Disruption of tumor neovasculature by microbubble enhanced ultrasound: a potential new physical therapy of anti-angiogenesis

Tumor angiogenesis is of vital importance to the growth and metastasis of solid tumors. The angiogenesis is featured with a defective, leaky and fragile vascular construction. Microbubble enhanced ultrasound (MEUS) cavitation is capable of mechanical disruption of small blood vessels depending on effective acoustic pressure amplitude. We hypothesized that acoustic cavitation combining high-pressure amplitude pulsed ultrasound (US) and circulating microbubble could potentially disrupt tumor vasculature. A high-pressure amplitude, pulsed ultrasound device was developed to induce inertial cavitation of circulating microbubbles. The tumor vasculature of rat Walker 256 was insonated percutaneously with two acoustic pressures, 2.6 MPa and 4.8 MPa, both with intravenous injection of a lipid microbubble. The controls were treated by the ultrasound only or sham ultrasound exposure. Contrast enhanced ultrasound (CEUS) and histology were performed to assess tumor circulation and pathological changes. The CEUS results showed that the circulation of Walker 256 tumors could be completely blocked off for 24 hours in 4.8 MPa treated tumors. The CEUS gray scale value (GSV) indicated that there was significant GSV drop-off in both of the two experimental groups but none in the controls. Histology showed that the tumor microvasculature was disrupted into diffuse hematomas accompanied by thrombosis, intercellular edema and multiple cysts formation. The 24 hours of tumor circulation blockage resulted in massive necrosis of the tumor. MEUS provides a new, simple physical method for anti-angiogenic therapy and may have great potential for clinical applications.     

诊断超声联合微泡对肿瘤微循环的作用

目的 探讨高机械指数诊断超声联合微泡对大鼠Walker-256肿瘤微循环的作用。 方法 将29只皮下荷Walker-256肿瘤SD大鼠随机分为超声微泡组(n=15)、单纯超声组(n=7)和假照组(n=7):对超声微泡组采用声辐射力脉冲(ARFI)成像模式下诊断超声连续激励20次辐照肿瘤,同时经尾静脉推注微泡0.04 ml;对单纯超声组在行超声辐照的同时以等量生理盐水代替微泡;对假照组则采用假照方式,仅推注等量微泡溶液,但不发射超声能量。对所有动物于辐照前、辐照后即刻、10、20 min行CEUS检查。最后每组随机选取3只动物获取肿瘤组织标本,行病理学检查。 结果 辐照后即刻,超声微泡组辐照区几乎无造影剂充填,呈负性显影,肿瘤区平均造影峰值强度(PI)由25.17%减低到12.01%(P<0.01);单纯超声组及假照组辐照后即刻可见造影剂快速充填,灌注良好(P>0.05)。10 min后,超声微泡组造影可见血流逐渐恢复,但PI仍降低;20 min后肿瘤血流基本完全恢复,呈高灌注(P>0.05)。 结论 高机械指数诊断超声联合微泡能特异性地暂时降低大鼠Walker-256皮下移植瘤的微循环。     

诊断超声产生的血流增强效应及肿瘤释药研究

目的采用诊断超声激励微泡的方法增强肿瘤组织的血流灌注,增加肿瘤组织局部阿霉素的释放。 方法选取健康雄性SD大鼠10只,双侧大腿内侧皮下种植Walker-256肿瘤20个,随机配对分为对照组（10例）与超声治疗组（10例）。治疗前后分别进行超声造影,对超声造影图像进行定量分析。治疗后获取部分肿瘤组织后行高效液相色谱法检测肿瘤组织的药物浓度,另外采用冰冻切片观察肿瘤组织内阿霉素的荧光强度。治疗组与对照组定量分析峰值强度（PI）、曲线下面积（AUC）及阿霉素药物质量浓度比较,采用配对t检验。 结果（1）超声治疗后视觉造影效果中,6个明显增强,4个无明显变化,定量分析PI及AUC明显高于治疗前（PI：75.74±17.67 vs 66.22±16.25,AUC：3354.91±796.15 vs 2937.52±677.51）,差异均有统计学意义（t=-5.212、-5.259,P均<0.001）;（2）治疗组阿霉素药物质量浓度是对照组的1.2倍[（1.15±0.25）μg/g vs（0.96±0.21）μg/g],差异有统计学意义（t=2.403,P<0.05）;（3）各组肿瘤组织光镜下表现：肿瘤细胞排列成条索状,核大深染,治疗组可见血管充血,有少量炎症细胞浸润;（4）激光共聚焦显微镜下可见治疗组肿瘤组织间质中外漏的阿霉素荧光明显多于对照组。 结论诊断超声激励微泡治疗可增强大鼠Walker-256肿瘤的血流灌注,有助于化疗药物局部释放。     

诊断超声联合微泡对兔VX2肿瘤的血流增强效应

目的探讨不同机械指数(MI)的诊断超声联合微泡对兔VX_2肿瘤的血流增强效应。方法选取健康雄性新西兰白兔40只,采用单侧大腿内侧瘤组织块接种法接种VX_2肿瘤,造模成功后将其随机分为实验1组(MI=0.3)、实验2组(MI=0.7)、实验3组(MI=1.4)及对照组,每组各10只。抽取0.2 ml"脂氟显"用5.0 ml生理盐水稀释后经耳缘静脉通道匀速推入,同时分别经不同机械指数辐照肿瘤,对照组予以超声假照,时间均为5 min。储存治疗前后动态造影图像,并用造影分析软件分析,记录峰值强度(PI)和曲线下面积(AUC)。结果实验1组、实验3组治疗前后PI比较差异均有统计学意义(P=0.028、0.018),实验2组、对照组治疗前后PI比较差异无统计学意义(P=0.994、0.978);实验3组治疗前后AUC值比较差异有统计学意义(P=0.009),实验1、2组及对照组治疗前后AUC值比较差异均无统计学意义(P=0.099、0.497、0.898)。结论低能量诊断超声(MI=0.3)联合微泡可丰富兔VX_2肿瘤血供,高能量诊断超声(MI=1.4)可减少血流灌注。     

Impact of Microbubble-Enhanced Ultrasound on Liver Ethanol Ablation

Ethanol ablation (EA) is a safe and effective method for treating small liver cancer. However, the ethanol is rapidly washed out by blood perfusion, preventing its accumulation within tumors. Microbubble-enhanced ultrasound (MEUS) is capable of disrupting tumor and liver circulation. We hypothesized that this disruption could be used to enhance EA of normal liver tissue. We treated surgically exposed rabbit liver with a combination of MEUS and EA. The controls were treated with only MEUS or 0.05 mL EA. MEUS treatment was administered with a high-pressure-amplitude, pulsed therapeutic ultrasound device and intra-venous injection of microbubbles. Therapeutic ultrasound was delivered at an acoustic pressure of 4.3 MPa and a duty cycle of 0.22%. Contrast-enhanced ultrasound was performed to estimate liver blood perfusion. Livers were harvested for necrotic volume measurements 48 h after treatment. Contrast-enhanced ultrasound demonstrated that liver perfusion was temporally arrested, with a significant peak intensity decline from −46.9 ± 3.8 to −64.0 ± 3.3 dB, after MEUS treatment. The mean volume ablated in MEUS + EA-treated livers (3.3 ± 2.3 cm³) was more than 10 times larger than that in livers treated only with EA (0.3 ± 0.2 cm³). The volume of liver ablated by MEUS treatment alone was minor, scattered and immeasurable. These results indicate that MEUS disruption of the liver circulation can greatly promote EA of liver.     

低能量脉冲式超声联合微泡对兔VX2肿瘤微循环的阻断作用

目的探讨低能量脉冲式超声联合微泡对兔VX2肿瘤微循环的阻断作用及其病理机制。方法将36只皮下VX2荷瘤兔随机平均分成3组:超声微泡组注入0.2ml/kg体质量微泡5ml,并辅以超声辐照10min;单纯超声组注入生理盐水5ml,辐照10min;单纯微泡组仅注入0.2ml/kg体质量微泡5ml,不进行超声辐照。CEUS观察各组治疗前、治疗后0、30min、60min时血流灌注情况,比较各时间点的灌注面积。治疗后即刻随机选取各组6只荷瘤兔处死,完整切取肿瘤,行病理学检查。结果超声微泡组治疗后即刻肿瘤血流灌注完全消失,灌注面积为0,但30min及60min后灌注有所恢复,各时间点治疗后灌注面积显著大于治疗前(均P<0.05);大体病理检查见肿瘤微血管扩张、管壁结构崩解,弥漫性充血、出血和肿瘤组织水肿,局部血肿,形成血栓等。单纯超声组及单纯微泡组治疗前、后造影剂灌注面积无差异,肿瘤内部未见出血、水肿等。结论低能量超声联合微泡能够阻断肿瘤微循环,可能是由于空化效应导致血管壁损伤,组织水肿对局部肿瘤血液循环产生阻力,从而阻断肿瘤血液循环。     

声辐射力脉冲成像鉴别诊断肾肿瘤

目的 探讨声辐射力脉冲成像(ARFI)鉴别诊断肾良恶性肿瘤的价值,以及ARFI所示肿瘤硬度与CEUS反映的肿瘤灌注之间的关系。 方法 对经手术或穿刺病理证实的35例肾肿瘤患者依次行ARFI及CEUS检查,运用声触诊组织量化(VTQ)技术测量肿瘤组织的剪切波速度(SWV),采用ROC曲线评价SWV对肾良恶性肿瘤的鉴别诊断价值并确定界值,并将ARFI所示肿瘤硬度与CEUS反映的肿瘤灌注情况进行对比。 结果 35例肾肿瘤患者中,VTQ测量的肾良恶性肿瘤的SWV值分别为(2.25±0.33)m/s和(2.72±0.46)m/s(P<0.05);以SWV=2.355 m/s为界值,鉴别诊断肾良恶性肿瘤的敏感度为83.30%,特异度为72.70%。22例(22/35,62.86%)肾肿瘤SWV值高于肾皮质,其中CEUS表现为高强化19例,低强化3例;13例(13/35,37.14%)肾肿瘤SWV值低于肾皮质,其中CEUS表现为高强化5例,低强化8例。不同硬度的肾肿瘤血流灌注程度不同,质地硬者灌注较高,质地软者灌注较低(P<0.05)。 结论 ARFI技术有助于鉴别良恶性肾肿瘤,其所示肾肿瘤硬度与血流灌注有关。     

Disruption of Splenic Circulation Using Microbubble-Enhanced Ultrasound and Prothrombin: A Preliminary Study

The spleen is a solid organ in which splenomegaly frequently develops and to which abdominal blunt trauma occurs. In this study, we demonstrated the potential therapeutic effect of microbubble-enhanced ultrasound (MEUS) combined with prothrombin to disrupt splenic circulation. A high-pressure-amplitude therapeutic ultrasound (TUS) device was used to treat 36 surgically exposed spleens in healthy New Zealand rabbits. Eighteen spleens were treated with either MEUS (n = 9) or MEUS combined with prothrombin (n = 9). The other 18 spleens were treated with TUS only or sham ultrasound exposure and served as the controls. The TUS was operated at a frequency of 831 kHz and a peak negative pressure of 4.8 MPa. Prothrombin was administered intravenously at 20 IU/kg. Contrast-enhanced ultrasound (CEUS) and acoustic quantification were performed to assess splenic blood perfusion. We found significant blood perfusion slowdown and drop-off in the MEUS-treated spleens. The peak intensity dropped from 20.2 ± 2.70 dB to 11.6 ± 4.58 dB immediately after treatment. The spleens treated with the combination of MEUS and prothrombin showed consistently poor perfusion within 1 h. In histologic examination of the MEUS-treated spleens, we found significant dilatation of splenic sinuses, hemorrhage, interstitial edema and thrombosis. This study demonstrated that the vascular effects induced by microbubble-enhanced, high-pressure ultrasound can slow down or block blood perfusion in the rabbit spleen. Prothrombin helps to enhance and extend the effects for up to 1 h.     

Ultrasound-Mediated Microbubble Cavitation Transiently Reverses Acute Hindlimb Tissue Ischemia through Augmentation of Microcirculation Perfusion via the eNOS/NO Pathway

Ultrasound-mediated microbubble cavitation improves perfusion in chronic limb and myocardial ischemia. The purpose of this study was to determine the effects of ultrasound-mediated microbubble cavitation in acute limb ischemia and investigate the mechanism of action. The animal with acute hindlimb ischemia was established using male Sprague-Dawley rats. The rats were randomly divided into three groups: intermittent high-mechanical-index ultrasound pulses combined with microbubbles (ultrasound [US] + MB group), US alone (US group) and MB alone (MB group). Both hindlimbs were treated for 10 min. Contrast ultrasound perfusion imaging of both hindlimbs was performed immediately and 5, 10, 15, 20 and 25 min after treatment. The role of the nitric oxide (NO) pathway in increasing blood flow in acutely ischemic tissue was evaluated by inhibiting endothelial nitric oxide synthase (eNOS) with N^ω-nitro-L-arginine methyl ester hydrochloride (L-NAME). In the US + MB group, microvascular blood volume and microvascular blood flow of the ischemic hindlimb were significantly increased after treatment (both p values <0.05), while the microvascular flux rate (β) increased, but not significantly (p > 0.05). The increases were observed immediately after treatment, and had dissipated by 25 min. Changes in the US and MB groups were minimal. Inhibitory studies indicated cavitation increased phospho-eNOS concentration in ischemic hindlimb muscle tissue, and the increase was significantly inhibited by L-NAME (p < 0.05). Ultrasound-mediated microbubble cavitation transiently increases local perfusion in acutely ischemic tissue, mainly by improving microcirculatory perfusion. The eNOS/NO signaling pathway appears to be an important mediator of the effect.     

超声辐照瘤内注射微泡空化效应的病理学研究

目的探讨超声辐照瘤内注射微泡引起的生物学效应。 方法将12只已建立24个Walker-256皮下移植瘤模型的SD大鼠随机分3组，A组超声监视下瘤内注射超声微泡，并用频率1MHz，强度2．0w／cm^2的超声辐照10min，B组单纯采用同等超声辐照相同时间，C组单纯瘤内注射超声微泡。各组作用后1h取肿瘤组织，HE染色观察病理改变以及用透射电镜硝酸镧示踪法观察边缘瘤组织细胞膜通透性的变化。 结果A组光镜可见大片肿瘤细胞凝固性坏死，电镜可见镧颗粒不但进入细胞间隙而且进入细胞内、以及血管内皮细胞连接。B、C组光镜均未见坏死，电镜B组偶可见少量镧颗粒进入细胞内，C组仅见镧颗粒分布于细胞间隙。 结论瘤内注射超声微泡联合超声辐照可增加细胞膜通透性并引起部分瘤细胞坏死。     

微泡增强的超声空化阻断肿瘤微循环的初步研究

目的研究微泡增强的超声空化阻断肿瘤微循环的可行性。方法 26只皮下VX_2肿瘤荷瘤兔随机分为超声微泡组、单纯超声组及假照组。超声微泡组经耳缘静脉推注微泡联合超声辐照肿瘤,单纯超声组以生理盐水代替微泡,假照组超声假照。各组治疗前、治疗后0、30和60min时间点对肿瘤进行超声造影,分析各时间点造影灌注峰值灰阶变化。结果超声微泡组肿瘤造影灰阶值(级)从治疗前的(67.8±13.3)级降至(29.7±20.1)级(P0.01),维持超过60min仍无明显再通;而单纯超声组、假照组肿瘤造影灰阶值无明显变化(P0.05)。结论微泡增强的超声空化能够有效阻断兔VX_2皮下肿瘤的微循环,其发生机制尚不清楚。     

Chemotherapy Augmentation Using Low-Intensity Ultrasound Combined with Microbubbles with Different Mechanical Indexes in a Pancreatic Cancer Model

The aim of the study was to explore the optimal mechanical indexes (MIs) for low-intensity ultrasound (LIUS) combined with microbubbles to enhance tumor blood perfusion and improve drug concentration in pancreatic cancer-bearing nude mice. Fifty-four nude mice bearing bilateral pancreatic tumors on the hind legs were randomly divided into three groups (the MI was set at 0.3, 0.7 and 1.1 in groups A, B and C, respectively). Five nude mice in each group were intravenously injected with the fluorescent dye DiR iodide (DiIC18(7),1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide); for each mouse, one tumor was treated with LIUS combined with microbubbles, and the contralateral tumor was exposed to sham ultrasound. In vivo fluorescence imaging was performed to detect the enrichment of intratumoral DiR iodide. Twelve mice in each group were intravenously injected with doxorubicin (DOX) and underwent ultrasound therapy as described above. Tumor blood perfusion changes were quantitatively evaluated with pre- and post-treatment contrast-enhanced ultrasound (CEUS, MI = 0.08). One hour after the post-treatment CEUS, nude mice were sacrificed to determine the DOX concentration in tumor tissue; one mouse in each group was sacrificed after ultrasound treatment for tumor hematoxylin–eosin staining examination. CEUS quantitative analysis and in vivo fluorescence images confirmed that LIUS at MI = 0.3 combined with microbubbles was able to enhance tumor blood flow and increase regional fluorescence dye DiR iodide concentration. The DOX concentration on the therapeutic side was significantly higher than that on the control side after ultrasound-stimulated (MI = 0.3) microbubble cavitation (USMC) treatment (1.45 ± 0.53 μg/g vs. 1.07 ± 0.46 μg/g, t = –5.163, p = 0.001). However, in groups B and C, there were no significant differences in DOX concentration between the therapeutic and control sides (Z = –0.297, –0.357, p = 0.766, 0.721). No hemorrhage or other tissue damage was observed in hematoxylin–eosin-stained tumor specimens of both sides in all groups. LIUS at MI = 0.3 combined with microbubbles was able to enhance tumor blood perfusion and improve local drug concentration in nude mice bearing pancreatic cancer.     

致敏树突状细胞对射频消融治疗大鼠实体瘤疗效的影响

目的通过观察射频消融(RFA)治疗大鼠Walker256实体瘤后局部应用树突状细胞(DC)的疗效,探讨其临床应用的可能性。方法经Walker256细胞反复冻融获得肿瘤抗原并致敏大鼠骨髓细胞衍化的DC,大鼠腋窝皮下接种Walker256细胞获得实体瘤模型。30只SD大鼠分成三组,每组10只:对照组1仅行RFA治疗;对照组2行RFA 未致敏DC治疗;实验组行RFA 冻融抗原致敏DC治疗。超声评价治疗前后各组肿瘤体积变化,记录大鼠的荷瘤生存期,各组间比较。结果实验组瘤体平均体积在治疗后第一天与对照组无显著差异,但在治疗后第2、3天测得瘤体体积显著小于其他两组对照组(P<0.05)。实验组生存期显著长于对照组(P<0.05),对照组间瘤体体积及荷瘤生存期的差异无统计学意义(P>0.05)。结论在RFA治疗大鼠Walker256实体瘤后应用致敏DC可有效地延缓肿瘤生长速度,延长大鼠荷瘤生存期,有可能为临床治疗肿瘤提供一新途径。     

Potential Application Value of Contrast-Enhanced Ultrasound In Neoadjuvant Chemotherapy of Breast Cancer

The purpose of this study was to investigate the value of contrast-enhanced ultrasound (CEUS) in evaluating the response of breast cancer to neoadjuvant chemotherapy (NAC). The study included 31 breast cancer patients who were treated with NAC between August 2010 and October 2011. All patients were evaluated by both conventional ultrasound (US) and CEUS. The tumor sizes measured by CEUS were larger and more accurately imaged than those evaluated by US. Necrosis at the tumor center could be detected by CEUS, which showed a local blood perfusion defect in 26 cases (83.9%) before NAC and 27 cases (87.1%) after NAC, whereas US did not show liquefaction in any patient. The CEUS time-intensity curve displayed quantitatively the tumors' blood-perfusion changes; after NAC, blood perfusion reduced, enhancement intensity decreased, time to peak increased, peak intensity reduced, and the wash-in slope reduced (p < 0.05). Overall, the CEUS is a promising tool for evaluating the response of breast cancer to NAC.     

乳腺肿瘤常规超声联合超声造影影像组学特征与乳腺癌分子分型相关性的研究进展

影像组学（radiomics）是一种从医学影像中高通量地提取影像特征来深入挖掘内部数据信息的技术方法,通过肿瘤分割、特征提取与模型建立来辅助临床对肿瘤的诊断与治疗。在精准医疗时代,乳腺癌（breast cancer,BC）的个体化早期诊治尤为重要。常规超声是诊断乳腺肿瘤的重要影像学方法,超声造影（contrast enhanced ultrasound,CEUS）可以实时显示乳腺肿瘤微血管灌注的形态学及功能学变化,在此基础上产生的超声及超声造影影像组学在乳腺肿瘤良恶性诊断及判断乳腺癌分子分型中具有潜在临床应用价值。本文就乳腺肿瘤常规超声联合超声造影影像组学特征与乳腺癌分子分型相关性方面进行综述。     

超声空化阻断对兔肝血流灌注的影响

目的观察微泡增强的超声空化效应在阻断兔肝血流实验中可能造成的不良反应。方法将21只健康新西兰大白兔随机均分为单纯超声组、一次超声空化组和两次超声空化组。超声空化处理采用经静脉注射脂质微泡(剂量0.1ml/kg体质量)联合峰值负压4.3MPa的脉冲式超声直接照射开腹暴露的肝脏5min。对一次超声空化组仅治疗1次;两次超声空化组治疗1次后间隔1h后重复治疗;单纯超声组用3ml生理盐水替代微泡。在治疗前及治疗后即刻、30、60min及48h对各组肝脏实施CEUS,计算各时间点峰值强度(PI)变化。实验结束后每组取一只动物,获取肝脏标本,行病理检查。结果一次超声空化治疗后即刻、30 min,靶区肝实质由此前的均匀增强变为无增强,其PI值由(-51.88±4.26)dB降至(-62.53±4.83)dB;48h后血流灌注恢复,PI值升至(-52.02±4.59)dB。两次超声空化治疗后治疗后即刻、30min,非增强缺损面积大于一次超声组,PI值变化与一次治疗组类似。单纯超声组治疗前、后CEUS无明显变化。病理发现一次超声空化组及两次超声空化组肝脏出现散在微小坏死灶。结论微泡超声空化阻断肝血流后,血流灌注可在48h后自行恢复,肝脏坏死范围较小。     

Effect of Microbubble-Enhanced Ultrasound on Radiofrequency Ablation of Rabbit Liver

Microbubble-enhanced ultrasound (MEUS) can non-invasively disrupt and block liver blood perfusion. It may potentially overcome the heat sink effect during a thermal ablation and consequently enhance radiofrequency ablation (RFA) of the liver. We propose a new strategy combining RFA with MEUS. For ultrasound treatment, an 831-kHz air-backed focused transducer directed 400-cycle bursts at 4.3?MPa to the liver at a 9-Hz rate. The treatment was nucleated by a lipids microbubble forming MEUS. Eighteen surgically exposed rabbit livers were treated using MEUS combined with RFA; the other 32 livers were treated using MEUS (n?=?14) or RFA (n?=?18) alone and served as the controls. Contrast ultrasound imaging confirmed that MEUS treatment significantly reduced liver blood perfusion by cutting contrast peak intensities in half (44.7%–54.1%) without severe liver function damage. The ablated liver volume treated using MEUS combined with RFA was 2.8 times greater than that treated using RFA alone. In conclusion, RFA of the liver can be safely and greatly enhanced by combination with MEUS pre-treatment.     

超声微泡空化增强临床胰腺癌血流灌注的研究

目的：探讨超声微泡空化对晚期胰腺癌患者肿瘤病灶血流灌注的增强效应。方法：选取经病理组织学或细胞学证实的胰腺癌患者21例,在每次临床化疗结束后120 min（白蛋白紫杉醇联合吉西他滨、FOLFIRINOX 方案、白蛋白紫杉醇联合替吉奥）内对病灶进行超声微泡空化治疗,空化治疗前后分别行超声造影动态观察肿瘤血流灌注情况,并根据肿瘤区域时间-强度曲线,分析峰值强度、曲线下面积等指标。结果：21例胰腺癌患者共计84次化疗联合超声微泡空化治疗,空化治疗后胰腺癌病灶的峰值强度由109.19 ± 2.64增加到110.62 ± 2.70(P = 0.16),曲线下面积由4752.76 ± 149.53增加到4863.67 ± 159.77(P = 0.33),二者均无统计学意义。结论：超声微泡空化治疗可增加胰腺癌患者肿瘤病灶的血流灌注量,有望改善胰腺癌因乏氧、乏血供导致的化疗抵抗问题。     

实时超声造影检测兔微小VX2肝肿瘤的实验研究

目的评估实时超声造影对最大径≤10mm的兔肝VX2微小肿瘤的检出效能。方法实时超声造影检查30只肝脏接种2个VX2肿瘤的新西兰大白兔,造影剂为注射用六氟化硫微泡（声诺维）,成像技术采用对比脉冲序列。观察兔肝VX2肿瘤的时间推移影像特征,并与普通超声及病理检查比较。结果30只动物肝脏大体病理检查共检出39个肿瘤,大小4．2—9．1mm。其中〈5．0mm的肿瘤结节造影前检出1个,造影后检出14个;5．0～10．0mm的肿瘤结节造影前检出4个,造影后检出17个;微小肿瘤检出率从造影前的12．8％提高到造影后79．5％。结论实时超声造影比普通超声显著提高了10．0mm以下兔微小VX2肿瘤的检出率。     

超声造影在卵巢肿瘤诊断中的初步应用

目的评价超声造影对卵巢肿瘤的诊断和鉴别诊断价值。方法45例盆腔内子宫旁肿块进行常规超声和超声造影检查,用明确诊断、提示可能、不确定、不符合4个等级表示超声检查价值,比较常规超声与造影对各组肿块的有意义诊断率（明确诊断＋提示可能）和明确诊断率。结果非赘生性囊肿超声造影的有意义诊断率和明确诊断率明显增高,并有统计学显著差异（P〈0.05）;卵巢良、恶性肿瘤及子宫浆膜下肌瘤有意义诊断率提高,但无统计学差异;卵巢恶性肿瘤的明确诊断率提高,具有统计学差异（P〈0.05）。结论超声造影能显示卵巢肿瘤瘤体内微小血管的血流灌注,超声造影结合二维超声形态学特点能进一步提高超声对卵巢肿瘤的诊断和鉴别诊断价值。