Magnetic microelastography for evaluation of ultrasound-induced softening of pancreatic cancer spheroids

Abstract

Pancreatic ductal adenocarcinoma is a devastating disease with very low survival rates 5 years after diagnosis. The main reason for this dismal prognosis is the thick stroma which both protects tumor cells from drug penetration and supports tumor development. Ultrasound inertial cavitation is a promising treatment with potential for stromal disruption, enhancing tumor cells’ sensitivity to chemical agents and biomodulators. Our goal was to develop a dedicated microelastography setup allowing us to measure the elasticity of in vitro tumor models called spheroids. In a second step, the impact of cavitation treatment on their mechanical properties was assessed. A transcranial magnetic stimulation clinical device was used to induce shear waves in the spheroids containing magnetic nanoparticles. Using an inverted optical microscope, particle imaging velocimetry, and noise correlation algorithms, the shear wave velocity, indicative of the medium’s elasticity, could be measured. Shear waves generated by the magnetic pulse inside the spheroids were detected and their velocity was measured using noise correlation elastography. This allowed the estimation of the spheroids’ elasticity. Cavitation treatment softened them significantly, and the impact of the exposure conditions and the spheroids’ composition have been studied. In the future, such a method could be used to monitor cavitation treatments. In addition, since it is now well established that mechanical constraints and elasticity play an important role in tumor growth, it is of great interest to measure the elasticity of tumor models to better understand the mechanisms of tumor growth.