F-FDG PET over DSE in detecting ischemia at 82Rb PET cardiac imaging was assessed by the likelihood ratio chi-square and net reclassification index. ResultsOn 82Rb-PET imaging, myocardial ischemia (ischemic total perfusion defect ≥ 5%) was detected in 20 (49%) patients. Inducible ischemia was found in 22 (54%) patients on DSE (biphasic or worsening response pattern in ≥ 1 segment) and in 21 (51%) patients on 18F-FDG PET (uptake score of 2 in ≥ 1 segment). 18F-FDG PET resulted as statistically significant predictor of ischemia on 82Rb-PET. The addition of 18F-FDG PET to DSE increased the likelihood of ischemia on 82Rb-PET (P < .05). 18F-FDG PET was able to reclassify the probability of stress-induced myocardial ischemia on both patient and vessel analyses. Conclusion18F-FDG PET performed after dobutamine stress test may provide incremental value to DSE in the evaluation of myocardial ischemia. These results suggest that stress-induced myocardial ischemia can be imaged directly using 18F-FDG PET after dobutamine stress test.

The prognostic role of PET myocardial perfusion imaging in patients with cardiac sarcoidosis: a systematic review

Abstract Funding Acknowledgements Type of funding sources: None. Background Sarcoidosis is a multi-systemic inflammatory disease of unknown etiology. Cardiac Sarcoidosis (CS) has been reported in as much as 25% of patients with systemic involvement. 18Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) has a high diagnostic sensitivity/specificity in the diagnosis of CS. Purpose The aim of this review is to summarize evidence on the prognostic role of FDG PET. Methods Studies were identified by searching MEDLINE from inception to October 2020. Medical Subject Headings (MeSH) terms for sarcoidosis; cardiac and FDG PET imaging were used. Studies of any design assessing the prognostic role of FDG PET in patients with either suspected or confirmed cardiac sarcoidosis imaging done at baseline were included. Abnormal PET was defined as abnormal metabolism (presence of focal or focal-on-diffuse uptake of FDG) OR abnormal metabolism and a perfusion defect. Studies reporting any outcome measure were included. Pooled risk ratio for the composite outcome of MACE was done. Results A total of 6 studies were selected for final inclusion (515 patients, 53.4% women, 19.8% racial minorities.) Studies were institution based, retrospective in design and enrolled consecutive patients. All were observational in nature and published in English. All studies used a qualitative assessment of PET scans (abnormal FDG uptake with or without abnormal perfusion). Two studies assessed quantitative metrics (summed stress score in segments with abnormal FDG uptake, standardized uptake value and cardiac metabolic activity.) All studies reported Major Adverse Cardiovascular Events (MACE) as a composite outcome. After a mean follow up ranging from 1.4 to 4.1 years, there were a total of 105 MACE. All studies included death (either all-cause death or sudden cardiac death) and ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation) as a component of MACE. Four of the six studies adjusted for several characteristics in their analysis. All four studies used Left Ventricular Ejection Fraction (LVEF). However, other adjustment variables were not consistent across studies. Five studies found a positive prognostic association with the primary outcome, two of which assessing right ventricular uptake. Conclusion Although available evidence indicates FDG PET can be used in the risk stratification of patients with CS, our findings show further studies are needed to quantify the effect in this patient group.

Potential Cardiac Amyloid PET/CT Imaging Targets for Differentiating Immunoglobulin Light Chain From Transthyretin Amyloidosis.

Cardiac involvement in amyloidosis plays a critical role in the clinical manifestation and prognostication. Since advanced treatment options for immunoglobulin light chains (AL) or liver-generated protein transthyretin (TTR) are quite different, a non-invasive and comprehensive imaging approach for the identification and characterization of these forms of cardiac amyloidosis is warranted. Various 18Flabeled radiotracers and positron emission tomography (PET) imaging have been appreciated as a as a valid and non-invasive diagnostic approach to identify and quantify disease activity of cardiac amyloidosis. Interestingly, applying 18F-florbetapen and delayed PET imaging may even afford the possibility to not only detect cardiac amyloidosis but also to reliably differentiate between AL and TTR, respectively. This review summarizes contributions of cardiac PET imaging for the non-invasive identification and potential differentiation between AL and TTR amyloidosis that likely holds promise to gear medical treatment in the individual patient for an improved outcome.

Improved PET/MRI accuracy by use of static transmission source in empirically derived hardware attenuation correction

BackgroundAccurate quantification of radioactivity, measured by an integrated positron emission tomography (PET) and magnetic resonance imaging (MRI) system, is still a challenge. One aspect of such a challenge is to correct for the hardware attenuation, such as the patient table and radio frequency (RF) resonators. For PET/MRI systems, computed tomography (CT) is commonly used to produce hardware attenuation correction (AC) maps, by converting Hounsfield units (HU) to a linear attenuation coefficients (LAC) map at the PET energy level 511 keV, using a bilinear model. The model does not address beam hardening, nor higher density materials, which can lead to inaccurate corrections.PurposeIn this study, we introduce a transmission-based (TX-based) AC technique with a static Germanium-68 (Ge-68) transmission source to generate hardware AC maps using the PET/MRI system itself, without the need for PET or medical CT scanners. The AC TX-based maps were generated for a homogeneous cylinder, made of acrylic as a validator. The technique thereafter was applied to the patient table and posterior part of an RF-phased array used in cardiovascular PET/MRI imaging. The proposed TX-based, and the CT-based, hardware maps were used in reconstructing PET images of one cardiac patient, and the results were analysed and compared.ResultsThe LAC derived by the TX-based method for the acrylic cylinder is estimated to be 0.10851 ± 0.00380 cm−1 compared to the 0.10698 ± 0.00321 cm−1 theoretical value reported in the literature. The PET photon counts were reduced by 8.7 ± 1.1% with the patient table, at the region used in cardiac scans, while the CT-based map, used for correction, over-estimated counts by 4.3 ± 1.3%. Reconstructed in vivo images using TX-based AC hardware maps have shown 4.1 ± 0.9% mean difference compared to those reconstructed images using CT-based AC.ConclusionsThe LAC of the acrylic cylinder measurements using the TX-based technique was in agreement with those in the literature confirming the validity of the technique. The over-estimation of photon counts caused by the CT-based model used for the patient table was improved by the TX-based technique. Therefore, TX-based AC of hardware using the PET/MRI system itself is possible and can produce more accurate images when compared to the CT-based hardware AC in cardiac PET images.

Learning to Denoise Gated Cardiac PET Images Using Convolutional Neural Networks

Noise and motion artifacts in Positron emission tomography (PET) scans can interfere in diagnosis and result in inaccurate interpretations. PET gating techniques effectively reduce motion blurring, but at the cost of increasing noise, as only a subset of the data is used to reconstruct the image. Deep convolutional neural networks (DCNNs) could complement gating techniques by correcting such noise. However, there is little research on the specific application of DCNNs to gated datasets, which present additional challenges that are not considered in these studies yet, such as the varying level of noise depending on the gate, and performance pitfalls due to changes in the noise properties between non-gated and gated scans. To extend the current status of artificial intelligence (AI) in gated-PET imaging, we present a post-reconstruction denoising approach based on U-Net architectures on cardiac dual-gated PET images obtained from 40 patients. To this end, we first evaluate the denoising performance of four different variants of the U-Net architecture (2D, semi-3D, 3D, Hybrid) on non-gated data to better understand the advantages of each type of model, and to shed more light on the factors to take in consideration when selecting a denoising architecture. Then, we tackle the denoising of gated-PET reconstructions, revising challenges and limitations, and propose two training approaches, which overcome the need for gated targets. Quantification results show that the proposed deep learning (DL) frameworks can successfully reduce noise levels while correctly preserving the original motionless resolution of the gates.

Cardiac Sympathetic Innervation Imaging with PET Radiotracers.

The present article reviews the pathophysiology of cardiac sympathetic denervation, the principles of positron emission tomography (PET) imaging of the sympathetic innervation of the heart and its potential clinical role, based on current and expected future evidence. Imaging of cardiac sympathetic denervation can be performed with radiolabeled noradrenaline analogues, e.g., 11C-hydroxyephedrine. A greater burden of sympathetic denervation carries prognostic significance, e.g., in patients with ischemic cardiomyopathy and a left ventricular ejection fraction ≤ 35%, who are more likely to experience sudden cardiac death. Abnormalities of sympathetic cardiac innervation have been demonstrated in hypertrophic, dilated, and arrhythmic right ventricular cardiomyopathies, and may be helpful in better phenotyping patients who will benefit from device therapy, e.g., cardiac resynchronization and implantable cardioverter-defibrillator implantation. The results of future trials, e.g., the Prediction of Arrhythmic Events with Positron Emission Tomography (PAREPET) II study, are awaited to inform on the role of PET cardiac sympathetic imaging in the selection of device therapy. PET cardiac sympathetic innervation imaging allows visualization and quantification of autonomic denervation secondary to various cardiac diseases, and has significant potential to influence clinical decision-making, e.g., the titration of pharmacotherapy and more directed selection of candidates for device implantation.

Prevalence of newly diagnosed sarcoidosis in patients with ventricular arrhythmias: a cardiac magnetic resonance and 18F-FDG cardiac PET study.

Cardiac sarcoidosis (CS) is known to be associated with ventricular tachycardia (VT); however, most investigations to date have focused on patients with known extra-cardiac sarcoidosis. The presence of CS is typically evaluated using 18F-fluorodeoxyglucose (18F-FDG) uptake on cardiac positron emission tomography (PET) or late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR). In this study, we sought to determine the prevalence of primary CS and the relationship between myocardial 18F-FDG uptake and LGE in patients with VT without known sarcoidosis. We retrospectively identified 67 patients without known sarcoidosis or active ischemic heart disease (i.e. significant ischemic disease that had not been previously revascularized) referred for both CMR and PET for evaluation of VT. Standard cine- and LGE- CMR and cardiac PET protocols were used. Myocardial LGE was defined as signal intensity > 5 SDs above the mean signal intensity of normal myocardium. Cardiac PET images were considered positive if there was focal myocardial 18F-FDG uptake having greater activity than the left ventricular blood pool. 45 patients (67%) had LGE, while only 4 (6%) had myocardial FDG uptake. Nine percent of patients with LGE had FDG-uptake while none without LGE did, and 10% of the cohort had indeterminate FDG uptake presumably from poor dietary preparation. Of those with both FDG uptake and LGE, 3/4 ultimately received a clinical diagnosis of CS. 4.5% of patients without previously known sarcoidosis or active ischemic heart disease presenting with VT have newly diagnosed CS. Detection of CS can be increased using a CMR first approach followed by cardiac PET for patients with non-ischemic LGE.

Fully Automated Radiosynthesis of [11C]Guanidines for Cardiac PET Imaging.

Radiolabeled guanidines such as meta-iodobenzylguanidine (MIBG) find utility in nuclear medicine as both diagnostic imaging agents and radiotherapeutics and, over the years, numerous methods for incorporating radionuclides into guanidines have been developed. In connection with a project developing new positron emission tomography (PET) radiotracers for cardiac sympathetic nerve density, we had cause to prepare [11C]3F-PHPOG. However, it quickly became apparent that radiolabeling of guanidine scaffolds with carbon-11 has remained challenging, and historical methods lack compatibility with modern automated radiochemistry synthesis platforms and current Good Manufacturing Practice (cGMP) requirements. To address this challenge, we report a new automated method for radiolabeling guanidines with carbon-11. The method was used to prepare a series of [11C]guanidines in good radiochemical yield (8-76% by radio-HPLC) and was found to have broad substrate scope and tolerance of unprotected OH and NH functional groups. The method was used to synthesize [11C]3F-PHPOG for preclinical imaging, and suitability of the radiotracer for preclinical use was demonstrated through preliminary cardiac PET in New Zealand white rabbits which revealed good cardiac uptake and expected retention in the heart.

Motion tracking of low‐activity fiducial markers using adaptive region of interest with list‐mode positron emission tomography

Motion compensated positron emission tomography (PET) imaging requires detecting and monitoring of patient body motion. We developed a semiautomatic list-mode method to track the three-dimensional (3D) motion of fiducial positron-emitting markers during PET imaging. A previously developed motion tracking method using positron-emitting markers (PeTrack) was enhanced to work with PET imaging. A novel combination of filtering methods was developed to reject physiological tracer background, which would drown out the events from the marker if unfiltered. The most critical filter rejects events whose line-of-response (LOR) is outside an adaptive region of interest (ADROI). The size of ROI was optimized by exploiting the distinct differences between the distributions of events from background and marker. The ADROI PeTrack method was evaluated with Monte Carlo and phantom studies. A 92.5-kBq Na marker moving sinusoidally in 3D was simulated with Monte Carlo methods. The simulated events were combined with list-mode data from cardiac PET imaging patients to evaluate the performance of the tracking. In phantom studies, three Na markers were placed on a dynamic torso phantom with an initial activity of 680MBq of Rb in its cardiac insert. The motion of the markers was tracked while the phantom simulated various types of patient motion. Motion correction on an event-by-event basis of the list-mode data was then applied and images were reconstructed. Simulation results show that the background rejection methods can significantly suppress the tracer background and increase the fraction of marker events by a factor of up to 2500. A 92.5-kBq marker can be tracked in 3D at a frequency of 2.0Hz with an accuracy of 0.8mm and a precision of 0.3mm. The phantom study experimentally confirms that the algorithm can track various types of motion. The relative accuracy of the experimental tracking is 0.26±0.14mm. Motion-corrected images from the phantom study show reduced blurring. An algorithm and background rejection methods were developed that can track the 3D motion of low-activity positron-emitting markers during PET imaging. The motion information may be used for motion-compensated PET imaging.

New Approaches in the Management of Sudden Cardiac Death in Patients with Heart Failure-Targeting the Sympathetic Nervous System.

Cardiovascular diseases (CVDs) have been considered the most predominant cause of death and one of the most critical public health issues worldwide. In the past two decades, cardiovascular (CV) mortality has declined in high-income countries owing to preventive measures that resulted in the reduced burden of coronary artery disease (CAD) and heart failure (HF). In spite of these promising results, CVDs are responsible for ~17 million deaths per year globally with ~25% of these attributable to sudden cardiac death (SCD). Pre-clinical data demonstrated that renal denervation (RDN) decreases sympathetic activation as evaluated by decreased renal catecholamine concentrations. RDN is successful in reducing ventricular arrhythmias (VAs) triggering and its outcome was not found inferior to metoprolol in rat myocardial infarction model. Registry clinical data also suggest an advantageous effect of RDN to prevent VAs in HF patients and electrical storm. An in-depth investigation of how RDN, a minimally invasive and safe method, reduces the burden of HF is urgently needed. Myocardial systolic dysfunction is correlated to neuro-hormonal overactivity as a compensatory mechanism to keep cardiac output in the face of declining cardiac function. Sympathetic nervous system (SNS) overactivity is supported by a rise in plasma noradrenaline (NA) and adrenaline levels, raised central sympathetic outflow, and increased organ-specific spillover of NA into plasma. Cardiac NA spillover in untreated HF individuals can reach ~50-fold higher levels compared to those of healthy individuals under maximal exercise conditions. Increased sympathetic outflow to the renal vascular bed can contribute to the anomalies of renal function commonly associated with HF and feed into a vicious cycle of elevated BP, the progression of renal disease and worsening HF. Increased sympathetic activity, amongst other factors, contribute to the progress of cardiac arrhythmias, which can lead to SCD due to sustained ventricular tachycardia. Targeted therapies to avoid these detrimental consequences comprise antiarrhythmic drugs, surgical resection, endocardial catheter ablation and use of the implantable electronic cardiac devices. Analogous NA agents have been reported for single photon-emission-computed-tomography (SPECT) scans usage, specially the 123I-metaiodobenzylguanidine (123I-MIBG). Currently, HF prognosis assessment has been improved by this tool. Nevertheless, this radiotracer is costly, which makes the use of this diagnostic method limited. Comparatively, positron-emission-tomography (PET) overshadows SPECT imaging, because of its increased spatial definition and broader reckonable methodologies. Numerous ANS radiotracers have been created for cardiac PET imaging. However, so far, [11C]-meta-hydroxyephedrine (HED) has been the most significant PET radiotracer used in the clinical scenario. Growing data has shown the usefulness of [11C]-HED in important clinical situations, such as predicting lethal arrhythmias, SCD, and all-cause of mortality in reduced ejection fraction HF patients. In this article, we discussed the role and relevance of novel tools targeting the SNS, such as the [11C]-HED PET cardiac imaging and RDN to manage patients under of SCD risk.

Therapeutic Effect of Fimasartan in a Rat Model of Myocardial Infarction Evaluated by Cardiac Positron Emission Tomography with [18F]FPTP.

We evaluated the efficacy of fimasartan on perfusion defects and infarction size in an animal model of myocardial infarction (MI), with echocardiography and positron emission tomography (PET) using a 18F-labeled phosphonium cation (5-[18F]-fluoropentyl-triphenylphosphonium salt, [18F]FPTP) as a mitochondrial voltage sensor for myocardial imaging. We induced MI in 33 rats by ligation of the left coronary artery, and checked their cardiac PET image using [18F]FPTP for evaluation of myocardial perfusion. Rats were grouped into 3 groups according to their administered drugs: no drug (n=11), fimasartan 3 mg/kg (n=10), and fimasartan 10 mg/kg (n=12). Each designated drug was administered for 4 weeks, and follow-up PET and histologic examinations were done. In the PET analysis, a perfusion defect size was markedly improved in fimasartan 10 mg/kg group (35.9±7.0% to 28.4±6.9%, p<0.001), whereas treatment with fimasartan 3 mg/kg induced only an insignificant reduction of perfusion defect size (35.9±7.9% to 33.9±7.3%, p=0.095). Using 2, 3, 5-triphenyltetrazolium chloride staining, infarction size was the largest in the control group (36.5±8.3%), and was insignificantly lower in the fimasartan 3 mg/kg group (31.5±6.5%, p for the difference between the control group=0.146) and was significantly lower in the fimasartan 10 mg/kg group (26.3±7.6%, p for the difference between the control group=0.011). PET imaging using a 18F-labeled mitochondrial voltage sensor, [18F]FPTP, is useful in evaluation and monitoring of myocardial perfusion states, and treatment with fimasartan decreases the infarction size in animal MI model.

Diagnostic and Prognostic Value of CMR and Cardiac PET Imaging in Patients with Cardiac Sarcoidosis

Background: Cardiac Magnetic Resonance (CMR) and Positron Emission Tomography (PET) are employed to diagnose Cardiac Sarcoidosis (CS). However, their role in prognosis and guiding treatment is not well established. Objective: To discern the utility of CMR and PET in diagnosing and predicting adverse outcomes in CS. Methods: “Cardiac Sarcoidosis*” AND “Magnetic Resonance Imaging” OR “Positron Emission Tomography” were searched on PubMED, EMBASE and SCOPUS on 21st of September 2018 yielding 1180 articles. After exclusions, 26 studies were included in the meta-analysis. Results: 8 and 13 studies compared diagnostic value of CMR and PET, respectively against the diagnostic criteria of either the Japanese Ministry of Health or the Heart Rhythm Society. These showed a sensitivity of 75.7% [69.3–81.4] and 81.4% [76.7–85.4] for CMR and cardiac PET, respectively, to diagnose CS. The risk of ventricular arrhythmia was increased in patients with late gadolinium enhancement (LGE) on CMR (HR 3.32 [0.59–18.51], I2 = 58; N = 4) or positive FDG uptake on cardiac PET (HR 2.91 [1.68–5.06]; N = 3). The LVEF in the group with and without LGE on CMR was 54±9 and 57±7%, respectively. Absence of LGE on CMR predicted absence of ventricular arrhythmia (NPV = 96.7% [88.2%–99.1%]). LGE on CMR was also associated with increased risk of major adverse cardiac events (MACE) (HR: 8.20 [2.28–29.45], I2 = 81; N = 5). Conclusion: LGE on CMR and positive FDG uptake on cardiac PET are associated with high risk of ventricular arrhythmia. LGE on CMR imaging predicts high risk for MACE.