Preclinical Comparison of H-scan Ultrasound and Diffusion-Weighted Magnetic Resonance Imaging for Monitoring Treatment Response in Breast Cancer

Abstract

The use of ultrasound (US) for tumor tissue characterization remains an exciting prospect. The purpose of this research project was to introduce a 3-dimensional (3-D) H-scan US imaging system to monitor response of breast cancer to neoadjuvant chemotherapy. Studies were conducted using female mice ( <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$N= 20$</tex> ) implanted with 1 million breast cancer cells (MDA-MB-231). Once tumors were formed, animals were treated with a sham drug or low or high doses of cisplatin. In vivo US imaging was performed using Vevo 3100 system (FUJIFILM VisualSonics Inc) equipped with an MX201 transducer and motorized positioner. To generate the H-scan US images, Gaussian-weighted Hermite polynomial filters were convolved with the radiofrequency (RF) data to measure the relative strength of the backscattered US signals. Animals also underwent diffusion-weighted magnetic resonance imaging (DW-MRI)) using a preclinical scanner (BioSpec 3T, Bruker Corp) for generation of apparent diffusion coefficient (ADC) maps as a measure of intratumoral water diffusion. In vivo results demonstrated that 3-D H-scan US imaging was more sensitive to tumor changes after neoadjuvant chemotherapy as compared to B-scan US. While there was no difference at baseline (p > 0.60), H-scan US images from the cisplatin treated tumors exhibited increased intensity at 7 d (36.4 ± 6.9% and 43.8 ± 8.1% for low and high dosed groups, respectively) indicating a decrease in aggregate US scatterer size. Collectively, these observations were confirmed by histological analysis. Overall, 3-D H-scan US imaging is a promising new tool for monitoring cancer response to neoadjuvant therapy. In vivo results matched those found using DW-MRI, which is an established modality for assessing anticancer treatment using apoptosis-inducing drugs.