Identification of Perfusion Abnormalities Using FSO69, a Novel Contrast Agent, in Conscious Dogs

Recent advances in the production of echocardiographic contrast agents has resulted in the ability to delineate areas of hypoperfusion after coronary occlusions and stenoses following their intravenous injection. Most of these studies though have been done in open chest animals. This study was done to determine if we could assess myocardial perfusion following the intravenous administration of FSO69, a suspension of perfluoropropane filled albumin microspheres (3.6 μm average microbubble size, concentration 8 × 10⁸), in spontaneously breathing closed chest dogs. Twenty-seven mongrel dogs were instrumented on day 1. The chest was then closed and the dogs were restudied 3–7 days later, while spontaneously breathing. Homogeneous perfusion was observed in most dogs by all three independent and blinded observers. Perfusion abnormalities were likewise identified in most instances by all blinded reviewers on interventions designed to decrease regional blood flow. A good correlation between perfusion defect size between investigators was observed. In summary, our data suggest that FSO69 can be used to assess regional myocardial perfusion in spontaneously breathing dogs. These results support its use in humans.     

Myocardial Viability Detected by Myocardial Contrast Echocardiography—Prognostic Value in Patients after Myocardial Infarction

Objective: This study aimed to assess the role of myocardial contrast echocardiography (MCE) as a predictor of cardiac events and death in patients with acute myocardial infarction (AMI). Methods: Eighty‐six patients underwent primary percutaneous coronary angioplasty for AMI. Segmental perfusion was estimated by MCE in real time at mean 5 days after PCI using low MI (0.3) after 0.3–0.5 ml bolus injection of intravenous Optison. MCE was scored semiquantitatively as: (1) normal perfusion (homogenous contrast effect), (2) partial perfusion (patchy myocardial contrast enhancement), (3) lack of perfusion (no visible contrast effect). A contrast score index (CSI) was calculated as the sum of MCE scores in each segment divided by the total number of segments. The patients were followed up for cardiac events and death. Results: A CSI of >1.68 was taken to be a predictor of cardiac events and death. Death occurred only in patients with CSI >1.68. Patients with CSI >1.68 had a significantly (P = 0.03) higher incidence of cardiac death or cardiac events (75%) compared to those with CSI <1.68 (27%). The absence of residual perfusion within the infarct zone was an independent predictor of death and cardiac events (P = 0.02). Conclusions: The absence of residual myocardial viability in the infarct zone supplied by an infarct‐related artery is a powerful predictor of cardiac events in patients after AMI. (Echocardiography 2010;27:430‐434)     

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.     

Myocardial Contrast Echocardiography in Assessment of Stable Coronary Artery Disease at Intermediate Dobutamine-Induced Stress Level

Background: Myocardial contrast stress echocardiography (stress MCE) is a novel method for diagnosing coronary artery disease (CAD). Few studies have compared the diagnosis of ischemia by stress MCE to angiographic CAD. Methods: Dobutamine stress MCE and SonoVue contrast infusion were performed before an elective percutaneous coronary intervention in 37 patients (8 women) aged 45–75 years with symptomatic CAD and at least one significant coronary artery stenosis measured by quantitative coronary angiography (QCA). The total and regional perfusion and wall motion (WM) were scored as normal or abnormal and attributed to the three main epicardial coronary arteries using a 17-segment left ventricular model. Results: An intermediate stress level was obtained in 29 (78%) patients, and 2 (5%) patients obtained peak stress. A perfusion defect was detected in 92% and WM abnormality in 57% of the patients at peak stress (P < 0.01). By perfusion, 70% of stenoses were both detected and correctly anatomically located, compared to 42% by WM (P < 0.01). All 21 patients with multivessel disease and/or proximal left anterior descending (LAD) stenosis measured by QCA were identified by stress-induced perfusion defects, while only 11 of them were identified by WM abnormalities (P < 0.01). Conclusion: Perfusion scoring is superior to WM scoring during stress MCE for diagnosing significant CAD in patients obtaining intermediate stress level, in particular, when multivessel disease or proximal LAD stenosis is present.     

Clinical Experience with SonoVue in Myocardial Perfusion Imaging

Ultrasound-enhancing agents have the potential to evaluate myocardial perfusion, adding a new dimension to echocardiography. This article summarizes the clinical studies involving SonoVue, a new intravenous ultrasound contrast agent, in assessing myocardial perfusion. Safe and well tolerated, SonoVue coupled with echocardiography has the capability to identify perfusion abnormalities, as confirmed by scintigraphic imaging. While the optimal modalities for ultrasound perfusion assessment are not yet determined, numerous technical advances have been introduced: continuous infusion or slow intravenous administration of the agent, harmonic intermittent imaging, pulse inversion, background subtraction, color coding, and others. SonoVue is a promising new agent in the booming field of myocardial contrast echocardiography.     

Rapid Three-Dimensional Myocardial Contrast Echocardiography: Volumetric Quantitation of Nonperfused Myocardium After Intravenous Contrast Administration

Current acquisition methods for quantitative three-dimensional myocardial contrast echocardiography require long acquisition times and therefore require the invasive administration of deposit contrast agents administered intra-arterially or into the left atrium. This study addressed the feasibility of obtaining accurate and precise quantitative volumetric measurements of nonperfused myocardium after an intravenous bolus of echocardiographic contrast agent using a rapid three-dimensional myocardial contrast echocardiographic acquisition technique. An open-chest pig model of acute left anterior descending coronary artery (LAD) occlusion was used. After LAD ligature, an intravenous bolus of contrast agent was given and images were obtained over a 12-second period using a continuously rotating transducer placed at the apical position. There was no significant microbubble destruction during the rotational acquisition period as measured by differences in mean gray scale values of apical, mid, and basal myocardial regions between the first and last image frames of acquisition. Calculated volumes of nonperfused myocardium demonstrated significant agreement and correlation (mean difference ± SD =–0.30 ± 1.71 cm³; r = 0.89; P < 0.01; y = 1.06x – 1.08) with anatomic specimens. When expressed as percent of total LV volume being nonperfused, the mean difference ± SD was 2.1 ± 3.6%, r = 0.94, P < 0.01, and y = 1.33x – 4.08. We conclude that accurate and precise measurements of nonperfused myocardium after an acute LAD coronary artery occlusion can be obtained after the intravenous bolus administration of a contrast material when a rapid 12-second acquisition with a continuously rotating transducer is used.     

静脉心肌声学造影在心肌梗死再灌注治疗及血管成形术中的应用

目的 :探讨静脉心肌声学造影 (MCE)评估急性心肌梗死再灌注治疗效果、冠状动脉介入治疗疗效以及预测存活心肌的价值。方法 :采用HP 5 5 0 0型超声心动仪 ,综合应用二次谐波、间歇成像和能量多普勒成像并采用高能量的超声波发射 ,对3 5例患者静脉注射利声显行MCE ,并行冠状动脉造影进行对比研究。结果 :3 5例患者完成MCE。 17例急性心肌梗死 (AMI)患者中 ,再灌注治疗患者MCE图象评分与保守治疗患者之间差异有显著性 (P <0 0 5 ) ;19例心肌梗死患者行介入治疗 ,共 63个血管重建术相关的心肌节段 ,在心肌梗死急性期 ,介入治疗前MCE显示心肌有灌注 ( 1分或 0 5分 )的心肌节段存活性及术后灌注改善的可能性显著高于MCE无灌注 ( 0分 )的心肌节段 (P <0 0 5 ) ,在心肌梗死陈旧期 ,介入治疗前MCE显示心肌灌注良好 ( 1分 )的心肌节段的存活性及术后灌注改善的可能性显著高于MCE灌注不佳 ( 0分或 0 5分 )的心肌节段 (P <0 0 5 )。结论 :结合多种成像技术 ,利声显可行静脉MCE。MCE可以评估AMI再灌注治疗的疗效 ,评估介入治疗的疗效并判断心肌存活性。     

Effect of a Residual Stenosis by Quantitative Angiography on the Myocardial Contrast Defect Observed Following Coronary Reperfusion Using Intermittent Harmonic Ultrasound Imaging and Intravenous Perfluorocarbon Ultrasound Contrast

Intermittent harmonic imaging following intravenously injected perfluorocarbon-containing microbubbles can detect myocardial perfusion abnormalities caused by ischemia. It is unknown whether this technique can differentiate viable, ischemic myocardium from infarcted myocardium immediately following coronary reperfusion. The objective of this paper was to determine whether intermittent harmonic imaging with intravenous microbubbles could define myocardial perfusion abnormalities following reperfusion. In 26 dogs, a prolonged total coronary occlusion (mean occlusion time 2.1 ± 0.4 hours) was followed by coronary reperfusion. Wall thickening (WT) and peak myocardial video intensity (PMVI) within and outside the risk area (PMVI ratio) were measured following intravenous perfluorocarbon microbubbles under resting conditions and during a 5 μ/kg per minute dobutamine [low dose dobutamine (LDD)] infusion in the presence and absence of a ≥ 50% diameter stenosis in the reperfused vessel. Infarct size was determined postmortem. The resting contrast defect in all dogs correlated closely (r = 0.93) with infarct size when no residual stenosis was present but correlated more closely with risk area (r = 0.88) when a ± 50% diameter residual stenosis was present. In dogs with infarction involving > 50% of the risk area, the PMVI ratio was lower under resting conditions (0.51 ± 0.27) than in dogs with no or partial infarction when no residual stenosis was present. However, in dogs with no or partial infarction, the PMVI ratio fell significantly when a ≥ 50% diameter stenosis was present, both under resting conditions and during LDD. We conclude that the myocardial contrast defect observed with intermittent harmonic imaging and intravenous ultrasound contrast is affected by both the infarct size and the presence of a significant residual stenosis.     

Bulls-Eye Display and Quantitation of Myocardial Perfusion Defects Using Three-Dimensional Contrast Echocardiography

Three-dimensional (3-D) myocardial contrast echocardiography (MCE) is able to derive parallel cutting planes of the left ventricle (LV). However, assessment of the site and extent of myocardial perfusion abnormalities has to rely on the reader's 3-D mental reconstruction from the tomograms, and a manual approach has to be employed for quantitative analysis. The objective of this study was to explore the display and quantitative capability of a bulls-eye format from contrast 3-D MCE in the assessment of perfusion abnormalities derived from a canine model of acute myocardial infarction (MI). Three-dimensional MCE data were acquired sequentially in a rotational scanning format during triggered harmonic imaging with an intravenous contrast agent. Reconstructed short-axis views of the LV were aligned in a bulls-eye format with the apex as the inner most ring. The total LV was divided into 120 sectors. The number of sectors with lack of contrast enhancement was used to derive the percent of the LV (%LV) with perfusion defect and was compared with the extent of MI calculated from postmortem triphenyl tetrazolium chloride (TTC) staining. The perfusion defect regions shown on bulls-eye images corresponded correctly with the territories of the occluded coronary arteries. Three-dimensional MCE perfusion defect mass (19.2 +/- 6.0 %LV) correlated well with anatomic MI mass (19.3 +/- 5.6 %LV; r = 0.92, SEE = 2.3%, mean differential = 0.1 +/- 2.4%). We conclude that bulls-eye display of contrast 3-D MCE demonstrates the site and extent of perfusion abnormalities in an easily appreciable manner. It also allows fast and accurate assessment of endangered myocardium.     

心肌声学造影在冠心病中的临床应用进展

心肌声学造影是诊断微循环水平心肌灌注的新技术。近年来无创性的心肌声学造影取得了突破性进展,已从实验室走向临床应用,现将心肌声学造影在冠心病方面应用的研究进展做一综述。     

心肌超声造影在冠心病中的应用进展

随着对超声造影剂及成像技术的深入研究,心肌声学造影(MCE)取得了极大的发展.作为一项评价心肌微循环灌注的新技术,通过分析心肌组织水平的血流灌注,可对急性心肌梗死及慢性缺血性心脏病进行综合评估,并可检测再灌注治疗后心肌的存活性及收缩功能恢复情况.MCE已成为临床上安全、准确评价冠心病的诊断技术,且在心脏疾病治疗中具有极大的潜在价值.     

超声二次谐波心肌声学造影评价心肌的血流灌注

目的探讨心肌声学造影对冠状动脉(冠脉)病变的诊断价值。 方法静脉注射声学造影剂利声显(levovist),通过超声二次谐波技术获取心肌灌注图像,对比冠脉造影显示的冠脉支配区域的心肌灌注与超声心肌声学造影获取的心肌灌注类型的关系。按心肌灌注积分指数将异常冠脉分为3组,心肌灌注积分指数1分(A组,27支),2分≥心肌灌注积分指数＞1分(B组,24支),＞2分(C组,33支)。 结果心肌灌注积分指数与冠脉狭窄度呈中度正相关(r＝0.75,P＜0.001),3组病人的冠脉狭窄程度、心肌灌注积分指数明显差异(P＜0.001)。冠脉狭窄度＜75%者,病人室壁灌注多为正常,随着冠脉狭窄程度加重,室壁灌注出现异常。 结论静脉心肌声学造影是反映心肌灌注的有效方法,能够反应冠脉血流的改变及微循环结构的完整性变化,从而弥补了冠脉造影仅能显示心外膜下的冠脉而无法观察毛细血管水平心肌灌注的缺限。     

冠状动脉造影正常的心肌梗塞患者核素心肌灌注显像

目的 :分析冠状动脉造影正常的心肌梗塞患者核素心肌灌注显像表现。　　方法 :回顾总结了 18例冠状动脉造影正常的心肌梗塞患者 99m锝 -甲氧基异丁基异腈 (99m Tc- MIBI)静息心肌断层显像。　　结果 :18例心肌梗塞患者心肌灌注显像均显示异常 ,12例有节段性缺损 ,6例未见缺损但可见心肌节段性稀疏。心肌灌注显像对心肌梗塞的定位与心电图 Q波比较 ,显示病变部位更明确。　　结论 :心肌灌注显像提供了冠状动脉造影正常的心肌梗塞患者心肌损伤部位及程度。     

Real-Time Contrast Echo Assessment of Myocardial Perfusion at Low Emission Power: First Experimental and Clinical Results Using Power Pulse Inversion Imaging

Power pulse inversion (PPI) has been developed for echocontrast specific imaging in order to reduce destruction of microbubbles. The purpose of this study was to evaluate PPI for real-time contrast echocardiography. Therefore, in vitro studies in a physiological flow-phantom and clinical examinations in patients with coronary artery disease were performed. The in vitro rersults of this study indicate that PPI allows real-time imaging at low emission power and is almost nondestructive to contrast microbubbles of Definity. At this low emission power a strong linear relationship between the dosage of the contrast agent and the resulting PPI signal intensity was found (R = 0.998, p < 0.001). In the clinical examinations real-time imaging using low mechanical index PPI resulted in strong myocardial signals and a complete filling of the cavities indicating absence of bubble destruction. Most striking was the ability of PPI to display myocardial thickening and wall motion simultaneously with the assessment of myocardial contrast replenishment following ultrasound induced bubble destruction by high power frames. We conclude that PPI allows nondestructive contrast imaging both in experimental and clinical settings. Therefore, real-time imaging of myocardial perfusion and real-time assessment of contrast replenishment following ultrasound induced destruction of microbubbles is feasible. Moreover, PPI allows simultaneous assessment of perfusion and myocardial function.     

Diagnosis of Coronary Artery Fistula Confirmed by Intravenous Contrast Echocardiography

Congenital coronary fistulae are rare, but their accurate diagnosis is important because of several complications. We describe the first case of the echocardiographic diagnosis using an intravenous contrast agent.     

Imaging of Myocardial Perfusion with SonoVue™ in Patients with a Prior Myocardial Infarction

Myocardial contrast echocardiography (MCE) is an evolving noninvasive imaging technique that can be used to assess regional myocardial perfusion. MCE relies upon the detection of nonlinear ultrasound signal from gas-filled microbubbles during their microvascular transit, resulting in tissue opacification. Provided that the relation between myocardial microbubble concentration and video intensity (VI) is within the linear range, VI measured from any myocardial region reflects the relative tissue concentration of microbubbles, which is influenced by three factors: (1) microbubble concentration in blood; (2) the myocardial blood volume fraction; and (3) microbubble destruction that occurs within the ultrasound beam. In this article, we discuss how these three factors may influence myocardial perfusion information provided by MCE and highlight the importance of image processing. In order to illustrate these concepts, we examine data obtained during perfusion imaging in patients with prior myocardial infarction using intermittent harmonic imaging at various ultrasound pulsing intervals (PIs) during bolus and continuous venous infusions of a second-generation microbubble agent (SonoVue™). Our results suggest that evaluation of resting perfusion is most accurate when both myocardial blood volume and blood velocity are assessed. This information is provided only with continuous infusions of microbubbles during imaging protocols that vary the ultrasound PI.     

运动-静息心肌灌注显像对冠心病病人心脏事件发生的预测价值

目的评价运动-静息心肌显像中不同显像方式及显像结果异常类型对心脏事件发生的影响。方法追踪了206例行运动-静息(SPECT)心肌灌注显像的病人,随访时间(1~56)个月,随访间期为(33.25±14.95)个月,出现心脏事件终止随访,未发生心脏事件者随访皆大于18个月。心脏事件包括心源性死亡、非致死性心肌梗死或梗死面积扩大及再血管化治疗。结果约206例在一周内经历运动-静息心肌显像,正常组133例,可逆性灌注缺损组20例,不可逆性灌注缺损组51例,心脏事件发生率分别为1.5%,65.0%,7.8%,经多样本率两两比较的χ2分割法分析可逆性灌注缺损灌注组心脏事件发生率与正常组和不可逆性灌注缺损组差别有统计学意义(P<0.01250),而后两组间无统计学意义(P>0.01250)。用Kaplan-Meier生存曲线分析3组累积未发生心脏事件率曲线,3组间差别有统计学意义(χ2=124.89,P<0.001),其中可逆性灌注缺损组预后最差;不同显像方式中,静息与运动方式均阴性或均阳性对心脏事件的发生有显著差异(χ2值分别为8.94和5.80,P<0.05)。结论运动-静息心肌灌注显像示可逆性灌注缺损是估测心脏事件发生的良好指标,运动显像阴性的病人心脏事件的发生率低于静息显像阴性者。