title: High-frequency ultrasound analysis of post-mitotic arrest cell death.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Physical Sciences, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada.
authors.forename: Maurice M
authors.initials: MM
authors.lastname: Pasternak
authors.affiliation: Department of Physics, Ryerson University, Toronto, ON M5B 2K3, Canada.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Wirtzfeld
authors.affiliation: Department of Physics, Ryerson University, Toronto, ON M5B 2K3, Canada.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Kolios
authors.affiliation: Department of Physical Sciences, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada; Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada; Departments of Medical Biophysics, and Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, ON M4N 3M5, Canada.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Czarnota
keywords: breast cancer; imaging; midband fit; quantitative ultrasound; spectral slope