Quantitative Ultrasound Characterization of Cancer Radiotherapy Effects In Vitro

PURPOSE: Currently, no routinely used imaging modality is available to assess tumor responses to cancer treatment within hours to days after radiotherapy. In this study, we demonstrate the preclinical application of quantitative ultrasound methods to characterize the cellular responses to cancer radiotherapy in vitro. METHODS AND MATERIALS: Three different cell lines were exposed to radiation doses of 2-8 Gy. Data were collected with an ultrasound scanner using frequencies of 10-30 MHz. As indicators of response, ultrasound integrated backscatter and spectral slope were determined from the cell samples. These parameters were corrected for ultrasonic attenuation by measuring the attenuation coefficient. RESULTS: A significant increase in the ultrasound integrated backscatter of 4-7 dB (p < 0.001) was found for radiation-treated cells compared with viable cells at all radiation doses. The spectral slopes decreased in the cell samples that predominantly underwent mitotic arrest/catastrophe after radiotherapy, consistent with an increase in cell size. In contrast, the spectral slopes did not change significantly in the cell samples that underwent a mix of cell death (apoptosis and mitotic arrest), with no significant change in average cell size. CONCLUSION: The changes in ultrasound integrated backscatter and spectral slope were direct consequences of cell and nuclear morphologic changes associated with cell death. The results indicate that this combination of quantitative ultrasonic parameters has the potential to assess the cell responses to radiation, differentiate between different types of cell death, and provide a preclinical framework to monitor tumor responses in vivo.