Differentiation of vascular distribution and flow patterns in tumors with Dynamic Contrast-Enhanced Ultrasound (DCE-US) perfusion maps

摘要

DCE-US, which allows follow up of tumor vasculature during therapy, is potentially a very useful tool to predict early response to therapy. In this study we act on the vascularization of two different tumor models, colorectal (CT26) and Lewis lung carcinomas (3LL), using sunitinib, an anti-angiogenic drug. Time-dependent perfusion parameters are explored to characterize tumor perfusion. Significant differences are highlighted in term of flow pattern for treated versus control mice in one tumor model. Differences are also identified for tumor filling between the two tumor models. For 3LL mice under therapy, modifications of functional vascularization begin at day 7 as characterized by slower filling compared to 3LL control mice. Results also exhibit slower filling patterns for CT26 relative to 3LL tumor controls. Histology results reveal smaller vessels (diameter <; 20μm) located primarily in the tumor periphery for CT26 whereas the vessels in the 3LL carcinoma are more homogeneously distributed. Preliminary measurements indicate a higher interstitial fluid pressure in CT26 (12.8 ± 4.6 mmHg) than 3LL carcinoma (2.8 ± 1.4 mmHg). Ultimately, better understanding of how vascular network density, capillaries tortuosity and interstitial fluid pressure impact filling flow patterns in tumor could lead to an in vivo biomarker reflecting state of the functional vascularization.