声诺维不良反应的相关因素分析及观察处理

目的：通过探讨声诺维在超声造影使用中不良反应的分析,建立防治措施,为提高医疗安全提供保障。 方法：回顾我院2016-1年至2017-12超声造影检查的1983位患者,分析造影过程中发生不良反应的相关因素,并制定相应的观察处理。 结果：本组不良反应发生率为 0.201%（4/1983）。发生严重不良反应1例,出现过敏性休克早期表现：心前区不适,烦躁,面部发红、即刻青紫、明显肿胀;一般不良反应3例,表现为全身皮疹伴瘙痒。超声造影不良反应的发生与造影剂使用目的（P=0.011）及造影剂使用月份（P=0.008）明显相关。 结论：应用声诺维行超声造影,相对安全,严重不良反应少见,但超声造影过程中应严格掌握禁忌症和注意事项,配有相应的监护和抢救设备。     

Interaction of Microbubbles with Ultrasound

The clinical need for bedside myocardial perfusion studies is obvious in the present era of revascularization. Animal and first clinical studies suggest that microbubbles can be used as intravascular tracers of perfusion in conjunction with echocardiography as an imaging modality. In order to fully appreciate the potential and limitations of this approach, the complex interactions of microbubbles within an acoustic field need to be elucidated. Most importantly, there is a strong dependence of bubble effects on the acoustic pressure. At low pressures, linear backscatter yields low signal intensities; at medium range of pressures, bubble resonance causes the reflection of nonlinear signals with harmonic frequencies; and at high pressures, spontaneous acoustic emission with high signal intensity occurs as a final signal of the bubble in its process of disintegration. Thus, in order to allow sufficient replenishment of bubbles to the imaging plane, triggered imaging should be used with one frame every second to eighth cardiac cycle. Traditional gray scale echocardiography was not successful as an imaging modality because of the similarity of gray shades between the myocardium and the contrast effect. Subsequently, second harmonic imaging was developed and was fairly successful in contrast detection, although inherent problems persisted due to the overlap of fundamental and harmonic frequencies in the filtered signals. Harmonic power Doppler imaging turned out as the most sensitive acquisition method, however, with an early dropout at medium range attenuation. In theory, the new technique of pulse inversion may be most promising as this bubble specific imaging modality should combine high sensitivity of detection with great tolerance for attenuation effects in humans. First in vitro studies have confirmed its superiority over harmonic power Doppler in combination with stabilized microbubbles such as SonoVue™. Thus, we will have to accomplish a lot more work and comparative studies in humans before myocardial contrast echocardiography can emerge as a reproducible technique for evaluating myocardial perfusion with high diagnostic accuracy.     

SonoVue微泡粒径对新型绒癌细胞靶向造影剂结合特性的影响

Objective:To evaluate the impact of the diameter of SonoVue microbubbles on binding characteristics, including the adhesion rate and stability, of a new contrast agent targeted to choriocarcinoma cells (JARs) in vitro, in order to establish a foundation to explore targeted ultrasound imaging for localization of tumor cell antigens and increase the early diagnostic rate for tumors. Methods:The objects were divided into three groups:the large microbubble group (n=15), the middling microbubble group (n=15) and the tiny microbubble group (n=15). The rosette formation rate was counted. JARs were calcu-lated by flow cytometry (FCM). The targeted contrast agent was prepared by mixing SonoVue microbubbles of different diam-eter with rabbit anti-human chorionic gonadotrophin (HCG) antibody. The binding rates of the targeted contrast agent to JARs before and after PBS rinse were analyzed. Results:The binding rate was significantly lower in the large microbubble group [(61.7±1.8)%] than in the middling microbubble group [(82.6±4.5)%] and the tiny microbubble group [(91.3±5.8)%] (P< 0.05). The binding rates of different diameter microbubbles to JARs before and after PBS rinse were different. The middling microbubbles were the most stable ones, with the binding rate of (82.3±4.5)% and (80.4±3.9)% before and after PBS rinse (P > 0.05). The binding rates of the targeted microbubbles labeled with fluorescence to JARs were 68.6%, 81.3% and 89.3% in the large microbubble group, the middling microbubble group and the tiny microbubble group, respectively (P< 0.05). Conclu-sion:The binding capacity of the targeted SonoVue microbubbles to JARs is related to the diameter of the microbubble, which is determined by the shaking method before preparation. Modulating the diameter of SonoVue microbubbles may increase the binding rate and stability of targeted microbubbles to JARs, thus to improve the image of JARs.     

Cavitation-enhanced extravasation for drug delivery

A flow-through tissue-mimicking phantom composed of a biocompatible hydro-gel with embedded tumour cells was used to assess and optimize the role of ultrasound-induced cavitation on the extravasation of a macromolecular compound from a channel mimicking vessel in the gel, namely a non-replicating luciferase-expressing adenovirus (Ad-Luc). Using a 500 KHz therapeutic ultrasound transducer confocally aligned with a focussed passive cavitation detector, different exposure conditions and burst mode timings were selected by performing time and frequency domain analysis of passively recorded acoustic emissions, in the absence and in the presence of ultrasound contrast agents acting as cavitation nuclei. In the presence of Sonovue, maximum ultraharmonic emissions were detected for peak rarefactional pressures of 360 kPa, and maximum broadband emissions occurred at 1250 kPa. The energy of the recorded acoustic emissions was used to optimise the pulse repetition frequency and duty cycle in order to maximize either ultraharmonic or broadband emissions while keeping the acoustic energy delivered to the focus constant. Cell viability measurements indicated that none of the insonation conditions investigated induces cell death in the absence of a therapeutic agent (i.e. virus). Phase contrast images of the tissue-mimicking phantom showed that short range vessel disruption can occur when ultra-harmonic emissions (nf0/2) are maximised whereas formation of a micro-channel perpendicular to the flow can be obtained in the presence of broadband acoustic emissions. Following Ad-Luc delivery, luciferase expression measurements showed that a 60-fold increase in its bioavailability can be achieved when broadband noise emissions are present during insonation, even for modest contrast agent concentrations. The findings of the present study suggest that drug delivery systems based on acoustic cavitation may help enhance the extravasation of anticancer agents, thus increasing their penetration distance to hypoxic regions and poorly vascularised tumour regions.     

超声造影在评估肝炎肝纤维化及肝硬化中的应用价值

目的利用声诺维（SonoVue）造影剂来评估超声造影在肝炎肝纤维化及肝硬化中的lI缶床价值。方法选取慢性肝炎患者40例,分为肝纤维化组30例,肝硬化组10例,均经超声引导下肝组织活检病理证实;对照组10例,来自健康的自愿者。在造影模式下,经肘静脉注射超声造影剂SonoVHe,记录造影剂到达肝动脉时间、到达门静脉时间、到达肝静脉时间及肝实质增强峰值时间。结果肝纤维化组超声造影剂到达肝静脉显影时间较对照组延长,差异无统计学意义,时间分别为（25．52±4．35）s、（21．40±4．87）S;肝硬化组超声造影剂到达肝静脉显影时间较肝纤维化组、对照组缩短,差异有统计学意义,时间分别为（16．45±2．86）s、（25．52±4．35）s、（21．40±4．87）s;肝纤维化组、肝硬化组的肝实质增强峰值时间较对照组延长,差异有统计学意义,时间分别为（43．53±8．63）S、（56．78±11．56）S、（28．45±8．32）s。超声造影剂到达肝肝动脉、门静脉显影时间在3组之间差异无统计学意义。结论超声造影技术在评估肝炎肝纤维化及肝硬化的诊断中有一定的临床价值,可以更好的指导临床治疗。     

常规超声检查难以定性的复杂盆腔包块超声造影增强特点

 摘要：【目的】探讨常规超声检查难以定性的盆腔肿块超声造影增强特点。【方法】对常规超声检查难以定性的137例盆腔肿块进行超声造影检查。分析病灶增强开始时间、增强水平、形态和增强模式的特点。【结果】良恶性病灶超声造影表现各不相同。增强时间早于子宫肌层呈高增强的恶性、良性病灶分别为85.3%（29/34）和13.7%（14/103）;增强形态不均匀的恶性、良性病灶分别为 97.1%（33/34）和31.0 % (32/103);增强模式I型的恶性、良性病灶分别为85.3%（29/34）和9.7%（10/103）,上述两组结果比较,差异均有统计学意义(p＜0.01)。【结论】复杂的盆腔良恶性肿块造影增强模式具有特征性,可为病变的定性诊断提供信息。     

Bleomycin delivery into cancer cells in vitro with ultrasound and SonoVue® or BR14® microbubbles

Abstract

Background: Cell exposure to ultrasound (US) in the presence of contrast agent microbubbles (MBs) can result in cell sonoporation that can be exploited for drug or gene delivery. Anticancer drug bleomycin (BLM), used in sonoporation, can effectively eliminate tumor cells in vitro and in vivo. Nevertheless, sonoporation mechanism is not known, thus different US parameters and MB types are used. Recently, we proposed that efficiency of cell sonoporation can be related to the efficiency of MB sonodestruction.

Purpose: We analyzed human tumor cells viability in response to BLM, US and MB treatment.

Methods: Human glioblastoma astrocytoma (U-87 MG) or colon cancer (HCT-116) cells were exposed to US in the presence of BLM and either SonoVue® or BR14® MBs. MB sonodestruction was evaluated according to US signal attenuation.

Results: Both HCT-116 and U-87 MG cell viability following US exposure decreased up to 30%. Decrease in cell viability followed similar tendency as MB sonodestruction, which suggests direct relationship between MB sonodestruction and BLM intracellular delivery.

Conclusion: Sonoporation is a feasible method to deliver BLM in to several types of human cancer cell lines. Efficiency of cell sonoporation correlated well with MB sonodestruction, providing a possibility to optimize US parameters by measuring MB sonodestruction.     

宫颈癌超声造影与MRI增强模式的比较研究

目的将宫颈癌超声造影（CEUS）与MRI增强模式进行对照分析,探讨超声造影在宫颈癌中的应用价值。方法57例宫颈癌患者首先进行超声造影检查,而后行增强MRI检查,并对其增强特点进行对比分析。结果57例宫颈癌超声造影时均有不同程度的强化。超声造影及MRI表现为明显强化的病例均为94.73％（54／57）;造影剂分布不均匀的病例分别为：CEUS59．65％（34／57）、MRI77.19％（44／57）,上述两组结果比较,差异无统计学意义（P〉0.05）。结论超声造影增强模式与MRI类似,可为宫颈癌的诊断提供更多信息。     

Novel Use of Contrast‐Enhanced Sonography in the Diagnosis of Central Uterine Necrosis Following Embolization for Postpartum Hemorrhage

Since 2007, we have identified 2 cases of central uterine necrosis after uterine arterial embolization for postpartum hemorrhage. Contrast‐enhanced sonography showed an absence of enhancement of the internal myometrium. Magnetic resonance imaging with gadolinium confirmed the diagnosis. The images obtained for the first case were corroborated by histologic analysis from a hysterectomy done for sepsis. For the second case, contrast‐enhanced sonography performed during a follow‐up period of conservative treatment revealed a reduction of necrosis. Our study shows that contrast‐enhanced sonography seems to be a useful examination as an adjunct to grayscale and power Doppler imaging in the diagnosis and follow‐up of uterine necrosis.     

Current status of vesicoureteral reflux diagnosis

In children, diagnostic imaging for vesicoureteral reflux (VUR) encompasses both radiologic and sonographic modalities. The former comprises voiding cystourethrography (VCUG), the most widespread method for examination for reflux, and radionuclide cystography (RNC). In RNC the radiation exposure is significantly less than in VCUG with continuous fluoroscopy, but the anatomic details depicted are much inferior. With the introduction of pulsed fluoroscopy, the radiation exposure of VCUG has been markedly curtailed. VCUG is the first imaging choice for the urethra. The sonographic diagnosis of VUR with the intravesical administration of an ultrasound (US) contrast agent—voiding urosonography (VUS)—is being used increasingly in the routine diagnostic imaging work-up of reflux. Various sonographic reflux examination methods had been tried in the past. The real breakthrough came with the availability of stabilized US contrast media. Further impetus came with the introduction of harmonic US imaging. The recent release of a second generation US contrast medium promises to make a further positive impact on VUS. The diagnostic accuracy of contrast-enhanced VUS has been found to be comparable to radiologic methods. VUS is primarily performed in follow-up studies and as the primary reflux examination modality in girls.