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.
Highlights
As the diversity of chemotherapeutic options for malignant tumour treatment increases, the detection of treatment response becomes imperative as cancers may start out as sensitive responders, only to develop therapeutic resistance after multiple rounds of chemotherapy
It is well documented that chemotherapeutically-induced tumour cell death is accompanied by vast structural changes leading to alterations in physical properties [4], and ultrasound imaging over treatment could permit the monitoring of the treatment efficacy through the quantification of cell death [5, 6]
The midband fit at 25 MHz increased from -37.2 dBr to -34.4 dBr whereas the spectral slope at 25 MHz decreased from 0.24 dBr/MHz to 0.12 dBr/MHz between time-matched control and 24 hours of paclitaxel exposure
Summary
As the diversity of chemotherapeutic options for malignant tumour treatment increases, the detection of treatment response becomes imperative as cancers may start out as sensitive responders, only to develop therapeutic resistance after multiple rounds of chemotherapy. High frequency ultrasound (HFUS; 20-60 MHz) coupled with spectral quantitative ultrasound analyses offers a non-invasive, high-resolution, and cost-effective imaging approach. It has previously been demonstrated that spectral ultrasound is sensitive to changes in physical properties of tissues, including the www.impactjournals.com/oncoscience scatterer number density, bulk modulus, and other factors. It is well documented that chemotherapeutically-induced tumour cell death is accompanied by vast structural changes leading to alterations in physical properties [4], and ultrasound imaging over treatment could permit the monitoring of the treatment efficacy through the quantification of cell death [5, 6]
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