Synergistic sonothrombolysis based on coaxial confocal dual-frequency focused ultrasound and vortex beams

Focused ultrasound (FU) acts as a non-invasive targeted therapy for thrombus dissolution, leveraging its mechanical and cavitation effects. The thrombolysis efficiency can be markedly improved with the incorporation of an assisted focused acoustic vortex (FAV). Nevertheless, when employing FAV-assisted FU thrombolysis with two focused transducers positioned orthogonally, the FAV's trapping force is reduced due to the co-directional acoustic radiation force (ARF) from the FU. We have devised a synergistic sonothrombolysis strategy that utilizes coaxial confocal dual-frequency FU and FAV beams, implemented through a focused sector array. The enhancement mechanism of thrombolysis was explored through comprehensive analyses of the focal area, trapping capability, and shear stress of both FAV and FU. Findings indicate that the rotational shear stress generated by FAV can disrupt the thrombus surface structure, dislodge debris from the clots, and aid in the penetration of drug molecules. The FAV's trapping force is strong enough to counteract the drag from venous flow, thereby enhancing the interaction between trapped clot debris and microbubbles within the focal region. Despite the FAV's peak pressure being lower than that of FU, the combined FAV + FU sonication exhibits enhanced cavitation effects, as evidenced by the increased absorbance of iodide ions and a faster rise in speed. These theoretical insights were confirmed by experimental measurements of free radicals, stable and inertial cavitation doses, and lysis rates, using FU and FAV for thrombolysis in both static conditions and blood flow. The results show that, with its trapping capability, FAV's thrombolysis efficiency in a blood flow condition (5 cm/s) is nearly unchanged from that in a stable environment and is significantly better than FU's. An impressive efficiency increase of up to 61 % was achieved using the synergistic thrombolysis method. The proposed synergistic thrombolysis strategy shows promise for developing a safer and more effective treatment for blood flow applications, utilizing a focused sector array and demonstrating significant potential for biomedical applications.