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1、超声造影（Contrast-enhanced ultrasound）PrefaceReview the history of the development of medical ultrasound, we see that the ultrasound rise in 70s (real-time grey-scale ultrasound) or B type ultrasound or gray-scale ultrasound tomography technology, laid the foundation of modern ultrasonic diagnosis, pavi
2、ng the way for the clinical application of ultrasound is very wide; color Doppler imaging technology developed in the 80s, the modern ultrasonic imaging diagnosis is very characteristic of nondestructive examination and cardiovascular hemodynamics and blood flow of the body organs and tissues to cre
3、ate a new field; since 90s, the emergence of many new ultrasound technology is one of the medical ultrasound emerge in an endless stream, the most influential and can further improve its status in modern imaging technology, than ultrasound contrast imaging. The contrast-enhanced ultrasonography (con
4、trast enhanced ultrasound). With the help of intravenous contrast ultrasound and contrast harmonic imaging technology, can clearly show the micro blood vessels and tissue perfusion, increase the image contrast resolution, greatly improve the sensitivity and specificity of ultrasound detected lesions
5、. This is very similar to the enhanced CT scan. Nowadays, radiography not only opens up the scope of clinical application, but also improves the diagnostic level of conventional grey scale / color Doppler ultrasonography, and has a good prospect in targeted therapy. In conclusion, CEUS is a major te
6、chnological innovation and research direction, and is a new milestone in the development of medical ultrasound.The concept of contrast-enhanced ultrasoundBarry B. Goldberg is a pioneer in the research and development of new ultrasound contrast agents in the world. He has shown great interest in the
7、research and application of various ultrasound contrast agents. Goldberg et al compared microbubbles to ultrasound contrast agents (vascularcontrast, agents) or vascular enhanced ultrasound contrast agents, which are different from oral contrast agents (oralagents) commonly used in gastrointestinal
8、imaging. Therefore, ultrasound contrast has 2 kinds of angiography agents and oral or enema contrast agents, and the former is also called microbubble contrast medium. For the past more than 10 years, contrast enhanced ultrasound or vascular contrast enhanced ultrasound has been the most rapidly dev
9、eloped. Microbubble ultrasound contrast agent in the initial research stage, the first gas is mainly used for imaging of air and oxygen, then, is to CO2 as the representative of the micro bubble shell membrane contrast agent intravenous injection and transcatheter arterial injection of contrast-enha
10、nced ultrasound. In 90s, a new type of ultrasound contrast agent came into being. The membrane contrast agent containing microbubbles was represented by Levovist (Li Fa), Albunex and Echvist, which is called the first generation of new contrast agents. Since then, more inert gas containing SonoVue (
11、SonoVue) and Options angiography as the representative of the shell membrane type agent, also known as the second generation of new contrast agent. The average diameter of the new contrast microbubbles is about 35 m, which can successfully pass through the pulmonary circulation, and realize the cont
12、rast enhancement of the left ventricle, the myocardium, and the organs, tissues and lesions of the whole body. The safety of microbubble ultrasound contrast agents: a large number of experimental studies and more than 10000 cases of clinical experience have proved that microbubble contrast agents ar
13、e safe. According to estimates, each time the intravenous injection of ultrasound contrast microbubbles containing air / gas amount is less than 200 L (0.2 ml), any no danger of air embolism; the contrast agent listed only in shell membrane was composed of acoustic ctose, the contrast agent with alb
14、umin, phospholipids or polymer. That is easy for human metabolism, toxic effects on the human body does not. Therefore, it is an ideal ultrasound contrast agent. The study pointed out that the second generation of new ultrasound contrast agent with high molecular weight and low solubility and low di
15、spersion of fluorine containing inert gas such as SF6, C3F8 etc., can significantly extend the microbubbles in the human body life, increase the stability of microbubbles.Principle of contrast-enhanced ultrasoundStudy of ultrasound contrast agent has experienced three stages, namely the first genera
16、tion of CO2 free micro shell membrane type bubble contrast agent as the representative, with Albunex and Levovist (Levovist) as the representative of the second generation of air containing micro bubble shell membrane model and contrast agent, containing an inert gas microbubble contrast agents such
17、 as SonoVue, Optison, Echogen etc.The basic principle of these contrast agents are by changing the sound attenuation, velocity and enhanced scattering, change the basic role of sonic and between organizations, namely the absorption, reflection and refraction, so that the location of the echo signal
18、enhancement. Ultrasound contrast agent microbubbles to ideal through small lung, heart and capillary circulation, so that the peripheral intravenous contrast can be simple, and can stably maintain its effect in acoustic imaging. It is found that low solubility and low dispersion of high molecular ga
19、s, such as fluorine gas, can increase the lifetime of microbubbles in blood and increase stability. With the development of polymer chemistry, some foreign scholars using biodegradable polymeric materials to replace the Human Albumin and other natural phospholipid substances, changing the compositio
20、n of micro bubble shell, thereby avoiding the problem of acoustic effect caused by the limitation of the nature of the material itself is not stable. At present the domestic and foreign research shows that polymer microbubble ultrasound contrast agent development is the most promising, it can change
21、 the polymerization conditions the acoustic properties can be designed for a tailored for the imaging condition of contrast agent, make the particle size distribution is more concentrated, after the sound attenuation is weak and prolonged in vivo the remaining time to be used in different physiologi
22、cal and pathological conditions and targeted drug delivery. With microbubbles especially halothane gas ultrasound contrast agent was developed and used in clinical, ultrasound contrast imaging technology is in rapid development, from the color Doppler imaging, intermittent harmonic gray-scale ultras
23、onography, contrast-enhanced ultrasound imaging quality has been greatly improved, the resolution is obviously improved, and greatly reduce the the artifacts, and can display real-time perfusion.Clinical application of contrast enhanced ultrasoundThe development of ultrasound contrast agents and con
24、trast-enhanced ultrasound has promoted the application of contrast-enhanced ultrasound in clinical diagnosis and treatment.1. contrast echocardiography (contrast, echocar-diography): it is reported that routine echocardiography results in technical difficulties in some 10% to 20% of patients. Microb
25、ubble contrast echocardiography is a useful method for improving endocardial findings and making cardiac function more accurate. In addition, it can visually display myocardial perfusion and improve the quantitative determination of myocardial viability, which can be successfully used to determine m
26、yocardial ischemia and necrosis.The room of ultrasonography in the diagnosis of septal defect sensitivity was 97%, higher than the same group of patients with cardiac catheterization sensitivity. It can also be used for the diagnosis of primary pulmonary hypertension,2. liver harmonic contrast enhan
27、ced ultrasonography:The effect of liver ultrasound contrast: 1., improve the detection rate of 2., location and qualitative changes of the lesions, 3. curative effect judgment, 4. portal vein blood flow study. Contrast observation contents: 1. enhanced mode: the overall enhanced peripheral enhanced
28、central enhanced (radial) enhanced 2. Distribution after the peak: homogeneous, cyclic, homogeneous enhancement of the 3. phase: according to the CT staging can be divided into arterial portal venous phase delay 0-40S 41-120S 121-200S 4. enhanced continuously the time.A large number of studies have
29、confirmed that harmonic ultrasound is the most successful clinical application in the liver, and has made a breakthrough in the application of liver tumors, and can be compared with CT angiography. First of all, the sensitivity of small tumors was improved significantly, especially for tumors less t
30、han 1cm. Secondly, the specificity was enhanced significantly. (1) liver tumors or lesions of benign and malignant differentiation, including hepatocellular carcinoma (HCC and metastasis), hemangioma, adenoma and focal nodular hyperplasia (FNH) with non-uniform distribution of fatty liver and other
31、identification; (2) liver cancer preoperative routine liver ultrasound, and further determine the size and scope of invasion tumor metastasis, there are no small hidden intrahepatic or multifocal tumors; (3) application in the diagnosis of liver tumors: interventional ultrasound contrast helps small
32、 tumor of liver in suspicious especially nodule biopsy puncture echo; (4) the application of interventional therapy liver neoplasms: in hepatic artery embolization chemotherapy after contrast-enhanced ultrasound, but also in the RF, microwave ablation, HIFU immediately after treatment of bedside ult
33、rasound angiography, determine the ablation effect and there is no residual tumor tissue, to determine further treatment, improve the curative effect.For without further treatment in patients with long-term follow-up; (5) the application of contrast-enhanced ultrasound in liver cancer operation: it
34、is reported that intraoperative angiography can detect / except other smaller tumors, surgical treatment or change range of ways in time; the primary lesion resection into intrahepatic metastasis occult examination and immediately decided to use resection or ablation; evaluate the nature and extent
35、of liver injury. In addition, in other liver diseases such as liver transplantation without vascular stenosis or occlusion of portal hypertension in patients with TIPS stent patency and Buchashi comprehensive ultrasound color Doppler syndrome detection is difficult, the application value of contrast
36、-enhanced ultrasound have certain liver.3. renal contrast radiography: renal artery stenosis is frequently encountered by ultrasonography. Renal contrast angiography can routinely display renal artery, improve the detection rate of renal artery stenosis, and make up for the deficiency of color Doppl
37、er ultrasonography. It is also helpful for the color Doppler examination of renal vessels. Animal studies have shown that radiography helps to detect renal tumors more sensitively, and the clinical significance remains to be further studied.4. splenic contrast ultrasonography: CEUS is helpful for th
38、e diagnosis of splenic tumor, splenic trauma and splenic infarction and the evaluation of its range. Chinese scholars have begun to evaluate the effect of microwave ablation in the treatment of hypersplenism.5. contrast-enhanced ultrasonography of pancreatic masses: reports of Levovist ultrasound co
39、ntrast agents in pancreatic tumors have been reported by Dai Lu Shu, which increased blood flow in the tumor by up to 100%. Malignant tumors were mainly vascularized, whereas benign tumors were less vascular. It improves the judgment of benign and malignant tumors.6. breast tumor ultrasound contrast
40、: by means of contrast-enhanced ultrasound, it can display the characteristics of tumor microvascular distribution, and can be used to identify benign and malignant tumors by using the time echo intensity curve matched with microbubbles.7. lymphoangiography enhanced (contrast): experimental studies
41、have confirmed that microbubble ultrasound angiography is helpful in showing drainage of lymph vessels and lymph nodes. CEUS is helpful in identifying lymph node metastasis of cancer. Therefore, it is possible to have sentinel lymph node metastasis in patients with breast cancer. It is of potential
42、clinical value.8. contrast enhanced ultrasonography is helpful to enhance two-dimensional transcranial Doppler (TCD) and color Doppler angiography of intracranial vessels and its real-time three-dimensional display.9. microbubble ultrasound contrast can be used to evaluate the function of liver, kid
43、ney and heart transplantation patients.Application of contrast-enhanced ultrasound in liver transplantation: 1. Preoperative evaluation of portal status, direction of blood flow, presence of portal vein thrombosis, portal cavernous degeneration, and hepatic artery occlusion;2, whether the postoperat
44、ive hepatic artery stenosis and occlusion (for patients after liver transplantation, two-dimensional and color Doppler can not see this point, it is very important, compared to the radiology department, DSA and a lot of convenience)Is there a false aneurysm?. The ultrasound contrast system of transp
45、lanted liver consists of selective arterial cannulation (invasive) or by peripheral vein (minimally invasive) injection of ultrasound contrast agent, which forms the ultrasonic interface of liver and liver in liver tissue, and the image is dense and strong echo. CEUS can observe the changes of the 3
46、 dynamic phases of the liver blood flow, that is, the arterial phase, the portal vein phase, and the liver parenchyma phase. Therefore, CEUS is helpful to detect the abnormal blood flow and intravascular lesions and the dilatation of the small bile duct. To observe the blood supply of the hepatic ar
47、tery after orthotopic liver transplantation with contrast-enhanced ultrasound, it is important to evaluate the prognosis after orthotopic liver transplantation.10. other: the microbubble contrast agent injected into the bladder will help to diagnose bladder ureter reflux; contrast agents injected in
48、to the uterine cavity will help to confirm the patency of the fallopian tubes in infertile women. It is reported that CEUS has good effect and is expected to replace traditional radiographic radiography with radioactivity. Gu Yurong reported that the application of ultrasound contrast agent Levovist
49、 can help CDFI to evaluate tumor blood vessels more accurately, and is of great value in the diagnosis, differential diagnosis and treatment of ovarian benign and malignant tumors.Application of ultrasound contrast agents in targeted therapyThe broad prospects of microbubble ultrasound contrast agents have been reported. In fact，The therapeutic effect of this new microbubble contrast agent is also promising and has attracted much attention. It has become one of the most impor