Comparison of consecutive bolus tracking and flash replenishment measurements for the assessment of tissue hemodynamics using contrast-enhanced ultrasound (CEUS) in an experimental human squamous cell carcinoma model.

PURPOSE: To evaluate "bolus-tracking" (BT) and "flash-replenishment" (FR) for the assessment of tissue hemodynamics by contrast-enhanced ultrasound (CEUS) in an experimental small-animal-squamous-cell-carcinoma-model. Since the underlying tissue is the same, strong correlations between parameter outcomes of both techniques are expected. METHODS AND MATERIALS: Human hypopharynx-carcinoma-cells were subcutaneously injected into the left flank of 18 female athymic-nude-rats. After 10 days of subcutaneous tumour growth, bolus tracking and flash-replenishment measurements were performed consecutively in the same imaging plane in each rat after bolus-injection of SonoVue via the lateral tail vein using a high-end ultrasound system with a 15 MHz probe. Video-sequences were analysed with dedicated software (VueBox®, Bracco-Suisse®). From BT measurements, the parameters peak enhancement (PEBT), wash-in area-under-the-curve (Wi-AUCBT), mean transit time (MTTBT), wash-in-rate (WiRBT) and perfusion-index (Wi-PIBT) were derived; FR yielded estimates of relative-blood-volume (rBVFR), mean transit time MTTFR, relative blood flow rBFFR and wash-in rate Wi-RFR. RESULTS: In all rats, BT and FR measurements could be completed successfully. Highly significant correlations were observed between rBVFR and PEBT, rBVFR and Wi-AUCBT, rBVFR and MTTBT, rBVFR and WiPIBT, MTTFR and MTTBT, rBFFR and PEBT, rBFFR and Wi-AUCBT, rBFFR and WiRBT, rBFFR and WiPIBT, WiRFR and PEBT, WiRFR and Wi-AUCBT, WiRFR and WiRBT and WiRFR and WiPIBT. CONCLUSION: Whereas bolus tracking can be used in a wide range of modalities including CEUS, CT and MR, FR as a technique for the assessment of tissue hemodynamics is unique to CEUS. Although BT and FR yield different parameters, the underlying tissue hemodynamics are equal. In this work, we were able to demonstrate strong correlations between different parameters of both modalities in a small-animal-tumor-model, indicating that flash-replenishment is a valid alternative to the more established bolus-tracking technique. Although the lack of absolute, quantitative parameters hinders a direct comparison of both modalities, FR and BT should both be suitable for a relative comparison, e.g. between baseline and follow-up examinations.

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

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.