Vascular tissue fusion by lasers is performed by directing a low energy beam at the apposed edges of the repair. The tissues are approximated with stay sutures or non-reflective instruments and laser energy is passed back-and-forth over the anastomotic site until fusion is achieved. Vessel welding is apparent to the trained eye, as is nonunion caused by inadequate energy delivery. Conversely, excessive energy delivery results in obvious tissue coagulation or vaporization. Fiberoptic laser transmission and hand-eye coordination are adequate for repair or anastomosis of vessels with diameters greater than 3 mm, whereas magnification and precise mechanical control of the laser beam are necessary for microanastomoses of smaller vessels. The laser power (watts, W), and the amount of energy and time required (energy fluence or power density) vary according to the type of laser and the size of the vessels. Although laser repairs can be fashioned in time intervals equal to or slightly longer than those required for suture repairs, the optimum wavelengths and laser parameters for different types of seals are not yet established.

We have demonstrated that 11cNc, laws stimulate collagen synthesis both in human stun fibroblast cultures and hairless mice in vivo. Subscqucnt studies on pig skin have also idcntificd the mechanism of the collagen stimulation. Both type 1 and typc 111 procolagcn mRNA, levels were markcdly elevated at day 17 and 26 in wounds treated by laser. Furthermore, typo ill procollagen was cicvatcd in carly stages of wound healing, at day 10, confirming the notion that typc 111 collagen accumulation precedes that of typc 1 in wound healing processes. (for summary,please see table and references below)

Quantitative dosimetry in clinical laser treatment requires information on propagation of light in tissue related to the optical properties of the tissue. This involves the solution of the integro-differential equation of radiative transfer, as well as experimental methods to determine the optical properties involved. These activities are summarized under the name tissue optics. This paper reviews the current status of tissue optics, distinguishing between the cases of: dominant absorption, dominant scattering, and scattering about equal to absorption. Most tissues or phantom tissues of which the optical properties are available show strongly forward scattering. The absorption and scattering data of skin layers show that in many cases scattering is more important than absorption. Under such circumstances, solutions to the transport equation under laser irradiation conditions are currently lacking.

The central theme in developing models of light propagation in tissues is the accurate prediction of the spatial distribution of the photon or energy fluence. Diffusion theory has been widely used and applies mainly far from sources and tissue boundaries in highly scattering media. By contrast, Monte Carlo simulations are most successful in describing the behavior of the fluence near sources and boundaries, and can incorporate any absorption and scattering conditions. Thus, a hybrid model combining these strengths may provide an optimal approach to calculating the light fluence distributions in tissue. The elements of such a hybrid model are described and evaluated for different external light beam and interstitial optical fiber source geometries, using optical absorption and scattering coefficients which are typical of soft tissues in the red part of the visible spectrum.

The optical properties of human aorta were measured during low power argon laser irradiation (~100 mW/mm2) . The delta-Eddington optical model was iterated to determine the optical properties. The results indicated that the transport albedo was nearly constant (-0.96) until the onset of tissue charring, after which it decreased quickly. The optical depth gradually declined (after an abrupt initial increase) until tissue charring when it dropped sharply. The anisotropy dropped initially and increased linearly with time of exposure.

Continuous wave (cw) and repetitively pulsed (rp) hydrogen fluoride (HF) and deuterium fluoride (DF) chemical laser interactions with human cardiovascular tissues have been studied in order to understand ablation phenomenology, effects, and mechanisms under well characterized laser irradiation conditions. CW HF/DF experiments were performed on normal and atherosclerotic tissues over a broad irradiance range (3-20 kW/cm2) to determine thermal coupling coefficients and effective enthalpies of ablation as a function of laser wavelength and tissue type. Similar experiments were completed using a rp HF chemical laser with a submicrosecond pulse duration. Plume probing experiments were also performed to characterize particle formation (i.e., spallation) generated by rp laser ablation. All of the data are used to consider the physical and chemical processes associated with thermal coupling phenomenology and thermochemical pyrolysis and ablation of cardiovascular tissues irradiated by infrared lasers.

We have developed an opto-thermal model for the interaction of laser light and the tissue of arterial walls, and have checked its validity with animal experiments. The mathematical model consists of a laser diffusing tip positioned intraluminally in a cylindrical artery, in which the diffused laser light is incident on a blood/tissue interface at a distance from the tip. Experimental values for the optical scattering, absorption, transmission, and reflection in biological media are taken from the literature. A temperature profile throughout the interface is obtained by considering the optical interaction and the thermal conduction and convection of the blood and tissue. For experimental verification, a diffusing tip was inserted in in vivo canine arteries and the temperature profile was measured by a thermocouple array. The rate of blood flow around the diffusing tip was varied by limiting the volume of blood; this simulated degrees of occlusion to determine the influence of blood flow on heat transport. The measured temperature profile compared favorably to the theoretical results. The theoretical model will be useful in predicting the depth of tissue ablation and extent of normal tissue damage for laser angioplasty treatment of atherosclerosis.

The interaction of CW CO₂ and Nd:YAG laser light with animal tissue produces large quantities of smoke which has been of concern to laser surgeons. Analysis of the chemical constituents present in smoke produced by CO₂ and Nd:YAG laser interaction with samples of beef liver were very similar. A significant quantity of benzene and lesser quantities of polycyclic aromatic hydrocarbons (PAH's) were found to be present. Since these chemicals are classified as carcinogens, adequate smoke exhaust devices should be used during all laser surgical procedures for the protection of patients and operating room personnel.

A quantitative treatment of the ultraviolet laser ablation of corneal tissue has been attempted by following the time-dependent approach that has been successful in modelling the ablative photodecomposition of organic polymers.

The special properties of far-uv light sources include tissue removal without major temperature rise and preparation of a surface well suited for cell locomotion and adherence. We have evaluated the use of the 193 nm excimer laser for large area surface ablation of the cornea. We have found that tissue removal can be accomplished with successful wound healing and corneal function by selecting the proper laser parameters. Available data suggest that an ablative excimer laser of uniform and predictable beam power can supplant existing procedures for treating some corneal dystrophies, and preparing graft beds. The natural healing properties of the cornea aid in such procedures yet may make minor refractive change difficult to accomplish.

The corneas of pigs' eyes were irradiated with ablative levels of 193, 248, and 308 nm and the spectra of the produced light recorded. In all cases there was an appreciable amount of uv light produced in the 300-400 nm band. The 193 nm irradiation exhibited a threshold at 0.5 J/cm²; markedly different spectra were produced below and above that threshold.

The ablation threshold of bovine lenses was determined for excimer laser radiatiF at 308 nanreters. The ablation th5eshold for bovine lenses was approximately 0.6J/cm +/-0.1J/cm , for cortex and 1J/cm for nucleus. The threshold for bovine nucleus was higher than the threshold for cortex and difference was statistically significant at the 0.05 level. The relatively low ablation threshold for bovine lenses demonstrates the potential effectiveness of excimer laser radiation at 308 nm for cataract surgery. An experimental prototype has been developed and results of its application demonstrated. Further experiments to demonstrate safety for the retina and adjacent ocular structures are necessary because of the well known hazards of ultraviolet radiation. The potential of theleymir laser for keratorefractive surgery is currently under intensive investigation. In preliminary studies the ablation behavior of bovine lenses was investigated. The objective of this study was to quantify ablation rates as the first step in determining the specification for a laser system which would be practical in the clinical setting. Although excimer laser systems are available at 193 nm (ArF), 248 (KrF) and 351 (xeF) we selected 308 nm because of the availability of fiberoptics for the transmission of 308 nm as well as the known absorbance of human lenses in the 280 nm region.

Freshly enucleated bovine globes were subjected to either knife incisions or excimer laser excisions and the corneal thickness was measured over a three-hour period. The corneal thickness increased a maximum of 10 percent over the knife incisions and exhibited significant edema. The corneal thickness increased a maximum of 1 percent over the excimer laser excisions and exhibited minimal edema. Histologic sections demonstrated an electron dense pseudomembrane over the excimer laser excisions. On the basis of these experiments, we concluded that the pseudomembrane sealed stromal lamellae and functioned as an effective osmotic barrier to prevent the leakage of stromal free water.

We describe an electro-optical apparatus capable of delivering a homogenized, intensity-contoured 193 nm wavelength laser beam to the anterior surface of the cornea. Beam fluence is adequate to produce controlled ablation over areas as large as 7 mm diameter. Preliminary experimental results demonstrating recontouring of the corneal surface as a means of correcting myopia are presented. Means to be used for reducing hyperopia and astigmatism also are described.

We report on ablation and recontouring of the anterior surface of human and animal corneas using an excimer laser beam delivery system. Experimental data on ablation rates, resultant surface smoothness, epithelium regrowth over ablated surfaces and clinical appearance of ablated corneas with time will be shown. Also discussed are some effects of UV beam quality on these topics.

The absorbed dose rate in tissues can be calculated knowing the absorptivity, radiant energy fluence rate, and concentration of the photosensitizer. The propagation of visible light in malignant and nonmalignant tissues has been calculated by the discrete ordinates method for solving the Boltzmann transport equation, using absorption and scattering coefficients derived from measurements in tissues. A photodetector with isotropically responding fiberoptic probe imbedded in the tissue has been calibrated and used to measure the energy fluence rate in vivo. The effect of absorption in blood and in the photosensitizer dihematoporphyrin ether (DHE) has been investigated in a scattering medium or phantom. The generation and propagation of long wavelength fluorescence from absorption in DHE and in endogenous fluors is important in an apparatus designed to measure the concentration of DHE in tissues.

A non-invasive isotropic fibre optic probe has been developed and used to determine the penetration depth of 630nm light in tumours of rats and a human patient during interstitial photodynamic therapy. The mean penetration depth of the light and standard error of the mean measured was 1.62 ± 0.18mm for a series of eight animal tumours and 1.99 ± 0.51mm in three human tumour nodules. The apparent penetration depth as observed from the area of illuminated skin at a distance from the tumour was also measured and its relevance to the light dosimetry discussed.

A two-component system of instrumentation and methods, IFB and RFP, when used in combination employing hematoporphyrin derivates, DHE, had highly satisfactory sensitivity (95%) and specificity (100%) for localizing carcinoma in situ lesions in the bronchi of individuals with early stage lung cancer, having a normal chest x-ray and detected by a positive sputum cytology test. The more detailed mapping of additional subjects may increase the specificity of RFP (Ratioing Fluorometer Probe) by itself to an adequate level. Digital computer subs traction of background antofluorescence may increase contrast to enhance the specificity of IFB (Imaging Fluorescence Bronchoscopy).

Metallopurpurins, metalloderivatives of a group of new photosensitizers called purpurins, have previously been reported to be excellent photosensitizers for the photodynamic treatment of experimental transplantable bladder tumors. Work in our laboratory has demonstrated that a dose of 1.0 mg/kg, of the metallopurpurin Sn etiopurpurin (II) dichloride, SnET2, is effective in producing significant tumor regression and cure in an experimental transplantable bladder tumor'. To confirm these findings a second tumor model using the transplantable R3327-AT prostatic adenocarcinoma was examined. In this model 1.0 mg/kg of SnET2 was ineffective in causing tumor regression. At 2.5 mg/kg there was obvious tumor regression although the results did not reach statistical significance. However, at this dose, 2/5 animals were free of tumor when examined histologically twelve days after treatment. In a set of related experiments blood flow measure-ments to this tumor were made using the radioactive microsphere technique. As with other photosensitizers, blood flow was reduced using metallopurpurin-PDT. In order to further establish the photodynamic activity of this drug, spontaneous canine tumors were treated with varying doses of light and drug. All animals tolerated the drug well. A photodynamic effect was apparent in all treated animals. These studies suggest that the netallopurpurin SnET2 may be an alter-native to the currently available drugs used for PDT.

The generation of strong oxidizing and reducing equivalents during tne photoexcitation process is very important to solar energy conversion, phototherapy of cancer, and several oasic processes in biochemical reactions. While most photochemical reactions involving porpnyrins involve the long-lived singlet and triplet states, it has been shown that photochemical reactions can pe catalyzed by iron (III) porphyrins which have a very short excited-state lifetime. It is known that in the presence of small amounts of pyridine photocatalytic oxidation of olefins is promoted at wavelengths shorter than 500 nm. We nave investigated the oxygen-bridged dimeric iron (III) tetraphenylporpnyrin (TPP) pnotoexcitation on the picosecond time scale. The excited states were generated with 530 or 355 nm, 25 psec pulses, aria probed uy time-delayed continuum from the same pulse. We have observed an initial state characterized uy oleacning of the original Soret at 405 and Q at 572 nm during the passage of the excitation pulse. A new Soret at 42u appears and continues to grow in intensity while shifting to 418 nm during tne first 10U psec. Tne Q banu bleaching at 572 does not change during this time. After 100 psec the spectrum decays to the initial state in 200-400 psec. The kinetics and spectra were independent of excitation wavelength. There was no difference between pyridine and benzene as solvents. No irreversiole changes were ooserved. Tne final spectra (100 psec) are compatible with the disproportionation of the starting dimer into tne Fe (II) and Fe (IV) = 0 TPP monomers, generation of a porphyrin-centered radical species, or the simple pnotodissociation into an ion-pair. The absorbance increases over the 600 - 700 nm range indicates that mucn of tne initial photoproduct is a porphrincentered radical.

Several relevant physical parameters, such as superficial blood perfusion, temperature rise and tumor fluorescence characteristics, were monitored in an attempt to perform well-controlled photodynamic thera-py (PDT) on several human malignant tumors. DHE (Photofrin TT) was used as a photosensitizer at a concentration of 2 mg/kg b.w. administered i.v. 48-120 hours before treatment. 630 nm radiation from a CW dye laser, normally at an energy dose of 60 J/c10, at a dose rate well below the hyper-thermal region was delivered to seven 1-4 mm thick basal cell carcinoma lesions. PDT and near-infrared light-induced hyperthermia were performed simultaneously on six 5- 10 mm thick lesions of recurrent breast cancer in another patient. A filtered slide projector running at a power of about 200 mW/c1.0 with radiation above 665 nm was used for the light-induced hyperthermia. All the tumors were eradicated. PDT parameters and tissue temperature recordings were used as input data for an analytical PDT/hyperthermia model. The measured parameters have to be supplemented with assumed values for several other parameters. Although highly qualitative the model provides some interesting insight into the relative importance of PDT and hyperthermia.

Laser induced fluorescence of human tissue has been discussed as a tool for control of laser application in surgery for some years. Differences in tissue composition create different spectra, thus leading to a unique identification. We have demonstrated that this method can be combined with the photoablative effect of excimer laser radiation. The irradiated and ablated material fluoresces in a characteristic manner, which can be used to control the further action of the excimer laser. The analysis of the spectrum is performed within 30 ms by computer thus allowing repetition rates of 30 shots per sec corresponding to a cutting speed of 0.5 mm per sec. A Combination of both, recognition of fluorescence spectra and subsequent computer-controlled laser emission leads the way to computer guided surgery (CGS) with resolution in the pm range.

The most attractive alternative to flashlamp pumping of solid state lasers is the diode laser. In the past two decades numerous laboratory devices have been assembled which incorporated single diode lasers, small laser diode arrays or LED's for pumping of Nd:YAG, Nd:glass and a host of other Nd lasers. The low power output, low packaging density, and extremely high cost of diode lasers prevented any serious applications for laser pumping in the past. The reason for the continued interest in this area stems from the potential dramatic increase in system efficiency and component lifetime, and reduction of thermal load of the solid-state laser material. The latter not only will reduce thereto-optic effects and therefore lead to better beam quality but also will enable an increase in pulse repetition frequency. The attractive operating parameters combined with low voltage operation and the compactness of an all solid-state laser system have a potential high payoff. The high pumping efficiency compared to flashlamps stems from the good spectral match between the laser diode emission and the rare earth activator absorption bands. A significant advantage of laser diode pumping compared to arc lamps is system lifetime and reliability. Laser diode arrays have exhibited lifetimes on the order of 10,000 hours in cw operation and 109 shots in the pulsed mode. Flashlamp life is on the order of 107 shots, and about 200 hours for cw operation. In addition, the high pump flux combined with a substantial UV content in lamp pumped systems causes material degradation in the pump cavity and in the coolant. Such problems are virtually eliminated with laser diode pump sources. The absence of high voltage pulses, high temperatures and UV radiation encountered with arc lamps leads to much more benign operating features for solid state laser systems employing laser diode pumps. Laser diode technology dates back to 1962 when laser action in GaAs diodes was first demonstrated. However, it took a decade to transform a fragile device requiring cryogenic temperatures into one capable of emitting a continuous beam at room temperature. In the last few years the rapid progress in fabricating diode lasers has increased interest in developing diode pumped solid state lasers. Device fabrication improvements such as double hetero-structures, multiple quantum well structures, monolithic phased arrays and multiple stripe lasers which were made possible by improved manufacturing technologies have produced a dramatic reduction of threshold current and increases of slope efficiency, lifetime and output power.

The ablative removal of vascular tissue and accompanying acoustic transients have been studied in a liquid environment using KrF and XeCl excimer lasers and a frequency doubled YAG laser.

Neodymium-yttrium aluminum garnet (Nd-YAG) lasers are finding increasing appli-cations in laser surgery of vascular tissues because of their good hemostatic properties. Heat penetration is deeper than the carbon dioxide laser, because the 1064 nm Nd-YAG emission is located in a "window" between the strong absorptions of oxyhemoglobin and tissue water. The basic physics of laser-tissue interactions suggests that damage to peripheral tissues can be confined by using sufficiently short pulses. In continuous mode (CW) operation, heat flow driven by temperature gradients leads to tissue heating external to the optical absorption profile. When the energy is delivered in pulses, however, conductive heat flow is minimized if the pulse duration (tn) is shorter than the thermal relaxation time constant (t ). Pulsed operation should be especially useful for the Nd-YAG laser, where the 1/e optical penetration depth (5) at 1064 nm is the order of 0.3 to 0.5 cm. Taking t" =2/2a, where a is the thermal diffusivity (the order of 0.001 cm2/s for tissues), typical values of t* for heat conduction are the order of 1-2 min. Heat removal by blood flow augments thermal conduction in vascularized tissues. The rate of this process is characterized by 1/Q, where Q is the volume blood perfusion rate. Values 1/Q range from the order of 15 s for human kidney and thyroid to more than 15 min for muscle.1 Accordingly, heat removal by conduction and blood flow during the pulse duration can be neglected for many tissues exposed to Nd-YAG laser pulses. This paper describes an analytical solution to the two dimensional laser bioheat equation applicable to pulsed operation. The theory was applied to measur-ements on potato tuber heated by low-power pulses from a clinical Nd-YAG laser. The initial temperature elevations are in satisfactory agreement with the analysis, but thermal relaxation was faster than predicted. The suggested explanation for the discrepancy involves evaporative heat transfer to internal water.

Under the laser continuous irradiation one can observe on tissues and organs a whole complex of dystrophic processes including the coagulation necrosis as well as impairements in hemo- and microcirculation. The peculiarity of the inflammatory reaction in the healing process in laser wounds lies in an absence of demarcation leucocytic infiltration and lack of edema on a border of intact tissues and those with thermal necrosis; the healing process is characterised as well as with early proliferative phase. The main role in the reparative process belongs to cells of mononuclear phagocytic system ( macrophages ), wich make the reparative process like an aseptic productive inflammation.

Scattered clinical reports suggest that low power (LP) laser irradiation may induce a biostimulation of cell growth and/or metabolism, especially relating to healing processes. On the other hand, few basic science, in-depth reports relating to such effects have appeared. Hence, a mechanism of action of LP laser irradiation on cells is unknown. A systematic evaluation has been undertaken in order to define more clearly the experimental conditions for producing biostimulation and to provide some basis for action of LP laser irradiation. A Ga-Al-As diode laser emitting in the near infrared (904 nm) was used to effectively penetrate cells at energy levels that are in the mW range. The LP laser was pulsed at 50 ns and 200 hz. Human fibroblasts growing in culture served as the experimental model. Since LP laser irradiation has been reported to stimulate collagen synthesis, we first investigated the induction of hydroxyproline formation, a collagen precursor. This biosynthetic process could be increased two-fold at a twice daily energy input of 4.5 mJ. With proline supplementation, hydroxylation increased eight-fold. At approximately the same energy level and irradiation conditions, cells also had a three-fold increased uptake of ascorbic acid, a required cofactor for hydroxylation of proline. These findings considered together with published biochemical studies of collagen suggest that higher levels of intracellular ascorbate catalyze hydroxylation of proline and, concomitantly, induce collagen formation. Other data relevant to cell morphology and viability suggest that the LP laser irradiation had no effect on cell proliferation but rather was a transient effect on intermediary metabolism manifested as changes that may be unique to collagen.

We report preliminary experimental trials using an excimer laser at 193 nm (ArF*) in the preparation of peripheral nerves prior to repair.