Can monodisperse microbubble-based three-dimensional contrast-enhanced ultrasound reduce quantitative heterogeneity? An in vitro study

Background. Heterogeneity within the tumor may cause large heterogeneity in quantitative perfusion parameters. Three-dimensional contrast-enhanced ultrasound (3D-CEUS) can show the spatial relationship of vascular structure after post-acquisition reconstruction and monodisperse bubbles can resonate the ul-trasound pulse, resulting in the increase in sensitivity of CEUS imaging. Objectives. To evaluate whether the combination of 3D-CEUS and monodisperse microbubbles could reduce the heterogeneity of quantitative CEUS. Materials and methods. Three in vitro perfusion models with perfusion volume ratio of 1:2:4 were set up. Both quantitative 2D-CEUS and 3D-CEUS were used to acquire peak intensity (PI) with 2 kinds of ultrasound agents. One was a new kind of monodisperse bubbles produced in this study, named Octafluoropropane-loaded cerasomal microbubbles (OC-MBs), the other was SonoVue (R). The coefficient of variation (CV) was calculated to evaluate the cross-sectional variability. Pearson's correlation analysis was used to assess the cor-relation between weighted PIs (average of PIs of 3 different planes) and perfusion ratios. Results. The average CVs of quantitative 3D-CEUS was slightly lower than that of 2D-CEUS (0.41 +/- 0.17 compared to 0.55 +/- 0.26, p = 0.3592). As for quantitative 3D-CEUS, the PI of the OC-MBs has shown better stability than that of SonoVue (R), but without a significant difference (average CVs: 0.32 +/- 0.19 compared to 0.50 +/- 0.10, p = 0.0711). In the 2D-CEUS condition, the average CVs of OC-MBs group and SonoVue (R) group were 0.68 +/- 0.15 and 0.41 +/- 0.17 (p = 0.2747). As for 3D-CEUS condition, using OC-MBs group and SonoVue (R), the r-values of the weighted PI and perfusion ratio were 0.8685 and 0.5643, respectively, while that of 2D-CEUS condition were 0.7760 and 0.3513, respectively. Conclusions. Our in vitro experiments showed that OC-MBs have the potential in acquiring more stable quantitative CEUS value, as compared to the SonoVue (R) in 3D-CEUS condition. The combination of 3D-CEUS and OC-MBs can reflect perfusion volume more precisely and may be a potential way to reduce quantitative heterogeneity.