A novel method of drug delivery for fibrinolysis with Ho:YAG laser-induced liquid jet.

Abstract

Two of the problems inherent in the treatment of cerebral emboli are the narrow therapeutic time window and the severe side effects of fibrinolytic drugs. Thus, it is necessary to develop a new method of removing a cerebral thrombus more rapidly and with smaller quantities of fibrinolytics. The behaviour of a bubble formed by holmium (Ho):YAG laser irradiation in a capillary tube filled with pure water was observed at various stand-off distances (L; distance between the end of optical fibre and the capillary exit). Subsequently, a liquid-jet generator was created by insertion of an optical fibre (core diameter: 0.6 mm) into a catheter (6 Fr) filled with pure water, and a pulsed Ho:YAG laser (pulse duration time=350 micros, laser energy=230 mJ/pulse) was used to irradiate the optical fibre. The maximum penetration depth, into a gelatin artificial thrombus, of a liquid jet generated with this device was measured for various stand-off distances. Additionally, the phenomenon and the pressure around the catheter exit were captured via shadowgraph and PVDF needle hydrophone, respectively. The laser-induced bubble in the capillary tube grew rapidly in the direction of propagation and generated a liquid jet. The maximum penetration depth of this liquid jet into an artificial thrombus increased in proportion to L and reached a maximum value (9 mm) when L was around 13 mm. A shock wave whose overpressure at a point 4 mm away from the catheter exit exceeded 12 MPa was captured by shadowgraph. It was concluded that Ho:YAG laser irradiation within a water-filled catheter caused liquid jet formation, which could penetrate straight into an artificial thrombus. Hence, this jet is expected to promote fibrinolysis by means of injecting fibrinolytics deeply into the thrombus. After resolving some problems, this system will be applied to an endovascular therapy for cerebral embolisms in the near future.