自制包裹氟烷气体的表面活性剂类超声造影剂观察肝肿瘤血流实验研究

目的研究含氟烷气体的表面活性剂类超声造影剂对肿瘤血流信号增强的情况。方法5只荷肝VX2肿瘤的新西兰大白兔麻醉后，经腹部探测肝脏，显示肝肿瘤的血流信号。经耳缘静脉注射表面活性剂类超声造影剂，剂量0．1mg／kg，观察肿瘤周围血管及内部血流信号增强情况及持续时间。结果肝肿瘤周边及内部能量多普勒血流信号明显增强，且增强时间较长。结论表面活性剂类超声造影剂经外周静脉注射后血管二维及血流信号增强显著，值得进一步研究。     

氟碳造影剂增强正常下肢动脉彩色血流信号的观察

目的：探讨氟碳声学造影剂对下肢动脉彩色血流信号的增强作用。方法：15例接受造影检查,超声造影剂经左前臂浅静脉弹丸式注射,剂量0.005ml/kg。结果：注射造影剂后下肢动脉彩色血流信号迅速增多、血流束增宽。高峰期持续时间20～30s(平均25±5s),消退期持续时间52～76s,平均61±6s。结论：氟碳声学造影剂能显著增强下肢动脉彩色血流信号,有助于了解深部血管血流状况。     

Doppler frequency shift and time-domain velocity enhancement induced by an ultrasonographic contrast agent.

The aim of this study was to evaluate in rabbit aorta the effect of three bolus doses of Levovist on velocity values measured with spectral Doppler sonography and with time-domain correlation method (color velocity imaging). At each step, a mean peak systolic velocity was calculated from five measurements. These measurements were taken before injection, at 20 s after, at every 30 s till the third minute, and at every minute until return to peak systolic velocity at baseline value. Total duration of enhancement was noted after each injection. After each injection, once the systolic velocity values return to baseline values, a 3 min delay was observed before the following intravenous contrast agent injection was done. With Doppler spectral analysis, after the first injection, peak systolic velocity enhancement was 15 +/- 8.4% (5 to 28%), with a 6.4 +/- 4.3 min duration. After the second injection, peak systolic velocity enhancement was 15.8 +/- 8.4% (5 to 28%) with an 8.8 +/- 4 min duration. After the third injection, it was 14 +/- 9.8% (5 to 34%) with a 13.6 +/- 7.6 min duration (P = 0.04). Peak systolic velocity measured with color velocity imaging remained unchanged after every injection. Doppler velocities were increased by a bolus injection of a contrast agent. Amplitude was not cumulative with the number of injections but was cumulative on its duration. Velocity measurement with time-domain correlation was not influenced by repeated injections.     

Contrast enhanced sonography of visceral perfusion defects in dogs

The purpose of this study was to assess the utility of an intravenous contrast agent (FS069) for visualization of normal visceral perfusion compared with perfusion after segmental infarction in a canine model. Six mongrel dogs were used as subjects. Splenic, renal, hepatic, and small bowel perfusion was assessed without and with intravenous microbubble contrast material using gray scale, color Doppler, pulsed Doppler, and color power Doppler sonography. Each organ was then reassessed after ligation of a segmental vessel. Imaging was again performed without and with contrast material using all four ultrasonographic modalities. In all organs color and spectral Doppler signals were significantly enhanced from normally perfused tissue after intravenous contrast agent injection. Ischemic areas were more conspicuous after contrast medium injection except in the liver. Hepatic perfusion was maintained by portal flow in the liver despite arterial ligation. Ligation of collateral arcades was required to produce bowel ischemia. Intravenous injection of FS069 improves evaluation of visceral perfusion and identification of focal visceral ischemia in dogs. These results suggest that this agent may increase sensitivity for detection of blood flow in small and deep vessels.     

A new Doppler signal enhancing agent for flow assessment in breast lesions.

OBJECTIVE: To determine the diagnostic performance of SonoVue (Bracco) in the enhancement of Doppler signals in breast lesions and in the improvement of diagnostic accuracy. METHODS: This multicenter study included 220 patients undergoing investigations of parenchymal lesions, 40 of which had breast tumors. After a baseline Doppler examination, intravenous doses of 0.3, 0.6, 1.2 and 2.4 ml SonoVue were injected. Doppler signal quality before and after injection was compared. Off-site assessment of the global quality of Doppler signal and duration of clinical useful enhancement, as well as off-site and on-site evaluation of quality of color and spectral Doppler, were performed. On-site evaluation of diagnostic accuracy was also carried out. Safety assessments included monitoring of adverse events up to 24 h following the last injection of SonoVue. RESULTS: On-site evaluations: baseline Doppler was conclusive in only 4/21 carcinomas and in 2/17 benign lesions. Enhanced Doppler improved differential diagnosis in 20/21 carcinomas and in 9/12 benign lesions. Time to color enhancement was 0.55 min for the lowest and 0.35 min for the highest dose. The total duration of enhancement was 3.47 min for the lowest and 5.62 min for the highest dose, respectively. Off-site assessment: SonoVue improved the quality of Doppler blood flow information both in parenchymal and focal lesions. Statistically significant changes from baseline in global quality of Doppler investigations were observed at all four SonoVue doses (P<0.05). The duration of clinically useful signal enhancement increased with doses and a significant dose relationship was obtained (P<0.001). Mild adverse events were observed in two patients only. CONCLUSION: The results obtained from this study, following both off-site and on-site assessment, demonstrate that the administration of SonoVue to patients with focal breast lesions provides significant improvement over the baseline of Doppler signal quality and a clinically useful duration of signal enhancement, related to the dose. SonoVue was shown to be a safe and well-tolerated compound.     

Contrast-enhanced color Doppler sonography of uveal melanomas

PURPOSE: The purpose of our study was to evaluate the use of the galactose microbubble-based contrast agent Levovist in color Doppler sonography of uveal melanomas. We also evaluated the use of the resistance index and pulsatility index in differentiating tumor-associated vessels from normal vessels in patients with uveal melanomas. METHODS: In this prospective study, 40 patients with uveal melanoma were examined with color Doppler sonography before and after the administration of the contrast agent Levovist. The Doppler signals were recorded from both the tumor and the orbit and were evaluated quantitatively and qualitatively. RESULTS: Tumor-associated vessels were detected without contrast enhancement in 36 of 40 patients and with contrast enhancement in 38 of 40 patients. The spectral characteristics of the Doppler signals did not change after the injection of Levovist. There were no differences-qualitative or quantitative-in Doppler signals between normal and tumor-associated vessels. CONCLUSIONS: The injection of Levovist slightly improved the detection of small vessels in uveal melanomas and the orbit but did not help to differentiate between normal vessels and tumoral vessels. The differentiation of a solid tumor from subretinal hemorrhage or effusion was improved.     

Contrast-enhanced power Doppler sonography: improved detection of characteristic flow patterns in focal liver lesions

PURPOSE: The aim of this study was to evaluate whether intravenous injection of an ultrasound contrast agent aids in the visualization of focal liver lesions on power Doppler images. METHODS: Fifty patients with focal liver lesions were studied by B-mode and power Doppler sonography before and after intravenous injection of the contrast agent Levovist (galactose-based microbubbles; 10 ml of a concentration of 300 mg/ml). Thirty-two patients had malignant liver lesions (19 metastases, 12 hepatocellular carcinomas, 1 cholangiocellular carcinoma), while 18 had benign lesions (12 hemangiomas, 2 focal nodular hyperplasias, 4 others). RESULTS: After contrast medium injection, the number of lesions with no intralesional flow dropped from 18 to 9. Flow signal intensity was rated subjectively as marked on contrast-enhanced images in 17 patients; only 4 patients had marked flow on precontrast images. On precontrast studies, central flow in 10 lesions and peripheral flow in 29 lesions could be observed. After enhancement, the numbers increased to 18 and 34 lesions, respectively. CONCLUSIONS: On power Doppler images, a greater number of intratumoral vessels are seen in focal liver lesions after contrast medium administration.     

自制脂膜氟碳声学造影剂长时间增强组织灰阶显像的机理初探

目的：通过对比观察自制脂膜氟碳声学造影剂“脂氟显”对正常兔肝，肾灰阶显像的增强效果，探讨其增强机理。方法：10只健康家兔经耳缘静脉团注0.01ml/k的脂氟显，采用视觉评分，动态观察肝，肾的二维灰阶增强效果。结果：脂氟显对肝实质，肾皮质的灰阶显像均有长时间增强效果，明显增强时间超过50分钟。结论：脂氟显能长时间增强组织的灰阶显像，其机理主要与造影剂在毛细血管的潴留有关。     

国产八氟丙烷微泡造影剂左心室超声显像效果研究

目的评价八氟丙烷微泡超声造影剂(C3F8)的左心室超声显像效果。方法7头实验猪分别接受低剂量(0．002ml／kg)和高剂量(0．02ml／kg)C3F8静脉注射，观察造影剂注射前后左心室显影等级、左室内膜边界改善效果和Simpson法左室射血分数测定，同时评价其对实验猪的心率、呼吸的影响。结果C3F8注射后左室显影等级强度和内膜边界增强节段数均显著改善，部分心肌也可以显影；对心率和呼吸未见明显影响。结论经静脉注射C3F8可使得左心室显影明显增强，显著改善左心室内膜边界显示，安全性好。     

自制脂膜氟碳声学造影剂增强兔颅内肿瘤彩色血流显像的实验研究

目的 观察自制脂膜氟碳声学造影“脂氟显”对家兔颅内肿瘤彩色血流信号显像的增强作用。方法 5只颅内种植VX2肿瘤的家兔经耳缘静脉团注0．01ml/kg“脂氟显”，动态观察颅内肿瘤彩色血流显像的增强效果。结果“脂氟显”对家兔颅内肿瘤彩色血流显像有明显增强效果，且持续时间长。结论 “脂氟显”能明显、长时间地增强家兔颅内肿瘤的彩色血流显像，有助于了解颅内占位情况。     

Power,spectral, and color flow Doppler enhancement by a new ultrasonographic contrast agent.

The ability of EchoGen contrast agent (Sonus Pharmaceuticals, Bothell, WA) to enhance aortic, renal, and scrotal spectral Doppler, color flow, and power Doppler sonography at doses from 0.01 ml/kg to 0.65 ml/kg was evaluated in dogs. Videotaped images were digitized and analyzed for Doppler signal strength at known postinjection times. Contrast agent increased aortic spectral Doppler peak height, spectral width, and brightness. Contrast agent increased renal and testicular color flow and power Doppler sonographic signal and enhanced the visualization of vascular anatomy. Intensity and duration of these effects increased with increasing dose of contrast agent. Enhancement effect varied in different organs. At higher doses, blooming and Doppler shift artifacts were observed and are believed to be due to machine limitation.     

经静脉超声造影增强肝肿瘤彩色血流信号的临床研究

目的探讨经静脉超声造影对肝肿瘤彩色血流信号的增强作用及其在肿瘤的诊断和鉴别诊断中的应用价值。方法经外周浅静脉注射声学造影剂后,观察３３例肝肿瘤７５个瘤结节造影前、后瘤结节内、外彩色血流增强情况。结果１６例原发性肝癌２５个瘤结节内及瘤周彩色血流明显增强;６例转移性肝癌２２个瘤结节内彩色血流无明显增强,但瘤周血流增强明显;１１例肝血管瘤２８个瘤结节内彩色血流在造影即刻无明显增强,延迟显影则有明显增强,     

Parenchymal enhancement and tumor visualization using a new sonographic contrast agent.

The purpose of this study was to assess the ability of a sonographic contrast agent to increase parenchymal echogenicity and improve tumor visibility. The agent is an emulsion that changes at body temperature from nonechogenic submicrometer liquid droplets to echogenic 1 to 5 microns microbubbles, capable of transversing the pulmonary and capillary circulations. Peripheral venous injections (dosages of 0.05 to 0.8 ml/kg) were administered to five woodchucks (three with multiple hepatomas), 12 rabbits (with renal VX-2 tumors), and four dogs. Ultrasonograms were acquired from kidney, liver, tumors (including tumor vessels) and normal vessels. Uptake and washout curves were generated via videodensitometry. Finally, Doppler shifts from a cuff transducer around the celiac trunk were analyzed to provide an in vivo dose-response curve. Vascular enhancement, including hepatoma and VX-2 tumor vessels, was seen for 2 to 3 min. Maximum enhancement was 18.7 dB for a 0.6 ml/kg dose. Enhancement of normal liver and kidney parenchyma was observed in all three species for up to 20 min. Small hepatomas became more echogenic centrally, but larger tumors showed no increase in central echogenicity. In conclusion, improved tumor visibility and parenchymal enhancement was demonstrated in animals.     

自制氟碳声学造影剂对正常兔腹主动脉造影的实验研究

目的 观察自制氟碳声学造影剂对正常兔腹主动脉的造影效果及不同造影剂注入方式造影的时间-强度曲线变化。 方法 经兔耳缘静脉注入0．5ml／kg自制造影剂，常规成像观察实时造影过程，间歇式触发成像定量分析团注和推注法（0．1ml／s）造影的时间-强度曲线变化。 结果 造影后腹主动脉灰阶及多普勒信号显著增强。团注法同推注方式比较，峰值强度显著增高，但曲线下降斜率快，平均通过时间短（P〈0．001）；而推注方式可显著延长造影剂平均通过时间（P〈0．001）。 结论 自制氟碳声学造影剂能够显著增强血流显像，根据不同检查目的选择合适的造影剂注入方式，对提高造影效果有重要价值。     

Effect of filling gases on the backscatter from contrast microbubbles: theory and in vivo measurements

Two surfactant-based contrast agents, ST44 and ST68, were produced according to US Patent # 5,352,436 and filled with either air, C4F10 (perfluorobutane) or SF6 (sulfur hexaflouride). Ten rabbits received i.v. injections of each agent/gas combination with 5 repetitions of each dose (range: 0.005-0.13 mL/kg). A custom-made 10-MHz cuff transducer was placed around the surgically exposed distal aorta and audio Doppler signals were acquired in vivo. Quantitative in vivo dose responses were calculated off-line using spectral power analysis and compared to a theoretical model of microbubble dissolution and enhancement. For qualitative comparisons, 10 rabbits were imaged pre- and postcontrast administration (dose: 0.1 mL/kg) in gray-scale and colour. All agent/gas combinations produced marked Doppler enhancement with air bubbles enhancing least of all (p < 0.0001) and ST68-SF6 best of all (maximum: 27.6 +/- 2.04 dB; p < 0.012). There were no significant differences between other agent/gas combinations (0.30 < p < 0.70). Theoretical enhancement was within 1 order of magnitude of the experimental observations (i.e., deviations of up to 10 dB). The duration of contrast enhancement was 1-2 min for air-filled bubbles, 3-5 min for SF6-filled bubbles and more than 7 min for C4F10-filled bubbles. In conclusion, ST68-SF6 microbubbles produced most in vivo enhancement of the agent/gas combinations studied. Theory matched the measurements within an order of magnitude.     

超声造影剂在正常人肝脏中的应用研究

经外周静脉注射，超声造影剂通过肺循环达到全身脏器和组织增强多普勒血流信号是造影剂的最新发展。我们运用Levovist对20例上常人肝脏进行了前瞻性研究，其结果显示19例多普勒血流信号增强达到Ⅲ级，占95％，1例达到Ⅱ级；平均增强开始时间、峰值出现时间和持续时间分别为14．1秒、23．6秒和167.1秒。有5例出现二维声像图增强，6例门静脉内出现点状强问声。超声造影剂能够有效增强彩色多普勒信号，有助于细小血管的显于，具有很高的潜在价值，将推动超声诊断水平的提高。     

利声显在多普勒超声心动图中的作用评价

为评价外周静脉注射造影剂利声显（Ｌｅｖｏｖｉｓｔ）对超声心动图多普勒信号的增强作用，对包括二尖瓣返流、主动脉瓣返流和房间隔缺损等３０例受试者进行研究。结果示：造影剂在右心腔显影后立即在左心腔显影；注射利声显后所有受试者的连续多普勒频谱信号评分增加，频谱示返流及分流的速度峰值及积分都增加；彩色多普勒示返流及分流束的面积和周长均增加。结论认为利声显是一种跨肺循环的造影剂，能增强二尖瓣返流、主动脉瓣返流及左向右分流的多普勒信号强度，安全性好     

三维超声观察静脉注射声学造影剂前后肿瘤血流灌注的实验研究

目的评价三维超声成像技术观察声学造影前后肿瘤血流灌注情况。方法造影前应用三维超声成像技术观察移植性兔肝脏、肾脏、肌肉和皮下ＶＸ２肿瘤的血流灌注情况,经静脉注射新型（第三代）声学造影剂ＦＸ５３０后再次检查。结果三维超声可良好地显示肿瘤血管及与周围组织血管的关系,经静脉注射造影剂后肿瘤血管明显增强,可观察肿瘤形态及肿瘤内网状的细小血管。结论三维超声（特别是经静脉声学造影后）提高了对肿瘤血流灌注的观察能力,为临床评价各种治疗疗效提供了依据。     

Ultrasonographic arterial portography with second harmonic imaging: evaluation of hepatic parenchymal enhancement with portal venous flow.

Ultrasonographic arterial portography was evaluated with second harmonic and conventional gray scale imaging after the administration of 0.001 to 0.1 ml/kg of FS069 (Optison) in 10 dogs (four dogs with ligation of the portal vein branch) and two woodchucks with hepatocellular carcinomas. Harmonic imaging was required to obtain good liver parenchymal enhancement for ultrasonographic arterial portography to be useful. The tumors were visible as regions of greater enhancement after intravenous injection and as hypoechoic regions after superior mesenteric artery injection. The segments with portal vein ligation were not detected after intravenous injection but were clearly seen after superior mesenteric artery injection. Doppler signal measurement verified a significant difference between the portal vein and hepatic vein after superior mesenteric artery injection and in the femoral artery after intravenous versus superior mesenteric artery injection, demonstrating that minimal levels of FS069 pass through the liver.     

Artifacts in ultrasonic contrast agent studies.

Intravenously injected ultrasonic contrast agents making use of encapsulated gas microbubbles have excellent clinical potential for both color and spectral Doppler studies. However, a number of artifacts are associated with sonographic contrast agent measurements. Three artifacts were identified: (1) color "blooming," (2) increased maximum Doppler shift, and (3) spectral "bubble noise." Experiments have been conducted with Albunex and Levovist. These agents were injected into rabbits and humans to allow the cause of the artifacts to be established. Color blooming occurs soon after the bolus injection and is seen as gray scale pixels changing to color display. This is caused by the increase in flow signal strength. The apparent increase in the maximum Doppler shift frequency is due to the limited dynamic range of the spectral display. Only signals above a certain threshold are visible. As the Doppler signal power is enhanced, the highest frequency visible also increases. Finally, very large excursions can sometimes be seen in the spectral display (bubble noise). These might be due to either the breakdown of microbubbles or individual very large bubbles. The color blooming and bubble noise artifacts are easily identifiable and will not influence diagnostic management. The increase in peak Doppler shifts is more troublesome as it prevents comparison of spectral parameters obtained before and after injection of contrast agent.