Focus on... PET/CT in cardiology: an area whose boundaries are still out of sight Giovanni Lucignani1, 2 1 Institute I of Radiological Sciences University of Milanand Unit of Molecular Imaging, Division of Radiation Therapy, European Institute of Oncology Via Ripamonti 435, 20141 Milan, Italy
Published online: 22 April 2006 © Springer-Verlag 2006 2006
Eur J Nucl Med Mol Imaging (2006) 33:621–623 DOI 10.1007/s00259-006-0095-5
Positron emission tomography (PET) and X-ray computed tomography (CT) performed with PET/CT cameras allow us to obtain concurrently information on the presence and degree of alterations of myocardial perfusion and metabolism and on coronary arteries calcification. Furthermore, by gated myocardial perfusion studies, PET may provide crucial information on regional coronary blood flow reserve and endothelial dysfunction. A number of recent papers provide some insight on the potential of PET/CT in cardiology and in the assessment of various cardiovascular diseases including various types of vasculitis and metabolic diseases. Synergic use of molecular imaging, X-ray CT and MRI: combining the advantages of each modality for the assessment of coronary artery disease Schwaiger et al. [1], from the Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar der TU, in Munich, Germany, have recently reviewed the strengths, weaknesses, opportunities and threats of PET/CT in cardiology. In the conclusion of their review the authors state that multislice CT technology is rapidly approaching the goal of allowing coronary angiography to be performed noninvasively with a diagnostic accuracy similar to that of invasive coronary angiography, while at the same time providing functional information, e.g. on myocardial perfusion, thereby adding to the information on plaque
The commentaries in this section derive from a literature search and include summaries of articles compiled and linked to each other by using extensively the text contained in the articles examined. Giovanni Lucignani ()) Institute of Radiological Sciences, University of Milan and Unit of Molecular Imaging,, Division of Radiation Therapy, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy e-mail:
[email protected]
morphology. Early detection of CAD will be improved by the use of detailed structural and molecular information. In their paper, Schwaiger et al. assert that coronary calcification measurements combined with specific tracer techniques for the characterisation of inflammatory processes may help to identify patients who are at high risk for the development of acute ischaemic syndromes. Tracer techniques will continue to be of use for the characterisation of myocardial tissue viability in patients with advanced CAD and heart failure and may also be applied to monitor new therapeutic strategies and in the drug development process. The authors conclude that the necessary validation studies represent an exciting challenge for nuclear cardiology but also require the development of interdisciplinary imaging groups to integrate the expertise necessary to exploit the diagnostic potential of PET/CT. In another paper, Berman et al. [2], from the Departments of Imaging and Medicine, Cedars-Sinai Medical Center, Burns and Allen Research Institute, Los Angeles, California, USA, discuss in depth the roles of nuclear cardiology, cardiac X-ray CT and cardiac MRI in the assessment of patients with suspected coronary artery disease. They provide a guide to the selection of a test (or tests) based on the question being asked and the ability of each test to answer this question, starting from the pretest likelihood of disease and a clinical assessment as the most important determinants of the initial test. They point out that PET/CT or SPECT/CT could emerge as important modalities combining the advantages of each modality for the assessment of coronary artery disease. They conclude that, while use of CT and MRI in the diagnostic evaluation of patients with coronary artery disease is likely to grow considerably over the next few years, myocardial perfusion scintigraphy and PET will continue to be very valuable techniques for this purpose. In a further paper, Bax et al. [3], from Leiden University Medical Centre, The Netherlands, examine the diagnostic and clinical perspectives of fusion imaging in cardiology by asking the question: is the total greater than the sum of the parts? Following an in-depth review of the role of different modalities in relation to several pathological conditions of the myocardium, they conclude with a few key statements. PET has established a role in clinical evaluation of perfusion and metabolism in patients with
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coronary artery disease. It will continue to have a role in research, particularly in molecular imaging. MRI and multi-slice computed tomography (MSCT) are emerging as technologies where clinical application is also being established. Pre-clinical definition of disease is becoming an important focus as early intervention therapies attempt to prevent the progression to established disease. All these advanced modalities provide unique and complementary information on pathophysiology and anatomy. Optimal use will require consideration of this complementary nature, facilitated by fusion and/or hybrid techniques. Continued research to optimise these technologies and to define their clinical role remains a priority for improving the diagnosis and the therapeutic evaluation of patients with cardiovascular disease. It is worth noting that Schuijf et al. [4], also from the Department of Cardiology, Leiden University Medical Center, The Netherlands, performed a metaanalysis of the available studies with MRI and MSCT for non-invasive coronary angiography and concluded that MSCT has a significantly higher accuracy in detecting or excluding significant coronary artery disease. To sum up, there is an exciting future for nuclear cardiology in this field, but interdisciplinary imaging groups will be required to integrate the expertise necessary to exploit the diagnostic potential of different imaging tools. Value of [18F]FDG in visualising and assessing focal and systemic vasculitis The association of vascular [18F]FDG uptake with vascular calcification has been examined by Dunphy et al. [5], from the Nuclear Medicine Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, in New York. The investigation examined the geographical relationship of focal vascular [18F]FDG uptake, as a marker of atherosclerotic inflammation, to arterial calcification detected by concurrent X-ray CT. The authors reviewed 78 [18F]FDG PET-CT studies from patients undergoing PET for tumour staging, for the presence of vascular [18F]FDG uptake and vascular calcification. Sites in the ascending and descending aorta, the carotid and iliac arteries, and the coronary territories were examined by PET, X-ray CT and fusion images. The authors evaluated whether the lesions were overlapping or discrete. The arteries typically displayed a patchwork of normal vessel, focal inflammation and calcification; inflammation and calcification overlapped in <2% of cases. The authors observed that arterial inflammation preceded calcification, in terms of mean patient age, and that coronary inflammation was more prevalent in patients with more cardiovascular risk factors. They concluded that vascular calcification and vascular metabolic activity rarely overlap, suggesting that these findings represent different stages in the evolution of atheroma. In another study, Kobayashi et al. [6], from the Department of Internal Medicine, Tokyo Medical and Dental University, Japan, examined the aortic wall inflammation due to Takayasu arteritis with [18F]FDG-PET and
contrast-enhanced X-ray CT. The authors evaluated the possibility of using [18F]FDG-PET to identify, localise and follow patients with Takayasu arteritis. They studied 14 patients with Takayasu arteritis (11 in the active stage and three in the inactive stage). Two patients with active disease were analysed by sequential [18F]FDG-PET scans during treatment. A variable grade of [18F]FDG accumulation was observed in patients in the active stage. No significant [18F] FDG accumulation was observed in the patients with inactive disease. The sensitivity of [18F]FDG-PET analysis in Takayasu arteritis was found to be 90.9%, and the specificity, 88.8%. The authors concluded that [18F]FDG images coregistered with enhanced X-ray CT images demonstrated the distribution and inflammatory activity in the aorta, its branches and the pulmonary artery in patients with active Takayasu arteritis, including even those who had weak [18F]FDG accumulation, and that the intensity of accumulation decreased in response to therapy. In a third study, Salvarani et al. [7], from Arcispedale S. Maria Nuova, Reggio Emilia, Italy, evaluated the presence and extent of large-vessel inflammation in patients with chronic peri-aortitis using [18F]FDG-PET. By examining a consecutive case series comprising seven patients with chronic peri-aortitis seen over a 3-year period, the authors demonstrated the presence of large-vessel vasculitis involving the abdominal aorta and common iliac arteries, which in some patients also extended to the thoracic aorta and/or its branches. Several other observations seem to suggest a relevant role for [18F]FDG in patients with various types of vascular disease. Yakushiji et al. [8], from the Cerebrovascular Division, Department of Medicine, National Cardiovascular Center, Osaka, Japan, observed in one patient multiple acute ischaemic brain lesions and increased [18F]FDG uptake in the ascending aorta. In this patient a dissection of the aorta, confirmed by X-ray CT, was followed by total aortic arch replacement and histopathological examination demonstrating macrophages and foam cells, each of which could be at least partially responsible for the increased FDG uptake. Two cases of fever due to vasculitis diagnosed with [18F]FDG have been described by Rozin et al. [9], from the B. Shine Department of Rheumatology, and Zalts et al. [10], from the Department of Internal Medicine, Rambam Medical Center and B. Rappaport Faculty of Medicine, Technion, Haifa, Israel. In one of these cases there was predominantly aortic involvement, and in the other, brachio-cephalic and carotid artery involvement. Pfadenhauer and Rull [11], from the Departments of Neurology and Clinical Neurophysiology in Augsburg, Germany, used a combined approach comprising ultrasound and [18F]FDG-PET for the diagnosis of giant cell arteritis of large arteries. Although [18F]FDGPET, in combination with X-ray CT, is not used as part of the routine evaluation of patients with vascular diseases of any origin, these reports highlight the possible role of [18F] FDG-PET in assessing the presence and stability of plaques in such patients, including those with embolic stroke, and in evaluating vasculitis involving the large vessels, e.g. the abdominal and thoracic aorta and its branches.
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Metabolic syndrome, cardiovascular risk factors and myocardial perfusion imaging In a paper published in the European Journal of Internal Medicine in September 2005, Tamsma et al. [12], from the Vascular Medicine, Department of General Internal Medicine, Leiden University Medical Center, The Netherlands, provide a vascular perspective on the metabolic syndrome, defined as a clustering of cardiovascular risk factors including hypertension, waist circumference, and fasting glucose, triglyceride and HDL-cholesterol levels. The authors point out that the prevalence of metabolic syndrome is increasing in our society owing to lifestyle changes that result in decreased physical activity and increased body weight. Patients with metabolic syndrome have a three times greater risk of coronary heart disease and stroke, and a two to four times greater risk of dying from atherosclerotic coronary heart disease than those without metabolic syndrome. Moreover, Wong CY et al. [13], from the University of Queensland, Brisbane, Australia, have reported that the metabolic syndrome is associated with cardiovascular risk exceeding that expected from atherosclerotic risk factors; in a study on 393 subjects with significant risk factors but no cardiovascular disease and negative stress echocardiographic findings, they observed that subclinical left ventricular dysfunction corresponded to the degree of metabolic burden and that these myocardial changes were associated with reduced cardiorespiratory fitness. They concluded that subjects with metabolic syndrome who also have subclinical myocardial abnormalities and reduced cardiorespiratory fitness may have a higher risk of cardiovascular disease events and heart failure. The results of these studies are in keeping with the observations of Wong ND et al. [14], from Cardiac Imaging, Cedars-Sinai Medical Center, Los Angeles, California, USA, who examined the relation between metabolic syndrome, coronary artery calcification (CAC) levels and myocardial ischaemia. They evaluated 1,043 patients without known coronary artery disease who underwent stress myocardial perfusion scintigraphy and X-ray CT. Metabolic abnormalities were present in 313 patients (30%), including 140 with diabetes (with or without metabolic syndrome) and 173 who had metabolic syndrome without diabetes. This study showed that, although CAC scores <100 identified a low likelihood (approximately 2%) of ischaemia, the presence (versus absence) of metabolic abnormalities (metabolic syndrome or diabetes) was a predictor of more frequent ischaemia among patients with CAC scores of 100–399 (13.0% vs 3.6%, p<0.02) or ≥400 (23.4% vs 13.6%, p=0.03). Similar trends were observed when patients with metabolic syndrome and diabetes were considered separately. Multiple logistic regression analysis revealed the odds of MPS ischaemia to be 4.3-fold greater per SD of log CAC (p<0.001) and 2.0-fold greater in the presence of metabolic abnormalities (p<0.01). The authors concluded that among patients with CAC scores ≥100, metabolic abnormalities, and even metabolic syndrome in the absence of diabetes,
predicted a higher likelihood of inducible ischaemia. These findings suggest the need for assessment of metabolic status when interpreting the results of CAC imaging among patients undergoing such testing because of suspected CAD. For those who are becoming familiar with the use of PET-CT and SPECT-CT, the message seems quite clear: go beyond the use of these wonderful modalities in oncology, into an area whose boundaries are still out of sight. References 1. Schwaiger M, Ziegler S, Nekolla SG. PET/CT: challenge for nuclear cardiology. J Nucl Med 2005;46(10):1664–78 2. Berman DS, Hachamovitch R, Shaw LJ, Friedman JD, Hayes SW, Thomson LE, et al. Roles of nuclear cardiology, cardiac computed tomography, and cardiac magnetic resonance: assessment of patients with suspected coronary artery disease. J Nucl Med 2006;47(1):74–82 3. Bax JJ, Beanlands RS, Klocke FJ, Knuuti J, Lammertsma AA, Schaefers MA, et al. Diagnostic and clinical perspectives of fusion imaging in cardiology: is the total greater than the sum of its parts? Heart 2005;Dec 30 [Epub ahead of publication] 4. Schuijf JD, Bax JJ, Shaw LJ, de Roos A, Lamb HJ, van der Wall EE, et al. Meta-analysis of comparative diagnostic performance of magnetic resonance imaging and multislice computed tomography for noninvasive coronary angiography. Am Heart J 2006;151(2):404–11 5. Dunphy MP, Freiman A, Larson SM, Strauss HW. Association of vascular 18F-FDG uptake with vascular calcification. J Nucl Med 2005;46(8):1278–84 6. Kobayashi Y, Ishii K, Oda K, Nariai T, Tanaka Y, Ishiwata K, et al. Aortic wall inflammation due to Takayasu arteritis imaged with 18F-FDG PET coregistered with enhanced CT. J Nucl Med 2005;46(6):917–22 7. Salvarani C, Pipitone N, Versari A, Vaglio A, Serafini D, Bajocchi G, et al. Positron emission tomography (PET): evaluation of chronic periaortitis. Arthritis Rheum 2005;53 (2):298–303 8. Yakushiji Y, Hasegawa Y, Fukuchi K, Nishigami K, Sasaki H, Ogino H, et al. Multiple acute ischemic brain lesions and increased fluorodeoxyglucose uptake in the ascending aorta. Cerebrovasc Dis 2005;20(6):480 9. Rozin AP, Bar-Shalom R, Strizevsky A, Jacob G. Fever due to aortitis. Clin Rheumatol 2005;Dec 21:1–3 [Epub ahead of print] 10. Zalts R, Hamoud S, Bar-Shalom R, Eilam O, Rozin A, Hayek T. Panaortitis: diagnosis via fluorodeoxyglucose positron emission tomography. Am J Med Sci 2005;330(5):247–9 11. Pfadenhauer K, Rull T. Ultrasonographic and FDG-PET imaging in active giant cell arteritis of the carotid arteries. VASA 2005;34(4):269–71 12. Tamsma JT, Jazet IM, Beishuizen ED, Fogteloo AJ, Meinders AE, Huisman MV. The metabolic syndrome: a vascular perspective. Eur J Intern Med 2005;16(5):314–20 13. Wong CY, O’Moore-Sullivan T, Fang ZY, Haluska B, Leano R, Marwick TH. Myocardial and vascular dysfunction and exercise capacity in the metabolic syndrome. Am J Cardiol 2005;96(12):1686–91 14. Wong ND, Rozanski A, Gransar H, Miranda-Peats R, Kang X, Hayes S, et al. Metabolic syndrome and diabetes are associated with an increased likelihood of inducible myocardial ischemia among patients with subclinical atherosclerosis. Diabetes Care 2005;28(6):1445–50
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