Preclinical Assessment of Breast Cancer and Early Response to Chemotherapy using 3-D H-Scan Ultrasound Imaging

Various ultrasound (US) approaches for tumor tissue characterization have shown promise for monitoring response to anticancer treatment. Our group has pioneered a new technology termed H-scan US imaging, which links differences in the frequency content of backscattered US signals to various-sized aggregate scatterers. The purpose of this research was to use a three-dimensional (3-D) H-scan US imaging system and method for tissue characterization in volume space and evaluate using a preclinical animal model of breast cancer. Preliminary studies were conducted using female mice (Charles River Laboratories) implanted with breast cancer cells (MDA-MB-231, ATCC). Animals were then received intraperitoneal injections of control saline or anticancer drug, namely, TRA-8, paclitaxel, or TRA-8 + paclitaxel ( $\boldsymbol{N}=5$ per group). Image data was obtained using an US system (Vantage 256, Verasonics Inc) equipped with a volumetric transducer (4DL7, Vermon) at baseline before drug dosing and again every 24 h for 3 d. Experimental data demonstrated that in vivo 3-D H-scan US imaging is very sensitive to tumor changes after administration of anticancer drug therapy. While there was no difference at baseline, H-scan US results from treated tumors exhibited progressive decreases in local image intensity that correlated with increased apoptotic activity and reduced nuclear size as validated by histological measures. Overall, 3-D H-scan US imaging is a promising modality for visualization of the heterogenous tumor microenvironment. It also allows noninvasive detection of an acute tumor response to apoptosis-inducing treatment in a preclinical animal model.