We owe the development of the free electron laser (FEL) to Dr. John M.J. Madey, formerly of Stanford University, and now at Duke University. In the early years of the research that lead ultimately to the device that actually produced coherent light, Dr. Madey had to work diligently to procure adequate funding for his FEL project. Sometimes it is much more difficult to find the appropriate funding source then it is to actually perform the research. After working with various basic research organizations, the Office of Naval Research, the Army Research Organization, the Air Force Office of Scientific Research, and others, to develop and test the basic scientific principles of the FEL, Dr. Madey looked to the future of the device. The FEL is indeed one of the principal defensive directed energy weapons under development in the Strategic Defense Initiative (SDI). However, Dr. Madey felt that the FEL could and should be used in the medical arena. The unique capabilities of the FEL certainly lend themselves to enhancing the practice of medicine which already uses lasers in the treatment of disease and in surgery. Dr. Madey and several physicians who also felt that the FEL belonged at least in medical research traveled to Washington, D.C., to visit the Congress and acquaint them with the potential of the FEL.

The LTH-9 program was set up in 1985 to study the potential effectiveness of repetitively pulsed lasers that might be used as weapons to attack a variety of strategic targets. As the name (L)ethality and (T)arget (H)ardening implies, the study is twofold, ranging over both the potential variations in pulsed laser weapon characteristics and over a wide range of possibilities for materials and techniques that might serve as a defense against those same laser weapons. The wavetrain characteristics of the lasers under consideratidn are shown in Figure 1. They cover RF LINAC driven (F)ree (E)lectron (L)asers, Induction LINAC driven FELs and Excimer lasers.

Laser-tissue interactions involve (1) the physical mechanism of interaction [photothermal, photochemical, photomechanical], (2) the biological level of interaction [tissue/organ, cellular, organellar], and (3) the time course of the interaction [immediate physical effect, short-term biological response, long-term healing and structure/function].

The Advanced Damage Model (ADAM) has been developed for simulating laser effects on aerospace composite materials, as well as several other classes of materials. Detailed local conservation of mass and energy are used to predict pressure and temperature profiles and material blow-off. The ADAM composite material model, with modifications presented here, can be used to model tissue ablation with laser surgery applications.

Detailed calculations of the thermal response and ablation of biological tissue exposed to 10p laser radiation are presented. For most of the calculations shown, tissue response was modeled using generalized computer codes that were originally developed to model the laser-induced response of a variety of non-biological materials. The models are applicable at any wavelength for which the absorption cross section in the tissue is large compared to the scattering cross section. In this initial study, soft tissue has been modeled as a single component material with thermal and optical properties very similar to that of water. The predominant phenomena treated are in-depth laser absorption, thermal conduction, and surface vaporization. In-depth thermal damage of tissue is calculated by incorporating into the codes a reaction for the thermal denaturation of tissue protein. Model calculations are presented for exposures ranging from low power CW exposures of a few watts per cm and exposure times of tens of seconds to single-pulse exposures with peak irradiances of several megawatts per cm2 and microsecond exposure durations. Where possible, model predictions are compared to available experimental data and the implications of the comparisons are discussed. Recommendations for future modeling improvements are also presented.

Assuming that the irradiance of the laser beam is much greater than the threshold for ablation, a simple expression is obtained for the depth of ablation crater as a function of incident fluence. It is expected to be valid even where mechanisms other than thermal dominate the ablation process. A high level of irradiance is necessary to avoid excessive heating of adjacent tissue by heat diffusion. Contrary to expectations based on non-ablative heating, short pulses are not necessarily more effective than longer pulses in minimizing heat diffusion to adjacent tissue. Peripheral heating can further be reduced by using a wavelength with high absorption (short penetration depth) in tissue. Under appropriate conditions of wavelength and irradiance, clean, "cold" cuts are possible with the thermal mechanism of ablation.

Techniques are described for modeling and analysis of composite materials exposed to laser radiation. The models consider pyrolysis of the organic resin matrix, convective transport of the gaseous pyrolysis products, and thermochemical ablation of the irradiated surface. Examples are provided of comparisons between measured materials response data and model predictions for exposures to both continuous wave (CW) and repetitively pulsed (RP) lasers.

Several new lasers that emit infrared laser radiation are being considered for surgical applications. In order to understand the irradiation and tissue parameters that control the infrared laser ablation process, three different, yet related, experiments were conducted. Ablation of guinea pig skin and bovine aorta, myocardium and liver using a TEA CO2 laser with a pulse duration of 2 μs was quantified by measuring the mass of tissue removed as a function of incident fluence per pulse. For per pulse fluences greater than 5 J/cm2 the ablation rate data are strongly dependent upon the mechanical strength of the tissue thus indicating a potential inadequacy of ablation models that do not consider tissue strength. The ablation of both soft and hard tissues using the normal-spiking-mode Er:YAG laser was quantified by measuring the number of pulses needed to perforate a measured thickness of tissue. The ablation of aorta and skin was more efficient than bone ablation. The ablation craters formed in skin and bone were the same shape as the incident laser beam, i.e. circular. In aorta, elliptical craters were formed at high fluence pulses; the long axis of the ellipse was always oriented perpendicular to the longitudinal axis of the aorta. Again, tissue mechanical properties were shown to be important. Er:YAG laser ablation dynamics were studied using flash photography and optical pump-probe techniques. The velocity of the plume front was found to be approximately Mach 4. It was also shown that each spike in the normal-spiking-mode pulse train was capable of ablating and rapidly ejecting tissue. The combined results of the three experiments indicate that removal of tissue by infrared laser radiation is an explosive process, the speed of which is determined in part by the mechanical strength of the tissue.

A comprehensive overview of the phenomenology associated with the interaction of intense laser beams with matter is presented. The beam is assumed to be incident on a solid or liquid target located within a transport medium. The discussion is first categorized by the type of this medium; namely, vacuum, gas, liquid, solid or particulate. Then the dependence of the interaction is further classified by the laser flux, pulselength, wavelength and the target properties. The various classes of behavior are discussed along with the conditions for their occurrence. Classes discussed include: slow bulk heating, transparent vapor from the target surface, secondary energy transport to the ablation surface, laser absorption at the critical surface, shock induced blowoff, photoelectric cross section dependence on temperature and density, laser supported combustion and detonation, contained vaporization and Mie scattering.

The interactions of laser radiation with animal tissue have become a vast field of study. The detailed chemical behavior of the photons with the tissue, while scientifically a fascinating topic for investigation, is difficult to study experimentally. We have used synthetic polymers and small molecules in the condensed phase as models for the study of non-linear photochemistry of all organic systems. While such extrapolations should always be used with caution, they have been helpful in suggesting new strategies for tissue ablation which may be adaptable to experiments in vivo.

Radiative transfer relates the macroscopic optical properties of a light scattering and absorbing material to microscopic parameters characterizing the individual particles, usually the absorption coefficient (k), total scattering coefficient (s), and mean cosine of the scattering angle (g). In densely scattering media the numerical values of these parameters must be calculated by fitting experimental quantities to theory, typically the transmission coefficient (T), reflection coefficient (R), and a third parameter such as the attenuation depth (3). Approximate radiative transfer theories have been employed to solve thT "inverse problem" for practical geometries. The recent review of Star t al. describes some mathematical models of current interest. The diffu ion approximation treats light propagation in a turbid medium as equiva-lent to particle diffusion. Comparisons of flux density distributions calculated with the diffusion approximation and Monte Carlo simulations suggest1 that the diffusion approximation is most accurate for k << s(1 - g) and low g. The parameter s' = s(1 g) is the reduced scattering coefficient. HoweyeE,3 recent measurements on animal tissues led to values of g close to unity. ' The purpose of the present work was to construct a diffuse optics spectro-photometer for measuring the optical properties of tissue layers over a wide spectral range and analyze the experimental results with two formulations of the one-dimensional diffusion approximation based on different angular scattering distributions or "phase functions".

Growing-absorption-site theories of the coupling of pulsed-laser energy into transparent targets are based on the absorption of the laser energy by microsites in the target and on laser-induced growth of these sites. The theories provide for the first time plausible explanations of the absorption mechanism and diverse experimental results, including the cutoff of the transmitted irradiance during the pulse, three absorption depths in different experiments, rep-pulse surface temperature, plasma generation, and shock generation.

The time spectrum of photons diffusely reflected from a turbid medium such as tissue following a short incident light pulse depends on the optical absorption and scattering properties of the medium. The results of diffusion model calculations are presented, together with preliminary experimental tests of the model using liquid phantoms to simulate tissue optical properties.

The purpose of this research was to gain better insight into the processes involved in ablation of biological media by continuous wave (CW) laser irradiation. In all experiments, a high-speed video camera and infrared camera were used simultaneously to observe and correlate the mechanical and thermal events associated with CW argon laser irradiation of various substances (porcine aortae, collagen fibers, and polyacrylamide control samples). Lateral temperature histories of rod specimens after ablation onset demonstrate the fact that the highest temperature achieved in each medium is located some distance along its axis rather than at the ablation front itself. Surface temperature recordings of tissue slabs describe the explosive nature of CW laser ablation of soft biological media, and threshold surface temperatures for argon CW laser ablation of various media were established. Fast video imaging reveals the dehydration, bubble formation, explosive events, subsequent boiling of remaining liquid, and eventual burning of the media corresponding to the thermal events recorded.

The use of lasers for ablation of biological tissues is becoming common place in many medical and surgical applications. However, the complete nature of the ablation mechanism is yet to be understood. Many authors have contributed to the theoretical understanding and modeling of the thermodynamics of ablation process by a laser. Some examples are [LANGERHOLC,1979; VAN GEMERT et al., 1985; ARMON and LAUFER, 1986; MCKENZIE, 1986; PARTOVI et al., 1987; RASTEGAR et al., 1988]. In a previous theoretical work the effect of optical properties on the ablation process has been shown [RASTEGAR et al., 19881)]. The effect of variation of power and exposure time over a constant fluence delivered on the tissue volume removed and the damage incurred on the surrounding tissue is shown in figure 1 [ RASTEGAR et al., 1988a]. This shows that for a given fluence, as power is increased and exposure duration is decreased the change on the volume removed is not significant while the damage to the surrounding tissue is significantly lessened. However these results, and those of the above references, are based on Fourier's law of heat conduction which is valid for relatively low power CW laser irradiation. The interaction of short pulsed high power lasers with tissues manifests a different behavior and application of Fourier's heat conduction law becomes questionable. In particular, in some experimental observations application of pulsed lasers has shown no apparent thermal damage to the surrounding tissue.

Studies were made of the propagation of both continuous wave, all line, argon ion (515,496,488,476 nm) and Nd:YAG (1060 nm) laser radiation from a spherically-tipped optical fiber through a blood-saline solution. It was found that the transmission of the argon ion laser light through the mixture increased as the power emitted from the tip increased. The transmission of Nd:YAG laser radiation through a similar mixture showed a reduction in transmission as power increased.

Treatment of tumors with hyperthermia with other agents can be effective under certain circumstances. However, often it is impossible to adequately treat tumors because of the difficulties in delivering uniform thermal doses throughout the entire tumor volume. This difficulty may be caused by many different factors including perfusion differences between tumor and normal tissue and differences in thermal properties between these tissues. With interstitial techniques however, some of these difficulties can be overcome. We have developed an interstitial laser system for delivery of heat to tissue. The system utilizes the output of an Nd:YAG laser directed into a fiberoptic probe which can be inserted into a tumor. Sapphire contact tips are used to deliver laser energy into the tissue. A series of animals were heated with a single probe. Temperature measured by small implanted thermocouples was controlled via a feedback circuit to a constant value over this interval. The control system was able to maintain temperature to within 0.3°C. This pilot study showed that this technique was suitable for interstitial hyperthermia. Continued work into the characterization of thermal profiles in tissue resulting from laser treatment must be performed. Ultimately, light from the interstitial probes will be used in combination with specific photosensitizers for delivery of photodynamic therapy in conjunction with hyperthermia.

High temperature (up to 450 °C) infrared absorption spectra of a cured epoxy resin (CER) and human corneal tissue (HCT) have been measured to identify changes in absorption coefficients due to the dehydration and decomposition of polymeric materials. The observed spectral changes are analyzed and related to thermogravimetric measurements and pulsed laser ablation experiments.

Repetitively pulsed (rp) hydrogen fluoride (HF) chemical laser interactions with human corneal tissue have been studied to understand tissue ablation phenomenology, effects, and mechanisms under well characterized laser irradiation conditions. RP HF chemical laser experiments have been performed at two wavelengths (? = 2.78 pm and 2.91 μm) over a fluence range of 0.6 to 10 J/cm2 to determine ablation efficiencies and effective enthalpies of ablation (Q*) as a function of wavelength and fluence. The experimental results are analyzed to consider the physical and chemical processes associated with thermochemical ablation of human corneal tissue by pulsed mid-infrared lasers.