Abstract 2196: Noninvasive description of natural tumor evolution
Authors: Griffon Jerome , Guillou-Buffello Delphine Le , Laifa Oumeima , Bridal Lori , Lamuraglia Michele 
Published: August 2018

Abstract
Background: Our goal is to investigate how quantitative parameters of Contrast Enhanced Ultrasound (CEUS) and Shear Wave Elastography (SWE) change during tumor growth and link them with morphological and histological indexes.
Methods: An ectopic model of murine colorectal carcinoma (CT26) was implanted in 46 mice (BALB/c ) at Day 0. On 5 subsequent days, data were acquired from subsets of these mice (D7, n=8 ; D10, n=9 ; D14, n=10 ; D16, n=9, D17, n=10) by scanning each tumor along its major, longitudinal axis in vivo to obtain conventional B-mode, SWE (SSI, Aixplorer, SL15-4 probe) and dynamic CEUS (Sequoia 512, 7-14 MHz probe, cadence contrast pulse sequencing) data. The ellipsoidal volume of each tumor was estimated from measurements of the width and thickness of the largest plane along the longitudinal and transversal plane using B-mode display on the Aixplorer device. Quantitative maps of tissue elasticity distribution in the tumor were obtained from SWE data. Average values and standard deviation of SWE data were calculated within regions selected to outline the tumor cross section on B-mode images. CEUS was performed after a syringe-pump-controlled bolus injection in the caudal vein of 40 μL of SonoVue (Bracco Suisse, Geneva, Switzerland) in a weight-adjusted volume of 0.5 mL/kg. A lognormal model was fit to the time intensity curve inside the tumor to estimate parameters related to microvascular volume and flow. All tumors imaged on a given day were excised and marked to conserve orientation and approximate position relative to the US imaging plane. Tumors were frozen with liquid nitrogen in an Optimal Cutting Temperature compound cube and stored at -80°C.
Results: Significance of correlations were evaluated using the non-parametric Spearman correlation coefficient (RS). Average SWE parameters were not significantly correlated with the CEUS parameters (p &gt; 0.03). Standard deviation of SWE in the tumor was well correlated with tumor volume (RS = 0.65 [p&lt;6x10^-7]). For CEUS only the Time To Peak and Latency Time correlated with tumor volume (RS = 0.62 [p&lt;4x10^-6] and RS = -0.72 [p&lt;2x10^-8], respectively). Correlation with histological assessment of tumor microstructure is still in the process of analysis.
Conclusions: These preliminary results probe the relationship between tumor volume, functional-flow and elastic properties in tumors. Both CEUS and SWE parameters were found that correlate with tumor growth and thus, appear to be sensitive to changes occurring during tumor development. Histological analysis of tumor microstructure is underway to more fully probe this point. Lack of correlation between SWE and CEUS parameters suggests that they provide complementary information. Better understanding of the sensitivity of these non invasive parameters to tumor growth changes will contribute to their eventual integration in procedures of tumor response criteria in clinical practice.
Citation Format: Jerome Griffon, Delphine Le Guillou-Buffello, Oumeima Laifa, Lori Bridal, Michele Lamuraglia. Noninvasive description of natural tumor evolution [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2196.