Reflected shear wave computed tomography for elasticity imaging of 3D cell cultures using a single-element transducer

Abstract

Shear wave elasticity imaging (SWEI) has long been used to quantify tissue stiffness in clinical diagnoses. In comparison with conventional bulk-based measurement methods, SWEI offers the distinct advantage of nondestructive sampling, thereby enabling the spatiotemporal monitoring of stiffness variations. However, applying SWEI to assessing millimeter-scale three-dimensional (3D) cell environments has faced limitations despite its potential in mechanobiology, and the existing techniques are insufficient for imaging inhomogeneous media environments. In this study, we investigated a computed tomography technique specifically designed for reflected SWEI (called R-SWCT) by rotational scanning in a sample using a 20-MHz ultrasound single-element transducer. We focused on samples containing a single inclusion with higher stiffness than the surrounding medium, mimicking the situation of a tumor sphere embedded in a 3D gel. Our method reconstructs the stiffness distribution using a curve-fitting method, wherein coefficients of Gaussian curves are fitted to the wavefronts of simulated signals. This reconstruction method yielded coefficients that closely approximated the wavefronts obtained experimentally, with a maximum difference between the measured and predicted shear wave speeds of only 0.1 m/s for phantom samples and 0.2 m/s for cell samples. The system and methodologies proposed in this research have demonstrated the feasibility of employing R-SWCT to study the remodeling dynamics of a cell group within its surrounding matrix in an in vitro setting. This noninvasive method also facilitates an exploration of how irradiation dosage used in radiation therapy can induce temporal alterations in the shear wave speed in 3D cancer cell cultures.