Korean J Radiol.  2008 Jun;9(3):243-249. 10.3348/kjr.2008.9.3.243.

Evaluation of Tumor Angiogenesis with a Second-Generation US Contrast Medium in a Rat Breast Tumor Model

• Ko EY
• Lee SH
• Kim HH
• Kim SM
• Shin MJ
• Kim N
• Gong G

• KMID: 1758458
• DOI: http://doi.org/10.3348/kjr.2008.9.3.243

Abstract

OBJECTIVE
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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: Contrast-enhanced US using a second-generation US contrast material was useful for the evaluation of tumor angiogenesis of breast tumors in the rat.

Keyword

Breast neoplasms; Breast, US; Contrast media; Experimental study

MeSH Terms

Animals
Contrast Media
Ethylnitrosourea
Female
Hemodynamics
Image Enhancement
Mammary Neoplasms, Experimental/chemically induced/pathology/*ultrasonography
Neovascularization, Pathologic/*ultrasonography
Rats
Rats, Sprague-Dawley

Figure

• 

  Fig. 1 US results of intraductal proliferation. Color Doppler US (A) shows input artery in right side of tumor (arrow) and intratumoral vasculature within tumor (arrowhead). Time-intensity curve of tumor (B) was obtained from three areas of enhancing parenchyma without vascular structures within tumor.

• 

  Fig. 2 Invasive ductal carcinoma induced by intraperitoneal injection of ethyl-N-nitrosourea. Tumor consists of infiltrating cords and tubules in background of atypical ductal hyperplasia. Arrows on right side indicate tumor necrosis (Hematoxylin & Eosin staining, × 100).

• 

  Fig. 3 Immunostaining for CD31. Endothelial cells (arrows) lining lymphovascular spaces are immunoreactive for CD31 (× 200).

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