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Background: 18F-FDG PET/CT imaging represents the most important functional imaging method in oncology. European Society of Medical Oncology and the National Comprehensive Cancer Network guidelines defined a crucial role of 18F-FDG PET/CT imaging for local/locally advanced breast cancer. The application of artificial intelligence on PET images might potentially contributes in the field of precision medicine. Objective: This review aims to summarize the clinical indications and limitations of PET imaging for comprehensive artificial intelligence in relation to breast cancer subtype, hormone receptor status, proliferation rate, and lymphonodal (LN)/distant metastatic spread, based on recent literature. Methods: A literature search of the Pubmed/Scopus/Google Scholar/Cochrane/EMBASE databases was carried out, searching for articles on the use of artificial intelligence and PET in breast tumors. The search was updated from January 2010 to October 2021 and was limited to original articles published in English and about humans. A combination of the search terms "artificial intelligence", “breast cancer”, “breast tumor”, “PET”, “Positron emission tomography”, “PET/CT”, “PET/MRI”, “radiomic”," texture analysis", “machine learning”, “deep learning” was used. Results: Twenty-three articles were selected following the PRISMA criteria from 139 records obtained from the Pubmed/Scopus/Google Scholar/Cochrane/EMBASE databases according to our research strategy. The QUADAS of 30 full-text articles assessed reported seven articles that were excluded for not being relevant to population and outcomes and/or for lower level of evidence. The majority of papers were at low risk of bias and applicability. The articles were divided per topic, such as the value of PET in the staging and re-staging of breast cancer patients, including new radiopharmaceuticals and simultaneous PET/MRI. Conclusion: Despite the current role of AI in this field remains still undefined, several applications for PET/CT imaging are under development, with some preliminary interesting results particularly focused on the staging phase that might be clinically translated after further validation studies.

Background Despite the demonstrated adverse outcome, it is difficult to early identify the risks for patients with ischemia and no obstructive coronary artery disease (INOCA). We aimed to explore the prognostic potential of CZT SPECT in INOCA patients. Methods The study population consisted of a retrospective cohort of 118 INOCA patients, all of whom underwent CZT SPECT imaging and invasive coronary angiography (ICA). Dynamic data were reconstructed, and MBF was quantified using net retention model. Major adverse cardiovascular events (MACEs) were defined as cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, heart failure, late coronary revascularization, or hospitalization for unstable angina. Results During a median follow-up of 15 months (interquartile range (IQR) 11–20), 19 (16.1%) MACEs occurred; both stress myocardial blood flow (sMBF) ($$p p < 0.001 ) and coronary flow reserve (CFR) ($$p p < 0.001 ) were significantly lower in the MACE group. Optimal thresholds of sMBF$$p=0.001$$ p = 0.001 ) and CFR (HR: 6.51; 95% CI 1.43–29.65; $$p=0.01$$ p = 0.01 ) were identified as prognostic factors for MACEs. Only sMBF$$p=0.005$$ p = 0.005 ) remained a robust predictor when sMBF and CFR were integrated considered. Compared with CFR, sMBF provides better prognostic model discrimination and reclassification ability (C-index improvement = 0.06, $$p=0.02$$ p = 0.02 ; net reclassification improvement (NRI) = 0.19; integrated discrimination improvement (IDI) = 0.10). Conclusion The preliminary results demonstrated that quantitative analysis on CZT SPECT provides prognostic value for INOCA patients, which may allow the stratification for early prevention and intervention.

Abstract The European Society of Cardiovascular Radiology (ESCR) is the European specialist society of cardiac and vascular imaging. This society’s highest priority is the continuous improvement, development, and standardization of education, training, and best medical practice, based on experience and evidence. The present intra-society consensus is based on the existing scientific evidence and on the individual experience of the members of the ESCR writing group on carotid diseases, the members of the ESCR guidelines committee, and the members of the executive committee of the ESCR. The recommendations published herein reflect the evidence-based society opinion of ESCR. We have produced a twin-papers consensus, indicated through the documents as respectively “Part I” and “Part II.” The first document (Part I) begins with a discussion of features, role, indications, and evidence for CT and MR imaging-based diagnosis of carotid artery disease for risk stratification and prediction of stroke (Section I). It then provides an extensive overview and insight into imaging-derived biomarkers and their potential use in risk stratification (Section II). Finally, detailed recommendations about optimized imaging technique and imaging strategies are summarized (Section III). The second part of this consensus paper (Part II) is focused on structured reporting of carotid imaging studies with CT/MR. Key Points • CT and MR imaging-based evaluation of carotid artery disease provides essential information for risk stratification and prediction of stroke. • Imaging-derived biomarkers and their potential use in risk stratification are evolving; their correct interpretation and use in clinical practice must be well-understood. • A correct imaging strategy and scan protocol will produce the best possible results for disease evaluation.

Aims Pulmonary transit time (PTT) is the time blood takes to pass from the right ventricle to the left ventricle via pulmonary circulation. We aimed to quantify PTT in routine cardiovascular magnetic resonance imaging perfusion sequences. PTT may help in the diagnostic assessment and characterization of patients with unclear dyspnoea or heart failure (HF). Methods and results We evaluated routine stress perfusion cardiovascular magnetic resonance scans in 352 patients, including an assessment of PTT. Eighty-six of these patients also had simultaneous quantification of N-terminal pro-brain natriuretic peptide (NTproBNP). NT-proBNP is an established blood biomarker for quantifying ventricular filling pressure in patients with presumed HF. Manually assessed PTT demonstrated low inter-rater variability with a correlation between raters >0.98. PTT was obtained automatically and correctly in 266 patients using artificial intelligence. The median PTT of 182 patients with both left and right ventricular ejection fraction >50% amounted to 6.8 s (Pulmonary transit time: 5.9–7.9 s). PTT was significantly higher in patients with reduced left ventricular ejection fraction (600 ng/L) was 0.70 (P < 0.001) with a specificity of 78% and sensitivity of 61%. Conclusion PTT as an easily, even automatically obtainable and robust non-invasive biomarker of haemodynamics might help in the evaluation of patients with dyspnoea and HF.

Background Despite clinical suspicion, many non-invasive tests for coronary artery disease (CAD) are normal. Coronary artery calcification score (CACS) is a well-validated method to detect and risk stratify CAD. Patients with zero calcium score (ZCS) rarely have abnormal tests. Therefore, aims were to evaluate CACS as a gatekeeper to further functional downstream testing for CAD and estimate potential radiation and cost savings. Methods Consecutive patients with suspected CAD referred for PET were included (n = 2640). Prevalence and test characteristics of ZCS were calculated in different groups. Summed stress score ≥ 4 was considered abnormal and summed difference score ≥ 7 equivalent to ≥ 10% ischemia. To estimate potential radiation/cost reduction, PET scans were hypothetically omitted in ZCS patients. Results Mean age was 65 ± 11 years, 46% were female. 21% scans were abnormal and 26% of patients had ZCS. CACS was higher in abnormal PET (median 561 vs 27, P P Conclusions ZCS is frequent, and most often consistent with normal PET scans. ZCS offers an excellent NPV to exclude an abnormal PET and ≥ 10% ischemia across different gender and age groups. CACS is a suitable gatekeeper before advanced cardiac imaging, and potential radiation/cost savings are substantial. However, further studies including safety endpoints are needed.

Drug delivery to the colon offers great promise for local treatment of colonic diseases as it allows bypassing systemic absorption in the small intestine, thereby increasing luminal drug concentrations in the colon. The primary objective of this in vivo pharmaco-scintigraphy study was to assess the colon drug targeting accuracy of a metronidazole benzoate colonic drug delivery system intended for local treatment of Clostridioides difficile infections. Additionally, it was assessed if the concept of mucoadhesion would increase colonic residence time and promote higher drug bioavailability. Two different capsule formulations were designed and tested in healthy human subjects. Capsules contained either non-mucoadhesive (NM) or mucoadhesive (M) microgranules, both loaded with 100 mg metronidazole benzoate (antibiotic prodrug) and 5 mg samarium oxide (scintigraphy tracer). Filled capsules were coated with a colonic-targeting technology consisting of two functional layers, which allow for accelerated drug release mediated by the intestinal pH in combination with or without colonic bacteria. Coated capsules were neutron-activated to yield the radioisotope 153Sm prior to administration to 18 healthy subjects. Gamma-scintigraphy imaging was combined with the measurement of drug plasma levels. Formulation NM showed high colon-targeting accuracy. Initial capsule disintegration within the targeted ileocolonic region was observed in 8 out of 9 subjects (89%) with colonic arrival times in the range of 3.5 to 12 h and reduced systemic exposure. In contrast, the mucoadhesive formulation M showed some inconsistency regarding the site of initial capsule disintegration (targeting accuracy 56%). Variability of drug release was attributed to self-adhesion and agglomeration of the mucoadhesive microparticles within the capsule. Accurate ileocolonic delivery of metronidazole-loaded microgranules was achieved following oral administration of colonic-targeted capsules. Delayed drug release from NM microparticles in the colon leads to a reduced systemic exposure compared to immediate-release data from literature and presumably elevated drug concentrations in the colonic lumen. This approach offers promising options for the local treatment of colonic diseases.

Background We aimed to compare coronary artery calcium scoring (CACS) with computed tomography (CT) with 80 and 120 kVp in a large patient population and to establish whether there is a difference in risk classification between the two scores. Methods Patients with suspected CAD undergoing MPS were included. All underwent standard CACS assessment with 120-kVp tube voltage and with 80 kVp. Two datasets (low-dose and standard) were generated and compared. Risk classes (0 to 25, 25 to 50, 50 to 75, 75 to 90, and > 90%) were recorded. Results 1511 patients were included (793 males, age 69 ± 9.1 years). There was a very good correlation between scores calculated with 120 and 80 kVp (R = 0.94, R2 = 0.88, P P = .03) and with CACS = 0 differed between the two protocols (n = 264 vs 437, P Conclusion In a large patient population, despite a good correlation between CACS calculated with standard and low-dose CT, there is a systematic underestimation of CACS with the low-dose protocol. This may have an impact especially on the prognostic value of the calcium score, and the established “power of zero” may no longer be warranted if CACS is assessed with low-dose CT.

PURPOSE We aimed to assess normal values for quantified myocardial blood flow (MBF) on a hybrid PET/coronary-CT scanner and to test their diagnostic performance in patients with suspected CAD. MATERIALS AND METHODS Patients underwent 82Rb-PET/CT and integrated CT-based coronary angiography (CCTA) and were classified as normal (no stenosis), with non-obstructive stenosis (< 50%) and with CAD (≥ 50%). Global and regional stress MBF (sMBF), rest MBF and myocardial flow reserve (MFR) were calculated. Ischemia was defined as SDS ≥ 2, severe ischemia as SDS ≥ 7. RESULTS 357 consecutive patients were included. Global sMBF and MFR were higher in normal patients than in patients with CAD (3.61 ± 0.71 vs 3.04 ± 0.77, P < 0.0001; 3.08 ± 0.84 vs 2.68 ± 0.79, P = 0.0001), but not different compared to patients with non-obstructive stenosis (3.61 ± 0.71 vs 3.43 ± 0.69, P = 0.052; 3.08 ± 0.84 vs 2.99 ± 0.82, P = 0.45). sMBF yielded superior accuracy over MFR in identifying both ischemia (AUC 0.74 vs 0.62, P = 0.003) and severe ischemia (AUC 0.88 vs 0.78, P = 0.012). Optimal threshold for global sMBF to rule out myocardial ischemia was 3.5 mL g-1 min-1. CONCLUSIONS Normal quantitative values are provided. Global sMBF provided higher diagnostic accuracy than MFR. Using sMBF-threshold of 3.5 mL·g-1·min-1 on 82Rb-PET/CT yielded similar NPV (96%) as CCTA to rule out CAD. Hence, resting scan could be omitted in patients with sMBF values above reference.

Cardiovascular disease (CVD) is the leading cause of mortality and disability in developed countries. According to WHO, an estimated 17.9 million people died from CVDs in 2019, representing 32% of all global deaths. Of these deaths, 85% were due to major adverse cardiac and cerebral events. Early detection and care for individuals at high risk could save lives, alleviate suffering, and diminish economic burden associated with these diseases. Carotid artery disease is not only a well-established risk factor for ischemic stroke, contributing to 10%-20% of strokes or transient ischemic attacks (TIAs), but it is also a surrogate marker of generalized atherosclerosis and a predictor of cardiovascular events. In addition to diligent history, physical examination, and laboratory detection of metabolic abnormalities leading to vascular changes, imaging of carotid arteries adds very important information in assessing stroke and overall cardiovascular risk. Spanning from carotid intima-media thickness (IMT) measurements in arteriopathy to plaque burden, morphology and biology in more advanced disease, imaging of carotid arteries could help not only in stroke prevention but also in ameliorating cardiovascular events in other territories (e.g. in the coronary arteries). While ultrasound is the most widely available and affordable imaging methods, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), their combination and other more sophisticated methods have introduced novel concepts in detection of carotid plaque characteristics and risk assessment of stroke and other cardiovascular events. However, in addition to robust progress in usage of these methods, all of them have limitations which should be taken into account. The main purpose of this consensus document is to discuss pros but also cons in clinical, epidemiological and research use of all these techniques.

Abstract The European Society of Cardiovascular Radiology (ESCR) is the European specialist society of cardiac and vascular imaging. This society’s highest priority is the continuous improvement, development, and standardization of education, training, and best medical practice, based on experience and evidence. The present intra-society consensus is based on the existing scientific evidence and on the individual experience of the members of the ESCR writing group on carotid diseases, the members of the ESCR guidelines committee, and the members of the executive committee of the ESCR. The recommendations published herein reflect the evidence-based society opinion of ESCR. The purpose of this second document is to discuss suggestions for standardized reporting based on the accompanying consensus document part I. Key Points • CT and MR imaging-based evaluation of carotid artery disease provides essential information for risk stratification and prediction of stroke. • The information in the report must cover vessel morphology, description of stenosis, and plaque imaging features. • A structured approach to reporting ensures that all essential information is delivered in a standardized and consistent way to the referring clinician.

Inflammatory cardiomyopathy (I-CMP) is defined as myocarditis in association with cardiac dysfunction and/or ventricular remodelling. It is characterized by inflammatory cell infiltration into the myocardium and has heterogeneous infectious and non-infectious aetiologies. A complex interplay of genetic, autoimmune, and environmental factors contributes to the substantial risk of deteriorating cardiac function, acute heart failure, and arrhythmia as well as chronic dilated cardiomyopathy and its sequelae. Multi-parametric cardiovascular magnetic resonance (CMR) imaging is sensitive to many tissue changes that occur during myocardial inflammation, regardless of its aetiology. In this review, we summarize the various aetiologies of I-CMP and illustrate how CMR contributes to non-invasive diagnosis.

A 66-year-old man presented with 4 weeks of bilateral buttock pain without previous trauma or intense exercise. He had been treated with immune checkpoint inhibitors because of metastasising melanoma and experienced immune-related adverse events requiring treatment with corticosteroids. Magnetic resonance imaging of the pelvis revealed bilateral avulsion of the proximal hamstring muscles. Treatment with physical therapy and nonsteroidal anti-inflammatory drugs led to a slow but lasting relief. This is, to our knowledge, the first report of symptomatic non-traumatic bilateral hamstring muscle avulsion following treatment with immune checkpoint inhibitors and corticosteroids.

While a visual interpretation of 99mTc-DPD scintigraphy by means of Perugini score can provide a reliable diagnosis of transthyretin-related (ATTR) cardiac amyloidosis (CA), a quantitative approach is expected to play a major role in risk stratification and therapy evaluation. The aim of our study was to test the feasibility of a quantitative assessment and to correlate various parameters to Perugini score. in this retrospective study, consecutive patients underwent a 99mTc-DPD whole-body bone scintigraphy and a SPECT/CT of the thorax. XSPECT-QUANT software was used to quantify the DPD uptake in the heart. Thirteen patients were included. CA was confirmed in 8 and rejected in 5. Myocardial SUVmax and SUVpeak showed a fairly strong correlation with Perugini score (both ρ = .71, P = .006). Same held true for to-bone normalized values (both ρ = .75, P = .003). There was a great degree of overlap for quantitative values in patients with Perugini score 2 and 3. Quantitative 99mTc-DPD SPECT/CT in suspected ATTR CA patients is feasible and allows for a more accurate assessment of myocardial uptake.

Aim Positron Emission Tomography with Computed Tomography (PET/CT) has been proven to be useful in the definition of Radiotherapy (RT) target volume. In this regard, the present expert review summarizes existing data for pancreas, prostate, gynecological and rectum/anal cancer. Methods A comprehensive search of published original article was made, based on SCOPUS and PubMed database, selecting the paper that evaluated the role of PET/CT in the definition of RT volume. Results FDG-PET has an important and promising role for pancreatic cancer. Choline PET/CT could be useful for identifying high-risk volumes for prostate cancer; while PSMA PET/CT is still under evaluation. FDG PET/CT in gynecological cancers has been shown to impact external-beam RT planning. The role of FDG-PET for Gross Tumor volume identification is crucial, representing a useful and powerful tool for anal and rectal cancer. Conclusion Taken together, molecular and functional imaging approaches offer a major step to individualize radiotherapeutic approach.

Funding Acknowledgements Type of funding sources: None. Introduction Most 82Rubidium-(Rb)-Positron emission tomography (PET) studies for myocardial perfusion, dipyridamole was used as vasodilator. Less data is available for adenosine and regadenoson. Purpose Therefore, the aim was to evaluate the influence of adenosine and regadenoson on left ventricular ejection fraction (LVEF), myocardial blood flow (MBF) and hemodynamics in vasodilator 82Rb-PET. Methods Consecutive patients (n = 2299) with suspected or known coronary artery disease (CAD) undergoing 82Rb-PET were studied and compared according to CAD status and normal/abnormal PET (abnormal defined as summed stress score ≥4). Differences between stress and rest values (LVEF, MBF, hemodynamics) were calculated. The threshold of stress LVEF able to exclude a relevant ischemia (as defined by ≥10% myocardium ischemic based on SDS score) was assessed. Results Rest and stress LVEF differed significantly depending on CAD status and scan results. In patients with suspected CAD, rest/stress LVEF were 68 ± 12% and 73 ± 12% (p Conclusions Rest/stress LVEF, LVEF reserve and MBF values are lower in abnormal compared with normal scans. Adenosine and regadenoson seem to have similar effect on stress LVEF, MBF and hemodynamics. A stress LVEF ≥70% has a high NPV to exclude relevant ischemia.

Aim 18F-Fluorodeoxyglucose (FDG) PET imaging may play an important role in the restaging of patients with small-cell lung cancer (SCLC),, nevertheless, a systematic review of literature was still missing in this setting. The aim of this review was to summarize the evidence on literature regarding the utility of 18F-FDG PET imaging in restaging patients with SCLC. Methods A literature search was performed to retrieve original studies using 18F-FDG PET or 18F-FDG PET/computed tomography (CT) in a minimum of 10 patients with SCLC at restaging. Results The selected literature (17 studies) was discussed in four sections: detection rate, impact on management, prediction of prognosis and evaluation of the response to therapy. According to the literature, PET imaging may result in discordance with conventional imaging, mainly contrast-enhanced CT (ceCT), and detect additional lesions in a certain proportion of cases, leading to upstaging or downstaging. A variable level of disagreement between PET and conventional imaging has been reported also in the evaluation of response to therapy. A positive PET study is associated with shorter survival, especially in the presence of distant metastases. According to some studies, semiquantitative parameters are also inversely associated with overall survival and progression-free survival. Although the retrieved articles proved the utility of 18F-FDG PET imaging in each clinical setting, literature is still limited. Conclusions This review encourages the use of 18F-FDG PET imaging, especially in conjunction with ceCT in recurrent SCLC patients. Further level I evidence is needed to further assess the diagnostic and prognostic capability of 18F-FDG PET/ceCT findings in SCLC.

AIMS In most Rubidium-(Rb)-positron emission tomography (PET) studies, dipyridamole was used as vasodilator. The aim was to evaluate vasodilator PET left ventricular ejection fraction (LVEF), myocardial blood flow (MBF), hemodynamics, and the influence of adenosine and regadenoson on these variables. METHODS AND RESULTS Consecutive patients (N = 2299) with prior coronary artery disease (CAD) or no prior CAD undergoing adenosine/regadenoson 82Rb-PET were studied and compared according to CAD status and normal/abnormal PET (summed stress score 0-3 vs. ≥4). Rest and stress LVEF differed significantly depending on CAD status and scan results. In patients with no prior CAD, rest/stress LVEF were 68% and 72%, in patients with prior CAD 60% and 63%. LVEF during stress increased 5 ± 6% in normal compared to 1 ± 8% in abnormal PET (P

When 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) is performed to detect cardiac infection or inflammation, an adequate suppression of the physiological cardiac glucose metabolism plays a pivotal role to increase the interpretability and diagnostic reliability of 18F-FDG PET studies. Many studies report on different strategies to suppress the physiological cardiac glucose metabolism, including dietary preparations, pharmacological approaches, or a combination of both. We here present a comprehensive literature review of the proposed algorithms as well as a practical proposal to help nuclear medicine physicians in clinical practice.

Funding Acknowledgements Type of funding sources: None. Background Patients with clinical suspicion of obstructive coronary artery disease (OCAD) are frequently referred for myocardial perfusion imaging (MPI). However, many are at low-to-moderate risk, and have normal MPI. A predictive model may help to identify patients who may not need MPI. Purpose To develop novel prediction models for OCAD using machine learning and to compare their performance to a clinical score and to coronary artery calcium score (CACS) to identify patients without OCAD. Methods All consecutive patients undergoing 82Rb MPI positron emission tomography (PET) from 2016 to 2020 at our centre and without prior OCAD were enrolled. As clinical data, we recorded age, gender, body mass index, cardiovascular risk factors, chest pain type and dyspnoea. CACS was measured on low-dose computed tomography scans in Agatston units (AU). OCAD was defined as a summed stress score ≥4 in PET. The patient sample was randomly split into a 70% derivation sample and a 30% validation sample. Using 22 different machine learning algorithms, we developed models based on clinical data and based on clinical data + CACS to predict OCAD in the derivation sample, with manual optimization and multiple cross-validation. Then, models were evaluated in the validation sample to select the highest area under the receiver operating characteristic curve (AUC, with 95% confidence intervals). Finally, the best models were compared to the pre-test probability of the European Society of Cardiology (PTP-ESC) and to CACS alone in the complete sample for AUC and for patients predicted as free of OCAD, using cut-offs at 95% sensitivity and Fisher’s exact test. Results We included 1426 patients (1000 for derivation and 426 for validation). Mean age was 64.3 years (standard deviation 11.3), median CACS 58 AU (interquartile range 363), 780 patients were male (54.7%), and 303 had OCAD on PET (21.2%). In model development, "extreme gradient boosting" (XGBoost) emerged as the best algorithm to predict OCAD with clinical data (AUC 0.74 [0.68-0.80]), and with clinical data + CACS (AUC 0.84 [0.80-0.88], P < 0.001 vs. XGBoost clinical, P < 0.001 vs. logistic regression). In the complete sample, PTP-ESC had an AUC of 0.67 (0.64-0.70), XGBoost clinical 0.75 (0.72-0.78), CACS 0.81 (0.78-0.84), and XGBoost clinical + CACS 0.86 (0.84-0.88), with all P < 0.001 (see Figure). PTP-ESC identified 17% of total patients as OCAD-free with a negative predictive value (NPV) of 93%, XGBoost clinical 24% as OCAD-free with NPV 96%, CACS 33% as OCAD-free with NPV 97%, and XGBoost clinical + CACS 41% as OCAD-free with NPV 97%, with all P < 0.001. Conclusion In patients referred for MPI with PET, machine learning using XGBoost can generate powerful predictive models based on clinical data and CACS to identify patients free of OCAD, better than with PTP-ESC or CACS. Such models may be used as gatekeepers before MPI to reduce radiation burden for patients and costs for the health system. Abstract Figure. Prediction of OCAD in complete sample

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss National Foundation for Research Background Asymptomatic diabetic patients with an abnormal myocardial perfusion scintigraphy (MPS) are known to be at an increased risk of major cardiac events (MACE) at 2-years follow-up. It remains unclear whether this finding holds true even for a follow-up of 5 years. Methods four hundred patients with type-2 diabetes without coronary artery disease were evaluated clinically and with MPS and followed up for 5 years. Major adverse cardiovascular events (MACE) were defined as cardiac death, myocardial infarction or late coronary revascularization. Results An abnormal MPS (SSS≥4 or SSS≥2) was found in 87 patients (21.8%). MACE within 5 years occurred in 14 patients with abnormal MPS (16.1%) and in 22 with normal scan (1.7%, p = 0.009); 15 deaths were recorded (3.8%). Patients with normal MPS had lower rates of MACEs than patients with abnormal scans (p = 0.016) (Figure 1A + B). Patients with abnormal MPS who had undergone revascularization had a lower mortality rate and a better event free survival from MI and revascularization than patients with abnormal MPS who had either undergone medical therapy only or could not be revascularized (Figure 1C + D). Conclusions Patients with normal MPS have a low event rate and may not need retesting within 5 years (warranty period). Patients with an abnormal MPS have higher event rates and may benefit from a combined medical and revascularization approach. Abstract Figure 1 A-D

Background The Basel Asymptomatic High-Risk Diabetics’ Outcome Trial (BARDOT) demonstrated that asymptomatic diabetic patients with an abnormal myocardial perfusion scintigraphy (MPS) were at increased risk of major adverse cardiovascular events (MACEs) at 2-year follow-up. It remains unclear whether this finding holds true even for a longer follow-up. Methods Four hundred patients with type 2 diabetes, neither history nor symptoms of coronary artery disease (CAD), were evaluated clinically and with MPS. Patients were followed up for 5 years. Major adverse cardiovascular events (MACEs) were defined as all-cause death, myocardial infarction, or late coronary revascularization. Results At baseline, an abnormal MPS (SSS ≥ 4 or SDS ≥ 2) was found in 87 of 400 patients (22%). MACE within 5 years occurred in 14 patients with abnormal MPS (16.1%) and in 22 with normal scan (1.7%), p = 0.009; 15 deaths were recorded. Patients with completely normal MPS (SSS and SDS = 0) had lower rates of MACEs than patients with abnormal scans (2.5% vs. 7.0%, p = 0.032). Patients with abnormal MPS who had undergone revascularization had a lower mortality rate and a better event-free survival from MI and revascularization than patients with abnormal MPS who had either undergone medical therapy only or could not be revascularized (p = 0.002). Conclusions MPS may have prognostic value in asymptomatic diabetic patients at high cardiovascular risk over a follow-up period of 5 years. Patients with completely normal MPS have a low event rate and may not need retesting within 5 years. Patients with an abnormal MPS have higher event rates and may benefit from a combined medical and revascularization approach.

Background With the present evolution of demographics and medical costs, algorithms able to predict the likelihood of coronary artery disease (CAD) may be valuable gatekeepers before advanced cardiac testing, but their value is unknown. Purpose We assessed whether clinical data, with or without coronary artery calcium score (CACS), combined with machine learning algorithms can predict ischaemia in position emission tomography (PET). Methods All consecutive patients undergoing 82Rb myocardial perfusion PET with CACS from 2016 to 2019 at our hospital were enrolled. Patients with known CAD were excluded. As clinical data, we used demographics, classical risk factors, chest pain type, dyspnoea and electrocardiogram with pathological Q waves or abnormal repolarization. CACS was measured from low-dose computed tomography scans in Agatston units (AU). Ischaemia was defined as a summed difference score ≥4 in PET. As prediction models, we compared the classical logistic regression, regularized regression (elastic net), decision trees, random forests and a boosting algorithm. The patient cohort was split into a 80% training cohort and a 20% test cohort. Models were carefully optimized with 10-fold cross-validation on the training cohort and applied to the test cohort to assess area under the curve (AUC) for ischaemia with 95% confidence intervals in receiver operating characteristic (ROC) analysis. Results We included 927 patients, of which 743 were in the training cohort and 184 in the test cohort. Mean age was 64.3±11.1 years, median CACS 55 AU (interquartile range 358) and 179 patients had ischaemia (19.3%). In the test cohort, we found the following AUC (see Figure): logistic regression with clinical data 0.62 (0.52–0.72, light blue) and CACS 0.73 (0.63–0.82, dark blue) with P=0.012, elastic net regression with clinical data 0.63 (0.54–0.73, light violet) and CACS 0.81 (0.75–0.88, dark violet) with P Conclusion Prediction of myocardial ischaemia is limited with clinical data only, but can be greatly improved with the use of CACS and machine learning with elastic net regression or a boosting algorithm, reaching a good performance. This approach could be further developed as a gatekeeper to select appropriate patients for further cardiac imaging. ROC curves: Prediction on test cohort Funding Acknowledgement Type of funding source: None

In this review, the performance of fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in the diagnostic workup of pancreatic ductal adenocarcinoma (PDAC) is evaluated. A comprehensive literature search up to September 2020 was performed, selecting studies with the presence of: sample size ≥10 patients and index test (i.e., “FDG” or “18F-FDG” AND “pancreatic adenocarcinoma” or “pancreas cancer” AND “PET” or “positron emission tomography”). The methodological quality was evaluated using the revised quality assessment of diagnostic accuracy studies (QUADAS-2) tool and presented according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Basic data (authors, year of publication, country and study design), patients’ characteristics (number of enrolled subjects and age), disease phase, type of treatment and grading were retrieved. Forty-six articles met the adopted research criteria. The articles were divided according to the considered clinical context. Namely, besides conventional anatomical imaging, such as computed tomography (CT) and magnetic resonance imaging (MRI), molecular imaging with FDG PET/CT is an important tool in PDAC, for all disease stages. Further prospective studies will be necessary to confirm the cost-effectiveness of such imaging techniques by testing its real potential improvement in the clinical management of PDAC.

Background To relate findings of qualitative evaluation of first-pass perfusion-CMR and anatomical evaluation on coronary angiography (CA) to the reference standard of quantitative perfusion, cardiac PET, in patients with suspected or known stable coronary artery disease (CAD). Methods and Results Forty-one patients referred for CA due to suspected stable CAD, prospectively performed adenosine stress/rest first-pass perfusion-CMR as well as 13N-NH3 PET on the same day, 4 ± 3 weeks before CA. Angiographers were blinded to PET and CMR results. Regional myocardial flow reserve (MFR) < 2.0 on PET was considered pathological. Vessel territories with stress-induced ischemia by CMR or vessels with stenosis needing revascularization had a significantly lower MFR compared to those with no regional stress-induced ischemia or vessels not needing revascularization (P < 0.001). In 4 of 123 vessel territories with stress-induced ischemia by CMR, PET showed a normal MFR. In addition, 12 of 123 vessels that underwent intervention showed normal MFR assessed by PET. Conclusion The limited performance of qualitative assessment of presence of stable CAD with CMR and CA, when related to quantitative 13N-NH3 cardiac PET, shows the need for fully quantitative assessment of myocardial perfusion and the use of invasive flow reserve measurements for CA, to confirm the need of elective revascularization. Electronic supplementary material The online version of this article (10.1007/s12350-018-01555-1) contains supplementary material, which is available to authorized users.

The pathological accumulation of different peptides is the common base of many neurodegenerative processes, such as Alzheimer’s disease (AD). AD is characterized by amyloid deposits which may cause alterations in neurotransmission, activation of inflammatory mechanisms, neuronal death and cerebral atrophy. Diagnosis in vivo is challenging as the criteria rely mainly on clinical manifestations, which become evident only in a late stage of the disease. While AD can currently be definitively confirmed by postmortem histopathologic examination, in vivo imaging may improve the clinician's ability to identify AD at the earliest stage. In this regard, the detection of cerebral amyloid plaques with positron emission tomography (PET) is likely to improve diagnosis and allow for a prompt start of an effective therapy. Many PET imaging probes for AD-specific pathological modifications have been developed and proved effective in detecting amyloid deposits in vivo. We here review the current knowledge on PET imaging in the detection of amyloid deposits and their application in the diagnosis of AD.

Life-threatening ventricular arrhythmias (VA) are a major cause of death in patients with congestive heart failure (HF). Among various factors, the sympathetic nervous system may give rise to VA in several pathophysiological pathways due to an impaired function of presynaptic sympathetic nerve terminals. Positron emission tomography (PET) with labeled catecholamine analogues represents a reliable tool to assess the sympathetic innervation activity. This review aims at summarising the most relevant and recent literature findings on the current role of PET in the evaluation of cardiac sympathetic activity in patients with heart failure. A comprehensive literature search strategy using PubMed databases was carried out looking for articles on the role of Positron emission tomography/Computed Tomography (PET/CT) in the assessment of myocardial sympathetic innervation in patients with heart failure. The literature search limited to the last 5 years retrieved 40 papers. Most of the papers dealt with PET studies with 11C-HED. 19 pre-clinical, first-in-human and clinical studies highlighting the current role of PET and future perspectives resulted eligible for inclusion in the present review. The assessment of myocardial sympathetic activity in patients with heart failure with PET will play a pivotal role in clinical practice. Its capability to predict the occurrence of life-threatening VA and the effectiveness of resynchronization therapy makes this technique ideal in the era of personalized medicine.

We discuss the current role of PET/CT in all phases of disease in RCC, potential advancements in the diagnostic and prognostic work up, including future perspectives regarding novel radiopharmaceuticals agents. A comprehensive search strategy was used based on SCOPUS and PubMed databases. From all studies published in English, we selected—for this Expert Review—the most relevant articles evaluating the use of PET/CT for the diagnostic assessment of patients with renal cancer. The use of PET/CT in RCC is still very limited due to low sensitivity in some cases, fragmentary data, and scarce numerosity of clinical trials in this setting. However, new potential applications have been proposed for the staging and restaging process of RCC with potential prognostic role, as well new radiotracers for the evaluation of tumor proliferation, neoangiogenesis, and to assess the response to target therapies. In high-risk patients, 18F-FDG PET/CT may be useful for preoperative staging, in the restaging process and to monitor targeted molecular therapies such as tyrosine kinase inhibitors. A new scenario could be open for risk stratification assessment using 18F-FDG PET/CT. New radiopharmaceuticals agents have been proposed; however, further trials are warranted to establish their role in clinical setting.