A study of laser irradiation-aided sonothrombolysis using gold nanoparticles-coated microbubbles via combined ultrasound (US) and photoacoustic (PA) imaging

Abstract

Blood clots or thrombi can occlude the blood vessels which may lead to diseases such as ischemic stroke, deep vein thrombosis, etc. Sonothrombolysis is a non-invasive procedure for breaking down the blood clots using focused ultrasound waves. Microbubbles (MBs) have been used as ultrasound (US) contrast agents and are known to increase the sonothrombolysis efficiency. In this work, we explore the use of gold nanorods-coated microbubbles (AuMBs) under a nanosecond-pulsed laser exposure within the maximum permissible energy (MPE) limit for sonothrombolysis. The thrombolysis efficiency needs to be compared using microbubbles alone under ultrasound waves and AuMBs under combined laser exposure and ultrasound waves. A dual modal ultrasound (US) and photoacoustic (PA) imaging clinical system is used to evaluate thrombolysis efficiency. While US imaging can be used to visualize the structure and density of blood clots, PA imaging enables the study of composition of the blood clot. Blood clots may be red, white or mixed due to the higher count of red blood cells (RBCs), white blood cells (WBCs) or it being a combination of RBCs and WBCs, respectively. Each clot type has a different PA signal. Hence, the changes in the composition of the blood clot over time can be monitored using PA imaging. Moreover, gold nanoparticles are widely used as PA contrast agents. It has been reported that AuMBs have a higher PA signal compared to gold nanoparticles alone. Hence, the PA signal from AuMBs can be used to ascertain the population of the microbubbles over the course of the thrombolysis treatment. The US and PA signal-to-noise ratios (SNR) of the blood clot and AuMBs, are measured at fixed time intervals during thrombolysis treatment.