Estimating the change in cellular size variance during cell death using the polydisperse structure factor model

Abstract : Quantitative UltraSound (QUS) techniques for determining the tissue microstructure are promising tools to detect and quantify cell death, and thus monitor the tumor response to therapy. Previous in vitro experimental studies suggested that the changes in the backscatter coefficient (BSC) during cell death were linked to the increase of the cellular size variance. The aim of this work was to estimate the change in cellular size variance from the polydisperse structure factor model (SFM) by using experimental ultrasonic measurement before and after therapy. The polydisperse SFM was recently demonstrated to be efficient for explaining the measured BSCs on cell pellet biophantoms. Cell pellet biophantoms consist in centrifugated densely packed cells and serve as simplified in vitro versions of real tumors. Ultrasonic backscatter measurements were performed at frequencies ranging from 10 to 42 MHz on colon adenocarcinoma cell pellet biophantoms treated with staurosporine, a drug which induces mainly cell apoptosis. Blind estimates of QUS parameters were performed by fitting one measured BSC with a standard ultrasonic scattering model, namely the fluid sphere model (FSM). A novel approach was also proposed to estimate QUS parameters from the polydisperse SFM by using two measured BSCs before and after therapy. Finally, the relationship between the actual cellular structures and QUS parameters was investigated.