灯盏细辛注射液联合尿激酶治疗下肢深静脉血栓

目的:观察灯盏细辛注射液联合尿激酶治疗下肢深静脉血栓的临床疗效。材料与方法:选择确诊的下肢深静脉血栓患者50例行下腔静脉造影,下腔静脉永久滤器植入后,经患肢静脉注射灯盏细辛注射液和小剂量尿激酶顺行溶栓治疗,根据临床症状的改善情况进行疗效分析和随访观察。结果:50例患者治愈12例(24%),显效26例(52%),好转9例(18%),无效3例(6%),总有效率为94%。无肺栓塞及重要脏器出血发生,未发现两种药物联合应用的不良反应。结论:下肢深静脉血栓患者,植入下腔静脉滤器后行灯盏细辛注射液联合小剂量尿激酶溶栓治疗,创伤小,安全,有肯定疗效。     

A Review of Phospholipid Encapsulated Ultrasound Contrast Agent Microbubble Physics

Ultrasound contrast agent microbubbles have expanded the utility of biomedical ultrasound from anatomic imaging to the assessment of microvascular blood flow characteristics and ultrasound-assisted therapeutic applications. Central to their effectiveness in these applications is their resonant and non-linear oscillation behaviour. This article reviews the salient physics of an oscillating microbubble in an ultrasound field, with particular emphasis on phospholipid-coated agents. Both the theoretical underpinnings of bubble vibration and the experimental evidence of non-linear encapsulated bubble dynamics and scattering are discussed and placed within the context of current and emerging applications.     

Microbubble Void Imaging: A Non-invasive Technique for Flow Visualisation and Quantification of Mixing in Large Vessels Using Plane Wave Ultrasound and Controlled Microbubble Contrast Agent Destruction

There is increasing recognition of the influence of the flow field on the physiology of blood vessels and their development of pathology. Preliminary work is reported on a novel non-invasive technique, microbubble void imaging, which is based on ultrasound and controlled destruction of microbubble contrast agents, permitting flow visualisation and quantification of flow-induced mixing in large vessels. The generation of microbubble voids can be controlled both spatially and temporally using ultrasound parameters within the safety limits. Three different model vessel geometries—straight, planar-curved and helical—with known effects on the flow field and mixing were chosen to evaluate the technique. A high-frame-rate ultrasound system with plane wave transmission was used to acquire the contrast-enhanced ultrasound images, and an entropy measure was calculated to quantify mixing. The experimental results were cross-compared between the different geometries and with computational fluid dynamics. The results indicated that the technique is able to quantify the degree of mixing within the different configurations, with a helical geometry generating the greatest mixing, and a straight geometry, the lowest. There is a high level of concordance between the computational fluid dynamics and experimental results. The technique could also serve as a flow visualisation tool.     

超声空化微气泡造影剂对人乳腺癌细胞影响的实验研究

目的观察不同浓度脂质体微气泡造影剂在超声照射下对体外培养的人乳腺癌细胞的影响。 方法12孔板培养人乳腺癌细胞并分为：（1）对照组；（2）单纯超声照射组；（3）单纯造影剂组；（4）造影剂＋超声照射组。不同造影剂浓度下，声波发射强度一3dB，照射时间60s。给予实验刺激后，原子力显微镜动态观察细胞膜形态的改变，PI染色后观察细胞的活性。 结果单纯超声照射组及造影剂组细胞膜形态与对照组比较无明显改变。造影剂＋超声照射组细胞膜出现大小不等的微孔，提高造影剂浓度，孔径增大，但细胞活性显著下降。 结论微气泡造影剂显著增强超声的空化效应，提高细胞的通透性，对细胞形态及细胞活性的影响与造影剂浓度有关。     

The Delayed Onset of Subharmonic and Ultraharmonic Emissions from a Phospholipid-Shelled Microbubble Contrast Agent

Characterizing the non-linear response of microbubble contrast agents is important for their efficacious use in imaging and therapy. In this article, we report that the subharmonic and ultraharmonic response of lipid-shelled microbubble contrast agents exhibits a strong temporal dependence. We characterized non-linear emissions from Targestar-p microbubbles (Targeson Inc., San Diego, CA, USA) periodically for 60 min, at 10 MHz excitation frequency. The results revealed a considerable increase in the subharmonic and ultraharmonic response (nearly 12–15 and 5–8 dB) after 5–10 min of agent preparation. However, the fundamental and the harmonic response remained almost unchanged in this period. During the next 50 min, the subharmonic, fundamental, ultraharmonic, and harmonic responses decreased steadily by 2–5 dB. The temporal changes in the non-linear behavior of the agent appeared to be primarily mediated by gas-exchange through the microbubble shell; temperature and prior acoustic excitation based mechanisms were ruled out. Further, there was no measurable change in the agent size distribution by static diffusion. We envisage that these findings will help obtain reproducible measurements from agent characterization, non-linear imaging, and fluid-pressure sensing. These findings also suggest the possibility for improving non-linear imaging by careful design of ultrasound contrast agents.     

Optimizing Sensitivity of Ultrasound Contrast-Enhanced Super-Resolution Imaging by Tailoring Size Distribution of Microbubble Contrast Agent

Ultrasound contrast-enhanced super-resolution imaging has recently attracted attention because of its extraordinary ability to image vascular features much smaller than the ultrasound diffraction limit. This method requires sensitive detection of separable microbubble events despite a noisy tissue background to indicate the microvasculature, and any approach that could improve the sensitivity of the ultrasound system to individual microbubbles would be highly beneficial. In this study, we evaluated the effect of varying microbubble size on super-resolution imaging sensitivity. Microbubble preparations were size sorted into different mean diameters and then were imaged at equal concentrations. Commercially manufactured Definity and Optison were also imaged for comparison. Both in vitro experiments in phantom vessels and in vivo experiments imaging rat tumors revealed that the sensitivity of contrast-enhanced super-resolution imaging can be improved by using microbubbles with a larger diameter.     

大剂量尿激酶治疗下肢深静脉血栓形成疗效观察

目的探讨不同剂量及给药途径对下肢深静脉血栓形成疗效的影响。方法 60例下肢深静脉血栓形成患者分为三组,A组20例,给予尿激酶100万IU,通过上肢静脉途径给药;B组20例,给予尿激酶50万IU,通过患肢深静脉途径给药;C组20例,给予尿激酶50万IU,通过上肢静脉途径给药。结果 A组和B组有效率均为95.0%,C组有效率为55.0%,三组比较有统计学意义,A组和B组分别与C组相比较,具有统计学差异(P<0.05)。结论大剂量尿激酶溶栓可以取得良好的溶栓效果,但同时也增加了出血的风险,经患肢深静脉给药可取得良好疗效,方法安全。     

Growth and Dissolution of an Encapsulated Contrast Microbubble: Effects of Encapsulation Permeability

Gas diffusion from an encapsulated microbubble is modeled using an explicit linear relation for gas permeation through the encapsulation. Both the cases of single gas (air) and multiple gases (perfluorocarbon inside the bubble and air dissolved in surrounding liquid) are considered. An analytical expression for the dissolution time for an encapsulated air bubble is obtained; it showed that for small permeability the dissolution time increases linearly with decreasing permeability. A perfluorocarbon-filled contrast microbubble such as Definity® was predicted to experience a transient growth because of air infusion before it dissolves in conformity with previous experimental findings. The growth phase occurs only for bubbles with a critical value of initial mole fraction of perfluorocarbon relative to air. With empirically obtained property values, the dissolution time of a 2.5-micron diameter (same as that of Definity), lipid-coated octafluoropropane bubble, with surface tension 25 mN/m, is predicted to be 42 min in an air-saturated medium. The properties such as shell permeability, surface tension and relative mole fraction of octafluoropropane are varied to investigate their effects on the time scales of bubble growth and dissolution, including their asymptotic scalings where appropriate. The dissolution dynamics scales with permeability, in that when the time is nondimensioanlized with permeability, curves for different permeabilities collapse on a single curve. Investigation of bubbles filled with other gases (nonoctafluoropropane perfluorocarbon and sulfur hexafluoride) indicates longer dissolution time because of lower solubility and lower diffusivity for larger gas molecules. For such micron-size encapsulated bubbles, lifetime of hours is possible only at extremely low surface tension (<1 mN/m) or at extreme oversaturation. (E-mail: sarkar@udel.edu)     

体外治疗性超声助溶兔股动脉血栓

目的 观察体外治疗性超声（ＥＴＵＳ）对尿激酶（ＵＫ）延迟溶栓的作用。方法 建立３４只新西兰白兔的双侧股动脉血栓模型,其中４只兔的动脉血栓不加任何处理;另８只兔的一侧股动脉血栓行早期ＥＴＵＳ（频率０．８ＭＨｚ,功率１．２５Ｗ／ｃｍ＾２）处理,对另一侧血栓行延迟ＥＴＵＳ处理;其余２２只兔随机分为二组：每组１１只兔分别于血栓形成早期或延迟阶段,经颈静脉注入ＵＫ（３００００ｕ／ｋｇ）,同时在一侧股动脉血栓     

靶向高分子造影剂的制备及其体外寻靶实验

目的制备一种特异性靶向肝癌细胞的高分子超声造影剂,并考察其体外寻靶能力。方法采用双乳化法制备高分子材料PLGA-COOH造影剂;并用碳二亚胺法将造影剂与抗体偶联制备出靶向高分子造影剂。检测该造影剂一般特性及体外寻靶能力,并与普通高分子造影剂做比较。结果高分子造影剂的平均粒径600.5 nm,体外寻靶试验显示,该靶向高分子造影剂较多并牢固的聚集到肝癌细胞表面;普通高分子造影剂对照组末见造影剂和细胞的结合。结论成功制备出特异性结合人肝癌抗体的靶向高分子超声造影剂。该造影剂在体外对肝癌细胞具有较强的特异性亲合力。     

下肢深静脉血栓形成的双向溶栓治疗研究

目的:探讨双向溶栓技术结合中医辩证施治在治疗下肢深静脉血栓形成中的应用价值。材料和方法:本文共12例,病程4天～4月。每天经髂股静脉留置导管及足背静脉各滴入尿激酶25万单位,治疗3～6天。1例在溶栓前安放了下腔静脉鸟巢式滤器。在介入溶栓的同时,结合中医辩证施治结果:12例患者中,症状完全消失者6例(50％),明显好转者3例(25％),疗效欠佳者3例(25％)。本文病例未出现严重并发症。结论:双向溶栓技术结合中医辩证施治对治疗下肢深静脉血栓形成有良好的疗效。     

球囊扩张术后局部溶栓治疗下肢深静脉血栓

目的 评价球囊扩张后经导管直接溶栓对治疗下肢DVT的价值。方法 13例下肢静脉栓塞患者经Guo静脉入路引入球囊导管,自血栓近心端逆行向血管远心端扩张,再行导管局部溶栓治疗。术后每24h静脉造影观察溶栓效果。结果 8例经Guo静脉路径成功完成球囊扩张术及局部溶栓治疗,5例24h完全溶栓,3例72－96h,溶栓剂用量平均106.25万u。结论 球囊扩张术后局部溶栓治疗能快速恢复血液循环,增强溶栓效果,迅速缓解患者症状。     

治疗超声介导微泡造影剂对体外血栓的助溶研究

目的运用本科自制脂膜氟烷超声造影剂“脂氟显”结合治疗超声对组织纤溶酶原激活物(tissue-plasminogen activator,t-PA)助溶体外血栓的有效性进行研究。方法取健康人全血制成质量约200~300mg血栓,频率1MHz治疗超声结合“脂氟显”和t-PA进行溶栓治疗。计算治疗前后的血栓质量,得到溶栓率,进行统计学分析。结果组间比较溶栓率超声+t-PA+“脂氟显”组(50.05±6.59)%与单纯超声辐照(24.14±3.93)%、单纯t-PA组(35.66±3.34)%、超声+t-PA组(41.85±4.78)%及超声+“脂氟显”组(29.51%±5.17)%间差异均有十分显著性意义(P<0.01);超声+“脂氟显”组与单纯超声辐照组间比较差异有显著性意义(P<0.05)。结论微泡超声造影剂在治疗超声介导下对t-PA助溶体外血栓有显著效果。     

High-Accuracy Ultrasound Contrast Agent Detection Method for Diagnostic Ultrasound Imaging Systems

An accurate method for detecting contrast agents using diagnostic ultrasound imaging systems is proposed. Contrast agents, such as microbubbles, passing through a blood vessel during ultrasound imaging are detected as blinking signals in the temporal axis, because their intensity value is constantly in motion. Ultrasound contrast agents are detected by evaluating the intensity variation of a pixel in the temporal axis. Conventional methods are based on simple subtraction of ultrasound images to detect ultrasound contrast agents. Even if the subject moves only slightly, a conventional detection method will introduce significant error. In contrast, the proposed technique employs spatiotemporal analysis of the pixel intensity variation over several frames. Experiments visualizing blood vessels in the mouse tail illustrated that the proposed method performs efficiently compared with conventional approaches. We also report that the new technique is useful for observing temporal changes in microvessel density in subiliac lymph nodes containing tumors. The results are compared with those of contrast-enhanced computed tomography.     

微泡造影剂联合高强度聚焦超声治疗兔肝VX-2肿瘤的声像图监测

目的 探讨微泡造影剂联合高强度聚焦超声治疗兔肝VX-2肿瘤时声像图的变化特征及超声监控能力。 方法 45只荷瘤兔随机分为3组，一组接受单纯高强度聚焦超声治疗，另两组为高强度聚焦超声联合微泡造影剂治疗。 结果 高强度聚焦超声联合微泡造影剂治疗肝肿瘤可以大大缩短治疗时间。各治疗组声像图变化的病理学基础各不相同。联合治疗后10min靶区高回声面积与凝固性坏死面积相关性良好（r=0．986，P〈0．05）。 结论 微泡造影剂增强高强度聚焦超声疗效切实可行，联合治疗的声像图特征性变化能够有效判断治疗效果。     

亲血栓性靶向超声造影剂的鉴定及体外寻靶实验研究

目的 制备亲血栓性靶向超声造影剂，探讨其体外寻靶的特点和规律。方法 在自制的白蛋白氟碳超声造影剂的基础上，采用交连法将带有荧光标记的6-肽(FITC-KV-6)与自制的白蛋白氟碳微泡结合，制备血栓靶向微泡造影剂。体外实验分3组，A组：将带有FITC-KV-6的造影剂滴加于健康人新鲜血凝块上，普通光镜和荧光显微镜下观察微泡与血块的黏附情况；B组对照：普通白蛋白氟碳造影剂；C组对照：6-肽阻断实验。结果 靶向微泡荧光免疫染色实验为阳性，对照组为阴性。体外实验显示，A组：微泡在血凝块外围形成一条凝聚带，并顺着网格状的纤维素带延伸到血块内部，而2个对照组均未见微泡与血凝块的结合。结论 采用交连法可制备亲血栓性靶向白蛋白超声造影剂；该造影剂微泡在体外能与人新鲜血凝块高效特异结合。     

持续灌注微泡并低强度超声介导体外血栓溶栓的实验研究

目的研究持续灌注微泡并低强度超声介导体外血栓的溶栓效果。方法构建体外循环系统,新鲜牛血栓随机分为5组。组1为低强度超声联合导管内持续灌注微泡和尿激酶进行溶栓;组2为低强度超声联合血栓内一次性注射微泡和尿激酶进行溶栓;组3为低强度超声联合导管内持续灌注尿激酶进行溶栓;组4为低强度超声联合导管内持续灌注微泡进行溶栓;对照组为导管内持续灌注尿激酶进行溶栓。统计分析各组的溶栓率和溶解面积,观察血栓内部红细胞分布情况及纤维蛋白网结构的完整性。结果组1溶栓率及溶栓面积均高于其他各组,差异均有统计学意义(P均<0.05);其他各组之间均无显著差异。该组HE染色镜下显示红细胞分布更松散,免疫荧光染色镜下可见较多纤维蛋白网结构断裂。结论在体外实验中,低强度超声联合持续灌注微泡能够增强尿激酶的溶栓效果。     

Preliminary Observations on the Spatial Correlation Between Short-Burst Microbubble Oscillations and Vascular Bioeffects

The objective of this preliminary study was to examine the spatial correlation between microbubble (MB)-induced vessel wall displacements and resultant microvascular bioeffects. MBs were injected into venules in ex vivo rat mesenteries and insonated by a single short ultrasound pulse with a center frequency of 1 MHz and peak negative pressures spanning the range of 1.5–5.6 MPa. MB and vessel dynamics were observed under ultra-high speed photomicrography. The tissue was examined by histology or transmission electron microscopy for vascular bioeffects. Image registration allowed for spatial correlation of MB-induced vessel wall motion to corresponding vascular bioeffects, if any. In cases in which damage was observed, the vessel wall had been pulled inward by more than 50% of the its initial radius. The observed damage was characterized by the separation of the endothelium from the vessel wall. Although the study is limited to a small number of observations, analytic statistical results suggest that vessel invagination comprises a principal mechanism for bioeffects in venules by microbubbles.     

靶向超声造影剂促进反义基因转染的体外研究

目的 探讨超声破坏造影剂微泡联合半乳糖化多聚赖氨酸(G-PLL)对基因治疗肝癌的靶向促进作用.方法 将合成的超声造影剂微泡、G-PLL及c-myc反义寡核苷酸(ASODN)耦联物,结合超声辐照作用于表达c-myc基因的人肝癌及人肺癌细胞株进行体外效应研究.观察细胞形态学改变及耦合物与细胞结合情况并检测c-myc基因的表达情况.结果 镜下显示肝癌细胞较肺癌细胞更易于与耦联物结合,多数细胞呈凋亡改变.经超声辐照,耦联物作用后的人肝癌及肺癌细胞c-myc基因表达量均有降低,而G-PLL对肝癌细胞c-myc基因表达有明显抑制作用.结论 超声辐照下,造影剂结合G-PLL及反义基因耦联物可靶向性促进反义基因转染肝癌细胞.     

Investigation of the Relationship of Nonlinear Backscattered Ultrasound Intensity with Microbubble Concentration at Low MI

The aim of this study was to measure the relationship of image intensity with contrast agent concentration. In vitro experiments were performed with a flow phantom and a sulphur hexafluoride filled microbubble contrast agent (SonoVue) at different concentrations (0.004‰ to 4‰) covering the range commonly encountered in clinical practice. The concentration of microbubbles in the contrast agent solutions was confirmed optically. Images were collected with a diagnostic ultrasound system (iU22, Phillips Medical Systems, Bothell, WA, USA) and with a nonlinear imaging technique (power modulation) at low mechanical index (MI = 0.05) to avoid bubble destruction. The mean intensity within a region of interest was measured to produce time-intensity curves from linearized (absolute scale) data. The relationship of linearized image intensity to contrast agent concentration was found to be linear up to 1‰ and reached a plateau at approximately 2‰. To operate in the linear range of the intensity-concentration relationship the contrast agent dose should be adjusted to avoid those high values in vivo and the highest dynamic range of the ultrasound system should be used to avoid unnecessary signal saturation. (E-mail: maverk@ucy.ac.cy).