Ultrasound Microvessel Visualization in Cervical Cancer: Association Between Novel Ultrasound Techniques and Histologic Microvessel Densities.

Abstract

The aim of the work described here was to evaluate the feasibility of superb microvascular imaging (SMI) and vascular endothelial growth factor receptor 2 (VEGFR2)-targeted microbubble (MBVEGFR2)-based ultrasound molecular imaging (USMI) for visualizing microvessels in cervical cancer. Hela cells were used to establish subcutaneous cervical cancer models. SMI and MBVEGFR2-based USMI were performed, and the results were compared with intratumoral microvessel density (MVD) in four groups based on tumor diameter (<3 mm, 3-5 mm, 5-7 mm and ≥7 mm). The vascularization index (VI, %) was evaluated for SMI, and the normalized intensity difference (NID) for USMI. Tumors with diameters ranging from 3 to 5 mm had the highest VI (39.07 ± 1.58) in SMI, and VI significantly decreased with increasing tumor size (all p values <0.001). The strongest signal intensity was observed in very early tumors (d < 3 mm: 43.80 ± 3.58%) after MBVEGFR2 administration; the NID gradually decreased with increasing diameter of tumors (all p values=0.007). However, no significant differences were observed in NID after administration of non-targeted (control) microbubbles (MBCon) (all p values=0.125). MBVEGFR2-based USMI had the strongest correlation with MVD in displaying microvessels of cervical cancer compared with SMI and MBCon (R2=0.78 vs. R2=0.40 and R2=0.38). These findings validate the superiority and accuracy of MBVEGFR2-based USMI for microvessel imaging and monitoring of angiogenesis in cervical cancer compared with SMI and MBCon. Nonetheless, SMI remains an alternative to microvessel imaging when ultrasonic contrast agent use is contraindicated.