High Frequency Ultrasound Scattering from Mixtures of two Different Cells Lines: Tissue Characterization Insights

Ultrasound imaging in the most commonly used imaging modality in medicine today. Ultrasound images are based on the echoes received from scattering structures in the human tissues. However, these images are traditionally based on the intensity of the received ultrasound echoes, discarding the information that is present in the frequency dependence of the backscattered waves. In this paper we demonstrate how high frequency ultrasound (20MHz) is particularly sensitive to the sizes of the nucleus (or cells) in tightly packed cell aggregate models (cell pellets) and how the frequency dependence of the backscatter provides information about the size of the effective scattering structures in an inhomogeneous medium composed of two different cell lines. Two cell lines with distinct sizes (AML 11 μm, PC3 23 μm) were used and mixed together in different portions according to volumetric ratios. A VisualSonics VS40-B high frequency ultrasound imaging device, with full access to the radiofrequency (RF) data, was used to collect images of the cell pellets and the rf data associated with those images. Spectral analysis techniques were used to measure the spectral slope, mid-band fit (MBF) and intercept of the normalized power spectrum of the rf data. It was found that the PC3 cell pellet had a much greater scattering strength as determined by the MBF compared to the AML cells (-38dB vs. -54dB), even though the smaller AML cells have a cell number density (number of cells per unit volume) 5 times greater. Moreover, the spectral slope of the PC3 cell pellet was considerably smaller than then the spectral slope of the AML pellet (0.55 dBr/MHz vs. 0.91 dBr/MHz). Both these results are consistent with scattering theory when taking into account the sizes of the nuclei and cells. Spectral parameter values of the mixtures of the AML and PC3 cells were in-between the values obtained with the pure cell pellets. The work demonstrates the sensitivity of high frequency ultrasound spectroscopy to the cell nucleus size.