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.     

Myocardial perfusion imaging in ischemic heart disease anno 1990

The field of radionuclide myocardial perfusion imaging is in a rapid state of change. Stress-rest myocardial imaging is important not only for the detection of coronary artery disease but also for prognostic stratification of patients. In particular, assessment of myocardial viability in patients with left ventricular dysfunction is a recent focus of investigation. Single-photon emission computed tomography has become widely accepted as the preferred (albeit challenging) imaging modality for myocardial perfusion imaging. Silent myocardial ischemia and its clinical significance continues to be an intriguing aspect of the clinical manifestation of coronary artery disease. Myocardial perfusion imaging is an invaluable independent method to unravel this problem. Dipyridamole was approved for pharmacologic vasodilation in conjunction with myocardial perfusion imaging. At the same time, direct infusion of adenosine was proposed as an alternative method of effecting vasodilatory stress. In 1990, several new technetium-99m-labeled myocardial perfusion imaging agents have been introduced (teboroxime and hexakis-2-methoxyisobutyl-isonitrile [sestaMIBI]) that may have a profound impact on imaging techniques and applications of myocardial perfusion imaging.     

CT-Based Myocardial Perfusion Imaging-Practical Considerations: Acquisition, Image Analysis, Interpretation, and Challenges

Methods for non-invasive, cardiac risk assessment have historically relied on exercise stress testing with or without echocardiography or radionuclide imaging and pharmacological stress testing when appropriate. More recently, CT-based modalities like CT angiography (CTA) have been shown to reliably differentiate low from high-risk coronary disease. The advent of newer CT technology now allows for CT-based myocardial perfusion imaging (CTP) that provides functional information, that when analyzed with anatomic data from CTA, can provide a comprehensive risk assessment strategy. In this review, we discuss the research and implementation; as well as the quantitative, semiquantitative, and qualitative methods of image analysis of CT-based perfusion. We also discuss the present state of technology and challenges associated with the methodology. In each section, when appropriate, we provide some information regarding the translation of these methods being utilized in the international, multicenter CORE320 study that is evaluating the combined CT-based imaging (CTA and CTP) strategy of risk assessment in comparison to the combined reference standard of radionuclide myocardial perfusion imaging and invasive angiography.     

Diagnostic and Prognostic Value of Myocardial Perfusion Imaging in Patients with Known or Suspected Stable Coronary Artery Disease

Coronary artery disease is the leading cause of complications and death in the United States and other Western countries, and stress myocardial perfusion study is an important component of the clinical evaluation, stratification, and management. This imaging technique is a well-established modality and has been widely used for the past three decades. New quantitative techniques for the assessment of ventricular function using quantitative gated single-photon emission computed tomography in addition to myocardial perfusion will potentially enhance the role of nuclear cardiology in the management of these patients. This review summarizes the current knowledge of the diagnostic and prognostic uses of stress myocardial perfusion imaging using exercise and pharmacological stress in patients with stable coronary artery disease.     

Single photon emission computed tomography of technetium-99m tetrofosmin myocardial perfusion imaging in patients with systemic lupus erythematosus--a preliminary report

The purpose of this study was to evaluate the utility of single-photon emission computed tomography (SPECT) of technetium-99m tetrofosmin (Tc-99m TF) myocardial perfusion imaging to detect myocardial involvement in patients with systemic lupus erythematosus (SLE). Three groups of subjects-group 1: 25 SLE female patients with non-specific cardiac symptoms and signs, group 2: 25 female SLE patients without any cardiac symptoms and signs, and group 3: 25 female healthy controls-were evaluated by comparing rest and dipyridamole-stress Tc-99m TF myocardial perfusion SPECT. Tc-99m TF myocardial perfusion SPECT revealed perfusion defects in 88% and 40% of the cases in groups 1 and 2. respectively. However, no cases in group 3 demonstrated myocardial perfusion defects. Tc-99m TF myocardial perfusion SPECT is a useful noninvasive imaging modality to detect cardiac involvement in SLE patients with or without cardiac symptoms and signs.     

Myocardial Perfusion Imaging with Cardiac Computed Tomography: State of the Art

Cardiac computed tomography (CCT) has become an important tool for the anatomic assessment of patients with suspected coronary disease. Its diagnostic accuracy for detecting the presence of underlying coronary artery disease and ability to risk stratify patients are well documented. However, the role of CCT for the physiologic assessment of myocardial perfusion during resting and stress conditions is only now emerging. With the addition of myocardial perfusion imaging to coronary imaging, CCT has the potential to assess both coronary anatomy and its functional significance with a single non-invasive test. In this review, we discuss the current state of CCT myocardial perfusion imaging for the detection of myocardial ischemia and myocardial infarction and examine its complementary role to CCT coronary imaging.     

Stress CT perfusion: coupling coronary anatomy with physiology

While multiple different imaging tests can be used to evaluate patients with known or suspected coronary artery disease (CAD), each of them is designed to evaluate either coronary anatomy or physiology. Recently, it has been recognized that cardiac CT can be used to evaluate stress and rest myocardial perfusion in addition to its capabilities to image the coronary arteries, thus allowing for the simultaneous evaluation of the anatomical burden and physiological significance of CAD in a single exam. In this review, the strengths and the limitations of imaging coronary anatomy and myocardial perfusion will be discussed. Next, key technical aspects of how to perform and interpret CT perfusion imaging will be summarized while providing an update of the most recent data in this emerging field. Finally, future directions and opportunities for further research will be discussed.     

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.     

Myocardial perfusion imaging with contrast echocardiography

Advances in myocardial perfusion imaging have firmly established the use of noninvasive techniques capable of providing useful information over a broad range of diagnostic and therapeutic cardiovascular problems. Evaluating regional myocardial perfusion abnormalities is a cornerstone for the diagnosis of coronary artery disease, risk assessment in those with known disease, and determination of myocardial viability. The clinical use of myocardial perfusion imaging and the current limitations of existing techniques continue to promote the development of new technologies capable of assessing microvascular and capillary perfusion abnormalities on a global myocardial level. Myocardial contrast echocardiography is an emerging technique capable of rapidly assessing myocardial perfusion at the capillary level in many different clinical settings. This article focuses on myocardial contrast-enhanced ultrasound perfusion techniques, emphasizing the unique information this modality provides compared with other noninvasive perfusion imaging techniques.     

Myocardial perfusion defects in patients with autoimmune diseases: a prospective study. Analysis of two diagnostic tests

A significant correlation between autoimmune diseases and premature or accelerated coronary atherosclerosis has been found. The objectives of the study were: (a) to evaluate myocardial perfusion defects in patients with autoimmune diseases by contrast echocardiography and nuclear imaging; and (b) to evaluate the prevalence of alterations in subclinical myocardial perfusion defects in autoimmune diseases. Myocardial perfusion in 37 patients was evaluated by contrast echocardiography at rest and with dobutamine and with nuclear imaging. The agreement between the two diagnostic tests at rest was 0.72 (P < 0.0001) and with dobutamine was 0.65 (P < 0.0001). The prevalence of abnormalities in myocardial perfusion in autoimmune diseases by contrast echocardiography and nuclear imaging was 27% and in patients with primary antiphospholipid syndrome was 30%. We concluded that there is a high level of agreement between contrast ecocardiography and nuclear imaging for assessment of myocardial perfusion defects in patients with autoimmune diseases, and their prevalence is similar to that reported in the literature.     

Role of myocardial perfusion imaging for risk stratification in suspected or known coronary artery disease

Nuclear cardiology is an evolving specialty that has recently benefited from technological and radiopharmaceutical advances. As a result there has been an increase in the accuracy of myocardial perfusion imaging (MPI) with gated single photon emission computed tomography (SPECT) for assessing the diagnosis and prognosis of coronary artery disease. Moreover, ECG gated SPECT allows the simultaneous assessment of both myocardial perfusion and left ventricular function, which provides additional prognostic value. With increasing concern over early detection of coronary artery disease and its effective treatment, myocardial perfusion imaging is ideally placed to provide a full "one stop" functional assessment for any patient, irrespective of their exercise capacity. This applies not only to patients with chest pain but also to those with myocardial infarction, revascularisation, and heart failure, and those being assessed for non-cardiac surgery. The focus of this review is the use of myocardial perfusion imaging in risk stratification for coronary artery disease.     

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.     

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.     

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.     

Hybrid SPECT-CT: Integration of CT coronary artery calcium scoring and angiography with myocardial perfusion

A natural extension of current imaging paradigms for diagnosing coronary artery disease may well be the integration of CT with myocardial perfusion single-photon CT (SPECT). Although there is a wealth of clinical information regarding the utility of SPECT, the value of CT in the cardiology arena has only recently been explored. CT has the advantage of detecting coronary atherosclerosis at its earliest stages, allowing initiation of appropriate therapeutic measures well before development of obstructive coronary artery disease. However, SPECT can clarify the anatomic findings of CT based on a functional assessment of myocardial blood flow, thereby guiding management decisions. Hybrid imaging with SPECT and CT angiography may prove important from a diagnostic and therapeutic view point in several clinical scenarios, and it is likely that over the next decade fusion imaging may more precisely tailor therapy, reduce healthcare costs, and improve patient outcome.     

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.     

Cardiac PET-CT

Integrated positron emission tomography computed tomography (PET/CT) scanners allow a true integration of the structure and function of the heart. Myocardial perfusion PET provides a high sensitivity (91%) and specificity (89%) for the diagnosis of obstructive coronary artery disease (CAD). But, as with single photon emission CT, relative perfusion PET often uncovers only the territory subtended by the most severe coronary stenosis, leading to underestimation of the extent of CAD. In contrast, quantitative PET provides a noninvasive assessment of myocardial blood flow and coronary flow reserve and improves detection of preclinical and multivessel coronary atherosclerosis. Similarly, CT coronary angiography is an accurate means to image the entire continuum of anatomic coronary atherosclerosis from nonobstructive to obstructive CAD. However, not all coronary stenoses are hemodynamically significant and <50% of the patients with obstructive CAD on CT angiography demonstrate stress induced perfusion defects. Stress PET data complement the anatomic information on the CT angiogram by providing instant readings about the ischemic burden of coronary stenoses. Thus, combined PET/CT may be potentially superior to CT angiography alone for the guiding revascularization decisions. Further, fusion of the PET and CT angiogram images allows identification of the culprit stenosis in patients presenting with chest pain. Finally, the advances in molecular imaging and image fusion may soon make noninvasive detection of vulnerable coronary plaques a clinical reality. In summary, integrated PET/CT is a powerful new noninvasive modality that offers the potential for refined diagnosis and management of the entire spectrum of coronary atherosclerosis.     

NC100100, a new echo contrast agent for the assessment of myocardial perfusion--safety and comparison with technetium-99m sestamibi single-photon emission computed tomography in a randomized multicenter study

BACKGROUND AND HYPOTHESIS: Myocardial contrast echocardiography using second-generation agents has been proposed to study myocardial perfusion. A placebo-controlled, multicenter trial was conducted to evaluate the safety, optimal dose, and imaging mode for NC100100, a novel intravenous second-generation echo contrast agent, and to compare this technique with technetium-99m sestamibi (MIBI) single-photon emission computed tomography (SPECT). METHODS: In a placebo-controlled, multicenter trial, 203 patients with myocardial infarction > 5 days and < 1 year previously underwent rest SPECT and MCE. Fundamental and harmonic imaging modes combined with continuous and electrocardiogram-- (ECG) triggered intermittent imaging were used. Six dose groups (0.030, 0.100, and 0.300 microliter particles/kg body weight for fundamental imaging; and 0.006, 0.030, and 0.150 microliter particles/kg body weight for harmonic imaging) were tested. A saline group was also included. Safety was followed for 72 h after contrast injection. Myocardial perfusion by MCE was compared with myocardial rest perfusion imaging using MIBI as a tracer. RESULTS: NC100100 was well tolerated. No serious adverse events or deaths occurred. No clinically relevant changes in vital signs, laboratory parameters, and ECG recordings were noted. There was no significant difference between adverse events in the NC100100 (25.7%) and in the placebo group (17.9%, p = 0.3). Intermittent harmonic imaging using the intermediate dose was superior to all other modalities, allowing the assessment of perfusion in 76% of all segments. Eighty segments (96%) with normal perfusion by SPECT imaging also showed myocardial perfusion with MCE. However, a substantial percentage of segments (61-80%) with perfusion defects by SPECT imaging also showed opacification by MCE. This resulted in an overall agreement of 66-81% and a high specificity (80-96%), but in low sensitivity (20-39%) of MCE for the detection of perfusion defects. CONCLUSION: NC100100 is safe in patients with myocardial infarction. Intermittent harmonic imaging with a dose of 0.03 microliter particles/kg body weight can be proposed as the best imaging protocol. Myocardial contrast echocardiography with NC 100100 provides perfusion information in approximately 76% of segments and results in myocardial opacification in the vast majority of segments with normal perfusion as assessed by SPECT. Although the discrepancies between MCE and SPECT with regard to the definition of perfusion defects requires further investigation, MCE with NC 100100 is a promising technique for the noninvasive assessment of myocardial perfusion.     

Cardiac stress MRI evaluation of anomalous aortic origin of a coronary artery

Myocardial ischemia is an insult that is primarily thought of in an adult population. However, there are several congenital and acquired cardiac lesions that may lead to myocardial ischemia in a pediatric population. One of the prominent congenital lesions is anomalous aortic origin of a coronary artery (AAOCA). Anomalous aortic origin of a coronary artery is one of the leading causes sudden cardiac death in pediatric and young adult patients, and thus the assessment of myocardial perfusion is of the utmost importance. Over the past decade, pharmacologic stress MRI has proven to be a highly sensitive and accurate diagnostic examination for qualifying myocardial perfusion in adults with coronary artery disease. This noninvasive imaging modality may be a useful tool in assessing the function impact of AAOCA on myocardial perfusion.     

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.