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.

To investigate the contribution of photomechanical fracture to tissue ablation with short laser pulses, we performed a study in which experimental phenomena were compared to results of a theoretical model. In this mode the generation and one-dimensional propagation of thermoelastic stress waves caused by a laser pulse of finite duration is simulated and the dynamics of cavitation induced by the negative components of these stress waves are calculated. To experimentally observe the cavitation dynamics in water and gelatine, an optical pump- probe technique together with time-resolved imaging and stress detection methods was employed. With the pump-probe technique the lifetimes of individual cavitation bubbles until the first collapse could be measured. At low fluence values a good agreement between experiment and simulation was observed. At higher fluences, where the bubbles do not move independently from each other as it is assumed in the model, the experimental lifetimes were longer than the calculated ones. Additional properties of photomechanical damage such as the dependence of the cavitation process on the time-integral over the stress wave, the spatial occurrence of cavitation bubbles and the influence of viscosity in gelatine are demonstrated in the simulation.

In general, macroscopic material failure is a manifestation of irreversible changes at the microscopic level. Many tissues, which may appear to be macroscopically homogeneous, are, at a fundamental microscopic level, a composite material. For example, cornea is composed of a hyaluronic acid matrix in which layers of collagen fibers are overlaid in a crossing pattern. The points where the collagen fibers intersect are potential nucleation sites for microscopic defects, which under the action of tensile stress, nucleate, grow and coalesce to form macroscopic failure planes, or spall planes. Using a model based on microstructural evolution, this paper examines the failure process during photoablation. Specifically, the paper describes a physically motivated, micromechanical model based on the nucleation and growth of spherical voids. This model is then used to simulate photoablation of cornea. Potential for using this model to predict the stress wave and material damage measured by experiment is discussed.

A laser microbeam system has been set up for microsurgery on cell. The relations of laser wavelength, pulse duration and pulse energy to punching effects and self-healing are studied. The experimental results demonstrate that picosecond pulse laser microbeam offers many advantages in cell microsurgery. The mechanism of punching by picosecond microbeam is high field puncture instead of heat effect, and is irrelevant to cell kinds and colors. The diameter and depth of microsurgery can therefore be easily controlled by adjusting the laser pulse energy. The diameter of the minimum aperture is about 0.1 micrometers , much smaller than the theoretical limit ((lambda) /2) for optical microscope due to self- focusing effect. With ultrashort pulse laser microbeam, we can easily cut off any part of a cell. An example is that eight nuclei in the center of unicellular parasite Pneumocystis Carinii can be destroyed one by one by ultrashort pulse laser microbeam without cell wall injury. The holes can also be punched by ultrashort pulse laser microbeam from cell wall to cell nucleus. In a fraction of a second to several seconds after punching, the hole on cell wall or cell membrane can self-heal. Exogenous DNA can be introduced into the cell before its self- healing.

The dynamic evolution of the coagulation front in laser irradiated prostate tissue is simulated using a nonlinear finite element method (NFEM) which takes into account the temperature and thermal damage dependence of blood perfusion rate and optical properties. Using this nonlinear model, it was found that the hyperemic ring formed at the periphery of the coagulation front reduces heat penetration significantly and the increased scattering near the tissue surface reduces the light energy deposition in the deep region. The final damage depth would be overestimated by about 50% if the effect of temperature and damage dependence of blood perfusion and optical properties modeling is disregarded.

Porcine brain tissue is a model for human brain structures in laser induced thermo-therapy. However, its optical properties including possible heat-related changes were basically unknown so far. To simulate laser coagulation, 12 specimens (6 grey and 6 white matter) were heated in a saline bath (80°C, 2 hours) and compared to 11 untreated samples (5 grey and 6 white matter). The optical constants were obtained from transmission (total and collimated) and reflection (diffuse) measurements using the inverse Monte-Carlo method. The absorption coefficient ((mu) _a) of untreated grey substance decreased from 0.35 +/- 0.06/mm (340 nm) to 0.03 +/- 0.02/mm (800 nm). The scattering coefficient ((mu) _s) varied between 20.42 +/- 3.65/mm (340 nm) and 6.85 +/- 2.07/mm (800 nm). The anisotropy factor (g) increased from 0.848 +/- 0.013 (340 nm) to 0.889 +/- 0.009 (800 nm). Coagulation increased (mu) _a up to a factor of 2 (340-540 nm; p < 0.05), and (mu) _s by a factor up to 3 (340-800 nm, all data p < 0.001) while g was decreased up to 18% (340-560 nm; p < 0.05). White substance exhibited a (mu) _a between 0.24 +/- 0.07/mm (340 nm) and 0.04 +/- 0.02/mm (800 nm) while (mu) _s varied between 26.72 +/- 9.10/mm (340 nm) and 21.78 +/- 3.88/mm (800 nm). The g-value increased from 0.561 +/- 0.180 (340 nm) to 0.834 +/- 0.068 (800 nm). Coagulation increased (mu) _a by a factor up to 2 (340-800 nm; all data p < 0.05) while (mu) _s and g remained unchanged. Thermal denaturation changes the absorption and scattering properties of porcine brain significantly.

The results of several measurements of optical tissue properties often show a wide range of variety. This could be a reason for neglecting time-dependent alterations after the preparation or during the measurement procedure itself. To combine the opportunities optical tomography offers (i.e. structural and functional imaging) with two- or even three-dimensional spectroscopy without using any contrast means of fluorescence dyes, we measured several transmission spectra of various tissues of biological specimen. To prove reproducibility three consecutive measurements were carried out. Generally, a variation in the transmission or extinction could be seen. Their value and direction usually depends on the type of biological specimen. Living cells, freshly taken from the nutritive medium, showed a significant decrease in transmission in contrast to various types of originally frozen animal tissue, which revealed an increase in transmission. But here the value of increase was found to be dependent on the tissue, too. Furthermore, we have made investigations on the dependence of transmission alterations by changing the tissue preparation, e.g. the cutting area in regard to tissue properties. In general, the relative spectral response remained the same, thus resulting in a shift to higher or lower transmissions. The investigations were made with tissue of a thicknesses between 300 micrometers and 1 mm. Details will be explained in this paper. These measurements allow the conclusion, that thin biological specimen are subject to changes of optical properties at the time after having taken them out of a stable in vitro state. These changes are probably due to varying anisotropy. Finally, this leads to the conclusion, that for thin biological specimen the rules of geometrical optics have to be preferred rather than making radiation transport calculations. Optical rules should be part of common methods to determine optical properties of tissue.

In attempting to identify a tissue response suitable for monitoring interstitial laser photocoagulation (ILP) during treatment, we observed that the lesions produced in tissue by interstitial irradiation with the 1064 nm radiant energy produced by an Nd:YAG laser fluoresce when exposed to the long-wave ultraviolet light produced by a handheld UV fluorescent lamp. The visual extent of the fluorescence was correlated to the irradiation time and energy fluence rate. Fluorescence spectra of four tissue chromophores, serum albumin, Type 1 collagen, nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) exhibited similar spectra to the fluorescence of solubilized tissue. No significant changes in the fluorescent spectra were observed upon heating to 70°C for 5 minutes the chromophores or tissue sample prior to solubilization. In another experiment, the tissue was thermally damaged by immersion in phosphate buffered saline from 60-100°C for 30-90 seconds. The reflectance from 400-800 nm of the intact tissue was noted to increase with increasing thermal damage up to 80°C, and the decrease at 90°C and 100°C. Activation energies calculated from this data was suggestive of thermal damage to blood and other tissue constituents. In order to see if changes in electrophoretic mobility occurred upon heating, nondenaturing polyacrylamide gel electrophoresis (native PAGE) was done on heated that were solubilized by ultrasonication. The gels showed a quantitative loss of tissue proteins with increasing thermal damage, and the irreversible formation of heavy protein coagulums.

This in-vivo study examines the validity of fluorescence measurement of laser-induced release of temperature sensitive liposome-encapsulated dye for monitoring of temperature and prediction of tissue thermal damage. It is performed in rat liver after i.v. injection of liposomes loaded with a fluorescent dye and i.v. injection of Indocyanine Green (ICG) for diode laser potentiation. Temperature sensitive liposomes (DSPC: Di- Stearoyl-Phosphatidyl-Choline) are loaded with 5,6-Carboxyfluorescein (5,6-CF). These liposomes (1.5 ml solution) and ICG (1.5 ml solution-5 mg/kg) are injected to adult male wistar rats. Two hours later, the liver is exposed and irradiated with a 0.8 W diode laser using pulses lasting from 1 s to 6 s (fluence ranging from 16 to 98 J/cm+2)). Simultaneously, the fluorescence emission is measured with a fluorescent imaging system. Results show that the fluorescence intensity increases linearly form 18 J/cm² up to 75 J/cm². These fluences correspond to surface temperatures between 42°C to 64°C. The measurements appear to be highly reproducible. In this temperature range, the accuracy is +/- 3°C. The maximum intensity is observed immediately after the laser is switched off and a decrease of the fluorescence intensity is observed (27% in 20 minutes) due to the 5.6-CF clearance. However, the ratio (I_F/I_bck) remains almost stable over this period of time and the determination of the temperature is still possible with a good accuracy even 20 minutes after laser irradiation. In conclusion, temperature monitoring by using fluorescence measurement of laser-induced release of liposome-encapsulated dye is clearly demonstrated. This procedure could conceivably prove useful for controlling the thermal coagulation of biological tissues.

Microthermometric measurements on optically-trapped Chinese Hamster Ovary (CHO) cells and sperms cells re reported, using a noninvasive microfluorometric detection technique. Within an optical tweezer system that has been outfitted with a spectral fluorescence excitation and detection capability, the changes in temperature induced by the process of sample confinement by a focused laser beam has been quantified over micron-sized spatial regions of both motile and immotile cells. Our measurement technique is based on the use of environmentally sensitive fluorophores that can be incorporated into the cell membrane and used to sense local changes in temperature when the cell membrane is perturbed optically or via other environmental stress factors. Using a cw 1.064 micrometers Nd:YAG laser for trapping CHO and human sperm cells, a temperature increase of approximately equals 1°C per 100 mW laser power was observed. At this infrared wavelength, cellular heating as result of laser confinement appears to be mainly due to radiation absorption by water.

Thermal therapy using various heating sources such as lasers or microwaves to destroy benign and malignant lesions has recently gained widespread acceptance. However, the accurate prediction of thermal damage in tissue according to theoretical or computer modeling is difficult and unreliable due to target variability with respect to physical properties, geometry, and blood perfusion. Thus, one of the major obstacles to application of thermal therapies has been the lack of a noninvasive, real-time method that could determine the extent and geometry of treated tissue. To evaluate the effects of laser heating on tissue, we have developed an analog-digital hybrid Doppler ultrasound system to measure the phase and amplitude of ultrasonic echoes returned from the heated tissue. The system consists of an eight-gate pulsed Doppler detector, a 16-channel 12-bit A/D converter, and a signal analysis and visualization software package. In vitro studies using canine liver showed two distinct types of modulation of the echoes along the ultrasound beam path during laser irradiation using an 810 nm diode laser. Type 1 signals showed a small and slow variation in amplitude and phase, and were attributed to tissue coagulation. Type 1 signals showed a small and slow variation in amplitude and phase, and were attributed to tissue coagulation. Type 2 signals showed large and rapid variations in amplitude and phase which usually appeared after tissue surface explosion and were indicative of tissue ablation. We hypothesize that the observed phase changes in type 1 signals are due to thermal effects within the tissue consistent with tissue expansion and contraction while the phase changes in type 2 signals are likely due to formation and motion of gas bubbles in the tissue. A further development of the Doppler ultrasound technique could lead to the generation of feedback information needed for monitoring and automatic control of thermal treatment using various heating modalities such as laser, high intensity focused ultrasound, microwaves, or radio frequency waves.

A recurring problem in laser applications is estimating the thermal response of target tissues to laser irradiation. This typically involves using an optical model to determine the distribution of absorbed laser energy and then using a thermal model to establish the temperature during and after laser irradiation. To avoid such modelling and yet allow one to obtain fast, accurate estimates of temperature, a series of charts for laser irradiation of semi-infinite homogeneous media with adiabatic boundaries is presented. These charts were created using analytic solutions of the temperature for absorbing-only media with simple pulsed source geometries. Through the use of nondimensional parameters, these charts allow one to make rapid estimates of the spatial and temporal thermal distributions following laser irradiation for arbitrary pulse durations and absorption coefficients.

We sought to study the effect of fiber tip modification on the size and shape of lesions created by the interstitial application of a 805 nm diode laser. In order to clarify conflicting results of other authors, we performed a large number of burns in order to obtain definitive statistically significant data. The plastic cladding and jacket were removed from the distal 5 mm of a hard polymer clad fused silica fiber of 600 micrometers . Three tip modifications were compared: a bare cut tip with and without precharring and a conical diffused tip. Continuous wave laser radiation was applied over a 1.0 to 2.5 watt range at 0.5 watt increments for a duration of 5, 10, and 15 minutes in vitro using fresh pig liver. The liver burns were thinly cut in cross-sections, and photographed. The sizes of the resultant cavity and lesion were measured and analyzed for statistical significance.

Biological responses of cells to visible and near IR (laser) radiation occur due to physical and/or chemical changes in photoacceptor molecules, components of respiratory chains (cyt a/a₃ in mitochondria, and cyt d in E. coli). As a result of the photoexcitation of electronic states, the following physical and/or chemical changes can occur: alteration of redox properties and acceleration of electron transfer, changes in biochemical activity due to local transient heating of chromophores, one-electron auto-oxidation and O₂^- production, and photodynamic action and ¹O₂ production. Different reaction channels can be activated to achieve the photobiological macroeffect. The primary physical and/or chemical changes induced by light in photoacceptor molecules are followed by a cascade of biochemical reactions in the cell that do not need further light activation and occur in the dark (photosignal transduction and amplification chains). These reactions are connected with changes in cellular homeostasis parameters. The crucial step here is thought to be an alteration of the cellular redox state: a shift towards oxidation is associated with stimulation of cellular vitality, and a shift towards reduction is linked to inhibition. Cells with a lower than normal pH, where the redox state is shifted in the reduced direction, are considered to be more sensitive to the stimulative action of light than those with the respective parameters being optimal or near optimal. This circumstance explains the possible variations in observed magnitudes of low-power laser effects. Light action on the redox state of a cell via the respiratory chain also explains the diversity of low-power laser effects. Beside explaining many controversies in the field of low-power laser effects (i.e., the diversity of effects, the variable magnitude or absence of effects in certain studies), the proposed redox-regulation mechanism may be a fundamental explanation of some clinical effects of irradiation, for example the positive results achieved in treating wounds, chronic inflammation, and ischemia, all characterized by acidosis and hypoxia.

The experimental set up is discussed for yeast fermentation monitoring in connection with irradiation procedures. The key role of the PFK enzyme is examined and a model for ATP-ADP competition is presented.

Claims that low levels of He-Ne laser light (cw, (lambda) equals 632.8 nm) can provide clinical benefits and can enhance in vitro cellular growth are still controversial (T.I. Quickenden and L.L. Daniels, 1993, Photochem. Photobiol. 57, 272-278; L.L. Daniels and T.I. Quickenden, 1994, Photochem. Photobiol., 60, 481-485). The present study tests the suggestion (T.I. Karu, 1988, Lasers life Sci. 2, 53-74; H. Friedmann, R. Lubart, I. Laulicht and S. Rochkink, 1991, J. Photochem. Photobiol. B: Biol. 11, 87-91) that red light stimulates mitosis by raising intracellular pH via absorption by chromophores in the respiratory chain. In order to search for photoinduced changes in intracellular pH, the effect of 5 mW He-Ne laser irradiation on cultures of E. coli was examined using a 300 MHz Nuclear Magnetic Resonance (NMR) spectrometer. The pH difference between the intracellular and extracellular fluid was monitored in the presence and absence of radiation by determining the difference in chemical shift for ³¹P resonances arising from the H₂PO₄^- ⇔ HPO₄^2- + H⁺ equilibrium in the two environments.

The data had been obtained during the experiment in vitro by irradiation of solubilized lysosomal enzymes, retinal homogenates and native lysosomes enabled us to conclude that the laser beam ((lambda) equals 632.8 nm, power density from 0.1 to 15.0 mWt/cm²) acts on the level of membranous structures of lysosomes. During irradiation of rabbits eyes in vitro with an unfocused laser beam (power density on the cornea aur face from 0.01 to 15.0 mWt/cm² was shown, that low-energy, ranged from 0.01 to 1.0 mWt/cm² promotes stabilization of lysosomal membranes. Irradiation with laser beam of 8.0 mWt/cm² and more power induces destabilization of lysosomal membranes. We have also shown that vitamins A and E effecting membranotropic on lysosomes may be corrected by low-energy radiation of helium-neon laser. It is substantiated experimentally that the stabilizing effect of vitamin E may be intensified in case of the combined action of laser radiation on lysosomes. The labilizing effect of vitamin A on membranes of organelles, as was studied, may be weakened by application of laser radiation of low intensities.

Optical set-up for the discovering of distant interaction between cells monolayers is proposed. This set-up allows to show with high degree of trustworthiness, that animal cells monolayer (monolayer-inductor) having its mitotic activity as a result of outer influence emits electromagnetic radiation that causes adequate alterations in the cells monolayer (monolayer-detector) placed at some distance from monolayer- inductor. It is established that distant interaction between cells monolayers (mitosis synchronization) is realized by the radiation of visible spectral range. The effect of distant synchronization mitosis in a inductor-detector pair observes both in the case of cells stimulation mitotic activity and in the case of activity inhibition. The mitosis synchronization is absent when a filter absorbing light in visible spectral range is used or optical contact between monolayer-inductor and monolayer-detector is disturbed.

The investigations carried out in our group on biological systems of various organization level (enzyme molecules in solution, human and animal cell cultures), allowed us to conclude, that the light-induced changes of spatial structure of cells components form the basis of biological activity (and as a consequence therapeutic effect) of various wavelength low-intensity laser emission. Photophysical mechanism of these changes lies in the reorientation of highregulated anisotropic parts (domains) with the liquid-crystalline type of ordering of the cell components due to the interaction between the electric field and the light induced integral electric dipole of the domain. The mechanism of such reorientation is well established in physics of liquid crystals of nematic type and is known as light induced analogue of Frederix's effect. The following results enable us to draw the conclusion about the determining role of the orientations effects on the biological activity mechanism of low-intensity laser radiation: (i) the possibility of reversible modification of spatial structure and enzyme molecules functional activity under the influence of laser radiation outside the band of their own or admixture absorption; (ii) the dependence of biological effect of laser radiation on the functional activity of cells vs. polarization degree of the light with the maximum photobiological effects observed for linear-polarized radiation; (iii) the equivalence of a static magnetic field and low-intensity laser radiation in action on functional activity of the cells and the lowering of the laser field intensity for the achieving the difinite changes of the cell functional activity in the presence of static magnetic field.

Aim of this report was to investigate the adenylate pool and the energy charge in human white blood cells exposed to increasing time (15, 30 and 60 min) of HeNe laser treatment. EDTA treated human blood diluted 1:1 with 0.88% KCl was added (1:5) with NaCl-dextran solution to allow sedimentation of red blood cells. 6 ml of the white cells floating in the supernatant were layered on 3 ml of Lymphoprep in plastic tubes and each tube was centrifuged (from 50 to 5000 X g for 5 min). Granulocytes were concentrated in the lower phase, whilst lymphocytes were in the intermediated phase. After further purification cytological homogeneity was tested by a cell counter. Granulocytes and lymphocytes were irradiated at +22°C with HeNe (Space, Valfivre equipment). On these population ATP was tested by luminometric procedure, the adenylate pool was separated by HPLC (Jasco) on neutralyzed perchloric extracts. ATP concentration increased in lymphocytes (+63.9%, p < 0.01) and in granulocytes (+25.0%, p < 0.05) after 60 min irradiation. The adenylate pool (tested by HPLC) does not change significatively in lymphocytes or granulocytes after 30 min irradiation, whilst in 60 min irradiated lymphocytes and granulocytes a significative increment was observed in nucleotide concentration. No changes were observed in energy charge according to Atkinson.

This paper deals with the therapy by the He-Ne laser of low power, modulated pulse and low dosage of 365 nm optic source. To radiate the blood in vitro of patient's, at the time, the blood was treated with addition of oxygen. The treated blood was then retransfusion into the same patient. From 1993 to 1994, we have cured 202 cases with prominent therapeutic effect. The results of clinic and laboratory research showed: It greatly increased the immunologic function of the body, the total effective ratio achived 95% (cerebral vascular diseases), and greatly decreased the drug reaction of patients after the tumors were treated by chemotherapy and radiotherapy.

The effect of low power laser on the wound healing process was investigated at the site of anastomosis in rats. Tracheal reconstruction was performed after the tracheal transection and He-Ne laser (NEC,GLG5360, wavelength 632.8 nm)(3.3 X 10^-3 W/cm², 5 min) was irradiated to the site of anastomosis. Structural and functional recoveries were evaluated at 1 and 2 weeks postoperatively. Hydroxyproline content, epithelial condition, cellular infiltration, fiber proliferation, microstructure of cilia, mucociliary function and neovascularization were measured. Hydroxyproline was measured with Amino acid autoanalyzer (Hitachi 835-50). Microstructure of cilia was observed with scanning electron microscope (JSN-840, JEOL). Mucociliary function was evaluated by India ink movement. The hydroxyproline contents per 1 mg dry weight in irradiated group and control group were equivalent (approximately 20 (mu) g). Cellular infiltration of irradiated group was fewer than that of control group. The degree of mucociliary functional recovery in the irradiated group was better than that of control group. Among the cases that showed the structural recovery of cilia, the functional recovery was observed in whole irradiated group, and in 40% of control group. Neovascularization was more pronounced in irradiated group. From this study it is suggested that the laser irradiation may reduce the inflammation and promote the recovery of mucociliary function at the site of anastomosis.

We have tested the effects of early posttraumatic low-energy laser irradiation on injured neural tissues. Rat optic nerves were crushed by a calibrated forceps and the ensuing degenerative processes were followed up electrophysiologically and by on-line metabolism measurements, using nicotinamide adenine dinucleotide autofluorescence in response to anoxia. The irradiation not only decelerate the posttraumatic degenerative processes but also increased axonal survival as shown by visual evoked potential response recording. The irradiation also reduced significantly the very early posttraumatic reduction in the metabolic activity of the optic nerve. It seems that the low-energy irradiation, possibly by a photochemical mechanism and by modifying he cellular metabolism, prevents the spread of the injury effects from the injury site and along the axons. This action of low-energy laser irradiation is akin to the neuroprotective effects ascribed to various drugs, such as corticosteroids.

Repeated extended source Q-switched exposure centered on the macula has been shown to produce a Bullseye maculopathy. This paper provides a confocal scanning laser ophthalmoscopic evaluation with regard to the retinal nerve fiber layer (NFL) and deeper choroidal vascular network. Confocal imaging revealed that the punctate annular appearance of this lesion in the deeper retinal layers is associated with retinal nerve fiber bundle disruptions and small gaps in the retinal NFL. No choroidal dysfunction was noticed with Indocyanine green angiography. It is hypothesized that retinal NFL damage occurs either through disruption of retinal pigment epithelial cell layer support to the NFL or through direct exposure to high spatial peak powers within the extended source beam profile, causing direct microthermal injury to the NFL. The apparent sparring of the fovea reflects central retinal morphology rather than a lack of retinal damage to the fovea.

Investigations into the biological effects of low-energy laser radiation (LLR) are characterized by a score of challenges, which are due primarily to a cascade of laser-induced and sometimes antagonistic processes. To investigate these processes on various biologic levels, we analyzed local and general effects of LLR on the exocrine and endocrine functions of the accessory sex glands in experimentally induced orchitis and orchoepididymitis in rabbits, and in clinical studies on male patients. The results indicate that LLR may alter the inflammatory response, including the exudative reaction, macrophage migration, and fibroblast activity. Furthermore, LLR may result in changes in serum concentrations of LH, FSH, and ACTH, prolactin, testosterone, cortisol and aldosterone. Some of these changes may be at least partially responsible for the well-known anti-inflammatory effects of LLR.

Reflex therapy is one of numerous applications of low-energy laser radiation in medical treatment. The advantages of this therapy in comparison with traditional acupuncture include technical simplicity, absence of pain, and, as a consequence of the complete noninvasiveness of the procedure, the absence of risk of contracting AIDS or other infectious diseases. However, no definitive results have been published regarding the comparative effectiveness of the two approaches to reflex therapy. In view of the neurohumoral role in the curative effects of reflex therapy, we compared laser acupuncture and the traditional needle technique in relation to changes in the serum concentrations of the principal sexual and gonadotropic hormones in hypofertile men.

We tried to establish the efficiency of low energy (power) lasers (LEL), in various inflammatory and noninflammatory rheumatic diseases during five years. We treated 514 patients with osteoarthrosis, 326 patients with nonarticular rheumatism and 82 patients with inflammatory rheumatism, in four different ways: only with Galium-Aluminum-Arsenide (GaAs) infrared lasers; both GaAs lasers and Helium neon (HeNe) lasers; with placebo laser; with classical anti-inflammatory therapy. The results were analyzed using local objective improvements and the score obtained from a pain scale before and after the treatments. We also note some preliminary results obtained by the computer analysis of the evocated potentials after laser irradiation. We conclude that LEL (especially HeNe with GaAs) is obviously more efficient than placebo laser therapy and also had better or at least similar results, in most of the cases, than classical anti-inflammatory therapy.

The effect of repeated low power He-Ne laser on rabbit's corneal epithelium was studied after 3 daily sessions. Under certain irradiation parameters, low power He-Ne laser irradiation was found to change the mitotic rate in the basal layer of intact corneal epithelium. Three daily irradiations for 3 or 10 minutes increased the mitotic index while 30 minutes irradiations decreased it.

The problems of choice of live models for the study of laser and nonlaser light irradiation effects on animal organisms are discussed. Fish embryos are shown to fit many requirements related to the performance of experiments in clearly defined conditions. Laser Doppler microscopy yielding quantitative data on the dynamic response of the embryos irradiation have proved to be an adequate technique. Preliminary experimental data on the biological effects of light on different types of embryos are presented.

Irradiation of heparinized rat blood by He-Ne laser light ((lambda) - 632.8 nm, power density - 5 mW/cm²) during 15 or 30 min was performed in vitro experiments. The complex of biochemical parameters of erythrocytes, plasma and cytochemical parameters of polymorphonuclear leucocytes was studied. Laser irradiation was stated to cause different metabolic changes in red blood cells and neutrophils depending on the dose. In both doses of irradiation glucose-6-phosphate dehydrogenase activity lowers in erythrocytes, succinate dehydrogenase activity and lysosomal cationic proteins content increase in neutrophils. Stimulation of oxygen active forms production in cellular membranes of blood formed elements results in plasma malonic dialdehyde level increase and in the change of the balance between primary and secondary lipid peroxidation products. Cooperative interaction between different blood cells in the process of realization of system response to laser exposure is supposed to exist.

The effect of dynamic optical properties on the spatial distribution of light in laser therapy is studied via numerical simulations. A 2D, time dependent computer program called LATIS is used. Laser light transport is simulated with a Monte Carlo technique including anisotropic scattering and absorption. Thermal heat transport is calculated with a finite difference algorithm. Material properties are specified on a 2D mesh and can be arbitrary functions of space and time. Arrhenius rate equations are solved for tissue damage caused by elevated temperatures. Optical properties are functions of tissue damage, as determined by previous measurements. Results are presented for the time variation of the light distribution and damage within the tissue as the optical properties of the tissue are altered.

Erbium and Holmium lasers have both been shown to be suitable for orthopedic surgery performed under water. Erbium lasers emitting in the 3 micrometers wavelength region corresponding to the maximum water absorption peak effectively ablated biological tissues with high precision and minimal thermal damage. Holmium laser radiation at 2 micrometers , due to a lower absorption coefficient, is characterized by a greater extent of thermal damage leading to hemostasis. To combine the special advantages of each system we simultaneously coupled their radiation into a zirconium fluoride fiber (ZrF₄) which was protected with a quartz fiber tip. Pressure measurements performed in the liquid using a piezo electrical transducer, transmission measurements and video flash lamp schlieren imaging of the laser induced vapor bubble were used in order to determine optimum laser parameters. The cutting efficiency of the Erbium laser is drastically improved when a low energy Holmium laser pulse is additionally used which is just able to open a vapor channel through which the Erbium laser pulse can be transmitted. The dynamics of the channel formation, geometry and life time are measured as a function of the delay time between the two different laser pulses and the pulse energy applied. The combination of 2 micrometers and 3 micrometers radiation seems to be an ideal instrument for tissue treatment.

Plasma mediated ablation of collagen gels and porcine cornea was studied at various laser pulse durations in the range from 350 fs to 1 ns at 1053 nm wavelength. A time resolved stress detection technique was employed to measure transient stress profiles and amplitudes. Optical microscopy was used to characterize ablation craters qualitatively, while a wide band acoustic transducer helped to quantify tissue mechanical response and the ablation threshold. The ablation threshold was measured as a function of laser pulse duration and linear absorption coefficient. For nanosecond pulses the ablation threshold was found to have a strong dependence on the linear absorption coefficient of the material. As the pulse length decreased into the subpicosecond regime the ablation threshold became insensitive to the linear absorption coefficient. High quality ablation craters with no thermal or mechanical damage to surrounding material were obtained with 350 fs laser pulses. The mechanism of optical breakdown at the tissue surface was theoretically investigated. In the nanosecond regime, optical breakdown proceeds as an electron collisional avalanche ionization initiated by thermal seed electrons. These seed electrons are created by heating of the tissue by linear absorption. In the ultrashort pulse range, optical breakdown is initiated by the multiphoton ionization of the irradiated medium (6 photons in case of tissue irradiated at 1053 nm wavelength), and becomes less sensitive to the linear absorption coefficient. The energy deposition profile is insensitive to both the laser pulse duration and the linear absorption coefficient.