Assessment of the Nucleus-to-Cytoplasmic Ratio in MCF-7 Cells Using Ultra-high Frequency Ultrasound and Photoacoustics

Abstract

The nucleus-to-cytoplasmic (N:C) ratio of a cell is often used when assessing histology for the presence of malignant disease. In this proof of concept study, we present a new, non-optical method for determination of the N:C ratio using ultra-high Frequency ultrasound (US) and photoacoustics (PA). When using transducers in the 100 MHz–500 MHz range, backscattered US pulses and emitted PA waves are encoded with information pertaining to the dimension and morphology of micron-sized objects. If biological cells are interrogated, the diameter of the scattering or absorbing structure can be assessed by fitting the power spectra of the measured US or PA signals to theoretical models for US backscatter and PA emission from a fluid sphere. In this study, the cell and nucleus diameters of 9 MCF-7 breast cancer cells were determined using a new simplified model that calculates the theoretical values of the location of the power spectra minima for both US and PA signals. These diameters were then used to calculate the N:C ratio of the measured cells. The average cell diameter determined by US pulses from a transducer with a central frequency of 375 MHz was found to be $15.5\,\upmu \hbox {m}\pm \,1.8\,\upmu \hbox {m}$. The PA waves emitted by the cell nuclei were used to determine an average nuclear diameter of $12.0\,\upmu \hbox {m}\pm 1.3\,\upmu \hbox {m}$. The N:C ratio for these cells was calculated to be $1.9\pm 1.0$, which agrees well with previously reported N:C values for this cell type.