超声造影在心脏负荷实验中对心肌微血管的损伤效应

目的 观察在心脏负荷实验中,在超声触发显像方式下超声微泡空化对心肌微血管的损伤效应.方法 30只兔随机分为3组:单纯超声触发组、常规超声造影组、负荷超声造影组.负荷组用盐酸多巴酚丁胺和阿托品静滴提升心率.记录室性早搏的发生次数,用甲酰胺淬取法定量分析心肌伊文思蓝(Evans blue,EB)漏出量,视觉评分分析心肌出血.普通光镜观察心肌内红细胞漏出情况.结果 负荷组的心肌出血视觉评分等级明显高于常规组、单纯组(P<0.01);负荷组、常规组心肌EB漏出量明显高于单纯组(P<0.01);光镜观察负荷组心肌细胞间隙可见大量的红细胞,心肌细胞可见损伤.结论 在心脏负荷实验中,超声造影有更明显的微血管损伤作用.     

心肌声学造影对心肌损伤影响因素的实验研究

目的探讨不同剂量的国产左心声学造影剂“全氟显”在不同超声造影条件下（不同Ml或触发成像方式）心肌声学造影对大鼠心电及心肌组织损伤的影响。方法“全氟显”造影剂以125,250,625μl／kg三种剂量,0．56,0．99,1．80三种机械指数（MI）及两种触发方式（R波和T波触发）,对三种变量进行3×3×2析因分析。90只SD大鼠,分成18个组,每组5只。各组在造影前经静脉注入伊文思蓝（EB,50mg／kg）,随后注入微泡造影剂。观察指标为造影过程中室性早搏的发生数目、造影后心肌肌钙蛋白T（cTnT）的变化及心肌组织内EB含量。分别分析主效应及交互作用。结果根据析因分析结果,三种剂量间室性早博发生数比较差异无统计学意义（P〉0．05）;EB含量间比较（P=0．013）,差异具有统计学意义,高剂量组EB含量高于低剂量组,其他两组比较,P〉0．05。三种MI之间室性早博发生数比较（P=0．029）,高MI条件下产生室性早博的数目多于中MI,而其他两组间比较（P〉0．05）;EB含量亦有显著差异（P=0．006）,高MI下EB含量显著高于其他两组,其他两组间P〉0．05。R波与T波触发发生室性早博的次数比较（P〉0．05）,EB含量比较（P〈0．05）,R波触发组高于T波组。室性早博数目三因素间无显著交互效应（P〉0．05）;EB含量三因素间有显著交互效应（P=0．000）,EB含量最高发生于高剂量、高MI、R波触发组;各组cTnT均在正常范围。EB含量最高组大鼠心脏病理检查未见明显异常。结论在常规诊断超声条件下,注射高剂量造影剂在高MI及R波触发情况下毛细血管渗漏相对明显;高MI易致大鼠室性早博;各组cTnT含量在正常范围;心脏病理检查无明显异常。提示在本研究条件下,应用“全氟显”行动物心肌声学造影是安全的。     

诊断性超声造影对胎盘屏障通透性影响的实验研究

目的探讨不同机械指数的诊断性超声造影对胎盘屏障通透性的影响，以了解超声造影检查中超声强度的安全性。 方法14～16d（孕中期）清洁级SD孕鼠，经尾静脉注射剂量为1ml／kg的“声诺维”超声造影剂，不同机械指数（MI：0．13、1．0、1．4）的超声对孕鼠子宫进行连续及间歇辐照，时间5min，在荧光显微镜下观察胎盘及胎鼠组织伊文思蓝（Evans blue，EB）自发红色荧光情况。 结果诊断剂量超声造影，大体观察胎盘呈深蓝色，胎鼠呈半透明浅粉色。在荧光显微镜下，胎盘内可见明显的EB自发的红色荧光斑块，在胎鼠体内未见EB荧光显像。 结论高机械指数及低机械指数诊断性超声造影均不会导致孕鼠胎盘屏障通透性增加。     

经静脉心肌声学造影与心肌损伤及室性期前收缩关系的研究

目的 探讨经静脉心肌声学造影对心肌的损伤作用，证明心肌创伤是室性期前收缩的产生原因。方法 38只大鼠分5组：空白组、单纯超声心动图组、单纯声学造影剂组、实时超声心动图造影组与瞬间反应成像声学造影组。麻醉并尾静脉插管后37℃水浴中取左心室短轴观，超声造影剂采用Optison经静脉注射，剂量为0．5ml／kg，探头频率1．7MHz，发射调节至0dB(MI=1．7)，探测深度10cm。结果 实验组心脏全部发生室性期前收缩，照射区心肌损伤，血细胞及伊文思蓝染料透过损伤的毛细血管进入心肌组织。瞬间反应成像条件下的心肌损伤程度较实时显像严重。空白对照组、单纯超声照射以及单纯造影剂组均未造成心肌损伤，也无室性期前收缩发生。结论 常规临床超声能量暴露下经静脉照射声学造影剂能够对心肌组织产生明显的损伤作用，该损伤能够导致室性期前收缩。     

经冠状动脉选择性心肌声学造影指导经皮间隔心肌化学消融术

目的 评价经冠状动脉选择性心肌声学造影对指导肥厚梗阻型心肌病化学消融的作用。方法 对10例确诊为肥厚梗阻型心肌病的患者行冠状动脉造影,将球囊导管送入间隔支拟消融的靶血管,在球囊导管封堵靶血管后,经导管中心腔注入利声显2－3ml进行心肌声学造影,在声学造影确定靶血管所支配的心肌确系肥厚梗阻部位后再进行化学消融。结果 与未经心肌声学造影组比较,心肌声学造影组治疗后即刻显效率、治愈率及近期疗效均提高（P＜0．01）,心肌损伤减少（P＜0．01）,X线曝光时间缩短（P＜0．01）。结论 心肌声学造影对肥厚梗阻型心肌病的化学消融治疗有指导意义,可以提高对靶血管的选中率,提高疗效,减少对心肌的损伤。     

高机械指数联合高剂量造影剂行心肌声学造影的安全性研究

目的探讨高机械指数（MI）超声辐照联合高剂量国产超声造影剂心肌声学造影,对大鼠血流动力学及组织器官损伤情况的影响。方法20只正常SD大鼠,经颈静脉注射全氟丙烷人血白蛋白微球注射剂（1ml／kg）,在造影模式下调节MI至最大（MI=1．9）,采用R波触发,每6个心动周期一次。造影前后分别监测心率、心电图、血压、肌钙蛋白T,结束后取大鼠心、肝、肾进行病理检查。结果大鼠心率、血压、肌钙蛋白T测值在造影前后无明显变化（P〉0．05）;造影后心脏病理检查见轻微损伤（心肌纤维稍变粗,胞浆呈细颗粒状;间质血管扩张充血）,肝、肾未见异常结构改变;一只大鼠在注射造影剂的过程中出现室性期前收缩,注射结束5min后恢复正常。结论在常规超声条件下高MI及高剂量造影剂心肌声学造影对正常实验大鼠血流动力学无明显影响,肌钙蛋白T升高不明显,病理示心肌轻微损伤,偶致短暂室性早搏,但短时间内可恢复正常。本实验证实,高MI联合高剂量国产声学造影剂行心肌声学造影对于正常大鼠是安全的。     

伊文思蓝定量评估超声造影对鼠胎盘屏障通透性影响的实验研究

目的探讨不同机械指数诊断性超声造影对胎盘屏障通透性的影响。方法怀孕14～16d（孕中期）清洁级SD鼠60只,经尾静脉注射剂量为1ml/kg的“声诺维”超声造影剂,在不同机械指数下（MI：0.13,1.0,1.4）超声辐照孕鼠子宫,辐照时间（连续5min,间歇10s）,分光光度法测定胎盘及胎鼠组织内伊文思蓝（EB）含量。结果不同机械指数下的超声造影,胎鼠组织内EB含量与对照组相比差异无统计学意义。结论高机械指数及低机械指数诊断超声造影均不会导致孕鼠胎盘屏障通透性增加。     

肝癌诊治中声学造影模式的选择

目的：探讨不同模式声学造影在原发性肝癌（HCC）诊断和治疗中的应用。方法：原发性肝癌23例于非手术治疗前、后行声学造影和三相动态CT检查，声学造影使用造影剂Levovist，分别采用连续扫查的能量多普勒、间歇发射的能量多普勒和间歇发射的谐波能量图三种扫查模式评价HCC结节的血供和治疗效果，比较三种模式声学造影结果并与三相动态CT结果对照。结果：对于距体表不超过7cm的HCC结节，三种模式的声学造影检出肿瘤内血流信号的评分无显著差异（P＞0．05），但谐波能量图胜在较少噪音和彩色怒放现象，而能量多普勒因过多伪像而导致假阳性的出现；对远离体表（＞7cm）的病灶，谐波能量图的诊断敏感性显著低于连续扫查或间歇发射的能量多普勒（P＜0．05）。结论：间歇发射的谐波能量图能有效地评价HCC的肿瘤血管和浓染情况，并以较少的伪像优于连续扫查或间歇发射的能量多普勒，但对远离体表的病灶，连续扫查或间歇发射的能量多普勒具有较好的诊断敏感性。     

正常兔肝间歇二次谐波声学造影触发间隔与效应关系的声学定量分析

新型氟烷微气泡声学造影剂性能稳定，经外周浅静脉注射能通过肺微循环到达左心及全身各脏器血管，增强组织的灰阶图像。谢峰等报道触发成像能增强心肌造影效果，有关腹部声学造影中触发间隔对造影效果的影响文献报道较少，本研究应用实验性兔肝对二次谐波成像中的时间-效应关系进行声学定量分析。     

心肌声学造影最新进展—实时心肌声学造影

由于常规超声心动图的声功率水平会破坏造影剂微泡 ,近年来心肌声学造影 (MCE)均使用触发显像技术。触发显像改善了心肌显影的效果 ,但实际操作中技术难度较大 ,检查者需长时间维持切面稳定 ,另外不同的造影剂种类、剂量、注入方式和速度 ,往往难以确定适合的触发间期。更重要的是触发显像无法显示室壁运动 ,而室壁运动异常是常规及负荷超声心动图确定心肌缺血诊断冠心病的基础。再者使用触发显像容易出现后壁、侧壁与后间隔的衰减 ,造成假性充盈缺损的现象。以上因素均限制了 MCE的应用价值。1999年 Porter等 [1 ]报道通过降低机械指数…     

Impact of myocardial contrast echocardiography on vascular permeability: an in vivo dose response study of delivery mode, pressure amplitude and contrast dose

An in vivo rat model of myocardial contrast echocardiography (MCE) was defined and used to examine the dose range response of microvascular permeabilization and premature ventricular contractions (PVCs) with respect to method of imaging, peak rarefactional pressure amplitude (PRPA) and agent dose. A left ventricular short axis view was obtained on anesthetized rats at 1.7 MHz using a diagnostic ultrasound system with simultaneous ECG recording. Evans blue dye, a marker for microvascular leakage, and a bolus of Optison were injected i.v. Counts of PVCs were made from video tape during the 3 min of MCE. Hearts were excised 5 min after imaging and petechial hemorrhages, Evans blue colored area and Evans blue content were determined. No PVCs or microvascular leakage were seen in rats imaged without contrast agent followed by contrast agent injection without imaging. When PVCs were detected during MCE, petechial hemorrhages and Evans blue leakage were also found in the myocardium. Triggering 1:4 at end-systole produced the most PVCs per frame and most microvascular leakage, followed by end-systole 1:1, continuous scanning and end-diastole triggering 1:1. All effects increased with increasing Optison dosage in the range 25 to 500 microL kg(-1). Ultrasound PRPA was important, with apparent thresholds for PVCs at 1.0 MPa and for petechiae at 0.54 MPa. PVCs, petechial hemorrhages and microvascular leakage in the myocardium occur as a result of MCE in rats.     

Impact of myocardial contrast echocardiography on vascular permeability: comparison of three different contrast agents

Microvascular permeabilization, petechial hemorrhage and premature ventricular contractions (PVCs) have been demonstrated in an in vivo rat model of myocardial contrast echocardiography (MCE). The purpose of this study was to compare these effects for three US Food and Drug Administration (FDA)-approved ultrasound (US) contrast agents (US CA): Optison, Definity and Imagent. Evans blue dye, an indicator of microvascular permeability, and a contrast agent were injected IV in anesthetized rats suspended in a water bath to mimic scanning depths seen in clinical echocardiology. Diagnostic US B-mode scans with 1:4 end-systolic triggering were performed at 1.7 MHz using a cardiac phased-array scanhead to provide a short axis view of the left ventricle. To elicit readily measurable effects for comparisons, relatively high doses of the agent were used (50 to 500 microL kg(-1) for Optison, 25 to 200 microL kg(-1) for Imagent, 10 to 100 microL kg(-1) for Definity). Microvascular leakage was characterized by the area of Evans blue dye coloration on the hearts and by extraction of the dye from tissue samples. The number of petechia were counted on the epicardial surface of excised hearts. PVCs were counted from ECG traces recorded with the MCE images. Neither evidence of capillary leakage nor PVCs were seen in sham animals. Based on volume dose, Definity MCE produced more microvascular leakage, but there was no apparent difference between the three agents' microvascular damage potential, which increased linearly with dose at low doses, when expressed in terms of the number of stabilized microbubbles. Definity MCE resulted in fewer PVCs than the other agents. The effects increased strongly with peak rarefactional pressure amplitude, with apparent thresholds for petechiae at 0.4 MPa and for PVCs at about 1.0 MPa. These results should be of value for minimizing adverse potential in diagnosis and optimizing efficacy in therapeutic applications.     

Evans blue staining of cardiomyocytes induced by myocardial contrast echocardiography in rats: evidence for necrosis instead of apoptosis

High mechanical index (MI) echocardiography with contrast agent has been shown to induce Evans blue staining of cardiomyocytes, seen 1 d after exposure, in addition to contraction band necrosis, seen immediately after exposure. This research examined the roles of necrosis vs. apoptosis in these bioeffects. Myocardial contrast echocardiography at high MI with 1:4 electrocardiogram triggering was performed in anesthetized rats at 1.5 MHz. Histologically observable cell injury was accumulated by infusing a high dose of 50 μL/kg ultrasound contrast media via tail vein for 5 min at the start of 10 min of scanning. Evans blue dye or propidium iodide was injected as an indicator of cardiomyocyte plasma membrane integrity. Histologic sections were stained using the terminal dUTP nick-end labeling (TUNEL) method for labeling nuclei with DNA degradation (e.g., apoptosis). Evans blue fluorescent cells were counted on frozen sections or on hematoxylin-stained and TUNEL-labeled paraffin sections. In addition, transmission electron microscopy was used to assess potential apoptotic nuclei. Hypercontraction and propidium iodide staining were observed immediately after imaging exposure. Although TUNEL-positive cells were evident after 4 h, these also had indications of contraction band necrosis, and features of apoptosis were not confirmed by electron microscopy. Inflammatory cell infiltration was evident after 24 h. A second, more subtle injury was recognized by Evans blue staining, with minimal inflammatory cell infiltration at the morphologically intact stained cells after 24 h. Apoptosis was not detected by the TUNEL method in the cardiomyocytes stained with Evans blue at 24 h. However, Evans blue–stained cell numbers declined after 48 h, with continued inflammatory cell infiltration. The initial insult for Evans blue–stained cardiomyocytes apparently induced partial permeability of the plasma membrane, which led to gradual degeneration (but not apoptosis) and necrosis after 24 to 48 h. (E-mail: douglm@umich.edu)     

Premature ventricular contractions during triggered imaging with ultrasound contrast.

BACKGROUND: Premature ventricular contractions (PVCs) were observed during triggered second harmonic imaging of a contrast agent for myocardial perfusion assessment, with continuous infusion of the contrast agent. Further investigation into the relation of this phenomenon to both ultrasound energy and the contrast agent was carried out during a subsequent bolus-versus-infusion study. METHODS AND RESULTS: Two open-label studies in healthy male volunteers were performed. The initial study was a dose-response study in 10 subjects, which compared 3 infusion rates. Each volunteer received 3 continuous infusions with different infusion rates of the contrast agent for either 10 (n = 6) or 20 (n = 4) minutes. End-systolic triggered imaging with a mechanical index (MI) of 1.5 was used throughout this part of the study. The second study compared bolus injection with a continuous infusion in 9 volunteers, with a single-dose level but different imaging modalities: end-systolic and end-diastolic triggered imaging at MIs of both 1.1 and 1.5. Spontaneous baseline PVCs were uncommon: 10 in 344 minutes (0.03 PVC/min, maximal 1 PVC/min) of baseline imaging. During end-diastolic triggering, no increase in PVCs was seen, irrespective of MI. A significant increase to 1.06 PVC/min (P <.001) was seen during end-systolic imaging with an MI of 1.5, but not with an MI of 1.1. The increase in PVC rate was dose-dependent in the initial study. CONCLUSION: Imaging of contrast agents with high acoustic pressures can cause PVCs if end-systolic triggering is used. This effect is related to both the dose of contrast agent and acoustic pressure. It does not occur during end-diastolic triggered imaging. Precautionary measures would include using lower MIs or end-diastolic triggering.     

心肌声学造影评价梗死前心绞痛对心肌微循环损伤的保护作用

目的利用经静脉心肌声学造影(MCE)技术探讨梗死前心绞痛(PA)对急性心肌梗死心肌微血管损伤的影响。方法根据有无PA将首次急性心肌梗死(AMI)的37例患者分为两组,无PA组19例,有PA组18例。患者入院当天行心脏超声检查记录室壁运动和左室容积(EDV和ESV)。住院期间行MCE评价心肌危险区域中无再流范围。AMI后3个月再次行心脏超声检查评价左室重构。结果MCE显示无PA组心肌危险区域节段中无再流范围高于有PA组(P<0.05);EDV和ESV初诊时两组间无显著性差异。然而无PA组在3个月随访时超声结果显示左室容积较初诊时增加(P<0.0001),PA组左室容积较初诊时并无显著性改变。结论心肌梗死前心绞痛可以减少无再流,保护心肌微循环,有利于再血管化后左室功能的恢复,并防止左室重构的发生。     

多普勒能量组织成像定量左室缺血和梗塞心内膜面积

为探讨定量缺血和梗塞心肌的内膜面积新的可靠途径，用多普勒能量组织成像（DPTI）测量7条犬实验性急性左室缺血和梗塞心肌的内膜面积并和超声造影心肌灌注显像（MCE）、病理染色测量对照。结果表明：DPTI和MCE显示的缺血心肌的内膜面积无显著差异（P＞0．05），且高度相关（r=0．99，P＜0．01）；虽都大于病理染色显示的梗塞心肌的内膜面积（P均＜0．01），但均高度相关（r=0．78～0．82，P均＜0．01）。三种方法显示的左室内膜总面积无统计意义的差异（P均＞0．05）。因此可将DPTI作为定量缺血和梗塞心肌内膜面积的可靠方法。     

Coronary risk area measurement by intracardiac echocardiography and ultrasound contrast.

The perfusion bed of an occluded coronary artery-the coronary risk area-determines infarct size. Our objective was to evaluate the combined techniques of intracardiac echocardiography (ICE) and ultrasound contrast echocardiography for real-time estimation of the coronary risk area in an experimental model. We studied 13 pigs and 2 dogs. The left anterior descending coronary was occluded by inflating coronary balloons. An ultrasound contrast agent was injected either through the dilation catheter (distal to the inflated balloon) directly into the occluded artery to opacify the "positive" risk area or into the aortic root during coronary balloon inflation to determine the nonopacified "negative" risk area. Evans blue dye was injected into the occluded artery to stain the risk area, allowing an independent measurement. The mean left anterior descending negative risk area was 26% +/- 10% of the left ventricular myocardial area, the mean positive risk area was 24% +/- 10%, and the Evans blue-stained risk area was 25% +/- 9%. By Bland-Altman analysis, the positive Optison-Evans blue mean +/- SD difference was 1.42% +/- 6.42%; the negative Optison-Evans blue mean +/- SD difference was 1.02% +/- 7.56%. Coronary risk area can be determined with intracardiac echocardiography and ultrasound contrast.     

实时三维超声心动图声学造影定量评价存活心肌的实验研究

目的评价实时三维超声心动图心肌造影(CERT3DE)测量存活心肌质量的准确性。方法研究对象包括行开胸手术结扎冠状动脉分支造成心肌梗死的杂种犬22只(其中结扎左前降支15只,结扎左回旋支7支),分别于结扎后15min和结扎180min并再灌注30min后进行实时三维超声心动图心肌造影检查。采用静脉注射氟碳造影剂进行心肌造影,勾划心肌缺血15min后灌注缺损体积和心肌缺血180min、再灌注30min后灌注缺损体积,两者之差即为存活心肌体积,并与犬心肌密度相乘计算其质量。犬处死后采用Evansblue和TTC双重染色确定存活心肌范围并分离称重。结果Evansblue和TTC染色所测存活心肌的实际质量为(6.99±1.16)g,占整个左室质量的百分比为(11.3±1.5)%;CERT3DE所测左室存活心肌质量为(7.26±1.39)g,占整个左室质量的百分比(12.2±2.1)%;CERT3DE所测存活心肌质量和左室质量百分比与犬离体心脏实测结果明显相关(r=0.82,r=0.73)。结论CERT3DE能准确评价犬急性心梗模型的存活心肌质量,有望为临床定量评价冠心病患者心肌存活性提供一项新的手段。     

Noninvasive vessel-selective perfusion imaging with intravenous myocardial contrast echocardiography.

BACKGROUND: Intravenous myocardial contrast echocardiography (MCE) cannot identify each perfusion area of coronary vessels separately. However, by destroying microbubbles passing through a specific vessel using high-power ultrasound during intravenous MCE, vessel-selective perfusion imaging (VSPI) may be feasible. METHODS: In 10 open-chest dogs, intermittent short-axis images were obtained during contrast agent infusion using an ultrasound system. For VSPI, a probe coupled to another ultrasound machine was placed on the proximal left circumflex coronary artery (LCx). High-power ultrasound pulses were transmitted to destroy bubbles passing through the LCx. A negative contrast area on VSPI was considered to represent the perfusion area of the LCx (LCx-VSPI). A negative contrast area on conventional MCE during LCx occlusion and a region without staining by Evans blue dye were used as gold standards for defining the LCx perfusion area. LCx-VSPI was compared with a negative contrast area on conventional MCE during LCx occlusion and a region without staining by Evans blue dye. RESULTS: Despite lack of LCx occlusion, high-power destructive pulses produced a definite area of negative contrast on the LCx region. Decreased power of ultrasound pulses resulted in disappearance of the negative contrast area. An excellent relationship was demonstrated between both LCx-VSPI and a negative contrast area on conventional MCE during LCx occlusion (r = 0.93, P <.0001), and LCx-VSPI and a region without staining by Evans blue dye (r = 0.92, P =.0002). CONCLUSION: VSPI during intravenous MCE may be feasible for noninvasive assessment of perfusion areas associated with specific vessels.     

应用心肌超声造影首灌注成像时间参数定量评价心肌血流灌注的实验研究

目的 探讨首灌注血流通过冠状动脉时间(Tc)和心肌半灌注时间(Tm)评价缺血心肌血流灌注的价值.方法 18只健康杂种犬开胸后建立左前降支急性心肌梗死模型,180 min后经股静脉持续匀速推注造影剂(C3F8),应用实时三平面心肌超声造影(RT-TP-MCE)同步观察心肌内微气泡"从无到有再到稳定状态"的充填全过程(首灌注),然后行实时单平面心肌超声造影(RT-SP-MCE)观察心肌内微气泡被Flash破坏后再充填到稳定状态的过程(再灌注),两种方法均用单指数函数Y=A×(1-e-βt)+B来拟合时间-强度曲线.单平面法测量A值(平台期峰值强度)和β值(曲线斜率)来定量分析心肌血流量(A×β);RT-TP-MCE将左室心腔开始显影的时间标化为0点,测量Tc(即左室心肌开始显影的时间)、Tm(即心肌显影达50%平台期的时间).实验结束后处死犬,取出心脏行伊文思蓝和氯化三苯基四氮唑双重染色.结果 以染色结果为标准,将心肌节段分为正常组、缺血组和梗死组,分析正常组和缺血组.RT-TP-MCE正常组和缺血组Tc分别为(10.1±1.3)s和(20.4±7.1)s(P＜0.01),Tm分别为(17.1±2.2)s和(39.7±8.8)s(P＜0.01);缺血组心肌Tc、Tm与实时RT-SP-MCE测得的心肌血流量(A×β)均呈明显负性相关(r1=-0.876,P＜0.O1;r2=-0.894,P＜0.01).结论 RT_TP-MCE首灌注成像能同步定量评价心肌血流灌注;心肌缺血时,血流量越少,Tc和Tm越长.