A 3D finite element model to study the cavitation induced stresses on blood-vessel wall during the ultrasound-only phase of photo-mediated ultrasound therapy.

Abstract

Photo-mediated ultrasound therapy (PUT) is a novel technique utilizing synchronized ultrasound and laser to generate enhanced cavitation inside blood vessels. The enhanced cavitation inside blood vessels induces bio-effects, which can result in the removal of micro-vessels and the reduction in local blood perfusion. These bio-effects have the potential to treat neovascularization diseases in the eye, such as age-related macular degeneration and diabetic retinopathy. Currently, PUT is in the preclinical stage, and various PUT studies on in vivo rabbit eye models have shown successful removal of micro-vessels. PUT is completely non-invasive and particle-free as opposed to current clinical treatments such as anti-vascular endothelial growth factor therapy and photodynamic therapy, and it precisely removes micro-vessels without damaging the surrounding tissue, unlike laser photocoagulation therapy. The stresses produced by oscillating bubbles during PUT are responsible for the induced bio-effects in blood vessels. In our previous work, stresses induced during the first phase of PUT due to combined ultrasound and laser irradiation were studied using a 2D model. In this work, stresses induced during the third or last phase of PUT due to ultrasound alone were studied using a 3D finite element method-based numerical model. The results showed that the circumferential and shear stress increased as the bubble moves from the center of the vessel toward the vessel wall with more than a 16 times increase in shear stress from 1.848 to 31.060 kPa as compared to only a 4 times increase in circumferential stress from 211 to 906 kPa for a 2 µm bubble placed inside a 10 µm vessel on the application of 1 MHz ultrasound frequency and 130 kPa amplitude. In addition, the stresses decreased as the bubble was placed in smaller sized vessels with a larger decrease in circumferential stress. The changes in shear stress were found to be more dependent on the bubble–vessel wall distance, and the changes in circumferential stress were more dependent on the bubble oscillation amplitude. Moreover, the bubble shape changed to an ellipsoidal with a higher oscillation amplitude in the vessel’s axial direction as it was moved closer to the vessel wall, and the bubble oscillation amplitude decreased drastically as it was placed in vessels of a smaller size.