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.
Animals ; Contrast Media ; Humans ; Microbubbles ; Molecular Imaging/methods* ; Neovascularization, Pathologic/diagnostic imaging* ; Ultrasonography/methods* ; Vascular Endothelial Growth Factor Receptor-2/analysis*

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.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Contrast Media/*therapeutic use ; Female ; Humans ; Liver/diagnostic imaging/pathology ; Liver Neoplasms/blood supply/*diagnostic imaging/secondary ; Male ; Middle Aged ; Neovascularization, Pathologic/diagnostic imaging ; Ultrasonography/*methods ; Young Adult

Objective To investigate the correlation between ultrasound-guided diffuse optical tomography (US-DOT) and hypoxia-inducible factor-1Α (HIF-1Α) of breast cancer. Methods Totally 69 patients with pathologically confirmed breast cancer underwent preoperative conventional breast ultrasonography examinations and US-DOT at Peking Union Medical College Hospital From October 2007 to February 2010 were enrolled in this study.After surgery,immunohistochemical staining of HIF-1Α and CD34 were performed,and the differences of total hemoglobin concentration (THC) and microvessel density (MVD) between HIF-1Α positive and negative groups were analyzed. Results HIF-1Α was positive in 12 cases (17.4%) and negative in 57 cases (82.6%). The average THC and MVD of HIF-1Α-positive cases were (274.763±77.661) Μmol/L and (33.8±10.8)/0.2 mm(2) respectively. The average THC and MVD of HIF-1Α-negative cases were (228.059±65.760)Μmol/L and (28.4±7.4)/0.2 mm(2). MVD(t=2.049,P=0.04) and THC(t=2.167,P=0.034) of HIF-1Α-positive group were significantly higher than those of HIF-1Α-negative group. Conclusions HIF-1Α can promote tumor angiogenesis and thus increase the blood supply and THC. As an indicator of tumor blood supply,THC can indirectly reflect the angiogenic activity of breast cancer.
Breast Neoplasms ; diagnostic imaging ; metabolism ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Neovascularization, Pathologic ; Tomography, Optical ; Ultrasonography, Mammary

To investigate the correlations among total liver CT perfusion parameters, unpaired arteries (UAs) and microvessel area (MVA) in a rabbit liver VX2 tumor model, and to learn the tumoral angiogenesis condition and the mechanisms for perfusion imaging.
 Methods: Rabbits with or without the inoculated VX2 tumor in the liver underwent total liver CT perfusion imaging 2 weeks after the operation. Perfusion parameters included blood flow (BF), blood volume (BV), arterial liver perfusion (ALP), portal liver perfusion (PVP), hepatic perfusion index (HPI) for the tumor rim and the surrounding liver tissue. After the examination, the UAs and MVA of tumor tissues were obtained by immunohistochemical staining. The differences of perfusion parameters between the vital tumor rim and the surrounding liver tissue were compared. The correlations among perfusion parameters, UAs and MVA were analyzed.
 Results: There was significant difference between the CT perfusion parameters at the tumor rim and the surrounding liver tissue or liver tissue of the control group (P<0.05), but there was no significant difference between the perfusion parameters at the surrounding liver tissues of the experimental group and the control (P>0.05). There was positive correlation between UAs and MVA. UAs and MVA were positively correlated with BF, ALP and BV at the tumor rim. UAs and MVA were negatively correlated with PVP. HPI positively correlated with UAs, but it was not correlated with MVA.
 Conclusion: Total liver CT perfusion can provide quantitative information to evaluate the artery and portal vein perfusion of liver VX2 tumor, and to assess the degree of tumor angiogenesis.
Animals ; Arteries ; diagnostic imaging ; Blood Volume ; Carcinoma ; Immunohistochemistry ; Liver Circulation ; Liver Neoplasms ; blood supply ; diagnostic imaging ; Microvessels ; diagnostic imaging ; Neoplasm Transplantation ; Neoplasms, Squamous Cell ; Neovascularization, Pathologic ; diagnostic imaging ; Perfusion Imaging ; statistics & numerical data ; Portal System ; diagnostic imaging ; Rabbits ; Tomography, X-Ray Computed ; methods ; statistics & numerical data

Our country has been using maturity grading method, which was proposed by Grammum in 1979, to evaluate the placental function. However, this method is subjective to consequence because it totally depends on the observation and experiences of clinicians. With the development of ultrasound technology, therefore, we reviewed more novel applications in other aspects of placenta (such as blood flow, vascularization, etc). Over the past years, scholars in the world have done a lot of research around these topics. In this review we introduce placental maturity grading with B-mode ultrasound, placental vascularization qualitative and quantitative analysis with three-dimensional Doppler ultrasound and placental volume measurement, respectively.
Female ; Humans ; Imaging, Three-Dimensional ; Neovascularization, Pathologic ; Placenta ; diagnostic imaging ; Pregnancy ; Ultrasonography, Prenatal

This study investigated the relationship between carotid plaque neovascularization and diabetes mellitus (DM) by using contrast-enhanced ultrasonography. Contrast-enhanced ultrasonography was performed in 104 patients with carotid plaque thicker than 2.0 mm. There were 36 patients with DM and 68 patients without DM. The enhanced intensity in the plaque and the ratio of enhanced intensity in the plaque to that in the lumen of the carotid artery in patients with DM were significantly greater than those in patients without DM. Our study demonstrated that the enhanced intensity in patients with DM is greater than that their counterparts without DM, suggesting that carotid plaque in DM patients may have more neovessels and may be more vulnerable.
Aged ; Carotid Arteries ; diagnostic imaging ; physiopathology ; Contrast Media ; Diabetes Mellitus ; physiopathology ; Female ; Humans ; Image Enhancement ; methods ; Male ; Middle Aged ; Neovascularization, Pathologic ; diagnosis ; diagnostic imaging ; physiopathology ; Plaque, Atherosclerotic ; diagnosis ; diagnostic imaging ; physiopathology ; Reproducibility of Results ; Sensitivity and Specificity ; Ultrasonography ; methods

Carcinoma, Hepatocellular ; blood supply ; diagnostic imaging ; Humans ; Liver Neoplasms ; blood supply ; diagnostic imaging ; Microvessels ; diagnostic imaging ; Neovascularization, Pathologic ; diagnostic imaging ; Tomography, X-Ray Computed ; methods

OBJECTIVE: To determine whether quantitative perfusion parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) correlate with immunohistochemical markers of angiogenesis in rectal cancer. MATERIALS AND METHODS: Preoperative DCE-MRI was performed in 63 patients with rectal adenocarcinoma. Transendothelial volume transfer (Ktrans) and fractional volume of the extravascular-extracellular space (Ve) were measured by Interactive Data Language software in rectal cancer. After surgery, microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression scores were determined using immunohistochemical staining of rectal cancer specimens. Perfusion parameters (Ktrans, Ve) of DCE-MRI in rectal cancer were found to be correlated with MVD and VEGF expression scores by Spearman's rank coefficient analysis. T stage and N stage (negative or positive) were correlated with perfusion parameters and MVD. RESULTS: Significant correlation was not found between any DCE-MRI perfusion parameters and MVD (rs = -0.056 and p = 0.662 for Ktrans; rs = -0.103 and p = 0.416 for Ve), or between any DCE-MRI perfusion parameters and the VEGF expression score (rs = -0.042, p = 0.741 for Ktrans ; r = 0.086, p = 0.497 for Ve) in rectal cancer. TN stage showed no significant correlation with perfusion parameters or MVD (p > 0.05 for all). CONCLUSION: DCE-MRI perfusion parameters, Ktrans and Ve, correlated poorly with MVD and VEGF expression scores in rectal cancer, suggesting that these parameters do not simply denote static histological vascular properties.
Adult ; Aged ; Aged, 80 and over ; Contrast Media/*diagnostic use ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; Neoplasm Staging ; Neovascularization, Pathologic/diagnosis/metabolism ; Rectal Neoplasms/blood supply/*diagnosis/metabolism ; Retrospective Studies ; Tumor Markers, Biological/biosynthesis ; Vascular Endothelial Growth Factor A/*biosynthesis

OBJECTIVETo investigate the potential utility of microangiography with synchrotron radiation to detect murine hepatocellular carcinoma (HCC) angiogenesis using an ex vivo model system.

METHODSAn HCC xenograft model was established by implanting HCCLM3 cells into male mice livers (n = 6). Twenty-eight days later, three of the mice were randomly selected for barium sulfate infusion into the liver and tumor via the inferior vena cava followed by ligation of the arteries, veins and common bile duct; the remaining three mice were left untreated and served as controls. All mice were sacrificed to collect livers for analysis using the BL13W beamline X-ray imager (Shanghai Synchrotron Radiation Facility, China). In addition, the tumor vasculature was evaluated by immunostaining of formalin-fixed tissues for CD31, CD34, and F8.

RESULTSHigh resolution images of tumor angiogenesis were acquired and image analysis indicated that the normal blood vessels had been displaced by the fast growing tumors. Abundant and tortuous tumor angiogenesis in the tumor periphery area and sparse angiogenesis inside the tumor were also visualized clearly. These features were similar to the immunohistological results. The smallest tumor vessels visualized were approximately 20 mum in diameter.

CONCLUSIONMicroangiography with synchrotron radiation using barium sulfate as contrast agent is a viable imaging strategy for tumor angiogenesis.

Angiography ; methods ; Animals ; Carcinoma, Hepatocellular ; blood supply ; diagnostic imaging ; Cell Line, Tumor ; Humans ; Liver Neoplasms ; blood supply ; diagnostic imaging ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neovascularization, Pathologic ; diagnostic imaging ; Tomography, X-Ray ; Xenograft Model Antitumor Assays

The feasibility of contrast-enhanced ultrasonography in the assessment of atherosclerotic plaque neovascularization and its relation to histological findings were investigated. Abdominal aortic atherosclerotic plaque model was induced in 25 New Zealand white rabbits by a combination of high cholesterol-rich diet and balloon aortic denudation. Standard and contrast-enhanced ultrasonography was performed at the 16th week of the model induction period. The plaques were classified as echogenic plaques or echolucent plaques according to their echogenicity at standard ultrasonography. The maximum thickness of plaque was measured in the longitudinal section. Time intensity curve was used to quantify the enhanced intensity of the plaque. Animals were euthanized and abdominal aortas were harvested for histological staining of CD31 to evaluate the neovascularization density of atherosclerotic plaque. The results showed that the echolucent plaques had higher enhanced intensity during contrastenhanced ultrasonography and higher neovascularization density at CD31 staining than the echogenic plaques. The enhanced intensity of atherosclerotic plaque and its ratio to lumen were well correlated with histological neovascularization density (r=0.75, P<0.001; r=0.68, P<0.001, respectively). However, the maximum thickness of plaque was not correlated with neovascularization density (r=0.235, P=0.081). These findings demonstrated that the enhanced intensity in the plaque and ratio of enhanced intensity to that in the lumen of abdominal aorta may be more accurate in the evaluation of plaque neovascularization than maximum thickness. Our study indicates that contrast-enhanced ultrasonography provides us a reliable method for the evaluation of plaque neovascularization.
Animals ; Aorta, Abdominal ; diagnostic imaging ; Image Enhancement ; methods ; Image Interpretation, Computer-Assisted ; methods ; Neovascularization, Pathologic ; diagnostic imaging ; etiology ; Phospholipids ; Plaque, Atherosclerotic ; complications ; diagnostic imaging ; Rabbits ; Reproducibility of Results ; Sensitivity and Specificity ; Statistics as Topic ; Sulfur Hexafluoride ; Ultrasonography ; methods