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Correlation Between Estimates of Tumor Perfusion From Microbubble Contrast-Enhanced Sonography and Dynamic Contrast-Enhanced Magnetic Resonance Imaging

Institute of Imaging Science (T.E.Y., K.J.N., C.C.Q., R.R.P., J.C.G.) and Departments of Radiology and Radiological Sciences (T.E.Y., K.J.N., C.C.Q., A.C.F., R.R.P., J.C.G.), Radiation Oncology (J.H., D.W.K., A.C.F., D.E.H.), and Obstetrics and Gynecology (A.C.F.), Vanderbilt University, Nashville, Tennessee USA.

Address correspondence to Thomas E. Yankeelov, PhD, Institute of Imaging Science, Vanderbilt University Medical Center, R-1302 Medical Center North, Nashville, TN 37232-2675 USA. E-mail: thomas.yankeelov{at}vanderbilt.edu

Objective. We compared measurements of tumor perfusion from microbub-ble contrast-enhanced sonography (MCES) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in an animal tumor model. Methods. Seven mice were implanted with Lewis lung carcinoma cells on their hind limbs and imaged 14 days later with a Philips 5- to 7-MHz sonography system (Philips Medical Systems, Andover, MA) and a Varian 7.0-T MRI system (Varian, Inc, Palo Alto, CA). For sonographic imaging 100 µL of a perfluoropropane microbubble contrast agent (Definity; Bristol-Myers Squibb Medical Imaging, Billerica, MA) was injected and allowed to reach a pseudo steady state, after which a high–mechanical index pulse was delivered to destroy the microbub-bles within the field of view, and the replenishment of the microbubbles was imaged for 30 to 60 seconds. The MRI included acquisition of a T₁₀ map and 35 serial T₁-weighted images (repetition time, 100 milliseconds; echo time, 3.1 milliseconds; , 30°) after the injection of 100 µL of 0.2-mmol/kg gadopente-tate dimeglumine (Magnevist; Berlex, Wayne, NJ). Region-of-interest and voxel-by-voxel analyses of both data sets were performed; microbubble contrast-enhanced sonography returned estimates of microvessel cross-sectional area, microbubble velocity, and mean blood flow, whereas DCE-MRI returned estimates of a perfusion-permeability index and the extravascular extracellular volume fraction. Results. Comparing similar regions of tumor tissue seen on sonography and MRI, region-of-interest analyses revealed a strong (r² = 0.57) and significant relationship (P < .002) between the estimates of perfusion obtained by the two modalities. Conclusions. Microbubble contrast-enhanced sonography can effectively depict intratumoral heterogeneity in preclinical xenograft models when voxel-by-voxel analysis is performed, and this analysis correlates with similar DCE-MRI measurements.

Key Words: dynamic contrast-enhanced magnetic resonance imaging • microbubble contrast-enhanced sonography • microbubbles • tumor

Abbreviations: BF, blood flow • CA, contrast agent • CSA, cross-sectional area • DCE-MRI, dynamic contrast-enhanced magnetic resonance imaging • MCES, microbubble contrast-enhanced sonography • MR, magnetic resonance • MRI, magnetic resonance imaging • MV, microbubble velocity • ROI, region of interest • RR, reference region • TE, echo time • 3D, 3-dimensional • TOI, tissue of interest • TR, repetition time