Abstract 889: A comparison between quantitative ultrasound and histology in heterogeneous tumor structure
Authors: Griffon Jerome , Guillou-Buffello Delphine Le , Laifa Oumeima , Dizeux Alexandre , Oelze Micheal , Bridal Lori , Lamuraglia Michele 
Published: July 2017

Background: To investigate how QUS (Quantitative Ultrasound) maps reflect regional variations in heterogeneous tumor microstructure, we compared like-regions of QUS effective scatterer diameter (ESD, μm) and effective acoustic concentration (EAC, dB/cm) maps to whole-slice, virtual histology sections stained for vascular, cellular and other microstructural features.

Methods: An ectopic model of murine colorectal carcinoma (CT26) was implanted in 7 mice (BALB/c). US radiofrequency data were acquired for the longitudinal plane of tumors in vivo (SSI, Aixplorer, SL15-4 probe, research mode) on days 6 and 14 after start of therapy with an anti-angiogenic (AA: n = 3) or placebo (P: n = 4). The AA used is Pazopanib, an oral tyrosine kinase inhibitor of VEGF receptors 1/-2/-3, platelet-derived growth factor receptors (PDGFR) -alfa/-beta, and c-KIT. A daily dose of 2 mg of AA, diluted in 100µl of solution, was administered per os. Average backscattered power spectra were calculated (FFT, 512 pts, Rectangular gated RF), normalized with respect to a reference phantom and corrected for attenuation (0.4 dB/cm/MHz). ESD and EAC were mapped (2 x 2 mm blocks, with 75% axial and lateral overlap). Tumors were excised and marked to conserve orientation and approximate position relative to US imaging plane. Whole-slice, histological sections were prepared with fluorescent immunohistochemical markers at D6 and D14 for invasive assessment of cell nuclei, apoptosis and vascular endothelium. The Number of Nuclei (NU), the % area of Apoptosis (AP) and % area of Vascular (VA) marker were calculated with image analysis processing for each 333µm by 333µm region of histological sections. QUS and histological maps of each tumor were manually segmented and coregistered using an affine registration method so that matched regions could be compared.

Results: The absolute value of the non-parametric Spearman correlation coefficient (RS) was computed separately for each mouse to study the correlation between histological parameters and QUS parameters. Two mice of the AA group showed a moderate correlation (0.4&lt;=RS&lt;0.6) between NU and EAC. Only one mouse in the P group showed strong correlation (0.6&lt;=RS) for [AP vs. ESD], [AP vs. EAC], [VA vs. ESD] and [VA vs. EAC]. The other tumors (1 from AA group and 3 from P group) showed poor correlation (RS&lt;0,4). Additional data is available from 14 other mice (7 from AA group and 7 from P group) and will be analyzed to more fully investigate correlation between the QUS parameters and the histological parameters.

Conclusions: This original technique to compare QUS parameter maps and whole slice histology analysis shows a promising evolution for this non-invasive imaging technique. Complete results on 21 mice will be presented in April.

Citation Format: Jerome Griffon, Delphine Le Guillou-Buffello, Oumeima Laifa, Alexandre Dizeux, Micheal Oelze, Lori Bridal, Michele Lamuraglia. A comparison between quantitative ultrasound and histology in heterogeneous tumor structure [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 889. doi:10.1158/1538-7445.AM2017-889