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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
Kenneth J. Niermann; Arthur C. Fleischer; Jessica Huamani; Thomas E. Yankeelov; Dong W. Kim; Wendy D. Wilson; Dennis E. Hallahan(Profiled Author: Dong W Kim)
Journal of Ultrasound in Medicine. 2007;26(6):749-756.Abstract
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. © 2007 by the American Institute of Ultrasound in Medicine.
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