Björn Alexander Blomberg

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.

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.

Beta-Cell Imaging: Call for Evidence-Based and Scientific Approach

IntroductionAdvances in positron emission tomography (PET) imaging have provided opportunities to develop radiotracers specific for imaging insulin-producing pancreatic β-cells. However, a host of lingering questions should be addressed before these radiotracers are advocated for noninvasive quantification of β-cell mass (BCM) in vivo in the native pancreas.MethodWe 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.DiscussionVMAT2, a transporter protein expressed on pancreatic β-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.ConclusionThe assertion that BCM can be accurately quantified by tetrabenazine derived β-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.

Impact of Personal Characteristics and Technical Factors on Quantification of Sodium 18F-Fluoride Uptake in Human Arteries: Prospective Evaluation of Healthy Subjects

Sodium 18F-fluoride (18F-NaF) PET/CT imaging is a promising imaging technique for the assessment of atherosclerosis but is hampered by a lack of validated quantification protocols. Both personal characteristics and technical factors can affect quantification of arterial 18F-NaF uptake. This study investigated whether blood activity, renal function, injected dose, circulating time, and PET/CT system affect quantification of arterial 18F-NaF uptake. Methods: Eighty-nine healthy subjects were prospectively examined by 18F-NaF PET/CT imaging. Arterial 18F-NaF uptake was quantified at the level of the ascending aorta, aortic arch, descending thoracic aorta, and coronary arteries by calculating the maximum 18F-NaF activity (NaFmax), the maximum/mean target-to-background ratio (TBRmax/mean), and the maximum blood-subtracted 18F-NaF activity (bsNaFmax). Multivariable linear regression assessed the effect of personal characteristics and technical factors on quantification of arterial 18F-NaF uptake. Results: NaFmax and TBRmax/mean were dependent on blood activity (β = 0.34 to 0.44, P < 0.001, and β = −0.68 to −0.58, P < 0.001, respectively) and PET/CT system (β = −0.80 to −0.53, P < 0.001, and β = −0.80 to −0.23, P < 0.031, respectively). bsNaFmax depended on PET/CT system (β = −0.91 to −0.57, P < 0.001) but not blood activity. This finding was observed at the level of the ascending aorta, aortic arch, descending thoracic aorta, and the coronary arteries. In addition to blood activity and PET/CT system, injected dose affected quantification of arterial 18F-NaF uptake, whereas renal function and circulating time did not. Conclusion: The prospective evaluation of 89 healthy subjects demonstrated that quantification of arterial 18F-NaF uptake is affected by blood activity, injected dose, and PET/CT system. Therefore, blood activity, injected dose, and PET/CT system should be considered to generate accurate estimates of arterial 18F-NaF uptake.

A brief overview of novel approaches to FDG PET imaging and quantification

The widespread implementation of hybrid FDG PET/CT worldwide has brought about a paradigm shift in the use of diagnostic imaging—molecular imaging combining morphological and functional data is now at the forefront of patient management in many clinical settings, not only for initial diagnosis, staging, monitoring of response to treatment and detection of recurrence, but also for prognostication and disease characterization. Although developments have focused particularly on the qualitative visual analysis of images, FDG PET allows elaborate quantification, which should be explored much more in the future and ideally standardized worldwide. In this brief overview, we outline the state of the art of novel and quantitative approaches to FDG imaging, i.e. standard uptake value, partial volume effect and partial volume correction, multiple-time-point imaging, assessment of global disease burden and PET/MRI, all of which we expect to see evolving as powerful tools in the coming years and enhancing sensitivity and specificity in variety of clinical settings, in which FDG PET imaging has not yet shown its full potential.

Evolving Role of Molecular Imaging with 18F-Sodium Fluoride PET as a Biomarker for Calcium Metabolism

Abstract18F-sodium fluoride (NaF) as an imaging tracer portrays calcium metabolic activity either in the osseous structures or in soft tissue. Currently, clinical use of NaF-PET is confined to detecting metastasis to the bone, but this approach reveals indirect evidence for disease activity and will have limited use in the future in favor of more direct approaches that visualize cancer cells in the read marrow where they reside. This has proven to be the case with FDG-PET imaging in most cancers. However, a variety of studies support the application of NaF-PET to assess benign osseous diseases. In particular, bone turnover can be measured from NaF uptake to diagnose osteoporosis. Several studies have evaluated the efficacy of bisphosphonates and their lasting effects as treatment for osteoporosis using bone turnover measured by NaF-PET. Additionally, NaF uptake in vessels tracks calcification in the plaques at the molecular level, which is relevant to coronary artery disease. Also, NaF-PET imaging of diseased joints is able to project disease progression in osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. Further studies suggest potential use of NaF-PET in domains such as back pain, osteosarcoma, stress-related fracture, and bisphosphonate-induced osteonecrosis of the jaw. The critical role of NaF-PET in disease detection and characterization of many musculoskeletal disorders has been clearly demonstrated in the literature, and these methods will become more widespread in the future. The data from PET imaging are quantitative in nature, and as such, it adds a major dimension to assessing disease activity.

[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.

Whole-Body Visualization of Ectopic Bone Formation of Arteries and Skin in Pseudoxanthoma Elasticum

Pseudoxanthoma elasticum (PXE), CD73 deficiency, generalized arterial calcification of infancy, and progeria involve accelerated medial arterial calcification (MAC) leading to premature cardiovascular morbidity and mortality. MAC is also observed in diabetes mellitus, chronic kidney disease, and the

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 (18F-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 18F-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 18F-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 18F-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 18F-NaF uptake (adjusted R2=0.21; P<0.001). Coronary artery 18F-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 18F-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 18F-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 18F-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 (18F-FDG) and fluorine-18-sodium fluoride (18F-NaF) uptake in human arteries are unknown. The aim of this study was to determine age-specific and sex-specific reference values of arterial 18F-FDG and 18F-NaF uptake. Participants and methods Uptake of 18F-FDG and 18F-NaF was determined in the ascending aorta, aortic arch, and descending thoracic aorta. In addition, 18F-FDG uptake was determined in the carotid arteries and 18F-NaF uptake was determined in the coronary arteries. Arterial 18F-FDG and 18F-NaF uptake were quantified as the blood pool subtracted maximum activity concentration in kBq/ml (BS18 F-FDGmax and BS18 F-NaFmax, respectively). In addition to determining reference values, we evaluated the influence of age and sex on BS18 F-FDGmax and BS18 F-NaFmax. Results Arterial 18F-FDG and 18F-NaF uptake was assessed in 89 healthy adults aged 21–75 years (mean age: 44±14 years, 53% men). Both BS18 F-FDGmax and BS18 F-NaFmax increased with age. BS18 F-FDGmax increased with age in the descending aorta (&bgr;=0.28; P=0.003), whereas BS18 F-NaFmax increased with age in the ascending aorta (&bgr;=0.18; P<0.001), aortic arch (&bgr;=0.19; P=0.006), descending aorta (&bgr;=0.33; P<0.001), and coronary arteries (&bgr;=0.20; P=0.009), respectively. BS18 F-FDGmax and BS18 F-NaFmax were not influenced by sex, except for BS18 F-FDGmax in the ascending aorta. Conclusion Prospective evaluation of 89 healthy adults generated age-specific and sex-specific reference values of arterial 18F-FDG and 18F-NaF uptake. Our findings indicate that arterial 18F-FDG and 18F-NaF uptake tend to increase with age.