Research Progress of Targeted Ultrasound Contrast Agent BR55 / 中国医学科学院学报

BR55 is an ultrasound contrast agent targeting vascular endothelial growth factor receptor 2,which can be used to detect tumor neovascularization and improve the diagnostic accuracy.Overseas researchers have used BR55 for human ultrasound molecular imaging,which showed good safety and tolerance.We reviewed the research progress on BR55 applied in the evaluation of tumor neovascularization from the composition,characteristics,animal experiments,and clinical studies of BR55.

Wide-field angiography for diagnosis and follow-up of Eales disease: a case series / Angiografia de amplo campo para diagnóstico e monitoramento da doença de Eales: série de casos

ABSTRACT Wide-field angiography enables assessing peripheral areas with better quality and gives greater deep focus, which improves the image periphery. Some studies have proposed the usefulness of these angiographic systems in inflammatory diseases of the retina. However, few studies have evaluated this technique in Eales disease. We present a case series in which 5 eyes of 3 patients with Eales disease were evaluated by using retinal fluorescein angiography with 30º, 50º, and 150º lenses in a laser-scanning ophthalmoscope. These cases highlight the usefulness of wide-field fluorescein angiography in the diagnosis and follow-up of peripheral ischemic retinal areas in Eales disease, which enables better follow-up than possible with conventional fluorescein angiography images.

RESUMO A angiografia de campo amplo permite avaliar áreas periféricas com melhor qualidade e proporciona maior foco profundo, melhorando a imagem da periferia. Alguns estudos têm proposto a utilidade desses sistemas angiográficos nas doenças inflamatórias da retina. No entanto, poucos estudos avaliaram esta técnica na doença de Eales. Apresentamos uma série de casos em que 5 olhos de 3 pacientes com doença de Eales foram avaliados usando angiografia de fluoresceína da retina com lentes de 30º, 50º e 150º em um oftalmoscópio de varredura a laser. Esses casos destacam a utilidade da angiografia com fluoresceína de campo amplo no diagnóstico e no acompanhamento das áreas isquêmicas periféricas da retina na doença de Eales, permitindo um melhor acompanhamento do o possível com imagens por angiofluoresceinografia convencional.

Evaluation of Liver Metastases Using Contrast-Enhanced Ultrasound: Enhancement Patterns and Influencing Factors

BACKGROUND/AIMS: To evaluate the enhancement patterns of liver metastases and their influencing factors using dynamic contrast-enhanced ultrasound (CEUS). METHODS: A total of 240 patients (139 male and 101 female; 58.5±11.2 years of age) diagnosed with liver metastases in our hospital were enrolled in this study to evaluate tumor characteristics using CEUS. A comparison of enhancement patterns with tumor size and primary tumor type was performed using the chi-square test. The differences between quantitative variables were evaluated with the independent-sample t-test and one-way analysis of variance. RESULTS: The enhancement patterns of liver metastases on CEUS were categorized as diffuse homogeneous hyperenhancement (133/240, 55.4%), rim-like hyperenhancement (80/240, 33.3%), heterogeneous hyperenhancement (10/240, 4.2%), and isoenhancement (17/240, 7.1%). There were significant differences in the enhancement patterns during the arterial phase based on the nodule size (p=0.001). A total of 231 of the nodules showed complete washout during the portal phase, and 237 nodules were hypoenhanced during the delayed phase. The washout time was correlated with tumor vascularity, with a longer washout time observed in hypervascular metastases compared to hypovascular metastases (p=0.033). CONCLUSIONS: Diffuse homogeneous hyperenhancement followed by rapid washout was the most common enhancement pattern of liver metastases on CEUS and was affected by the nodule size and tumor vascularity. Small metastases were prone to show diffuse homogeneous hyperenhancement. Hyper-vascular metastases showed a significantly longer washout time compared to hypovascular metastases.

Perfusion CT in Colorectal Cancer: Comparison of Perfusion Parameters with Tumor Grade and Microvessel Density

OBJECTIVE: The purpose of this study was to prospectively compare pre-operative computed tomography (CT) perfusion parameters with tumor grade from colorectal adenocarcinoma (CRC) and to correlate pre-operative CT perfusion parameters with microvessel density (MVD) to evaluate angiogenesis in CRC. MATERIALS AND METHODS: Pre-operative perfusion CTs were performed with a 64-channel multidetector row CT in 27 patients (17 women and 10 men; age range 32-82 years) who were diagnosed with CRC involving the sigmoid and rectum between August 2006 and November 2007. All patients underwent surgery without pre-operative chemotherapy or radiation therapy. Dynamic perfusion CTs were performed for 65 seconds after intravenous injection of contrast medium (100 mL, 300 mg of iodine per mL, 5 mL/sec). Before surgery, blood flow (BF), blood volume, mean transit time (MTT), and permeability-surface area product were measured in the tumor. After surgery, one gastrointestinal pathologist evaluated tumor grade and performed immunohistochemical staining using CD 34 to determine MVD in each tumor. The Kruskal-Wallis test was used to compare CT perfusion parameters with tumor grade, and Pearson's correlation analysis was used to correlate CT perfusion parameters with MVD. RESULTS: In 27 patients with CRC, tumor grading was as follows: well differentiated (n = 8); moderately differentiated (n = 15); and poorly differentiated (n = 4). BF was higher in moderately differentiated CRC than well differentiated and poorly differentiated CRCs (p = 0.14). MTT was shorter in moderately differentiated than well differentiated and poorly differentiated CRCs (p = 0.039). The MVD was greater in poorly differentiated than well differentiated and moderately differentiated CRCs (p = 0.034). There was no significant correlation between other perfusion parameters and tumor grade. There was no significant correlation between CT perfusion parameters and MVD. CONCLUSION: BF and MTT measurement by perfusion CT is effective in predicting moderately differentiated CRCs. However, perfusion CT is limited in distinguishing well differentiated and poorly differentiated CRCs. Pre-operative perfusion CT does not reflect the MVD of CRCs.

Evaluation of Tumor Angiogenesis with a Second-Generation US Contrast Medium in a Rat Breast Tumor Model

OBJECTIVE: Tumor angiogenesis is an important factor for tumor growth, treatment response and prognosis. Noninvasive imaging methods for the evaluation of tumor angiogenesis have been studied, but a method for the quantification of tumor angiogenesis has not been established. This study was designed to evaluate tumor angiogenesis in a rat breast tumor model by the use of a contrast-enhanced ultrasound (US) examination with a second-generation US contrast agent. MATERIALS AND METHODS: The alkylating agent 19N-ethyl-N-nitrosourea (ENU) was injected into the intraperitoneal cavity of 30-day-old female Sprague-Dawley rats. Three to four months later, breast tumors were detected along the mammary lines of the rats. A total of 17 breast tumors larger than 1 cm in nine rats were evaluated by gray-scale US, color Doppler US and contrast-enhanced US using SonoVue. The results were recorded as digital video images; time-intensity curves and hemodynamic parameters were analyzed. Pathological breast tumor specimens were obtained just after the US examinations. The tumor specimens were stained with hematoxylin and eosin (H & E) and the expression of CD31, an endothelial cell marker, was determined by immunohistochemical staining. We also evaluated the pathological diagnosis of the tumors and the microvessel density (MVD). Spearman's correlation and the Kruskal-Wallis test were used for the analysis. RESULTS: The pathological diagnoses were 11 invasive ductal carcinomas and six benign intraductal epithelial proliferations. The MVD did not correlate with the pathological diagnosis. However, blood volume (BV) showed a statistically significant correlation with MVD (Spearman's correlation, p < 0.05). CONCLUSION: Contrast-enhanced US using a second-generation US contrast material was useful for the evaluation of tumor angiogenesis of breast tumors in the rat.

Colour Doppler flow imaging findings in portal biliopathy.

Biliary abnormalities in extrahepatic portal vein obstruction (EHPVO) have been described in detail on endoscopic retrograde cholangiopancreaticography (ERCP), but have never before been reported on colour Doppler flow imaging (CDFI). These changes occur either due to extrinsic compression of the bile ducts or due to ischaemic biliary stenosis. The aim of this study was to evaluate the role of CDFI in demonstrating the biliary changes in patients with EHPVO. Three out of 46 patients with EHPVO (7%), who presented clinically with obstructive jaundice, were subjected to a detailed CDFI study of the abdomen, followed by ERCP and splenoportovenography (SPV). One of the patients also underwent a repeat CDFI examination at 8 weeks following a lienorenal shunt. In all 3 cases, CDFI easily distinguished the anechoeic structures seen on ultrasound at the porta hepatis as periportal collaterals, the hepatic artery and dilated bile ducts. It revealed the actual indentation made on the common bile duct (CBD) by the collaterals besides showing the presence of biliary calculi. Gallbladder varices were also well demonstrated in all the cases. ERCP confirmed the presence of portal biliopathy besides showing other changes, such as angulation, displacement and stricture of the CBD. SPV confirmed the presence of EHPVO. One patient who underwent shunt surgery showed persistent dilatation of the CBD with calculi. CDFI is a rapid, non-invasive and widely available modality which can be used to demonstrate the biliary changes in patients with EHPVO with obstructive jaundice. It may thus help screen patients who require a further by ERCP examination for the planning of treatment.

Percutaneous transmyocardial revascularization induces angiogenesis: a histologic and 3-dimensional micro computed tomography study

The purpose of this study was to visualize the spatial patterns and connection of channels created after percutaneous transmyocardial revascularization (PTMR) in normal porcine hearts, and to estimate the relative contributions of transmyocardial and coronary perfusion. Six pigs underwent PTMR creating channels using radiofrequency ablative energy. Three-dimensional computed tomography imaging of channels 1 hr after PTMR showed the direct connection of PTMR channels to the myocardial capillary network and to epicardial coronary vessels. In the heart, examined 28 day after PTMR, there was a fine, extensive, network of microvessels originating from the site of the original PTMR channel, also connecting the left ventricular cavity to myocardial capillaries. Histopathologic examination of the 1-hr specimens showed numerous regions of myocardial hemorrhage and associated inflammatory cell infiltration. In the 28-day specimens, newly developed new vascular network suggested neovascularization within the core of these channel remnants. The immunoreactivity for basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were intense within myocardium and neovascular structure surrounding PTMR channel remnants. The vascular connections occur by direct communication with existing myocardial vasculature acutely, and angiogenesis in these channel remnant chronically.