Coronary fluorine-18-sodium fluoride uptake is increased in healthy adults with an unfavorable cardiovascular risk profile: results from the CAMONA study.

OBJECTIVE: Coronary artery fluorine-18-sodium fluoride (F-NaF) uptake reflects coronary artery calcification metabolism and is considered to be an early prognostic marker of coronary heart disease. This study evaluated the relationship between coronary artery F-NaF uptake and cardiovascular risk in healthy adults at low cardiovascular risk. PARTICIPANTS AND METHODS: Study participants underwent blood pressure measurements, blood analyses, and coronary artery F-NaF PET/CT imaging. In addition, the 10-year risk for the development of cardiovascular disease, on the basis of the Framingham Risk Score, was estimated. Multivariable linear regression evaluated the dependence of coronary artery F-NaF uptake on cardiovascular risk factors. RESULTS: We recruited 89 (47 men, 42 women) healthy adults aged 21-75 years. Female sex (0.34 kBq/ml; P=0.009), age (0.16 kBq/ml per SD; P=0.002), and BMI (0.42 kBq/ml per SD; P<0.001) were independent determinants of increased coronary artery F-NaF uptake (adjusted R=0.21; P<0.001). Coronary artery F-NaF uptake increased linearly according to the number of cardiovascular risk factors present (P<0.001 for a linear trend). The estimated 10-year risk for the development of cardiovascular disease was on average 2.4 times higher in adults with coronary artery F-NaF uptake in the highest quartile compared with those in the lowest quartile of the distribution (8.0 vs. 3.3%, P<0.001). CONCLUSION: Our findings indicate that coronary artery F-NaF PET/CT imaging is feasible in healthy adults at low cardiovascular risk and that an unfavorable cardiovascular risk profile is associated with a marked increase in coronary artery F-NaF uptake.

Reference values for fluorine-18-fluorodeoxyglucose and fluorine-18-sodium fluoride uptake in human arteries: a prospective evaluation of 89 healthy adults.

OBJECTIVE: Reference values of fluorine-18-fluorodeoxyglucose (F-FDG) and fluorine-18-sodium fluoride (F-NaF) uptake in human arteries are unknown. The aim of this study was to determine age-specific and sex-specific reference values of arterial F-FDG and F-NaF uptake. PARTICIPANTS AND METHODS: Uptake of F-FDG and F-NaF was determined in the ascending aorta, aortic arch, and descending thoracic aorta. In addition, F-FDG uptake was determined in the carotid arteries and F-NaF uptake was determined in the coronary arteries. Arterial F-FDG and F-NaF uptake were quantified as the blood pool subtracted maximum activity concentration in kBq/ml (BS F-FDGmax and BS F-NaFmax, respectively). In addition to determining reference values, we evaluated the influence of age and sex on BS F-FDGmax and BS F-NaFmax. RESULTS: Arterial F-FDG and F-NaF uptake was assessed in 89 healthy adults aged 21-75 years (mean age: 44±14 years, 53% men). Both BS F-FDGmax and BS F-NaFmax increased with age. BS F-FDGmax increased with age in the descending aorta (ß=0.28; P=0.003), whereas BS F-NaFmax increased with age in the ascending aorta (ß=0.18; P<0.001), aortic arch (ß=0.19; P=0.006), descending aorta (ß=0.33; P<0.001), and coronary arteries (ß=0.20; P=0.009), respectively. BS F-FDGmax and BS F-NaFmax were not influenced by sex, except for BS F-FDGmax in the ascending aorta. CONCLUSION: Prospective evaluation of 89 healthy adults generated age-specific and sex-specific reference values of arterial F-FDG and F-NaF uptake. Our findings indicate that arterial F-FDG and F-NaF uptake tend to increase with age.

Thoracic aorta calcification but not inflammation is associated with increased cardiovascular disease risk: results of the CAMONA study.

PURPOSE: Arterial inflammation and vascular calcification are regarded as early prognostic markers of cardiovascular disease (CVD). In this study we investigated the relationship between CVD risk and arterial inflammation (18F-FDG PET/CT imaging), vascular calcification metabolism (Na18F PET/CT imaging), and vascular calcium burden (CT imaging) of the thoracic aorta in a population at low CVD risk. METHODS: Study participants underwent blood pressure measurements, blood analyses, and 18F-FDG and Na18F PET/CT imaging. In addition, the 10-year risk for development of CVD, based on the Framingham risk score (FRS), was estimated. CVD risk was compared across quartiles of thoracic aorta 18F-FDG uptake, Na18F uptake, and calcium burden on CT. RESULTS: A total of 139 subjects (52 % men, mean age 49 years, age range 21 - 75 years, median FRS 6 %) were evaluated. CVD risk was, on average, 3.7 times higher among subjects with thoracic aorta Na18F uptake in the highest quartile compared with those in the lowest quartile of the distribution (15.5 % vs. 4.2 %; P < 0.001). CVD risk was on average, 3.7 times higher among subjects with a thoracic aorta calcium burden on CT in the highest quartile compared with those in the lowest two quartiles of the distribution (18.0 % vs. 4.9 %; P < 0.001). CVD risk was similar in subjects in all quartiles of thoracic aorta 18F-FDG uptake. CONCLUSION: Our findings indicate that an unfavourable CVD risk profile is associated with marked increases in vascular calcification metabolism and vascular calcium burden of the thoracic aorta, but not with arterial inflammation.

3D black blood VISTA vessel wall cardiovascular magnetic resonance of the thoracic aorta wall in young, healthy adults: reproducibility and implications for efficacy trial sample sizes: a cross-sectional study.

BACKGROUND: Pre-clinical detection of atherosclerosis enables personalized preventive strategies in asymptomatic individuals. Cardiovascular magnetic resonance (CMR) has evolved as an attractive imaging modality for studying atherosclerosis in vivo. Yet, the majority of aortic CMR studies and proposed sequences to date have been performed at 1.5 tesla using 2D BB techniques and a slice thickness of 4-5 mm. Here, we evaluate for the first time the reproducibility of an isotropic, T1-weighted, three-dimensional, black-blood, CMR VISTA sequence (3D-T1-BB-VISTA) for quantification of aortic wall characteristics in healthy, young adults. METHODS: In 20 healthy, young adults (10 males, mean age 31.3 years) of the AMBITYON cohort study the descending thoracic aorta was imaged with a 3.0 T MR system using the 3D-T1-BB-VISTA sequence. The inter-scan, inter-rater and intra-rater reproducibility of aortic lumen, total vessel and wall area and mean and maximum wall thickness was evaluated using Bland-Altman analyses and Intraclass Correlation Coefficients (ICC). Based on these findings, sample sizes for detecting differences in aortic wall characteristics between groups were calculated. RESULTS: For each studied parameter, the inter-scan, inter-rater and intra-rater reproducibility was excellent as indicated by narrow limits of agreement and high ICCs (ranging from 0.76 to 0.99). Sample sizes required to detect a 5% difference in aortic wall characteristics between two groups were 203, 126, 136, 68 and 153 per group for lumen area, total vessel area and vessel wall area and for mean and maximum vessel wall thickness, respectively. CONCLUSION: The 3D-T1-BB-VISTA sequence provides excellent reproducibility for quantification of aortic wall characteristics and can detect small differences between groups with reasonable sample sizes. Hence, it may be a valuable tool for assessment of the subtle vascular wall changes of early atherosclerosis in asymptomatic populations.

Quantifying [¹8F]fluorodeoxyglucose uptake in the arterial wall: the effects of dual time-point imaging and partial volume effect correction.

PURPOSE: The human arterial wall is smaller than the spatial resolution of current positron emission tomographs. Therefore, partial volume effects should be considered when quantifying arterial wall (18)F-FDG uptake. We evaluated the impact of a novel method for partial volume effect (PVE) correction with contrast-enhanced CT (CECT) assistance on quantification of arterial wall (18)F-FDG uptake at different imaging time-points. METHODS: Ten subjects were assessed by CECT imaging and dual time-point PET/CT imaging at approximately 60 and 180 min after (18)F-FDG administration. For both time-points, uptake of (18)F-FDG was determined in the aortic wall by calculating the blood pool-corrected maximum standardized uptake value (cSUVMAX) and cSUVMEAN. The PVE-corrected SUVMEAN (pvcSUVMEAN) was also calculated using (18)F-FDG PET/CT and CECT images. Finally, corresponding target-to-background ratios (TBR) were calculated. RESULTS: At 60 min, pvcSUVMEAN was on average 3.1 times greater than cSUVMAX (P < .0001) and 8.5 times greater than cSUVMEAN (P < .0001). At 180 min, pvcSUVMEAN was on average 2.6 times greater than cSUVMAX (P < .0001) and 6.6 times greater than cSUVMEAN (P < .0001). CONCLUSION: This study demonstrated that CECT-assisted PVE correction significantly influences quantification of arterial wall (18)F-FDG uptake. Therefore, partial volume effects should be considered when quantifying arterial wall (18)F-FDG uptake with PET.

Effects of age and cardiovascular risk factors on (18)F-FDG PET/CT quantification of atherosclerosis in the aorta and peripheral arteries.

OBJECTIVE: To quantify fluorine-18 fluorodeoxyglucose ((18)F-FDG) uptake in the aorta and peripheral arteries and assess the variation of (18)F-FDG uptake with age and cardiovascular risk factors. METHODS: The subject population of this retrospective study comprises melanoma patients who underwent whole-body (18)F-FDG PET/CT scans. The patients' medical records were examined for cardiovascular risk factors and for a history of coronary artery disease or peripheral artery disease. Fluorine-18-FDG uptake in the peripheral arteries (iliac and femoral) and aorta was semi-quantified as a weighted-average mean standardized uptake value (wA-SUVmean), while background noise was accounted for by measuring mean venous blood pool SUV (V-SUVmean) in the superior vena cava. Atherosclerosis was semi-quantified by the tissue-to-background ratio (TBR) (wA-SUVmean divided by V-SUVmean). A regression model and t-test were used to evaluate the effect of age and location on the degree of atherosclerosis. To assess the effect of cardiovascular risk factors on atherosclerotic burden, the wA-SUVmean of patients with at least one of these risk factors was compared to that of patients without any risk factors. RESULTS: A total of 76 patients (46 men, 30 women; 22-91 years old) were included in this study. The average TBR of the aorta and peripheral arteries were 2.68 and 1.43, respectively, and increased with age in both locations. In regression analysis, the beta coefficients of age for TBR in the aorta and peripheral arteries were 0.55 (P<0.001) and 0.03 (P<0.001), respectively. In all age groups, the TBR of the aorta was significantly greater than that of the peripheral arteries. The Pearson correlation coefficients between the four age groups and the TBR of the aorta and peripheral arteries were 0.83 (P<0.001) and 0.75 (P<0.001), respectively. The wA-SUVmean of patients with cardiovascular risk factors was only significant (P<0.05) in the aorta. CONCLUSION: An increase in (18)F-FDG uptake was observed in the peripheral arteries and aorta with increasing age. Cardiovascular risk factors were significantly correlated with (18)F-FDG uptake in aorta. The early detection of atherosclerosis with (18)F-FDG PET may allow for the initiation of preventative interventions prior to the manifestation of significant structural abnormalities or symptoms of disease.

Diagnostic accuracy of stress myocardial perfusion imaging compared to invasive coronary angiography with fractional flow reserve meta-analysis.

BACKGROUND: Hemodynamically significant coronary artery disease is an important indication for revascularization. Stress myocardial perfusion imaging is a noninvasive alternative to invasive fractional flow reserve for evaluating hemodynamically significant coronary artery disease. The aim was to determine the diagnostic accuracy of myocardial perfusion imaging by single-photon emission computed tomography, echocardiography, MRI, positron emission tomography, and computed tomography compared with invasive coronary angiography with fractional flow reserve for the diagnosis of hemodynamically significant coronary artery disease. METHODS AND RESULTS: The meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. PubMed, EMBASE, and Web of Science were searched until May 2014. Thirty-seven studies, reporting on 4721 vessels and 2048 patients, were included. Meta-analysis yielded pooled sensitivity, pooled specificity, pooled likelihood ratios (LR), pooled diagnostic odds ratio, and summary area under the receiver operating characteristic curve. The negative LR (NLR) was chosen as the primary outcome. At the vessel level, MRI (pooled NLR, 0.16; 95% confidence interval [CI], 0.13-0.21) was performed similar to computed tomography (pooled NLR, 0.22; 95% CI, 0.12-0.39) and positron emission tomography (pooled NLR, 0.15; 95% CI, 0.05-0.44), and better than single-photon emission computed tomography (pooled NLR, 0.47; 95% CI, 0.37-0.59). At the patient level, MRI (pooled NLR, 0.14; 95% CI, 0.10-0.18) performed similar to computed tomography (pooled NLR, 0.12; 95% CI, 0.04-0.33) and positron emission tomography (pooled NLR, 0.14; 95% CI, 0.02-0.87), and better than single-photon emission computed tomography (pooled NLR, 0.39; 95% CI, 0.27-0.55) and echocardiography (pooled NLR, 0.42; 95% CI, 0.30-0.59). CONCLUSIONS: Stress myocardial perfusion imaging with MRI, computed tomography, or positron emission tomography can accurately rule out hemodynamically significant coronary artery disease and can act as a gatekeeper for invasive revascularization. Single-photon emission computed tomography and echocardiography are less suited for this purpose.

[¹8F]-fluorodeoxyglucose PET imaging of atherosclerosis.

[(18)F]-fluorodeoxyglucose PET ((18)FDG PET) imaging has emerged as a promising tool for assessment of atherosclerosis. By targeting atherosclerotic plaque glycolysis, a marker for plaque inflammation and hypoxia, (18)FDG PET can assess plaque vulnerability and potentially predict risk of atherosclerosis-related disease, such as stroke and myocardial infarction. With excellent reproducibility, (18)FDG PET can be a surrogate end point in clinical drug trials, improving trial efficiency. This article summarizes key findings in the literature, discusses limitations of (18)FDG PET imaging of atherosclerosis, and reports recommendations to optimize imaging protocols.

Delayed ¹8F-fluorodeoxyglucose PET/CT imaging improves quantitation of atherosclerotic plaque inflammation: results from the CAMONA study.

BACKGROUND: This study aimed to determine if delayed (18)F-fluorodeoxyglucose ((18)FDG) PET/CT imaging improves quantitation of atherosclerotic plaque inflammation. Blood-pool activity can disturb the arterial (18)FDG signal. With time, blood-pool activity declines. Therefore, delayed imaging can potentially improve quantitation of vascular inflammation. METHODS AND RESULTS: 40 subjects were prospectively assessed by dual-time-point PET/CT imaging at approximately 90 and 180 minutes after (18)FDG administration. For both time-points, global uptake of (18)FDG was determined in the carotid arteries and thoracic aorta by calculating the blood-pool corrected maximum standardized uptake value (cSUVMAX). A target-to-background ratio (TBR) was calculated to determine the contrast resolution at 90 and 180 minutes. Furthermore, we assessed whether the acquisition time-point affected the relation between cSUVMAX and the estimated 10-year risk for fatal cardiovascular disease (SCORE %). A significant increase in carotid cSUVMAX (23%, P < .0001), carotid TBR (20%, P < .0001), aortic cSUVMAX (14%, P < .0001), and aortic TBR (20%, P < .0001) was observed with time. At 90 minutes, cSUVMAX did not relate to SCORE %, whereas at 180 minutes significant positive relations were observed between SCORE % and carotid (τ = 0.25, P = .045) and aortic (τ = 0.33, P = .008) cSUVMAX. CONCLUSIONS: Delayed (18)FDG PET/CT imaging at 180 minutes improves quantitation of atherosclerotic plaque inflammation over imaging at 90 minutes. Therefore, the optimal acquisition time-point to assess atherosclerotic plaque inflammation lies beyond the advocated time-point of 90 minutes after (18)FDG administration.

The pivotal role of FDG-PET/CT in modern medicine.

The technology behind positron emission tomography (PET) and the most widely used tracer, 2-deoxy-2-[18F]fluoro-D-glucose (FDG), were both conceived in the 1970s, but the latest decade has witnessed a rapid emergence of FDG-PET as an effective imaging technique. This is not least due to the emergence of hybrid scanners combining PET with computed tomography (PET/CT). Molecular imaging has enormous potential for advancing biological research and patient care, and FDG-PET/CT is currently the most widely used technology in this domain. In this review, we discuss contemporary applications of FDG-PET and FDG-PET/CT as well as novel developments in quantification and potential future indications including the emerging new modality PET/magnetic resonance imaging.

Delayed sodium 18F-fluoride PET/CT imaging does not improve quantification of vascular calcification metabolism: results from the CAMONA study.

BACKGROUND: This study aimed to determine if delayed sodium (18)F-fluoride (Na(18)F) PET/CT imaging improves quantification of vascular calcification metabolism. Blood-pool activity can disturb the arterial Na(18)F signal. With time, blood-pool activity declines. Therefore, delayed imaging can potentially improve quantification of vascular calcification metabolism. METHODS AND RESULTS: Twenty healthy volunteers and 18 patients with chest pain were prospectively assessed by triple time-point PET/CT imaging at approximately 45, 90, and 180 minutes after Na(18)F administration. For each time point, global uptake of Na(18)F was determined in the coronary arteries and thoracic aorta by calculating the blood-pool-corrected maximum standardized uptake value (cSUV(MAX)). A target-to-background ratio (TBR) was calculated to determine the contrast resolution at 45, 90, and 180 minutes. Furthermore, we assessed whether the acquisition time-point affected the relation between cSUV(MAX) and the estimated 10-year risk for fatal cardiovascular disease (SCORE %). Coronary cSUV(MAX) (P = .533) and aortic cSUV(MAX) (P = .654) remained similar with time, whereas the coronary TBR (P < .0001) and aortic TBR (P < .0001) significantly increased with time. Even though the contrast resolution improved with time, positive correlations between SCORE % and coronary cSUV(MAX) (P < .020) and aortic cSUV(MAX) (P < .005) were observed at all investigated time points. CONCLUSIONS: Delayed Na(18)F PET/CT imaging does not improve quantification of vascular calcification metabolism. Although contrast resolution improves with time, arterial Na(18)F avidity is invariant to the time between Na(18)F administration and PET/CT acquisition. Therefore, the optimal PET/CT acquisition time-point to quantify vascular calcification metabolism is achieved as early as 45 minutes after Na(18)F administration.

Delayed time-point 18F-FDG PET CT imaging enhances assessment of atherosclerotic plaque inflammation.

OBJECTIVE: The aim of this study was to determine the ideal circulation time of fluorine-18 fluorodeoxyglucose (F-FDG) in order to detect and quantify atherosclerotic plaque inflammation with PET computed tomography (CT) imaging. METHODS: Fifteen patients underwent multiple time-point imaging at ∼60, 120, and 180 min after F-FDG administration. For each time point, global assessment of aortic and carotid F-FDG uptake was determined qualitatively by visual assessment and semiquantitatively by calculation of the mean and maximum standardized uptake values (SUV) and the corresponding target-to-background ratio (TBR). RESULTS: Delayed imaging achieved significant improvement in visualization of atherosclerotic plaque inflammation [Friedman's χ statistic (d.f.=2, n=15)=24.13, P<0.001, Kendall's W=0.80]. This observation was confirmed by semiquantitative image analysis. At 1 h, the aortic and carotid SUVmean-calculated TBR was 1.05 [95% confidence interval (CI)=0.98, 1.11] and 0.88 (95% CI=0.81, 0.96), respectively. At 3 h, the TBR significantly increased to 1.57 (95% CI=1.28, 1.86; P=0.001) for the aorta and to 1.61 (95% CI=1.36, 1.87; P<0.001) for the carotid arteries. SUVmax-calculated TBRs showed a similar increase over time. CONCLUSION: One- and 2-h F-FDG PET CT imaging is suboptimal for global assessment of atherosclerotic plaque inflammation compared with imaging at 3 h. Our data support the utilization of 3-h delayed imaging to obtain optimal data for the detection and quantification of atherosclerotic plaque inflammation in human arteries.

Beta-cell imaging: call for evidence-based and scientific approach.

INTRODUCTION: Advances in positron emission tomography (PET) imaging have provided opportunities to develop radiotracers specific for imaging insulin-producing pancreatic ß-cells. However, a host of lingering questions should be addressed before these radiotracers are advocated for noninvasive quantification of ß-cell mass (BCM) in vivo in the native pancreas. METHOD: We provide an overview of tetrabenazine-based PET tracers developed to image and quantify BCM and discuss several theoretical, technical, and biological limitations of applying these tracers in clinical practice. DISCUSSION: VMAT2, a transporter protein expressed on pancreatic ß-cells, has been advocated as a promising target for PET imaging tracers, such as dihydrotetrabenazine. However, the lack of radiotracer specificity for these proteins hampers their clinical application. Another important argument against their use is a striking discrepancy between radiotracer uptake and BCM in subjects with type I diabetes mellitus and healthy controls. Additionally, technical issues, such as the finite spatial resolution of PET, partial volume effects, and movement of the pancreas during respiration, impede PET imaging as a viable option for BCM quantification in the foreseeable future. CONCLUSION: The assertion that BCM can be accurately quantified by tetrabenazine derived ß-cell-specific radiotracers as density per unit volume of pancreatic tissue is not justifiable at this time. The fallacy of these claims can be explained by technical as well as biological facts that have been disregarded and ignored in the literature.

The value of radiologic interventions and (18)F-DOPA PET in diagnosing and localizing focal congenital hyperinsulinism: systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to quantify the diagnostic performance of pancreatic venous sampling (PVS), selective pancreatic arterial calcium stimulation with hepatic venous sampling (ASVS), and (18)F-DOPA positron emission tomography (PET) in diagnosing and localizing focal congenital hyperinsulinism (CHI). PROCEDURES: This systematic review and meta-analysis was conducted according to the PRISMA statement. PubMed, EMBASE, SCOPUS and Web of Science electronic databases were systematically searched from their inception to November 1, 2011. Using predefined inclusion and exclusion criteria, two blinded reviewers selected articles. Critical appraisal ranked the retrieved articles according to relevance and validity by means of the QUADAS-2 criteria. Pooled data of homogeneous study results estimated the sensitivity, specificity, likelihood ratios and diagnostic odds ratio (DOR). RESULTS: (18)F-DOPA PET was superior in distinguishing focal from diffuse CHI (summary DOR, 73.2) compared to PVS (summary DOR, 23.5) and ASVS (summary DOR, 4.3). Furthermore, it localized focal CHI in the pancreas more accurately than PVS and ASVS (pooled accuracy, 0.82 vs. 0.76, and 0.64, respectively). Important limitations comprised the inclusion of studies with small sample sizes, high probability of bias and heterogeneity among their results. Studies with small sample sizes and high probability of bias tended to overestimate the diagnostic accuracy. CONCLUSIONS: This systematic review and meta-analysis found evidence for the superiority of (18)F-DOPA PET in diagnosing and localizing focal CHI in patients requiring surgery for this disease.