Hou Likang, Guo Zhili, Liu Shun, Liang Xiaowen, Du Meng, Chen Zhiyi
Key Laboratory of Medical Imaging Precision Theranostics and Radiation Protection, College of Hunan Province, the Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, China.
Institute of Medical Imaging, Hengyang Medical School, University of South China, Hengyang, China.
J Ultrasound Med. 2025 Sep;44(9):1555-1568. doi: 10.1002/jum.16710. Epub 2025 May 5.
To assess the severity of intrauterine adhesion (IUA) after endometrial injury via ultrasound molecular imaging (USMI) of vascular endothelial growth factor receptor 2 (VEGFR2) expression on the uterine endothelium.
MB was constructed via "biotin-avidin-biotin" bridging technology. A rat IUA animal model was constructed via chemical injury. Fourteen days after the model was constructed, MB and MB contrast agents were injected into the standard group and the model group of rats, and simultaneous ultrasound molecular imaging was carried out and ultrasound molecular imaging was performed and the changes in ultrasound signals in vivo were normalized to differential targeted enhancement (dTE). In addition, immunohistochemistry was used to detect the expression levels of VEGFR2 and α-SMA in the uterine tissues of the rats in both groups.
Targeted-VEGFR2 microbubble (MB) was successfully constructed, the average particle size of the targeted VEGFR2 microbubble contrast agent was 2309.6 ± 234.3 nm, with the average zeta potential -16.9 ± 0.15 mV and the dispersity coefficient less than 0.4. In addition, its essential performance and biosafety were examined, which revealed that the MB contrast agent had an appropriate size, stable imaging performance, good target adhesion, and good biocompatibility. In vivo, ultrasound imaging results revealed that after the injection of the targeted MB, the contrast ultrasound signal intensity of uterine tissues in the model group (62.5 ± 17.9 dB) was higher than in the normal group (33.5 ± 12.5 dB), and the difference was statistically significant (P < .05). The immunohistochemistry results revealed that the expression of VEGFR2 and α-SMA in the uterine tissue of the model group was greater than that in the standard group (P < .05), further indicating that the signal intensity of the MB contrast agent can reflect the expression level of VEGFR2 molecules.
Ultrasound molecular imaging based on MB can be used to evaluate the expression level of VEGFR2 in uterine vascular endothelial cells. This provides a potential approach for the early diagnosis and treatment monitoring of intrauterine adhesions after endometrial injury.
通过对子宫内皮细胞上血管内皮生长因子受体2（VEGFR2）表达进行超声分子成像（USMI），评估子宫内膜损伤后宫腔粘连（IUA）的严重程度。
通过“生物素-抗生物素蛋白-生物素”桥接技术构建微泡（MB）。通过化学损伤构建大鼠IUA动物模型。模型构建后14天，将MB及MB造影剂注入大鼠标准组和模型组，同时进行超声分子成像，并将体内超声信号变化归一化为差异靶向增强（dTE）。此外，采用免疫组织化学法检测两组大鼠子宫组织中VEGFR2和α-SMA的表达水平。
成功构建靶向VEGFR2微泡（MB），靶向VEGFR2微泡造影剂的平均粒径为2309.6±234.3nm，平均ζ电位为-16.9±0.15mV，分散系数小于0.4。此外，对其基本性能和生物安全性进行检测，结果显示MB造影剂粒径合适、成像性能稳定、靶向粘附良好且生物相容性良好。在体内，超声成像结果显示，注射靶向MB后，模型组子宫组织的超声造影信号强度（62.5±17.9dB）高于正常组（33.5±12.5dB），差异具有统计学意义（P<0.05）。免疫组织化学结果显示，模型组子宫组织中VEGFR2和α-SMA的表达高于标准组（P<0.05），进一步表明MB造影剂的信号强度可反映VEGFR2分子的表达水平。
基于MB的超声分子成像可用于评估子宫血管内皮细胞中VEGFR2的表达水平。这为子宫内膜损伤后宫腔粘连的早期诊断和治疗监测提供了一种潜在方法。
