The Year in Cardiac Imaging
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Archive for 'Nuclear Imaging'
Coronary Arterial 18F-Sodium Fluoride Uptake: A Novel Marker of Plaque Biology
OBJECTIVES: With combined positron emission tomography and computed tomography (CT), we investigated coronary arterialuptake of 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) as markers of active plaque calcification and inflammation, respectively. The noninvasive assessment of coronary artery plaque biology would be a major advance particularly in the identification of vulnerable plaques, which are associated with specific pathological characteristics, including micro-calcification and inflammation.
METHODS: We prospectively recruited 119 volunteers (72 ± 8 years of age, 68% men) with and without aortic valve disease and measured their coronary calcium score and 18F-NaF and 18F-FDG uptake. Patients with a calcium score of 0 were used as control subjects and compared with those with calcific atherosclerosis (calcium score >0).
RESULTS: Inter-observer repeatability of coronary 18F-NaF uptake measurements (maximum tissue/background ratio) was excellent (intra-class coefficient 0.99). Activity was higher in patients with coronary atherosclerosis (n = 106) versus control subjects (1.64 ± 0.49 vs. 1.23 ± 0.24; p = 0.003) and correlated with the calcium score (r = 0.652, p < 0.001), although 40% of those with scores >1,000 displayed normal uptake. Patients with increased coronary 18F-NaF activity (n = 40) had higher rates of prior cardiovascular events (p = 0.016) and angina (p = 0.023) and higher Framingham risk scores (p = 0.011). Quantification ofcoronary 18F-FDG uptake was hampered by myocardial activity and was not increased in patients with atherosclerosis versus control subjects (p = 0.498).
CONCLUSIONS: 18F-NaF is a promising new approach for the assessment of coronary artery plaque biology. Prospective studies with clinical outcomes are now needed to assess whether coronary 18F-NaF uptake represents a novel marker of plaque vulnerability, recent plaque rupture, and future cardiovascular risk. (An Observational PET/CT Study Examining the Role of Active Valvular Calcification and Inflammation in Patients With Aortic Stenosis; NCT01358513).
PMID: 22516444
Diagnostic Performance of Noninvasive Myocardial Perfusion Imaging Using Single-Photon Emission Computed Tomography, Cardiac Magnetic Resonance, and Positron Emission Tomography Imaging for the Detection of Obstructive Coronary Artery Disease
OBJECTIVES: This study aimed to determine the diagnostic accuracy of the 3 most commonly used noninvasive myocardial perfusion imaging modalities, single-photon emission computed tomography (SPECT), cardiac magnetic resonance (CMR), and positron emission tomography (PET) perfusion imaging for the diagnosis of obstructive coronary artery disease (CAD). Additionally, the effect of test and study characteristics was explored. Accurate detection of obstructive CAD is important for effective therapy. Noninvasive myocardial perfusion imaging is increasingly being applied to gauge the severity of CAD.
METHODS: Studies published between 1990 and 2010 identified by PubMed search and citation tracking were examined. A study was included if a perfusion imaging modality was used as a diagnostic test for the detection of obstructive CAD and coronary angiography as the reference standard (
50% diameter stenosis).
RESULTS: Of the 3,635 citations, 166 articles (n = 17,901) met the inclusion criteria: 114 SPECT, 37 CMR, and 15 PET articles. There were not enough publications on other perfusion techniques such as perfusion echocardiography and computed tomography to include these modalities into the study. The patient-based analysis per imaging modality demonstrated a pooled sensitivity of 88% (95% confidence interval [CI]: 88% to 89%), 89% (95% CI: 88% to 91%), and 84% (95% CI: 81% to 87%) for SPECT, CMR, and PET, respectively; with a pooled specificity of 61% (95% CI: 59% to 62%), 76% (95% CI: 73% to 78%), and 81% (95% CI: 74% to 87%). This resulted in a pooled diagnostic odds ratio (DOR) of 15.31 (95% CI: 12.66 to 18.52; I 2 63.6%), 26.42 (95% CI: 17.69 to 39.47; I 2 58.3%), and 36.47 (95% CI: 21.48 to 61.92; I 2 0%). Most of the evaluated test and study characteristics did not affect the ranking of diagnostic performances.
CONCLUSIONS: SPECT, CMR, and PET all yielded a high sensitivity, while a broad range of specificity was observed. SPECT is widely available and most extensively validated; PET achieved the highest diagnostic performance; CMR may provide an alternative without ionizing radiation and a similar diagnostic accuracy as PET. We suggest that referring physicians consider these findings in the context of local expertise and infrastructure.
Patient Management After Noninvasive Cardiac Imaging – Results From SPARC (Study of Myocardial Perfusion and Coronary Anatomy Imaging Roles in Coronary Artery Disease)
OBJECTIVES: This study examined short-term cardiac catheterization rates and medication changes after cardiac imaging. Noninvasive cardiac imaging is widely used in coronary artery disease, but its effects on subsequent patient management are unclear.
METHODS: We assessed the 90-day post-test rates of catheterization and medication changes in a prospective registry of 1,703 patients without a documented history of coronary artery disease and an intermediate to high likelihood of coronary artery disease undergoing cardiac single-photon emission computed tomography, positron emission tomography, or 64-slice coronary computed tomography angiography.
RESULTS: Baseline medication use was relatively infrequent. At 90 days, 9.6% of patients underwent catheterization. The rates of catheterization and medication changes increased in proportion to test abnormality findings. Among patients with the most severe test result findings, 38% to 61% were not referred to catheterization, 20% to 30% were not receiving aspirin, 35% to 44% were not receiving a beta-blocker, and 20% to 25% were not receiving a lipid-lowering agent at 90 days after the index test. Risk-adjusted analyses revealed that compared with stress single-photon emission computed tomography or positron emission tomography, changes in aspirin and lipid-lowering agent use was greater after computed tomography angiography, as was the 90-day catheterization referral rate in the setting of normal/nonobstructive and mildly abnormal test results.
CONCLUSIONS: Overall, noninvasive testing had only a modest impact on clinical management of patients referred for clinical testing. Although post-imaging use of cardiac catheterization and medical therapy increased in proportion to the degree of abnormality findings, the frequency of catheterization and medication change suggests possible undertreatment of higher risk patients. Patients were more likely to undergo cardiac catheterization after computed tomography angiography than after single-photon emission computed tomography or positron emission tomography after normal/nonobstructive and mildly abnormal study findings.
Assessment of Valvular Calcification and Inflammation by Positron Emission Tomography in Patients With Aortic Stenosis
OBJECTIVES: The pathophysiology of aortic stenosis is incompletely understood and the relative contributions of valvular calcification and inflammation to disease progression are unknown.
METHODS: Patients with aortic sclerosis and mild, moderate and severe stenosis were prospectively compared to age and sex-matched control subjects. Aortic valve severity was determined by echocardiography. Calcification and inflammation in the aortic valve were assessed by sodium 18-fluoride (18F-NaF) and 18-fluorodeoxyglucose (18F-FDG) uptake using positron emission tomography. One hundred and twenty one subjects (20 controls; 20 aortic sclerosis; 25 mild, 33 moderate and 23 severe aortic stenosis) were administered both 18F-NaF and 18F-FDG.
RESULTS: Quantification of tracer uptake within the valve demonstrated excellent inter-observer repeatability with no fixed or proportional biases and limits of agreement of ±0.21 (18F-NaF) and ±0.13 (18F-FDG) for maximum tissue-to-background ratios (TBR). Activity of both tracers was higher in patients with aortic stenosis than control subjects (18F-NaF:2.87±0.82 vs 1.55±0.17; 18F-FDG: 1.58±0.21 vs 1.30±0.13; both P1.97) and 35% increased 18F-FDG (>1.63) uptake. A weak correlation between the activities of these tracers was observed (r(2)= 0.174, P
CONCLUSIONS: Positron emission tomography is a novel, feasible and repeatable approach to thee valuation of valvular calcification and inflammation in patients with aortic stenosis. The frequency and magnitude of increased tracer activity correlates with disease severity, and is strongest for 18F-NaF.
PMID: 22090163
Cardiovascular Magnetic Resonance and Single-Photon Emission Computed Tomography for Diagnosis of Coronary Heart Disease (CE-MARC): A Prospective Trial
OBJECTIVES: In patients with suspected coronary heart disease, single-photon emission computed tomography (SPECT) is the most widely used test for the assessment of myocardial ischaemia, but its diagnostic accuracy is reported to be variable and it exposes patients to ionising radiation. The aim of this study was to establish the diagnostic accuracy of a multiparametric cardiovascular magnetic resonance (CMR) protocol with x-ray coronary angiography as the reference standard, and to compare CMR with SPECT, in patients with suspected coronary heart disease.
METHODS: In this prospective trial patients with suspected angina pectoris and at least one cardiovascular risk factor were scheduled for CMR, SPECT, and invasive x-ray coronary angiography. CMR consisted of rest and adenosine stress perfusion, cine imaging, late gadolinium enhancement, and MR coronary angiography. Gated adenosine stress and rest SPECT used 99mTc tetrofosmin. The primary outcome was diagnostic accuracy of CMR.
RESULTS: In the 752 recruited patients, 39% had significant CHD as identified by x-ray angiography. For multiparametric CMR the sensitivity was 86·5% (95% CI 81·8—90·1), specificity 83·4% (79·5—86·7), positive predictive value 77·2%, (72·1—81·6) and negative predictive value 90·5% (87·1—93·0). The sensitivity of SPECT was 66·5% (95% CI 60·4—72·1), specificity 82·6% (78·5—86·1), positive predictive value 71·4% (65·3—76·9), and negative predictive value 79·1% (74·8—82·8). The sensitivity and negative predictive value of CMR and SPECT differed significantly (p<0·0001 for both) but specificity and positive predictive value did not (p=0·916 and p=0·061, respectively).
CONCLUSIONS: CE-MARC is the largest, prospective, real world evaluation of CMR and has established CMR’s high diagnostic accuracy in coronary heart disease and CMR’s superiority over SPECT. It should be adopted more widely than at present for the investigation of coronary heart disease.
Quantitative Relationship Between the Extent and Morphology of Coronary Atherosclerotic Plaque and Downstream Myocardial Perfusion
OBJECTIVES: Although the relationship between coronary stenosis and myocardial perfusion is well established, little is known about the contribution of other anatomic descriptors of atherosclerosis burden to this relationship. The purpose of this study was to quantify the effects of coronary atherosclerosis morphology and extent on myocardial flow reserve (MFR).
METHODS: We evaluated the relationship between atherosclerosis plaque burden, morphology, and composition and regional MFR (MFRregional) in 73 consecutive patients undergoing Rubidium-82 positron emission tomography and coronary computed tomography angiography for the evaluation of known or suspected coronary artery disease.
RESULTS: Atherosclerosis was seen in 51 of 73 patients and in 107 of 209 assessable coronary arteries. On a per-vessel basis, the percentage diameter stenosis (p = 0.02) or summed stenosis score (p = 0.002), integrating stenoses in series, was the best predictor of MFRregional. Importantly, MFRregional varied widely within each coronary stenosis category, even in vessels with nonobstructive plaques (n = 169), 38% of which had abnormal MFRregional (<2.0). Total plaque length, composition, and remodeling index were not associated with lower MFR. On a per-patient basis, the modified Duke CAD (coronary artery disease) index (p = 0.04) and the number of segments with mixed plaque (p = 0.01) were the best predictors of low MFRglobal.
CONCLUSIONS: Computed tomography angiography descriptors of atherosclerosis had only a modest effect on downstream MFR. On a per-patient basis, the extent and severity of atherosclerosis as assessed by the modified Duke CAD index and the number of coronary segments with mixed plaque were associated with decreased MFR.
Imaging Intraplaque Inflammation in Carotid Atherosclerosis With 11C-PK11195 Positron Emission Tomography/Computed Tomography
OBJECTIVES: We sought to determine whether intraplaque inflammation could be measured with positron emission tomography/computed tomography angiography (PET/CTA) using (11)C-PK11195, a selective ligand of the translocator protein (18 kDa) (TSPO) which is highly expressed by activated macrophages.
METHODS: (n = 32; mean age 70 ± 9 years) with carotid stenoses (n = 36; 9 symptomatic and 27 asymptomatic) underwent (11)C-PK11195 PET/CTA imaging. (11)C-PK11195 uptake into carotid plaques was measured using target-to-background ratios (TBR). On CTA images, plaque composition was assessed by measuring CT attenuation of the carotid plaque. Eight patients underwent carotid endarterectomy and ultrathin contiguous sections were processed for TSPO and CD68 (using immunohistochemical staining, (3)H-PK11195 autoradiography, and confocal fluorescence microscopy).
RESULTS: Carotid plaques associated with ipsilateral symptoms (stroke or transient ischaemic attack) had higher TBR (1.06 ± 0.20 vs. 0.86 ± 0.11, P = 0.001) and lower CT attenuation [(median, inter-quartile range) 37, 24-40 vs. 71, 56-125 HU, P = 0.01] than those without. On immunohistochemistry and confocal fluorescence microscopy, CD68 and PBR co-localized with (3)H-PK11195 uptake at autoradiography. There was a significant correlation between (11)C-PK11195 TBR and autoradiographic percentage-specific binding (r = 0.77, P = 0.025). Both TBR and CT plaque attenuation had high negative predictive values (91 and 92%, respectively) for detecting symptomatic patients. However, the best positive predictive value (100%) was achieved when TBR and CT attenuation were combined.
CONCLUSIONS: Imaging intraplaque inflammation in vivo with (11)C-PK11195 PET/CTA is feasible and can distinguish between recently symptomatic and asymptomatic plaques. Patients with a recent ischaemic event had ipsilateral plaques with lower CT attenuation and increased (11)C-PK11195 uptake.
Cardiac PET/CT for the Evaluation of Known or Suspected Coronary Artery Disease
Positron emission tomography (PET) is increasingly being applied in the evaluation of myocardial perfusion. Cardiac PET can be performed with an increasing variety of cyclotron- and generator-produced radiotracers. Compared with single photon emission computed tomography, PET offers lower radiation exposure, fewer artifacts, improved spatial resolution, and, most important, improved diagnostic performance. With its capacity to quantify rest-peak stress left ventricular systolic function as well as coronary flow reserve, PET is superior to other methods for the detection of multivessel coronary artery disease and, potentially, for risk stratification. Coronary artery calcium scoring may be included for further risk stratification in patients with normal perfusion imaging findings. Furthermore, PET allows quantification of absolute myocardial perfusion, which also carries substantial prognostic value. Hybrid PET-computed tomography scanners allow functional evaluation of myocardial perfusion combined with anatomic characterization of the epicardial coronary arteries, thereby offering great potential for both diagnosis and management. Additional studies to further validate the prognostic value and cost effectiveness of PET are warranted.
PMID: 21918042
Rates of Downstream Invasive Coronary Angiography and Revascularization: Computed Tomographic Coronary Angiography vs. Tc-99m Single Photon Emission Computed Tomography
OBJECTIVES: Computed tomographic coronary angiography (CTA) appears to be a useful modality for the detection of obstructive coronary artery disease (CAD). Recent data suggest that CTA may reduce the frequency of normal invasive coronary angiograms. However, there remains concern that the implementation of CTA could increase referrals to invasive coronary angiography (ICA). To further support the clinical acceptance of CTA, it is important to compare CTA to another accepted modality such as single photon emission computed tomography (SPECT). We followed a cohort of 64-slice CTA patients and a matched cohort of Tc-99m SPECT patients to determine downstream referrals for ICA and revascularization.
METHODS: Consecutive CTA patients (without history of revascularization or cardiac transplantation) were prospectively enrolled and compared with a Tc-99m SPECT cohort (matched for age, gender, and Morise score). Each CTA and SPECT was evaluated for obstructive CAD and patients were followed for downstream ICA and revascularization.
RESULTS: Of the 1221 patients in each cohort, 129 (10.6%) CTA patients and 125 (10.2%) SPECT patients were referred to ICA. Of those referred to ICA, obstructive CAD was confirmed in 105 (81.4%) CTA patients and in 88 (70.4%) SPECT patients. Differences in false positive rates were significantly lower in the CTA than the SPECT cohort (9.7 and 25.8%, respectively, P = 0.009). Rates of revascularization were similar in the CTA and SPECT cohorts (6.2 vs. 5.9%, respectively).
CONCLUSIONS: Compared with SPECT, CTA had similar referrals for ICA and revascularization rates but lower false positive rates. Computed tomographic coronary angiography appears to be a viable non-invasive diagnostic modality and does not appear to negatively impact upon ICA resources.
PMID: 21893487
Pharmacology in Nuclear Cardiology
Although exercise remains the preferred method of cardiac stress testing, pharmacological stress plays an important role in nuclear cardiology. The globally ageing population will see an expansion of the application of pharmacological stress testing, and with this, comes the need to understand the pharmacological basis, mechanisms of action, potential interactions and adverse effects to inform usage in less-than-ideal circumstances. This study aims to enhance the decision-making process in day-to-day clinical nuclear cardiology practice through a better understanding of nuances relevant to the pharmacological agents used for cardiac stress testing.
PMID: 21471849
Hypoxia But Not Inflammation Augments Glucose Uptake in Human Macrophages Implications For Imaging Atherosclerosis With (18)Fluorine-Labeled 2-Deoxy-D-Glucose Positron Emission Tomography
OBJECTIVES: Patient studies suggest that positron emission tomography (PET) using (18)fluorine-labeled 2-deoxy-D-glucose FdG can detect “active” atherosclerotic plaques, yet the mechanism giving rise to FdG signals remains unknown. This study investigated the regulation of glucose uptake in cells that participate in atherogenesis by stimuli relevant to this process, to gain mechanistic insight into the origin of the FdG uptake signals observed clinically.
METHODS: We exposed cells to conditions thought to operate in atheroma and determined rates of glucose uptake.
RESULTS: Hypoxia, but not pro-inflammatory cytokines, potently stimulated glucose uptake in human macrophages and foam cells. Statins attenuated this process in vitro, suggesting that these agents have a direct effect on human macrophages. Immunohistochemical study of human plaques revealed abundant expression of proteins regulating glucose utilization, predominantly in macrophage-rich regions of the plaques-regions previously proved hypoxic. Smooth-muscle cells and endothelial cells markedly increased rates of glucose uptake when exposed to pro-inflammatory cytokines.
CONCLUSIONS: Glucose uptake and, probably, FdG uptake signals in atheroma may reflect hypoxia-stimulated macrophages rather than mere inflammatory burden. Cytokine-activated smooth-muscle cells also may contribute to the FdG signal.
PMID: 21798423
Environmental Impact of Cardiac Imaging Tests For the Diagnosis of Coronary Artery Disease
OBJECTIVES: The use of cardiovascular imaging is growing inexorably and concerns have been expressed about its cost and radiation safety.
METHODS: In this study, the relative environmental impact of MRI, single photon emission tomography and cardiac ultrasound (echo) for the diagnosis of coronary artery disease were examined.
RESULTS: The results emphasise that echo causes the least environmental impact at each stage of its life cycle. The effect of one echo on human health, ecosystem effects and resource use was of the order of 1-20% of those of the alternative methods.
CONCLUSIONS: Although there are circumstances in which one imaging modality is preferred on clinical grounds, when everything else is equal, these results support the selection of echocardiography as the preferred test on environmental grounds.
PMID: 21685481
Integrated SPECT/CT for Assessment of Haemodynamically Significant Coronary Artery Lesions in Patients With Acute Coronary Syndrome
OBJECTIVES: Early risk stratification in patients with non-ST elevation acute coronary syndromes (NSTE-ACS) is important since the benefit from more aggressive and costly treatment strategies is proportional to the risk of adverse clinical events. In the present study we assessed whether hybrid single photon emission computed tomography (SPECT)/coronary computed tomography angiography (CCTA) technology could be an appropriate tool in stratifying patients with NSTE-ACS.
METHODS: SPECT/CCTA was performed in 90 consecutive patients with NSTE-ACS. The Thrombolysis in Myocardial Infarction risk score (TIMI-RS) was used to classify patients as low- or high-risk. Imaging was performed using SPECT/CCTA to identify haemodynamically significant lesions defined as >50% stenosis on CCTA with a reversible perfusion defect on SPECT in the corresponding territory.
RESULTS: CCTA demonstrated at least one lesion with >50% stenosis in 35 of 40 high-risk patients (87%) as compared to 14 of 50 low-risk patients (35%; TIMI-RS <3; p <0.0001). Of the 40 high-risk and 50 (16%) low-risk TIMI-RS patients, 16 (40%) and 8 (16%), respectively, had haemodynamically significant lesions (p = 0.01). Patients defined as high-risk by a high TIMI-RS, a positive CCTA scan or both (n = 45) resulted in a sensitivity of 95%, specificity of 49%, PPV of 35% and NPV of 97% for having haemodynamically significant coronary lesions. Those with normal perfusion were spared revascularization procedures, regardless of their TIMI-RS.
CONCLUSIONS: Noninvasive assessment of coronary artery disease by SPECT/CCTA may play an important role in risk stratification of patients with NSTE-ACS by better identifying the subgroup requiring intervention.
PMID: 21688049
Cost-Effectiveness of Coronary Computed Tomography and Cardiac Stress Imaging in the Emergency Department a Decision Analytic Model Comparing Diagnostic Strategies for Chest Pain in Patients at Low Risk of Acute Coronary Syndromes
OBJECTIVES: Emergency department presentations with chest pain are expensive and often unrelated to coronary artery disease (CAD). Coronary computed tomographic angiography (CTA) may allow earlier discharge of low-risk patients, resulting in cost savings.
METHODS: We modeled clinical and economic outcomes of diagnostic strategies in patients with chest pain and at low risk of CAD: exercise electrocardiography (ECG), stress single-photon emission computed tomography (SPECT), stress echocardiography, and a CTA strategy comprising an initial CTA scan with confirmatory SPECT for indeterminate results.
RESULTS: Our results suggest that a 2-step diagnostic strategy of CTA with SPECT for intermediate scans is likely to be less costly and more effective for the diagnosis of a patient group at low risk of CAD and a prevalence of 2% to 30%. The CTA strategies were cost saving (lower costs, higher quality-adjusted life-years) compared with stress ECG, echocardiography, and SPECT.
CONCLUSIONS: Confirming intermediate/indeterminate CTA scans with SPECT results in cost savings and quality-adjusted life-year gains due to reduced hospitalization of patients who returned false-positive initial CTA test. However, CTA may be associated with a higher event rate in negative patients than SPECT, and the diagnostic and prognostic information for the use of CTA in the emergency department is evolving. Large comparative, randomized, controlled trials of the different diagnostic strategies are needed to compare the long-term costs and consequences of each strategy in a population of defined low-risk patients in the emergency department.
PMID: 21565744
