Barua Animesh, Bitterman Pincas, Bahr Janice M, Basu Sanjib, Sheiner Eyal, Bradaric Michael J, Hales Dale B, Luborsky Judith L, Abramowicz Jacques S
Departments of Pharmacology, Obstetrics and Gynecology, Pathology, Rush University Medical Center, Chicago, Illinois, USA.
J Ultrasound Med. 2011 Mar;30(3):333-45. doi: 10.7863/jum.2011.30.3.333.
Our goal was to examine the feasibility of using laying hens, a preclinical model of human spontaneous ovarian cancer, in determining the kinetics of an ultrasound contrast agent indicative of ovarian tumor-associated neoangiogenesis in early-stage ovarian cancer.
Three-year-old White Leghorn laying hens with decreased ovarian function were scanned before and after intravenous injection of a human serum albumin-perflutren contrast agent at a dose of 5 μL/kg body weight. Gray scale morphologic characteristics, Doppler indices, the arrival time, peak intensity, and wash-out of the contrast agent were recorded and archived on still images and video clips. Hens were euthanized thereafter; sonographic predictions were compared at gross examination; and ovarian tissues were collected. Archived clips were analyzed to determine contrast parameters and Doppler intensities of vessels. A time-intensity curve per hen was drawn, and the area under the curve was derived. Tumor types and the density of ovarian microvessels were determined by histologic examination and immunohistochemistry and compared to sonographic predictions.
The contrast agent significantly (P < .05) enhanced the visualization of microvessels, which was confirmed by immunohistochemistry. Contrast parameters, including the time of wash-out and area under the curve, were significantly different (P < .05) between ovaries of normal hens and hens with ovarian cancer and correctly detected cancer at earlier stages than the time of peak intensity.
The laying hen may be a useful animal model for determining ovarian tumor-associated vascular kinetics diagnostic of early-stage ovarian cancer using a contrast agent. This model may also be useful for testing the efficacy of different contrast agents in a preclinical setting.
我们的目标是研究使用蛋鸡这一人类自发性卵巢癌的临床前模型，来确定一种超声造影剂在早期卵巢癌中指示卵巢肿瘤相关新生血管生成的动力学的可行性。
对卵巢功能减退的3岁白来航蛋鸡，在静脉注射剂量为5 μL/kg体重的人血清白蛋白-全氟丙烷造影剂之前和之后进行扫描。记录灰度形态特征、多普勒指数、造影剂的到达时间、峰值强度和消退情况，并存储在静态图像和视频片段中。此后对蛋鸡实施安乐死；在大体检查时比较超声预测结果；并收集卵巢组织。分析存储的片段以确定血管的造影参数和多普勒强度。绘制每只蛋鸡的时间-强度曲线，并得出曲线下面积。通过组织学检查和免疫组织化学确定肿瘤类型和卵巢微血管密度，并与超声预测结果进行比较。
造影剂显著（P < .05）增强了微血管的可视化，这通过免疫组织化学得到证实。正常蛋鸡和患有卵巢癌的蛋鸡的卵巢之间，包括消退时间和曲线下面积在内的造影参数存在显著差异（P < .05），并且在比峰值强度出现时间更早的阶段正确检测到了癌症。
蛋鸡可能是一种有用的动物模型，可用于使用造影剂确定诊断早期卵巢癌的卵巢肿瘤相关血管动力学。该模型也可能有助于在临床前环境中测试不同造影剂的疗效。
