Towards understanding the nature of high frequency backscatter from cells and tissues: an investigation of backscatter power spectra from different concentrations of cells of different sizes

During cell death, a series of structural changes occur within the cell. We have shown that cell ensembles and tissues undergoing structural changes associated with various cell death pathways can be detected using high-frequency ultrasound. In our effort to understand better the nature of backscatter from collections of cells (which emulate tissues), we have collected raw RF backscatter data from cells of two different sizes (human acute myeloid leukemia, AML, cells and transformed prostate cells) in solutions for a series of concentrations or in pellet form. It was found that the backscatter power (as measured by the mid-band fit) increased by ∼3 dB for both cell types in dilute solutions for which the volumetric concentration was doubled for a specific range of cell concentrations (which was dependent on cell size). In pellet form, the backscatter power from the prostate cell pellets was ∼12-14 dB greater than the AML cell pellets. A comparison of the spectral slopes also strongly suggests a change in the scattering source contributions when the cells are in pellets: the spectral slope was negative for all concentrations for prostate cells imaged at 40 MHz, but positive when measured in pellets. This is consistent with an increased contribution to the backscatter of smaller sized scatterers (such as the cell nucleus) that manifests itself only when the cells are in pellets but not in solution. These data are compared to theoretical predictions and their significance discussed.