Quantification of myocardial blood flow and assessment of its transmural distribution with real-time power modulation myocardial contrast echocardiography.

BACKGROUND: The purpose of this study was to examine the ability of real-time myocardial contrast echocardiography (MCE) with power modulation to quantitate myocardial blood flow (MBF) and to assess its transmural distribution in open-chest dogs undergoing partial or total coronary stenoses. METHODS AND RESULTS: MBF was measured in 12 dogs instrumented with a cuff occluder around the left anterior descending coronary artery at rest, during partial coronary stenosis (during infusion of adenosine), and during coronary occlusion. The MCE-derived rate of microbubble velocity, beta, and myocardial blood volume, A, were obtained by curve fitting of videointensity versus time plots, after the transient destruction of microbubbles by high-energy ultrasound. The data were compared with MBF measured with radiolabeled microspheres. Significant correlations were found between radiolabeled microsphere-derived MBF and both beta (r = 0.93) and the product of A x beta (r = 0.91). MCE beta reserve also correlated well with microsphere-derived flow reserve. Comparing endocardial/epicardial MCE ratios and microsphere-derived MBF ratios, significant correlation was also found between endomicropsheres/epimicrospheres MBF ratio and both endo/epi beta (r = 0.90) and endo/epi A x beta (r = 0.88). CONCLUSIONS: Real-time power modulation MCE allows for an accurate quantification of MBF and of its transmural distribution in open-chest dogs undergoing partial or total coronary stenoses.     

Effect of microbubble fragility on transit rate measurement by contrast echography

We sought to propose a simplified method to measure flow velocity based on ultrasonic microbubble destruction, and investigated the effect of microbubble shell fragility on such measurement. Acoustic density (AD) from the second harmonic short axis image of flow was obtained at variable velocities (2 to 73 mm/s) in an in vitro model during long (1000 ms) and short (33 ms) interval ultrasound (US) pulsing, allowing complete and partial microbubble replenishment between pulses, respectively. Microbubbles with shell elastic modulus of 0.4 MPa and 16 MPa were tested. By shortening pulsing interval, AD diminished gradually, rather than abruptly, to a plateau level for both microbubbles. The extent of AD decay was greater for the fragile than the strong microbubbles. A linear relationship existed between the magnitude of AD decay and flow velocity only in the higher and lower velocity range for the fragile and the strong microbubbles, respectively. Thus, difference in contrast intensities during long and short pulsing intervals, respectively, allowing complete and partial replenishment may provide for velocity measurement, in which choice of optimal microbubble fragility for the range of velocity to measure may increase the accuracy.     

心肌造影超声心动图对糖尿病大鼠心肌微循环的评价

目的 研究心肌造影超声心动图(MCE)技术结合潘生丁负荷试验是否能够早期检测糖尿病(DM)大鼠左室心肌微循环的功能障碍.方法 雄性SD大鼠18只,腹腔注射链脲菌素复制DM模型,另12只体质量匹配的雄性SD大鼠腹腔注射生理盐水作为对照.分别在静息状态和潘生丁负荷后,对两组大鼠(12周)乳头肌水平左室短轴行MCE检查,测定各室壁感兴趣区域峰值声学强度(PI)、造影剂灌注速率(β)及声学强度达峰时间(TTP)等指标,计算心肌血流量(MBF)和心肌血流储备(MFR).MCE检查完毕后,对心肌组织分别行~(99m)Tc-MIBI核素摄取量及毛细血管密度测定.结果 无论静息状态还是负荷后,同组大鼠后壁的MBF较前壁、侧壁和室间隔的MBF显著减低(P<0.05);取前壁心肌进行组间比较,静息状态和负荷后,DM组的PI、MBF和MFR均较对照组显著减低(P<0.05).潘生丁负荷后,DM组β也较对照组显著减低,TTP显著延长(P<0.05).DM组各室壁的核素摄取量和毛细血管密度均显著减低(P<0.05).结论 MCE检测的PI、β、TTP、MBF及MFR等指标可以敏感地检测出DM早期的心肌微循环功能障碍.     

Quantitative parameters of myocardial perfusion with contrast echocardiography in human beings: Influence of triggering mode

To facilitate quantitation of myocardial contrast echocardiography (MCE) in human beings, dual- or triple-triggered flash imaging has been advocated. However, the effect of this modality on quantitative blood-flow parameters of MCE is not known. Accordingly, MCE was quantitated in 71 myocardial regions of 22 patients (age: 57 +/- 16 years) during continuous infusion of Optison (12-18 mL/h). Two sets of images with end-systolic gating (1:1, 1:2, 1:3, 1:4, 1:6, and 1:8) from the apical 4-chamber view were acquired: single and dual triggering for the first 15 patients; and single and triple triggering for the other 7 patients. During gated imaging, MCE of the first, second, and third frame were quantitated. Curves of intensity versus pulsing intervals were fitted to an exponential function: y = A (1-e(-betat)). Where beta is myocardial blood velocity or the rate of rise of myocardial contrast intensity (MCI), and A is myocardial blood volume or the plateau of MCI reached. Continuous imaging, and the second and third frame in 1:1 gating only, provided similar intensity to precontrast imaging. Beyond 1:1 gating, MCI of the second frame in dual triggering mode gradually increased with incremental pulsing interval. This was still present but less pronounced in triple triggering. During dual and triple triggering, a lower beta was observed compared with single triggering. Application of image subtraction with the flash procedure further decreased beta, A, and the A(*)beta product, a quantitative parameter of blood flow by MCE. Thus, flash subtraction imaging alters the quantitative parameters of myocardial blood velocity and flow derived from MCE. Continuous imaging, and the second or third frame in flash imaging at 1:1 gating only, result in MCI similar to precontrast imaging and can be used for background subtraction to quantitate MCE parameters.     

Measurement of myocardial blood flow velocity reserve with myocardial contrast echocardiography in patients with suspected coronary artery disease: comparison with quantitative gated Technetium 99m sestamibi single photon emission computed tomography.

BACKGROUND: The ability of high and low mechanical index (MI) imaging methods during myocardial contrast echocardiography (MCE) to assess the physiologic significance of coronary stenoses were compared with technetium 99m sestamibi single photon emission computed tomography (SPECT) in patients. METHODS: Intermittent ultraharmonic imaging (high MI) and power modulation angio (low MI) were performed during continuous infusions of the echo-enhancing contrast agent, Optison, at rest and after dipyridamole stress in 39 patients. Technetium 99m sestamibi SPECT was performed simultaneously. Images from the 3 apical windows were divided into 6 walls. Myocardial blood flow (MBF) velocity and MBF velocity reserve were quantified from pulsing interval versus acoustic intensity MCE curves in each wall using postprocessed images. RESULTS: Approximately 25% of the myocardial walls could not be analyzed from MCE because of artifacts. MBF velocity and MBF derived from both MCE methods increased significantly after dipyridamole in healthy patients (n = 143 and 129 walls for high and low MI, respectively), compared with those with either reversible (n = 11 and 10 walls for high and low MI, respectively) or fixed defects (n = 18 and 14 walls for high and low MI, respectively) on SPECT. Consequently, MBF velocity and MBF reserve were significantly greater for patients with normal perfusion. Receiver operator characteristic curves obtained for MBF velocity reserve provided a sensitivity and specificity of 82% and 87%, respectively, for high MI; versus 64% and 96%, respectively, for low MI imaging after uninterpretable images were excluded from analysis. CONCLUSIONS: Both high and low MI MCE imaging techniques can be used to determine the presence of perfusion defects as identified by technetium 99m sestamibi SPECT. Low MI imaging methods have a number of drawbacks that limit its sensitivity compared with high MI techniques.     

心肌声学造影定量急性心肌梗塞后心肌血流量的实验研究

目的　评价心肌声学造影定量心肌梗塞心肌血流灌注的价值。方法　对６条犬急性心肌梗塞模型进行心肌声学造影, 采用自身对照的方法分析缺血区和非缺血区心肌显影时间－强度曲线各参数之比与心肌血流量的关系。结果　梗塞区时间－强度曲线各参数中, 曲线下面积（ＡＵＣ）和峰值强度（ＰＩ）与心肌相对血流量高度相关（ｒ＝ ０．９２和０．８４, Ｐ＜ ０．０１）, 与心肌绝对血流量相关性良好（ｒ＝ ０．７７和０．７１, Ｐ＜ ０．０１）。不同水平心肌血流量间的ＡＵＣ、ＰＩ均存在显著性差异（Ｐ均小于０．０１）, 且随着血流量的减少而呈下降趋势。三项时间指标与心肌绝对血流量无直接关系。结论　心肌造影时间－强度曲线参数中的曲线下面积和峰值强度可准确定量心肌梗塞后局部心肌血流量。     

Potential pitfalls of visualization of myocardial perfusion by myocardial contrast echocardiography with harmonic gray scale B-mode and power Doppler imaging

OBJECTIVE: The present study compared the regional variation of myocardial signal intensity in visualizing myocardial perfusion by myocardial contrast echocardiography (MCE) between harmonic gray scale and power Doppler imaging. METHODS: MCE was performed in 12 patients by electrocardiographic (ECG)-gated intermittent triggered MCE with harmonic gray scale and power Doppler imaging following slow intravenous injection of 0.5 ml contrast agent (Optison). The interval between the ECG triggers (pulsing interval) was increased from every heart beat (1:1) to every 2 (1:2), 4 (1:4), and 8 (1:8) cardiac cycles to allow incremental microbubble (contrast agent) replenishment. The MCE images were recorded when attenuation produced by the left ventricular cavity was minimal. The background-subtracted videointensity was measured in 7 segments in an apical 4-chamber view: 3 (apical, mid, and basal) septal segments, 3 (apical, mid, and basal) lateral segments, and 1 apex segment (apical cap). RESULTS: The background-subtracted videointensity for each segment was greater with the power Doppler than the gray scale imaging (p < 0.01). With the gray scale imaging, the background-subtracted videointensity in the basal septal segment demonstrated a negative value at all pulsing intervals, and the value (-9 +/- 13) was significantly lower than that (22 +/- 20) in the apical lateral segment at a pulsing interval of 1:8 (p < 0.01). With power Doppler imaging, the background-subtracted videointensity was high even in the basal septal segment (112 +/- 33), and no significant difference was observed among each segment. CONCLUSIONS: The findings indicate that quantitative assessment of myocardial perfusion based upon background-subtracted video-intensity may be difficult in the far field with harmonic gray scale imaging although the attenuation is not apparent by visual analysis. Harmonic power Doppler is more sensitive for detecting basilar perfusion in the far field compared with harmonic gray scale imaging.     

静脉输注国产声学造影剂定量心肌血流灌注的实验研究

目的：评价应用国产左心声学造影剂“全氟星”定量心肌血流灌注的可行性。方法：建立犬前降支缺血模型，经外周静脉持续匀速输注“全氟星”，存取不同触发间隔的造影图像，通过计算造影剂再充填曲线的平台声强度及微泡再充填速率估测心肌血流量。以正常区为参照、放射微球测定心肌血流量为“金标准”，判定应用国产左心声学造影剂定量心肌血流灌注的可行性。结果：放射微球测定心肌血流量与心肌声学造影定量结果相关良好（r=0.8913，P＜0．001）。结论：静脉均速输注“全氟显”可用于估测心肌血流量。     

Effect of transducer standoff on the detection, spatial extent, and quantification of myocardial contrast defects caused by coronary stenoses.

Intermittent harmonic imaging during a continuous infusion of microbubbles may be able to quantify myocardial perfusion abnormalities. Measurements of the spatial extent of these perfusion abnormalities depends on homogenous destruction of the microbubbles in the elevation plane of the transducer. We hypothesized that uneven microbubble destruction caused by attenuation of beam intensity could alter quantitative measurements of perfusion abnormalities during stress. To test this hypothesis, we measured the spatial extent of perfusion defects at peak dobutamine stress with a continuous intravenous infusion of perfluorocarbon-exposed sonicated dextrose albumin and intermittent harmonic imaging in dogs with nonflow-limiting coronary stenoses in the left anterior descending artery. The spatial extent of perfusion defects was also measured during total occlusion of the artery. Measurements were made at standoffs of 2- to 3-cm and 4- to 5-cm distance from transducer surface to myocardium. These spatial extents were correlated with risk area determined after death. The risk area during left anterior descending occlusion at a standoff of 2 to 3 cm was significantly larger at a 1500-ms pulsing interval (6.5 +/- 2.6 cm(2) for 2- to 3-cm standoff versus 3.7 +/- 1.4 cm(2) for 4- to 5-cm standoff; P =.01). The spatial extent at the 2- to 3-cm standoff more closely approximated risk area measured with Monastral Blue (7.8 +/- 2.7 cm(2)). Myocardial perfusion abnormalities during peak dobutamine stress were significantly smaller with the 4- to 5-cm standoff and undetectable in 4 of the 5 dogs. We conclude that ultrasound beam attenuation can reduce the size of a myocardial perfusion abnormality observed with intermittent harmonic imaging during a continuous infusion of microbubbles. This may reduce the sensitivity of this technique when transthoracic imaging is used.     

静脉弹丸注射氟碳造影剂对冠脉狭窄程度和心肌灌注声学密度定量相关性的研究

目的　探讨静脉弹丸注射氟碳造影剂后心肌显影强度与冠脉狭窄程度的相关性。方法　检测１０条犬冠状动脉左旋支（ＬＣＸ）不同程度狭窄时, 静脉弹丸注射全氟显后左室后壁心肌声学密度。结果　基础状态到ＬＣＸ轻、中、重度狭窄左室后壁心肌声学造影（ＭＣＥ）时间－强度曲线的峰值强度（ＰＩ）和曲线下面积（ＡＵＣ）均逐渐减低, 但相邻两组间差别不显著, ＬＣＸ完全阻断时, ＰＩ、ＡＵＣ均显著减低。结论　ＭＣＥ所测得参数与冠脉狭窄程度呈非线性相关, 但尚不能用于准确区分狭窄程度。     

Quantification of transmural gradient of blood flow in myocardial ischemia with real-time myocardial contrast echocardiography and dipyridamole stress test

Transmural redistribution of myocardial blood flow (MBF) is the earliest sign of myocardial ischemia. We aimed to evaluate the ability of real-time myocardial contrast echocardiography (MCE) combined with dipyridamole stress to quantify the transmural gradient of MBF during graded coronary stenosis. Real-time MCE was performed in 14 open-chest dogs at seven experimental stages: baseline; hyperemia induced by 6-min infusion of dipyridamole; 50%, 75% and 90% reduction of hyperemic flow after constriction in each stage for 10 min; reperfusion for 10 min; and subtotal occlusion of the left anterior descending coronary artery (LAD) for 90 min. We obtained MCE perfusion parameters from subendocardial (A-endo, beta-endo and A x beta-endo) and subepicardial (A-epi, beta-epi and A x beta-epi) layers of the ventricular septum and calculated their transmural gradients (A-EER, beta-EER and A x beta-EER) and systolic wall thickening (SWT). The sensitivity and specificity of each parameter for predicting 75% reduction of hyperemic flow, which was defined as mild myocardial ischemia, were derived by receiver operating characteristic (ROC) curve analysis. No transmural gradients were found at baseline; during maximal hyperemia and 50% reduction of hyperemic flow. beta-endo, A x beta-endo, beta-EER and A x beta-EER decreased significantly when the hyperemic flow was reduced by 75% or more. In contrast, SWT remained unchanged until the hyperemic flow was reduced by 90%. Among all parameters measured, beta-EER and A x beta-EER had the highest and SWT the lowest sensitivity and specificity in predicting mild myocardial ischemia. In conclusion, real-time MCE combined with dipyridamole stress allows for quantification of the transmural gradient of MBF. beta-EER and A x beta-EER are more sensitive than SWT and other MCE parameters in detecting mild myocardial ischemia.     

多巴酚丁胺和腺苷对心肌血流速度和容积的影响及其评价冠脉狭窄的意义

目的　评价多巴酚丁胺和腺苷对冠脉微循环的直接效应。方法　建立 8条一支冠脉 (左前降支或左回旋支 )轻中度狭窄的犬模型 ,直接冠脉内输注多巴酚丁胺和腺苷。采用经外周静脉微泡连续输注法 ,在谐波和递增性间断超声发射下进行心肌声学造影 (MCE) ,测定微泡速度 (MV)和心肌血流容积 (MBV )。以放射性微球测定心肌血流量 (MBF)。结果　在正常冠脉供血区中 ,虽然两种药物引起MBF明显增加 [静息时 ( 1.1± 0 .4)ml/(min·g) ;输注多巴酚丁胺和腺苷时分别为 ( 3 .7± 1.2 )ml/(min·g)和 ( 4 .7± 1.0 )ml/(min·g) ] ,而MBV仅轻微增加 (分别为 13 % ,17% ) ,但是MV增加的程度与MBF相一致 (静息时 5 .0± 0 .9;多巴酚丁胺和腺苷分别为12 .3± 4.1,13 .8± 4.1)。在狭窄冠脉供血区中 ,虽然两种药物引起了一定程度的MBF增加 (P <0 .0 5 ) ,但MBV较静息状态降低 (P <0 .0 5 ) ;然而MV明显高于静息状态 (P <0 .0 5 ) ,两种药物间比较无差异。两种药物负荷时的MV比值 (狭窄 /正常 )与MBF比值之间有良好的线性相关 (P <0 .0 0 5 ,r分别为 0 .85和 0 .68)。结论　冠脉内直接输注多巴酚丁胺和腺苷时 ,两种药物对狭窄和正常冠脉供血区微循环的影响相似。因此 ,两种药物可在冠脉狭窄的评价中交互使用。     

利声显经静脉心肌声学造影评价心肌梗死后患者的心肌灌注

目的 心肌造影超声心动图（MCE）采用触发谐频能量多普勒显像模式并用静脉持续输液利声显,观察心肌梗死后患者的心肌灌注情况,方法,使用谐频频率1．8－3．6MHZ的能量多普勒模式,于心电图T波终末处,按1：4心动周期进行触发,利声显浓度为300mg/ml,采用微量输液泵将所配心肌造影剂于患者左肘静脉内持续输注4 min(2ml/min),25例心肌梗死后患者的血压和心率变化并对心肌灌注情况进行半定量分析。结果 （1）MCE前后,患者血压和心率改变无明显差异;（2）触发谐频能量多普勒显像模式并用静脉持续输液min的心肌显影效果,而后方衰减可以避免。结论 触发谐频能量多普显像并用静脉持续输注利声显,可以产生较好的心肌灌注显像效果。     

Human cerebral perfusion analysis with ultrasound contrast agent constant infusion: a pilot study on healthy volunteers

With ultrasound (US) contrast agent (UCA) continuous infusion providing a steady state, mean tissue microbubble velocity can be assessed by analyzing the reappearance rate after microbubble destruction with US energy (refill kinetics). In this study, we investigated this new approach for the assessment of human cerebral perfusion. A total of 12 healthy volunteers were investigated transtemporally with increasing pulsing intervals (250, 500, 750, 1000, 1250, 1500, 2000, 3000 and 4000 ms) and two UCA infusion rates (0.5 and 1.0 mL/min of Optison). Intensity vs. pulsing interval curves were analyzed using an exponential curve fit and parameters of the curve (plateau echo enhancement, A, representing the microbubble concentration within the interrogated tissue; rate constant, beta, which is related to blood flow and their product, F = Abeta) were compared. For 20/20 investigations being available for further analysis, it was possible to generate a typical exponential intensity vs. pulsing interval curve from the ipsilateral thalamus. The plateau echo enhancement A showed a significant (p = 0.02), and the beta as well as the F values displayed a nonsignificant (p = 0.06, both), increase with infusion rate. The qualitative analysis of beta and F parameter images displayed the most homogeneous visualisation of perfusion in the ipsilateral thalamus and main territory of the middle cerebral artery. In conclusion, it is possible to display the UCA refill kinetics in human cerebral microcirculation after microbubble destruction by transcranial US. Grey-scale harmonic imaging allows a quantitative approach to cerebral perfusion with a large interindividual variation of the parameters.     

心肌声学造影无创评价犬急性冠状动脉闭塞缺血心肌及侧支循环的状态

目的：探讨经静脉心肌志学造影在动态评价犬急性冠状动脉闭塞时缺血、坏死心肌，及侧支循环逐步建立开放中的价值。方法：7只健康杂种犬，分别于基础状态，左冠前降支（LAD）结扎即刻、结扎后3h行经静脉心肌声学造影（MCE）。定量分析冠脉闭塞后心肌低灌注区视频密度峰值（VI），测量充盈缺损区面积，监测血流动力学变化。结果：1只犬于LAD结扎2min时因发生室颤死亡，统计分析时剔除，其余6只犬经静脉MCE未见血流动力学影响。LAD结扎3h的造影充盈缺损面积小于结扎即刻（P＜0．001）；LAD结扎3h的心肌低灌注区视频密度峰值较结扎即刻明显增加（P＜0．001）；心肌病理染色确定的坏死心肌部位在MCE的充盈缺损范围内。结论：MCE是反映心肌血流灌注的安全、有效方法，可准确评价冠脉急性闭塞时心肌血流灌注的变化及侧支循环状态。     

Quantification of myocardial perfusion and determination of coronary stenosis severity during hyperemia using real-time myocardial contrast echocardiography

Although regional myocardial perfusion can be currently quantified with myocardial contrast echocardiography (MCE) by using intermittent harmonic imaging (IHI), the method is tedious and time-consuming in the clinical setting. We hypothesized that regional myocardial perfusion can be quantified and the severity of coronary stenosis determined during hyperemia with MCE using real-time imaging (RTI) where microbubbles are not destroyed. Six open-chest dogs were studied during maximal hyperemia induced by adenosine in the absence or presence of coronary stenoses varying from mild to severe. Myocardial blood flow (MBF) was measured at each stage by using radiolabeled microspheres. MCE was performed using both IHI and RTI. Data for the latter were acquired in both end-systole and end-diastole. No differences were found between myocardial flow velocity (MFV) derived from IHI and RTI when end-systolic frames were used for the latter. MFV was consistently higher for RTI (P <.01) when end-diastolic frames were used. A linear relation was noted between MFV and radiolabeled microsphere-derived MBF ratios from the stenosed and the normal beds when end-systolic frames were used for RTI (r = 0.78, P <.001), whereas no relation was found when end-diastolic frames were used (r = 0.08, P =.78). The scatter for assessing MBF (A.beta) was minimal for IHI and RTI (9%-10%) with end-systolic frames, whereas that for RTI with end-diastolic frames was large (30%). Furthermore the correlation with radiolabeled microsphere-derived MBF was significantly (P <.01) weaker with RTI when end-diastolic frames were used (r = 0.53) than when end-systolic frames (r = 0.94) or IHI was used (r = 0.99). Data acquisition for IHI was 10 minutes, whereas it was 8 seconds for RTI. Thus, RTI can be used to quantify regional myocardial perfusion and stenosis severity during MCE. Only end-systolic frames, however, provide accurate data. RTI offers a rapid and easy means of assessing regional myocardial perfusion with MCE.     

Evaluation of blood flow in the cerebral microcirculation: analysis of the refill kinetics during ultrasound contrast agent infusion

By means of harmonic imaging, it is possible to display brain perfusion qualitatively using ultrasound (US) contrast agent (UCA) bolus injection. With UCA continuous infusion reaching a steady state, mean microbubble velocity can be measured, analyzing the reappearance rate after microbubble destruction by US (refill kinetics). We performed an animal pilot study to investigate this new method for the assessment of brain perfusion. Using harmonic grey-scale imaging, five sedated male beagle dogs were investigated through the intact skull with increasing pulsing intervals (250 to 8000 ms) and three UCA infusion rates (0.5, 1.0 and 1.5 mL/min of Optison). Cerebral blood flow was increased by acetazolamide (30 mg/kg BW). Intensity vs. pulsing interval curves were analyzed using an exponential curve fit [I(t) = A(1-e(-beta t))] and parameters of the curve were compared. We found that increasing the pulsing interval above 4000 ms led to no further increase of echo enhancement for infusion rates. Mean beta values were not influenced by infusion rate (p = 0.25 and p = 0.55). Mean F values increased nonsignificantly with rising infusion rate (p = 0.25 and p = 0.86). Acetazolamide led to an increase of mean beta and F values (p = 0.18 and p = 0.025, respectively). It is possible to evaluate changes in brain perfusion through the intact skull by analyzing the UCA refill kinetics after US-induced microbubble destruction.     

Accuracy and reproducibility of coronary flow rate assessment by real-time contrast echocardiography: in vitro and in vivo studies.

Real-time myocardial contrast echo (MCE) provides the potential to assess myocardial blood flow from time-intensity refilling curves after high-energy bubble destruction. This study validated the accuracy of this approach and the effect of specific examination variables and instrument settings on results. The effects of examination depth and angle as well as dynamic range, pulse repetition frequency, and line density were assessed with the use of in vitro incremental flow rates produced in an in vitro tissue phantom. In vivo recordings of real-time imaging with an infusion of a contrast agent (Optison) were obtained in 7 open-chest dogs with graded left anterior descending artery stenosis at baseline and during adenosine hyperemia, and were compared with flow probe measurements. After bubble destruction, time-intensity data were fitted to an exponential function, and the rate of intensity increase (b) and peak plateau intensity (A) were derived from refilling curves. In vivo real-time values for b, but not A, correlated closely with flow probe measures (r = 0.93). A similar correlation for b was observed in vitro (r = 0.98). The correlation between flow rate and b was influenced by several examination variables, including depth, angle, and instrument settings. Real-time MCE provides accurate quantification of coronary flow by assessing the rate of microbubble refilling. However, this parameter may be affected by several examination and instrument variables. Therefore, real-time MCE refilling measures are best applied by comparing baseline values with those of stress studies.     

Assessment of coronary stenoses of graded severity by myocardial contrast echocardiography.

BACKGROUND: Myocardial contrast echocardiography (MCE) has potential value in the assessment and quantitation of myocardial perfusion defects. However, the severity of stenosis detectable by MCE and its diagnostic accuracy remain undefined. Thus, we produced coronary stenoses of variable severity and quantified their effect on MCE. METHODS AND RESULTS: Three grades of left anterior descending (LAD) obstructions were produced in 7 open-chest swine. The stenoses were nonflow-limiting at rest, but decreased coronary hyperemia by 31.3% +/- 4.7%, 69.9% +/- 5.3% and 98.9% +/- 1.1%, respectively. Regional myocardial blood flow (RBF) was measured with fluorescent microspheres and was expressed as the ratio of LAD and control (LCx) beds. MCE was performed with 0.3 mg/kg intravenous AF0150 during ECG-gated harmonic imaging in short-axis view. Background-subtracted peak intensity (PI) was expressed as the ratio of LAD/LCx beds. Both RBF and PI ratios progressively decreased with increasing grades of stenosis. MCE showed a significant correlation with RBF (r = 0.74; P <.0001). Ratios of both PI and RBF differed significantly from baseline when coronary hyperemia was reduced more than 50%. An LAD/LCx ratio less than 0.6 by MCE yielded 61% and 83% sensitivity and 85% and 76% specificity with stenosis that reduced coronary hyperemia more than 50% and more than 75%, respectively. CONCLUSION: MCE with intravenous AF0150 during vasodilation correctly depicted the progressive reduction of flow ratios produced by graded coronary stenoses. A significant reduction of PI ratio was observed with stenosis causing more than 50% reduction of coronary hyperemia. An MCE ratio in stenosed/control beds could be selected, which exhibited good sensitivity and specificity in the identification of coronary stenosis.     

负荷心肌超声造影测定冠状动脉血流储备的临床应用

目的:探讨负荷心肌超声造影测定冠状动脉血流储备(Coronary flow reserve,CFR)的无创方法,并将其应用于评价冠状动脉微循环功能障碍(Coronary microcirculation dysfunction,CMD)。方法:人选161例因胸痛住院的非阻塞性冠状动脉疾病患者,所有患者均进行三磷酸腺苷负荷心肌造影,用QLab定量分析静息和负荷后平台期信号强度(A)和信号强度增加率(β)。心肌血流量(Myocardial blood flow,MBF)用A×β表示,CFR=MBF负荷/MBF静息。CMD定义为CFR<2.0。用Logistie多元回归分析筛选CMD的影响因素。结果:在非阻塞性胸痛患者中CMD发生率为51.6%;与冠状动脉微循环功能正常者相比,CMD中糖尿病高脂血症和E/e'>15比例明显增加,Logistic多元回归分析显示,E/e'>15是CMD发生的独立危险因素。结论:负荷心肌超声造影是测定CFR的有效无创方法;在非阻塞性胸痛患者中CMD发病率高,且与左室舒张末压升高有关。