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.
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.
Niermann
Kenneth J
KJ
Departments of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2675, USA.
Fleischer
Arthur C
AC
Huamani
Jessica
J
Yankeelov
Thomas E
TE
Kim
Dong W
DW
Wilson
Wendy D
WD
Hallahan
Dennis E
DE
D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media; D005466:Fluorocarbons; D019788:Fluorodeoxyglucose F18; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000517:prevention & control*; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014463:Ultrasonography / Q000379:methods*
D003287:Contrast Media; D005466:Fluorocarbons; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C042852:perflutren