H‐Scan Ultrasound Monitoring of Breast Cancer Response to Chemotherapy and Validation With Diffusion‐Weighted Magnetic Resonance Imaging

Abstract

Objectives H‐scan ultrasound (US) imaging is a novel tissue characterization technique to detect apoptosis‐induced changes in cancer cells after the initiation of effective drug treatment. The objective of the proposed research was to assess the sensitivity of 3‐dimensional (3D) H‐scan US technique for monitoring the response of breast cancer‐bearing animals to neoadjuvant chemotherapy and correlate results to diffusion‐weighted magnetic resonance imaging (DW‐MRI) measurements of programmed cancer cell death. Methods Experimental studies used female mice (N = 18) implanted with human breast cancer cells. Animals underwent H‐scan US and DW‐MRI imaging on days 0, 1, 3, 7, and 10. After imaging at day 0, breast tumor‐bearing nude mice were treated biweekly with an apoptosis‐inducing drug. Texture analysis of H‐scan US images explored spatial relationships between local US scattering. At day 10, H‐scan measurements were compared with DW‐MRI‐derived apparent diffusion coefficient (ADC) values and histological findings. Results H‐scan US imaging of low and high dose cisplatin‐treated cancer‐bearing animals revealed changes in image intensity suggesting a progressive decrease in aggregate US scatterer size that was not observed in control animals. Longitudinal trends discovered in H‐scan US result matched with texture analysis and DW‐MRI (P < .01). Further, analysis of the H‐scan US image intensity and corresponding DW‐MRI‐derived ADC values revealed a strong linear correlation (R2 = .93, P < .001). These changes were due to cancer cell apoptotic activity and consider as early detectable biomarker during treatment. Conclusions The 3D H‐scan technique holds promise for assisting clinicians in monitoring the early response of breast cancer tumor to neoadjuvant chemotherapy and adding value to traditional diagnostic ultrasound examinations.