超声微泡造影剂靶向治疗现状及研究进展

1968年Gramiak首次报道了可增强显影的小气泡,即超声微泡造影剂（UCA）,它的出现开创了无创超声诊断和治疗的新领域。随着对其研究的不断深入,人们发现超声微泡造影剂不仅是一种良好的超声显像对比剂,     

高强度聚焦超声联合超声造影剂增强治疗效果的研究进展

高强度聚焦超声(HIFU)以其安全性、无创性、有效性的特点正日益成为治疗和辅助治疗多种肿瘤的新方法。超声造影剂(UCA)通过改变靶组织声学特性显著地提高了HIFU的治疗效果,在HIFU临床应用过程中显示了重要的应用价值。本文就HIFU联合UCA治疗的作用机理及其增强治疗效果的实验研究进展进行综述。     

超声微泡造影剂在疾病诊断与治疗中的研究进展

超声微泡造影剂在疾病诊断与治疗中的作用日渐明显.超声微泡造影剂可用于对心脏、肝脏、肿瘤等的声学造影诊断,具有靶向性的超声微泡造影剂对组织、血栓及肿瘤的靶向显影应用前景广阔.目前的研究表明,超声微泡造影剂在治疗中也显示出巨大潜力,可作为一种有效的基因或药物运载工具.而低功率超声辐射微泡治疗肿瘤研究亦有望取得突破性进展.     

靶向超声造影剂在肿瘤诊治中的研究现状

超声具有可实时显影、简便易行,在引导组织活检及介入治疗等方面应用广泛[1],特别对肿瘤等疾病的诊断具有较高价值.随着超声造影剂的出现及不断发展,超声造影技术在肿瘤诊断中的价值明显提高,对肿瘤的早期诊断具有一定意义;造影剂不仅可用于显像,还可作为药物或基因的载体,在超声波的作用下介导药物或基因的定位释放用于肿瘤等疾病的治疗[2],有望为肿瘤的治疗开辟一条新的途径.     

超声微泡血栓助溶效应研究进展

<正>迄今为止,超声造影剂(ultrasound contrast agent,UCA)的研究和应用已经走过了30余年历史。从UCA的早期发展历史不难看出,只有利用包膜微泡造影剂在谐振频率场中表现出的     

新型超声造影剂临床应用进展

经过近年研究,静脉法(或可用于体腔)超声造影剂(UCA)可分五个剂型:水溶液;乳状液;胶体混悬液;游离气体微泡;包裹性(Encapsula-ted)气体微泡。其造影机制有三,由于反(背)向散射(Backscatter)效应;衰减效应;超声的速度     

超声造影在肾脏肿瘤中的应用进展

新型超声造影剂声诺维（SonoVue）用于临床以来得到了迅速发展。目前其在肝脏及心血管中的研究已较成熟,在肾脏肿瘤中的研究尚处于探索阶段。超声造影（Contrast—Enhanced Ultrasound,CEUS）利用造影剂显示肿瘤的血流灌注,可用于肾脏肿瘤的诊断和治疗评价：诊断方面主要判断是否为肿瘤和良恶性肿瘤鉴别;治疗方面主要评价肾脏肿瘤消融是否彻底、局部治疗后有否残留及随访中有无复发。超声造影技术的出现可提高肾脏肿瘤鉴别诊断准确性,尤其对无或乏血供肿瘤显示较好,其在。肾脏肿瘤中的应用有其优势但也有不足之处。     

超声造影剂介导靶向治疗的研究进展

新型超声造影剂的制备及其应用研究是近年来超声医学研究的热点和前沿。与目前临床已经广泛应用的CT、MRI造影剂相比，超声造影剂具有更广阔的市场开发前景。近年来超声造影剂在应用研究方面取得了突破性进展，使之不仅可用于诊断，而且可用于治疗。超声造影剂介导靶向治疗研究近年来发展很快，主要集中在以下几个领域。     

妇科超声造影临床应用指南

本指南叙述的超声造影(contrast-enhanced ultrasound,CEUS),是指使用微泡超声造影剂(ultrasound contrast agent,UCA)和低机械指数(mechanical index,MI)的造影成像技术。主要用于检查普通超声难以确诊的妇科病变、子宫肌瘤非手术治疗后的疗效评估及怀疑女性输卵管阻塞的患者。造影时应使用具备超声造影功能的超声检查     

超声造影剂的研究进展

超声造影剂(ultrasonic contrast agent,UCA)也被称为声学增强剂(echo enhancing media),是在血液中加入声阻抗值与血液截然不同的微气泡等介质,使血液的散射增强,以提高血管、心腔和组织的显像[1].超声造影(contrast-enhanced ultrasonography,CEU)是近年发展起来的一种评价微循环和组织灌注的新技术.随着基础理论、造影剂和显像技术的迅速发展,CEU从早期的右心显影发展到在毛细血管水平评价组织血流灌注.超声造影成为超声领域中最前沿的跨学科研究重点.随之,超声造影剂的研究也得到了快速发展.……     

Relationship between retention of a vascular endothelial growth factor receptor 2 (VEGFR2)-targeted ultrasonographic contrast agent and the level of VEGFR2 expression in an in vivo breast cancer model.

OBJECTIVE: The aim of this study was to characterize the relationship between retention of a vascular endothelial growth factor receptor 2 (VEGFR2)-targeted ultrasonographic contrast agent (UCA) and VEGFR2 expression in tumor vasculature of breast cancer. METHODS: 67NR breast cancer tumors implanted in mice were evaluated in vivo with both VEGFR2-targeted and nontargeted UCAs, and a high-frequency ultrasound system. A bolus of the UCA was injected and allowed to circulate for 4 minutes to allow binding of targeted microbubbles. After that, 2 sets of images before and after a high-power ultrasonic destruction sequence were acquired. The average video intensity of predestruction and postdestruction images was measured and used as a relative measure of retention of the UCA in the tumor. Levels of VEGFR2 expression and tumor vascular density were quantified by immunohistochemical staining and compared with retention of the VEGFR2-targeted UCA. RESULTS: Retention of VEGFR2-targeted microbubbles in tumors was significantly higher than retention of nontargeted microbubbles (mean +/- SD, 47.75+/-9.85 versus 18.5+/-5.46 dB; P< .001). Retention of the VEGFR2-targeted UCA was found to correlate with the level of VEGFR2 expression in the studied tumors (r(2)=0.41). In contrast, retention of the nontargeted UCA was not correlated with the level of VEGFR2 expression (r(2)=0.08). Furthermore, retention of the VEGFR2-targeted UCA was not correlated with the level of tumor vascularity. CONCLUSIONS: The magnitude of the molecular ultrasonographic signal from a VEGFR2-targeted UCA retained by tissue correlates with VEGFR2 expression. These results validate the use of molecular ultrasonography for in vivo detection and quantification of VEGFR2 expression in this breast cancer model.     

超声与微泡在血栓性疾病诊断与治疗中的作用

临床上早期准确地检出血栓并加以治疗,对于降低血栓并发症的发生率非常重要。采用特异性配体(包括抗体、受体蛋白等)与白蛋白或脂质体连接形成靶向超声造影剂可能是一种很有前途的导向诊断和治疗方法。制备一种能与血栓靶向黏附的超声微泡以及寻找一种适当强度的超声能量来有效诱导增强超声空化作用是达到靶向诊断与助溶治疗的条件。     

Contrast-agent-enhanced ultrasound thermal ablation

The small thermal lesions induced when using high-intensity focused ultrasound (HIFU) to ablate tumors results in long treatment duration. In this study, the effect of using ultrasound contrast agent (UCA, Definity) to enhance the ultrasound (US) thermal effects and, thus to enlarge the lesion size, was studied in transparent tissue phantoms insonified by 1.85-MHz US with acoustical powers of 28.9 and 40.4 W. The experimental results show that the lesion size depended strongly on the electrical power and the concentration of UCA. UCA also reduced the power required to form a lesion of a certain size by about 30%. However, UCA moved the greatest heating position from the transducer focus, by 2.16 cm for 0.015% UCA at 40.4 W, and with lesions forming at the surface for UCA concentrations higher than 0.1%. An optimal result was obtained when using 0.001% UCA and 28.9-W US, which produced a lesion 12 times larger and an acceptable shift (less than half of the lesion length). UCA can effectively increase the size of the HIFU lesions, but lesion shift should be carefully considered while performing HIFU ablations.     

Investigation of Acoustic Changes Resulting from Contrast Enhancement in Through-Transmission Ultrasonic Imaging

Through-transmitted ultrasonic waves can be used for computed projection imaging of the breast. The goal of this research was to analyze the acoustic properties changes associated with the propagation of ultrasonic waves through media before and after ultrasound contrast agent (UCA) injection and to study the feasibility of a new imaging method combining projection imaging and UCA. Two transmission techniques were examined: Gaussian pulses and pulse inversion. In the latter, three different double inverted pulses were studied: double Gaussian, double square and double sine. A computerized automatic ultrasonic scanning system was used for imaging. To simulate blood vessels, a phantom, consisting of a latex tube through which saline was circulated, was assembled. The phantom was placed within the scanner and sets of acoustic projection images were acquired. Then, a suspension of the UCA Definity™ was added to the saline and a new set of images was obtained. The pre and postcontrast images were quantitatively compared in terms of amplitude and time-of-flight (TOF). In addition, nonlinearity was evaluated by comparing the relative alteration of the positive and negative parts of the signal. Statistically significant (p < 0.001) changes in the projection images resulting from the UCA injection were observed in wave amplitude (22% ± 13%), TOF (7.9 ns ± 6.3 ns) and nonlinear properties (35% ± 32% and 56% ± 17% for Gausian pulses and pulse inversion, respectively). One in vivo study of a female breast is also presented and its preliminary outcomes discussed. Together, these results indicate the technical feasibility of the suggested method and its potential to detect breast tumors. (E-mail:haim@bm.technion.ac.il)     

光热型纳米金-共聚物超声造影剂的制备和体内外显像

目的 制备外包纳米金壳内载全氟丙烷(C₃F₈)的聚乳酸羟基乙酸(PLGA)光热型超声造影剂,观察其在体内外的超声显像效果及体外的光热效能。方法 通过改进的乳化溶剂挥发法制备PLGA纳米粒子,包载C₃F₈气体后,再用种子生长法在PLGA表面形成纳米金壳,制备C₃F₈@PLGA@Au纳米粒子;检测其一般特性,并用近红外激光和超声成像仪评估其体外光热效能及体内外成像效果。结果 成功制备C₃F₈@PLGA@Au纳米粒子,该粒子的平均直径为268.2±80.5 nm,分散性好,无明显细胞毒性;在808 nm激光辐照下,粒子有很好的溶液光热效果;体内外超声成像实验中均有增强显像。结论 成功制备了光热型纳米超声造影剂,其有良好的体外光热性能和体内外超声显像效果,为乳腺癌疾病诊治提供了新思路。     

Ultrasonographic portography with low mechanical index gray-scale imaging in hepatic VX2 tumor

To evaluate the characteristics of portal blood supply of hepatic tumors by ultrasonographic portography (USP), an in vivo model was studied using SonoVue, a second-generation ultrasound contrast agent (UCA) and low mechanical index (MI), gray-scale harmonic imaging. SonoVue (0.05 mL) was administrated through catheter placed into the main trunk of portal vein at laparotomy, followed by a 0.5 mL saline flush, in 12 rabbits with hepatic VX2 tumor, implanted by VX2 tumor tissue cubes of approximately 1 mm3 from carrier rabbit. Results showed that low MI gray-scale imaging delineated clearly the dynamic enhancement of tumors and liver parenchyma. Among 22 tumors, seven tumors were diffusely increased, with the intensity of enhancement weaker than that of the surrounding liver parenchyma. The UCA was washed out earlier from tumors than from surrounding liver parenchyma. Three tumors showed the branches of portal vein. Five tumors showed peripheral contrast enhancement and a central coarse unenhanced hypoechoic area. Seven tumors displayed no actual enhancement. All lesions (100% [22 of 22]) were depicted clearly in the whole duration of enhancement, especially in the early and late phase, regardless of enhancement pattern, and portal blood flow was manifested in 15 of 22 (68%) tumors, by USP. The enhancement pattern of the tumors corresponded to the pathologic findings. The results indicated that ultrasonographic portography, combined with low MI levels and second-generation UCA, is a sensitive and safe method to study portal blood supply for liver cancer. It may contribute to improvement of the detectability and diagnostic ability and assist the choice of a therapeutic strategy for treatment of liver cancer. However, applicability of the method to human may be problematic because of high invasiveness and great difficulty in administering contrast medium.     

Influence of scanning frequency and ultrasonic contrast agent on reproducibility of left ventricular measurements in the mouse.

BACKGROUND: Mice are now widely used as models of cardiovascular disease. Their small size and fast heart rates are technically challenging to echocardiography. This study examined the influence of different scanning frequencies and ultrasonic contrast agent (UCA) on the accuracy and reproducibility of measurements of left ventricular (LV) structure and function. METHODS: Normal mouse hearts (C57BL6) were imaged at 3 different scanning frequencies before and after intravenous injection of the UCA, Optison. Coronary artery ligation mice and sham-operated controls were scanned at 10-22 MHz with and without UCA. RESULTS: Scanning frequency had no significant effect on intraobserver or interobserver variation of LV measurements in normal mice under baseline conditions. Use of UCA significantly reduced estimated ejection fraction at 10-22 MHz compared with baseline (baseline 50.8 +/- 7.6% vs UCA 39.7 +/- 7.6%; P = .03) and significantly increased values for LV cavity dimensions (eg, LV area diastole 20.74 +/- 1.20 vs 23.23 +/- 0.98 mm 2 ; P = .002). UCA significantly reduced intraobserver and interobserver variation in LV ejection fraction. CONCLUSIONS: Scanning frequency had no significant effect on reproducibility of LV measurements in the mouse but UCA significantly reduced interobserver variation. Use of UCA could reduce the number of mice required in any given experiment to observe a statistically significant change in LV function.     

超声微泡造影剂在肿瘤治疗应用中的进展

近年来,超声微泡造影剂在肿瘤治疗中的作用日臻明显.超声微泡造影剂在超声能量作用下发生空化效应,定向释放药物和基因,提高局部的浓度,达到定向治疗的目的.研究表明,超声微泡造影剂作为药物和基因的载体将有可能为肿瘤的治疗提供一条新的途径.     

一种新型声学造影剂对兔肾VX2肿瘤显像的实验研究

目的通过与增强CT对比研究评价本科实验室制作的声学造影剂"脂氟显"对兔肾VX2肿瘤显像的能力.方法 14只左肾种植有VX2肿瘤的家兔,超声造影前和造影后观察肿瘤的大小、数目和能发现的最小肿瘤,在24 h内做CT平扫和增强对照,实验完后处死动物与病理对照.结果 14只兔声学造影后共发现46个肿瘤,增强CT发现的肿瘤数为44个,P值0.336,相关系数r=0.988,病理肿瘤52,与声学造影比较P值0.082,相关系数r=0.978.声学造影能观察到最小肿瘤直径0.32 cm,增强CT发现的最小肿瘤直径0.32 cm,和病理比较无显著性差异.结论脂氟显能有效增强兔肾肿瘤的显像,提高肾脏肿瘤的检出率,与增强CT相当,对肾窦肿瘤优于增强CT.