经多功能心腔内超声导管超声辐照破坏微泡对犬心肌组织的生物学效应

目的观察经多功能心腔内超声(ICE)导管超声辐照破坏微泡对动物心肌产生的生物学效应,探索基因治疗缺血性心脏病的新方法。方法 15只犬随机分为US+MB组、US组、对照组3组,每组5只。以介入法将多功能ICE导管送入犬心室。对US+MB在ICE监控下向左心室游离壁注射0.5ml微泡,并以1 W/cm2的声能对注射部位辐照1min;对US组以相同条件行左心室壁辐照,但不注射微泡;对照组在插入导管后不进行任何处理。术后3天处死动物,观察心肌组织大体改变,并行HE染色观察细微结构变化。结果ICE能对注射针的进针深度、微泡注射及辐照过程进行实时监控。观察期内所有动物均正常存活。US+MB组心肌辐照部位出现充血、心肌细胞间隙增宽、少量炎性细胞浸润等改变,US组心肌组织仅出现轻微充血;对照组动物心肌无异常变化。结论经ICE导管超声辐照破坏微泡能在靶区域产生相应生物学效应,内置ICE可对心肌内微泡注射、超声辐照过程进行实时监控。此款新型多功能导管可能为基因治疗缺血性心脏病提供新的、更加安全有效的途径。     

国产多晶阵心腔内超声成像换能器性能的初步测试

目的 检验自行设计研发的多晶阵心腔内超声成像换能器性能,为多功能心腔内超声导管系统的研制提供基础.方法 通过超声体模检测该心腔内超声成像换能器的分辨率.观察离体及在体心腔内结构并在犬急性心肌梗死模型中(n=6)测试其对室壁运动的评估能力.结果 此心腔内超声成像换能器为32晶阵侧向分布,导管化后外径为8F,其横向分辨率和纵向分辨率均为1.0 mm.离体及在体条件下均显示清晰的心腔内结构.在急性心肌梗死模型中观察到左前降支结扎2 h后,左心室前壁心肌收缩末期厚度变薄(1.03±0.29 cm vs 0.51±0.22 cm)、增厚率降低(56.31%±10.18% vs9.23%±1.52%)、最大搏幅下降[(0.58±0.08)cm vs (0.13±0.03)cm](P均<0.01).结论 此多晶阵心腔内超声成像换能器达到介入尺寸要求,其成像性能初步满足设计需求.     

经多功能导管化学消融犬左心室前组乳头肌

目的 观察利用多功能心腔内超声（ICE）导管化学消融犬左心室前组乳头肌（APM）的可行性。方法 将15只杂交犬随机分均为0.2 ml组、0.4 ml组及0.8 ml组，每组5只。在ICE图像定位和监控下于左心室APM基底部注射不同剂量无水乙醇进行化学消融。于消融前及消融5天后行经胸超声，检测二尖瓣反流面积（MRA）及射流紧缩口宽度（VC）。之后处死动物，观察APM大体及病理变化。结果 ICE图像可清晰显示左心室APM结构，并实时监测进针深度及消融过程。消融5天后0.2 ml及0.4 ml组MRA、VC无明显改变，0.8 ml组MRA及VC较消融前明显增加（P均<0.05）。APM基底部可见中央呈苍白色的消融灶，0.2 ml、0.4 ml及0.8 ml无水乙醇在APM基底部形成的消融灶体积分别为（0.37±0.07）cm²、（0.69±0.08）cm²、（0.96±0.19）cm²，较高剂量组消融灶体积均大于较低剂量组（P均<0.05）。光镜下见消融灶内心肌细胞呈不可逆性坏死改变。结论 采用ICE导管注射低剂量无水乙醇可安全、有效消融左心室APM，有望为治疗左心室APM起源室性心律失常提供新的策略。     

低频超声联合SonoVue微泡促进裸鼠基因体内转染的可行性

目的 探讨利用低频超声联合SonoVue微泡造影剂促进基因转染人前列腺癌裸鼠皮下移植瘤的可行性。方法 采用人前列腺癌PC-3细胞建立裸鼠皮下移植瘤模型,成瘤后随机分为空白组（仅注射生理盐水）、单纯质粒组（注射生理盐水和质粒混悬液）、低频超声组（注射生理盐水和质粒混悬液后超声辐照）和低频超声+微泡组（注射超声微泡造影剂和质粒混悬液后超声辐照）。超声辐照条件：功率3 W/cm²,占空比5：5,频率80 kHz,辐照10 min。基因转染3天后在激光共聚焦显微镜下观察各组绿色荧光蛋白表达情况,并分析其平均荧光强度;同时行常规病理检查,观察低频超声联合微泡辐照对组织的损伤程度。结果 4组中,仅低频超声+微泡组可见明显绿色荧光,与其他各组差异均有统计学意义（P均<0.05）;空白组、单纯质粒组和低频超声组均未见明显绿色荧光。各组均未见明显组织损伤。结论 SonoVue微泡造影剂在低频超声辐照下能够安全有效地促进pEGFP基因转染进入人前列腺癌裸鼠皮下移植瘤组织内。     

不同声学参数对血栓内微泡介导的超声辅助溶栓效果的影响

目的 探讨经导管向血栓内注射微泡和尿激酶后超声溶栓的体外实验中,不同声压和占空比对溶栓效果的影响。方法 制备稀释的超声微泡并组装体外实验设备。将90份新鲜人血血栓样本平均分为9组,包括8个实验组(实验1~8组)及1个对照组。向血栓内注射0.02 ml微泡稀释液及2万U尿激酶,并对各组进行不同的超声辐照;实验1~4组固定占空比为10%,声压分别为285 kPa、512 kPa、708 kPa和931 kPa;实验5~8组固定声压为931 kPa,占空比分别为1%、2%、5%和10%;对照组不予超声辐照。计算并比较各组溶栓率的差异,并通过超声观察血栓表现及微泡分布情况。结果 超声辐照后微泡在血栓内有均匀扩散并逐渐减少的趋势。固定占空比时,实验3、4组溶栓率明显高于对照组(P< 0.01),实验4组溶栓率高于实验1组(P< 0.05);固定声压时,实验6、7、8组溶栓率均明显高于对照组(P均< 0.01),实验8组溶栓率明显高于实验5组(P< 0.01)。其余各组间溶栓率差异均无统计学意义(P均> 0.05)。结论 向血栓内注射微泡和尿激酶有助于增强超声溶栓效果,超声辐照时以声压708 kPa、占空比> 2%为宜。     

微泡增强的超声空化阻断肿瘤微循环的病理观察

目的 探讨微泡增强的超声空化阻断肿瘤微循环的病理机制。方法 建立兔肝VX2转移瘤模型18只,随机分为超声微泡组(n=6)、单纯超声组(n=6)及假照组(n=6)。对超声微泡组经耳缘静脉注射微泡,并进行超声辐照;对单纯超声组以生理盐水代替微泡,并进行超声辐照;对假照组注射生理盐水,并进行超声假照。观察辐照后各组病理变化。结果 大体解剖观察,超声微泡组辐照面可见较多出血点;单纯超声组及假照组辐照后肿瘤组织均未见明显改变。光镜下观察,超声微泡组肿瘤组织可见大片出血,血管内皮细胞损伤、连续性中断,红细胞外溢;单纯超声组可见局灶性小片状出血,血管内皮尚完整;假照组肿瘤组织未见明显出血,血管内皮完整。电镜下观察,超声微泡组肿瘤血管内皮破损严重,可见大量红细胞渗出,线粒体肿胀及吞饮小泡;单纯超声组及假照组仅见内质网略水肿。结论 微泡增强的超声空化阻断兔VX2肝脏肿瘤微循环的机制可能为血管机械性损伤。     

高强度聚焦超声辐照离体牛肝组织后B超声像图出现强回声的原因

目的 研究B超监控高强度聚焦超声(HIFU)治疗后声像图中强回声出现的原因。方法 HIFU定点辐照离体牛肝组织,深度为15 mm,辐照功率分别采用50、100、150、200、250和300 W,通过MR测温仪得到不同功率下组织最高温度达到55℃时所需辐照时间。将结果用于B超监控HIFU中,并通过被动空化检测(PCD)实时观察辐照过程中声信号的频域特性。结果 辐照功率50 W时虽有组织凝固性坏死,但B超声像图中无强回声出现,且通过PCD在频域信号中未观察到二分之一次谐波;功率≥100 W时出现凝固性坏死,且声像图中有强回声出现,频域信号中可明显观察到二分之一次谐波。结论 无沸腾气泡产生时,HIFU辐照离体牛肝组织后,空化效应产生的空化泡致使B超声像图中出现强回声。     

实时三维诊断超声激励瘤内注射微泡增强兔VX2移植瘤化疗效果

目的 探讨实时三维诊断超声激励瘤内注射微泡增强VX2移植瘤化疗效果的价值。方法 将24个兔VX2移植瘤模型随机分为4组,每组6只,分别为空白对照组(A组)、单纯多柔比星(Dox)组(B组)、实时三维诊断超声+微泡组(C组)、实时三维诊断超声+微泡+Dox组(D组)。对实验兔静脉注射Dox 1.2 ml/kg,瘤内注射微泡、约为肿瘤体积的1/2,辐照时间为20 min,机械指数(MI)1.3。于第1、3、5、8天对每组肿瘤进行治疗,共治疗4次。治疗后第10天剥离肿瘤,计算各组肿瘤体积总体生长率。结果 治疗后第10天,D组肿瘤体积明显小于其余3组(P<0.05);4组肿瘤体积总体生长率分别为A组100%,B组15.11%,C组118.22%,D组-30.81%。D组肿瘤体积在治疗后1~3天内略有增大,之后明显下降。结论 实时三维诊断超声激励瘤内注射微泡联合静脉注射Dox能够明显抑制兔VX2移植瘤的生长。     

靶向和非靶向微泡联合尿激酶超声溶栓的电镜表现

目的 比较靶向和非靶向微泡联合尿激酶超声溶栓的电镜表现。方法 将精氨酸-甘氨酸-天冬氨酸-丝氨酸片段（RGDS）与尿激酶（UK）以及超声微泡（SonoVue）通过机械振荡法,制备成靶向微泡。于30只新西兰大白兔单侧股动脉制备在体混合性血栓,并分为单纯超声辐照组（US组）、超声辐照+非靶向微泡造影剂+UK组（US+M+UK组）、超声辐照+靶向微泡造影剂+UK组（US+RGDS+UK组）。通过超声及多普勒血流仪观察溶栓效果,然后对股动脉离体标本行HE染色,并观察电镜表现。结果 溶栓20 min后,与US组和US+M+UK组比较,US+RGDS+UK组血流量明显恢复（P均<0.05）,US组与US+M+UK组比较差异无统计学意义（P均>0.05）。US+M+UK组HE染色显示管腔内充满血栓,血小板梁呈颗粒状、不致密,扫描电镜示粗大束状的胶原纤维上疏松附着少量细小纤维蛋白丝,大部分断裂;透射电镜示血栓大部分溶解为空泡状,可见白细胞或血小板降解的碎片。US+RGDS+UK组HE染色显示血栓完全溶解;扫描电镜示血栓的纤维网状结构被破坏,纤维蛋白完全的溶解;透射电镜示血栓降解为高电子密度的颗粒。结论 血栓结构的空泡化、纤维蛋白网架结构完全崩解和纤维蛋白的完全溶解是靶向微泡和UK联合溶栓的主要电镜改变。     

靶向微泡造影剂促进兔心肌梗死骨髓干细胞移植后血管新生及心肌力学改变

目的 应用斑点追踪技术评价靶向微泡造影剂注射后兔心肌梗死区域骨髓干细胞移植疗效。 方法 制备靶向微泡超声造影剂(携CD34单克隆抗体)。将36只新西兰大白兔随机分为对照组(单纯移植组)、普通造影剂组(移植+C组)及靶向造影剂组(移植+T组),分别于急性心肌梗死(AMI)前、AMI后3天、干细胞移植术后4周行心肌超声造影(MCE),采用彩色编码参数量化(PQ)技术对比各组干细胞移植前后梗死区域心肌灌注参数,同时对3组动物心肌梗死干细胞移植区域心肌的径向应变率(SrR)、圆周应变率(SrC)、旋转率(RotR)、收缩期S峰值及心肌扭转角度(Rot)进行斑点追踪分析,并于移植4周后检测微血管密度。 结果 干细胞移植后各心肌节段的A、β和A×β值均较本组内移植前改善,移植+T组改善最为明显(P均<0.05)。各组左心室前壁的SrR、SrC、RotR及Rot均较本组内移植前增高(P均<0.01),并与左心室射血分数相关。 结论 靶向微泡造影剂对兔骨髓干细胞移植后微血管新生具有一定作用。     

多功能心腔内导管移植骨髓干细胞治疗犬心肌梗死

目的观察多功能心腔内导管经心内膜移植骨髓间充质干细胞(MSCs)治疗心肌梗死(MI)的可行性及疗效。方法采用密度梯度离心法获得犬MSCs。结扎犬左冠状动脉前降支建立MI模型,1周后将建模成功的动物随机分成移植组和对照组,每组6只,移植组注射0.2ml MSCs,对照组注射等量的磷酸盐缓冲液。细胞移植4周后,以超声心动图检测心功能变化,之后取心肌组织作石蜡切片,用HE和Masson三色染色法显示MI区的组织结构。结果多功能心腔内导管能显示心腔内解剖结构,并能监控注射针位置。心功能检测和组织学染色显示移植组较对照组左心室射血分数增高,而心肌纤维化程度减低。结论多功能心腔内导管移植MSCs治疗犬MI能改善心功能,减少心肌纤维化。     

Intracardiac echocardiography (9 MHz) in humans: methods, imaging views and clinical utility

A new low-frequency (9 MHz, 9 Fr) catheter-based ultrasound (US) transducer has been designed that allows greater depth of cardiac imaging. To demonstrate the imaging capability and clinical utility, intracardiac echocardiography (ICE) using this lower frequency catheter was performed in 56 patients undergoing invasive electrophysiological procedures. Cardiac imaging and monitoring were performed with the catheter transducer placed in the superior vena cava (SVC), right atrium (RA) and/or right ventricle (RV). In all patients, ICE identified distinct endocardial structures with excellent resolution and detail, including the crista terminalis, RA appendage, caval and coronary sinus orifices, fossa ovalis, pulmonary vein orifices, ascending aorta and its root, pulmonary artery, RV and all cardiac valves. The left atrium and ventricle were imaged with the transducer at the limbus fossa ovalis of the interatrial septum and in the RV, respectively. ICE was important in identifying known or unanticipated aberrant anatomy in 11 patients (variant Eustachian valve, atrial septal aneurysm and defect, lipomatous hypertrophy, Ebstein's anomaly, ventricular septal defect, tetralogy of Fallot, transposition of the great arteries, disrupted chordae tendinae and pericardial effusion) or in detecting procedure-related abnormalities (narrowing of SVC-RA junction orifice or pulmonary venous lumen, atrial thrombus, interatrial communication). In patients with inappropriate sinus tachycardia, ICE was the primary ablation catheter-guidance technique for sinus node modification. With ICE monitoring, the evolution of lesion morphology with the three imaging features including swelling, dimpling and crater formation was observed. In all patients, ICE was contributory to the mapping and ablation process by guiding catheters to anatomically distinct sites and/or assessing stability of the electrode-endocardial contact. ICE was also used to successfully guide atrial septal puncture (n = 9) or RA basket catheter placement (n = 4). Thus, ICE with a new 9-MHz catheter-based transducer has better imaging capability with a greater depth. Normal and abnormal cardiac anatomy can be readily identified. ICE proved useful during electrophysiological mapping and ablation procedures for guiding interatrial septal puncture, assessing placement and contact of mapping and ablation catheters, monitoring ablation lesion morphological changes, and instantly diagnosing cardiac complications.     

Preclinical Testing of Frequency-Tunable Capacitive Micromachined Ultrasonic Transducer Probe Prototypes

In intracardiac echocardiography (ICE) it may be beneficial to generate ultrasound images acquired at multiple frequencies, having the possibility of high penetration or high-resolution imaging in a single device. The objective of the presented work is to test two frequency-tunable probe prototypes in a preclinical setting: a rigid probe having a diameter of 11 mm and a new flexible and steerable 12-Fr ICE catheter. Both probes feature a forward-looking 32-element capacitive micromachined ultrasonic transducer array (aperture of 2 × 2 mm²) operated in collapse mode, which allows for frequency tuning in the 6-MHz–18-MHz range. The rigid probe prototype is tested ex vivo in a passive heart platform. Images of an aortic valve acquired in high-penetration (6 MHz), generic (12 MHz) and high-resolution (18 MHz) mode combine satisfying image quality and penetration depth between 2.5 cm and 10 cm. The ICE catheter prototype is tested in vivo using a porcine animal model. Images of an aortic valve are acquired in the 3 imaging modes with the ICE catheter placed in an ascending aorta at multiple depths. It was found that the combination of the forward-looking design and frequency-tuning capability allows visualizing intracardiac structures of various sizes at different distances relative to the catheter tip, providing both wide overviews and detailed close-ups.     

Intracardiac echocardiography: current developments

Intracardiac echocardiography refers to the method of imaging cardiac structures from intracardiac locations with the use of ultrasound catheters. Advances in catheter-based interventional cardiologic procedures to treat cardiovascular lesions and the problems encountered during those procedures due to inadequate guidance provided by fluoroscopy have given the impetus to develop other guidance modalities. Experimental explorations with intracardiac ultrasound probes have indicated that detailed visualization of cardiac structures in real-time is possible by intracardiac ultrasound. Recent advances in catheter-based ultrasound technology make it feasible to safely pass small-sized catheters in humans into various intracardiac locations and acquire images of valvular structures and various chambers. Experience with 20 MHz ultrasound catheters indicates that high resolution images of normal and abnormal structures can be obtained if the catheter is manipulated close to the region of interest. The problem of the limited depth of field associated with 20 MHz catheters has led to the fabrication of catheters with lower frequency ultrasound elements. Experimental and clinical experience with 12.5 MHz ultrasound catheters points to the capability and potential of intracardiac echocardiography to not only display normal structures but also aid in the identification of valvular abnormalities, chamber dysfunction and pericardial effusions. In addition, aortic disorders such as acute dissection, coarctation and atherosclerotic disease could be delineated. Similarly, abnormalities involving the pulmonary arteries such as pulmonary embolism, organized thrombi, peripheral pulmonary arterial stenoses, and pulmonary hypertension-induced vascular changes could be recognized. Many modifications in the catheter design are being explored. With further work in the area of catheter technology and ultrasound image processing, intracardiac echocardiography is likely to become a clinical tool.     

产前超声三血管多切面和主动脉冠状及矢状切面诊断胎儿先天性血管环

目的 观察产前超声三血管多切面和主动脉冠状及矢状切面诊断胎儿先天性血管环的价值。方法 回顾性分析42胎经产前超声诊断的先天性血管环胎儿,于超声三血管多切面、主动脉冠状及矢状切面观察上腔静脉、主动脉弓、肺动脉及动脉导管与气管的位置关系等,并结合产后随访结果分析各切面用于诊断胎儿先天性血管环的价值。结果 42胎中,19胎为右位主动脉弓,其中16胎为右位主动脉弓+迷走左锁骨下动脉+左侧动脉导管,3胎为右位主动脉弓伴镜像分支+左侧动脉导管;17胎为左位主动脉弓伴迷走右锁骨下动脉;3胎为双主动脉弓,其中2胎为右弓优势型、1胎为均衡型;3胎为肺动脉吊带。15胎合并心内畸形。8名孕妇因胎儿染色体异常终止妊娠,9名孕妇于外院分娩而失访;25例新生儿超声心动图或CTA所见均与产前检查结果相符。结论 产前超声三血管多切面结合主动脉冠状及矢状切面有助于检出胎儿先天性血管环。     

Phased-array intracardiac echocardiographic imaging of acute cardiovascular emergencies: Experimental studies in dogs

Background: We evaluated a newly developed phased-array intracardiac echocardiographic catheter. Objective: Our aim was to evaluate the imaging capability of this new ICE catheter in an animal model simulating acute cardiovascular abnormalities. Methods: ICE images were obtained from the right atrium during (1) acute left ventricular dysfunction; (2) acute coronary occlusion; (3) pericardial effusion and tamponade; and (4) pulmonary embolism. Results: Left ventricular dysfunction, induced experimentally by halothane inhalation, resulted in a fall in echocardiography-calculated ejection fraction from 47% ± 11% to 25% ± 10%, P < .01. Regional contraction abnormalities after acute coronary occlusion were identified without and with the ultrasound contrast agent Optison. Pericardial effusion produced by saline infusion into the pericardium was detected in amounts as small as 15 mL. Right ventricular and atrial compression and respiratory variation in right ventricular inflow during tamponade were demonstrated. After injection of intravenous thrombin to create venous thromboembolism, we demonstrated right ventricular dilatation and dysfunction and thrombi attached to the tricuspid and pulmonary valves and in the pulmonary artery. Conclusion: This new phased-array ICE catheter may be a useful clinical tool for the diagnosis of heart failure, ischemia, tamponade, and pulmonary embolism. (J Am Soc Echocardiogr 2002;15:1309-14.)     

三维斑点追踪技术评价类风湿关节炎患者左心室收缩功能

目的 应用三维斑点追踪技术（3D-STI）评价类风湿关节炎（RA）患者左心室收缩功能。方法 对40例RA患者（RA组）、40名健康体检者（对照组）行常规超声心动图检查,测量参数左心室舒张末期内径（LVDd）、左心室收缩末期内径 （LVDs）、室间隔舒张末期厚度（IVSd）、左心室后壁舒张末期厚度（LVPWd）、二尖瓣口舒张期E峰、A峰、E/A值、左心室舒张末期容积（EDV）、左心室收缩末期容积（ESV）、左心室射血分数（LVEF）;同时采集3D-STI图像,并应用4D Auto LVQ软件分析计算出左心室收缩期整体纵向应变（LVGLS）、左心室收缩期整体径向应变（LVGRS）、左心室收缩期整体圆周应变（LVGCS）、左心室收缩期整体面积应变（LVGAS）,比较RA组与对照组常规超声心动图及3D-STI参数的差异。结果 RA组与对照组LVDd、LVDs、 IVSd、LVPWd、E峰、A峰、E/A值、EDV、ESV、LVEF的差异均无统计学意义（P均>0.05）。两组间LVGLS、LVGRS、LVGCS、LVGAS差异均有统计学意义（P均<0.05）。结论 3D-STI技术可较常规超声心动图更早地检测出RA患者左心室收缩功能的改变。