HanQun Shangguan

Pressure effects on soft tissues monitored by changes in tissue optical properties

For pulsed laser tissue welding, an appropriate pressure needs to be applied to the tissues to achieve successful welds. In this study, we investigated the influences of pressure on in vitro optical properties of elastin biomaterial. The optical properties were measured as a function of pressure with a double integrating-sphere system. A He-Ne laser (633 nm) was used for all measurements. Each sample was sandwiched between microscope slides and then compressed with a spring-loaded apparatus. Transmittance and diffuse reflectance of each sample were measured under a pressure (0 - 1.5 kg/cm2 and then released to 0). Absorption and reduced scattering coefficients were calculated using the inverse doubling method from the measured transmittance and reflectance values. Results from this study demonstrated: (1) The overall transmittance increased while the reflectance decreased as the tissue thicknesses were reduced up to 72% and the tissue weights were decreased about 40%, (2) The absorption and scattering coefficients increased with increasing the pressure, and (3) The pressure effects on the tissue optical properties were irreversible. Possible mechanisms responsible for the changes in the tissue optical properties were also investigated by changing tissue thicknesses or weights (through dehydration). This study implies that changes in tissue thickness and water content are important factors that affect tissue optical properties in different ways.

Drug delivery with microsecond laser pulses into gelatin

Photo acoustic drug delivery is a technique for localized drug delivery by laser-induced hydrodynamic pressure following cavitation bubble expansion and collapse. Photoacoustic drug delivery was investigated on gelatin-based thrombus models with planar and cylindrical geometries by use of one microsecond laser pulses. Solutions of a hydrophobic dye in mineral oil permitted monitoring of delivered colored oil into clear gelatin-based thrombus models. Cavitation bubble development and photoacoustic drug delivery were visualized with flash photography. This study demonstrated that cavitation is the governing mechanism for photoacoustic drug delivery, and the deepest penetration of colored oil in gels followed the bubble collapse. Spatial distribution measurements revealed that colored oil could be driven a few millimeters into the gels in both axial and radial directions, and the penetration was less than 500 µm when the gelatin structure was not fractured.

Microsecond laser ablation of thrombus and gelatin under clear liquids: Contact versus noncontact

Laser thrombolysis is a procedure for removing blood clots in occluded arteries using pulsed laser energy. The laser light is delivered through an optical fiber to the thrombus. The ablation process is profoundly affected by whether the optical fiber tip is inside a catheter or is in contact with the thrombus. This study measured ablation efficiency of 1-/spl mu/s laser pulses to remove a porcine clot confined in a silicone tube. The cavitation process was investigated by visualizing laser-induced bubble formation on gelatin targets with flash photography and measuring the acoustic transients with a pressure transducer. The laser spot size did not affect the mass of material removed. The efficiency of the contact ablation was at least three times greater than that of the noncontact ablation. Finally, the mass removed was closely correlated with the measured bubble expansion pressure.

Photoacoustic drug delivery: the effect of laser parameters on the spatial distribution of delivered drug

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.

Investigation of cavitation bubble dynamics using particle image velocimetry: implications for photoacoustic drug delivery

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.

Photographic Studies of Laser-Induced Bubble Formation in Absorbing Liquids and on Submerged Targets: Implications for Drug Delivery with Microsecond Laser Pulses

Pulsed laser ablation of blood clots in a fluid-filled blood ves- sel is accompanied 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 expan- sion 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. We investigate the effects of boundary con- figurations and materials on bubble formation with time-resolved flash photography and high-speed photography. Potential applications in drug delivery using microsecond laser pulses are also discussed.

Effects of material properties on laser-induced bubble formation in absorbing liquids and on submerged targets

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.

Novel cylindrical illuminator tip for ultraviolet light delivery

The design, processing, and sequential testing of a novel cylindrical diffusing optical fiber tip for ultraviolet light delivery is described. This device has been shown to uniformly (+/- 15%) illuminate angioplasty balloons, 20 mm in length, that are used in an experimental photochemotherapeutic treatment of swine intimal hyperplasia. Our experiments show that uniform diffusing tips of < 400 micron diameter can be reliably constructed for this and other interstitial applications. Modeling results indicate that this design is scalable to smaller diameters. The diffusing tips are made by stripping the protective buffer and etching away the cladding over a length of 20 mm from the fiber tip and replacing it with a thin layer of optical epoxy mixed with Al2O3 powder. To improve the uniformity and ease of fabrication, we have evaluated a new device configuration where the tip is etched into a modified conical shape, and the distal end face is polished and then coated with an optically opaque epoxy. This is shown to uniformly scatter approximately 70% of the light launched into the fiber without forward transmission.

Estimation of scattered light on the surface of unclad optical fiber tips: a new approach

Unclad multimode optical fiber tips are often the basis for diffusing tips in photodynamic therapy or scalpels in laser surgery. In this study, we report an approximated Gaussian-beam model for the calculation of the light distribution along the surface of unclad fiber tips. The results are compared with detailed experimental measurements. The model yields quite good qualitative agreement with experimental results.

Penetration of fluorescent particles in gelatin during laser thrombolysis

The use of pulsed laser energy to clear arteries obstructed by thrombus (blood clot) and plaque has emerged as a promising method for the treatment of cardiovascular diseases such as myocardial infarction and stroke. Current techniques for laser thrombolysis are limited because they cannot completely clear the clot in arteries, especially where a large volume clot is presented. Mural clot is a potent stimulus for reocclusion. We suggest that the combination of laser thrombolysis and localized intramural delivery of clot-dissolving drugs during the procedure may be a solution to this limitation. Ninety pulses of 30 - 70 mJ were delivered onto gelatin-based thrombus model with a flushing catheter. A solution of 1 micrometer fluorescent particles as a drug model was injected at a rate of 4 mL/min in coincidence with the laser delivery. The controls were performed by injecting drug after laser thrombolysis. We measured the penetration of the particles in gelatin and the sizes of the lumen and stained areas. The results of this study demonstrated the possibility of enhancing laser thrombolysis by delivering drugs into thrombus. It was found that the particles could be driven several hundred micron in gelatin, and the lumen areas would be increased up to 25% if the areas were dissolved by the drugs.