The Effect of Volume Fraction on the Backscatter from Nucleated Cells at High Frequencies

Small variations in scatterer volume fraction, which can result from changes in tissue microstructure due to cancer therapies or organ preservation, may have a significant impact on ultrasound backscatter. 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 were insonified with broadband 20 MHz and 40 MHz pulses. 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 may have implications in the development of new quantitative, ultrasound-based tissue characterization techniques.