Modelling high frequency ultrasound scattering of cellular ensembles to deduce the apoptotic index
Baddour R, Kolios M, Sherar M
Objective: It has been previously shown that high-frequency ultrasound (20–100 MHz) can be used to detect cellular structure changes, including apoptosis, in tissues and cell ensembles. The detection of apoptosis is based on changes in the intensity and frequency spectrum of the backscattered ultrasound. However, as these changes in backscatter are not fully understood, it is not possible to accurately measure the apoptotic index, the percentage of cells in a volume undergoing apoptosis. Measuring the apoptotic index with high-frequency ultrasound would have implications in a broad range of fields, from cancer treatment monitoring to organ transplantation. We are investigating the use of an ultrasound scattering model of cell ensembles in deducing the apoptotic index.
Methods: We have previously proposed a theoretical model for studying how changes in the sizes, spatial distribution, and acoustic impedances of the scattering sources within cells are related to the resulting backscattered ultrasound signal from a cell ensemble. A simulation was designed to implement this theoretical model to simulate a packed ensemble of OCI-AML-5 cells. The density, diameter, speed of sound, and Poisson ratio of the subcellular scatterers are adjusted to attempt to simulate apoptosis. In addition, the proportion and distribution of simulated cells undergoing apoptosis is varied.
Results: By varying the acoustic properties and spatial distribution of the subcellular scatterers, it is possible to generate predicted values of scattering that agree with the spectral parameters of measured radiofrequency data collected from spun-down pellets of apoptotic OCIAML-5 cells. When the simulated apoptotic index is increased, an increase in the intensity and spectral slope of the backscatter is predicted. This is in agreement with previous experimental results. We are presently investigating the sensitivity of the resulting backscatter to different conformations of the same apoptotic index.
Conclusions: Using an ensemble model of ultrasound scattering, it may be possible to develop a method to deduce the apoptotic index of cell ensembles. This method would likely have to be calibrated for each cell type of interest.