High-frequency ultrasound analysis of post-mitotic arrest cell death

Maurice M. Pasternak1,2, Lauren A. Wirtzfeld3, Michael C. Kolios3, Gregory J. Czarnota2,4,5

1Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada

2Department of Physical Sciences, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada

3Department of Physics, Ryerson University, Toronto, ON M5B 2K3, Canada

4Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada

5Departments of Medical Biophysics, and Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, ON M4N 3M5, Canada

Correspondence to:

Gregory J. Czarnota, email: Gregory.Czarnota@sunnybrook.ca

Keywords: quantitative ultrasound, breast cancer, imaging, midband fit, spectral slope

Received: September 23, 2015     Accepted: February 02, 2016     Published: April 15, 2016     


Non-invasive monitoring of cancer cell death would permit rapid feedback on treatment response. One technique showing such promise is quantitative ultrasound. High-frequency ultrasound spectral radiofrequency analysis was used to study cell death in breast cancer cell samples. Quantitative ultrasound parameters, including attenuation, spectral slope, spectral 0-MHz-intercept, midband fit, and fitted parameters displayed significant changes with paclitaxel-induced cell death, corresponding to observations of morphological changes seen in histology and electron microscopy. In particular, a decrease in spectral slope from 0.24±0.07 dB/MHz to 0.04±0.09 dB/MHz occurred over 24 hours of treatment time and was identified as an ultrasound parameter capable of differentiating post-mitotic arrest cell death from classical apoptosis. The formation of condensed chromatin aggregates of 1 micron or greater in size increased the number of intracellular scatterers, consistent with a hypothesis that nuclear material is a primary source of ultrasound scattering in dying cells. It was demonstrated that the midband fit quantitatively correlated to cell death index, with a Pearson R-squared value of 0.99 at p<0.01. These results suggest that high-frequency ultrasound can not only qualitatively assess the degree of cancer cell death, but may be used to quantify the efficacy of chemotherapeutic treatments.

PII: 301