Contrast and quantitative ultrasound mapping of heterogeneous Tumor function and structure

Abstract

This preclinical study on two data sets looks at the local tumor heterogeneity by analyzing information from three techniques: Dynamic Contrast-Enhanced Ultrasound (DCE-US); Immunohistochemistry (IHC) and Quantitative Ultrasound, (QUS). The first data set included DCE-US sequences and whole slice IHC data acquired 14 days after the start of an antiangiogenic (AA1) therapy with Pazopanib in mice with subcutaneous murine colorectal carcinoma tumors, CT26, (AA1, n = 7; Control C1, n = 8). The second data set included DCE-US and QUS data acquired 13 days after the start of an AA2 therapy with Sunitinib in mice with subcutaneous murine Lewis Lung Carcinoma (LLC) tumors (cohort 1: AA2a, n = 6; C2a, n = 5 and cohort 2: AA2b, n = 12; C2b, n = 2). DCE-US data were used to identify vascular (V) and nonvascular (NV) zones inside tumors. IHC was used to assess the Number of Nuclei per mm2 (NU), the Number of T Lymphocyte per mm2 (NTL), the percent area of Apoptosis (AP) and percent area of Vascular Endothelium (VE). QUS parameters of Effective Scatterer Diameter (ESD, urn) and Effective Acoustic Concentration (EAC, dB/cm) were measured. IHC and QUS parameters were then compared between V, NV and Whole Tumor (WT) zones. All the parameters of the IHC features were higher in the V zone compared to the NV zone (for groups AA1 and C1). Furthermore, the values of the WT were dominated by that of the V zones because the majority (100 to 72% surface area) of most of the tumors was well perfused. A higher level of VE marking was observed in the C1 group relative to the AA1 group in NV zones. For QUS, only one parameter (EAC) showed an apparent difference between the V and NV zones (C2a). However, this difference was no longer detectable after addition of the second cohort in the analysis. The differences in tumor microstructure observed with fflC between V and NV zone show that there are local properties within tumor that vary along with the vascularization.