Correlation of quantified contrast-enhanced sonography with in vivo tumor response

Objective. The purpose of our study was to establish in vivo criteria for monitoring tumor treatment response using 3-dimensional (3D) volumetric gray scale, power Doppler, and contrast-enhanced sonography. Methods. Twelve mice were implanted with Lewis lung carcinoma cells on their hind limbs and categorized to 4 groups: control, chemotherapy, radiation therapy, and chemoradiation. A high-frequency ultrasound system with a 40-MHz probe was used to image the tumors. Follow-up contrast-enhanced sonography was performed on days 7 and 14 of treatment with two 50-μL boluses of a perflutren microbubble contrast agent injected into the tail vein. The following contrast-enhanced sonographic criteria were quantified: time to peak, peak intensity, α (microvessel cross-sectional area), and β (microbubble velocity). Three-dimensional power Doppler images were also obtained after the acquisition of contrast data. On day 15, the tumors were excised for immunohistochemical analysis with CD31 fluorescent staining. Results. The tumor size and 3D power Doppler vascular index showed no statistically significant correlation with microvascular density in all examined groups. Among all of the analyzed contrast-enhanced sonographic parameters, relative α showed the strongest correlation with the histologic microvessel density (Pearson r = 0.93; P < .01) and an independent association with the histologic data in a multiple regression model (beta = .93; R² = 0.86; P < .01). Conclusions. Of the various examined sonographic parameters, a has the strongest correlation with histologic microvessel density and may be the parameter of choice for the noninvasive monitoring of tumor angiogenic response in vivo.