Tomohiro Ohki

Laser-ablation-assisted microparticle acceleration for drug delivery

Localized drug delivery with minimal tissue damage is desired in some of the clinical procedures such as gene therapy, treatment of cancer cells, treatment of thrombosis, etc. We present an effective method for delivering drug-coated microparticles using laser ablation on a thin metal foil containing particles. A thin metal foil, with a deposition of a layer of microparticles is subjected to laser ablation on its backface such that a shock wave propagates through the foil. Due to shock wave loading, the surface of the foil containing microparticles is accelerated to very high speeds, ejecting the deposited particles at hypersonic speeds. The ejected particles have sufficient momentum to penetrate soft body tissues, and the penetration depth observed is sufficient for most of the pharmacological treatments. We have tried delivering 1 \mu m tungsten particles into gelatin models that represent soft tissues, and liver tissues of an experimental rat. Sufficient penetration depths have been observed in these experiments with minimum target damage.

A laser-induced liquid jet catheter system: a novel endovascular device for rapid and reliable fibrinolysis in acute cerebral embolism.

OBJECTIVE Mechanical removal of intravascular clots in addition to administration of tissue plasminogen activator are both desirable for improved outcome in acute embolic stroke. We have developed a novel endovascular catheter system for rapid and reliable mechanical recanalization of cerebral embolisms with little or no requirement for fibrinolytic agents. Here, we describe the evaluation of this device in vitro. MATERIALS Pulsed liquid jets were generated and ejected from the catheter exit by accelerating cold physiological saline (4 degrees C, 40 mL/h) using the energy of a pulsed holmium:yttrium-aluminum-garnet (YAG) laser (3 Hz, 1.2 W). Accessibility beyond the tortuous cavernous portion of the internal carotid artery to the M1 and A1 regions was confirmed using a transparent model of the human cerebral artery. Mechanical characteristics of the liquid jets were evaluated with a high-speed camera. Liquid jets of physiological saline or urokinase solution (1,200 IU/mL) were exposed to artificial thrombi made of human blood under temperature monitoring. Remnants of thrombi were collected and incubated at 37 degrees C for 10 min for estimation of fibrinolysis rates. RESULTS The jet velocity (maximum: 5 m/s) was controlled by changing the laser energy. The fibrinolysis rates (mean+/-SD) after exposure to jets of saline or urokinase solution for 45 s were 62.2+/-16.4 and 94.0+/-3.4%, respectively, and were significantly better than the rate of 8.1+/-2.0% with administration of urokinase alone. The local temperature rise was less than 8 degrees C. CONCLUSIONS The results show that the laser-induced liquid jet catheter system may be a powerful tool for mechanical destruction of emboli and augmentation of the effect of fibrinolytic agents beyond the tortuous part of the internal carotid artery.

Experimental study of micro shock wave focusing for precise medical applications

For applying shock waves to sensitive medical procedures like cranioplasty in a close vicinity of the brain or treatment of myocardial dysfunction, generation of micro underwater shock waves plays an important role. Such delicate applications make limits on usage of conventional shock wave (SW) sources. In the present research a half‐ellipsoidal cavity with 20.0‐mm minor diameter and the ratio of major to minor diameters of 1.41 was designed as a compact extracorporeal SW source. Silver azide AgN3 pellets ranging from 1.0 to 20 μg with their energy ranging from 1.9 to 38 mJ were used to generate shock waves at the first focal point F1 inside the reflector. Irradiation of a Q‐switched Nd:YAG laser beam through a 400‐μm optical fiber was used to ignite the pellet. The whole sequences of the shock wave generation, propagation, and focusing were visualized by quantitative double pulse holographic interferometry and time‐resolved high speed shadowgraph methods. Pressure histories were measured at the shock wav...

Experimental application of Holmium:yttrium‐aluminum‐garnet laser‐induced shock wave as a drug delivery system

One of the possible applications of shock waves is enhancement of drug delivery in the central nervous system. To achieve such a goal, it is necessary to develop a suitable shock wave source with the ability to be integrated with an endoscope or a catheter. We have developed a shock wave generator using a pulsed Ho:YAG laser as the energy source; this device is remarkable for its ability to expose shock wave to target tissue in a localized area. The physical feature and characteristics of the generator were clarified. The overpressures of Ho:YAG laser‐induced cavitational shock waves were measured by using a PVDF needle hydrophone. Maximum overpressure of 19 MPa at 4‐mm distance from tip of the device was obtained. As a preliminary experiment, the device was applied to evaluate the enhancement of chemotherapeutic effects of shock wave in vitro, using human gastric cancer cell (GCIY cell) line and an anticancer drug (Bleomycin: BLM). Proliferation rate of the cells decreased to 90% and 45%, after applicati...

Experimental application of pulsed Ho:YAG laser-induced liquid jet for neuroendoscopic hematoma removal

To develop the novvel device for neuroendoscopic hematoma removal, we describe the Ho:YAG laser-induced liquiud jet system for hematoma fragmentation and liquefaction. Two types of nozzle were used (nozzle 1: internal diameter: 200 μm, nozzle 2: internal diameter: 1000 μ, each length: 5mm) and the pressure profiles of LILJ ejected from those nozzles were measured. And also the effectiveness of present system was evaluated by calculating liquefaction rate (measured as the percentage of the weight loss of the treated artificial hematoma) in vitro experiments.

Development of Ho: YAG laser-induced cavitational shock wave generator for endoscopic shock wave exposure

Recently, the application of shock waves in medicine has been extended to the treatment for more delicate, localized, and deeper lesions. Therefore, it is now obligatory to develop a specialized shock wave generator that is suitable for those purpses, with the ability to be deployed by endoscope or catheter.