Ko Eun Young, Lee Sang Hoon, Kim Hak Hee, Kim Sung Moon, Shin Myung Jin, Kim Namkug, Gong Gyungyub
Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Korean J Radiol. 2008 May-Jun;9(3):243-9. doi: 10.3348/kjr.2008.9.3.243.
Tumor angiogenesis is an important factor for tumor growth, treatment response and prognosis. Noninvasive imaging methods for the evaluation of tumor angiogenesis have been studied, but a method for the quantification of tumor angiogenesis has not been established. This study was designed to evaluate tumor angiogenesis in a rat breast tumor model by the use of a contrast-enhanced ultrasound (US) examination with a second-generation US contrast agent.
The alkylating agent 19N-ethyl-N-nitrosourea (ENU) was injected into the intraperitoneal cavity of 30-day-old female Sprague-Dawley rats. Three to four months later, breast tumors were detected along the mammary lines of the rats. A total of 17 breast tumors larger than 1 cm in nine rats were evaluated by gray-scale US, color Doppler US and contrast-enhanced US using SonoVue. The results were recorded as digital video images; time-intensity curves and hemodynamic parameters were analyzed. Pathological breast tumor specimens were obtained just after the US examinations. The tumor specimens were stained with hematoxylin and eosin (H & E) and the expression of CD31, an endothelial cell marker, was determined by immunohistochemical staining. We also evaluated the pathological diagnosis of the tumors and the microvessel density (MVD). Spearman's correlation and the Kruskal-Wallis test were used for the analysis.
The pathological diagnoses were 11 invasive ductal carcinomas and six benign intraductal epithelial proliferations. The MVD did not correlate with the pathological diagnosis. However, blood volume (BV) showed a statistically significant correlation with MVD (Spearman's correlation, p < 0.05).
Contrast-enhanced US using a second-generation US contrast material was useful for the evaluation of tumor angiogenesis of breast tumors in the rat.
肿瘤血管生成是影响肿瘤生长、治疗反应及预后的重要因素。人们已对用于评估肿瘤血管生成的非侵入性成像方法展开研究，但尚未建立肿瘤血管生成的定量方法。本研究旨在通过使用第二代超声造影剂的超声造影检查来评估大鼠乳腺肿瘤模型中的肿瘤血管生成情况。
将烷化剂19N - 乙基 - N - 亚硝基脲（ENU）注入30日龄雌性斯普拉格 - 道利大鼠的腹腔。三到四个月后，在大鼠乳腺线上检测到乳腺肿瘤。使用声诺维，通过灰阶超声、彩色多普勒超声和超声造影对9只大鼠中17个直径大于1 cm的乳腺肿瘤进行评估。结果记录为数字视频图像；分析时间 - 强度曲线和血流动力学参数。超声检查后立即获取乳腺肿瘤病理标本。肿瘤标本用苏木精和伊红（H&E）染色，并通过免疫组织化学染色测定内皮细胞标志物CD31的表达。我们还评估了肿瘤的病理诊断和微血管密度（MVD）。采用Spearman相关性分析和Kruskal - Wallis检验进行分析。
病理诊断为11例浸润性导管癌和6例良性导管内上皮增生。MVD与病理诊断无关。然而，血容量（BV）与MVD显示出统计学上的显著相关性（Spearman相关性，p < 0.05）。
使用第二代超声造影剂的超声造影对评估大鼠乳腺肿瘤的血管生成是有用的。
