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Objectives: This study aimed to evaluate the level of evidence of expert recommendations and guidelines for clinical indications and procedurals in hybrid nuclear cardiovascular imaging., Methods: From inception to August 2023, a PubMed literature analysis of the latest version of guidelines for clinical hybrid cardiovascular imaging techniques including SPECT(/CT), PET(/CT), and PET(/MRI) was performed in two categories: (1) for clinical indications for all-in primary diagnosis; subgroup in prognosis and therapy evaluation; and for (2) imaging procedurals. We surveyed to what degree these followed a standard methodology to collect the data and provide levels of evidence, and for which topic systematic review evidence was executed., Results: A total of 76 guidelines, published between 2013 and 2023, were included. The evidence of guidelines was based on systematic reviews in 7.9% of cases, non-systematic reviews in 47.4% of cases, a mix of systematic and non-systematic reviews in 19.7%, and 25% of guidelines did not report any evidence. Search strategy was reported in 36.8% of cases. Strengths of recommendation were clearly reported in 25% of guidelines. The notion of external review was explicitly reported in 23.7% of cases. Finally, the support of a methodologist was reported in 11.8% of the included guidelines., Conclusion: The use of evidence procedures for developing for evidence-based cardiovascular hybrid imaging recommendations and guidelines is currently suboptimal, highlighting the need for more standardized methodological procedures., (© 2024. The Author(s).)

Cardiotoxicity may present as (pulmonary) hypertension, acute and chronic coronary syndromes, venous thromboembolism, cardiomyopathies/heart failure, arrhythmia, valvular heart disease, peripheral arterial disease, and myocarditis. Many of these disease entities can be diagnosed by established cardiovascular diagnostic pathways. Nuclear medicine, however, has proven promising in the diagnosis of cardiomyopathies/heart failure, and peri- and myocarditis as well as arterial inflammation. This article first outlines the spectrum of cardiotoxic cancer therapies and the potential side effects. This will be complemented by the definition of cardiotoxicity using non-nuclear cardiovascular imaging (echocardiography, CMR) and biomarkers. Available nuclear imaging techniques are then presented and specific suggestions are made for their application and potential role in the diagnosis of cardiotoxicity., (© 2022. The Author(s).)

The use of cardiac PET, and in particular of quantitative myocardial perfusion PET, has been growing during the last years, because scanners are becoming widely available and because several studies have convincingly demonstrated the advantages of this imaging approach. Therefore, there is a need of determining the procedural modalities for performing high-quality studies and obtaining from this demanding technique the most in terms of both measurement reliability and clinical data. Although the field is rapidly evolving, with progresses in hardware and software, and the near perspective of new tracers, the EANM Cardiovascular Committee found it reasonable and useful to expose in an updated text the state of the art of quantitative myocardial perfusion PET, in order to establish an effective use of this modality and to help implementing it on a wider basis. Together with the many steps necessary for the correct execution of quantitative measurements, the importance of a multiparametric approach and of a comprehensive and clinically useful report have been stressed.

Purpose: We aimed to investigate the influence of both hypothyroidism and thyroid-stimulating hormone (TSH) suppression on vascular inflammation, as assessed with 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/computed tomography (CT)., Methods: Ten thyroid carcinoma patients underwent an 18 F-FDG PET/CT during post-thyroidectomy hypothyroidism and during thyrotropin (TSH) suppression after 131 I (radioiodine) ablation therapy. We analysed the 18 F-FDG uptake in the carotids, aortic arch, ascending, descending, and abdominal aorta to investigate the effects of thyroid hormone status on arterial inflammation. Target-to-background ratios (TBRs) corrected for blood pool activity were established for all arterial territories. Results were further compared to euthyroid historic control subjects., Results: In general, there was a trend towards higher vascular TBRs during TSH suppression than during hypothyroidism (TBR max all vessels = 1.6 and 1.8, respectively, p = 0.058), suggesting a higher degree of arterial inflammation. In concurrence with this, we found increased C-reactive protein (CRP) levels after levothyroxine treatment (CRP = 2.9 mg/l and 4.8 mg/l, p = 0.005). An exploratory comparison with euthyroid controls showed significant higher TBRs during TSH suppression for the carotids, aortic arch, thoracic descending aorta, and when all vascular territories were combined (TBR max p = 0.013, p = 0.016, p = 0.030 and p = 0.018 respectively)., Conclusions: Arterial inflammation is increased during TSH suppression. This finding sheds new light on the underlying mechanism of the suspected increased risk of cardiovascular disease in patients with TSH suppression.

Cardiovascular disease is the major cause of morbidity and mortality in developed countries and atherosclerosis is the major cause of cardiovascular disease. Atherosclerotic lesions obstruct blood flow in the arterial vessel wall and can rupture leading to the formation of occlusive thrombi. Conventional diagnostic tools are still of limited value for identifying the vulnerable arterial plaque and for predicting its risk of rupture and of releasing thromboembolic material. Knowledge of the molecular and biological processes implicated in the process of atherosclerosis will advance the development of imaging probes to differentiate the vulnerable plaque. The development of imaging probes with high sensitivity and specificity in identifying high-risk atherosclerotic vessel wall changes and plaques is crucial for improving knowledge-based decisions and tailored individual interventions. Arterial PET imaging with 18 F-FDG has shown promising results in identifying inflammatory vessel wall changes in numerous studies and clinical trials. However, due to its limited specificity in general and its intense physiological uptake in the left ventricular myocardium that impair imaging of the coronary arteries, different PET tracers for the molecular imaging of atherosclerosis have been evaluated. This review describes biological, chemical and medical expertise supporting a translational approach that will enable the development of new or the evaluation of existing PET tracers for the identification of vulnerable atherosclerotic plaques for better risk prediction and benefit to patients.

Purpose: Radiopharmaceutical extravasation can potentially lead to severe soft tissue damage, but little is known about incidence, medical consequences, possible interventions, and effectiveness of these. The aims of this study are to estimate the incidence of extravasation of diagnostic and therapeutic radiopharmaceuticals, to evaluate medical consequences, and to evaluate medical treatment applied subsequently to those incidents., Methods: A sensitive and elaborate literature search was performed in Embase and PubMed using the keywords "misadministration", "extravasation", "paravascular infiltration", combined with "tracer", "radionuclide", "radiopharmaceutical", and a list of keywords referring to clinically used tracers (i.e. "Technetium-99m", "Yttrium-90"). Reported data on radiopharmaceutical extravasation and applied interventions was extracted and summarised., Results: Thirty-seven publications reported 3016 cases of diagnostic radiopharmaceutical extravasation, of which three cases reported symptoms after extravasation. Eight publications reported 10 cases of therapeutic tracer extravasation. The most severe symptom was ulceration. Thirty-four different intervention and prevention strategies were performed or proposed in literature., Conclusions: Extravasation of diagnostic radiopharmaceuticals is common. 99m Tc, 123 I, 18 F, and 68 Ga labelled tracers do not require specific intervention. Extravasation of therapeutic radiopharmaceuticals can give severe soft tissue lesions. Although not evidence based, surgical intervention should be considered. Furthermore, dispersive intervention, dosimetry and follow up is advised. Pharmaceutical intervention has no place yet in the immediate care of radiopharmaceutical extravasation.

Purpose: Amyloid-beta (Aβ) peptides are involved in the inflammatory pathology of atherosclerosis. 18 F-Florbetaben is a PET tracer for clinical imaging of cerebral Aβ plaques in Alzheimer's disease (AD). We sought to determine whether specific uptake of 18 F-florbetaben in the carotid arteries can be identified using a fully integrated hybrid PET/MRI system and whether this uptake is associated with clinical cardiovascular disease (CVD) risk factors., Methods: Carotid 18 F-florbetaben uptake was quantified as the mean of the maximum target-to-background ratio ( mean TBR max ) in 40 cognitively impaired subjects (age 68.2 ± 9.5 years) undergoing 18 F-florbetaben PET/MRI to diagnose AD. Associations between carotid 18 F-florbetaben uptake and several CVD risk factors were assessed by univariate analysis followed by a multivariate linear regression analysis. Furthermore, carotid 18 F-florbetaben uptake was compared between patients with and without a positive cerebral Aβ PET scan., Results: 18 F-Florbetaben uptake was clearly visualized in the carotid arteries. Values of mean TBR max corrected for the blood pool activity of the tracer showed specific 18 F-florbetaben uptake in the carotid wall. Male gender was associated with carotid 18 F-florbetaben uptake in the univariate analysis, and was found to be an independent predictor of 18 F-florbetaben uptake in the multivariate regression analysis (standardized regression coefficient β = 0.407, p = 0.009). Carotid 18 F-florbetaben mean TBR max in patients with a positive cerebral Aβ scan did not differ from that in patients without cerebral Aβ deposits., Conclusion: Specific 18 F-florbetaben uptake in human carotid arteries was detected. Male gender was identified as an independent clinical risk factor. Therefore, 18 F-florbetaben PET/MRI might provide new insights into the pathophysiological process in atherosclerosis.

The trade-off between resolution and count sensitivity dominates the performance of standard gamma cameras and dictates the need for relatively high doses of radioactivity of the used radiopharmaceuticals in order to limit image acquisition duration. The introduction of cadmium-zinc-telluride (CZT)-based cameras may overcome some of the limitations against conventional gamma cameras. CZT cameras used for the evaluation of myocardial perfusion have been shown to have a higher count sensitivity compared to conventional single photon emission computed tomography (SPECT) techniques. CZT image quality is further improved by the development of a dedicated three-dimensional iterative reconstruction algorithm, based on maximum likelihood expectation maximization (MLEM), which corrects for the loss in spatial resolution due to line response function of the collimator. All these innovations significantly reduce imaging time and result in a lower patient's radiation exposure compared with standard SPECT. To guide current and possible future users of the CZT technique for myocardial perfusion imaging, the Cardiovascular Committee of the European Association of Nuclear Medicine, starting from the experience of its members, has decided to examine the current literature regarding procedures and clinical data on CZT cameras. The committee hereby aims 1) to identify the main acquisitions protocols; 2) to evaluate the diagnostic and prognostic value of CZT derived myocardial perfusion, and finally 3) to determine the impact of CZT on radiation exposure.

Until recently, PET was regarded as a luxurious way of performing myocardial perfusion scintigraphy, with excellent image quality and diagnostic capabilities that hardly justified the additional cost and procedural effort. Quantitative perfusion PET was considered a major improvement over standard qualitative imaging, because it allows the measurement of parameters not otherwise available, but for many years its use was confined to academic and research settings. In recent years, however, several factors have contributed to the renewal of interest in quantitative perfusion PET, which has become a much more readily accessible technique due to progress in hardware and the availability of dedicated and user-friendly platforms and programs. In spite of this evolution and of the growing evidence that quantitative perfusion PET can play a role in the clinical setting, there are not yet clear indications for its clinical use. Therefore, the Cardiovascular Committee of the European Association of Nuclear Medicine, starting from the experience of its members, decided to examine the current literature on quantitative perfusion PET to (1) evaluate the rationale for its clinical use, (2) identify the main methodological requirements, (3) identify the remaining technical difficulties, (4) define the most reliable interpretation criteria, and finally (5) tentatively delineate currently acceptable and possibly appropriate clinical indications. The present position paper must be considered as a starting point aiming to promote a wider use of quantitative perfusion PET and to encourage the conception and execution of the studies needed to definitely establish its role in clinical practice.

Cardiovascular diseases are the leading cause of death not only in Europe but also in the rest of the World. Preventive measures, however, often fail and cardiovascular disease may manifest as an acute coronary syndrome, stroke or even sudden death after years of silent progression. Thus, there is a considerable need for innovative diagnostic and therapeutic approaches to improve the quality of care and limit the burden of cardiovascular diseases. During the past 10 years, several retrospective and prospective clinical studies have been published using (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to quantify inflammation in atherosclerotic plaques. However, the current variety of imaging protocols used for vascular (arterial) imaging with FDG PET considerably limits the ability to compare results between studies and to build large multicentre imaging registries. Based on the existing literature and the experience of the Members of the European Association of Nuclear Medicine (EANM) Cardiovascular Committee, the objective of this position paper was to propose optimized and standardized protocols for imaging and interpretation of PET scans in atherosclerosis. These recommendations do not, however, replace the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual study protocols used and the individual patient, in consultation with the patient and, where appropriate and necessary, the patient's guardian or carer. These recommendations suffer from the absence of conclusive evidence on many of the recommendations. Therefore, they are not intended and should not be used as "strict guidelines" but should, as already mentioned, provide a basis for standardized clinical atherosclerosis PET imaging protocols, which are subject to further and continuing evaluation and improvement. However, this EANM position paper might indeed be a first step towards "official" guidelines on atherosclerosis imaging with PET.

Purpose: The objective of the study was to systematically assess aortic inflammation in patients with granulomatosis with polyangiitis (GPA) using (18)F-2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) positron emission tomography (PET)/CT., Methods: Aortic inflammation was studied in PET/CT scans obtained from 21 patients with GPA; 14 patients with sarcoidosis were included as disease controls, 7 patients with stage I or II head and neck carcinoma ascertained during routine clinical practice were used as healthy controls (HC) and 5 patients with large vessel vasculitis (LVV) were used as positive controls. Aortic (18)F-FDG uptake was expressed as the blood-normalized maximum standardized uptake value (SUVmax), known as the target to background ratio (mean TBRmax)., Results: The mean TBRmax (interquartile range) of the aorta in patients with GPA, sarcoidosis, HC and LVV were 1.75 (1.32-2.05), 1.62 (1.54-1.74), 1.29 (1.22-1.52) and 2.03 (1.67-2.45), respectively. The mean TBRmax was significantly higher in patients suffering from GPA or LVV compared to HC (p < 0.05 and p < 0.005, respectively) and tended to be higher in patients suffering from sarcoidosis, but this did not reach statistical significance (p = 0.098). The mean TBRmax of the most diseased segment was significantly higher compared to HC [1.57 (1.39-1.81)] in LVV patients [2.55 (2.22-2.82), p < 0.005], GPA patients [2.17 (1.89-2.83), p < 0.005] and patients suffering from sarcoidosis [2.04 (1.88-2.20), p < 0.05]. In GPA patients, the mean TBRmax of the aorta was significantly higher in patients with previous renal involvement [2.01 (1.69-2.53)] compared to patients without renal involvement in the past [1.60 (1.51-1.80), p < 0.05]. Interrater reproducibility with a second reader was high (all intraclass correlation coefficients >0.9)., Conclusion: Patients suffering from GPA show marked aortic FDG uptake.

Purpose: There is evidence that the link between obesity and cardiovascular disease might relate to inflammation in both fat tissue and the arterial wall. (18)F-FDG uptake on PET is a surrogate marker of vessel wall inflammation. The aim of the study was to measure FDG uptake in both regions using PET and identify links between adipose and arterial inflammation., Methods: Included in the study were 173 cardiovascular patients who were prospectively imaged with FDG PET/CT. Arterial FDG uptake was measured in the carotid arteries and ascending aorta. The same was done in fat tissue in the neck, the presternal region (both subcutaneous) and the pericardium. FDG uptake was quantified as average maximal target-to-background ratio (mean TBR max). Multivariate regression analyses were performed to identify significant associations between arterial and adipose tissue FDG uptake and clinical variables as given by the standardized correlation coefficient (β)., Results: FDG uptake values in all fat tissue regions were highly predictive of vascular FDG uptake in both the carotids (β 0.262, p < 0.0001, in the neck subcutaneous region) and aorta (β 0.22, p = 0.008, in the chest pericardial region; β 0.193, p = 0.019, in the chest subcutaneous region). Obesity was significantly associated with elevated FDG uptake in adipose tissue (β 0.470, p < 0.0001, in the neck subcutaneous region; β 0.619, p = 0.028, in the chest subcutaneous region; β 0.978, p = 0.035, in the chest pericardial region)., Conclusion: FDG uptake in diverse fat tissue regions was significantly associated with arterial FDG uptake, a reasonable surrogate of inflammation. Increasing body weight significantly predicted the level of fatty inflammation. FDG PET therefore provides imaging evidence of an inflammatory link between fat tissue and the vasculature in patients with cardiovascular disease.

Purpose: Brown adipose tissue (BAT) has transformed from an interfering tissue in oncological (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to an independent imaging research field. This review takes the perspective from the imaging methodology on which human BAT research has come to rely on heavily., Methods: This review analyses relevant PubMed-indexed publications that discuss molecular imaging methods of BAT. In addition, reported links between BAT and human diseases such as obesity are discussed, and the possibilities for imaging in these fields are highlighted. Radiopharmaceuticals aiming at several different biological mechanisms of BAT are discussed and evaluated., Results: Prospective, dedicated studies allow visualization of BAT function in a high percentage of human subjects. BAT dysfunction has been implicated in obesity, linked with diabetes and associated with cachexia and atherosclerosis. Presently, (18)F-FDG PET/CT is the most useful tool for evaluating therapies aiming at BAT activity. In addition to (18)F-FDG, other radiopharmaceuticals such as (99m)Tc-sestamibi, (123)I-metaiodobenzylguanidine (MIBG), (18)F-fluorodopa and (18)F-14(R,S)-[(18)F]fluoro-6-thia-heptadecanoic acid (FTHA) may have a potential for visualizing other aspects of BAT activity. MRI methods are under continuous development and provide the prospect of functional imaging without ionizing radiation., Conclusion: Molecular imaging of BAT can be used to quantitatively assess different aspects of BAT metabolic activity.

Purpose: (18)F-FDG PET is increasingly used for imaging of vessel wall inflammation. However, limited data are available on the impact of methodological variables, i.e. prescan fasting glucose, FDG circulation time and injected FDG dose, and of different FDG uptake parameters, in vascular FDG PET imaging., Methods: Included in the study were 195 patients who underwent vascular FDG PET/CT of the aorta and the carotids. Arterial standardized uptake values (meanSUVmax), target-to-background ratios (meanTBRmax) and FDG blood-pool activity in the superior vena cava (SVC) and the jugular veins (JV) were quantified. Vascular FDG uptake values classified according to the tertiles of prescan fasting glucose levels, the FDG circulation time, and the injected FDG dose were compared using ANOVA. Multivariate regression analyses were performed to identify the potential impact of all variables described on the arterial and blood-pool FDG uptake., Results: Tertile analyses revealed FDG circulation times of about 2.5 h and prescan glucose levels of less than 7.0 mmol/l, showing a favorable relationship between arterial and blood-pool FDG uptake. FDG circulation times showed negative associations with aortic meanSUVmax values as well as SVC and JV FDG blood-pool activity, but positive correlations with aortic and carotid meanTBRmax values. Prescan glucose levels were negatively associated with aortic and carotid meanTBRmax and carotid meanSUVmax values, but were positively correlated with SVC blood-pool uptake. The injected FDG dose failed to show any significant association with vascular FDG uptake., Conclusion: FDG circulation times and prescan blood glucose levels significantly affect FDG uptake in the aortic and carotid walls and may bias the results of image interpretation in patients undergoing vascular FDG PET/CT. The injected FDG dose was less critical. Therefore, circulation times of about 2.5 h and prescan glucose levels less than 7.0 mmol/l should be preferred in this setting.

Purpose: Inflammation and neovascularization in vulnerable atherosclerotic plaques are key features for severe clinical events. Dynamic contrast-enhanced (DCE) MRI and FDG PET are two noninvasive imaging techniques capable of quantifying plaque neovascularization and inflammatory infiltrate, respectively. However, their mutual role in defining plaque vulnerability and their possible overlap has not been thoroughly investigated. We studied the relationship between DCE-MRI and (18)F-FDG PET data from the carotid arteries of 40 subjects with coronary heart disease (CHD) or CHD risk equivalent, as a substudy of the dal-PLAQUE trial (NCT00655473)., Methods: The dal-PLAQUE trial was a multicenter study that evaluated dalcetrapib, a cholesteryl ester transfer protein modulator. Subjects underwent anatomical MRI, DCE-MRI and (18)F-FDG PET. Only baseline imaging and biomarker data (before randomization) from dal-PLAQUE were used as part of this substudy. Our primary goal was to evaluate the relationship between DCE-MRI and (18)F-FDG PET data. As secondary endpoints, we evaluated the relationship between (a) PET data and whole-vessel anatomical MRI data, and (b) DCE-MRI and matching anatomical MRI data. All correlations were estimated using a mixed linear model., Results: We found a significant inverse relationship between several perfusion indices by DCE-MRI and (18)F-FDG uptake by PET. Regarding our secondary endpoints, there was a significant relationship between plaque burden measured by anatomical MRI with several perfusion indices by DCE-MRI and (18)F-FDG uptake by PET. No relationship was found between plaque composition by anatomical MRI and DCE-MRI or (18)F-FDG PET metrics., Conclusion: In this study we observed a significant, weak inverse relationship between inflammation measured as (18)F-FDG uptake by PET and plaque perfusion by DCE-MRI. Our findings suggest that there may be a complex relationship between plaque inflammation and microvascularization during the different stages of plaque development. (18)F-FDG PET and DCE-MRI may have complementary roles in future clinical practice in identifying subjects at high risk of cardiovascular events.

Purpose: To compare pretherapy (124)I PET/CT and posttherapy (131)I SPECT/CT in the identification of pathological lesions and the staging of patients with differentiated thyroid carcinoma., Methods: (124)I SPECT with low-dose CT in addition to a standard whole-body scan was performed 5 days following (131)I therapy with the administration of 1,110-7,728 MBq. Pretherapy (124)I PET/CT was done 24 h and 96 h after oral ingestion of 20-28 MBq, including a noncontrast high-dose CT scan. Scans were evaluated by two independent experienced nuclear physicians. In addition to the total number of lesions found, patient-based analyses and lesion-based analyses were performed to ascertain the discrepancies between the findings of the two scanning techniques, as well as to evaluate the clinical impact of the findings., Results: A group of 20 consecutive patients were analysed. In the lesion-based analysis, a total of 62 foci were found with all modalities together. Of these, (124)I PET/CT found 57 (92 %), (131)I SPECT/CT 50 (81 %) and planar imaging 39 (63 %). In the patient-based analysis, in 50 % of patients complete concordance between the findings of (124)I PET and (131)I SPECT was seen, in 5 % complete discordance and in the remaining 45 % partial discordance, i.e. a focus or some foci seen with both modalities but another or others seen more or less with one or other modality. In 5 of the 20 patients (25 %), tumour stage was changed according to the findings of one of the modalities. In 60 % of these patients this was only with the findings of (124)I PET/CT., Conclusion: This study showed that (124)I PET/CT is preferred over (131)I imaging for staging differentiated thyroid carcinoma.

Purpose: Recently published data indicated (18)F-fluorocholine to be feasible for imaging vulnerable atherosclerotic plaques in an animal model., Methods: Five patients undergoing whole-body (18)F-fluoromethylcholine-((18)F-FMCH-) PET/CT for imaging of prostate cancer disease were retrospectively evaluated. Whole-body PET scans were started immediately after i.v. injection of (18)F-FMCH. About 5-15 min after tracer injection, acquisition of scans of the pelvis and abdomen was performed. PET, CT, and PET/CT slices were generated for review and visual analyses of the abdominal aorta and the common iliac arteries were performed. Vascular findings in examined arteries and surrounding structures due to artifacts were excluded from further analysis. The lower threshold of (18)F-FMCH uptake was set above the background activity within the examined vessels. Morphological classification of vessel wall alterations (WA) included structural wall alterations without additional calcification (SWA), structural wall alterations associated with calcifications (SWC), and solely calcified lesions (CL). They were correlated with (18)F-FMCH uptake qualified as present and vice versa., Results: A total of 31 WA were identified. Positive (18)F-FMCH uptake was found in 14 lesions (SWA: n = 5; SWC: n = 9). Sixteen of 17 (18)F-FMCH negative lesions were identified as CL without additional structural vessel wall alteration. One SWA did not show any (18)F-FMCH accumulation. None of the CLs as well as unaltered parts of the vessel wall showed (18)F-FMCH uptake., Conclusions: Our initial data in five patients with a total of 31 vessel wall alterations show promising results indicating for the first time the feasibility of (18)F-FMCH for in vivo imaging of structural WA in humans.