Enhanced Laser Thrombolysis With Photomechanical Drug Delivery: An In Vitro Study HanQun Shangguan, PhD, 1 Kenton W. Gregory, MD, 1 Lee W. Casperson, PhD, 2 and Scott A. Prahl, PhD 1 * 1 Oregon Medical Laser Center, Portland, Oregon 97225 2 Department of Electrical Engineering, Portland State University, Portland, Oregon 97207 Background and Objective: Current techniques for laser throm- bolysis are limited because they can not completely clear throm- botic occlusions in arteries, typically leaving residual thrombus on the walls of the artery. The objective of this study was to investigate the possibility of using photomechanical drug deliv- ery to enhance laser thrombolysis by delivering drugs into mu- ral thrombus during laser thrombolysis. Study Design/Materials and Methods: Three experimental pro- tocols were performed in vitro to quantitatively compare the effectiveness of thrombolysis by 1) constant infusion of drug, 2) laser thrombolysis, and 3) photomechanical drug delivery. A fi- ber-optic flushing catheter delivered drug (a solution of 1 m fluorescent microspheres) and light ( a 1 s pulsed dye laser) into a gelatin-based thrombus model. The process of laser- thrombus interaction was visualized using flash photography and the laser-induced pressure waves were measured using an acoustic transducer. Results: Lumen sizes generated by mechanically manipulating the catheter through the thrombus were smaller than those gen- erated by laser ablation. The microspheres could be driven sev- eral hundred microns into the mural thrombus. Conclusion: Photomechanical drug delivery has potential for enhancement of laser thrombolysis. Two mechanisms seem to be involved in photomechanical drug delivery: 1) mural deposi- tion of the drug at the ablation site and 2) increased exposure of the thrombus surface area to the drug. Lasers Surg. Med. 23: 151–160, 1998. © 1998 Wiley-Liss, Inc. Key words: localized drug delivery; high-speed photography; hydrodynamic flow INTRODUCTION Laser thrombolysis is a promising method of clearing arteries that are obstructed by thrombi [1]. It has potential advantages over surgery, bal- loon angioplasty, and other forms of vascular in- tervention. Laser pulses can be delivered into ar- teries through fiber-optic catheters, thereby avoiding major surgery. The thrombus is removed by the laser pulses rather than by mechanically overstretching the arterial wall, potentially re- ducing the high rate of restenosis that occurs with balloon angioplasty. Ablation can be achieved by using nearly any laser source, e.g., a holmi- um:YAG laser [2–4], but wavelengths that are strongly absorbed by thrombus and poorly ab- sorbed by vascular tissue allow safe, selective tar- geting of thrombus. Use of small fiber-optic cath- eters offers the possibility of removing thrombus in small vessels (e.g., cerebral vessels) or in larger *Correspondence to: Scott Prahl, Oregon Medical Laser Center, 9205 SW Barnes Road, Portland, OR 97225. E-mail:prahl@ece.ogi.edu Accepted 30 June 1998 Lasers in Surgery and Medicine 23:151–160 (1998) © 1998 Wiley-Liss, Inc.