Characterizing reflections from intraocular lens implants.

OBJECTIVE: To develop a test method for characterizing glare from intraocular lenses (IOLs) and to confirm a clinical finding that the haptic insertion in the optic of a three-piece IOL produces extraneous line images. METHOD: The method consists of directing a collimated Gaussian laser beam to various parts of the IOL to be tested in a water-filled model eye. Reflected images produced in the retinal plane are photographed with a digital camera. RESULTS: A test method was developed to characterize the source of glare images from IOLs. The test method developed was used to confirm a clinical finding that the haptic insertion in the optic of a three-piece IOL produces extraneous line images. CONCLUSIONS: The method developed can be used to characterize and pin point the source of extraneous glare images from intraocular lens implants. The haptic insertion in the optic of a three-piece IOL has been identified as a source of line images.

Influence of illumination-collection geometry on fluorescence spectroscopy in multilayer tissue.

Device-tissue interface geometry influences both the intensity of detected fluorescence and the extent of tissue sampled. Previous modelling studies have often investigated fluorescent light propagation using generalised tissue and illumination-collection geometries. However, the implementation of approaches that incorporate a greater degree of realism may provide more accurate estimates of light propagation. In this study, Monte Carlo modelling was performed to predict how illumination-collection parameters affect signal detection in multilayer tissue. Using the geometry and optical properties of normal and atherosclerotic aortas, results for realistic probe designs and a semi-infinite source-detection scheme were generated and compared. As illumination-collection parameters, including single-fibre probe diameter and fibre separation distance in multifibre probes, were varied, the signal origin deviated significantly from that predicted using the semi-infinite geometry, The semi-infinite case under-predicted the fraction of fluorescence originating from the superficial layer by up to 23% for a 0.2mm diameter single-fibre probe and over-predicted by 10% for a multifibre probe. These results demonstrate the importance of specifying realistic illumination-collection parameters in theoretical studies and indicate that targeting of specific tissue regions may be achievable through customisation of the illumination-collection interface. The device- and tissue-specific approach presented has the potential to facilitate the optimisation of minimally invasive optical systems for a wide variety of applications.

Long-term effects of photodynamic therapy on fluorescence spectroscopy in the human esophagus.

Clinical interest in laser-induced fluorescence (LIF) spectroscopy and photodynamic therapy (PDT) is growing rapidly and may ultimately lead to close parallel use of these techniques. However, variations in LIF due to photosensitizer retention as well as tissue damage and healing processes may interfere with autofluorescence-based diagnostic methods. We have investigated the compatibility of these two techniques by quantifying PDT-induced changes in LIF in the human esophagus. Fluorescence spectra were collected endoscopically at excitation wavelengths (lambda ex) of 337, 400 and 410 nm in 32 patients. Measurements were performed immediately before and after PDT treatment with porfimer sodium and during follow-up procedures. In the months following PDT regions of reepithelialized squamous showed reduced autofluorescence in comparison with untreated squamous regions (P = 0.0007). Photosensitizer fluorescence was undetectable with lambda ex = 337 nm during follow-up procedures, whereas for lambda ex = 400 and 410 nm porfimer sodium fluorescence was noted for nearly a year after treatment. Therefore, residual photosensitizer fluorescence is likely to affect certain LIF-based diagnostic techniques during a period when patients are at high risk for tumor recurrence. Modification of LIF systems and/or the use of alternative photosensitizers may be required to optimize the detection of lesions in the post-PDT patient. Given the potential of LIF as a method for surveillance following cancer therapy, further investigation of the compatibility of specific LIF approaches with cancer pharmaceuticals may be warranted.

Photothermal coagulation of blood vessels: a comparison of high-speed optical coherence tomography and numerical modelling.

Optical-thermal models that can accurately predict temperature rise and damage in blood vessels and surrounding tissue may be used to improve the treatment of vascular disorders. Verification of these models has been hampered by the lack of time- and depth-resolved experimental data. In this preliminary study, an optical coherence tomography system operating at 4-30 frames per second was used to visualize laser irradiation of cutaneous (hamster dorsal skin flap) blood vessels. An argon laser was utilized with the following parameters: pulse duration 0.1-2.0 s, spot size 0.1-1.0 mm, power 100-400 mW. Video microscopy images were obtained before and after irradiations, and optical-thermal modelling was performed on two irradiation cases. Time-resolved optical coherence tomography and still images were compared with predictions of temperature rise and damage using Monte Carlo and finite difference techniques. In general, predicted damage agreed with the actual blood vessel and surrounding tissue coagulation seen in images. However, limitations of current optical-thermal models were identified, such as the inability to model the dynamic changes in blood vessel diameter that were seen in the optical coherence tomography images.

A perspective on laser lithotripsy: the fragmentation processes.

This paper describes in simple terms the physics of laser-calculus interactions and introduces a method with which physicians can understand or evaluate the application of any new laser technique for use in lithotripsy or other medical fields. Tissue optical properties and laser parameters govern the mechanism(s) of fragmentation of urinary or biliary calculi. Laser pulse energies for clinical lithotripsy range from Q0 = 20 mJ to 2 J for short-pulsed lasers to long-pulsed lasers, respectively. Lasers with short pulse durations (i.e., less than a few microseconds) fragment calculi by means of shockwaves following optical breakdown and plasma expansion of ionized water or calculus compositions or by cavitation collapse, thus manifesting a photoacoustical effect. Laser-tissue interactions involving dominant photomechanical or photoacoustical effects are usually stress confined. Long-pulsed lasers (i.e., >100 microsec), on the other hand, generate minimal acoustic waves, and calculi are fragmented by temperatures beyond the thresholds for vaporization of calculus constituents, melting, or chemical decomposition.

Pulsed laser-induced thermal damage in whole blood.

An investigation of the effects of laser irradiation with a wavelength of 532 nm and pulse duration of 10 ms on whole blood was performed in vitro. Threshold radiant exposures for coagulation were quantified and transient radiometric temperatures were measured. The progression of effects with increasing radiant exposure--from evaporation to coagulation-induced light scattering to aggregated coagulum formation to ablation--is described. Results indicate that coagulation and ablation occur at temperatures significantly in excess of those assumed in previous theoretical studies. An Arrhenius rate process analysis based on hemoglobin data indicates good agreement with experimental results.

Dynamics of pulsed holmium:YAG laser photocoagulation of albumen.

The pulsed holmium:YAG laser (lambda = 2.12 microm, tau(p) = 250 micros) has been investigated as a method for inducing localized coagulation for medical procedures, yet the dynamics of this process are not well understood. In this study, photocoagulation of albumen (egg white) was analysed experimentally and results compared with optical-thermal simulations to investigate a rate process approach to thermal damage and the role of heat conduction and dynamic changes in absorption. The coagulation threshold was determined using probit analysis, and coagulum dynamics were documented with fast flash photography. The nonlinear computational model, which included a Beer's law optical component, a finite difference heat transfer component and an Arrhenius equation-based damage calculation, was verified against data from the literature. Moderate discrepancies between simulation results and our experimental data probably resulted from the use of a laser beam with an irregular spatial profile. This profile produced a lower than expected coagulation threshold and an irregular damage distribution within a millisecond after laser onset. After 1 ms, heat conduction led to smoothing of the coagulum. Simulations indicated that dynamic changes in absorption led to a reduction in surface temperatures. The Arrhenius equation was shown to be effective for simulating transient albumen coagulation during pulsed holmium:YAG laser irradiation. Greater understanding of pulsed laser-tissue interactions may lead to improved treatment outcome and optimization of laser parameters for a variety of medical procedures.

Bioheat transfer analysis of cryogen spray cooling during laser treatment of port wine stains.

BACKGROUND AND OBJECTIVE: The thermal response of port wine stain (PWS) skin to a combined treatment of pulsed laser irradiation and cryogen spray cooling (CSC) was analyzed through a series of simulations performed with a novel optical-thermal model that incorporates realistic tissue morphology. STUDY DESIGN/MATERIALS AND METHODS: The model consisted of (1) a three-dimensional reconstruction of a PWS biopsy, (2) a Monte Carlo optical model, (3) a finite difference heat transfer model, and (4) an Arrhenius thermal damage calculation. Simulations were performed for laser pulses of 0.5, 2, and 10 ms and a wavelength of 585 nm. Simulated cryogen precooling spurts had durations of 0, 20, or 60 ms and terminated at laser onset. Continuous spray cooling, which commenced 60 ms before laser onset and continued through the heating and relaxation phases, was also investigated. RESULTS: The predicted response to CSC included maximal pre-irradiation temperature reductions of 27 degrees C at the superficial surface and 12 degrees C at the dermoepidermal junction. For shorter laser pulses (0.5, 2 ms), precooling significantly reduced temperatures in superficial regions, yet did not effect superficial vessel coagulation. Continuous cooling was required to reduce significantly thermal effects for the 10-ms laser pulse. CONCLUSIONS: For the PWS morphology and treatment parameters studied, optimal damage distributions were obtained for a 2-ms laser pulse with a 60-ms precooling spurt. Epidermal and vascular morphology as well as laser pulse duration should be taken into account when planning CSC/laser treatment of PWS. Our novel, realistic-morphology modeling technique has significant potential as a tool for optimizing PWS treatment parameters.

Holmium:YAG laser lithotripsy: A dominant photothermal ablative mechanism with chemical decomposition of urinary calculi.

BACKGROUND AND OBJECTIVE: Evidence is presented that the fragmentation process of long-pulse Holmium:YAG (Ho:YAG) lithotripsy is governed by photothermal decomposition of the calculi rather than photomechanical or photoacoustical mechanisms as is widely thought. The clinical Ho:YAG laser lithotriptor (2.12 microm, 250 micros) operates in the free-running mode, producing pulse durations much longer than the time required for a sound wave to propagate beyond the optical penetration depth of this wavelength in water. Hence, it is unlikely that shock waves are produced during bubble formation. In addition, the vapor bubble induced by this laser is not spherical. Thus the magnitude of the pressure wave produced at cavitation collapse does not contribute significantly to lithotripsy. STUDY DESIGN/MATERIALS AND METHODS: A fast-flash photography setup was used to capture the dynamics of urinary calculus fragmentation at various delay times following the onset of the Ho:YAG laser pulse. These images were concurrently correlated with pressure measurements obtained with a piezoelectric polyvinylidene-fluoride needle-hydrophone. Stone mass-loss measurements for ablation of urinary calculi (1) in air (dehydrated and hydrated) and in water, and (2) at pre-cooled and at room temperatures were compared. Chemical and composition analyses were performed on the ablation products of several types of Ho:YAG laser irradiated urinary calculi, including calcium oxalate monohydrate (COM), calcium hydrogen phosphate dihydrate (CHPD), magnesium ammonium phosphate hexahydrate (MAPH), cystine, and uric acid calculi. RESULTS: When the optical fiber was placed perpendicularly in contact with the surface of the target, fast-flash photography provided visual evidence that ablation occurred approximately 50 micros after the initiation of the Ho:YAG laser pulse (250-350 micros duration; 375-400 mJ per pulse), long before the collapse of the cavitation bubble. The measured peak acoustical pressure upon cavitation collapse was negligible (< 2 bars), indicating that photomechanical forces were not responsible for the observed fragmentation process. When the fiber was placed in parallel to the calculus surface, the pressure peaks occurring at the collapse of the cavitation were on the order of 20 bars, but no fragmentation occurred. Regardless of fiber orientation, no shock waves were recorded at the beginning of bubble formation. Ablation of COM calculi (a total of 150 J; 0.5 J per pulse at an 8-Hz repetition rate) revealed different Ho:YAG efficiencies for dehydrated calculus, hydrated calculus, and submerged calculus. COM and cystine calculi, pre-cooled at -80 degrees C and then placed in water, yielded lower mass-loss during ablation (20 J, 1.0 J per pulse) compared to the mass-loss of calculi at room temperature. Chemical analyses of the ablated calculi revealed products resulting from thermal decomposition. Calcium carbonate was found in samples composed of COM calculi; calcium pyrophosphate was found in CHPD samples; free sulfur and cysteine were discovered in samples composed of cystine samples; and cyanide was found in samples of uric acid calculi. CONCLUSION: These experimental results provide convincing evidence that long-pulse Ho:YAG laser lithotripsy causes chemical decomposition of urinary calculi as a consequence of a dominant photothermal mechanism.

Holmium: YAG lithotripsy: photothermal mechanism.

OBJECTIVE: A series of experiments were conducted to test the hypothesis that the mechanism of holmium:YAG lithotripsy is photothermal. METHODS AND RESULTS: To show that holmium:YAG lithotripsy requires direct absorption of optical energy, stone loss was compared for 150 J Ho:YAG lithotripsy of calcium oxalate monohydrate (COM) stones for hydrated stones irradiated in water (17+/-3 mg) and hydrated stones irradiated in air (25+/-9 mg) v dehydrated stones irradiated in air (40+/-12 mg) (P < 0.001). To show that Ho:YAG lithotripsy occurs prior to vapor bubble collapse, the dynamics of lithotripsy in water and vapor bubble formation were documented with video flash photography. Holmium:YAG lithotripsy began at 60 microsec, prior to vapor bubble collapse. To show that Ho:YAG lithotripsy is fundamentally related to stone temperature, cystine, and COM mass loss was compared for stones initially at room temperature (approximately 23 degrees C) v frozen stones ablated within 2 minutes after removal from the freezer. Cystine and COM mass losses were greater for stones starting at room temperature than cold (P < or = 0.05). To show that Ho:YAG lithotripsy involves a thermochemical reaction, composition analysis was done before and after lithotripsy. Postlithotripsy, COM yielded calcium carbonate; cystine yielded cysteine and free sulfur; calcium hydrogen phosphate dihydrate yielded calcium pyrophosphate; magnesium ammonium phosphate yielded ammonium carbonate and magnesium carbonate; and uric acid yielded cyanide. To show that Ho:YAG lithotripsy does not create significant shockwaves, pressure transients were measured during lithotripsy using needle hydrophones. Peak pressures were <2 bars. CONCLUSION: The primary mechanism of Ho:YAG lithotripsy is photothermal. There are no significant photoacoustic effects.

Simultaneous irradiation and imaging of blood vessels during pulsed laser delivery.

BACKGROUND AND OBJECTIVE: Simultaneous irradiation and viewing of 10-120 microm cutaneous blood vessels were performed to investigate the effects of 2-micros 577-nm dye laser pulses. STUDY DESIGN/MATERIALS AND METHODS: A modified scanning laser confocal microscope recorded vessel response to different radiant exposures (J/cm2). Probit analysis determined the 50% probability ("threshold") radiant exposure necessary to cause embolized or partly occluding coagula, coagula causing complete blood flow stoppage, and hemorrhage. RESULTS: A statistically significant difference in the threshold radiant exposure existed for each damage category for blood vessels 10-30 microm in diameter, but not for larger vessels. For vessels over 60 microm, complete flow stoppage was unattainable; increasing laser pulse energy produced hemorrhage. In larger vessels, coagula often were attached to the superficial vessel wall while blood flowed underneath. Monte Carlo optical and finite difference thermal modeling confirmed experimental results. CONCLUSION: These results provide insight into the role of pulse duration and vessel diameter in the outcome of pulsed dye laser irradiation.

Modeling laser treatment of port wine stains with a computer-reconstructed biopsy.

BACKGROUND AND OBJECTIVE: The efficacy of laser treatment of port wine stains (PWS) has been shown to be highly dependent on patient-specific vasculature. The effect of tissue structure on optical and thermal mechanisms was investigated for different pulse durations by using a novel theoretical model that incorporates tissue morphology reconstructed tomographically from a PWS biopsy. STUDY DESIGN/MATERIALS AND METHODS: An optical-thermal numerical model capable of simulating arbitrarily complex, three-dimensional tissue geometries was developed. The model is comprised of (1) a voxel-based Monte Carlo optical model, (2) a finite difference thermal model, and (3) an Arrhenius rate process calculation to predict the distribution of thermal damage. Simulations based on previous computer-based reconstruction of a series of 6 microm sections from a PWS biopsy were performed for laser pulse durations (taup) of 0.5, 5.0, and 10.0 ms at a wavelength of 585 nm. RESULTS: Energy deposition rate in the blood vessels was primarily a function of vessel depth in skin, although shading effects were evident. Thermal confinement and selectivity of damage were seen to be inversely proportional to pulse duration. The model predicted blood-specific damage for taup = 0.5 ms, vascular and perivascular damage for taup = 5 ms, and widespread damage in superficial regions for taup = 10 ms. The effect of energy deposition in the epidermis was most pronounced for longer pulse durations, resulting in increased temperature and extent of damage. CONCLUSION: Pulse durations between 0.5 and 5 ms are likely optimal for the PWS analyzed. The incorporation of a tomographically reconstructed PWS biopsy into an optical-thermal model represents a significant advance in numerical modeling of laser-tissue interaction.

Laser fluence for permanent damage of cutaneous blood vessels.

Treatment of vascular disorders may be improved by a more thorough understanding of laser-blood vessel interaction. In this study, the probability of permanent damage to a given type and size of blood vessel was determined as a function of fluence at the top (superficial edge) of the vessel lumen. A 532 nm wavelength, 10 ms pulse duration, 3 mm spot size laser was used to perform approximately 250 irradiations of subdermal blood vessels in the hamster dorsal skin flap preparation. The radiant exposure required for a 50% probability of permanent damage was calculated using a probit analysis of experimental results. Threshold radiant exposure increased with larger blood vessel diameters and was greater for arterioles than venules. Monte Carlo modeling of a typical blood vessel geometry revealed that fluence at the top of the blood vessel lumen was amplified by a factor of approximately 2.4 over tissue surface radiant exposure, due to light scattering in the tissue and internal reflection at the skin-air interfaces.

Laser-tissue interaction during transmyocardial laser revascularization.

BACKGROUND: The clinical procedure known as transmyocardial revascularization has recently seen its renaissance. Despite the promising preliminary clinical results, the associated mechanisms are subject to much discussion. This study is an attempt to unravel the basics of the interaction between 800-W CO2 laser radiation and biological tissue. METHODS: Time-resolved flash photography was used to visualize the laser-induced channel formation in water and in vitro porcine myocardium. In addition, laser-induced pressures were measured. Light microscopy and birefringence microscopy were used to assess the histologic characteristics of laser-induced thermal damage. RESULTS: The channel depth increased logarithmically with time (ie, with pulse duration) in water and porcine myocardium. Pressure measurements showed the occurrence of numerous small transients during the laser pulse, which corresponded with channel formation, as well as local and partial channel collapse during the laser pulse. Twenty millimeters of myocardium was perforated in 25 ms. Increasing the pulse duration had a small effect on the maximum transversable thickness, but histologic analysis showed that thermal damage around the crater increased with increasing pulse duration. CONCLUSIONS: Several basic aspects of the interaction of high-power CO2 laser radiation with myocardial tissue and tissue phantoms were studied in vitro. Although the goal of this study was not to unravel the mechanisms responsible for the beneficial effects of transmyocardial revascularization, it provided important information on the process of channel formation and collapse and tissue damage.