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.     

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.     

IQ·SPECT、碲锌镉探测器SPECT和传统SPECT在心肌灌注显像中的应用分析

IQ·SPECT与碲锌镉（CZT）探测器SPECT是心肌灌注显像新技术,与传统SPECT相比,具有灵敏度和空间分辨率高、采集时间短、注射显像剂剂量少及辐射剂量低等优点。与传统SPECT不同（低能高分辨率平行孔准直器）,IQ·SPECT使用SMART-ROOM准直器及心脏为焦点的采集模式,提高了灵敏度;CZT探测器SPECT的探测器为半导体,取代了传统NaI晶体探测器,提高了能量分辨率、空间分辨率、灵敏度及信噪比等,并可定量分析心肌血流储备。笔者主要对三者的成像原理、性能参数及临床应用进行综述。     

Significance of 99mTc-labeled perfusion agents in the simultaneous assessment of myocardial perfusion and cardiac function

Simultaneous assessment of left ventricular myocardial perfusion and systolic function was accomplished by utilizing ECG-gated myocardial perfusion SPECT. This development in nuclear cardiology will be attributed to the recent advances in new 99mTc-labeled perfusion agents, multi-detector SPECT system and software for automatic edge-detection of the left ventricle. In this article, we described about the clinical utilities of this method in detecting "hibernating myocardium," severe coronary artery disease patients with exercise-induced LV dysfunction, in predicting functional recovery after reperfusion therapy for acute myocardial infarction patients and in diagnosing patients with right heart diseases.     

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.     

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.     

Visual assessment of left ventricular perfusion and function with electrocardiography-gated SPECT has high intraobserver and interobserver reproducibility among experienced nuclear cardiologists and cardiology trainees

BACKGROUND: Stress electrocardiography (ECG)-gated single photon emission computed tomography (SPECT) for assessment of left ventricular perfusion and function improves the confidence of interpretation and enhances specificity for detection of coronary artery disease. The reproducibility of visual interpretation of ECG-gated SPECT images and the significance of training and experience have not been reported previously in a large series of consecutive patients. We evaluated both intraobserver and interobserver agreement of interpretation of ECG-gated SPECT images among 3 cardiology trainees and 3 experienced nuclear cardiologists from 3 institutions. METHODS AND RESULTS: Three nuclear cardiologists and 3 cardiology trainees who had fulfilled American College of Cardiology/American Society of Nuclear Cardiology Core Cardiology Training Symposium (ACC/ASNC COCATS) guidelines for level II training in nuclear cardiology independently evaluated 106 consecutive technetium 99m sestamibi SPECT images with ECG gating of either the stress or rest images. All cases were interpreted blindly, twice in random sequence, without clinical data. We assessed intraobserver and interobserver agreement for myocardial perfusion, left ventricular regional and global systolic function, and overall clinical impression, by means of percent agreement and Cohen's kappa statistic. Intraobserver agreement was good (82%-92%, kappa = 0.54-0.84) for assessment of myocardial perfusion, systolic function, and overall impression. Interobserver agreement was also good, ranging from 65% to 90% (kappa = 0.32-0.76), with better agreement found for assessment of function (77%-85%, kappa = 0.52-0.7) than for perfusion (65%-80%, kappa = 0.32-0.6). For all measures, there were no significant differences in reproducibility between nuclear cardiologists and cardiology trainees. CONCLUSIONS: Interpretation of ECG-gated SPECT images has high reproducibility and agreement among both nuclear cardiologists and cardiology trainees.     

Automatic and visual reproducibility of perfusion and function measures for myocardial perfusion SPECT

Background  

We define the repeatability coefficients (RC) of key quantitative and visual perfusion and function parameters that can be derived by the QGS/QPS automated software and by expert visual observer from gated myocardial perfusion SPECT (MPS) scans.     

Molecular imaging will replace myocardial perfusion imaging

Conclusion   “The order is rapidly fadin’. And the first one now will later be last ...” In 2008 myocardial perfusion imaging is the main-stay of nuclear cardiology. However, the lyrics of Dylan from the 1960s are applicable today, as we are in rapidly changing times in medicine. We are seeing a paradigm shift in disease detection and treatment from a focus on cardiovascular morphology, function, and pathophysiology to genetic and molecular events. Cardiovascular molecular imaging will be the vanguard of noninvasive imaging in this era. Nuclear cardiology is uniquely positioned to play a central role in both the clinical and research applications of cardiovascular molecular imaging. The question should not be whether myocardial perfusion imaging will remain the dominant clinical application but how does nuclear cardiology transition to embrace and foster cardiovascular molecular imaging. If we do not do this, there are several other imaging specialties that will be more than willing to fill this void.     

Quantitative myocardial perfusion SPECT

In recent years, there has been much interest in the clinical application of attenuation compensation to myocardial perfusion single photon emission computed tomography (SPECT) with the promise that accurate quantitative images can be obtained to improve clinical diagnoses. The different attenuation compensation methods that are available create confusion and some misconceptions. Also, attenuation-compensated images reveal other image-degrading effects including collimator-detector blurring and scatter that are not apparent in uncompensated images. This article presents basic concepts of the major factors that degrade the quality and quantitative accuracy of myocardial perfusion SPECT images, and includes a discussion of the various image reconstruction and compensation methods and misconceptions and pitfalls in implementation. The differences between the various compensation methods and their performance are demonstrated. Particular emphasis is directed to an approach that promises to provide quantititve myocardial perfusion SPECT images by accurately compensating for the 3-dimensional (3-D) attenuation, collimator-detector response, and scatter effects. With advances in the computer hardware and optimized implementation techniques, quantitatively accurate and highquality myocardial perfusion SPECT images can be obtained in clinically acceptable processing time. Examples from simulation, phantom, and patient studies are used to demonstrate the various aspects of the investigation. We conclude that quantitative myocardial perfusion SPECT, which holds great promise to improve clinical diagnosis, is an achievable goal in the near future. Supported in part by the US Public Health Service grant No CA39463 of the Cancer Institute. The contents of this work are solely the responsibility of the authors     

Normal values for nuclear cardiology: Japanese databases for myocardial perfusion,fatty acid and sympathetic imaging and left ventricular function

Myocardial normal databases for stress myocardial perfusion study have been created by the Japanese Society of Nuclear Medicine Working Group. The databases comprised gender-, camera rotation range- and radiopharmaceutical-specific data-sets from multiple institutions, and normal database files were created for installation in common nuclear cardiology software. Based on the electrocardiography-gated single-photon emission computed tomography (SPECT), left ventricular function, including ventricular volumes, systolic and diastolic functions and systolic wall thickening were also analyzed. Normal databases for fatty acid imaging using ¹²³I-beta-methyl-iodophenyl-pentadecanoic acid and sympathetic imaging using ¹²³I-meta-iodobenzylguanidine were also examined. This review provides lists and overviews of normal values for myocardial SPECT and ventricular function in a Japanese population. The population-specific approach is a key factor for proper diagnostic and prognostic evaluation.     

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.     

Clinical myocardial perfusion PET/CT.

The field of nuclear cardiology is witnessing growing interest in the use of cardiac PET for the evaluation of patients with coronary artery disease (CAD). The available evidence suggests that myocardial perfusion PET provides an accurate means for diagnosing obstructive CAD, which appears superior to SPECT especially in the obese and in those undergoing pharmacologic stress. The ability to record changes in left ventricular function from rest to peak stress and to quantify myocardial perfusion (in mL/min/g of tissue) provides an added advantage over SPECT for evaluating multivessel CAD. There is growing and consistent evidence that gated myocardial perfusion PET also provides clinically useful risk stratification. Although the introduction of hybrid PET/CT technology offers the exciting possibility of assessing the extent of anatomic CAD (CT coronary angiography) and its functional consequences (ischemic burden) in the same setting, there are technical challenges in the implementation of CT-based transmission imaging for attenuation correction. Nonetheless, this integrated platform for assessing anatomy and biology offers a great potential for translating advances in molecularly targeted imaging into humans.     

Improvement in PET myocardial perfusion image quality and quantification with flurpiridaz F 18

Rubidium-82 (⁸²Rb), the currently commercially available radiotracer for positron emission tomography (PET) myocardial perfusion imaging (MPI), has led to wide availability of PET-MPI for stress-rest imaging. Compared to SPECT MPI, myocardial perfusion PET images have higher spatial and contrast resolution, are less affected by radiotracer scatter, benefit from more precise attenuation correction, and allow dynamic first pass imaging. In addition, PET imaging allows assessment of myocardial function at peak stress and measurement of absolute myocardial blood flow, thus providing critical data not available with SPECT imaging. Further enhancements of the high quality of PET perfusion images may be realized by technologies under development such as respiratory gating, combined respiratory, and ECG gating to generate “motion-frozen” cardiac images, automated patient motion correction software, and high-definition PET, which reduces distortions introduced by the circular geometry of the scanner. Early studies indicate that the experimental PET radiopharmaceutical flurpiridaz F 18 provides high-quality, high-resolution myocardial perfusion images that may enable improved clinical MPI, and has properties well suited to optimized performance by application of these quantitative analytic technologies.     

Two- and three-dimensional assessments of myocardial perfusion and function by using technetium-99m sestamibi gated SPECT with a combination of count- and image-based techniques

BACKGROUND: Although the myocardial gated single photon emission computed tomography (SPECT) technique makes it possible to assess concurrent myocardial perfusion and function, quantitative methods for analyzing and displaying gated SPECT data in 2- and 3-dimensional presentations for regional and global cardiac assessment have not been established. METHODS AND RESULTS: We have developed an automated quantitative method for assessing perfusion and function by means of technetium-99m sestamibi gated SPECT with a computerized technique combining count-based and image-based methods. We have examined its validity in 91 patients by comparing its results with those of conventional techniques: contrast left ventriculography and radionuclide angiocardiography. In addition to color-scale displays of regional function, simultaneous 3-dimensional presentations of regional wall motion and perfusion have been produced. High reproducibility of gated SPECT analysis with this algorithm was demonstrated; interoperator errors (%CV) were 2.6% to 5.5%, and good intraobserver reproducibility was confirmed by means of high correlation coefficients (0.954 to 0.989). Left ventricular volumes assessed by means of contrast left ventriculography and by means of the gated SPECT technique showed significant correlations (left ventricular end-diastolic volume, y = 1.01x - 9.7, r = 0.845, P<.001, standard errors of the estimate [SEE] = 14 mL; left ventricular end-systolic volume, y = 1.03x - 1.4, r = 0.902, P<.001, SEE = 6 mL). Left ventricular ejection fraction determined by means of gated SPECT with the new algorithm closely correlated with that determined by means of radionuclide ventriculography (y = 1.05x - 0.6, r = 0.891, P<.001, SEE = 3 %). These parameters quantified by means of the present method correlated closely with those derived from the QGS program (r = 0.926 to 0.987). CONCLUSION: In comparison with conventional techniques, myocardial gated SPECT with automated quantitative analysis provides accurate and reproducible data for global and regional function. Quantitative concurrent assessment of myocardial perfusion and function by using 2-and 3-dimensional representations appears to be superior to other modalities and to contribute to nuclear cardiology practice.     

门控心肌灌注SPECT在冠心病方面的应用进展

门控心肌灌注SPECT能同时获得心肌血流灌注情况和左心室功能参数,是目前核素心脏检查中常用的方法。此法可重复性强,在临床应用广泛,为冠心病患者的诊断、危险度分层、心肌活力评价、治疗、预后及疗效的评价提供了可靠的依据。     

Creation and characterization of Japanese standards for myocardial perfusion SPECT: database from the Japanese Society of Nuclear Medicine Working Group

Objective Standards for myocardial single-photon emission computed tomography (SPECT) adapted for a Japanese population were not available. The purpose of this study was to create standard files approved by the Japanese Society of Nuclear Medicine and to make known the characteristics of the myocardial perfusion pattern of this population. Methods With the collaboration of nine hospitals, a total of 326 sets of exercise–rest myocardial perfusion images were accumulated from subjects with a low likelihood of cardiac diseases. The normal database included a ^99mTc-MIBI/tetrofosmin myocardial perfusion study with 360° (n = 80) and 180° (n = 56) rotations, ²⁰¹Tl study with 360° (n = 115) and 180° rotations (n = 54) and a dual-isotope study with 360° rotation (n = 27). 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, myocardial counts in the septal segment differed significantly between 180° and 360° rotation acquisitions. Regional differences were observed between men and women in the inferior and anterior regions. A tracer difference between ^99mTc and ²⁰¹Tl was also observed in some segments. The attenuation patterns differed significantly between subjects from the United States and those from Japan. Conclusions Myocardial perfusion data that were specific for the Japanese population were generated. The normal database can serve a standard for nuclear cardiology work conducted in Japan. All author are members of the JSNM Working Group of Standardization of Myocardial SPECT in a Japanese Population.     

Assessment of cardiac function and myocardial metabolism by nuclear medicine]

Simultaneous assessment of myocardial perfusion and cardiac function came to be possible by 99mTc myocardial perfusion agents. We can use ECG-gated SPECT and first pass radionuclide angiocardiography for it. ECG-gated SPECT made it possible to assess wall motion using wall thickening and QGS (quantitative gated SPECT) analysis, which are useful in various clinical situations. First pass radionuclide angiocardiography gives good assessment of cardiac function during stress, and supports the diagnosis of myocardial ischemia. On the other hand, the assessment of myocardial metabolism is another specific feature of nuclear cardiology. 123I-BMIPP SPECT is applicable to various cardiac diseases such as ischemic heart disease, and 18F-FDG PET has been considered as the gold standard of myocardial viability. Recently, gamma camera for 18F-FDG imaging has been developed, which may make FDG imaging more popular.     

Noninvasive stress testing of myocardial perfusion defects: head-to-head comparison of thallium-201 SPECT to MRI perfusion

Background  To evaluate the diagnostic value of magnetic resonance imaging (MRI) of myocardial perfusion in the assessment of flow-limiting epicardial stenosis in a head-to-head comparison with abnormal thallium-201 (²⁰¹TI) single photon emission tomography (SPECT) studies in patients with predominantly known coronary artery disease (CAD). Methods and Results  Twenty-one patients (mean age 65 ± 10 years) with reversible myocardial perfusion defects on ²⁰¹TI-SPECT images during dipyridamole-stimulated hyperemia were recruited for study purpose. Within 5 days of the ²⁰¹TI-SPECT study, myocardial perfusion was studied again with MRI during dipyridamole stimulation and at rest. Overall, ²⁰¹TI-SPECT identified 30 reversible regional perfusion defects. The sensitivity to detect hypoperfused segments was 70% (21/30) with the GRE-MRI perfusion analysis with ²⁰¹TI-SPECT as reference. When patients were subgrouped according to the extent of regional reversible perfusion defects on ²⁰¹TI-SPECT, mild- (SDS: 2-4), moderate- (SDS: 5-8), and severe- (SDS > 8) perfusion defects were also identified by GRE-MRI perfusion analysis in 75% (6/8), in 56% (9/16) and 100% (6/6), respectively. Conclusions  GRE-MRI first-pass stress perfusion imaging may not identify up to 30% of mild-to-moderate perfusion defects in a group of preselected patients with predominantly known CAD and abnormal ²⁰¹TI-SPECT studies.     

Nuclear medicine studies of the heart

Nuclear imaging techniques are well established diagnostic tools in clinical cardiology, providing noninvasive information about myocardial perfusion, function and metabolism. The cost-effectiveness of radionuclide imaging in the diagnostic work-up of patients with coronary artery disease has been demonstrated. Additionally, the documented prognostic value of scintigraphic parameters is of clinical importance to guide decision making. Advances in technology, new radiotracers and new applications contribute to continuous growth in the field of nuclear cardiology. Multi-headed gamma camera systems lead to higher spatial resolution and sensitivity of cardiac single photon emission tomography (SPECT), and they also provide the opportunity for attenuation correction or electrocardiographic gating of SPECT images. Objective quantitative values of perfusion, function and metabolism are derived from scintigraphic data by use of improved software and hardware. With the latest developments in tracer technology, imaging of myocardial necrosis, receptor systems and autonomic innervation has become a reality and will lead to new clinical applications in the future. Received 12 December 1997; Revision received 16 February 1998; Accepted 18 February 1998