The effect of volume fraction on the backscatter from nucleated cells at high frequencies
Baddour RE, Kolios MC
Recently, new high frequency ultrasound devices have emerged with better system signal-to-noise ratio characteristics, which make it possible to measure ultrasound scattering in tissues so that small variations in scatterer volume fraction, which can result from changes in tissue microstructure due to cancer therapies, may have a significant impact on the backscattered signal. Although the effect of volume fraction has been studied for non-biological scatterers and red blood cells, this study addresses the case of nucleated cells. Suspensions with volume fractions up to 70% of acute myeloid leukemia cells (OCI-AML-5 cell line; mean cell diameter 12 µm, mean nucleus diameter 10 µm, as determined by optical confocal microscopy of bisbenzimide-stained cells with ultraviolet illumination) in phosphate buffered saline solution were insonified with broadband (100% 6 dB bandwidth) 20 MHz and 40 MHz pulses at 300 independent positions. The resultant average normalized backscatter intensities plotted as a function of volume fraction demonstrated a better agreement with the Yagi-Nakayama continuum scattering theory rather than the Mo-Cobbold particle scattering model (using hard sphere packing). Normalized backscatter increased with cell volume fraction up to a maximum value (occurring between 20 and 30% volume fraction), varying with frequency and then decreased with further increases in volume fraction. This result has implications in the development of new quantitative ultrasound-based monitoring techniques for cancer therapies.