A new method to fabricate dielectric-coated hollow waveguides has been proposed based on all liquid-phase techniques. Long silver tubes with an extremely smooth inner surface have been fabricated by using a new process of silver mirror reaction and loss reduction of short silver waveguides has been made by liquid flow-coating of a fluorocarbon polymer.

Hollow glass waveguides have been fabricated with losses as low as 0.2 dB/m at 10.6 micrometers . These guides were fabricated from polyimide-coated, glass tubing in which we deposited an inside metallic layer followed by a thin dielectric coating to enhance the reflectivity of the metal film. The inner diameters of the tubing ranges from 320 to 700 micrometers and we have made lengths as long as 3 m. The bending radii of the guides is less than 5 cm for bore sizes less than 500 micrometers . We have used these waveguides to deliver over 80 W of CO₂ laser and several watts of Er:YAG laser power. Finally, the hollow glass guides are inexpensive, robust, and EtO sterilizable.

A monolithic hollow waveguide called Fiberlase ^R has been developed capable of delivering a wide range of wavelengths at very high power for surgical and industrial applications. Operational wavelengths of 3 microns through 10.6 microns have been demonstrated and core diameters of 400 microns and 1000 microns are now in production. Practical lengths of up to 3 meters with a 1000 micron core are being produced. It is expected that Fiberlase will replace the articulated arm of CO₂ lasers in the near future. Unique to Fiberlase is its monolithic substrate structure, avoiding multi-layers, simplifying the manufacturing process, maximizing the heat dissipating properties, and allowing very low manufacturing costs. Discussion includes power handling, bend performance and beam characteristics.

From our basic experiments of interaction of ArF laser and biotissue, the biotissue cutting quality of excimer beam was sharp and a non-thermal treatment. Namely no particular thermal damage is recognized in the case of ArF laser. The use of ArF laser in medicine is expected to produce new therapy, especially for hard biotissue. But, as is well known, usual quartz fiber is difficult to use for the UV-C region beam transmission. We have been investigating UV beam delivery techniques with the special quartz fiber and the hollow tube.

Single-crystal sapphire fibers are produced by the Saphikon edge-defined, film-fed growth (EFG_TM) technique. Total losses below 3 dB/meter have been measured at the Erbium:YAG laser wavelength of 2.94 microns. Fibers with lengths greater than a meter have delivered over 400 mJ of Er:YAG laser energy. EFG fibers have been shown to lose less than 10% transmission when bent to a 6 cm radius. The apparent numerical aperture (NA) has been measured as 0.31 for an unclad fiber, and 0.38 for fiber clad with teflon FEP. Scattering losses were shown to dominate loss, with measurements at both visible and 3 micron wavelengths using integrating spheres. Spectroscopy was used to identify absorptive losses in the EFG fibers.

Single-crystal sapphire fibers have been grown, using the laser heated pedestal technique, with losses as low as 0.7 dB/m and with lengths up to 150 cm. We have applied polymer and sol- gel coatings to the fibers and we have evaluated the performance of these coatings as optical cladding. The best coating seems to be teflon AF even though the coatings are reasonably thin and low temperature.

The IR transmittance of silver-halide fibers was measured while they were undergoing various flexing procedures leading to mechanical fatigue. The fatigue experiments consisted of repetitive bending, going from small bending radii (plastic regime) to large bending radii (elastic regime). Various types of fibers have been investigated including unclad fibers, fibers with a core-clad structure, fibers of various AgCl_xBr_1-x compositions and fibers of different diameters. The optical measurements which were done during the flexing experiments involved CO₂-laser transmission and spectral (FTIR) transmission. The results for the various conditions are reported and discussed in terms of high-cycle and low- cycle fatigue. Such investigations are of practical importance in characterizing fibers useful for endoscopic surgery and IR detection.

We describe a Fourier transform infrared-attenuated total internal reflectance (FTIR-ATR) technique for samples of 10 - 30 (mu) g deposited on a polycrystalline silver halide fiber. A protein deposit consists of approximately two molecular layers, for which the kinetics and extent of exchange with D₂O/N₂ are readily measured. We have extended the technique in several ways. Formation of complexes with modest association constants by taking advantage of the combination of protein mobility on the fiber with the absence of water. Association is thus favored, and the rates and extent of deuterium-hydrogen exchange may be followed as well as conformational changes. Polarized spectra of red blood cell ghosts have been measured on a flattened silver halide fiber. The cells containing the silver halide fibers have a design that allows controllable access to the sample. In addition to requiring only small quantities for good spectra, the cell is readily cleaned and handled. We anticipate the application of these techniques to many other biological samples, including mutant proteins.

The new family of IR transmitting glasses, the TeX glasses, based on the association of tellurium and halide (Cl, Br, or I) are characterized by a wide optical window extending from 2 to 18 micrometers and a strong stability towards devitrification. Optical fibers drawn from these glasses exhibit low losses in the 7 - 10 micrometers range (less than 1 dB/m for single index fibers, 1 - 2 dB/m for fibers having a core-clad structure). The TeX glass fibers have been used in a remote analysis set-up which is mainly composed of a FTIR spectrometer coupled with a HgCdTe detector. This prototype system permits qualitative and quantitative analysis in a wide wavelength region lying from 3 to 13 micrometers , covering the fundamental absorption of more organic species. The evolution of a lactic and an alcoholic fermentation has been monitored by means of this set-up.

Damage thresholds of bulk samples and fibers made of high-purity chalcogenide glass of As-S system for YAG:Er laser ((lambda) equals 2.94 micrometers ) are investigated. An accumulation effect is found both in fibers and bulk samples, which reduces stability of repetitive pulse laser operation. Correlation between damage thresholds and heterophase inclusion concentration has been observed experimentally. In samples with impurity concentration less than 10⁴ cm^-3 the damage thresholds exceed 1 kJ/cm² for single shot pulse and approximately twice as low in the repetitive pulse regime. Fibers made of glass samples with minimum concentration of impurities are capable of increasing YAG:Er laser radiation power transmitted through a fiber.

For the XeCl Excimer laser (308 nm, 115 ns), special design multifiber laser catheters were developed and theoretically as well as experimentally evaluated. Monte Carlo simulations showed that the penetration depth of 308 nm XeCl excimer light varied from 50 to 200 micrometers for fiber diameters from 50 to 550 micrometers and larger. Tissue ablation is expected to be restricted to this irradiated area. In order to ablate larger tissue areas, a flexible bundle of fibers is used introducing gaps in the irradiance distribution due to dead space in between the individual fibers. Multifiber catheters were developed for a unique neurosurgery bypass procedure and for urethra stricture surgery. Real-time, close-up, high speed video imaging showed that tissue ablation mechanism of these catheters is predominately governed by explosive short-life vapor bubbles fragmenting the tissue to small particles. In order to temper the ablation process, laser energy was delivered in 8 pulses divided over 8 sectors of a multifiber catheter (multiplexing), keeping the same fluence instead of one pulse addressing all the fibers at once.

A novel technique for quantitatively examining the 3-D light distribution from optical fiber diffusers was developed. This system provides a rapid and sensitive method for characterizing light output, while remaining easily adaptable to a variety of tip configurations. We have used this technique to evaluate the longitudinal and azimuthal uniformity of the light output from cylindrical diffusing tips as well as the output distributions of spherical and microlens diffusers. Upon considering the clinical requirements of the cylindrical diffuser tips, we have determined a configuration which yields a realistic and informative view of the light output. As an example of the sensitivity and accuracy of this method, the mode-dependence of the output intensity distribution of cylindrical optical fiber diffusers was investigated by examining the effect of bending the fibers. The precision and reproducibility of this characterization scheme allow it to be a valuable tool not only for evaluating existing diffusers, but for assisting in the development of improved fiber optic diffusers.

The spherical fiber optic diffuser is for producing a spherical scattering light field. A uniform light intensity distribution is the most desired pattern for many medical applications. This paper presents a theoretical model for describing the surface irradiance and the far-field intensity distribution, which are expressed as a function of scattering coefficient, radius of the diffuser, and the maximum semi-angle of the output beam from fiber end. Experimental results are given and compared with the theoretical model.

Improved fluorescent-tip fiber optical fluence-rate detectors with solid state fluorophores are presented. In these optical fibers a small end-section of the core is doped with rare earth ions (Nd³⁺, Er³⁺) or is replaced by a fluorescent crystal such as ruby. Thus, this section of the core emits fluorescent light when irradiated with the treatment light to be measured. Angular isotropy and spectral response characteristics of these light detectors are presented. An advantage of solid state probes is their narrow fluorescence emission band and large Stokes shift, allowing also for fluorescence measurements of endogenous or exogenous fluorophores in the tissue. The possibility of simultaneous quantitative fluence-rate and photosensitizer dosimetry by interstitially implanted fiber optic detectors is discussed.

Metal-coated (Al) tapered all-silica fibers with core diameter up to 1.2 mm, the input/output diameter ratio up to 3:1, the tapered length 1.5 - 2 m, and the core-clad refractive index difference up to 0.017 have been prepared for high energy laser pulses delivery. The increased input diameter allows us to launch higher energy into the fiber keeping the surface power density well below the threshold of radiation-induced surface damage. Using laser radiation with the beam divergence of 3 mrad, the transmission of the fibers has been found to be 85%. Both free running and Q-switched TEM₀₀-mode regimes of Nd:YAG laser have been used to demonstrate stable operation of the fibers for the following set of input parameters: 40 mJ pulse energy, 25 ns pulse duration, and 15 Hz pulse repetition rate.

We have been working with the association of two techniques -- the static perimetry and the video-oculography -- to obtain automatic and objective determinations of dynamic pupillary reflexes in both eyes to measure the visual fields. For the static perimetry we designed and developed an instrument based on a fiber optic-projection target using a plastic fiber optic like light guide. By means of a rotary mechanical-optical device (step motor), controlled by a PC interface, we select the proximal end of one of 200 plastic fiber optics; we adhere all distal extremes on a translucent-material hemisphere; we assure the projection of localized and constant area light stimulus. We controlled the light intensity and stimulus duration. We employed a calibrated light source capable of providing 358 lux light intensity. In color perimetry results we provided the use of color filters controlled by small electro-mechanical gates. For the video-oculography the eye image is captured by a closed circuit TV camera on line. At the same time the image of the pupil is recorded in a VCR to analyze the pupillary reflexes with a computer system and image processing.

Amorphous Materials has developed a unique method for preparing optical fibers from chalcogenide glasses. Fiber is drawn through a hole in the bottom of a heated, pressurized chamber containing a cylinder of a chalcogenide core glass. The fiber is passed through two heated split dies which apply a cladding glass and a plastic coating continuously. The fiber is pulled using a one meter drum equipped with accurate speed and pitch control. The method is ideally suited for the formation of IR glass ribbons which can be stacked upon one another to form coherent fiber bundles. Results of our first efforts are reported in this paper.

Quantitative size measurements of gastrointestinal tract lesions (i.e., ulcers and polyps) viewed during endoscopy are helpful in assessing the rate of healing or growth. We report a novel technique for quantitatively measuring the two-dimensional size of a feature viewed remotely via a video imager. Our instrument's small size makes it a suitable candidate for use in endoscopes. Computing the size of a feature displayed on a two-dimensional video monitor necessitates measuring the distance between the imager and the surface under observation because an undistorted video image preserves the angular content of a scene. We have developed a prototype ranging system that exploits the tendency of light emerging from the tip of an optical fiber to diverge. Our device uses two fibers with different divergence characteristics. The separation between the imaging sensor and the viewed surface is determined by inspecting the relative sizes of the spots cast by each of the fibers. Our device, which measures distances between 2 and 8 cm, is sufficiently small to be accommodated in an endoscope's accessory channel.

The ultrathin fiberscope, in which the outer diameter is under 1.0 mm, has made possible the direct observation of narrow portions within the human body. The fiberscope mainly consists of the imagefiber, the objective lens, and the illumination fiber, and each advance of these devices has brought the reduction of the scope-diameter. We have investigated the silica based rod lens for the following merits: (1) The fiberscope can be sterilized by the (gamma) -ray instead of ethylene oxide gas which has the problem of carcinogenicity, because the silica glass has high radiation resistant characteristics. (2) The silica based rod lens can be spliced with the imagefiber without any adhesive agent by using the arc fusion splicing machine. As a result, the reliability of the fiberscope can be significantly improved. The silica based rod lens with 125 micrometers in diameter was fabricated by drawing from preform rod made by the vapor phase axial deposition method. The characteristics of their images were evaluated by the modulation transfer function method. This paper presents the details of the fabrication technique of the silica based rod lens and its characteristics.

The question of the image quality evaluation in microendoscopy ((phi) < 0.5 mm) and of its improvements is addressed in this article. The MTF has been carefully evaluated by a precise and reproducible method and reveals significant differences between the various multicore fibers tested (twelve different fibers from three firms). The measuring conditions, such as the aperture of the incident light beam, the orientation of the sampling direction, and the position of the evaluation point on the bundle section, were also of concern in the evaluation of the image quality. The measurement of the overall contrast loss is related not only to the limit of sampling by the density of fiber cores, but also to the intercore fiber coupling.

In this paper we present an update on the Mini-Excimer photorefractive keratectomy (PRK) laser system with an emphasis on the scanning device. We also compare the systems of various manufacturers. This paper also presents PMMA ablation profiles and clinical results from China with over 100 cases of myopic corrections ranging from -2.5 D to -12 D. In contrast to the old technology which uses industrial-type high-power excimer lasers, the advanced Mini-Excimer system uses the most recent technology involving a compact, high repetition-rate excimer laser operated at a much smaller beam spot size of (0.8 - 1.2) mm in a scanning mode which requires a beam energy per pulse of only (0.9 - 1.2) mJ on the corneal surface to achieve the same range of fluence (or energy density) (160 - 200) mJ/cm² as that of the high-power excimer lasers.

A new cavity has been designed to allow the amplification of both stimulated and spontaneous emission. Mercury-vapor in the new cavity produces peak wavelengths at 404, 436, 546, and 577 nm which are very close to the blood absorption peaks. The excitation techniques include both direct current and optical pumping of the mercury-vapor medium, to increase the power density of the output light, therefore, making it suitable for most medical applications. OptoDerm^TM is a new skin lesion treatment system, based on the mercury-vapor- unilaser. The output is gated quasi-pulsed, with high power pulses of 3 millisecond duration, in addition to a low level continuous wave beam as the aiming beam. The power supply is designed to match the plasma region, and is capable of pumping the cavity at high currents to produce the high power output pulses. The proper choice of the plasma region and the power supply, resulted in a very small, lightweight, and affordable system ideal for clinical and laboratory environments.

Forty years ago, a leading cataract surgeon in the United States announced, with an air of finality, that the "perfect operation' for cataract extraction had been developed.' He believed cataract surgeons had reached their zenith and that no more time should be wasted looking for alternatives or refinements. The procedure he was describing was an intracapsular cataract extraction. The cataract was delivered at that time with forceps, often with "just a little vitreous". Sutures were just beginning to be used, but weeks of postoperative immobilization were still the norm. Patients undergoing the procedure could look forward to a lifetime of visual impairment and to a loss of confidence and self-esteem brought about by both the functional impairment and the unflattering appearance of these spectacles. This "perfect operation" marked the end of the productive life for most individuals. With the introduction of the first ultrasonic phacoemulsification equipment in the 1970's and the development of small incision intraocular lenses in the 1980's, all of us have witnessed a remarkable leap in the evolution of cataract surgery. Like our colleague forty years ago, some of us think that we have reached a plateau, but this evolution will continue. What is needed in ophthalmic surgery today is a single, versatile, reliable, and inexpensive multipurpose device which can perform all these surgical functions with equivalent or superior results. Such a device would allow cost-conscious surgery facilities to offer a full range of state-of-the-art surgery, while purchasing only a single unit - a unit which would be no more expensive than existing phacoemulsification devices.

Copper vapor lasers (CVLs) are widely used in the treatment and management of vascular, benign pigmented, and cutaneous lesions and malformations. Recent improvements in laser output powers and delivery systems, including automated scanning devices, have greatly increased the utility of these lasers. Increased laser powers have enabled the duration of treatment exposures to be shortened allowing better target tissue thermal relaxation time matching for improved clinical results. Product enhancements, including reduced warm-up times, and improved manufacturing methods have significantly reduced the cost of this technology which has in turn greatly increased the private office acceptance of CVLs. Gold vapor lasers and copper vapor lasers pumped dye lasers are also extensively used in photodynamic therapy clinical trials.

The Vanderbilt free electron laser (FEL) operates between 2.0 and 8.0 micrometers with high peak intensities and a pulsed structure. Both the tunability of the FEL and the unique pulse structure make this an attractive tool for surgery. To be used effectively in surgery, one must be concerned with the control and delivery of the laser light from the FEL wiggler to the operating room. Several innovative delivery and monitor systems are being developed in our computer assisted surgical techniques (CAST) program at the FEL. To use the fastest pulse repetition rates and maintain minimal lateral thermal damage, a computer controlled scanning system is used. In the surgical applications of lasers, it is often necessary to know when a laser has penetrated a bone. We are developing a method to detect when the bone has been penetrated by measuring the photo acoustic signal generated by a pulsed laser.

The free electron laser (FEL) has long been proposed as a flexible tool for a variety of medical applications, and yet the FEL has not seen widespread acceptance in the medical community. The issues have been the laser's size, cost, and complexity. Unfortunately, research on applications of FELs has outpaced the device development efforts. This paper describes the characteristics of the FEL, as they have been demonstrated in the U.S. Army's FEL technology development program, and identifies specific medical applications where demonstrated performance levels would suffice. This includes new photodynamic therapies for cancer and HIV treatment, orthopedic applications, tissue welding applications, and multiwavelength surgical techniques. A new tunable kilowatt class FEL device is described, which utilizes existing hardware from the U.S. Army program. An assessment of the future potential, based on realistic technology scaling is provided.

Most attractive for surface sterilization are compact repetitive low-energy high-current accelerators RADAN. When equipped with an on-site shielding, they may successively be used in a conventional room. Moreover, owing to their simplicity to service, the operating and maintenance personnel may not be highly qualified. These accelerators offer good promise for the creation of desktop sterilizing devices which might be placed near the doctor's job position.

In this paper we describe a multiwatt Nd³⁺ fiber laser pumped via a second cladding by the DIOMED 25 laser diode unit. This multiple diode array source is designed for coupling up to 25 Watts of diode power into a plastic-clad silica fiber of 400 micrometers diameter. The double-clad laser fiber is interchangeable with the normal PCS delivery fiber. The device operates at 1.058 micrometers with a slope efficiency > 50% and a 150 times brightness enhancement. This laser though useful in itself is also a key intermediate laser for generation of high powers at other wavelengths. Tandem pumping of Tm³⁺ and Er³⁺/Yb³⁺ fiber lasers at 1.058 micrometers enables efficient generation of 2.0 micrometers and 1.55 micrometers radiation respectively. In addition the Nd³⁺ laser can be operated close to 1.3 micrometers and there are prospects for in-fiber frequency doubling of the 1.06 micrometers line to generate a high power source in the green.

A design is presented of a high-power diode laser system that may be mass produced at minimum cost. The system consists of: an array of semiconductor lasers (stacked bars each with a multiplicity of stripe lasers); a mass-produced array of collimating lenses to `collimate' each of the laser output beams; an array of diffractive corrector lenses, each custom milled using an excimer laser, to correct for faults in the first two components; a diffractive optic transformer to geometrically transform the beam into a close packed symmetric virtual source that is focused to a spot or into a medical fiber. In this scheme, the outputs from the diode lasers are combined incoherently. While the design is for power outputs of the order of 100 W, the brightness theorem (the second law of thermodynamics) is theoretically consistent with incoherent combination of diode laser beams in a 600 micrometers diameter medical fiber with power over 1000 W.

Due to their high reliability, modest electrical and cooling requirements, and their compact size, diode laser systems are attractive high power, fiber-coupled laser sources for surgical and therapeutics procedures. We describe Applied Optronics Corporation's LM series of portable air-cooled diode laser systems delivering 25 W or 50 W of cw power from the distal end of a disposable, 0.37 NA optical fiber with a core size of 600 micrometers or 1 mm respectively. In comparative tissue interaction studies using the 980 nm laser source, three laser interaction regimes are identified and characterized for laser interactions with six types of cadervic soft tissue.

A randomized study of interstitial hyperthermia with diode laser was performed on 40 Swiss nu/nu mice. The series was divided as follows: group 1 a control group; and group 2 treated by diode laser. The tumor model was a subcutaneous HT29 colonic carcinoma treated at the same size. The diode laser (830 nm) was applied through a 300 micrometers optic fiber implanted in the tumor and delivered at a power output of 200 mW and 1800 sec exposure time (360 J). The temperature range was 46 degree(s)C in the center of tumor and 42 degree(s)C in its peripheral part. In both groups, the tumor was removed 3 days after laser treatment. The tumor volume (TV) was evaluated and compared using nonparametric tests (Kruskal Wallis). Microscopic examination of tumors showed extensive and complete necrosis in group 1. By day 30 after removal the tumoral recurrence rate was 20% in group 2 versus 55% in group 1. The technical advantages of diode laser are pointed out.

A high average power tunable laser system that can easily be accommodated in an operating room is described. Seventeen watts of TEM₀₀ average power at 630 nm with a dye lifetime of thousands of watt-hours or hundreds of thousands of photons of pump laser power per molecule of dye has been achieved. This was accomplished at a repetition rate of 25 kHz with a wall plug efficiency of .33%. The system utilizes the high efficiency KTiOPO₄ (KTP) frequency doubled Nd:YAG laser to pump a tunable dye laser system designed specifically for low maintenance and high reliability required in photodynamic therapy. Seventeen watts of TEM₀₀ average power at 577 nm with rhodamine 6G (R6G) was also obtained. Comparison to other high average power tunable systems as well as long term system performance including dye stability data are presented.

The Applied Optronics Corporation's model LM-400 is the first commercially available visible diode laser system which can meet the light source requirements for photodynamic therapy (PDT). PDT is a treatment for cancer which uses the topical illumination by a precise wavelength of light to photochemically activate an otherwise nontoxic drug, resulting in the localized necrosis of cancerous cells. Following a discussion of the light source requirements for PDT, we describe the system design and performance of AOC's self-contained, all solid- state, visible diode laser system. When compared to dye laser systems pumped by secondary lasers, diode laser systems offer significant advantages in terms of cost, simplicity of operation, portability, and negligible installation and maintenance requirements.

A laboratory version of an LED-array light source centered at 664 nm was reviewed last year in Biomedical Optics '93. Since that time, primary development efforts have been directed toward the development of two LED-array light sources for preclinical trials, one centered at 630 nm and the other at 800 nm. The first array is targeted as an alternative to the argon- pumped dye laser for photodynamic therapy (PDT) procedures based on the Photofrin II photosensitizer. The second array at 800 nm is directed at deep tissue penetration with a new photosensitizer recently developed at the University of Utah, bacteriochlorin derivative (bcd). While the first array is viewed as a lower-cost, more reliable, user-friendly replacement for traditional PDT dye lasers, the second is being developed in unison with bcd to significantly expand the range of applications of PDT to previously undeveloped cancer treatment modalities such as breast cancer. The 800 nm array has demonstrated an optical output of 5.13 watts while the 630 nm source radiates with a maximum optical power output of 1.63 watts.

On the basis of the diffusion theory model, frequency-domain spectroscopy allows for a quantitative determination of the absorption ((mu) _a) and scattering ((mu) _s') coefficient spectra of a homogeneous multiple scattering medium. We performed measurements using an intensity modulated light emitting diode (LED) as the light source. The LED's spectral distribution permits the study of a spectral region extending for about 80 nm. Data sets (phase shift and average intensity) at two different source-detector distances are acquired: the absorption and scattering coefficient spectra of the medium are then calculated from analytical expressions for (mu) _a and (mu) _s'. Methylene blue (peak absorption wavelength 656 nm) is used as a test absorbing material. The methylene blue is dissolved in an aqueous Liposyn solution which serves as the multiple scattering medium. The relative amounts of absorber and scatterer are chosen such that the values of (mu) _a and (mu) _s' match typical values in tissues. The results obtained for (mu) _a((lambda) ) with this LED based technique are in quantitative agreement with those obtained with a standard spectrophotometer in a nonscattering regime.

The paper focuses on the moire technique as a tool of biomedical measurement. The real advantage of moire measurement in muscle pulsing lies in solving no contact requirement problems for which the measured system needs whole field monitoring and quick response. With the moire optical measurement system and a video camera we obtained the detail analysis of the behavior of muscle pulsing. Post-processing procedures were performed by an image processing system. The moire system was compared with a fiber optical sensor, our fiber sensing head is multiple fiber bounding with novel devices to prevent the confusion on front slope and back slope in the relation of displacement and signal intensity. The fiber optical sensor gives the reference displacement and velocity value of the major point of the muscle. In this study we also discuss the possible applications of the moire auto-measurement system in muscle pulsing.

From their use in compact disc players and telecommunications to supermarket scanners, semi-conductor diode lasers now play an ever important role in medicine. Beginning in ophthalmology, as replacements for ion photocoagulator lasers, and used for several years outside of the United States for biostimulation of aching muscles and to treat chronic ulcers and wounds, high-powered diode systems are now finding their way into surgery and, in the future, will be used to activate photoactive dyes in the photodynamic therapy treatment of cancers, and perhaps to weld tissue to replace sutures. In this presentation, we attempt to cover the above applications as well as some newer ones, discussing the companies involved, the systems in use or under development, and some exciting new developments about to unfold.

An engineer or scientist devises a patentable technology on a device that offers a unique product advantage. Why then is it difficult to convince a medical manufacturer to market the device? A clinical research team conceives new applications that have unquestionable value. Why can't they obtain support for their research from the medical manufacturer environment? These are questions that medical laser manufacturers are constantly evaluating. There are many issues that a corporation must consider, including product life cycles, current market focus, technological production ability, regulatory compliance, and many more. This presentation reviews issues such as these in the current changing medical arena. An inside view of strategies for approaching corporations for support is discussed.

Now there exists no clear complete knowledge about mechanisms and pathways by which low level laser bioactivation works. Modulated laser light action has been investigated two new ways: dynamical infrared thermography and computing image of living brain. These ways permit observation in real time laser action on peripheral blood flow, reflex reactions to functional probes, thermoregulation mechanisms as well as brain electrical activity changes of humans. We have designed a universal apparatus which produced all regimes of the output laser light. It has a built-in He-Ne laser with an acousto-optic modulator and an infrared GaAs laser. The device provided spatial combination of both the light beams and permitted us to irradiate an object both separately and simultaneously. This research shows that the most effective frequencies range from several to dozens of hertz. The duty factor and frequency scanning are also important. On the basis of these results in Russian clinics new treatment methods using modulated light are applied in practical neurology, gynecology, etc.

The basic theory behind conventional colorimetric and fluorimetric optical sensors for CO₂ is examined with respect to the effect on sensor response of the key parameters of initial base concentration and dye acid dissociation constant, K_D. Experimental results obtained in aqueous solution using a variety of different dyes and initial base concentrations are reported and found to be consistent with the predictions made by the theoretical model. A series of model-generated pK_D versus %CO₂ curves for different initial base concentrations allow those interested in constructing an optical CO₂ sensor to readily identify the optimum dye/initial base combination for their sensor; the response of the sensor can be subsequently fine-tuned through minor adjustment of the initial base concentration. The model appears also to apply to the new generation of plastic film CO₂ sensor which have just been developed.

Luminescent transition metal complexes show great promise as sensors and molecular probes. Recent advances as well as problems associated with their utilization are discussed. Particular emphasis is given to oxygen sensors based on luminescence quenching.

The SensiCath^TM arterial blood gas (ABG) monitoring system allows rapid blood gas and pH measurements using fiber optic sensors in a paracorporeal device. The paracorporeal device location allows blood to be withdrawn from a vascular access, measured and returned to a patient, without direct handling and blood loss associated with traditional sampling techniques. The disposable device contains three fiber optic sensors and one temperature sensor. The sensors are monitored using a three-channel, solid-state instrument of minimal size and weight. Measurements of pH, pCO₂, and pO₂ are made at the point of care, on demand, with results available in 60 seconds. Calibration is performed using two prepackaged, sterile, nontoxic, nonpyrogenic solutions. The paracorporeal location allows access for calibration before or during patient utilization, and for quality assurance checks at any time during use. Laboratory data are presented which assess precision and accuracy of the SensiCath system by comparing its performance measured against tonometered gases and a calibrated pH glass electrode. In vivo animal data using a rabbit model indicate the SensiCath system performance is compared against two independent standard blood gas analyzers. The clinical utility of the SensiCath system incorporated into standard arterial lines is discussed.

This paper describes some of the issues faced by developers of intravascular blood gas sensors. These issues are illustrated from the experiences of the Abbot Research Hemometrix^TM program. After briefly describing the technology, we discuss the standards against which these sensors are compared. Then we indicate typical bench, animal, and clinical data. Finally, we discuss some of the in vivo problems associated with clinical use and the solutions to those problems developed by Abbott.

Continuous intra-arterial blood gas monitoring is a potentially valuable tool in the surgical and intensive care arenas. A continuous blood gas monitoring system utilizing transmitted light sensors and LED light sources is presented. Transmitted light sensors incorporate a tight 180 degree bend at the tip of the optical fiber and provide a true transmission measurement of the signal through the chemical indicator systems. This configuration may be used with either absorbance or fluorescent based chemical indicator systems. The unique sensor design results in significant optical, mechanical, manufacturing, and clinical advantages. Utilization of all LED light sources is desirable to reduce the cost, size, and complexity of the electro-optical instrumentation. Low cost compact instrumentation will facilitate interfacing blood gas monitors to existing modular point of care monitoring equipment. In vitro results from a prototype system that utilizes all LED light sources are presented. In addition, clinical results and anecdotes from recent clinical trials utilizing low power halogen sources are shown. Long term stability, accuracy, and clinical utility are discussed.

Blood gas analysis has been shown to be the most critical factor in determining patient survivability in a trauma care environment. Present techniques of non-invasive measurement of blood gases in the trauma care unit such as optical pulse oximetry and transcutaneous electrodes are inadequate due to complexity and inaccuracy. The crux of the solution to this problem is the application of a recent, DOD/NASA developed micro-optic spectrophotometer to perform blood gas analysis via fiber optic transmission. The newly developed blood gas analyzer described here will not only overcome the aforementioned drawbacks but also be highly accurate, durable, and safe in hazardous environments: e.g., oxygen rich environments. This spectrophotometer is driven by a microprocessor based `Kalman filter' algorithm which not only controls the monitoring of all the patients in the care center but also separates the patient's superimposed blood gas spectra into its individual components to allow a number of gases critical for trauma care to be analyzed simultaneously.

Spectroscopic measurement of myoglobin oxygenation has been made in the presence of hemoglobin using visible light. Although the spectral changes with oxygen binding are smaller, near infrared wavelengths have deeper tissue penetration. This offers an attractive means for making noninvasive muscle oxygenation measurements. Visible and near-infrared spectra of myoglobin with decreasing oxygen saturation in the presence of both oxyhemoglobin and deoxyhemoglobin were obtained. Fractional oxygen saturations were determined from the visible region. The near-infrared spectra were divided into calibration and test sets and analyzed by the method of multiple linear regression. Baseline offsets were reduced by preprocessing the data using spectral second derivatives to enhance the significant features of the spectra. This method of analysis demonstrated good correlation of the near- infrared spectra with the calibration saturation data. These results show that myoglobin oxygen saturation measurements in vitro can be made in the presence of hemoglobin as an interferant, using near-infrared spectroscopy.

A novel single mode tapered optical fiber loop biochemical sensor based on fluorescence spectroscopy has been developed. The fundamental fiber mode propagating through the tapered portion of the waveguide has evanescent fields which penetrate into the aqueous environment where the biochemical recognition event occurs. The model measurands were conjugated with a fluorescent dye, fluorescein isothiocyanate. When excited by the input laser light from the near end of the taper, generated fluorescence is coupled into the guided mode of the fiber and collected at the far end of the taper. Several radioactive and fluorescent quantification methods have been explored to determine the density of available binding sites immobilized on the fiber, and thus the ultimate sensitivity of the device. A generic avidin- biotin system has been tested as a model immunological diagnostic system. The high sensitivity of a single mode tapered loop device combined with a simple immobilization method provides a powerful tool for performing immunoassays.

An evanescent wave immunoassay for cholera antitoxin immunoglobulins was performed using a single mode tapered optical fiber loop sensor. The transducer was silanized with 3- glycidoxypropyltrimethoxysilane and chemically modified to link covalently either cholera toxin B subunit or a synthetic peptide derived from it, CTP3. The sensor was exposed to seral fluids, obtained from human volunteers having been exposed to live virulent Vibrio cholerae 01 and shown to produce rice-water stools. Other toxins of interest, such as Clostridium botulinum toxin A, have been tested on similar systems. The bound unlabelled immunoglobulins were then exposed to a mixture of FITC-anti-IgG and TRITC-anti-IgA, without requirement for a separation step. The emanating fluorescent emissions of fluorescein and rhodamine, excited by the input laser light, were coupled back into the guided mode of the tapered fiber, and used to determine the concentrations of the complementary antigens.

A sensor capable of simultaneous imaging and pH measurements has been prepared by coating the distal tip of a single imaging fiber with a pH sensitive material. The coated fiber is fabricated using photochemical polymerization with a spin coating technique, and results in a fairly uniform coating of polyHEMA/fluorescein on the order of 10 micrometers thick. Performance data, and imaging capabilities, as well as instrumentation requirements and deposition chemistry, are discussed.

Surface plasmon resonance (SPR) is currently used as an optical immunassay technique for the detection of various analytes. The uniformity of the metal film and the wavefront structure of the incident beam have an effect on the sensitivity of the SPR technique, yet most analysis methods are not capable of considering inhomogeneous layers or nonplanar excitation beams. We have applied a new numerical electromagnetic method, called finite-difference time- domain (FDTD), to this problem. To correctly model the time domain behavior of the electron oscillations, the dynamic force equation is applied to a Drude free electron model of the metal. We have analyzed a particular SPR configuration consisting of an incident beam of finite size (approximating a focused beam) onto a smooth silver film, and have obtained Poynting vector plots and reflectivity data for this configuration. The angle and magnitude of minimum reflectivity are similar for the FDTD results compared to theoretical predictions, but the angular width of the reflectivity minimum is broadened. We have also analyzed a model of a rough metal film, and find that the local electric fields are enhanced near the metal edges.

Vibrational spectroscopy and chemometrics together can be used to identify and quantify low concentrations of small molecules, but the Raman effect has been considered too weak to be employed for remote fiber optic sensing of such gases. Preliminary data are presented suggesting that it is possible to enhance Raman signals of gases from a small probe. Polymers that have large partition coefficients for small nonpolar molecules such as general anesthetics can be used as selective absorbents for these gases. As long as the polymers do not luminesce or Raman scatter at interfering frequencies, they increase the signal-to-noise ratio of signals from absorbed molecules. Multipass cells are often used to enhance Raman scattering from gases. Forming an absorbent polymer into a ring with one or more optical `taps' allows recirculation of the excitation light, and extraction of the contrarotating Raman scattered light. Such a ring could be the basis of a small probe to be connected to a compact Raman instrument by optical fibers. These two methods of amplification improve signal-to-noise ratio, extend sensing range, and reduce both instrumental complexity and cost of sensors.

The emphasis of this project has been to initially detect the displacements of the eardrum by using a laser interferometer. A small cobalt-samarium magnet (typically weighing less than 4 mg) was placed on human cadaver eardrums and positioned inside a solenoid coil. An ac modulated signal, having a frequency range of 500 - 2500 Hz, was passed through the coil. This signal created an ac magnetic field inside the coil that caused the magnet to vibrate at the modulation frequency. A commercial (TSI) laser interferometer as well as a laboratory-based fiber-optic interferometer, both operating at 632 nm, were used to examine the displacements initially. For measurements made with the fiber-optic interferometer at a frequency of 1500 Hz, the displacement of the eardrum was approximately 68 nm. The response decreased linearly at a rate of 0.02 nm/Hz for frequencies greater than 1500 Hz. This paper reports on the experimental apparatus as well as the experimental results. Details on the design of the driving circuit and the interferometers also are presented.

An interferometric type fiber-optic pressure sensor is constructed by attaching a 125 micrometers single-mode fiber inside a 1.4 mm outer diameter miniature tubing capped with a 2.5 micrometers diaphragm. The optical fiber looks at the diaphragm displacement caused by pressure. The gap between the fiber end and the diaphragm forms a Fabry-Perot interferometer. The number of optical fringes at the output is directly related to the pressure acting on the diaphragm. A second sensor is constructed using a 925 micrometers outer diameter micro bellows. The fiber- optic sensor data compares well with a strain gauge type pressure transducer.

A two bandpass prototype radiometer utilizing a silver halide optical fiber for temperature measurements was constructed for the first time. Preliminary results show the feasibility of the two bandpass method for ambient temperature measurements. This method eliminates errors arising from geometrical factors, and reduces the sensitivity to emissivity changes.

This paper discusses a real-time augmented kinematic feedback system which can be used as a diagnosis tool for individuals with motor disabilities. The system captures and analyzes movement via color targets attached to an individual and then feeds back information about movement kinematics. This target tracking approach has a high potential for achieving a real- time kinematic assessment capability. The approach recognizes distinct moving colored targets using video data. Multiple colored targets are attached to an individual at strategic locations and then target movement is tracked using a video data acquisition system. The ability to track and assess movement in real-time allows researchers and practitioners to better study and potentially treat various motor disabilities. Recent research has suggested that kinematic feedback can enhance motor recovery of disabled individuals. This approach addresses the need for a real-time measure of human movement and discusses using kinematic feedback to enhance disability recovery.

In clinical chemistry, sensors are needed that can detect small analyte concentrations in complex physiological media. During hemodialysis it is especially important to determine the urea concentration on line in order to monitor the completion of the purification. In this paper we describe a multicomponent fiberoptical biosensor for use in hemodialysis monitoring. Since no substrate flow is required in the sensor head, this technology is especially suited for monitoring in physiological solutions (no electrical contact to the patient is necessary).

An optically powered sensor for measuring pressure which linked by optical fiber is developed in a new scheme. Its pulse position modulation (PPM) optical signal and optical supply power for electronics in probe are transmitted to and fro via a single optical fiber. The optical power is carried by a laser diode (LD) source with 1300 nm wavelength and the sensing data are carried by LED 850 nm source. The remote probe uses all CMOS chips and particular modulations (PPM and PWM). Its electrical consumption including signal manipulation and LED driven current from optical conversion is less than 100 (mu) W. The laser diode supplies 5 mW of optical power into the fiber. An advanced photodetector converts sufficiently the section of this power into electrical power to drive the whole probe operation. The optically powered distance gets up to 500 m. The novel sensor combines advanced optical fiber and electronics technology into a system. It continuously measures pressure in real time. Because of using the principle of ratio measurement between mesurand and reference signals, as well as light feedback for light source stability, the system is available with high reliability, outstanding accuracy, and repeatability.

This paper is concerned with the design of high-sensitive, with noise equivalent power (NEP) less than 10^-17 WHz^-1/2, detectors and imagers of infrared (including submillimeter) radiation. Excitonic detectors are based on IR-quenching effects for secondary visible radiation of crystal and represent the new generation of IR-detectors, because they use optical (contactless) read-out of information from an IR-sensor. It is possible also to create a matrix version of such devices, which supposes the use of light fiberoptics and corresponding processing methods. As a result of our proposition both the single detectors for use in the radiometers, which determine the temperature difference, and visualizers or TV- photocathodes for IR-band, particularly for its far longwave (submillimeter) region, may be created. As it was supposed, just in submillimeter range the exchange by genetic information is realized. The intra-cell water strongly absorbs the submillimeter radiation, however, the nervous fibers are seen to be the dielectric waveguides in the submillimeter band.

We report the feasibility study of a versatile optical configuration consisting of a phase conjugate Michelson interferometer in conjunction with microscopic imaging optics for image processing and trapping of microscopic objects. Our test samples include phase gratings, amplitude gratings (i.e., Ronchi rulings), polystyrene microspheres, and biological samples such as liposomes and yeast cells. We have experimentally demonstrated (1) the novelty filtering feature which enhances the image of moving phase objects by suppressing the stationary background, (2) contrast reversal which is useful for the imaging of light absorbing (or scattering) particles, (3) the aberration correction capability of the system to enhance the image quality of microscopic objects embedded in or otherwise distorted by aberrators, and (4) optical trapping of polystyrene microspheres. The potential of using this technique for the manipulation and diagnosis of biological cells and tissues is discussed.

The temperature of the reaction zone is one of the main parameters for the characterization of laser-tissue-interaction. IR-radiometry, a noncontact temperature measurement method, is used to determine the temperature of the reaction zone. To be able to measure the inside of cavities, especially of hollow organs, we used IR-fibers to guide the temperature radiation to the complex receiver device. During the laser-tissue interaction the IR-radiation field of the reaction zone is focused on an IR-optical fiber made of AgCl_xBr_1-x. The temperature is measured for Nd:YAG laser application with different power densities and compared with standard thermographic equipment.

This paper looks back on the transmission of acoustical shock waves via optical fibers. After that it presents recent results on an optical and acoustical system of a new combined endoscopical laser and ultrasound surgical therapy (LUST) for coagulation and tissue disintegration. Theoretical calculations concerning the transmission of acoustic energy via optical fibers are shown. In first experiments on the transmission of high power ultrasound via a silica fiber of 800 mm length a longitudinal elongation of up to 30 micrometers at the distal end with a simultaneous laser transmission was achieved. A magnetostrictive ultrasound transducer with a frequency of 26 kHz and a Nd:YAG laser (25 W cw) was used.

In the upper respiratory tract, a new endoscopic procedure with ultra-thin and miniature fiberoptics (290 micrometers - 2 mm) finds a wide range of application in the differential diagnosis and treatment of pathological changes, especially within the nasal cavities and the paranasal sinuses. In order to restore the normal condition of ventilation and drainage of the paranasal sinuses or to remove internal inflammation the given foramina or ducts are widened mechanically. In case of the ostium nasomaxillaris `anatomical landmarks' can be used for orientation. But in case of the ostium nasofrontalis ((theta) 1 - 3 mm) or revision surgery where the anatomical conditions are not definitely defined or totally changed, problems can occur due to a lack of orientation. Dangerous complications which can occur due to surgical disorientation are the injury of the optic nerve and the dura mater. This paper presents an endoscopic variation of the infrared idaphanoscopy (IRD), a band-limited cw transillumination method, which enables localization of the foramina or ducts during the endoscopic procedure resulting in a reduction in the risk of disorientation.

Scattering measurements were performed on samples of waveguides used for CO₂ laser energy transmission for medical purposes. The scattering results are a sensitive tool which indicate the relative transmission of laser energy through the waveguide.

Flexible plastic waveguides (FPW) were first developed for CO₂ laser radiation. Further investigation of the factors which influence the quality of the reflecting and refracting layers, have led to the development of a method of smoothing of the substrate and the layers. A mechanism of controlling the dielectric layer thickness was also devised. Based on this knowledge we produced waveguides which can transmit several wavelengths of laser radiation. Measurements of the transmission characteristics of FPW coupled to Er-YAG (2.94 micrometers ), and Ho-YAG (2.1 micrometers ), CO (5.5 micrometers ), CO₂ (10.6 and 9.6 micrometers ), and TEA laser (9.6 micrometers ), under various conditions (power, bending) were made and show good results. The use of the FPW in transmitting these types of laser radiation may broaden the spectrum of uses of the waveguides in medical application, i.e., hard tissues (bone, teeth) and in the eyes.

A novel process called substrate induced quenching (SIQ) and a mathematical derivation of an empirical relation describing it are presented. Based on this a model is proposed for a dehydrogenase enzymatic system that includes the effects due to dynamic/static quenching of the fluorophore by either the enzyme substrate or the product. The validity of the model is shown by comparison with experimental results for the SIQ based ethanol assay involving the alcohol dehydrogenase enzyme. Various applications of this novel technique are discussed.

A novel optical procedure for measuring L-glutamate concentrations is described that exploits the quenching of thionine fluorescence by NADH, the latter being generated due to the reduction of NAD⁺ in an enzymatic reaction between L-glutamate dehydrogenase (GlDH) and L-glutamate. A substrate induced quenching (SIQ) constant of 660 (+/- 140) M^-1 at 200 s is obtained. The reported method was investigated over the L- glutamate concentration range of 0 - 800 (mu) M and offers a detection limit of 6 (mu) M.

Quenching of the molecular excimer fluorescence is proposed for measuring the concentrations of an analyte. The validity of this concept is demonstrated by constructing an oxygen sensor that is based on the quenching of the pyrene excimer fluorescence. The Stern-Volmer type analysis of the quenching data obtained for the monomer and excimer fluorescence reveals that for the excimer fluorescence the oxygen quenching is 3 times faster than for the monomer quenching. Furthermore, the excimer quenching plot is linear while the monomer quenching plot shows a downward curvature. The response of a 0.1 mm thick sensing layer made out of silicone rubber is fully reversible with a response time of less than 5 sec. An empirical relation that correlates the fluorescence intensity of the two excited species to the quencher concentration is presented. This relation is suitable for exploitation in developing `ratio sensors.' Various factors contributing to improved sensor performance are discussed.

Photon fusion is proposed as a new method for molecular sensor development. In a molecular system, higher wavelength radiation is absorbed, and a lower wavelength radiation is emitted that is quenched by an analyte. This concept is demonstrated by developing a sensitive assay for reduced nicotinamide adenine dinucleotide (NADH). Indicator benzopurpurin 4B, when excited at 458 nm, emits at 357 nm. This latter fluorescence is quenched extremely efficiently by NADH, with a half quenching concentration of 40 (mu) M and a Stern-Volmer constant of 25 X 10³ M^-1. The advantages of this method are outlined.

Use of more than one indicator, each responding to a different parameter or bio-reaction component, is proposed to improve the sensor performance. In order to demonstrate the feasibility of this concept, glucose was chosen as model analyte, and the well known glucose oxidase (GOD) reaction was employed to measure its concentration. An analytical signal was obtained by using two indicators, one sensitive to the oxygen and the other one sensitive to pH changes that result due to the enzymatic activity. Indicators with common absorption wavelengths but different fluorescence emissions were chosen. A further condition for choosing these indicators was their overlapping absorption spectra with GOD. Energy transfer between the various resulting pairs, namely GOD-ruthenium complex, GOD-fluoresceine, fluoresceine-ruthenium was investigated. This preliminary work suggests that the photostability of a biomolecule, and hence that of the sensing element in an optical biosensor, can be augmented by using a suitable indicator combination.

A novel method for the fluorometric measurement of an analyte is described that is based on the anti-Stokes fluorescence of an indicator. The validity of the concept is demonstrated by developing a sensitive assay for NADH. Thionine, a thiazine dye, when excited using radiation of a wavelength 630 nm, emits a broad fluorescence, peaking at 620 nm. Similar to the Stokes fluorescence, this anti-Stokes' fluorescence of thionine is efficiently quenched by NADH. Stern-Volmer plots of the quenching data reveal a quenching constant of 0.7 X 10³ M^-1. The process of quenching is attributed to a photo-reaction between the excited thionine and NADH, resulting in NAD⁺.

A compact, light, easy to use, and low cost instrument with technical solutions that make it suitable for wide clinical use is presented. It is specifically designed for rehabilitation of patients after heart failure. The instrument makes use of low power laser diodes, at 750 and 810 nm, and a remote fiber optic probe. Reflectance change at two wavelengths is used to determine variations of the oxygen content of tissues. A time-variant filter enhances signal to noise ratio and rejects stray light. This specific electronic device allows the use of a low-cost, small and reliable photodiode in place of a photomultiplier tube. Time division techniques is used to process both 750 and 810 signals with a single collecting fiber, photodiode, and preamplifier. The instrument output is two analog signals proportional to the reflectance intensities at 750 and 810 nm, so it is possible to acquire these signals by a PC with a standard A/D board to drive directly a chart recorder. Some clinical tests during the exercise are presented.

Endoscopy has been widely applied for visual inspection in difficult to access environments. In the medical field, endoscopy is not only the method of diagnosis but also the method of treatment. In regular endoscopy there are some fundamental limitations that can affect the proper diagnosis or treatment. When a three-dimensional object is imaged by means of an endoscope, only a two-dimensional display is possible. So, the endoscopic image does not provide any quantitative information about the size of objects. In modern diagnostics, however, it can be necessary to know the size and the shape of objects or to perform some deformation analysis. The optical methods for reconstructing the 3-D object shape from a 2-D endoscopic image are described and illustrated with some examples.