Abstract
A new noninvasive method for the detection of DNA damage using mid-to high-frequency ultrasound (10–60 MHz) has been developed. Ultrasound imaging and quantitative analysis methods are used to detect cell death occurring in response to anticancer therapies in cell samples in vitro, in rat brain tissue ex vivo, and in cancer mouse models in vivo. Experimental evidence indicates that the mechanism behind this ultrasonic detection is linked to changes in the size and acoustic properties of the cell nucleus occurring with forms of cell death, and in particular apoptosis. Nuclear changes associated with cell death can result in up to 16-fold increase in ultrasound backscatter intensity and changes in spectral slope that are consistent with theoretical predictions. Furthermore, color-coded images can be generated based on specific ultrasound parameters in order to identify the regions of cell death in tumor ultrasound images with treatments. These results provide a foundation for future investigations regarding the use of ultrasound in preclinical and clinical settings to noninvasively monitor tumor responses to specific interventions that induce cell death.
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Acknowledgments
We gratefully thank Drs. Fei-Fei Liu and Deborah Foster for providing some of the cell lines used in this work. We thank Drs. Nehad Alajez, Sebastian Brand, and Anoja Giles for providing technical support. We thank Tennyson and Bradbury D. Bear for continued indefatigable scientific discourse. This research was supported by the American Institute of Ultrasound in Medicine’s Endowment for Education and Research Grant, Canadian Institutes of Health Research Strategic Training Fellowship Excellence in Radiation Research for the twenty-first century to RMV; Natural Sciences Engineering Research Council of Canada, Canada Research Chair Programme, Canadian Institutes of Health Research, Canadian Foundation of Innovation/Ontario Innovation Trust, Ryerson University to MCK; Sunnybrook Health Sciences Centre, Natural Sciences Engineering Research Council of Canada, Cancer Care Ontario Cancer Imaging Network of Ontario grants to GJC. Support from a Tier II Canada Research Chair Award and GJC from a Ontario Clinician Scientist Award from the Ontario Ministry of Health and Long-Term Care.
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Vlad, R.M., Kolios, M.C., Czarnota, G.J. (2011). Ultrasound Imaging of Apoptosis: Spectroscopic Detection of DNA-Damage Effects at High and Low Frequencies. In: Didenko, V. (eds) DNA Damage Detection In Situ, Ex Vivo, and In Vivo. Methods in Molecular Biology, vol 682. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-409-8_13
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DOI: https://doi.org/10.1007/978-1-60327-409-8_13
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