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 assess the performance of high-frequency ultrasound in evaluating articular lesions in a rat of model collagen-induced arthritis model (CIA).

METHODSSixty Wistar rats randomized into CIA group (n=50) and the control group (n=10), and in the former group, CIA was induced by immunization with collagen type II. On day 45, the ankle joint was assessed based on the arthritic index (AI) and examined with high-frequency ultrasound in all the rats. Histological evaluations of the joint were performed and the results were compared with ultrasound findings.

RESULTSIn CIA group, 62 ankles were confirmed pathologically to have synovitis with typical inflammatory cell infiltration and pannus formation. AI score-based diagnosis was confirmed in 42 ankles with a detection rate of 68% (42/62), significantly lower than the rate of 87% (54/62) with high-frequency ultrasound (P<0.05).

CONCLUSIONHigh-frequency ultrasound is an ideal method for observing CIA in rats in vivo. High-frequency ultrasound can show blood flow in rheumatoid arthritis and is useful in studies of RA synovial angiogenesis.

Animals ; Arthritis, Experimental ; diagnostic imaging ; Arthritis, Rheumatoid ; Collagen Type II ; Joints ; diagnostic imaging ; Neovascularization, Pathologic ; Rats ; Rats, Wistar ; Ultrasonography

OBJECTIVETo explore the feasibility of volume perfusion CT imaging to dynamically monitor and evaluate the response of rabbit VX2 soft-tissue tumor to antiangiogenic treatment.

METHODSTo establish an experimental animal model of VX2 soft tissue tumor on 20 New Zealand white rabbits. Twenty rabbits were randomly divided into 2 groups. The therapy group was treated with recombinant human endostatin (3 mg·kg⁻¹·d⁻¹) for 7 days, and the control group received saline in the same dose only. Four times of CT volume perfusion scan were performed before treatment and on the second, forth, seventh days of treatment, respectively. The value of blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability (PMB) in the VX2 tumors were measured after scanning. The microvessel density (MVD) and expression of vascular endothelial growth factor (VEGF) in the tumors were determined using immunohistochemical staining.

RESULTSThe tumor volume of the therapy group was (1.36 ± 0.73) cm³ on the forth day of treatment and (1.69 ± 0.68) cm³ on the seventh day of the treatment. The tumor volume of the control group was (2.35 ± 0.62) cm³ on the fourth day of treatment and (3.87 ± 0.93) cm³ on the seventh day of the treatment (P < 0.05). On the seventh day of treatment, tumor necrosis ratio of the therapy group and the control group was (25.58 ± 5.51)% and (42.93 ± 4.34)%, respectively (P < 0.05). Comparing the perfusion parameters between the two groups on the same day, and the second, forth, seventh days of treatment, the value of PMB of the therapy group was (70.36 ± 23.46) ml·100 ml⁻¹·min⁻¹, (79.64 ± 13.68) ml·100 ml⁻¹·min⁻¹ and (84.76 ± 3.55) ml·100 ml⁻¹·min⁻¹, respectively, and that in the control group was (26.61 ± 6.47) ml·100 ml⁻¹·min⁻¹, (33.74 ± 16.47) ml·100 ml⁻¹·min⁻¹ and (30.47 ± 10.64) ml·100 ml⁻¹·min⁻¹, respectively (P < 0.05). The value of BF in the therapy group and control group was (71.19 ± 12.21) ml·100 ml⁻¹·min⁻¹ and (43.56 ± 12.21) ml·100 ml⁻¹·min⁻¹, respectively, on the seventh day of treatment (P < 0.05). The parameters on different days in the same group were compared. In the control group, the value of BF on the seventh day of treatment was significantly lower than that before and on the second and forth days of treatment (P < 0.05). However, in the therapy group, the value of PMB on the second, forth, and seventh days of treatment was significantly higher than that before treatment (P < 0.05). MVD of tumor in the control group was increased gradually, whereas increased on the first day and then decreased more in the therapy group. The VEGF expressions did not differ significantly between the experimental and control groups.

CONCLUSIONSVolume perfusion CT is helpful to quantify the tumor perfusion and evaluate the functional changes of tumor vasculature, and then evaluate the early therapeutic effect of antiangiogenic treatment.

Angiogenesis Inhibitors ; therapeutic use ; Animals ; Antineoplastic Agents ; therapeutic use ; Blood Volume ; Capillary Permeability ; Cone-Beam Computed Tomography ; methods ; Endostatins ; therapeutic use ; Female ; Male ; Microvessels ; pathology ; Neovascularization, Pathologic ; diagnostic imaging ; Perfusion Imaging ; Rabbits ; Random Allocation ; Regional Blood Flow ; Soft Tissue Neoplasms ; blood supply ; diagnostic imaging ; drug therapy ; pathology ; Tumor Burden ; Vascular Endothelial Growth Factor A ; metabolism