Non-invasive contrast enhanced ultrasound for quantitative assessment of tumor microcirculation. Contrast mixed mode examination vs. only contrast enhanced ultrasound examination

Abstract

Purpose: To evaluate the different ultrasound techniques for quantification of contrast enhanced ultrasound (CEUS) in an experimental rat prostate carcinoma model. Method and materials: Prostate carcinoma (MLLB-2) cells were subcutaneously injected into the right flank of male rat (Charles River, Sulzfeld, Germany, 180 to 220 g body weight). Following 18 days of subcutaneous tumor growth 9 rats underwent CEUS examination. Real time CEUS was performed after a bolus injection of SonoVue (0.2 ml, Bracco, Italy) via the lateral tail vein using a high end ultrasound system (Siemens Sequoia 512^®/Acuson, Mountain View) with an 15 Mhz probe. Two different CEUS techniques, pure contrast (pc) and contrast with background (cbg) examination, were analyzed (CPS-software). Exported signal intensity (SI)-time curves and the normalized area under the curve (AUC) for the active tumor tissue, whole tumor and necrosis were compared. Results: The mean normalized AUC for the active tumor tissue and the whole tumor was 0.84 and 0.5 in the pure contrast examination group and 0.49 and 0.3 for the contrast examination with background signal. Therefore the signal intensity of the pc group was in every examination significant higher than of the cbg group (p < 0.02). The advantage of using the additional background information is to detect the anatomic landmarks in the solid tumor model in comparison to the pure contrast enhanced ultrasound examination. Conclusion: The complete extension of the tumor is much easier to detect with the cbg technique due to orientation of the anatomic landmarks. As the signal intensity of the pc group is always significant higher we recommend this technique for quantification of contrast enhanced ultrasound, especially for the follow up of tumor microcirculation.