Assessment of high-intensity focused ultrasound treatment of rodent mammary tumors using ultrasound backscatter coefficients

Fischer 344 rats with subcutaneous mammary adenocarcinoma tumors were exposed to therapeutic ultrasound at one of three exposure levels (335, 360, and 502 W/cm² spatial-peak temporal-average intensity). Quantitative ultrasound estimates were generated from ultrasound radio frequency (RF) data from tumors before and after high-intensity focused ultrasound treatment. Treatment outcome was independently assessed by triphenyl tetrazolium chloride (TTC) staining, histological analysis by a pathologist, and thermocouple data. The average backscatter coefficient (BSC) and integrated backscatter coefficient (IBSC) were estimated before and after therapeutic ultrasound exposure for each tumor from RF data collected using clinical (Ultrasonix Sonix RP) and small-animal (Visualsonics Vevo 2100) array systems. Changes in the BSC with treatment were comparable to inter-sample variation of untreated tumors, but statistically significant differences in the change in the IBSCs were observed when comparing the exposures collectively (p < 0.10 for Sonix RP, p < 0.05 for Vevo 2100). Several exposure levels produced statistically significant differences in the change in IBSC when examined pair-wise, including two exposures having similar intensities (p < 0.05, Vevo 2100). A comparison of the IBSC results with temperature data, histology, and TTC staining revealed that the BSC was not always sensitive to thermal insult and that peak exposure pressure appeared to correlate with observed BSC increases.