Pulsed laser ablation of blood clots in a fluid-filled blood vessel is accomplished by an explosive evaporation process. The resulting vapor bubble rapidly expands and collapses to disrupt the thrombus (blood clot). The hydrodynamic pressures following the bubble expansion and collapse can also be used as a driving force to deliver clot-dissolving agents into thrombus for enhancement of laser thrombolysis. Thus, the laser-induced bubble formation plays an important role in the thrombus removal process. In this study the effects of material properties on laser-induced cavitation bubbles formed in liquids and on submerged targets have been visualized with a microsecond strobe or high speed framing camera.
This paper presents studies of microsecond ablation phenomena that take place during laser thrombolysis. The main goals were to optimize laser parameters for efficient ablation, and to investigate the ablation mechanism. Gelatin containing an absorbing dye was used as the clot model. A parametric study was performed to identify the optimal wavelength, spot size, pulse energies, and repetition rate for maximum material removal. The minimum radiant exposures to achieve ablation at any wavelength were measured. The results suggest that most visible wavelengths were equally efficient at removing material at radiant exposures above threshold. Ablation was initiated at surface temperatures just above 100 degrees Celsius. A vapor bubble was formed during ablation. Less than 5% of the total pulse energy is coupled into the bubble energy. A large part of the delivered energy is unaccounted for and is likely released partly as acoustic transients from the vapor expansion and partly wasted as heat. The current laser and delivery systems may not be able to completely remove large clot burden that is sometimes encountered in heart attacks. However, laser thrombolysis may emerge as a favored treatment for strokes where the occlusion is generally smaller and rapid recanalization is of paramount importance. A final hypothesis is that laser thrombolysis should be done at radiant exposures close to threshold to minimize any damaging effects of the bubble dynamics on the vessel wall.
Laser thrombolysis uses microsecond laser pulses to remove thrombus-blocked arteries in the heart and the brain. Rapidly expanding and collapsing vapor bubbles are formed upon absorption of the laser energy by the thrombus. The goal of this study was to visualize the process of ablation and assess the effects of pulse repetition rate. The differences between contact versus non-contact of the laser delivery device with the thrombus were also investigated. Initial experiments were conducted with a gel-based clot model confined in 3 mm inner diameter silicone tubes. Subsequent experiments used 24 hour old porcine blood clots. Laser pulses of 50 mJ pulse energy were delivered via a quartz fiber contained in a flushing catheter. Pulse repetition rates of 1 Hz, 3 Hz, and 6 Hz were used. Wavelengths of 506 nm and 577 nm were used to ablate clot. Bubble action was captured by flash photography using a CCD camera and recorded on video. The amount of material removed was measured using a spectrophotometric technique. Bubble action was similar on clot and the clot model. No significant differences in bubble action or mass removal were observed at the three pulse repetition rates and the two wavelengths. Contact between the catheter and the clot did not result in a pistoning effect of the catheter at the pulse energy used.
Photoacoustic drug delivery is a technique for delivering drugs to localized areas in the body. In cardiovascular applications, it uses a laser pulse to generate a cavitation bubble in a blood vessel due to the absorption of laser energy by targets (e.g., blood clots) or surrounding liquids (e.g., blood or injected saline). The hydrodynamic pressure arising from the expansion and collapse of the cavitation bubble can force the drug into the clots and tissue wall tissue. Time-resolved particle image velocimetry was used to investigate the flow of liquids during the expansion and collapse of cavitation bubbles near a soft boundary. A gelatin-based thrombus model was used to simulate the blood clot present during laser thrombolysis. An argon laser chopped by an acousto-optic modulator was used for illumination and photography was achieved using a CCD camera. The implications of this phenomenon on practical photoacoustic drug delivery implementation are discussed.
Photoacoustic drug delivery is a technique for delivering drugs to localized areas by timing laser-induced pressure transients to coincide with a bolus of drug. This study explores the effects of target material, laser energy, absorption coefficient, fiber size, repetition rate, and number of pulses on the spatial distribution of delivered drug. A microsecond flash-lamp pumped dye laser delivered 30-100 mJ pulses through optical fibers with diameters of 300-1000 micrometers . Vapor bubbles were created 1-5 mm above clear gelatin targets submerged in mineral oil containing a hydrophobic dye (D&C Red#17). The absorption coefficient of the oil-dye solution was varied from 50-300 cm-1. Spatially unconfined geometry was investigated. We have found that while the dye can be driven a few millimeters into the gels in both the axial and radial directions, the penetration was less than 500 micrometers when the gel surface remained macroscopically undamaged. Increasing the distance between the fiber tip and target, or decreasing the pulse energy reduced the extend of the delivery.
The efficiency of laser ablation of thrombus depends on spot size, pulse energy and repetition rate. A 1 microsecond(s) pulsed dye laser (504 nm) was used to ablate a gelatin-based thrombus model containing an absorbing dye under water. The gelatin was confined in 3 mm inner diameter tubes and pulse energies of 25-100 mJ were delivered via 300, 600, and 1000 micrometers core diameter fibers. The experiments were conducted at pulse repetition rates of 3 Hz and 10 Hz. The amount of gelatin removed was measured using a spectrophotometric method and ablation efficiency was defined as mass removed per pulse per unit energy. Flash photography was used to visualize the ablation process in 1 cm cuvettes. Results: More material was removed using bigger fibers in the 3 mm tubes at similar pulse energies. The amount of gelatin removed per pulse increased linearly with pulse energy. There was no significant change in the amount removed at pulse repetition rates of 3 Hz and 10 Hz. In the 1 cm cuvettes, the ablation mass was roughly the same with both the 300 micrometers and 1000 micrometers fibers. Flash photography of the ablation process in 1 cm cuvettes showed that less than 1% of the laser energy went into formation of a vapor bubble. The mass removed increased roughly linearly with bubble energy. Conclusions: Ablation mass increases linearly with pulse energy, but does not have a direct relationship with radiant exposure. It is independent of the repetition rate under 10 Hz.
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