Challenges for measurement of myocardial perfusion and perfusion reserve by SPECT imaging

Conclusions  The present study by Storto et al¹ provides additional evidence that quantitative estimates of myocardial perfusion and perfusion reserve can be derived from SPECT myocardial perfusion images by use of equipment, tracers, and techniques that are available in most nuclear cardiology laboratories. Additional clinical studies are needed to optimize the methods used to derive the quantitative estimates of perfusion and perfusion reserve from the SPECT imaging studies and, ultimately, to determine the applicability of these measurements to the daily practice of nuclear cardiology.     

Fluorine-18-deoxyglucose SPECT and coincidence imaging for myocardial viability: clinical and technologic issues

Beyond myocardial blood flow and contractile function, the clinical practice of nuclear cardiology is on the verge of expanding its procedures to include the characterization of myocardial metabolism in various cardiovascular disorders. FDG provides the opportunity to probe the glucose utilization status of the human heart. This opportunity is no longer confined to a single technology, such as PET, with a dedicated cyclotron facility, or a single disease condition, such as assessment of myocardial viability. The potential of FDG imaging with a modified gamma camera would enable the application of FDG (as well as other positron-labeled tracers in the future) to the daily clinical practice of nuclear cardiology in concert with conventionally used single-photon tracers, such as Tl–201 and Tc–99m–labeled perfusion tracers.     

Myocardial perfusion imaging agents: SPECT and PET

The advent of myocardial perfusion imaging 30 years ago was a major landmark, which heralded the emergence of the field of nuclear cardiology into clinical practice. Over the years, the different tracers cited in this review have been used with SPECT or PET imaging technologies for the noninvasive evaluation of regional myocardial blood flow, which has enhanced our ability to diagnose CAD, assess prognosis, detect viable myocardium, and evaluate the efficacy of therapies aimed at improving myocardial blood flow. In the future, new SPECT perfusion agents should be developed and validated in the experimental laboratory for feasibility in the clinical setting. Hopefully, such new radiolabeled perfusion agents will have a high first-pass extraction, will be more linear with flow increases in the hyperemic range, and will be labeled with Tc-99m. The clearance rates from the myocardium after initial uptake should be slow enough, as with Tl-201, to acquire high-quality poststress gated SPECT images. Ideally, such perfusion agents should also be extracted intracellularly with quantitative uptake reflecting the degree of viability (eg, as with Tl-201). Absolute quantitation of myocardial blood flow in milliliters per minute per gram by use of SPECT technology would be highly desirable, particularly to increase the detection rate of multivessel disease in which flow reserve is uniformly diminished. This is often categorized as balanced ischemia. Absolute quantitation is a major strength of PET perfusion tracers, as is the ability to accurately correct for attenuation, thereby providing high sensitivity and specificity for CAD detection. The roll-off or plateau in myocardial uptake with hyperemia is also seen with the PET perfusion tracers such as N-13 ammonia and Rb-82. Despite the advent of molecular imaging and the introduction of new imaging agents by which to noninvasively evaluate biologic processes such as apoptosis and angiogenesis in vivo, myocardial perfusion imaging will remain the mainstay of nuclear cardiology in the near future. Continued research and development for this imaging technique are warranted for the reasons cited in this review.     

Quantification of nuclear cardiac images: The Yale approach

Conclusion  Quantification of nuclear cardiac images provides a secondary support in reading myocardial perfusion images and improves the reproducibility in the diagnosis of cardiovascular diseases. The technology for the remote Web reading of nuclear cardiac images and the quantitative data allows for an easy and secured access to patient studies without the limitations of time and space. The recent increasing interests and applications in molecular targeted imaging have opened a new field in nuclear cardiology, and absolute image quantification of the focal tracer uptake in the myocardium is exceedingly critical for the quantitative analysis of molecular targeted images.     

Acute myocardial perfusion imaging for the technologist

Conclusion  Acute myocardial perfusion imaging involves careful planning from the nuclear medicine or nuclear cardiology laboratory to ensure optimal results are achieved. The role of the technologist is to ensure a high-quality study is performed on every patient who is referred to the laboratory. This is one of the most important roles because the decision for further evaluation can be based on the interpretation of the acute images. When acute myocardial perfusion imaging is used appropriately, in conjunction with standard methods of evaluation for patients presenting to the emergency department with chest pain syndromes perceived to be cardiac in origin, it can be of great benefit. It offers a more definitive diagnosis of chest pain syndromes and can be used to reduce the expense of otherwise costly hospital stays, even in patients with moderate risk of ischemic heart disease.     

Nonperfusion applications in nuclear cardiology: Report of a task force of the American society of nuclear cardiology

Conclusions  In conclusion, there seems to be a combination of factors that have contributed to the underutilization of nonperfusion applications of nuclear cardiology. For some procedures (i.e., infarct-avid imaging, probe radiocardiography, and functional evaluation with mental stress) there is a perceived lack of clinical application. For these, further clinical validation and education of referring physicians is necessary. Other nonperfusion studies (i.e., equilibrium RNV) have not kept pace technologically with competing modalities. For these, camera and computer manufacturers should be encouraged to develop and implement appropriate new hardware and software. For others (i.e., ¹²³I MIBG “nerve” imaging and fatty acid analog metabolic imaging) radiopharmaceutical availability, particularly in the United States, is severely limited. For these, radiopharmaceutical companies should be encouraged to sponsor clinical trials validating clinical efficacy and cost-effectiveness, and if justified, appropriate applications should be filed with federal agencies. Last, and perhaps most important, physicians practicing nuclear cardiology must be motivated to embrace these nonperfusion radionuclide applications when appropriate, target patient populations in their institutions who will most benefit, and convince referring physicians of the clinical efficacy and cost effectiveness. For these and so many other facets of nuclear cardiology, the old cliché applies: “Nothing ventured, nothing gained.” One of the concerns I had when I started my term as President of the ASNC was the lack of clinical or research activities in the other areas of nuclear cardiology outside of perfusion imaging. It seemed to me that we had put all of our eggs in one basket! Although perfusion imaging was and is still on the rise, other important technniques that we often used in the past have now been relegated to the group of techniques seldom used. To address this concern, we created a task force on the nonperfusion uses of nuclear cardiology to summarize the state of the art in those other areas, to try to understand the reasons for a deceleration in their use, and to propose ways to reverse this process. Gordon DePuey did a superb job with a group of top expers who met several times to discuss these less-used techniques. Their conclusions and suggestions are thought generating and I hope will serve as a stepping stone for nuclear cardiologists to reevaluate these other important components of nuclear cardiology. Mario S. Verani, MD Past President, ASNC     

A historical perspective on measurement of ventricular function with scintigraphic techniques: Part II-Ventricular function with gated techniques for blood pool and perfusion imaging

Conclusion  In this 2-part article, we have tracked the development of nuclear cardiology from its rudimentary but inventive beginnings to its current, somewhat unenviable position at the pinnacle of all diagnostic and prognostic imaging in our health care system. The tools have changed, but the goal has essentially been constant. For all of its biochemical, endovascular, valvular, and neural complexity, the heart is ultimately and simplistically still just a hydraulic pump. Thus any relevant cardiac imaging modality or therapy will begin with, parallel, target, or end with the assessment of cardiac function. As nuclear cardiology moves into the future with multimodality image integration (eg, hybrid imaging with SPECT or positron emission tomography perfusion and computed tomography calcium scoring and angiography), dynamic assessment of ventricular function will predictably be a critical ingredient to the clinical success of these new modalities.     

慢性稳定型冠心病的核素心肌灌注显像临床应用进展

多项临床试验证明,核素心肌灌注显像在冠心病诊断、危险度分层、预后判断、病人处理方案等方面具有突出的作用和优越的价值。在ACC/AHA(美国心脏病学院/美国心脏学会)有关冠心病和核心脏病学指南中,心肌灌注显像的上述作用得到了充分肯定。合理应用该项技术可以提高对冠心病诊断、处理的整体水平,并使有限的医疗资源得到更合理利用,这在我国目前显得十分迫切和需要。     

Myocardial viability: Seeking relevance and redefinition

Conclusions  More than any other discipline, nuclear cardiology has contributed to understanding of myocardial viability, including the concepts of hibernation and stunning. It must be recognized, however, that these concepts are used as models to drive the process of scientific inquiry. These models may describe components of the pathophysiology of ventricular dysfunction in CAD. Integration of the models of hibernation and stunning may represent the next step toward a more complete understanding of how CAD causes ventricular dysfunction. As such, we are now poised to redirect the field of viability assessment. Although the development of improved instrumentation, new tracers, and better software are important, the areas of investigation that will have the most significant effect on cardiology as a whole are those that will elucidate the pathophysiologic components of LV dysfunction in CAD. The knowledge can then be applied to clinical processes such as viability assessment, with attention to how new techniques affect prognosis and cost of health care. The nuclear imaging community should strive to develop techniques that are complementary to “competing” technologies such as magnetic resonance imaging and echocardiography, providing incremental information. Significant contributions to these lines of investigation will require cooperative studies to achieve adequate statistical power, including collaboration with the PET community. With studies addressing both the pathophysiology and the impact on clinical outcomes of myocardial viability and its assessment, the nuclear cardiology community will have much to contribute to our understanding of CAD.     

Direct imaging of myocardial ischemia: a potential new paradigm in nuclear cardiovascular imaging

Myocardial perfusion imaging has been in clinical use for over 30 years, serving as an effective, reliable, and relatively simple tool for diagnosis, risk stratification, and long-term follow-up of patients with suspected or known coronary artery disease. However, a unique strength of nuclear imaging is its ability to provide tools for imaging biochemical and metabolic processes and receptor and transporter functions at molecular and cellular levels in intact organisms under a wide variety of physiologic conditions. Despite their high resolution and technical sophistication, other imaging modalities currently do not have this capability. Metabolic imaging techniques using radiolabeled free fatty acid and glucose analogs provide a unique ability to image myocardial ischemia directly in patients with known or suspected coronary artery disease. These techniques can potentially overcome some of the limitations of currently used stress-rest perfusion imaging and also provide a unique opportunity to detect and image an episode of ischemia in the preceding hours even in the absence of other markers of ongoing myocardial ischemia. We describe recent studies using fluorine 18-labeled deoxyglucose and iodine 123 β-methyl-p-iodophenyl-pentadecanoic acid for imaging myocardial ischemia.     

Nuclear medicine procedures in cardiovascular diseases. An evidence based approach.

The aim of evidence-based medicine is to integrate individual clinical expertise with the best available external clinical evidence from systematic research. The aim of this article is to introduce the concept of evidence based medicine and to review the evidence for applying cardiovascular nuclear medicine in various clinical settings. A systematic review is defined as a scientific technique to identify and summarize evidence on effectiveness of interventions and to allow the consistency of research. Different clinical applications of nuclear medicine procedures in cardiology have been reviewed. Radionuclide imaging techniques appear to be appropriate in risk assessment, prognosis and evaluation of therapy in patients after acute myocardial infarction. In patients with unstable angina, radionuclide testing is indicated in the identification of ischemia within the distribution of the "culprit" lesion or in remote areas. Exercise and pharmacological cardiac perfusion imaging are appropriate and useful in the diagnosis and prognosis of chronic coronary artery disease. Nuclear medicine procedures are also useful in the assessment of myocardial viability in patients with left ventricular dysfunction, in the assessment of interventions for the evaluation of patients after percutaneous transluminal coronary angioplasty and coronary artery bypass grafting. There has been rapid evolution in radionuclide imaging technologies and both the number and the complexity of choices for the clinician have increased. Further progress in technology and clinical applications of nuclear cardiology may be expected. The development of new instrumentation and of new agents will allow consistent progress and improve the state-of-art of nuclear cardiology. Thus, guidelines for the use of cardiac radionuclide imaging have been difficult to develop and apply. An evidence-based approach may be useful for the best use of nuclear medicine procedures in cardiovascular diseases.     

Characterization of Japanese standards for myocardial sympathetic and metabolic imaging in comparison with perfusion imaging

Objective  The standard patterns of myocardial radiotracer distribution of ¹²³I-metaiodobenzylguanidine (MIBG) and ¹²³I-β-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) should be defined in a Japanese population. The purpose of this study was to present and provide data on the characteristics of MIBG and BMIPP with respect to myocardial single photon emission computed tomography. Methods  The normal database included ¹²³I-MIBG and ¹²³I-BMIPP imaging and a ^99mTc-sestamibi/tetrofosmin myocardial perfusion study. The projection images were transferred by digital imaging and communications in medicine (DICOM) format and reconstructed and analyzed with polar maps. Results  The projection data from multiple centers were successfully transferred to a common format for SPECT reconstruction. When the average values were analyzed using a 17-segment model, MIBG uptake in the inferior and apical wall appeared to be slightly lower than anterior uptake (P < 0.05). The inferior and apical uptake of MIBG has a larger standard deviation (10.7 units in males, 12.6 units in females). BMIPP uptakes in the septal wall have higher than that of ^99mTc-tracer uptake (P < 0.05). Conclusion  Myocardial sympathetic nerve and metabolic scintigraphy data that were specific for the Japanese population were generated and found to be different from that of perfusion tracers. The normal database can serve as a standard for nuclear cardiology work conducted in Japan.     

Eighth Annual Mario S. Verani,MD Memorial Lecture: Nuclear cardiology in the era of multimodality cardiac imaging: Can we survive?

Nuclear cardiology is the best noninvasive imaging method for measuring myocardial blood flow to diagnose coronary artery disease, assess the risk for adverse cardiac events, and identify long-term cardiac outcome. Our strengths include: reliance on physiology rather than anatomic definition; standardized and efficient techniques that can be performed in large hospitals and academic centers and in small hospitals and outpatient offices; a large body of evidence-based supporting clinical data; and profitability. We have defined training; committed to quality improvement through development of guidelines and appropriateness criteria; certified physicians and accredited laboratories; and implemented a strong payer advocacy program. Despite success, we find ourselves under attack for not being relevant within the new paradigm of atherosclerosis, being complacent, being used inappropriately, and exposing patients to radiation. We are facing cuts in reimbursement that will make it nearly impossible to provide services. By failing to develop new radiotracers and techniques, we find ourselves measuring only myocardial perfusion. Advances in echocardiography, cardiovascular magnetic resonance imaging, and computed tomography are providing alternative robust methods and redefining available options for noninvasive cardiovascular imaging. Given the attacks on nuclear cardiology and the existence of alternative methods, we have the option of becoming defensive and protective of our turf, or embracing the opportunity to build on our accomplishments and redefine the new practice of noninvasive cardiovascular imaging. It is in the best interest of nuclear cardiology and patients to pursue the latter course.     

Progress in nuclear cardiology: new imaging beyond perfusion and function

The rapid development of nuclear medicine instruments and the widespread availability of new radiopharmaceutical agents has created a new era of nuclear cardiology. This review will introduce new techniques beyond perfusion and function that have recently become available in Japan. Tc-99m perfusion imaging agents provide excellent myocardial perfusion images that may enhance diagnostic accuracy in the study of coronary artery disease. In addition, greater photon flux from the tracer permits simultaneous assessment of regional perfusion and function with the use of first-pass angiography or ECG-gated acquisition. In addition, Tc-99m perfusion agents are available for acute patients in emergency departments. When the tracer is administrated at both the acute and subacute phases of myocardial infarction, perfusion SPECT imaging permits accurate estimates of areas at risk and salvaged myocardium. Nuclear cardiology has progressed toward biochemical imaging in vivo. Positron emission tomography (PET) enables metabolic assessment in vivo. Preserved FDG uptake indicates ischemic but viable myocardium that is likely to improve regional dysfunction after revascularization. While FDG-PET is available only in a limited number of facilities, FDG-SPECT using ultrahigh energy collimators and branched fatty acid analog I-123 BMIPP SPECT offer potential for metabolic imaging in routine clinical settings. Less uptake of BMIPP than thallium is often observed in the ischemic myocardium and hypertrophic cardiomyopathy. Such a perfusion-metabolic mismatch as that in FDG-PET seems to be similarly observed in BMIPP SPECT. Severe ischemia is identified as reduced BMIPP uptake at rest despite normal or normalized perfusion, suggesting a significant role of BMIPP in ischemic memory imaging. I-123 MIBG uptake in the myocardium reflects adrenergic neuronal function in vivo. In the study of coronary artery disease, neuronal denervation is often observed around the infarcted myocardium and post-ischemic region as well. More importantly, reduced MIBG uptake in these patients can assess the severity of congestive heart failure. In addition, the improvement in MIBG can be seen in relation to improved patient condition following medical treatment. These new techniques will provide insights into new pathological states in ischemic heart disease and a variety of myocardial disorders. Nuclear cardiology plays an important role in selecting optimal treatments for these patients.     

Cardiac imaging using nuclear medicine and positron emission tomography

This article concentrates on specific issues that are of current interest in mainstream nuclear cardiology. These include developments in myocardial perfusion technique, the potential diagnostic benefits of ECG-gating and attenuation correction, nuclear imaging in the diagnosis of hibernating myocardium, and the cost-effectiveness of perfusion imaging in patients with suspected angina.     

KSNM60 in Cardiology: Regrowth After a Long Pause

The Korean Society of Nuclear Medicine (KSNM) is celebrating its 60th anniversary in honor of the nuclear medicine professionals who have dedicated their efforts towards research, academics, and the more comprehensive clinical applications and uses of nuclear imaging modalities. Nuclear cardiology in Korea was at its prime time in the 1990s, but its growth was interrupted by a long pause. Despite the academic and practical challenges, nuclear cardiology in Korea now meets the second leap, attributed to the growth in molecular imaging tailored for many non-coronary diseases and the genuine values of nuclear myocardial perfusion imaging. In this review, we describe the trends, achievements, challenges, and perspectives of nuclear cardiology throughout the 60-year history of the KSNM.     

Quantitation in gated perfusion SPECT imaging: The Cedars-Sinai approach

Cedars-Sinai’s approach to the automation of gated perfusion single photon emission computed tomography (SPECT) imaging is based on the identification of key procedural steps (processing, quantitation, reporting), each of which is then implemented, in completely automated fashion, by use of mathematic algorithms and logical rules combined into expert systems. Our current suite of software applications has been designed to be platform- and operating system-independent, and every algorithm is based on the same 3-dimensional sampling scheme for the myocardium. The widespread acceptance of quantitative software by the nuclear cardiology community (QGS alone is used at over 20,000 locations) has provided the opportunity for extensive validation of quantitative measurements of myocardial perfusion and function, in our opinion, helping to make nuclear cardiology the most accurate and reproducible modality available for the assessment of the human heart.     

Advances in quantitative perfusion SPECT imaging

Quantitative software for myocardial perfusion single photon emission computed tomography (SPECT) has advanced significantly over the last 25 years. The strength and availability of quantitative tools for perfusion SPECT have in many ways provided a competitive advantage to nuclear cardiology compared with other higher-resolution noninvasive imaging modalities for the detection of coronary artery disease. The purpose of this report is to review the advances in quantitative diagnostic software for cardiac SPECT over the past 25 years. The time period ending with the 1980s ("the past") saw the origins of nuclear cardiology with the development of planar thallium 201 imaging and perfusion SPECT imaging without electrocardiographic gating. The period from 1990 to the present saw the development of gated SPECT imaging providing both perfusion and functional information and attenuation correction SPECT with improved perfusion information. The report concludes with a look into the future, where hybrid multimodality imaging systems may provide a comprehensive noninvasive evaluation with previously unmatched accuracy in a single imaging session.     

Advances in radionuclide molecular imaging in myocardial biology

Molecular imaging is a new and evolving field that employs a targeted approach to noninvasively assess biologic processes in vivo. By assessing key elements in specific cellular processes prior to irreversible end-organ damage, molecular tools will allow for earlier detection and intervention, improving management and outcomes associated with cardiovascular diseases. The goal of those working to expand this field is not just to provide diagnostic and prognostic information, but rather to guide an individual’s pharmacological, cell-based, or genetic therapeutic regimen. This article will review molecular imaging tools in the context of our current understanding of biological processes of the myocardium, including angiogenesis, ventricular remodeling, inflammation, and apoptosis. The focus will be on radiotracer-based molecular imaging modalities with an emphasis on clinical application. Though this field is still in its infancy and may not be fully ready for widespread use, molecular imaging of myocardial biology has begun to show promise of clinical utility in acute and chronic ischemia, acute myocardial infarction, congestive heart failure, as well as in more global inflammatory and immune-mediated responses in the heart-like myocarditis and allogeneic cardiac transplant rejection. With continued research and development, molecular imaging promises to be an important tool for the optimization of cardiovascular care.     

Assessing the need for nuclear cardiology and other advanced cardiac imaging modalities in the developing world

Background

In 2005, 80% of cardiovascular disease (CVD) deaths occurred in low- to middle-income countries (i.e., developing nations). Cardiovascular imaging, such as myocardial perfusion SPECT, is one method that may be applied to detect and foster improved detection of at-risk patients. This document will review the availability and utilization for nuclear cardiology procedures worldwide and propose strategies to devise regional centers of excellence to achieve quality imaging around the world.

Methods

As a means to establish the current state of nuclear cardiology, International Atomic Energy Agency member and non-member states were queried as to annual utilization of nuclear cardiology procedures. Other sources for imaging statistics included data from medical societies (American Society of Nuclear Cardiology, European Society of Cardiology, and the European Association of Nuclear Medicine) and nuclear cardiology working groups within several nations. Utilization was calculated by dividing annual procedural volume by 2007 population statistics (/100,000) and categorized as high (>1,000/100,000), moderate-high (250-999/100,000), moderate (100-249/100,000), low-moderate (50-99/100,000) and low (<50/100,000).

Results

High nuclear cardiology utilization was reported in the United States, Canada, and Israel. Most Western European countries, Australia, and Japan reported moderate-high utilization. With the exception of Argentina, Brazil, Colombia and Uruguay, South America had low usage. This was also noted across Eastern Europe, Russia, and Asia. Utilization patterns generally mirrored each country’s gross domestic product. However, nuclear cardiology utilization was higher for developing countries neighboring moderate-high “user” countries (e.g., Algeria and Egypt); perhaps the result of accessible high-quality training programs.

Conclusions

Worldwide utilization patterns for nuclear cardiology vary substantially and may be influenced by physician access to training and education programs. Development of regional training centers of excellence can guide utilization of nuclear cardiology through the application of guideline- and appropriateness-driven testing, training, continuing education, and quality assurance programs aiding developing nations to confront the epidemics of CVD.