The use of speckle decorrelation OCT to detect nanobubbles in cell pellet aggregates

Abstract

Nanobubbles (NBs) have demonstrable potential for ultrasound imaging and therapeutic applications. Recent studies have even shown their capacity for cellular internalization, which has important implications for their in-vivo stability and bioaccumulation. Traditional methods for observing NBs often involve fluorescence labelling, which can influence NB behaviour. Moreover, these methods are unsuitable for detecting intact (acoustically active) NBs within a cellular environment. This study introduces a label-free approach employing optical coherence tomography (OCT) to investigate the temporal variations in speckle intensity of the OCT backscatter signal of cells interacting with NBs. The temporal variations in the signal intensity of cell aggregates result from the motion of subcellular scatterers within the cellular environment. In this work, we investigate whether internalized NBs modify the temporal variations in the signal intensity. For our experimental imaging set-up, we used a Thorlabs MEMS-VCSEL Swept Source OCT system with a central wavelength of 1300 nm to acquire M-Mode and B-Mode acquisitions. PC3 prostate cancer cells and in-house lipid-shelled NBs were used. The sensitivity of the speckle decorrelation technique was tested on our system using an intensity autocorrelation function on polystyrene microspheres and diluted NBs. Our study demonstrates that speckle decorrelation OCT can effectively detect NBs within a compact cell pellet under specific conditions and was verified using contrastenhanced ultrasound. This approach provides an additional optical method for NB detection within cellular environments and holds the potential for broader applications in detecting NBs in in-vivo applications.