A new optical fluorescence-based microsensor has been developed to continuously monitor intra-arterial blood gases (pH, pCO2, p02) with a probe sufficiently small to share the lumen of a 20 gauge arterial catheter without compromising pressure fidelity or ease of blood withdrawal. The evaluation of performance has proceeded through a combination of in-vitro, animal and clinical studies. Each has had its own unique problems. This series of studies has re-emphasized the fact that acceptable clinical performance of even the best designed systems is not assured by success in in-vitro or even animal studies. In-vitro studies were conducted to quantify the precision and time response of the sensors and to obtain an assessment of performance characteristics in the in-vitro environment. System precision (1 S.D.) in tonometered bovine blood was 0.03 (pH units), 2 mm Hg (pCO2), and 4 mm Hg (p02). These results were collected over 40 points at two different temperatures (28 and 37 F). Average drift measured over a 200 hour continuous study period showed 0.005 pH units, 0.9 mm Hg pCO2, and 2.1 mm Hg p02 per 24 hour period. In-vivo animal studies (dog, pig, sheep, and rabbit) demonstrated the need for antithrombogenic materials. The probe system employs a covalently bound Heparin coating. However, maintenance of a patent IV drip line and adequate arterial flow was found to be critical. With proper attention to these factors, overall probe performance was found to be equivalent to that predicted by the in-vitro studies. Clinical trials in volunteers, and in critical care and surgical patients, have re-affirmed the need for antithrombogenic probe materials and adequate arterial blood flow. In addition, human studies revealed factors which can lead to sensor offsets, unless properly compensated by probe design. Subsequent clinical trials in volunteers and clinical subjects have verified that continuous monitoring of blood gases is feasible with accuracies approaching that of the in-vitro blood gas analyzer.

Instrumentation requirements for sensors based on the measurement of light passing through multi-mode fiber optics are discussed. A model is presented which treats the light source, optics, fiber optic sensor, and photodetector as an integrated system regardless of the mechanism of signal transduction, e.g. absorbance, fluorescence, etc. Analytical models for prediction of the performance of incandescent and flash lamps are presented along with comparative experimental data. Photodetection schemes utilizing solid state photodiodes and photomultiplier tubes are analyzed and analytical models for prediction of detection limits are presented. Criteria for optimization of the overall system performance are laid out.

The whole field of biosensing has been enhanced by the development of optical fibers(l). They provide a means of activating the sensors and of carrying the sensor's signal back to the detector. The small dimensions and flexibility of the fibers allow the development of miniaturized sensor packages capable of introduction into a patient's vascular system. Several in vitro systems are already competing in high risk operations with standard laboratory procedures to provide more timely and accurate analysis of the patient's condition. During the next decade real time sensing in vivo together with various endoscopic and developing laser surgery techniques will provide doctors and patients with many new and delicate alternative procedures to common surgery. Not only will trauma be minimized, but with better and quicker knowledge of the patient's blood gas levels and other body conditions, doctors will be able to efficiently correct for unforeseen difficulties while controlling the known problems effectively. To achieve these wonders extremely small sensing areas will be available so that the sensor systems must be highly efficient. The optical fibers must activate all or at least most of the sensor's area and must be able to gather as much of the return signal from the sensor as possible. This places some strong requirements on the optical properties of the fibers. The need for flexible, yet sturdy, devices places requirements on the mechanical properties of the fibers. For the preferred silica based fibers, the fact that body fluids are primarily water place additional demands on the fibers' mechanical properties. Obviously the sensing system being in contact or close proximity with the body or its fluids must satisfy certain biocompatibility and sterilization requirements. This paper further describes these requirements and presents details about a new optical fiber which meets these requirements and provides some additional very useful properties. This new fiber which has a high numerical aperture, a hard cladding, and a pure silica core is called High NA, HCS* fiber.

The development of energy transfer based fiber-optic sensors provides a new approach to optical sensing and offers greater flexibility in the choice of analyte specific dyes. We have successfully constructed a physiological pH fiber-optic chemical sensor based on energy transfer from a pH insensitive fluorophore, eosin, to a pH sensitive absorber, phenol red. As the pH increases, phenol red's absorption increases in the spectral region that overlaps with the emission spectrum of eosin. Since the extent of energy transfer is proportional to the spectral overlap integral, the amount of energy transfer increases as the pH increases resulting in a diminished fluorescence intensity. Our present efforts are aimed at preparing pH sensitive dyes based on intramolecular energy transfer. Since the energy transfer efficiency is inversely proportional to the sixth power of the distance between the donor and acceptor, the small intramolecular distance should lead to very efficient energy transfer. Several types of intramolecular systems are being investigated.

The speed and specificity characteristic of immunochemical complex formation has encouraged the development of numerous antibody-based analytical techniques. The scope and versatility of these established methods can be enhanced by combining the principles of conventional immunoassay with laser-based fiber-optic fluorimetry. This merger of spectroscopy and immunochemistry provides the framework for the construction of highly sensitive and selective fiber-optic devices (fluoroimmuno-sensors) capable of in-situ detection of drugs, toxins, and naturally occurring biochemicals. Fluoroimmuno-sensors (FIS) employ an immobilized reagent phase at the sampling terminus of a single quartz optical fiber. Laser excitation of antibody-bound analyte produces a fluorescence signal which is either directly proportional (as in the case of natural fluorophor and "antibody sandwich" assays) or inversely proportional (as in the case of competitive-binding assays) to analyte concentration. Factors which influence analysis time, precision, linearity, and detection limits include the nature (solid or liquid) and amount of the reagent phase, the method of analyte delivery (passive diffusion, convection, etc.), and whether equilibrium or non-equilibrium assays are performed. Data will be presented for optical fibers whose sensing termini utilize: (1) covalently-bound solid antibody reagent phases, and (2) membrane-entrapped liquid antibody reagents. Assays for large-molecular weight proteins (antigens) and small-molecular weight, carcinogenic, polynuclear aromatics (haptens) will be considered. In this manner, the influence of a system's chemical characteristics and measurement requirements on sensor design, and the consequence of various sensor designs on analytical performance will be illustrated.

Optically active organic molecules have been entrapped in a porous silica gel host for use as an opto-chemical transducer. Organic dye molecules were incorporated into the inorganic glassy matrix via the so called "sol-gel" technique. Sol-gel derived glasses are typically synthesized at room temperature and result in the formation of a relatively low density network structure, capable of supporting the rapid transport of atoms and small molecules. This "cage-like" network, however, serves to entrap larger molecules, such as organic dyes. The guest probe molecules do not migrate through the silica host. Fluorescence characteristics of optically active dye species, in many cases, are known to change in solution with respect to the activity of factors such as oxygen and pH. We have fabricated silica gel films containing organic probes, and measured changes in emission spectra of entrapped pyranine dye due to variations in the pH of ambient aqueous solution.

Following a brief review on the history of optical oxygen sensing (which shows that a variety of ideas exists in the literature that awaits the extension to fiber optic sensing schemes), the present state of probing oxygen by optical methods is discussed in terms of new methods and materials for sensor construction. Promising sensing schemes include simultaneous measurement of parameters such as oxygen and carbon dioxide with one fiber, measurement of fluorescence lifetimes and radiative energy transfer efficiency as well as phosphorescence quenching. New longwave-excitable fluorophores have been introduced recently, two-band emit-ting indicators can help to eliminate drift problems, and new methods have been found by which both indicators and enzymes may be entrapped in silicone rubber, which opens the way for the design of new biosensors. In a final chapter, the application of fiber optic oxygen sensors for blood gas measurement and as transducers in biosensors are presented.

Phosphatidyl choline-cholesterol and stearic acid monolayers and multilayers were deposited onto borosilicate glass, quartz and crystalline silicon surfaces by transfer from the air-water interface of a Langmuir-Blodgett trough. Contact angle, ellipsometric, X-ray photoelectron and fluorescence measurements provided characterization of phospholipid monolayers on hydrated or alkylated silicate surfaces. A fluorescent lipid film supported on a quartz optical fiber demonstrated the feasibility of preparation of an evanescent-wave based intrinsic optrode. Further development of intrinsic biosensors based on lipid membrane structures is described in terms of optical conduction of lipid multilayer wave guides, and new membrane-soluble fluorescence probes such as trans-4-dimethylamino-4'-(1-oxobutyl)stilbene.

A fluorescence-based optical affinity glucose sensor which offers the advantage of equilibrium reactions has been developed. However, our efforts to miniaturize its optical components is hampered by unavailability of a suitable solid state emitter. An absorbance-based sensor is investigated to overcome the miniaturization difficulty of the optical system. A suitable dye is selected and tagged to the dextran. A small and portable optical detector using a photodiode and a red LED is fabricated. Our preliminary in vitro, results indicates the feasibility of this approach as an ambulatory glucose sensor.

Optrodes employing immobilized enzymes were developed using covalent attachment of sensor reagents. This development is an extension of the original application of this sensor technology in which a pH sensor was constructed with the pH sensitive dye fluorescein incorporated into a polymer covalently attached to the fiber tip. This sensor displayed significantly improved response times over previous fiber optic sensors because of reduced diffusion limitations. In addition, the signal intensities were greatly enhanced by the high concentration of fluorescent dye localized at the fiber tip. With the anticipation that these qualities would be preserved, a class of sensors based on the immobilization of biomolecules in the polymer matrix became the next goal. This paper will first describe a fiber optic probe prepared by immobilizing esterase in a crosslinked polyacrylamide matrix. The immobilized esterase converts the nonfluorescent fluoresceindiacetate into fluorescein. Both the steady state level and kinetic generation of fluorescence can be related to the concentration of fluoresceindiacetate. A fiber optic sensor for penicillin has been made by coimmobili zing penicillinase with a pH sensitive fluorescent dye. Penicillinase converts penicillin to penicilloic acid which produces a microenvironmental pH change in the dye-containing polymer matrix resulting in a concommitant change in fluorescence. The change in fluorescence is proportional to the concentration of penicillin and a 95% response is reached in 40-60 seconds. The sensor has a detection limit of 2.5 x 10-4 M. Another class of sensors using immobilized bioreceptors will be based on the principles of fluoroimmunoassay. This paper will discuss some basic principles and problems of 1) fluorescence quenching immunoassays, 2) fluorescence excitation transfer immunoassays, and 3) energy transfer immunoassays for digoxin. Both advantages and inherent problems for these sensor preparations will be addressed.

A prototype fiber optic oxygen sensor was fabricated by grafting poly(2-hydroxyethylmethacrylate) (PHEMA), containing the oxygen quenchable fluorescent dye, 9,10-diphenylanthracene (9,10-D), to a glass fiber. The PHEMA-glass fiber graft was optimized to maximize stability in hydrolytic environments. The fluorescence of the dye was quenched 20% when the sensor went from an oxygen-free to an oxygen-saturated environment. Transient response times of the sensor were reduced when the PHEMA graft thickness was reduced. Modeling of the transient data gave a diffusion coefficient of oxygen in PHEMA of 2.15 x 10-6 cm2/sec. Glucose oxidase (GOO) was incorporated into PHEMA for the ultimate purpose of converting the fiber optic oxygen sensor into a glucose sensor. Immobilization of glucose oxidase was accomplished through a physical entrapment in the PHEMA matrix. Immobilization parameters such as thickness of the polymer layer, enzyme loading, and polymerization conditions were adjusted to give adequate sensitivity in the desired range of glucose concentrations. Immobilized GOx activity was measured over a wide range of enzyme loadings and glucose concentrations. The feasibility of using PHEMA containing 9,10-D and GOx as a material sensitive to physiological levels of glucose was demonstrated.

An indicator system consisting of a potential sensitive fluorescent dye in the presence of liposomes and valinomycin has been shown to reversibly and selectively respond to changes in potassium concentration.

We performed angioscopy on 31 patients with suspected chronic pulmonary arterial ob-struction using three prototype angioscopes. The instruments varied in length (80, 90, and 120 cm), outside diameter (3.2 and 4 mm), and distal tip deflection (70, 90, and 180 degrees). All had a distal viewing balloon. Conventional diagnostic studies were performed and decisions about diagnosis and operability were made prior to angioscopy. An independent assessment of diagnosis and operability was then made based on the results of angioscopy. Surgical confirmation was obtained in most cases and clinical or autopsy data were obtained in the remainder. Angioscopy led to a change in the diagnosis of 6 patients (19%). Four of 25 patients with chronic pulmonary emboli were felt to be inoperable based on the angioscopic findings. Two of these 4 underwent surgery and were found to be inoperable. 21 of the remaining 25 patients were felt to have operable disease and 19 underwent surgery. In 14 of these 19 (74%), the conventional studies were either negative or equivocal with respect to operability and the decision to operate was based on angioscopic data. We conclude that good visualization of the central pulmonary arteries can be achieved with the optical balloon technique; that the procedure can be performed safely in patients with severe pulmonary hypertension; and that the information obtained by angioscopy can significantly affect clinical decisions in patients with chronic pulmonary artery obstruction.

A new thin coronary angioscope which has a inflatable balloon at its distal tip is described in this paper. This angioscope is formed into very thin flexible catheter, less than 4F(1.33mm) in sheath outer diameter at the catheter tip. The angioscope contains two penetrated lumina which utilize for either flushing blood or manipulating of a guiding wire. A selective intracoronary visualization in left anterior descending coronary artery (LAD) and circumuflex(CX) of dogs up to 15kg in their weight were carried out during up to 20s until occurring of ST segment change of the electro-cardiogram(ECG).

The most suitable structure of the ultrathin silica based imagefiber for the medical usage were investigated by evaluating the image transmission characteristics and the mechanical characteristics. As a result, following facts have been clarified, 1) In the case of NA 0.43, the suitable structural parameters are core-cladding ratio 1.5 and pixel diameter 5 μm. 2) The 0.27 mm diameter imagefiber can stand more than 103 times repeated bending in 10 mm radius.

The paper contains considerations on the physical and technical limits to miniaturization of high-quality optical fibre image guides for medical applications. We have shown the possibility of manufacturing a 500 um diameter image-guide of TV quality. The technological experiments were performed using a newely developed mosaic-assembling technology of preform manufacturing and fibre pulling. The paper closed with a real -life medical application considerations for this micro-image-guide-cathether.

Fiberoptic temperature sensors have found valuable application in several areas of research and treatment in biology and medicine. These include tissue monitoring during electromagnetic heating for cancer therapy, catheter-tip sensors as part of multi-purpose fiberoptic probes, patient monitoring during magnetic resonance imaging (MRI), and microwave biohazards studies. The advantage of fiberoptic probes compared to more conventional temperature sensors such as thermistors or thermocouples lies in the nonconductive property of the glass or plastic fibers used. This avoids shock hazard to the patient, and perturbation of the readings in electromagnetic environments. Fiberoptic temperature sensors may be classified into one of three general categories: 1) intensity, 2) wavelength, and 3) time-domain. Types of optical sensors which have been successfully employed with fibers include fluorescent materials, semiconductors, birefringent crystals, and Fabry-Perot interferometers. An example of a wavelength-based sensor is described herein; it is a new technique based upon wavelength shifts in a GaAs sensor using broadband illumination and a fast-scanning spectrometer, and appears useful over the biological temperature range of 25-50°C.

An all optical fiber interferometric temperature sensor suitable for microwave environments is discussed. The sensor is capable of continuously and accurately monitoring temperatures safely and reliably. The transducer features small volume (as small as .35 mm in diameter and 2 mm in length), with an operating temperature span of 22.5°C that may be centered about a specific temperature in the range of 50°C to >250°C. Because phase modulation is employed, the transducer can be hundreds of meters from the demodulation package. Since it uses Fabry-Perot geometry, it exhibits minimal lead sensitivity. The fiber-optic system is constructed of all dielectric material and thus is immune to EMI. The sensor has a resolution of .002°C and an accuracy of ±.01°C. It can be packaged in an array to measure temperatures at multiple locations.

Hypothermia is a condition which results from prolonged exposure to a cold environment. Rapid and efficient heating is needed to rewarm the patient from 32-35°C to normal body temperature. Hyperthermia in cancer treatment involves heating malignant tumors to 42.5-43.0°C for an extended period (e.g. 30 min.) in an attempt to obtain remission. Microwave or radio frequency heating is often used for rewarming in hypothermia or for temperature elevation in hyperthermia treatment. One severe problem with such heating is the accurate measurement and control of temperature in the presence of a strong electro-magnetic field. For this purpose we have developed a fiberoptic radiometer system which is based on a non-metallic, infrared fiber probe, which can operate either in contact or in non-contact modes. In preliminary investigations the radiometer worked well in a strong microwave or radiofrequency field, with an accuracy of ±0.5°C.

Microsensor with double core optical fiber for temperature measurement is presented herein. Double core optical fiber is used in order to diminish size of a probe in which there is a semiconductor sample glued to the end of the fiber. During doubled passage of light through the semiconductor sample, the amount of absorbed light changes due to temperature - caused shifts in the absorption edge.

Fiber optic biosensing probes for several bioanalytes of clinical and biomedical importance are described. The development of biosensors based on immobilization of a deaminating enzyme at the tip of a fiber optic ammonia sensor is illustrated with a biosensing probe for urea. In addition, biosensors based on the direct fluorometric detection of reduced nicotinamide adenine dinucleotide (NADH) at the tip of an optical fiber device are presented. Probes for lactate and pyruvate illustrate this concept. Finally, preliminary results from an investigation to prepare NADH sensing probes based on immobilized bacterial luciferase are given.

Fiber optic chemical sensors capable of detecting glucose and penicillin were developed. Each consists of a polymer membrane that is covalently attached to the tip of a glass optical fiber. The membrane contains the enzyme and a pH-sensitive fluorescent dye (fluorescein). A signal is produced when the enzyme catalyzes the conversion of the analyte (glucose or penicillin) into a product (gluconic or penicilloic acid, respectively) that lowers the microenvironmental pH of the membrane and, consequently, lowers the fluorescence intensity of the dye. Each sensor is capable of responding to analyte concentrations in the range of ~0.1 to 100 mM. The penicillin optrode response time is 40 to 60 s while that for glucose is ~5 to 12 min.

The potential of fiber optic chemical sensors (FOGS) for medical applications is an accepted fact. Indeed, many companies are arduously pursuing the pH, pCO2, and p02 sensors. These, however, only represent the beginning of what, eventually, could be the next generation approach to diagnostics and monitoring. The key to a good FOGS system is to: (i) make, or adapt, accepted laboratory chemistry so that it works, without loss of sensitivity or specificity, on a fiber optic; (ii) assure that sensor neither affects, or is affected by, the biological meltum into which it is placed; (iii) have optimized, dedicated instrumentation to illuminate the sensor, and to handle and process its output signal; and (iv) perform a necessary diagnostic, monitoring or clinical function better, faster, more accurately or less expensively than existing approacbes. Theoretically, there are no limits to the reactions that can be selected to identify and quantify a particular chemical or physical happening using a species specific FOGS. In practice, however, the choices are restricted because: (i) many of the existing tests use sample prepreparation, such as concentration and purification, which is not possible for many FOGS usages; (ii) the chemistry on the fiber must meet FDA criteria; (iii) the chemistry is not stable enough for long term storage and (iv) measurements which are marginal in the laboratory, will not work on a fiber. In the present research the potential of using enzymes as the sensing material is being evaluated. To date emphasis has been placed on the immobilization of the enzyme on the fiber optic without loss of activity or specificity. The selected enzyme for this effort is 3α-hydroxysteroid dehydrogenase. It was selected with the eventual goal of analyzing bile acid concentrations.

A single fibre fluoroprobe using excitation from an argon ion laser has been constructed. The probe has been used to measure fluorescence from a dye in aqueous solution and simultaneously to detect Raman scattering from the water. It has been shown that the measured fluorescence decreases as scatterer is added to the solution but that the ratio of fluorescence to Raman signal is constant for a given dye concentration. This ratio did not remain constant when an absorbing ink was added.

Spectrometry of potential-sensitive dyes permits now the monitoring of membrane potential (MP) variations on excitable tissues. It is also possible to monitor qualitatively the electromechanical activity (EMA) on contractile tissues using this same method. We improved two new optical fiber systems for measuring fluorescence. System 1 used two 200 um optical fibers permitting fluorescence excitation of the potential sensitive dye (PSD) (1st Fiber) and the measurement of its fluorescence (2nd Fiber). System 2 used two 200 um optical fibers for a differencial measurement of excitation reflexion and fluorescence through two different optical filters. The two fibers are assembled in a tube to constitute the "Optrode". In System 1, a single photodiode placed behind a 665 nm high pass optical filter (HPOF) is preamplified by a LH-0022 op. amplifier. In system 2, two photodiodes are placed respectively behind a 645 nm and a 665 nm HPOFs and differencialy preampli-fied by a AD-521 instrumentation amplifier. Analogic signals are lowpass filtered with a LT-1062 digital filter. PSDs WW781 and RH 237 were used respectively on myocardial and nervous tissues. Fluorescence excitation of PSD WW 781 was performed with a 5 mWatts Helium-Neon LASER (He-Ne) beam focused into the first opti-cal fiber of System 1 or illuminating directly the stained tissue. Fluorescence excitation of PSD RH 237 was performed with a 100 Watts filament lamp through a 400-500 nm blue bandpass filter (BBPF). These two systems are now used to study MP variations on myocardial and nervous tissues. We are now able to study the effects of different drugs on the EMA of heart muscle. This technique is usable "in Vitro" and "in Vivo". This optical fiber method easy to improve for a low cost permits now to perform studies on excitable tissues in a non traumatic way with foreseeable applications to pharmacological investigations on experimental models.

Reflectance spectrophotometry has been used to investigate tumour and normal tissue responses to porphyrin mediated photodynamic therapy of cancer. Subcutaneously implanted isogenic fibrosarcomas were treated when they had grown to 10-12mm diameter. An Argon-ion pumped tunable dye laser provided 630nm cw light, which was delivered to the tumours either interstitially through a 200μm cleaved end fibre inserted into the centre of the tumour or transcutaneously through a 600μm cleaved end fibre mounted at distance from the overlying skin surface. A reflectance spectrophotometer employing fibre optic bundles to deliver light to and collect from the tissue was used to measure reflectance spectra (450-700nm) pre- and post-treatment in tumour and adjacent normal tissue of animals with and without photosensitiser. The reflectance data were converted to a parameter LIR (Logarithm of the Inverse Reflectance) whichmay be shown to be proportional to absorbance and therefore to tissue pigment concentration. Indices of total tissue haemoglobin and oxygen saturation levels have been derived based upon the differences in the shape of the LIR spectra of oxygenated and deoxygenated haemoglobin between 500 and 600nm. These indices provided information on the vascular state of tumours before treatment and the changes that occurred during and immediately after treatment. Preliminary results indicate a large decrease in tumour blood oxygenation during treatment with little recovery, at the dose level used, up to 2 hours post treatment in photosensitised animals, suggesting a decrease in tumour blood flow. After an immediate reduction in the haemoglobin index at the start of illumination, haemoglobin levels progressively rose throughout the treatment period and up to 2 hours post treatment. No significant changes occurred in non-photosensitised animals.

The recent development of low-loss infrared zirconium fluoride fibers allows remote sensing of infrared signals. In this paper a detection device for the intravascular measurement of substances absorbing in the infrared wave length range is described. The applicability of the technique is demonstrated by the measurement of small concentrations of heavy water (D20) in blood. The method is based on the well-known fact that D20 strongly absorbes radiation in the 4 μm range while H2O and blood are comparably well transmitted at that wave length. A catheter was designed that can be inserted in arterial blood vessels. The catheter tip is constructed such that the radiation is guided by the fiber to a gold reflector. Between the reflector and the fiber, blood is withdrawn through a gap of ca. 0.1 mm. The radiation thus passes the medium twice and is guided back to the same fiber. Concentrations below 1 ml D20/1000 ml blood can be determined accurately and indicator kinetics can be recorded with time constants of the entire system below 0.05 s. The advantages of this technique are the low withdrawal rate and neglectable delay of the recorded indicator kinetics and no need for reinfusion of blood. D20 has been used to determine physiological parameters such as extravascular lung water, cardiac output and total body water. The study demonstrates that such measurements are feasable with the described fiberoptic device and that the fiberoptic approach offers distinct advantages over conventional blood withdrawal methods with external analysis. Injectate volumes as small as 0.05 ml/kg body weight are sufficient to obtain indicator kinetics with acceptable signal to noise ratio. By use of appropriate filters concentrations of other substances and their intravascular kinetics can be measured. According to their physicochemical properties a variety of information on physiological parameters appears to be accessible with this approach.

Polycrystalline alkali halide fibers were fabricated using a hot extrusion technique. Core/clad fibers of KBr/KC1 had losses as low as 0.1 dB/m at 10.6 μm, but the average loss for 800/1000 μm fiber was 0.69 ± .32 dB/m. The salt fibers were coated with teflon to mini-mize surface fracture from microcleavage cracks and to protect the fiber from contamination. The maximum output power we have obtained from the fiber is 67 watts of cw CO2 laser power. This corresponds to a power density of 13.3 kW/cm2. The 1000 μsalt fiber has been bent into a 12 cm diameter circle with a 5% reduction in transmission.

The results on the investigation of optical and mechanical properties of polycrystalline IR fibers from the point of view of their application in power delivery for laser surgery are discussed in the talk.

A theoretical ray model was developed for energy distribution of IR radiation, transmitted through hollow straight and bent fibers. The theoretical results were compared with the experimental data obtained from measurements of our plastic hollow fibers. A satisfactory agreement between the experimental and theoretical data was achieved. Application of the plastic hollow fibers in surgery (on certain organic tissues) is described.

With high power lasers electrical field strengths of light above the threshold of optical breakdown can be generated. The amplitudes of the emitted shockwaves are high enough to fracture all kinds of stones deposited in the human body. Via a special device light pulses of 70 mJ and 20 ns generated by a q-switched Nd:YAG laser are coupled into a flexible optical fiber. The parameters of the laser system are optimized for the beam transmission in thin quartz-glass fibers of down to 0.6 mm in diameter. In the vicinity of the concrement the electromagnetic energy of the light pulse is converted into acoustic shockwave energy by means of special optical devices or opto-acoustic couplers. These systems are combined with miniaturized acoustic reflectors which direct the shockwaves towards the calculus. An essential feature of these devices is their endoscopic applicability.

In the course of laser induced shock wave lithotripsy (LISL) by means of a flashlamp pumped dye laser a plasma is formed on the stone's surface. Spectral analysis of the plasma flash leads to chemical stone analysis during the procedure. A time resolved integral analysis of scattered and laser induced fluorescence light makes stone detection possible and avoids tissue damage. We used a 200 μm fiber to transmit a 2 μs, 50 mJ pulse to the stone's surface and a second 200 μ fiber for analysis. This transmission system is small and flexible enough for controlled endoscopic use in the treatment of human ureter or common bile duct stones. Under these conditions the stone selective effect of lasertripsy leads only to minor tissue injury.

The clinician interested in using the CO2 laser endoscopically in the tracheobronchial tree presently has limited options due to problems in fiberoptic transmission. Three delivery systems have been used in a laboratory setting in a canine model: a CO2 laser coupler with a specially modified rigid bronchoscope (Cooper LaserSonics), a metallic waveguide (Laakmann Electro-Optics) and a polycrystalline fiber (Cooper LaserSonics). The most efficient laser delivery system for clinical application occurred with the wave-guide requiring 32 joules to create a standard 5 mm2 lesion, as compared to 54 and 184 joules for the coupler and fiber respectively. Limited bend radius with both the fiber and the waveguide limited clinical usefullness even through rigid bronchoscopes. In addition, only 60% power transmission was possible with the waveguide (bend radius of 6 cm). This loss of power was not associated with the fiber use. Waveguide and fiber transmission of the CO2 laser have the advantages of open bronchoscope systems with excellent telescopic optics. Unfortunately, due to the awkward, semi-flexible nature of the current waveguide and fiber deliver systems flexible bronchoscopes can not be utilized and the clinician is still obliged to use the laser coupler for most clinical applications.

We have described our experience in the application of high energy argon and Nd:YAG lasers for endoscopic surgical manipulations. Laser was used for the removal of polyps with a wide base, villi tumours in colon, for the elimination of scar strictures in colon anastomosis, for the formation of primary-delayed colon anastomosis and for the removal of timoral stenosis in esophagus and in colon. Laser therapy has certain advantages over other endoscopic manipulations: long-term and immediate results are better. One can use this therapy in combination with others (radial therapy, surgical treatment). We have worked out a classification of polyps and stenosing tumours in the digestive system to determine indications for laser endoscopy and to choose the best parameters of laser irradiation.

The metal and polymer compound hollow tube is effective guide for cw CO2laser beam transmission. We have tride to high peak pulse CO2laser beam delivery with the hollow tube guide. Using the CO2 pulse laser have high peak (46MW max. ,short pulse width(80ns) and repeat pulses(under lOpps). In this experiments, the laser beam transmittance was obtained ca.90%/m. So the hollow tube are confirmed as useful beam guide technique for also pulse CO2 laser. We are having also investigates of UV laser beam transmission with the hollow tube as CO2 laser beam. We have used KrF excimer laser(248nm wavelength). We found that the random polarized beam transmittance was ca.26%/m, if polarized beam was ca.37%/m, delivery average power and energy were ca.1 watt(220kW peak power) and 5m.J. per pulse respectively. On the other hand, we have been developing UV optical fiber for Kr F laser, Results so far were obtained above 80%/m transmittance by OH ion added quartz glass fiber.

We report measurements of damage threshold and transparency of quartz fibers for the λ= 248, 308 and 351 nm radiation. Thresholds and specific energy for tissue photoablation have been determined for these wavelengths. Results of clinical applications of UV fiber laser scalpels for angioplasty and extirpation of tumours from bronchi are discussed.

The first use of excimer laser radiation delivered through a fiber optic cable to recanalize totally occluded right coronary arteries on human patients is described.

The dependence of the transmittance efficiency on input pulse energy density and flux is given. Several fibres showed a decrease in the transmittance efficiency after long term irradiation. Spectroscopic measure-ment of transmitted and fluorescent light will be presented. The dependence of damage thresholds for 1000, 600, 400 and 300 μm core diameter quartz fibres as a function of pulse length (6-300 ns), energy densities (up to 32 J/cm2), fibre preparation and the surrounding environment at the input and output of the fibre is also shown. This paper shows the results obtained when short pulsed high power UV laser radiation is transmitted through a fibre. Coupling of this laser radiation with non adequate parameters at 308 nm into quartz fibres will lead to a result as shown in Fig. 1. It shows material processing of the front surface of a 600 pm quartz fibre. One can see the beam profile of the laser punched into the fibre.

In medicine a number of fiber-applications for laser power transmission are used on a routine basis. For example several watts of laser power out of an argon laser ( λ = 488 nm and 514 nm) are transmitted through fibers for ophthalmic surgery. Especially adapted fibers with core diameters of 50 μm or 80 μm are used. But this laser is not considered to be a "high power laser". High power lasers used in medicine are - the CO2-laser ( λ = 10.6 μm) for cutting and - the Nd:YAG-laser ( λ = 1060 μm and 1320 nm) mainly for coagulation. The beam powers are 20 - 180 W. Because fibers for the CO-laser are presently under development and thus are not yet ready for clinical use we will restrict our scope to Nd:YAG-lasers. The high power beam of the Nd:YAG-laser is usually guided through 600 μm silica fibers. But also thinner fibers should be possible. In our paper we would like to discuss whether thinner fibers are advantageous and what are the limits for reducing the fiber diameter. After a short recapitulation of fiber data the different aspects correlated to the fiber diameter are reviewed. Each aspect is discussed in detail and finally conclusions are given as to which fiber diameter seems most appropriate depending on the desired application.

Recently many researchers, doctors and instrument companies have begun developing fiber optic laser power delivery systems to accomplish less traumatic surgery or localized irradiation treatment(1). With high power levels, particularly in short bursts, large core fibers are needed to keep the power densities from approaching the damage threshold of silica. Among the many advantages of using optical fibers in laser surgery are the following: microsurgery can be employed, trauma is reduced, access to interior through catheter introduction into vascular, gastrointestinal or respiratory tracts, accurate application of laser power through a flexible lightweight medium to provide localized irradiation as well as surgical removal, and the devices are sterilizable and of moderate cost permitting one-time use (disposable) probes. To achieve these wonderful gains in surgical procedures, the optical fibers must satisfy many optical and mechanical requirements. In use the optical fibers are often required to bend around curves or obstructions to reach the desired application area. Large tensile stresses can occur on the outer radius of the bent fiber, especially with large core fibers, thus high strength fibers are needed. Furthermore, since body fluids are primarily water, stress corrosion and fatigue(2-6) will occur. Therefore, the fibers should have excellent fatigue resistance as well as high strength. This paper further describes these requirements and presents details about an optical fiber which meets these requirements and provides additional very useful properties. These fibers with pure silica cores are called Hard Clad Silica, HCS*, fibers because of their hard bonded cladding over silica structure.

Using lasers for therapeutic applications is getting more and more accepted. In ophthalmology Ar-lasers for intraocular applications are quite common. The Nd:YAG-laser is used as a high power tool in connection with silica fibers for different extracorporal and intracorporal applications. The CO2-laser is the cutting laser, one problem being the beam transmission: The state of the art in fibers is not sufficient up to now. Because of the high power used safety against laser radiation hazard is of great importance. The safety in laser use is primarily dependent on the surgeons cautiousness, e.g. using laser protection goggels, observing that the spot of the aiming beam is present etc. On the other hand the laser and fiber system has to be inherently safe by appropriate technical means as far as possible. An additional aspect adding to safety is the handling: With easier system handling less attention of the surgeon is necessary for driving the apparatus. Thus he can concentrate on the patient and on the procedure. In considering the fiber system one important point in handling and safety is the coupling of the fiber to the laser head. The development philosophy in this coupling may be divided into two groups: - one is trying to use standard connectors which were initially developed for data transmission; - the other is using special connectors. One example of the first group is the guiding of the laser beam from the Ar-laser to the slit-lamp in ophtalmology. Here the well-known F-SMA connectors together with a special fiber with adapted numerical aperture are used. The advantage of such a system is the low price of the connector. For high power lasers such as the clinical Nd:YAG lasers with 40 to 150 W those connectors are not suitable. Up to now every laser manufacturer developed his own connector system in this field.

A fiber optic ultraviolet (UV) sterilizing system, which has the ability to irradiate 10 to 100 times higher germicidal UV light than ordinary germicidal lamps, has been developed. The system consists of two functional parts: one is a light source which emits germicidal UV light, the other is flexible quartz fibers which transmit light with low attenuation. Optical characteristics and biological effects of the system are described.

Infrared (IR) fibers are an intriguing and potentially important component of future surgical laser systems, allowing the development of less invasive procedures in a variety of medical specialties. Although a decade-long technological development by numerous laboratories around the world of surgical grade fibers is now reaching completion, we must carefully re-examine the business aspects of this market to determine the range of applications which can be profitable, based on the assumed fiber cost. Many of the higher-volume applications will only be penetrated if the fiber cost is low (with the fiber/catheter being a disposable). A simple analysis shows that the total quantity of IR fibers required for all potential laser procedures currently identified is of the order 1,000 kilometers per year; this is a small volume of fiber, especially compared to the amount required in the telecommunications industry. It is possible that a few large (500 Km/yr or more) applications will be developed using IR fibers; such applications, however, are generally cost sensitive, and will be subject to competition from alternative technologies. While the technological and clinical potential of surgical IR fibers remains exciting, the total OEM surgical market for IR fiber will probably be of the order $3-5 million per year, and will not exceed $20-30 million per year for the next 5-10 years, even given the most optimistic projections for the adoption of IR fibers in surgical applications.

This paper describes the use of a 100u second pulsed Nd-YAG laser at 1.064 um wavelength in the treatment of critical ischemia of the lower limb in five human subjects. Laser energy was delivered percutaneously to superficial femoral artery occlusions using standard angiography access techniques. The fiber tip was modified by the use of a 2.2mm hemispherical sapphire tip in contact with the tissue and laser energy was delivered at 0.5 Joules per pulse at a repetition rate of 10Hz. Patients were selected because of their unsuitability for standard treatment, either through technical inoperability of poor general health. Their mean age (±SD) was 74 ± 11 years and the mean occlusion length (+SD) in the five patients was 16.3 ± 11.9 cm. Passage of a guidewire across the occlusion was attempted, but failed, in every case. The laser crossed all these occlusions with a mean energy delivery of 129 + 76 Joules. Mean ankle-brachial pressure index (ABPI) in the successful cases doubled from 0.25 to 0.5. Two of the recanalised segments closed within 24 hours due to poor runoff but remained open in the remaining three patients for a followup period of up to one year, averting amputation in one of them. These are poor risk patients with deteriorating critical ischemia and little hope of alternative treatment. Laser angioplasty using a pulsed Nd-YAG laser has been shown to be feasible in femoropopliteal disease and should now be applied in patients with less severe symptoms.

The laser angioplasty is now clinically used, but complications like perforation, dissection and aneurysm formation reduce its large utilisation in arteriosclerotic arterial diseases. Many technical improvements have been done, without full satisfaction. Rounded sapphire tips (RST) are now used. To found their action mechanism, we studied their thermal behaviour (without cooling, with gas cooling, and with saline cooling) with an infrared thermographic camera, and we studied their optical properties with a power meter and a beam scanner. Three RST have been used : a clear and frosted RST from LASERSONICS (LS), and a frosted RST from SURGICAL LASER TECHNOLOGY (SLT). Two lasers have been used. The power used was 10, 15, and 20 watts with the Nd:YAG, and 1, 2, and 3 watts with the argon. The time exposure was 1 and 2 seconds. The optical transmittance, defined by the power ratio with/without the sapphire, and varied from 57% to 88% . The light distribution from the sapphire tip showed a focusing effect, different for each sapphire, with a focal length varied from 0.3 mm to 2 mm. The beam surface ratio, defined by surface at contact/surface at a focal length, varied from 1.3 to 7.9 . The thermal behaviour showed no increase of temperature for the Lasersonics clear sapphire (LS.C), with both lasers. Lasersonics frosted sapphire (LS.C), heat up with the Nd:YAG with a temperature always inferior to 110°C. Surgical laser technology (SLT) sapphire heat up with both Nd: YAG and argon laser with a temperature always inferior to 300°C. The atraumatic shape of RST compare to the bare fiber, and its less thermal increasing compare to the hot tip, can be interesting for laser angioplasty.

In this paper, we demonstrate the possibility as well as usefulness of the usage of CO lasers for the laser coronary angioplasty. CO lasers, approximately 5μm of their wavelength, have strong ablation capacity to water-containing living tissue due to intensive attenuation by water. Accordingly, a precise ablation of intravascular obstruction without a perforation may be possible by the CO laser irradiation. As a fundamental study, the design of the fiber energy delivery of CO lasers for the coronary angioplasty and the ablation effect of the CO laser irradiation to human atheroma are revealed. The CO laser irradiation method in the flushing medium of a coronary angioscope is also discussed.

Pulses from a commercial Er:YAG laser (Quantronics, Smithtown) have been transmitted through prototype commercial zirconium fluoride optical fibers (Infrared Fiber Systems, Silver Spring) to ablate atheromatous arteries in a wet field in order to evaluate the feasibility of such a system for laser angioplasty.

Stenotic or occlusive (two different techniques) lesions were surgically induced in the canine common carotid artery. The lesions were evaluated angiographically prior to as well as after laser angiosurgery (LAS). LAS was performed in 30 dogs using a continuous wave (CW) argon ion laser (Innova 20) coupled to a multifiber, quartz-shielded, fiberoptic catheter. Successful removal of lesion tissue was achieved in 89% of the animals with stenoses and in 40% and 82% in each of the two groups of dogs with occlusions. In the latter two groups, perforation of the vessel wall during LAS was encountered in 60% and 18%, respectively. No perforations occurred in the stenotic animals, where long-term follow-up was possible for up to 60 days with a patency rate of 63% and morphological evidence of excellent healing with complete reendothelialization.

A novel fiber optic probe for laser angioplasty has been realized consisting of a cone fiber tip inserted in a quartz microcapsule. This capsule is sealed on the top by a toroidal shaped lens-structure which avoids the on-axis radiation and gives rise to a sharp corolla shaped beam. These characteristics should minimize the risk both of mechanical and laser perforation. Preliminary tests carried out on aorta segments from cadaver seem to confirm the expected advantages of the new fiber probe.

Laser ablation of calcific plaque in human arteries has been demonstrated with visible radiation at intensities (107 W/cm2) that are readily transmitted by flexible (320 μm diameter) quartz optical fibers. The ablative mechanism involves formation of a plasma with mechanical fragmentation of the plaque by stress waves rather than simply thermal vaporization. By appropriate selection of laser pulse duration (<50 μsec), wavelength and exposure, the laser pulse can ablate the calcified plaque but will not ablate normal artery. These optimized laser parameters may enhance the safety and efficacy of laser endarterectomy.

Open laser endarterectany has progressed from a laboratory to a clinical procedure for peripheral vascular disease. Argon ion laser endarterectamy was performed in 3 patients using power 1.0W to 1.5W delivered through a 300 μm quartz fiber. Endarterectamy length ranged from 6.0 cm to 30.0 cm. No laser complications have occurred and arterial patency has been confirmed at up to one year follow-up.

Laser-induced fluorescence spectroscopy can discriminate atherosclerotic from normal arteries in-vitro and may thus potentially guide laser angioplasty. To evaluate the feasibility of laser-induced fluorescence spectroscopy in a living blood-filled arterial system we performed fiberoptic laser-induced fluorescence spectroscopy in a rabbit model of focal femoral atherosclerosis. A laser-induced fluorescence spectroscopy score was derived from stepwise linear regression analysis of in-vitro spectra to distinguish normal aorta (score>0) from atherosclerotic femoral artery (score<0). A 400 u silica fiber, coupled to a helium cadmium laser and optical multichannel analyzer, was inserted through a 5F catheter to induce and record in-vivo fluorescence from femoral and aortoiliac arteries. Arterial spectra could be recorded in all animals (n=10: 5 occlusions, 5 stenoses). Blood spectra were of low intensity and were easily distinguished from arterial spectra. The scores (mean ± SEM) for the in-vivo spectra were -0.69 ± 0.29 for artherosclerotic femoral, and +0.54 ±. 0.15 for normal aorta (p<.01; p=NS compared to in-vitro spectra). In-vitro, a fiber tip to tissue distance <50 u was necessary for adequate arterial LIFS in blood. At larger distances low intensity blood spectra were recorded (1/20 the intensity of tissue spectra). Thus, fiberoptic laser-induced fluorescence spectroscopy can be sucessfully performed in a blood filled artery provided the fiber tip is approximated to the tissue.

In conjunction with our project in laser angiosurgery, our group has demonstrated that laser-induced auto-fluorescence can be a reliable means of distinguishing normal artery from atherosclerotic plaque. Recently a number of groups have become interested in this technique as a means of directing ablation of arterial obstructions in vivo. However, until now, diagnostic spectroscopy has been conducted almost solely on excised cadaveric tissues. As a result, questions still remain about 1) the validity of correlating cadaveric tissue fluorescence spectra with those collected in vivo, and 2) the ability to collect reliable florescence spectra from a subject as dynamic as a living patient.

The use of light emitted accompanying a laser procedure on diseased sites within the heart and circulatory system, a procedure called laser angioplasty, provides a potentially simple, available monitor of the properites of the tissue target site. The nature and physical makeup of the site to be lased, as well as the evolution of the photoablation of the site, may be monitored in a fluorescence measurement.

kn effective and noninvasive new arrangement to measure the function of microcirculation blood flow is presented in this paper. This set-up has been used in many hospitals and medical institutes to observe how the microcirculation blood flow of men or animals is affected by medicaments and pathology phenomenon etc.. Major merits of the set-up are that it can continuously measure both blood flow velocities and diameter for a single vasa. Using the arrangement, we can obtain the average value of blood flow velocities and pulsation wave of blood flow. We can also record variation curves of the microvasa diameter and the blood flow velocities over a long period with a multichannel voltage recorder. The experimental results show that this set-up will make notable impact on the biomedicine research with its definite clinical application value.