ABSTRACT
BACKGROUND: The study here investigated quantitative ultrasound (QUS) parameters to assess tumour response to ultrasound-stimulated microbubbles (USMB) and hyperthermia (HT) treatment in vivo. Mice bearing prostate cancer xenografts were exposed to various treatment conditions including 1% (v/v) Definity microbubbles stimulated at ultrasound pressures 246 kPa and 570 kPa and HT duration of 0, 10, 40, and 50 min. Ultrasound radiofrequency (RF) data were collected using an ultrasound transducer with a central frequency of 25 MHz. QUS parameters based on form factor models were used as potential biomarkers of cell death in prostate cancer xenografts. RESULTS: The average acoustic concentration (AAC) parameter from spherical gaussian and the fluid-filled spherical models were the most efficient imaging biomarker of cell death. Statistical significant increases of AAC were found in the combined treatment groups: 246 kPa + 40 min, 246 kPa + 50 min, and 570 kPa + 50 min, in comparison with control tumours (0 kPa + 0 min). Changes in AAC correlates strongly (r2 = 0.62) with cell death fraction quantified from the histopathological analysis. CONCLUSION: Scattering property estimates from spherical gaussian and fluid-filled spherical models are useful imaging biomarkers for assessing tumour response to treatment. Our observation of changes in AAC from high ultrasound frequencies was consistent with previous findings where parameters related to the backscatter intensity (AAC) increased with cell death.