H-Scan Ultrasound Monitoring of Breast Cancer Response to Chemotherapy and Validation with Diffusion-Weighted Magnetic Resonance Imaging.

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.