Including myocardial flow reserve by PET in prediction models: Ready to fly?

N

Relation between myocardial blood flow and cardiac events in diabetic patients with suspected coronary artery disease and normal myocardial perfusion imaging

Background: We assessed the prognostic value of structural abnormalities and coronary vasodilator function in diabetic patients referred to a PET/CT for suspected coronary artery disease (CAD). Methods: We studied 451 diabetics and 451 nondiabetics without overt CAD and normal myocardial perfusion. Myocardial blood flow (MBF) was computed from the dynamic rest and stress imaging. Myocardial flow reserve (MFR) was defined as ratio of hyperemic to baseline MBF and was considered reduced when < 2. Results: During a mean follow-up of 44 months 33 events occurred. Annualized event rate (AER) was higher in diabetic than nondiabetic patients (1.4% vs 0.3%, P < .001). Diabetic patients with reduced MFR had higher AER compared to those with preserved MFR (3.3% vs 0.4%, P < .001). At Cox analysis, age, BMI and reduced MFR were independent predictors of events in diabetic patients. Patients with diabetes and reduced MFR had lower event-free survival compared to nondiabetic patients and MFR < 2 (P < .001). Event-free survival was similar in patients with diabetes and normal MFR and those without diabetes and reduced MFR. Conclusions: Diabetic patients with reduced MFR had higher AER and lower event-free survival compared to those with preserved MFR and to nondiabetic patients

Quantification of Coronary Artery Atherosclerotic Burden and Muscle Mass: Exploratory Comparison of Two Freely Available Software Programs

Abstract: Coronary artery calcification and sarcopenia may have a relevant prognostic impact in oncological and non‐oncological patients. The use of freeware software is promising for quantitative evaluation of these parameters after whole‐body positron emission tomography (PET)/computed tomography (CT) and might be useful for one‐stop shop risk stratification without additional radiation ionizing burden and further charges to health care costs. In this study, we compared two semiautomatic freeware software tools (Horos Medical Image software and LIFEx) for the assessment of coronary artery calcium (CAC) score and muscle mass in 40 patients undergoing whole‐body PET/CT. The muscle areas obtained by the two software programs were comparable, showing high correlation with Lin’s concordance coefficient (0.9997; 95% confidence intervals: 0.9995–0.9999) and very good agreement with Bland–Altman analysis (mean difference = 0.41 cm2, lower limit = −1.06 cm2, upper limit = 1.89) was also found. For CAC score, Lin’s concordance correlation coefficient was 0.9976 (95% confidence intervals: 0.9965–0.9984) and in a Bland–Altman analysis an increasing mean difference from 8 to 78 by the mean values (intercept = −0.050; slope = 0.054; p < 0.001) was observed, with a slight overestimation of Horos CAC score as compared to LIFEx, likely due to a different calculation method of the CAC score, with the ROI being equal for the two software programs. Our results demonstrated that off‐line analysis performed with freeware software may allow a comprehensive evaluation of the oncological patient, making available the evaluation of parameters, such as muscle mass and calcium score, that may be relevant for the staging and prognostic stratification of these patients, beside standard data obtained by PET/CT imaging. For this purpose, the Horos and LIFEx software seem to be interchangeable

Impact of COVID-19 pandemic on 2-[18F]FDG PET/CT imaging work-flow in a single medical institution: comparison among the three Italian waves

Purpose: To compare the impact of COVID-19 pandemic on 2-[18F]FDG PET/CT imaging work-flow during the three waves in a medical institution of southern of Italy. Methods: We retrospectively reviewed the numbers and results of 2-[18F]FDG PET/CT studies acquired during the following three periods of the COVID-19 waves: 1) February 3-April 30, 2020; 2) October 15, 2020–January 15, 2021; and 3) January 18-April 16, 2021. Results: A total of 861 PET/CT studies in 725 patients (388 men, mean age 64 +/- 4 years) was acquired during the three waves of COVID-19 pandemic. The majority (94%) was performed for diagnosis/staging (n = 300) or follow-up (n = 512) of neoplastic diseases. The remaining 49 studies (6%) were acquired for non-oncological patients. The distribution of number and type of clinical indications for PET/CT studies in the three waves were comparable (p < 0.06). Conversely, the occurrence of patients positive for COVID-19 infection progressively increased (p < 0.0001) from the first to third wave; in particular, patients with COVID-19 had active infection before PET/CT study as confirmed by molecular oro/nasopharyngeal swab. Conclusion: Despite the restrictive medical measures for the emergency, the number of 2-[18F]FDG PET/CT studies was unchanged during the three waves guaranteeing the diagnostic performance of PET/CT imaging for oncological patients

Prognostic value of heart rate reserve in patients with suspected coronary artery disease undergoing stress myocardial perfusion imaging

Background. Chronotropic incompetence is common in patients with cardiovascular disease and is associated with increased risk of adverse events. We assessed the incremental prognostic value of heart rate reserve (HRR) over stress myocardial perfusion single-photon emission computed tomography (MPS) findings in patients with suspected coronary artery disease (CAD). Methods. We studied 866 patients with suspected CAD undergoing exercise stress-MPS as part of their diagnostic program. The primary study endpoint was all-cause mortality. All patients were followed for at least 5 years. HRR was calculated as the difference between peak exercise and resting HR, divided by the difference of age-predicted maximal and resting HR and expressed as percentage. Results. During 7 years follow-up, 61 deaths occurred, with a 7% cumulative event rate. Patients experiencing death were older (P < .001), and had a higher prevalence of male gender (P < .001) and diabetes (P < .05). Patients with event also had lower values of HRR (65% ± 27% vs 73% ± 18%, P < .0001) and higher prevalence of stress-induced myocardial ischemia (25% vs 8%, P < .0001). Male gender, HRR and stress-induced ischemia were independent predictors of all-cause mortality (all P < .01). HRR improved the prognostic power of a model including clinical data and MPS findings, increasing the global v2 from 66 to 82 (P < .005). Conclusions. Chronotropic incompetence has independent and incremental prognostic value in predicting all-cause mortality in patients with suspected CAD undergoing exercise stress-MPS. Hence, the evaluation of HRR may further improve patients’ risk stratification

R0 surgical resection of giant dedifferentiated retroperitoneal liposarcomas in the COVID era with and without nephrectomy: A case report

: Retroperitoneal sarcomas (RPSs) are rare findings that can grow into large masses without eliciting severe symptoms. At present, surgical resection is the only radical therapy, whenever it can be performed with the aim to achieve a complete removal of the tumor. The present report describes two consecutive cases of RPSs that resulted in dedifferentiated liposarcomas (DDLPSs) and these patients underwent R0 surgical resection with and without a nephron-sparing procedure. The diagnostic workup, the surgical approach, the impact of late surgical management due to the COVID pandemic and the latest literature on the topic are discussed and analyzed. The patients, who refused to undergo any medical examination during the prior 2 years due to the COVID pandemic, were admitted to Federico II University Hospital (Naples, Italy) complaining about weight loss and general abdominal discomfort. In the first case, a primitive giant abdominal right neoplasm of retroperitoneal origin enveloping and medializing the right kidney was observed. The second patient had a similar primitive retroperitoneal giant left neoplasm, which did not affect the kidney. Given the characteristics of the masses and the absence of distant metastases, after a multidisciplinary discussion, radical surgical removal was carried out for both patients. The lesions appeared well-defined from the surrounding tissues, and markedly compressed all the adjacent organs, without signs of infiltration. In the first patient, the right kidney was surrounded and undetachable from the tumor and it was removed en bloc with the mass. The second patient benefited from a nephron-sparing resection, due to the existence of a clear cleavage plane. The postoperative courses were uneventful. Both the histological examinations were oriented towards a DDLPS and both patients benefited from adjuvant chemotherapy. In conclusion, the treatment of giant RPS is still challenging and requires multidisciplinary treatment as well as, when possible, radical surgical removal. The lack of tissue infiltration and the avoidance of excision or reconstruction of major organs (including the kidney) could lead to an easier postoperative course and an improved prognosis. When possible, surgical management of recurrences or incompletely resected masses must be pursued. Since the COVID pandemic caused limited medicalization of a number of population groups and delayed diagnosis of other oncologic diseases, an increased number of DDLPSs could be expected in the near future

State of the art of 18F-FDG PET/CT application in inflammation and infection: a guide for image acquisition and interpretation

Aim The diagnosis, severity and extent of a sterile inflammation or a septic infection could be challenging since there is not one single test able to achieve an accurate diagnosis. The clinical use of 18F-fluorodeoxyglucose ([F-18]FDG) positron emission tomography/computed tomography (PET/CT) imaging in the assessment of inflammation and infection is increasing worldwide. The purpose of this paper is to achieve an Italian consensus document on [F-18]FDG PET/CT or PET/MRI in inflammatory and infectious diseases, such as osteomyelitis (OM), prosthetic joint infections (PJI), infective endocarditis (IE), prosthetic valve endocarditis (PVE), cardiac implantable electronic device infections (CIEDI), systemic and cardiac sarcoidosis (SS/CS), diabetic foot (DF), fungal infections (FI), tuberculosis (TBC), fever and inflammation of unknown origin (FUO/IUO), pediatric infections (PI), inflammatory bowel diseases (IBD), spine infections (SI), vascular graft infections (VGI), large vessel vasculitis (LVV), retroperitoneal fibrosis (RF) and COVID-19 infections. Methods In September 2020, the inflammatory and infectious diseases focus group (IIFG) of the Italian Association of Nuclear Medicine (AIMN) proposed to realize a procedural paper about the clinical applications of [F-18]FDG PET/CT or PET/MRI in inflammatory and infectious diseases. The project was carried out thanks to the collaboration of 13 Italian nuclear medicine centers, with a consolidate experience in this field. With the endorsement of AIMN, IIFG contacted each center, and the pediatric diseases focus group (PDFC). IIFG provided for each team involved, a draft with essential information regarding the execution of [F-18]FDG PET/CT or PET/MRI scan (i.e., indications, patient preparation, standard or specific acquisition modalities, interpretation criteria, reporting methods, pitfalls and artifacts), by limiting the literature research to the last 20 years. Moreover, some clinical cases were required from each center, to underline the teaching points. Time for the collection of each report was from October to December 2020. Results Overall, we summarized 291 scientific papers and guidelines published between 1998 and 2021. Papers were divided in several sub-topics and summarized in the following paragraphs: clinical indications, image interpretation criteria, future perspectivess and new trends (for each single disease), while patient preparation, image acquisition, possible pitfalls and reporting modalities were described afterwards. Moreover, a specific section was dedicated to pediatric and PET/MRI indications. A collection of images was described for each indication. Conclusions Currently, [F-18]FDG PET/CT in oncology is globally accepted and standardized in main diagnostic algorithms for neoplasms. In recent years, the ever-closer collaboration among different European associations has tried to overcome the absence of a standardization also in the field of inflammation and infections. The collaboration of several nuclear medicine centers with a long experience in this field, as well as among different AIMN focus groups represents a further attempt in this direction. We hope that this document will be the basis for a "common nuclear physicians' language" throughout all the country

Comparison of the prognostic value of SPECT after nitrate administration and metabolic imaging by PET in patients with ischaemic left ventricular dysfunction

PURPOSE: We compared the prognostic value of 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) after nitrate administration and positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in patients with ischaemic left ventricular (LV) dysfunction. METHODS: Eighty-nine patients with previous myocardial infarction and LV dysfunction (LV ejection fraction 33 +/-10%) underwent 99mTc-tetrofosmin SPECT under control conditions (baseline) and after sublingual administration of 10 mg of isosorbide dinitrate (nitrate). Within 1 week, all patients underwent PET imaging with 18F-FDG. Four patients were excluded because of inadequate FDG uptake caused by severe diabetes. Follow-up data were obtained by phone contact with patients and by review of hospital or physicians' records. Cardiac death, myocardial infarction and late revascularisation for unstable angina were considered as events. Follow-up data were not available in three patients. Follow-up was 96% complete at a mean period of 29 +/- 19 months. RESULTS: At baseline SPECT, 59 (72%) patients had evidence of viable myocardium, while 23 did not. Of these latter patients, 12 (52%) demonstrated viable myocardium after nitrate and 13 (56%) had preserved metabolic activity. Cardiac events (cardiac death, myocardial infarction and late revascularisation for unstable angina) occurred in 24 (29%) patients. Event-free survival was similar in patients with and patients without viable myocardium at baseline SPECT (p = 0.8). In contrast, event-free survival was lower in patients with viable myocardium at nitrate SPECT and PET compared to those without viable myocardium (both p<0.05). CONCLUSION: In patients with ischaemic LV dysfunction, the prognostic value of SPECT imaging after nitrate is comparable to that of PET metabolic imaging

Emerging Role of Nuclear Medicine in Prostate Cancer: Current State and Future Perspectives

Prostate cancer is the most frequent epithelial neoplasia after skin cancer in men starting from 50 years and prostate-specific antigen (PSA) dosage can be used as an early screening tool. Prostate cancer imaging includes several radiological modalities, ranging from ultrasonography, computed tomography (CT), and magnetic resonance to nuclear medicine hybrid techniques such as single-photon emission computed tomography (SPECT)/CT and positron emission tomography (PET)/CT. Innovation in radiopharmaceutical compounds has introduced specific tracers with di- agnostic and therapeutic indications, opening the horizons to targeted and very effective clinical care for patients with prostate cancer. The aim of the present review is to illustrate the current knowledge and future perspectives of nuclear medicine, including stand-alone diagnostic techniques and theragnostic approaches, in the clinical management of patients with prostate cancer from initial staging to advanced disease

Early 18F-FDG uptake as a reliable imaging biomarker of T790M-mediated resistance but not MET amplification in non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors

Background: The two main mechanisms of resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) are the occurrence of T790M secondary mutation in the kinase domain of EGFR and METamplification. The aim of the present study was to test whether early changes of 18F fluorodeoxyglucose (18F-FDG) uptake in animal models bearing erlotinib-resistant NSCLC may have different imaging patterns of response to erlotinib depending on the molecular mechanisms underlying resistance. Animal tumor models were developed using NSCLC H1975 cells bearing the T790M mutation and H1993 cells with MET amplification. Nude mice bearing erlotinib-resistant H1975 and H1993 xenografts (four animals for each cell line and for each treatment) were subjected to 18F-FDG PET/CT scan before and immediately after treatment (50 mg/kg p.o. for 3 days) with erlotinib, WZ4002, crizotinib, or vehicle. A three-dimensional region of interest analysis was performed to determine the percent change of 18F-FDG uptake in response to treatment. At the end of the imaging studies, tumors were removed and analyzed for glycolytic and mitochondrial proteins as well as levels of cyclin D1. Results: Imaging studies with 18F-FDG PET/CT in H1975 tumor-bearing mice showed a reduction of 18F-FDG uptake of 25.87 % ± 8.93 % after treatment with WZ4002 whereas an increase of 18F-FDG uptake up to 23.51 % ± 9.72 % was observed after treatment with erlotinib or vehicle. Conversely, H1993 tumors showed a reduction of 18F-FDG uptake after treatment with both crizotinib (14.70 % ± 1.30 %) and erlotinib (18.40 % ± 9.19 %) and an increase of tracer uptake in vehicle-treated (56.65 % ± 5.65 %) animals. The in vivo reduction of 18F-FDG uptake was always associated with downregulation of HKII and p-PKM2 Tyr105 glycolytic proteins and upregulation of mitochondrial complexes (subunits I–IV) in excised tumors. Conclusions: 18F-FDG uptake is a reliable imaging biomarker of T790M-mediated resistance and its reversal in NSCLC whereas it may not be accurate in the detection of MET-mediated resistance