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Tumor Vascularity: Evaluation in a Murine Model with Contrast-enhanced Color Doppler US—Effect of Angiogenesis Inhibitors¹

¹ From the Departments of Radiology (I.I., P.D., G.A.T.) and Surgery (C.B., B.Z.), Children’s Hospital and Harvard Medical School, 300 Longwood Ave, Boston, MA 02115. Received March 26, 2001; revision requested April 23; revision received June 8; accepted July 5. Address correspondence to G.A.T. (e-mail: george.taylor@tch.harvard.edu).

PURPOSE: To determine the ability of contrast material–enhanced ultrasonography (US) to depict tumor growth and vascularity in a murine model of prostate carcinoma treated with an angiogenic inhibitor.

MATERIALS AND METHODS: Thirty-five genetically engineered mice with spontaneously occurring prostate tumors were monitored on a weekly basis with gray-scale and color Doppler US with a 15-MHz linear transducer. Eighteen mice were treated with an adenoviral vector to deliver a soluble form of the Flk1 receptor (VEGFR-2), a vascular endothelial growth factor receptor designed to block tumor angiogenesis. The remaining 17 animals were injected with saline and used as controls. Tumor volumes were calculated on the basis of serial US measurements. Color Doppler US was performed in every tumor before and after intravenous injection of 0.1 mL per kilogram of body weight of a US contrast agent. US images were evaluated for tumor size, pattern of vascularity, and extent of vascularity (vascularity index). Findings at US were correlated with findings at autopsy in 30 animals.

RESULTS: Estimates of tumor volume at US correlated well with tumor measurements at autopsy (r = .89, P < .001). Marked differences in tumor size and slope of increasing tumor volume were evident at US between treated and control mice after treatment (P < .016, analysis of variance). The US contrast agent markedly increased color Doppler US signal intensity with an 800% (from 10% to 12,700%) change in the mean number of color pixels per imaging field, and showed vascularity in areas of tumor not identified on precontrast images in 70% (109 of 156 studies). No correlation was found between the pattern of vascularity or vascularity index before or after contrast material administration and tumor size, treatment status, or histologic assessment of tumor vascularity.

CONCLUSION: Contrast-enhanced US improves visualization of tumor vascularity. However, histologic patterns of tumor vascularity do not correlate with Doppler US depiction of blood flow in these vessels.

Index terms: Angiogenesis • Prostate neoplasms, 844.32 • Prostate neoplasms, US, 844.12983, 844.12988 • Ultrasound (US), Doppler studies, 844.12983, 844.12988

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