Cardiac Imaging in the Diagnosis of Coronary Artery Disease

Coronary artery disease (CAD) continues to be a leading cause of morbidity and mortality worldwide. Although invasive coronary angiography has previously been the gold standard in establishing the diagnosis of CAD, there is a growing shift to more appropriately use the cardiac catheterization laboratory to perform interventional procedures once a diagnosis of CAD has been established by noninvasive imaging modalities rather than using it primarily as a diagnostic facility to confirm or refute CAD. With ongoing technological advancements, noninvasive imaging plays a pre-eminent role in not only diagnosing CAD but also informing the choice of appropriate therapies, establishing prognosis, all while containing costs and providing value-based care. Multiple imaging modalities are available to evaluate patients suspected of having coronary ischemia, such as stress electrocardiography, stress echocardiography, single-photon emission computed tomography myocardial perfusion imaging, positron emission tomography, coronary computed tomography (CT) angiography, and magnetic resonance imaging. These imaging modalities can variably provide functional and anatomical delineation of coronary stenoses and help guide appropriate therapy. This review will discuss their advantages and limitations and their usage in the diagnostic pathway for patients with CAD. We also discuss newer technologies such as CT fractional flow reserve, CT angiography with perfusion, whole-heart coronary magnetic resonance angiography with perfusion, which can provide both anatomical as well as functional information in the same test, thus obviating the need for multiple diagnostic tests to obtain a comprehensive assessment of both, plaque burden and downstream ischemia. Recognizing that clinicians have a multitude of tests to choose from, we provide an underpinning of the principles of ischemia detection by these various modalities, focusing on anatomy vs physiology, the database justifying their use, their prognostic capabilities and lastly, their appropriate and judicious use in this era of patient-centered, cost-effective imaging.     

Multimodality imaging in coronary artery disease – “The more the better?”

Multimodality imaging in coronary artery disease (CAD) comprises a combination of information from more than one imaging technique. These combinations, performed in a side-by-side or fusion mode, include computed tomography (CT) and single photon emission computed tomography (SPECT), positron emission tomography (PET) and CT, and PET with magnetic resonance imaging (MRI). Data thus obtained lead to either a summative or synergistic gain of information. For instance, morphology (coronary plaques/stenosis) can be depicted by coronary CT angiography, whereas functional aspects of CAD such as myocardial perfusion abnormalities or myocardial metabolism can be evaluated by the complementary technique in order to separate a hemodynamic significant coronary stenosis from a hemodynamic non-significant stenosis. Distinguishing these two entities has an important impact on patient management. Beyond the diagnostic yield, some of these combinations in multimodality imaging also have prognostic implications. In this article, we will describe different multimodality imaging approaches (CT/SPECT, PET/CT and PET/MRI) for evaluation of CAD in patients with suspected or known CAD and put them into the context of current knowledge.     

CT Perfusion: Ready for Prime Time

Advancements in computed tomography (CT) technology have revolutionized clinical practice, particularly regarding the noninvasive assessment of coronary artery disease (CAD). The versatility of cardiac CT has rendered multiple applications including assessment of cardiac structure and function, myocardial viability, and coronary anatomy. The merits of cardiac computed tomography angiography (CTA) have been proven for the detection, and particularly the exclusion, of CAD. However, CTA becomes limited in the presence of significant CAD. Its inability to consistently identify lesion-associated ischemia may necessitate additional radionuclide myocardial perfusion imaging. Myocardial computed tomography perfusion imaging (CTP) has emerged as a useful and convenient method to immediately assess myocardial ischemia. In this review, we discuss the current state of CTP including available technology, its performance to date from current literature, and future challenges to this field.     

Hybridbildgebung in Diagnostik und Therapie der chronischen Myokardischämie

Clinical studies have consistently shown that there is only a very weak correlation between the angiographically determined severity of coronary artery disease (CAD) and disturbance of regional coronary perfusion. On the other hand, the results of randomized trials with a fractional flow reserve (FFR)-guided coronary intervention (DEFER, FAME I, FAME II) showed that it is not the angiographically determined morphological severity of coronary artery disease but the functional severity determined by FFR that is critical for prognosis and the indications for revascularization. A non-invasive method combining the morphological image of the coronary anatomy with functional imaging of myocardial ischemia is therefore particularly desirable. An obvious solution is the combination of coronary computed tomography angiography (CCTA) with a functional procedure, such as perfusion positron emission tomography (PET), perfusion single photon emission computed tomography (SPECT) or perfusion magnetic resonance imaging (MRI). This can be performed with fusion imaging or with hybrid imaging using PET-CT or SPECT-CT. First trial results with PET CCTA and SPECT CCTA carried out as cardiac hybrid imaging on a 64 slice CT showed a major effect to be a decrease in the number of false positive results, significantly increasing the specificity of CCTA and SPECT. Although the results are promising, due to the previously high costs, low availability and the additional radiation exposure, current data is not yet sufficient to give clear recommendations for the use of hybrid imaging in patients with a low to intermediate risk of CAD. Ongoing prospective studies such as the SPARC or EVINCI trials will bring further clarification here.     

Myocardial perfusion imaging in coronary artery disease

Radionuclide myocardial perfusion imaging (MPI) can be used to demonstrate the presence of coronary heart disease and to risk stratify and guide management of patients with known disease. It has the ability to localize hemodynamically important coronary stenoses, and assess the extent and severity of coronary obstruction by the presence and extent of perfusion defects. A normal stress MPI indicates the absence of coronary obstruction and hence of clinically significant disease. Cardiac PET has the advantage from SPECT of higher spatial and temporal resolution, and a decreased radiation exposure to patients. Hybrid cardiac imaging combining SPECT or PET with CT data appears to offer superior diagnostic and prognostic information in patients with intermediate risk for CAD. A significant progress in better quantification of myocardial blood flow and coronary flow reserve has recently been seen. Also several studies have demonstrated that the combination of imaging apoptosis and matrix metalloproteinases production can help imaging vulnerable plaque and identifying the group of high-risk asymptomatic patients who will benefit most by an imaging procedure.     

Comprehensive cardiac CT study: evaluation of coronary arteries, left ventricular function, and myocardial perfusion--is it possible?

With advances in multidetector computed tomography (MDCT) technology, the new generation of 64-slice MDCT scanners with submillimeter collimation and a faster gantry rotation allows imaging of the entire heart in a single breath-hold with excellent temporal and spatial resolution. This potentially permits a comprehensive assessment of coronary anatomy, left ventricular function, and myocardial perfusion. As will be seen in this review of the current literature regarding 16- and 64-slice MDCT, there is great promise for a comprehensive cardiac computed tomography (CT) study. The available data support the notion that CT coronary angiography may be an alternative to invasive coronary angiography in symptomatic patients with a low to intermediate likelihood of having coronary artery disease. By use of the same data acquired for CT coronary angiography, evaluation of global and regional left ventricular function and myocardial perfusion can be added to the MDCT evaluation without additional exposure to contrast medium or radiation and may provide a more conclusive cardiac workup in these patients. The potential applications and limitations of coronary stenosis detection, global and regional left ventricular function, and myocardial perfusion assessment by MDCT will be reviewed. The full potential of cardiac MDCT is just beginning to be realized.     

MRI versus CT for the detection of coronary artery disease: Current state and future promises

CT and MR are two noninvasive imaging techniques that are capable of detecting different aspects of coronary artery disease (CAD). Both techniques can directly and noninvasively visualize the coronary artery tree, allowing detection of atherosclerotic plaques, coronary stenosis, or occlusion. In addition to direct anatomic visualization, MR also allows assessment of stress-induced ischemia. Both dobutamine stress and dipyridamole or adenosine perfusion MR can be used for this purpose with high sensitivity and specificity. Both MR and multidetector CT can also reveal the functional consequences of CAD, that is, reduced regional and global cardiac function, as well as the presence of myocardial infarction. Finally, there is promise that in the future, both techniques may predict individual risk of unstable CAD by identifying vulnerable plaques that are prone to rupture.     

Cardiac and coronary CT comprehensive imaging approach in the assessment of coronary heart disease

Cardiac CT is a rapidly advancing technology. Non-invasive CT coronary angiography is an established technique for assessing coronary heart disease with accuracy similar to invasive coronary angiography. CT myocardial perfusion imaging can now identify perfusion defects in animal models and humans. MRI is the current 'gold standard' for the assessment of myocardial viability, but it is now also possible to assess delayed enhancement by CT. This has led to the possibility of a 'one-stop shop' for cardiovascular imaging that would provide information on anatomy, function, perfusion and viability in one rapid diagnostic test at a radiation dose equivalent to contemporary nuclear medicine imaging. This review discusses the current status of 'one-stop shop' cardiac CT assessment, clinical utility and directions for future research.     

Positron emission tomography and molecular imaging

The use of positron emission tomography (PET) in cardiology is growing rapidly. Technical features make PET a strong technology for the non-invasive evaluation of cardiac physiology. It is currently considered the most reliable tool for the identification of myocardial viability and also allows accurate assessment of myocardial perfusion and detection of coronary artery disease (CAD). The unique feature of PET is that myocardial perfusion can be measured in absolute terms, improving sensitivity in the detection of multivessel of disease and also allowing evaluation of very early changes in coronary vasoreactivity and the progression or regression of CAD. Use of the newest generation of PET systems with integrated multislice computed tomography (CT) is becoming a standard technique for cardiac imaging. Since the PET and CT techniques ideally complement each other the combination is particularly attractive for the non-invasive assessment of CAD but also has other functions. Finally, there are also promising future applications that involve molecular imaging of cardiac targets, which may further enhance the clinical utility of PET and hybrid imaging.     

Multi-slice computed tomography coronary angiography: anatomic vs functional assessment in clinical practice.

Non-invasive imaging plays an increasingly important role in the diagnosis and risk stratification of coronary artery disease (CAD). Several techniques such as stress echocardiography and myocardial perfusion imaging have become available to assess cardiac function and myocardial perfusion. With the arrival of multi-slice computed tomography coronary angiography (CTA), non-invasive imaging of coronary anatomy has also become possible. Studies concerning the diagnostic accuracy have demonstrated a good agreement with conventional coronary angiography resulting in a sensitivity and specificity of approximately 86% and 96%, respectively. The high negative predictive value of 97% renders it particularly useful to rule out the presence of CAD in patients with an intermediate pretest likelihood. Moreover, comparative studies have demonstrated that anatomic imaging with CTA may provide information complementary to the traditionally used techniques for functional assessment. From these studies can be derived that only approximately 50% of significant stenoses on CTA are functionally relevant; a large proportion of significant (>50%) lesions on CTA does not result in perfusion abnormalities. Alternatively, many patients with a normal perfusion CTA show considerable atherosclerosis on CTA. Therefore, the combined use of these techniques may enhance the assessment of the presence and extent of CAD. In the future diagnostic algorithms, combining non-invasive anatomic and functional imaging need to be evaluated in large patient populations to establish their efficacy, safety, and cost effectiveness. Importantly, these investigations should result in the development of comprehensive guidelines on the use of CTA in clinical practice as well.     

Cardiac CT and CT coronary angiography: technology and application

Multislice computed tomography (MSCT) is an additional potential tool for the assessment of coronary artery disease. It can provide information about stenoses in coronary arteries and coronary artery bypass grafts, ventricular size and function, cardiac structure and masses, pulmonary vein anatomy, myocardial perfusion and coronary artery plaque. In this review the recent developments in CT technology that have made cardiac imaging possible are examined and the benefits of the latest 64-slice and dual-source CT scanners explained. Information on how to perform cardiac CT and evidence for its various clinical applications are given. Problems and limitations of cardiac CT and the radiation dose are discussed. Future developments and the likely impact of this rapidly evolving technique on clinical cardiology are considered.     

Aktueller Stellenwert von CT und MRT in der Koronardiagnostik

Coronary catheter angiography is the current reference standard for assessing coronary artery disease (CAD). Novel advanced cardiac imaging methods, such as CT and MRI, are opening new opportunities for the noninvasive assessment of morphologic and functional aspects of CAD and provide new options for prevention and for guiding invasive strategies. Especially in patients with low to intermediate pretest likelihood, cardiac CT has been firmly established for ruling out significant CAD (coronary CT angiography) and for evidence-based risk classification (calcium scoring). The strength of cardiac MRI lies in the functional evaluation of CAD. MRI-based myocardial perfusion and function measurements enable accurate evaluation of potential myocardial ischemia. In addition, late enhancement studies enable high resolution imaging of myocardial scar and viability.     

Developments in nuclear cardiology: transition from single photon emission computed tomography to positron emission tomography-computed tomography

Recent advances in positron emission tomography (PET) instrumentation have paralleled those of multichannel computed tomography (CT) for cardiac applications. Whereas multichannel CT angiography provides information on the presence and extent of anatomical luminal narrowing of epicardial coronary arteries, stress myocardial perfusion PET provides information on the downstream functional consequences of such anatomic lesions. With the advent of hybrid PET/CT systems, such complementary information of anatomy and physiology can be realized immediately at the same imaging session. By acquiring dynamic, gated myocardial perfusion data, PET studies provide insight into impairment of regional coronary blood flow reserve and microvascular endothelial dysfunction. This paper presents recent developments in PET detector materials, acquisition modes, combined PET/CT scanners, rubidium-82 (Rb-82) gated myocardial perfusion studies and analysis methods for absolute myocardial blood flow quantification.     

Minimizing liver uptake of cationic Tc radiotracers with ether and crown ether functional groups

Ischemia-related diseases, particularly coronary artery disease (CAD), account for the majority of deaths worldwide. Myocardial ischemia is a serious condition and the delay in reperfusion of ischemic tissues can be life-threatening. This is particular true in the aged population. Rapid and accurate early detection of myocardial ischemia is highly desirable so that various therapeutic regiments can be given before irreversible myocardial damage occurs. Myocardial perfusion imaging with radiotracers is an integral component in evaluations of patients with known or suspected CAD. (99m)Tc-Sestamibi and (99m)Tc-Tetrofosmin are commercial radiopharmaceuticals currently available for myocardial perfusion imaging. Despite their widespread clinical applications, both (99m)Tc-Sestamibi and (99m)Tc-Tetrofosmin do not meet the requirements of an ideal perfusion imaging agent, largely due to their high liver uptake. The intense liver uptake makes it difficult to interpret the heart activity in the inferior and left ventricular wall. Photon scattering from the high liver radioactivity accumulation remains a significant challenge for diagnosis of heart diseases. This review will summarize the most recent research efforts to minimize the liver uptake of cationic (99m)Tc radiotracers by using ether and crown ether-containing chelators. Fast liver clearance will shorten the duration of imaging protocols (< 30 min post-injection), and allow for early acquisition of heart images with high quality. Improvement of heart/liver ratio may permit better detection of the presence and extent of coronary artery disease. Identification of such a new radiotracer that allows for the improved noninvasive assessment of myocardial perfusion would be of considerable benefit in treatment of patients with suspected CAD.     

腺苷负荷试验心肌核素显像对冠心病诊断价值的评估

目的分析腺苷负荷试验心肌核素显像对于冠心病诊断的敏感性、特异性及其特点。方法住院患者同时行冠状动脉（冠脉）造影和腺苷负荷试验心肌核素显像。腺苷总量为840μg／kg,6min匀速静脉泵入,腺苷泵入3min时静脉推注^99m锝-甲氧基异丁基异腈核素显像925MBq,1．5h后进行心肌断层显像,若异常,次日行静息心肌显像。结果冠脉造影阳性50例中,心肌核素显像阳性44例。29例冠脉造影无明显狭窄,其中19例心肌核素显像阴性。腺苷负荷试验心肌核素显像对于冠心病诊断的敏感性和特异性为88．O％和65．5％。前降支病变40例,心肌核素前壁区域低灌注32例,回旋支病变27例,侧壁区域低灌注21例,右冠脉病变32例,下壁区域低灌注31例,右冠脉病变较前降支或回旋支病变的心肌核素显像阳性率高（P〈0．05）。结论腺苷负荷试验心肌核素显像对于冠心病诊断的敏感性、特异性较高。     

Cardiac magnetic resonance imaging in patients with coronary disease

Opinion statement Cardiac magnetic resonance (CMR) has emerged as a versatile noninvasive tool for the comprehensive evaluation of patients with suspected or established coronary artery disease (CAD). In a single imaging session, CMR can assess left ventricular anatomy and function, myocardial perfusion, viability, and coronary luminal stenosis. Using specific pulse sequences, left ventricular global and regional function can be assessed by cine CMR at rest and in response to inotropic stress; first-pass perfusion quantified by vasodilator stress; myocardial viability evaluated by delayed enhancement imaging and also by functional reserve; and coronary artery stenosis assessed by angiography. All these modalities can be achieved with high spatial resolution and image contrast, without exposure to ionizing radiation, and within a reasonable time frame of about 1 hour of scan time. Also, the imaging planes can be programmed to provide identical views of the heart for each type of image, thereby facilitating intermodality comparisons. There is early but accumulating evidence that the accuracy and prognostic values of many of these modalities are comparable or superior to radionuclide scintigraphy and echocardiography in head-to-head studies. Current limitations unique to CMR include the inability to perform exercise stress testing inside the CMR suite and exclusion of patients with indwelling metallic devices such as defibrillators and pacemakers. Despite these limitations, CMR is unique in its multifaceted approach that can be specifically tailored to the clinical question at hand, making it arguably the best tool for the diagnosis and management of CAD. With the rapid pace of advancement in CMR hardware and pulse sequence technologies, the clinical use of this powerful technique is likely to grow even greater in this area.     

腺苷负荷心肌灌注显像在冠心病诊断中的应用

目的:评价腺苷负荷心肌灌注显像试验对冠心病的诊断价值。方法:60例住院患者均行腺苷负荷心肌灌注显像和冠状动脉造影(CAG),腺苷以0.14mg/(kg.min)的速度外周静脉输入,第3分钟时,静脉注射放射性核素99mTc-MIBI740MBq,1.5h后进行心肌断层显像,若异常,次日行静息心肌显像,分析腺苷负荷试验心肌核素显像对于冠心病诊断的敏感性、特异性及其特点。结果:CAG阳性42例中,心肌核素显像阳性37例(敏感性88%)。18例CAG无明显狭窄,其中13例心肌核素显像阴性(特异性为72%)。前降支病变36例,心肌核素前壁区域低灌注20例,回旋支病变22例,侧壁区域低灌注14例,右冠脉病变28例,下壁区域低灌注27例,右冠脉病变较前降支或回旋支病变的心肌核素显像阳性率高(P0.05)。在应用过程中,腺苷未出现明显不良反应。结论:腺苷负荷试验心肌核素灌注显像对于冠心病诊断的敏感性、特异性较高,对诊断冠心病具有重要意义。     

99mTc-MIBI心肌灌注断层显像与心电图对冠心病的诊断价值

目的评估^99mTc—MIBI心肌灌注断层显像与心电图（ECG）在冠心病（CAD）诊断的价值。方法对28例冠心病和可疑冠心病患者进行心电图检查和^99mTc—MIBI心肌灌注断层显像（同时采用半定量方法分析患者左心室心肌血流灌注情况），其中13例患者行冠状动脉造影术（CAG）。结果心肌灌注断层显像与ECG阳性率分别为42．9％、53．6％，两者阳性率间差异无显著性意义（P〉0．05）。ECG诊断冠心病的敏感性为3／3，特异性为3／10，阳性预测值为3／10，阴性预测值为3／3，准确度为6／13。心肌灌注显像诊断冠心病的敏感性为3／3，特异性为8／10，阳性预测值为3／5，阴性预测值为8／8，准确度为11／13。心肌灌注断层显像和ECG与CAG阳性率间差异均无显著性意义（P〉0．05）。结论^99mTc—MIBI心肌灌注层显像与心电图是安全、无创伤、方便及费用低的检查方法，临床联合应用对冠心病的诊断、治疗和预后判断有重要的价值。     

Cardiac PET,CT, and MR: What Are the Advantages of Hybrid Imaging?

Cardiac hybrid imaging combines different imaging modalities in a way where both modalities equally contribute to image information. Hybrid positron emission tomography-computed tomography (PET-CT) imaging is a promising tool for evaluation of coronary artery disease (CAD) because it enables detection of coronary atherosclerotic lesions by CT angiography and their consequences on myocardial blood flow by PET perfusion in a single study. This appears to offer superior diagnostic accuracy in patients with intermediate risk for CAD compared with stand-alone imaging. Novel, commercially available hybrid scanners containing PET and magnetic resonance as well as development of targeted probes to evaluate molecular and cellular disease mechanisms are expected to provide many new applications for cardiac hybrid imaging. This article focuses on the advantages of cardiac hybrid imaging in the detection of CAD in light of currently available clinical data and discusses the potential future applications.     

Anatomic correlates of a normal perfusion scan using 64-slice computed tomographic coronary angiography

Both myocardial perfusion imaging (MPI) and multislice computed tomography (MSCT) are currently used to detect coronary artery disease (CAD). However, MSCT permits early detection of atherosclerosis while myocardial perfusion is still normal. In addition, MPI results can be normal despite the presence of high-risk CAD (left main and balanced 3-vessel CAD). In this study, the range of anatomic findings using MSCT in patients with normal MPI results was evaluated. In 180 patients presenting with chest pain, MPI (with gated single-photon emission computed tomography) and 64-slice MSCT were performed. In patients with normal MPI results, prevalences of completely normal coronary arteries, nonobstructive CAD, and obstructive CAD were determined using MSCT. The occurrence of high-risk CAD, including left main and 3-vessel disease, was also evaluated. Normal MPI and adequate MSCT findings were obtained in 97 patients (54%; 50% women; average age 58 +/- 12 years; 5% with known CAD). A total of 38 patients (39%) showed normal coronary anatomy, whereas nonsignificant and significant CAD were observed in 37 (38%) and 18 patients (19%), respectively. Importantly, only 4 patients (4%) presented with high-risk CAD using 64-slice MSCT, 2 with left main and 2 with 3-vessel disease. In conclusion, a normal MPI result can be associated with a wide range of anatomic observations and cannot exclude the presence of both nonobstructive and obstructive CAD. However, importantly, the prevalence of high-risk CAD was rare.