18F-Flurpiridaz PET绝对定量心肌血流显像的研究进展

PET绝对定量心肌血流（MBF）显像在冠心病的诊断、危险分层和预后评估方面均具有重要的临床增益价值，但由于传统正电子心肌灌注显像剂的限制，其尚未在临床上广泛应用。2-叔丁基-氯-5[4-(2-氟-18F-乙氧基甲基)苯基甲氧基]-3(2H)-哒嗪酮（18F-Flurpiridaz）的成功研发开创了正电子心肌灌注显像剂的新领域，其具有良好的绝对定量MBF和心肌血流储备的性能，且相较于经典的正电子心肌灌注显像剂，其在物理性质、心肌摄取率和临床应用的方便性等方面具有明显优势，目前已进入临床Ⅲ期研究，成为最有前景的18F标记的PET心肌灌注显像剂。笔者就18F-Flurpiridaz PET绝对定量MBF显像的研究进展进行综述。     

PET心肌灌注显像及其定量分析的研究进展

近些年,随着PET/CT设备及心脏正电子示踪剂的快速发展,PET心肌血流灌注显像（PET-MPI）在临床上的作用逐渐加强。心肌血流灌注定量分析提供了心肌血流的客观评价标准,可以客观、准确地发现早期灌注异常,准确地对冠心病进行危险分层、预后评价和客观判断治疗效果,为冠心病临床诊治、心脏的生理和病理生理学领域的活体无创性研究提供重要信息。笔者就PET-MPI及其定量分析的研究进展进行综述。     

腺苷试验与运动试验201Tl心肌灌注显像对冠心病诊断价值的比较

目的比较腺苷试验与运动试验^201Tl心肌灌注显像对冠心病的诊断价值。方法将41例临床疑诊冠心病患者随机分为两组,一组进行腺苷试验^201Tl心肌灌注显像,一组进行运动试验^201Tl心肌灌注显像。两组试验对象均同期（2周内）行冠状动脉造影术。以冠状动脉狭窄≥50%作为冠心病诊断的“金标准”,比较两种负荷方法对冠心病的诊断价值。结果腺苷试验^201Tl心肌灌注显像对冠心病诊断的灵敏度、特异度、阳性预测率、阴性预测率、准确率分别为92.86%、57.14%、81.25%、80.0%、80.95%,运动试验^201Tl心肌灌注显像分别为100%、60.0%、71.43%、100%、80.0%,两种负荷方法对病变冠状动脉的检出率分别为66.67%和72.22%。结论两种负荷方法诊断冠心病的总体效能无显著差异。     

^99Tc^m—MIBI静息心肌断层显像对年轻心肌梗死患者心肌损 …

目的：用＾９９Ｔｃ＾ｍ－甲氧基异丁基异腈（ＭＩＢＩ）静息ＳＰＥＣＴ显像评价年轻心肌死患者的心肌损伤。方法总结分析了４例年龄〈４０岁的心肌梗死患者＾９９Ｔｃ＾ｍ－ＭＩＢＩ静息心肌灌注断层显像,并与冠状动脉造影和ＥＣＧ进行比较,结果４２例年轻心肌梗死患者,９０％（３８例）心肌灌注显像异常,１０％（４例）未见明显异常,诊断灵敏度为９０％。与ＥＣＧ相比,心肌灌注显像对梗死灶定位更准确,特别是心尖和后壁梗死     

运动-静息心肌灌注显像正常的疑诊冠心病患者临床特点和预后分析

在临床实践中发现有些心肌显像正常的患者冠状动脉（简称冠脉）造影证实其冠脉存在狭窄甚至严重病变,所以临床应注意心肌显像的假阴性.本研究旨在探讨运动-静息心肌灌注显像正常的临床疑诊冠心病患者的临床特点及预后。     

门控~（99m）Tc－MIBI心肌断层显像诊断多支冠状动脉病变和心肌缺血

目的：评价门控心肌显像诊断冠心病（ＣＡＤ）的临床意义。方法：对３２例ＣＡＤ患者的９９ｍＴｃ—甲氧基异丁基异腈（ＭＩＢＩ）门控。非门控心肌断层显像和冠状动脉造影进行了比较，以及对４０例ＣＡＤ患者的门控与常规潘生丁─静息心肌断层显像也作了比较。结果：１．门控与非门控显像法诊断ＣＡＤ的灵敏度和特异性无差别，但前者对检测病变冠状动脉和诊断多支冠状动脉病变性ＣＡＤ的灵敏度高于后者，而特异性无差别。２．射血分数（ＥＦ）值显著影响非门控图像的病变显示。３．与非门控显像比较，门控显像能观察到更多的再分布节段和较少的无再分布节段。静息门控心肌显像除发现较多的灌注异常外，还观察到了许多单纯收缩功能受损节段。后者虽然可判断８４％的灌注再分布节段，但特异性不高。结论：门控心肌断层显像对诊断ＣＡＤ无优势，但对诊断ＥＦ值较高的或多支冠状动脉病变性ＣＡＤ、检测病变冠状动脉和心肌缺血有一定价值。     

~(99m)TC-MIBI心肌灌注显像在小儿病毒性心肌炎中的应用价值

目的：观察病毒性心肌炎患儿的心肌ＳＰＥＣＴ 显像特点,及心肌灌注显像在病毒性心肌炎（ＶＭＣ） 的诊断和治疗中的作用。材料和方法：对临床诊断为ＶＭＣ 的８９ 例患者进行心肌灌注显像,并与心电图、超声心动图、聚合酶链反应（ＰＣＲ） 等进行比较。结果：８９ 例患儿中有４５ 例（５０ ．５６ ％ ） 心肌显像出现不同程度的放射性分布异常区,有２０ 例出现单节段放射性减低,１９ 例多节段出现放射性分布异常,６ 例呈花斑样改变。２ 例患者在治疗后进行随访,其治疗后显像结果比治疗前有明显好转。结论：ＳＰＥＣＴ 心肌灌注显像有助于对病毒性心肌炎的诊断,对治疗疗效评价有一定的临床价值。     

糖尿病冠状动脉粥样硬化性心脏病的发病机制及核素心肌灌注显像的研究进展

糖尿病发病率不断升高，心血管系统病变是其主要并发症，冠状动脉疾病是导致糖尿病患者死亡的主要原因。负荷核素心肌灌注显像可早期诊断糖尿病患者中罹患心脏病者，判断预后及进行危险度分层，为早期防治糖尿病冠状动脉粥样硬化性心脏病提供依据，从而提高糖尿病患者生活质量、降低糖尿病冠状动脉粥样硬化性心脏病死亡率。     

运动负荷核素心肌灌注显像诊断不典型胸痛心肌缺血的临床价值

运动负荷核素心肌灌注显像对冠心病心肌缺血的诊断准确性高。为明确冠心病心肌缺血诊断，2006年1月～2006年12月对81例有不典型胸痛的患者分别行运动负荷核素心肌灌注显像和冠状动脉（简称冠脉）造影检查，以评价运动负荷核素心肌灌注显像诊断不典型胸痛患者心肌缺血的临床价值。     

腺苷与运动负荷心肌灌注显像诊断不典型胸痛心肌缺血的临床价值

目的评价腺苷和运动负荷心肌灌注显像诊断不典型胸痛患者心肌缺血的价值。方法不典型胸痛患者67例行腺苷负荷心肌灌注显像，81例行运动负荷心肌灌注显像，结果分别与冠状动脉（简称冠脉）造影比较，得到显像诊断冠心病心肌缺血的灵敏度、特异性和准确性。结果腺苷负荷心肌灌注显像组67例中，23例冠脉造影有狭窄病变，腺苷负荷心肌灌注显像检出可逆性灌注异常即诊断心肌缺血16例，44例冠脉造影阴性者中，腺苷心肌灌注显像正常41例。腺苷负荷心肌灌注显像诊断冠心病心肌缺血的灵敏度为70％，特异性93％，准确性85％。运动负荷心肌灌注显像组81例中，31例冠脉造影阳性，运动负荷心肌灌注显像检出心肌缺血22例，50例冠脉造影阴性者中，运动负荷心肌灌注显像正常48例。运动负荷心肌灌注显像诊断冠心病心肌缺血的灵敏度为71％，特异性96％，准确性86％。结论腺苷或运动负荷心肌灌注显像出现可逆性灌注异常对诊断不典型胸痛患者冠心病心肌缺血有重要意义。     

Comparison of myocardial blood flow and coronary flow reserve during dobutamine and adenosine stress: implications for pharmacologic stress testing in coronary artery disease

BACKGROUND: Mechanistic differences between pharmacologic stressors may offer different clinical benefits. Therefore the effects of dobutamine and adenosine on absolute myocardial blood flow (MBF) and coronary flow reserve (CFR) were compared. METHODS AND RESULTS: We divided 36 patients (mean age, 61 +/- 8 years) with coronary artery disease into 2 groups based on stenosis severity as follows: greater than 50% but less than 75% (n = 16) and greater than 75% (n = 20). In addition, 18 normal volunteers (mean age, 46 +/- 7 years) served as control subjects. Groups of equal sizes received either dobutamine or adenosine. MBF at rest and peak MBF were measured by use of positron emission tomography in territories subtended by the stenosis (ischemic) and remote myocardium (remote), whereas left ventricular MBF was used in control subjects. CFR was calculated as peak MBF divided by MBF at rest. CFR was significantly greater with adenosine than with dobutamine stress in control subjects and remote CFR. Ischemic CFR was blunted to a similar degree with each stressor. Therefore adenosine achieved flow heterogeneity across all coronary stenosis severities greater than 50%. However, dobutamine achieved flow heterogeneity only in the presence of a severe coronary stenosis greater than 75% despite provoking a greater ischemic stimulus. CONCLUSION: Adenosine stress demonstrated a higher sensitivity and dobutamine demonstrated a higher specificity with quantitative perfusion imaging. Therefore adenosine is superior for diagnostic perfusion imaging, whereas dobutamine is better suited in combination with visual imaging and in the functional assessment of a known coronary stenosis.     

Global myocardial blood flow and global flow reserve measurements by MRI and PET are comparable

Coronary flow reserve (CFR) measurements have been widely used in assessing the functional significance of coronary artery stenosis because they are more sensitive in predicting major cardiac events than angiographically detected reductions of coronary arteries. Myocardial blood flow can be determined by measuring coronary sinus (CS) flow with velocity-encoded cine magnetic resonance imaging (VEC-MRI). The purpose of this study was to compare global myocardial blood flow (MBF) and CFR measured using VEC-MRI with MBF and CFR measured using positron emission tomography (PET). We measured MBF at baseline and after dipyridamole-induced hyperemia in 12 male volunteers with VEC-MRI and PET. With VEC-MRI, MBF was 0.64 +/- 0.09 (ml/min/g) at baseline and 1.59 +/- 0.79 (ml/min/g) at hyperemia, which yielded an average CFR of 2.51 +/- 1.29. With PET, MBF was 0.65 +/- 0.20 (ml/min/g) at baseline and 1.78 +/- 0.72 (ml/min/g) at hyperemia, which yielded an average CFR of 2.79 +/- 0.97. The correlation of MBFs between these two methods was good (r = 0.82, P < 0.001). The CFRs measured by MRI correlated well with those measured using PET (r = 0.76, P < 0.004). These results suggest that MRI is a useful and accurate method to measure global MBF and CFR. Therefore, it would be suitable for studying risk factor modifications of vascular function at an early stage in healthy volunteers.     

Assessment of coronary flow reserve using single photon emission computed tomography with technetium 99m-labeled tracers

The quantitative assessment of coronary flow reserve (CFR) may be useful for the functional evaluation of coronary artery disease (CAD), allowing judgment of its severity, tracking of disease progression, and evaluation of the anti-ischemic efficacy of therapeutic strategies. Invasive techniques, such as intracoronary Doppler ultrasound and the pressure-derived method, which directly assess CFR velocity and fractional flow reserve, have been used for the evaluation of the physiologic significance of coronary lesions. Considerable progress has been made in the improvement of technologies directed toward the noninvasive quantification of myocardial blood flow and CFR. Positron emission tomography has emerged as an accurate technique to quantify CFR. The absolute measurements obtained with this noninvasive approach have been widely validated. Nevertheless, it has not been applied to routine studies because of its high cost and complexity. On the other hand, technetium 99m-labeled tracers have been largely used for the evaluation of myocardial perfusion with single photon emission computed tomography (SPECT) imaging in patients with suspected or known CAD. Recently, attempts to estimate CFR with SPECT tracers have been made to obtain, with noninvasive methods, data for quantitative functional assessment of CAD. This review analyzes the relative merit and limitations of CFR measurements by cardiac SPECT imaging with Tc-99m-labeled tracers and describes the potential clinical applications of this technique.     

PET measurements of myocardial blood flow post myocardial infarction: Relationship to invasive and cardiac magnetic resonance studies and potential clinical applications

This review focuses on clinical studies concerning assessment of coronary microvascular and conduit vessel function primarily in the context of acute and sub acute myocardial infarction (MI). The ability of quantitative PET measurements of myocardial blood flow (MBF) to delineate underlying pathophysiology and assist in clinical decision making in this setting is discussed. Likewise, considered are physiological metrics fractional flow reserve, coronary flow reserve, index of microvascular resistance (FFR, CFR, IMR) obtained from invasive studies performed in the cardiac catheterization laboratory, typically at the time of PCI for MI. The role both of invasive studies and cardiac magnetic resonance (CMR) imaging in assessing microvascular function, a key determinant of prognosis, is reviewed. The interface between quantitative PET MBF measurements and underlying pathophysiology, as demonstrated both by invasive and CMR methodology, is discussed in the context of optimal interpretation of the quantitative PET MBF exam and its potential clinical applications.     

SPECT定量心肌血流及冠状动脉血流储备的研究进展

应用SPECT、单光子显像剂及示踪动力学技术能方便地定量心肌血流量（MBF）及冠状动脉血流储备（CFR）。特别是碲锌镉心脏专用SPECT的使用,能更快速、准确地获得定量结果。MBF、CFR的获得对冠心病诊断准确性的提高、患者的再分层及进一步预后评估具有重要意义,并且为冠状动脉微血管疾病的诊断提供客观依据。但是使用SPECT定量MBF及CFR仍存在一些不足之处尚待解决。笔者旨在对SPECT定量MBF及CFR的不同方法、初步应用结果及临床意义作一综述。     

Relation of coronary vasoreactivity and coronary calcification in asymptomatic subjects with a family history of premature coronary artery disease

Electron-beam computed tomography (EBCT) allows non-invasive imaging of coronary calcification and has been promoted as a screening tool for coronary artery disease (CAD) in asymptomatic high-risk subjects. This study assessed the relation of coronary calcifications to alterations in coronary vascular reactivity by means of positron emission tomography (PET) in asymptomatic subjects with a familial history of premature CAD. Twenty-one subjects (mean age 51±10 years) underwent EBCT imaging for coronary calcifications expressed as the coronary calcium score (CCS according to Agatston) and rest/adenosine-stress nitrogen-13 ammonia PET with quantification of myocardial blood flow (MBF) and coronary flow reserve (CFR). The mean CCS was 237±256 (median 146, range 0–915). The CCS was <100 in eight subjects and >100 units in 13. As defined by age-related thresholds, 15 subjects had an increased CCS (>75th percentile). Overall mean resting and stress MBF and CFR were 71±16 ml 100 g^–1 min^–1, 218±54 ml 100 g^–1 min^–1 and 3.20±0.77, respectively. Three subjects with CCS ranging from 114 to 451 units had an abnormal CFR (<2.5). There was no relation between CCS and resting or stress MBF or CFR (r=0.17, 0.18 and 0.10, respectively). In asymptomatic subjects a pathological CCS was five times more prevalent than an abnormal CFR. The absence of any close relationship between CCS and CFR reflects the fact that quantitative myocardial perfusion imaging with PET characterises the dynamic process of vascular reactivity while EBCT is a measure of more stable calcified lesions in the arterial wall whose presence is closely related to age.     

Combined evaluation of regional coronary artery calcium and myocardial perfusion by <Superscript>82</Superscript>Rb PET/CT in the identification of obstructive coronary artery disease

Purpose

Cardiac imaging with PET/CT allows measurement of coronary artery calcium (CAC), myocardial perfusion and coronary vascular function. We investigated whether the combined assessment of regional CAC score, ischemic total perfusion deficit (ITPD) and quantitative coronary vascular function would further improve the diagnostic accuracy of PET/CT in predicting obstructive coronary artery disease (CAD).

Methods

We analyzed 113 patients with suspected CAD referred to ⁸²Rb PET/CT myocardial perfusion imaging with available coronary angiographic data. Obstructive CAD was defined as ≥75% stenosis. The receiver operating characteristic area under curve (AUC) was applied to evaluate the ability of CAC score, ITPD, hyperemic myocardial blood flow (MBF) and coronary flow reserve (CFR) to identify CAD.

Results

Vessels with obstructive CAD (71 vessels) had higher ITPD (4.6?±?6.2 vs. 0.6?±?1.3) and lower hyperemic MBF (1.01?±?0.5 vs. 1.75?±?0.6 ml/min/g) and CFR (1.56?±?0.6 vs. 2.38?±?0.7; all p?<?0.001) than those without. In prediction of per-vessel CAD, the AUCs for the models including CAC/ITPD/hyperemic MBF (0.869) and CAC/ITPD/CFR (0.875) were higher (both p?<?0.01) than for the model including CAC/ITPD (0.790). Compared with CAC/ITPD, continuous net reclassification improvement was 0.69 (95% bootstrap confidence interval, CI, 0.365–1.088) for the CAC/ITPD/hyperemic MBF model and 0.99 (95% bootstrap CI 0.64–1.26) for the CAC/ITPD/CFR model.

Conclusion

Hyperemic MBF and CFR provide incremental information about the presence of CAD over CAC score and perfusion imaging parameters. The combined use of CAC, myocardial perfusion imaging and quantitative coronary vascular function in may help predict more accurately the presence of obstructive CAD.

     

PET measurement of adenosine stimulated absolute myocardial blood flow for physiological assessment of the coronary circulation

Considerable awareness has been raised of late of the need to reduce radiation exposure and control costs of x-ray and radionuclide imaging procedures. PET/CT cameras are now widely available and in conjunction with appropriate radionuclides and commercially available software make quantitative measurement of absolute MBF feasible for routine clinical practice. Quantitative measurement of absolute MBF under condition of coronary vasodilation permits independent assessment of the functional status of each of the three major coronary perfusion zones and so obviates the need for rest MBF determination in the great majority of cases. Coronary microvascular function also may be assessed in this same way. Thus, the stress-only protocol with quantitative PET measurement of MBF provides essential information required for clinical decision making related to need for catheterization and intervention for patients with known or suspected ischemic heart disease. Moreover, the single PET determination of maximal MBF in contrast to the usual rest/stress procedure addresses both safety and cost concerns. The present review focuses on: (1) quantitative PET measurements of myocardial blood flow for physiological assessment of the coronary circulation and (2) the value and potential limitations of performing stress only imaging in the clinical context.