ABSTRACT
Objective To develop a vulnerable plaque targeting ultrasound contrast agent (UCA) and to evaluate its affinity and imaging performance in vitro.Methods E-selectin receptor-targeting UCA,which conjugated with monoclonal antibody of E-selectin,was prepared with filming-rehydration method and biotin-avidin linkage.The size and distribution of UCA were measured with particle size analyzer,the connectivity condition of microbubbles with E-selectin antibody was also detected with fluorescence analysis.The cytotoxicity from microbubble and ultrasound irradiation was evaluated through cell counting kit-8 (CCK8) assay.The adhesion effect of UCA was assessed after co-incubated with activated mouse endothelial cells (bEnd.3) and compared with that of free antibody intervention group and control group.The imaging performance of UCA at different time points was observed on an ultrasound equipment with a high-frequency transducer.Two-sample t test and one-way analysis of variance were performed to analyze the data.Results E-selectin receptor-targeting UCA was successfully prepared.The cytotoxicity result with CCK8 assay demonstrated the favorable biocompatibility of UCA.The connection amount of UCA on activated bEnd.3 cells ((6.23 ± 0.45) bubbles/cell) was significantly higher than that of the free antibody intervention group ((1.57±0.34) bubbles/cell) and control group ((0.07±0.03) bubbles/cell;F=291.43,P＜0.01).The performance of in vitro ultrasonography at the same time points showed no obvious difference between targeting UCA and control UCA (all t＜0.51,all P＞0.05).Conclusions The prepared E-selectin receptor-targeting UCA has favorable targeting and imaging capabilities.It might be a potentially ultrasound molecular imaging agent for early detection and prognosis evaluation of vulnerable plaque.
ABSTRACT
Objective: To explore the echocardiographic cardiac geometric morphology and hemodynamics in premature infants at different gestational age with the inlfuencing factors. Methods: A total of 150 premature infants and 150 full-term control infants were enrolled in this study. Based on gestational age, premature infants were divided into 3 groups:①(28-32+6 ) weeks,②(33-34+6 ) weeks,③(35-36+6) weeks; and full term control infants were divided into 2 groups:①’(37-38+6) weeks and②’ (39-41+6) weeks respectively. An iE33 Philips ultrasound examination was conducted to measure left ventricular end-diastolic diameter (LVEDD), LVESD, interventricular septum thickness, posterior wall thickness, left ventricular end-diastolic volume (LVEDV), LVESV, stroke volume, LVEF, left ventricular fractional shortening (LVFS), cardiac output, stroke index, cardiac index, left ventricular mass, left ventricular mass index (LVMI), left ventricular relative wall thickness, left ventricular remodeling index (LVRI) and LVEDVI. Results: With adjusted body surface area, all parameters for cardiac geometric morphology and hemodynamics were similar among different groups,P>0.05. The day-old age (P=0.001), height (P=0.001) and body weight for low weight born infant (P=0.012), for normal weight born infant (P=0.003), for giant infant (P=0.016) were the independent inlfuencing factors for LVMI. The impact of anthropometry and the basic life indexes were similar on LVRI among groups (χ2=42.88,P=0.076), while the covariates were different on LVMI among groups (χ2=123.6,P Conclusion: Cardiac morphology and hemodynamics measured by echocardiography has important clinical meaning for assessing the development and maturity of neonatal hearts in premature infants.
ABSTRACT
Objective To develop and validate a ultrasonographic (US)imaging agent with targeted microbubbles that attaches to chemokine receptor 2 (CCR2)and to compare the US single obtained from targeted microbubble with that from control microbubble in murine breast tumor model.Methods The microbubble which carried CCR2 antibody (MBCCR2 )and isotype-macthed immunoglobulin G-labled control microbubble (MBcontrol ) were prepared. The microbubble size and distribution were assessed by AccuSizer780.Binding specificities of targeted microbubble compared with control microbubble were tested with murine microvascular endothelial cells (bEnd.3 ).Orthotopic breast tumor model was estabished in BALB/c mice with mouse breast cancer 4T1 cell.In vivo imaging signals of contrast material-enhanced ultrasound by use these two different types of microbubble which were injected respectively into each mouse at random order and 30 min interval.Tumor tissue was stained for CCR2 and CD3 1 .Results Automatic Particle Sizer showed size uniform of two kinds of microbubbles,and narrow distribution of particle size (mean diameter of about 1 -2 μm),which were not significantly different (P >0.05).Adhension to bEnd. 3 endothelial cells was significantly higher (P < 0.001 )for MBCCR2 (mean,9.50 ± 1 .5 1 )than that for MBcontrol (mean,0.01 ±0.01).Imaging signal in the murine tumor model was significantly higher for MBCCR2 [mean,(6.76±0.26)dB]than that for MBcontrol [mean,(1 .06 ±0.62)dB,P <0.001 ].Immunofluorescence confirmed expression of CCR2 on tumor vasculature.Conclusions The targeted microbubbles with CCR2 monoclonal antibody had been successfully prepared,which precisely targeted to CCR2 of tumor angiogenesis in the murine breast cancer xenograft tumor models in vivo.These results suggest that the targeted microbubbles as a kind of ultrasound molecular imaging agent with a better specificity can be used for both evaluating tumor neovascularization and monitoring therapeutic effect of anti-angiogenesis.