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*

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

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 evaluate whether suppression of tumor microvasculature by double anti-angiogenic protein (DAAP) treatment could increase the extent of radiofrequency ablation (RFA)-induced coagulation in a murine renal cell carcinoma model. MATERIALS AND METHODS: Renal cell carcinoma cell lines were implanted subcutaneously into 10 nude mice. Four mice received adenoviral DAAP treatment and 6 mice received sterile 0.9% saline solution as DAAP-untreated group. The effect of DAAP was evaluated according to the vascularity by contrast-enhanced ultrasound (CEUS) using microbubbles. Four DAAP-treated mice and 4 DAAP-untreated mice were then treated with RFA, resulting in 3 groups: no-therapy (n = 2), RFA only (n = 4), and RFA combined with DAAP treatment (n = 4). Immediately after RFA, the size of coagulation necrosis and mitochondrial enzyme activity were compared between the groups using analysis of variance (ANOVA) and post hoc test. RESULTS: The contrast enhancement ratio for tumor vascularization on CEUS was significantly lower in the DAAP treated group than in DAAP-untreated group (30.2 +/- 9.9% vs. 77.4 +/- 17.3%; p = 0.021). After RFA, the mean coagulation diameter was 0 mm for no-therapy group, 6.7 +/- 0.7 mm for the RFA only group and 8.5 +/- 0.4 mm for the RFA with DAAP group (ANOVA, p < 0.001). The area of viable mitochondria within the tumor was 27.9 +/- 3.9% in no-therapy group, 10.3 +/- 4.5% in the RFA only group, and 2.1 +/- 0.7% in the RFA with DAAP group (ANOVA, p < 0.001). CONCLUSION: Our results suggest the potential value of combining RFA with anti-angiogenic therapy.
Adenoviridae ; Angiogenic Proteins/*antagonists & inhibitors ; Animals ; Carcinoma, Renal Cell/blood supply/surgery/*therapy ; Catheter Ablation/*methods ; Combined Modality Therapy ; Contrast Media ; Kidney Neoplasms/blood supply/surgery/*therapy ; Male ; Mice ; Mice, Nude ; Microbubbles ; Neovascularization, Pathologic/surgery/*therapy/ultrasonography ; Recombinant Proteins

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

OBJECTIVETo investigate the role of quantitative three-dimensional (3D) power Doppler ultrasound in differentiating malignant and benign thyroid nodule.

METHODSA total of 92 lesions in 86 patients were preoperatively examined using 3D power Doppler ultrasound. The Virtual Organ Computer-aided Analysis(VOCAL)-imaging program was used to analyze the stored volume ultrasound. The differences in the mean gray value (MG), vascularization index (VI), flow index(FI), and vascularization flow index (VFI) were compared between benign and malignant lesions.

RESULTSThe MG of the malignant thyroid nodules was significantly lower than that of the benign ones (28.27±7.21 vs. 32.89±8.73,P=0.007). The benign nodules had significantly higher VI,FI,and VFI than the malignant nodules [VI:(40.43±26.55)% vs. (26.87±23.06)%,P=0.011;FI:41.03±7.19 vs. 37.51±7.17,P=0.022;VFI:18.23±14.60 vs. 11.47±12.47, P=0.009]. Also,76.5% (39/51) of the malignant nodules and 92.7% (38/41) of the benign nodules had higher VIs in the shell of the lesion than that of the whole lesion,and 80.4%(41/51) of the malignant nodules and 95.1% (39/41) of the benign nodules had higher FIs in the shell of the lesion than that of the whole lesion.

CONCLUSIONSQuantitative 3D power Doppler ultrasound provides a useful tool in distinguishing benign and malignant thyroid nodules. The malignant thyroid nodules have lower echoes than the benign nodules, wherese the benign nodules have larger blood flow than the malignant nodules.

Angiography ; Humans ; Imaging, Three-Dimensional ; Neovascularization, Pathologic ; Thyroid Diseases ; Thyroid Neoplasms ; Thyroid Nodule ; Ultrasonography, Doppler ; Vascular Surgical Procedures

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

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

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

OBJECTIVETo assess the feasibility of usage of microbubbles conjugated with RGD peptides and contrast enhanced ultrasound (CEU) in detection of tumor angiogenesis.

METHODSLipid microbubbles (MB) were prepared, and the RGD peptides were covalently conjugated to the lipid shell of MB (MB(RGD)). Six nude mice with tumor created by dorsal inoculation of HepG2 tumor cells were used as the test group. Six nude mice without tumor were served as the control group. 10 minutes after bolus injection of MB and MB(RGD) randomly (30 min interval) via a tail vein catheter, CEU was performed on the tumors of the test group and the thigh skeletal muscles of control group. The video intensity (VI) of tumors and the skeletal muscles were measured. The tumors and the skeletal muscles were harvested for immunohistochemical examination.

RESULTSOnly a slight contrast enhancement of the tumor was seen with MB, and the VI was 5.33 ± 1.71. While a remarkable enhancement of the tumor was observed after injection of MB(RGD). The VI was up to 17.03 ± 3.58, 3.18 folds higher as compared with that obtained by injection of MB (P < 0.05). As expected, there were no obvious contrast enhancement of the skeletal muscles with both MB(RGD) and MB. There was a high expression of αvβ3-integrin in tumor neovascular endothelium, however, no apparent expression of αvβ3-integrin was observed in the skeletal muscle vascular endothelium.

CONCLUSIONCEU with MB(RGD) can be used to effectively evaluate the angiogenesis of tumors, and it may greatly contribute to the early judgement of the nature of tumor.

Animals ; Cell Line, Tumor ; Contrast Media ; Endothelium, Vascular ; diagnostic imaging ; metabolism ; Female ; Humans ; Integrin alphaVbeta3 ; metabolism ; Liver Neoplasms ; blood supply ; diagnostic imaging ; metabolism ; pathology ; Male ; Mice ; Mice, Nude ; Microbubbles ; Muscle, Skeletal ; blood supply ; Neoplasm Transplantation ; Neovascularization, Pathologic ; diagnostic imaging ; metabolism ; pathology ; Oligopeptides ; Ultrasonics ; methods ; Ultrasonography