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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.

Objective: To investigate the value of contrast-enhanced ultrasound targeting vascular endothelial growth factor receptor-2 (VEGFR-2) in non-invasive monitoring of anti-angiogenesis response in subcutaneous transplantation tumor model of hepatocellular carcinoma in nude mice. Methods: Sixteen nude mice were randomly divided into control group and bevacizumab treatment group (treatment group). Two weeks later, the model of subcutaneous transplanted tumor was established. The mice in the treatment group were intratumorally injected with 0.2 mg bevacizumab, while the control group was given the same amount of saline, three times a week for 2 weeks. Ultrasound microbubbles targeting VEGFR-2 were prepared by biotin avidin method. Ultrasound examinations were performed before treatment, 7 days and 14 days after treatment, and the time intensity curve (TIC) was drawn to quantitatively analyze the differences of parameters with treatment time. The expression of CD31 in tumor tissues was detected by immunohistochemistry. Results: After 14 days of treatment, the volume of tumor tissue in the treatment group and the control group were (0.247±0.019) mm(3) and (0.307±0.031) mm(3,) respectively, the difference was statistically significant ( P <0.01). After 7 days of treatment, the rise slope (K(1)), time to peak (TTP) and peak intensity (PI) of TIC curve in the treatment group were 3.77±0.62, (3.82±0.21) s and (24.35±3.34) dB, respectively, which were significantly different from 2.93±0.31, (4.47±0.50) s and (30.10±2.35) dB in the control group, respectively ( P <0.05). Immunohistochemistry showed that the PI of contrast enhanced ultrasound was positively correlated with microvessel density ( r (2)=0.898, P =0.017). Conclusions: The therapeutic effect of bevacizumab on tumor angiogenesis evaluated by contrast-enhanced ultrasound targeting VEGFR-2 is related to the differences of parameters such as K(1), TTP and PI of TIC index. Contrast enhanced ultrasound targeting VEGFR-2 is of great value in non-invasive monitoring of subcutaneous transplanted tumor model of hepatocellular carcinoma in nude mice.

Objective: To evaluate the feasibility of intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DWI MRI) in the evaluation of tumor vascular normalization in a mouse model of colorectal cancer induced by recombinant human endostatin (rhES). Methods: The CT26 colorectal cancer xenograft model of BALB/c mice were established and divided into rhES group and control group, with 20 mice in each group. The mice of rhES group were intravenously injected with rhES 5 mg·kg(-1)·d(-1) once daily for 12 days, while the mice of the control group were intravenously injected with the same volume of 0.9% saline. 5 mice of rhES group and control group were randomly selected to perform IVIM-DWI MRI as following times: before treatment and four, eight, twelve days after treatment. The parameters of IVIM-DWI were recorded, including true diffusion coefficient(D), pseudo-diffusion coefficient (D(*)) and perfusion fraction (f). Meanwhile, microvessel density (MVD), pericyte coverage and tumor perfusion in tumor tissues were detected by immunofluorescence, respectively. Results: The tumor volumes of control group and rhES group before treatment were (154.42±24.65) mm(3) and (174.24±28.27)mm(3,) respectively, without statistically significant difference ( P =0.440). From day 2 to day 12 after treatment, the tumor volume of rhES group was significantly smaller than that of control group (all P <0.05). There were no statistical significances of D value between the rhES group and control group before and after treatment (all P >0.05). The D(*) values of the rhES group were (10.940±2.834)×10(-3)mm(2)/s and (12.940±2.801)×10(-3)mm(2)/s in day 4 and 8 after treatment respectively, significantly higher than (6.980±1.554)×10(-3)mm(2)/s and (7.898±1.603)×10(-3)mm(2)/s of control group ( P <0.05). Moreover, compared with control group, the D(*) value of rhES group was significantly lower in day 12 (6.848±1.460)×10(-3)mm(2)/s vs (9.950±2.596)×10(-3)mm(2)/s, ( P <0.05). The f value of rhES group in day 8 was (0.226±0.021)%, significantly higher than (0.178±0.016)% of control group ( P <0.01). The MVD of rhES group was significantly lower than that of control group ( P <0.05), while the pericyte coverage and tumor perfusion of rhES group were significantly higher than those of control group in day 4 and 8 after treatment (all P <0.05). In addition, we found D(*) value of IVIM-DWI in rhES group was significantly related with MVD, pericyte coverage and tumor perfusion ( r =-0.354, r =0.555, r =0.559, all P <0.05). Meanwhile, the f value in rhES group was also significantly related with MVD, pericyte coverage and tumor perfusion ( r =-0.391, r =0.538, r =0.315, all P <0.05). Conclusions: IVIM-DWI MRI can effectively evaluate the vascular normalization in rhES-induced CT26 colorectal tumor.The parameters D(*) and f are closely related to intratumorally microvessel density, pericyte coverage and perfusion, which can effectively monitor the occurrence of tumor vascular normalization time.

The development and metastasis of uterine tumors depend highly on tumor angiogenesis. Multiphase dynamic contrast-enhanced magnetic resonance imaging can quantitatively describe the hemodynamic changes of uterine tumors based on a variety of tracer kinetic models and time-signal curves and by simulating the distribution of contrast inside and outside the blood vessels. Functional parameters can accurately and noninvasively assess tumor angiogenesis. It provides a non-invasive functional evaluation method for the differential diagnosis,staging,response evaluation,and prognostic prediction of uterine tumors.

Objective To explore the diagnostic value of superb micro-vascular imaging (SMI) for patients with vulnerable plaque of carotid artery. Methods Totally 69 patient with carotid hypoechoic or predominantly hypoechoic plaque (108 plaques),which were identified by conventional ultrasound,underwent SMI and contrast-enhanced ultrasound (CEUS). Based on the scores of CEUS and SMI (0,1,and 2 points),the consistency of SMI and CEUS in detecting plaque neovascularization was assessed. Results SMI could more clearly display the profile and morphology of the plaques than conventional ultrasound. SMI showed that there were neovascularization in 75 plaques,and CEUS showed that there were neovascularization in 76 plaques;the number of scoring consistency in the plaque neovascularization under SMI and CEUS was 90,suggesting these two results were highly consistent (Kappa value=0.748). There were 6 ulcerated carotid plaques detected by SMI,and the same 6 ulcerated carotid plaques were detected by CEUS,showing complete consistency. Of these 108 plaques,55 caused stenosis of the lumen,and SMI showed there was no correlation between plaque neovascularization and stenosis of the lumen caused by plaques (P=0.473). Conclusion SMI can clearly display the morphology and outline of the plaques and the plaque neovascularization. Therefore,it can be used for evaluating plaque vulnerability.

Objective: To study the CT features for solitary fibrous tumor (SFT) in the abdomen and pelvis and to improve the diagnostic accuracy.
 Methods: Fourteen patients with SFT were collected in our hospital from January, 2011 to December, 2015. Characteristic of images were analyzed and compared for 10 SFT, which located outside the abdominal organs with extragastrointestinal stromal tumors (EGIST), leiomyosarcoma, and schwannoma.
 Results: Necrosis and cystic formation were frequently present in SFT in the abdomen and pelvis. CE-CT showed serpentine vessels along the periphery, while pattern of enhancement was map-like inhomogeneous progressive. Comparing with the EGIST or schwannoma, the difference of CT value in non-contrast and the arterial phase were statistically significant (P<0.05). The numbers of peritumoral circuity vessel were significantly different between SFT and EGIST (χ²=18.27, P<0.008) or between SFT and schwannoma (χ²=19.25, P<0.008). Comparing with the leiomyosarcoma or schwannoma, SFT located outside the abdominal organs. We found that tumor necrosis rate was significantly different between SFT and leiomyoscarcoma (χ²=8.00, P<0.008).
 Conclusion: SFT in the abdomen and pelvis show certain CT characteristics. The CT value in non-contrast and at the arterial phase, tumor necrosis rate, and serpentine vessels along the periphery were pivotal in differentiating SFT from leiomyosarcoma, EGIST and schwannoma.

Objective: 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.

Objective: To observe the characteristics of pterygium with in vivo confocal microscopy (IVCM) and understand pterygium activity with the density of inflammatory cells, formation of new blood vessels, and the number of activated keratocytes within the stroma. Methods: A prospective case-controlled study. Thirty-six pterygia from 28 patients were analyzed in this study. A pterygium activity score was obtained by summing four scores of ocular discomfort, pterygium hyperemia, keratitis, and the presence of Fuchs patches. Among them, the low activity of pterygium (PAS score less than 3 points) appeared in 12 eyes and high activity of pterygium (PAS score ≥ 4 points) in 24 eyes. All Patients underwent pterygium IVCM quantitative analysis by observing the boundaries between the pterygium and the adjacent cornea, the density of goblet cells and dendritiform inflammatory cells and Fuchs patches. The correlation of pterygium activity between IVCM and PAS with slit lamp was analyzed with Spearman correlation analysis. Results: The presence of inflammatory cells, numerous blood vessels, and irregular boundary between the cornea and the pterygium with infiltration of hyper-reflective cells in the adjacent corneal epithelium were signs observed with IVCM associated with pterygium activity. With IVCM technique, epithelial cells, goblet cells, and dendritiform inflammatory cells of various sizes were observed within the pterygium epithelium.The active (PAS ≥4) pterygium showed irregular boundaries between the pterygium and the adjacent cornea (score, 0.84±0.51) comparing with inactive subjects (score 0.23±0.12, t= 2.68, P= 0.009). Fuchs patches were observed as islets of hyper-reflective polygonal cells in front of the pterygium head with blurred boundary. The score (0.75±0.25) in active group showed significant changes as compared with normal subjects (0.23±0.12, t= 3.79, P= 0.001). The score of dendritiform inflammatory cells, activated keratocytes, and goblet cells in active group were 2.75±0.76, 1.92±0.68, and 2.08±0.42, which were significantly higher than those in inactive group (1.25±0.55, 0.50±0.25, 1.15±0.32, P= 0.035, 0.030, <0.01). There was significant positive correlation between IVCM activity and traditional slit lamp PAS. Conclusion: Quantitative analysis of dendritiform inflammatory cells, vascular proliferation and activated keratocytes of pterygium by IVCM may be a reliable evaluation method to evaluate the activity of pterygium. (Chin J Ophthalmol, 2016, 52: 755-763) .

This research is to explore the perfusion time-intensity curve parameters of a lung adenocarcinoma xenograft into nude mouse model with contrast enhanced ultrasonography(CEUS);and to investigate the angiogenesis features of tumor at different growth time.Twenty one lung adenocarcinoma xenografted nude mice were divided into three groups and inculcated with human lung adenocarcinoa.Time window for examining CEUS were respectively in7-day,14-day and 28-day.The perfusion parameters including rise time(RT),peak intensity(PI),area under the curve(AUC)of lung tumor were obtained on CEUS images by using off-line software Q lab.Immunohistochemically staining for CD34 was used to observe the microvessel density(MVD).The 7-day group had the highest AUC and PI;AUC and PI of 14-day and 28-day group decreased gradually(P<0.05).RT was increased as tumor growth.In tumor with necrosis,AUC and PI of non-necrosis part were also larger than necrosis part(P<0.05).Immunohistochemically staining for CD34 of all tumors reflected that the density of microvessels in necrosis tumor was significantly higher than those without necrosis(7.50±3.44 vs.12.44±5.74,P=0.034).Pearson correlation indicated that PI was positively related with MVD(r=0.668,P=0.008).Lung adenocarcinoma perfusion characteristic can be accessed from time-intensity curve parameters by using noninvasively and non-radiative contrast enhanced ultrasonography.Time-intensity curve parameters including AUC,PI and RT may reflect tumor angiogenesis.

Objective: To examine the characteristics of carotid arteriosclerotic plaques in contrast-enhanced ultrasonography (CEUS) of neovascularization., Methods: Seventy-eight patients with carotid atherosclerotic plaques were examined with real-time CEUS. The perfusion modes of neovascularization in relation to the carotid arteriosclerotic plaques were identified. Patients were categorized into four groups according to their plaque echo. Five patients with serious atherosclerotic carotid artery disease received carotid endarterectomy. The intra-plaque neovascularization recorded by CEUS were validated by post-surgery pathology examinations of the tissues., Results: In routing ultrasound examinations, 23 (29. 49%) plaques were identified with low-echo, 30 (38.46%) with mixed echo, 20 (25. 64%) with equal-echo, and 5 (6. 41%) with high-echo. The CEUS imaging revealed 60 carotid atherosclerotic plaques (76. 9%) with various degrees of enhancement in intra-plaque neovascularization. The thickness of plaques was correlated with the enhanced intensity of ultrasonography, with a Pearson correlation coefficient of 0. 686 (P < 0. 05). Compared with equal and high echo plaques, the enhanced intensity of ultrasonography in low and mixed echo plaques was higher (P<0. 05). The intra-plaque neovascularization recorded by CEUS was correlated with the grade of neovascularization resulted from post-surgery examinations (Spearman coefficient= 0. 886, P 0. 05)., Conclusion: The real-time CEUS can assess the neovascularization in carotid atherosclerotic plaques non-invasively and quantitatively.

Objective: To investigate the role of contrast-enhanced ultrasonography (CEUS) with pulsed inversion harmonic imaging in the evaluation of angiogenesis in ovarian tumors., Methods: Forty-two patients of ovarian tumor received CEUS examination, in which the rise time (RT), peak intensity (PI), area under the curve (AUC), time from peak to one half (TTH) and time to peak (TTP) of ovarian tumors were measured. The post- surgical specimens of ovarian tumors were analysed by the stain with polyclonal antibodies against vascular endothelial growth factor (VEGF) and CD34. Correlations between the index of VEGF, microvessel density (MVD) and ultrasonic perfusion parameters were studied., Results: MVD and VEGF index of ovarian tumors were significantly correlated with CEUS perfusion parameters including PI, AUC and TTH. The correlation coefficients of MVD with PI, AUC and TTH were 0. 569, 0. 623 and 0. 585 respectively; and the correlation coefficients of VEGF with PI, AUG and TTH were 0. 516,0. 640 and 0. 591 respectively. There were significant differences of the perfusion parameters between high and low MVD group., Conclusion: The perfusion parameters PI, AUC and TTH in CEUS were correlated with MVD and VEGF in ovarian tumors, which may be useful in the evaluation of tumors angiogenesis.

Objective: To investigate the potential utility of microangiography with synchrotron radiation to detect murine hepatocellular carcinoma (HCC) angiogenesis using an ex vivo model system., Methods: An 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., Results: High 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., Conclusion: Microangiography with synchrotron radiation using barium sulfate as contrast agent is a viable imaging strategy for tumor angiogenesis.

Objective: To explore the feasibility of volume perfusion CT imaging to dynamically monitor and evaluate the response of rabbit VX2 soft-tissue tumor to antiangiogenic treatment., Methods: To 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., Results: The 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., Conclusions: Volume 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.

This study was aimed to analyze the correlation between CT perfusion parameters, e. g. perfusion (PF), blood volume (BV), peak enhancement image (PEI), time to peak (TTP), and the microvessel density (MVD) of cervical cancer. CT perfusion scans were carried out in 31 patients with cervical cancer. After their surgical resections, we obtained 31 cases of cervical cancer specimens, and 15 cases of adjacent normal cervical specimens as control group, then these 46 specimens were used in MVD detection through immunohistochemical CD34 staining. The MVDs of the tumor group were significantly higher than those in the control group, and the former seems to increase with the clinical stages with a positive correlation. The PF and PEI values have positive correlations with corresponding MVD values. The PF value of squamous carcinoma group has correlation with corresponding MVD value. The PF and PEI values of poorly differentiated group have correlations with corresponding MVD values. The PF, PEI and BV values of II-III stage group are positively correlated with corresponding MVD values. The PF value of lymph metastasis or non-lymph metastasis group both have correlations with corresponding MVD values. We found that CT perfusion parameters were positively correlated with corresponding MVD values in cervical cancer. Our results suggest that CT perfusion is a new method which could reflect tumor angiogenesis, histological malignant grade, invasion, and clinical stage. It will help us determine the tumor staging and prognosis.

Microvessel networks were imaged by means of synchrotron radiation CT, A sliced loading and double threshold method was utilized for extracting vessels from large quantities of data (2 GB-5 GB). Preliminary analysis on the development of tumor microvessel networks was performed by statistically analyzing volume rendering and two qualitative factors, micro vessel density (MVD) and fractal dimension(FD).

Objective: To investigate the relation between multi-slice spiral CT pulmonary perfusion imaging and the cavity of microvessel in lung cancer., Methods: Altogether 36 patients with malignant nodules who underwent multi-slice spiral CT perfusion scan were examined.The perfusion parameters were collected and compared with the microvessel density (MVD), the incomplete lumen MVD, and the differentiation of non-small cell lung cancer (NSCLC). The patients were divided into a hyper-perfusion group and a hypo-perfusion group by the value of perfusion parameters. The maturity of microvessel and the degree of differentiation in NSCLC between the 2 groups was analyzed., Results: Blood flow (BF), blood volume (BV), and peak enhancement image(PEI) of the malignant nodules were (39.7±11.5) mL/(100 mg.min), (8.6±3.8)mL/100 g, and (20.1±8.6)HU, respectively. There was a positive correlation between PEI and MVD(r=0.645,P<0.01), and a negative correlation between BF and MVD(r=-0.280,P=0.048). There were negative correlations of BF, BV, PEI with the incomplete lumen MVD (P<0.05). BF had the highest correlation coefficient(r=-0.882,P<0.01).The incomplete lumen MVD of the hyper-perfusion group was significantly lower than that of hypo-perfusion group (P<0.05),but there was no significant difference in MVD between the 2 groups. There were negative correlations of BF, BV,PEI with the degree of differentiation (P<0.05). BF had the highest correlation coefficient(r=-0.751,P<0.01)., Conclusion: Multi-slice spiral CT pulmonary perfusion imaging is helpful to evaluate the degree of differentiation and status of angiogenesis in lung cancer, and its basis is the cavity of microvessel.

Objective: To assess the feasibility of usage of microbubbles conjugated with RGD peptides and contrast enhanced ultrasound (CEU) in detection of tumor angiogenesis., Methods: Lipid 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., Results: Only 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., Conclusion: CEU 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.

Objective: To study possibility of dynamic monitoring tumor angiogenesis in vivo by 3D-CTA on a 64-row multidetector CT and 4D-CE-MRA on a 3T MR scanner; compare the advantages and faults of these two methods; and analyze the relationship between tumor angiogenesis and tumor growth., Methods: This study had been approved by the institutional animal care and use committee. Thirty New Zealand white rabbits with implanted VX2 tumors in the right thigh muscle were randomly divided into five groups according to survive time (n = 6). The rabbits were scanned by a 64-row multidetector CT and a 3T MR at 4, 7, 10, 13, 16 days after tumor implantation respectively, and then sacrificed to extract the tumor. The tumors' long diameters, short diameters and volume measurements derived from CT and MR imaging were compared with pathological data. The minimum tumor diameter and the number of new tumor blood vessels detectable by 3D-CTA and 4D-CE-MRA were also compared. The morphologic process of tumor angiogenesis was monitored and described., Results: (1) The volume of tumors measured by CT imaging, MR imaging and pathological data had no significant difference (P > 0.05). (2) The minimum diameter of tumor vessels displayed on 3D-CTA and 4D-CE-MRA images was 0.68 mm +/- 0.07 mm and 0.85 mm +/- 0.12 mm respectively. The minimum diameter of tumor vessels displayed on 3D-CTA imaging was significantly smaller than 4D-CE-MRA imaging (t = -6.5075, P = 0.005). (3) The number of tumor vessels on 3D-CTA imaging and 4D-CE-MRA imaging had no significant difference at 4, 7, 10 days after tumor implantation. The number of tumor vessels on 3D-CTA images were significantly more than that on 4D-CE-MRA images at 13, 16 days after tumor implantation (all P < 0.01). (4) The morphologic process of tumor angiogenesis was demonstrated as sprouting from pre-existing blood vessel, forming lots of new vessels around tumor, and forming the immature vessels web with lots of tortuous, dilated, irregular vessels penetrating into the tumor at last., Conclusions: Volume CT and high magnet field MR can monitor tumor growth in vivo. 3D-CTA and 4D-CE-MRA can dynamicly monitor morphological changes of tumor angiogenesis in vivo. Of the two methods, 3D-CTA has better spatial resolution, but 4D-CE-MRA allows better temporal resolution of tumor angiogenesis monitoring.

Objective: To determine the significance of MSCT perfusion scan on differentiation of NSCLC and to investigate its possible mechanisms., Methods: Forty four NSCLC patients underwent CT perfusion scan by MSCT. Among them, 22 cases were selected to detected the two-dimensional tumor microvascular architecture phenotype (2D-TMAP), the relationships between CT perfusion parameters (BF, BV, PEI, TIP), and the differentiation of NSCLC were analysed by using the correlation analysis and trend test. Spearman correlation analysis was used to study the relationships between CT perfusion parameters, differentiation, and 2D-TMAP., Results: The total BF, BV and PEI decreased with decreasing differentiation of NSCLC (P<0.05). The total PEI showed a positive correlation with the total MVD (P<0.05). There were negative correlations between the surrounding area BF, the total BF, BV, and PEI, the uncomplete lumen of the surrounding area MVD, and expression of PCNA, respectively (P<0.05). There were positive correlations between degree of differentiation and the uncomplete lumen of the surrounding area MVD (P<0.05). It was the same as degree of differentiation and expression of PCNA, VEGF, respectively. There were positive correlations between the uncomplete lumen of the surrounding area MVD and expression of VEGF, ephrinB2, EphB4, and PCNA, respectively (P<0.05)., Conclusion: Perfusion parameters reflect the difference of density of vassels with mature functional lumen. Careful evaluation of the differences of blood flow pattern in pulmonary space-occupying lesions by MSCT perfusion scan can be used to identify the degree of NSCLC differentiation.

The aim of this study was to elucidate the characteristics of time attenuation curve and CT perfusion parameters for pulmonary adenocarcinomas and squamous cell carcinomas. 58 cases of pulmonary adenocarcinomas and 27 cases of squamous cell carcinomas underwent first pass CT perfusion imaging with 64-row MDCT. Data were analyzed using commercial software to generate time attenuation curve (TAC) and CT perfusion parameters, including perfusion, peak enhanced (PE), time to peak (TTP), and blood volume (BV). For TAC, there were 36.2% of type I and 63.8% of type II in adenocarcinomas, while there were 22.2% of type I and 77.8% of type II in squamous cell carcinomas. There was not significant difference (P>0.05). Perfusion, PE, TTP and BV of adenocarcinomas were 63.2 +/- 45.4 ml x min(-1) x ml(-1), 60.2 +/- 46.6 Hu, 34.8 +/- 10.2 s and 34.3 +/- 23.6 ml x 100 g(-1), respectively, while 54.3 +/- 50.2 ml x min(-1) x ml(-1), 48.5 +/- 34.9 Hu, 36.1 +/- 11.2 s and 27.6 +/- 21.7 ml x 100 g(-1), for squamous cell carcinoma, respectively. No significant differences were found between groups (P>0.05). No significant differences in TAC and CT perfusion parameters were found between adenocarcinomas and squamous cell carcinomas.

Objective: To study the effects of angiogenesis on tumorigenesis and the progression of breast carcinoma and precancerous lesion., Methods: Real time ultrasound contrast enhanced microvascular imaging (MVI) and time-intensity curve quantitative analysis were conducted on 30 normal controls, 30 cases with simple hyperplasia, 30 cases with atypical hyperplasia (AH), 20 cases with intraductal carcinoma in situ, and 50 cases with invasive ductal carcinoma, all female. Specimens of breast tissues were obtained and immunohistochemistry was used to detect the expression of CD34, a marker of vascular endothelial cells, and vascular endothelial growth factor (VEGF) and its receptor Flk-1/KDR., Results: With the progression of malignant transformation of breast tissue, the expression levels of VEGF and Flk-1/KDR increased gradually, the framework of the vessels became disordered, the levels of MVD and the perfusion parameters, such as peak intensity (PI), area under the curve (AUC), and wash-out time (WOT), increased. Obvious changes in these parameters began since the AH stage. There were not significant differences in the PI, AUC, and WOT levels between the groups of AH and in situ cancer, however, the VEGF and Flk-1/KDR levels of the in situ carcinoma group were significantly higher than those of the AH group (both P<0.05)., Conclusion: Angiogenesis plays an important role in the development of breast carcinoma. Contrast MVI and the main perfusion parameters reflect the rule of angiogenesis activity changing in different precancerous lesions, and can be used as non-invasive methods to screen high risk population.

Objective: To explore the differences between the angioarchitecture, hemodynamics, ultrastructure of neovasculr endothelial cells, and vascular distribution in different perfusion regions in benign and malignant breast tumors., Methods: 30 cases of breast carcinoma (33 lesions) and 30 cases of breast fibroadenoma (34 lesions) were examined by contrast enhanced microvascular imaging (MVI), and perfusion indexes were collected both inside and at the margin of each focus according to time-intensity quantitative analysis, including peak intensity (PI), area under the curve (AUC), time to peak (TTP) and wash-out time (WOT). The ultrastructure of neovascular endothelial cells was examined by transmission electron microscopy. The expression of CD34, VEGF, Flk-1/KDR in both two groups were detected by immuhistochemistry., Results: Significant differences were found between the two groups characterized with filling defect, vascular distortion, dilatation and uneven enhancement. Most of the curves of malignant group (87.9%, 29/33) ascended rapidly and dropped slowly while those of the benign group (79.4%, 27/34) ascended slowly and dropped rapidly. The AUC and WOT of malignant tumor group were significantly higher than those of benign group, while the PI and TTP had statistically no significant difference. In the malignant tumor group, PI, AUC and WOT collected from the margin of foci were significantly different from those collected inside the foci, however, there was no significant difference in the benign group. The margin of foci was characterized with dilated and distorted vessels, and the center of the foci was occupied by narrow or occluded blood vessels, sometimes with contracted endothelial cells and pericytes. Abundant microvascular areas located at the margin of foci. The ultrastructure of endothelial cells in the newly formed blood vessels of malignant group showed strong ability to divide, which was different from normal endothelium cells., Conclusion: The perfusion pattern, mode of time-intensity curve, mean perfusion parameter and variation of regional perfusion parameters provide a valuable diagnostic basis in distinguishing benign and malignant breast tumors. The density, morphology, distribution, structure and function of newly formed microvessels in tumor foci are also crucial factors when tumors are assessed by imaging examination.

Objective: To investigate the clinical application of first-pass perfusion MDCT in the assessment of tumor angiogenesis in carcinoma of esophagus and cardia., Methods: CT perfusion was performed with multi-detector row CT (MDCT) in 44 patients with carcinoma of esophagus and esophagogastric junction, who was diagnosed with pathological results and did not received any anti-tumor therapy. Twenty-one patients with peripheral lung cancer but normal esophagus were served as controls. Perfusion parameters were compared between normal and malignant esophagus, between adenocarcinoma and squamous cell carcinoma, as well as between tumors with metastases and those without metastases., Results: Carcinoma of esophagus and esophagogastric junction showed higher blood flow, peak enhancement index, blood volume, and shorter time to peak compared with normal esophagus (P < 0.05). There were no statistically significant differences in perfusion parameters between adenocarcinoma and squamous cell carcinoma (P > 0.05), whereas tumors with metastases showed higher blood flow and shorter time to peak compared with those without metastases (P < 0.05)., Conclusion: MDCT perfusion could assess tumor vascularity in carcinoma of esophagus and esophagogastric junction, and tumor vascularity or angiogenesis was not influenced by its histological type. However, high blood flow and short time-to-peak may be helpful to predict tumor metastases.

Objective: To investigate the correlation between power Doppler vascularity index (PDVI) and microvessel density (MVD) and evaluate the angiogenesis in high-grade gliomas and the adjacent edema in patients with glioma using intraoperative power Doppler ultrasound (PDUS) during gross total resection., Methods: In 25 cases of high-grade gliomas undergoing gross total tumor resections, PDUS was performed intraoperatively and the regions of interest within the tumor and the adjacent edema were analyzed with Photoshop software to measure the tumoral and peritumoral blood flow quantified as PDVI. The tumoral and adjacent MVD were determined using immunohistochemical staining for CD34. The correlation between PDVI in the gliomas and the adjacent edema and MVD in the corresponding areas were analyzed using Spearman correlation test., Results: The measurement of both PVDI and MVD revealed significant difference in vascularity between the gliomas and the adjacent edema (t=0.000, P<0.01), and PDVI was positively correlated to MVD measurement (r=0.7248 in the tumors and r=0.6608 in the adjacent edema)., Conclusions: The difference in the vascularity between the tumor and adjacent edema allows their distinction by PDUS during operation for high-grade glioma. Intraoperative PDUS provides an accurate and reliable means for measuring vascularity in the glioma and the adjacent edema tissue.

Objective: To investigate the role of first pass dynamic 16-slice spiral computed tomography in the evaluation of tumor angiogenesis in patients with non-small cell lung cancer (NSCLC) and to assess its importance in predicting pathologic characteristics., Methods: The first pass dynamic 16-slice spiral computed tomography was performed in 33 patients with NSCLC. Their peak heights (PH) were measured with dynamic evaluation software. Their angiogenesis were labelled by anti-CD34 monoclonal antibody. The first pass peak heights (PH) in 33 patients with NSCLC were compared with their microvessel densities (MVD) and their relationships were assessed by linear regression analysis., Results: Among the 33 patients with NSCLCs, the mean first pass PH and MVD of N1-2 were significantly higher than those at stage No (P < 0.01). The first pass PH of 33 NSCLC was correlated positively with MVDs. To differentiate stage N0 from stage N1-2 with 12 HU cutoff value of the first pass PH, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 88.0%, 75.0%, 84.8%, 91.7% and 66.7%, respectively., Conclusion: The first pass dynamic contrast enhanced CT may be a predictor of tumor angiogenesis in patients with NSCLC and its pathologic characteristics, and may be helpful to improve the accuracy of lymph node staging with conventional CT.

Objective: To discuss CT and MRI characteristics of hepatic angiomyolipoma based on pathological findings., Methods: The CT and MRI appearances with related pathohistological subtypes of 11 hepatic angiomyolipomas from 10 patients were retrospectively analyzed., Result: Ten patients with hepatic angiomyolipomas were subcategorized into lipomatous (3 cases), angiomatous (1 case), myomatous (1 case) and mixed (5 cases) subtypes. Lesions of the lipomatous type were mainly composed of adipocytes which could be easily recognized on both CT and MRI. Abnormal vessels were commonly seen in the angiomatous lesions, which showed pronounced enhancement in the early arterial phase and remained higher than or isodense with the normal parenchyma in the portal phase. The myomatous type was predominantly composed of leiomyoid cells mixed with small amount of adipocytes. The mixed type was the most frequent,evenly comprising sheets of epithelioid muscle cells admixed with islands of adipocytes and abnormal vessels, and showing homogeneously low density on plain CT and low signal intensity on T1-weighted,intermediately high signal intensity on T2-weighted MRI scans. On dynamic study with both CT and MRI, the mixed type exhibited obvious enhancement, which retained to some degree during the portal phase., Conclusion: The discrete CT and MRI appearances of hepatic angiomyolipomas with different pathological subtypes depend on the components of the tumor.

Objective: To investigate the value of transabdominal ultrasonography (TAUS) in preoperative assessment of TNM stage and tumor angiogenesis for patients with gastric carcinoma., Methods: Sixty- four patients with gastric carcinoma preoperatively underwent TAUS, in whom transabdominal color Doppler ultrasonography was used for measuring color Doppler vascularity index (CDVI) of each tumor in 37 cases and microvessel density (MVD) was evaluated by using immunohistochemical staining of surgical specimens with anti- CD34 antibody., Results: The overall accuracy rate was 56.0% for T staging of gastric carcinoma (T (1) 2/3 cases, T (2) 28.6% , T (3) 73.1% , T (4) 50.0% , respectively) by TAUS. The diagnostic accuracy rate was 63.3% for lymph node status of gastric carcinoma. The diagnostic sensitivity and specificity for lymph node metastasis was 37.9% and 100% respectively. The overall accuracy for N staging of gastric carcinoma was 57.1% (N (0) 100% , N (1) 16.7% , N (2) 35.3% , respectively). The diagnostic sensitivity and specificity for determining distant metastases was 58.3% and 100% respectively. The CDVI of gastric carcinoma determined by color Doppler ultrasonography was significantly correlated to vascular invasion (P=0.0418), a linear correlation between CDVI and MVD was determined by logistic regression analysis (r=0.5628, P< 0.01)., Conclusion: TAUS can be a routine diagnostic approach for preoperative gastric carcinoma patients.

Objective: To investigate whether there is any correlation between minimum resistance index (RImin) and microvessel density (MVD) in ovarian tumors., Methods: The intratumor artery RImin of 61 patients with ovarian tumor was measured by color doppler ultra-sound (CDU) preoperatively. MVD identified by von Willebrand factor was evaluated postoperatively. The relationship between RImin and MVD was analyzed., Results: Compared with the RImin of benign ovarian tumors, the RImin in ovarian cancers was significantly lower (P < 0.001). MVD of ovarian cancer was significantly higher than that of benign tumor both at a 100 magnification (P < 0.01) and a 400 magnification (P < 0.03). There was a significant negative correlation between RImin and MVD at a 100 magnification in benign group (r = -0.67, P < 0.01), in malignant group (r = -0.91, P < 0.01), and in both of groups (r = -0.84, P < 0.01)., Conclusion: Low RImin reflects high MVD in ovarian tumor.