Scattering of high-frequency ultrasound by cells and cell ensembles: In search of the dominant scattering source

High-frequency ultrasound (HFU) imaging (in the range of 20–60 MHz) has been recently enabled by advances in transducer technology and electronics. These high frequencies afford greater image resolution, on the order of 40 microns, at the expense of penetration depth, limited to a few centimeters. The associated ultrasound wavelengths of HFU are 25–75 microns, on the order of the size of cells. Therefore, it is hypothesized that at these frequencies ultrasound tissue characterization will provide more meaningful information about the physical characteristics of cells and any changes that occur in their structure during cancer treatment. The late Dr. Frederic Lizzi pioneered ultrasound tissue characterization and the seminal papers he published provided the impetus for this work. Here, backscatter from individual cells and tightly packed cell aggregates of the same cells (emulating tumors) are examined and compared to theoretical models of ultrasound backscatter. Recent work with a series of cells lines with different sizes and physical characteristics will be presented. It will be shown that for in vitro and in vivo experiments, the backscatter signal characteristics best correlate with nuclear size.