An investigation of the high-frequency ultrasonic backscatter from ensembles of cells and cell analogues

Baddour RE, Czarnota GJ, Kolios MC


OBJECTIVE:
The nucleus to cell volume ratio has recently been shown to influence the ultrasound backscatter spectrum from single, isolated cells at high frequencies. In addition, published data has suggested that the cell nucleus more strongly contributes to backscatter when cells are in a dense ensemble, rather than in a suspension. The aim of this work is to further investigate the influence of cell nuclei on high-frequency backscattering from ensembles by contrasting nucleated cells with non-nucleated cells and cell analogues.

METHODS:
Centrifuged pellets of human acute myeloid leukemia cells (OCI-AML-5 line), prostate cancer cells (PC-3 line), baker’s yeast (Saccharomyces cerevisiae), sea urchin oocytes (Strongylocentrotus purpuratus) and Superdex™ 200 gel beads (GE Healthcare Inc., Piscataway, NJ, USA) were prepared in degassed, dilute phosphate buffered saline. B-mode images and raw, radiofrequency backscatter data were acquired using a VS40b ultrasound instrument (VisualSonics Inc., Toronto, ON, Canada) with 20MHz and 40MHz transducers (each with nearly 100% -6dB bandwidths).

RESULTS:
For the pellets of nucleated cells, the measured backscattered spectra were linear across the bandwidths of each transducer. Spectral slopes measured from the OCI-AML-5 cell pellets were consistently higher than those from the PC-3 pellets. In contrast, the spectra from the non-nucleated samples were more complex, exhibiting resonant-like peaks. In particular, the backscatter responses from the Superdex™ 200 and sea urchin oocyte pellets exhibited agreement with fluid sphere scattering theory.

CONCLUSIONS:
The presence of a nucleus is a strong determinant of the backscatter frequency response from ensembles at high frequencies. For ensembles of cells and cell-like scatterers that do not contain a nucleus, it may be possible to model the backscatter as an aggregate of fluid spheres.