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Measuring Tumor Perfusion in Control and Treated Murine Tumors

Correlation of Microbubble Contrast-Enhanced Sonography to Dynamic Contrast-Enhanced Magnetic Resonance Imaging and Fluorodeoxyglucose Positron Emission Tomography

Departments of Radiation Oncology (K.J.N., J.H., D.W.K., D.E.H.), Radiology and Radiological Sciences (K.J.N., A.C.F., T.E.Y., W.D.W.), and Obstetrics and Gynecology (A.C.F.), Vanderbilt University Medical Center, Nashville, Tennessee USA.

Address correspondence to Arthur C. Fleischer, MD, Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, RR-1213 MCN, 1161 21st Ave N, Nashville, TN 37232-2675 USA. E-mail: arthur.fleischer{at}vanderbilt.edu

Objective. 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. Methods. 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. Results. 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. Conclusions. 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.

Key Words: blood flow • magnetic resonance imaging • microbubble contrast • sonography • tumor

Abbreviations: DCE-MRI, dynamic contrast-enhanced magnetic resonance imaging • FDG-PET, fluorodeoxyglucose positron emission tomography • MCES, microbubble contrast-enhanced sonography • ROI, region of interest • SI, signal intensity

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