Quantitative ultrasound characterization of therapy response in prostate cancer in vivo

Quantitative ultrasound (QUS) is a non-invasive imaging modality that permits the detection of tumor response following various cancer therapies. Based on ultrasound signal scattering from the biological system, scatterer size, and concentration of microscopic scatterers, QUS enables the rapid characterization of tumor cell death. In this study, tumor response to ultrasound-stimulated microbubbles (USMB) and hyperthermia (HT) in tumor-bearing mice, with prostate cancer xenografts (PC3), was examined using QUS. Treatment conditions included 1% (v/v) Definity microbubbles stimulated at ultrasound pressures (0, 246, and 570 kPa) and HT treatment (0, 10, 40, and 50 minutes). Three ultrasound backscatter parameters, mid-band fit (MBF), 0-MHz spectral intercept (SI), and spectral slope (SS) were estimated prior to, and 24 hours after treatment. Additionally, histological assessment of tumor cell death and tissue microstructural changes was used to complement the results obtained from ultrasound data. Results demonstrated a significant increase in QUS parameters (MBF and SI) followed combined USMB and HT treatment (P<0.05). In contrast, the backscatter parameters from the control (untreated) group, and USMB only group showed minimal changes (P>0.05). Furthermore, histological data demonstrated increased cell death and prominent changes in cellular and tissue structure, nucleus size, and subcellular constituent orientation followed combined treatments. The findings suggested that QUS parameters derived from the ultrasound backscattered power spectrum may be used to detect HT treatment effects in prostate cancer tumors in vivo.