Measuring Tumor Perfusion in Control and Treated Murine Tumors

Abstract

The purpose of this study was to evaluate the ability of dynamic microbubble contrast-enhanced sonography (MCES), in comparison with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET), to quantitatively characterize tumor perfusion in implanted murine tumors before and after treatment with a variety of regimens. Seventeen mice with Lewis lung carcinoma implants were categorized to control, radiation therapy alone, antiangiogenic chemotherapy alone, and combined chemoradiation. On day 0 of each treatment regimen, MCES and DCE-MRI of each tumor were performed. On day 5 of treatment, dynamic FDG-PET, MCES, and DCE-MRI were performed. Microbubble contrast-enhanced sonography showed that intratumoral perfusion, blood volume, and blood velocity were highest in the untreated control group and successively lower in each of the treatment groups: radiation therapy alone resulted in a two-thirds reduction of perfusion; antiangiogenic chemotherapy resulted in a relatively larger reduction; and combined chemoradiotherapy resulted in the largest reduction. Microbubble contrast-enhanced sonography revealed longitudinal decreases in tumor perfusion, blood volume, and microvascular velocity over the 5-day course of chemoradiotherapy (all P < .01); conversely, these values rose significantly for the untreated control tumors (P < .01). Dynamic contrast-enhanced MRI showed a smaller and statistically insignificant average decrease in relative tumor perfusion for treated tumors. Dynamic PET revealed delayed uptake of FDG in the tumors that underwent chemoradiotherapy. Microbubble contrast-enhanced sonography is an effective tool in the noninvasive, quantitative, longitudinal characterization of neovascularization in murine tumor models and is correlative with DCE-MRI and FDG-PET. Microbubble contrast-enhanced sonography has considerable potential in the clinical assessment of tumor neovascularization and in the assessment of the response to treatment.