Contemporary inventors and investors are faced with new challenges and difficulties that have not been experienced by past generations of inventors. This basically is the result of the exponential increase in the amount of knowledge and the tough global competition. A magic formula for success does not exist, but following some basic rules to be discussed here, will greatly increase the inventor / entrepreneur's chance for success. Two examples, the Video capsule and a 3D imaging Camera that are based on the author's past inventions are described and analyzed to demonstrate some of the rules.

Minimally invasive medical procedures will benefit from flexible endoscopes that are extremely thin yet produce high quality images. Current devices use fiber bundles or silicon image sensors placed in the distal tip where each pixel in the image is derived from an element in the distal tip, such that improving resolution requires increasing distal tip diameter. The University of Washington has developed the scanning fiber endoscope (SFE) to provide full color, high resolution images from a flexible endoscope with a small distal tip diameter. The SFE uses a single mode fiber vibrating in resonance to scan a focused laser spot over the tissue and a detector to record the time-multiplexed backscatter signal. The SFE contains a 400 micron diameter piezoelectric tube through which a length of singlemode optical fiber is placed. The tube drives the fiber tip at its resonant frequency (currently 5 KHz) in an expanding pattern of 250 spirals (500 pixel diameter image) at a frame rate of 15 Hertz. Imaging parameters are determined by the lens system placed in the 1.06 mm diameter distal tip. Prototype systems with 70 degree field-of-view and 10 micron resolution have been developed. Color images are created with red, green, and blue laser sources coupled into the single scanning fiber. Backscattered light is collected with twelve 250 micron multimode fibers placed around the periphery of the microscanner resulting in a total distal tip diameter of 1.6 mm. Frame sequential color, fluorescence, and continuous color imaging modes have been demonstrated in the non-confocal geometry.

Temporal measurements of fluorescence emitted from biological tissue provide information on biochemistry and morphology which may be useful in identifying neoplasia onset. Depth-selective detection of time-resolved fluorescence may enable enhanced discrimination of signals originating from individual tissue layers and thus improve device efficacy. In this study, we investigate how illumination-collection design parameters influence a device's ability to measure fluorophore lifetime and changes in superficial layer thickness. A two-layer, time-resolved Monte Carlo model of fluorescence light propagation in colonic polyps was used to simulate temporal decay curves. Several normal- and oblique-incidence geometries were investigated. Also, the efficacy of a convolution-based, bi-exponential lifetime calculation is compared to a full-width-half-max decay curve metric. Results indicate that interface design has a significant effect on the accuracy of fluorophore lifetime estimates and the ability to discriminate changes in tissue morphology. This is due to changes in the relative contribution of each tissue layer to the total detected signal.

We present how fiber-optic temperature or pressure sensors could be applied to minimally invasive diagnostics and therapies. For instance a miniature pressure sensor based on micro-optical mechanical systems (MOMS) could solve most of the problems associated with fluidic pressure transduction presently used for triggering purposes. These include intra-aortic balloon pumping (IABP) therapy and other applications requiring detection of fast and/or subtle fluid pressure variations such as for intracranial pressure monitoring or for urology diagnostics. As well, miniature temperature sensors permit minimally invasive direct temperature measurement in diagnostics or therapies requiring energy transfer to living tissues. The extremely small size of fiber-optic sensors that we have developed allows quick and precise in situ measurements exactly where the physical parameters need to be known. Furthermore, their intrinsic immunity to electromagnetic interference (EMI) allows for the safe use of EMI-generating therapeutic or diagnostic equipments without compromising the signal quality. With the trend of ambulatory health care and the increasing EMI noise found in modern hospitals, the use of multi-parameter fiber-optic sensors will improve constant patient monitoring without any concern about the effects of EMI disturbances. The advantages of miniature fiberoptic sensors will offer clinicians new monitoring tools that open the way for improved diagnostic accuracy and new therapeutic technologies.

The feasibility of integrating laser-based therapy using a singlemode fiberoptic delivery system in an endoscopic procedure has been investigated. The maximum transmissible optical power in a high-resolution scanning fiber endoscope system is limited by the requirement for small-core singlemode light propagation, thus impeding the capacity for optical therapies. Since the scanning fiber endoscope can be fabricated from low-cost components, the maximum power capacity of the singlemode optical fiber can be approached in the single use of the medical device. In preparation for future tissue studies, 29.4 micron nominally thick samples of Low Density Poly-Ethylene (LDPE) were used as standardized targets. To model the transient pulse-sample interaction of a scanning fiber endoscope, a pulsed, 50mW, 404nm Coherent Cub^TM laser system was used to replicate the conditions present in a scanning fiber endoscope that images by measuring the backscatter of combined red, green, and blue laser illumination. Preliminary tests indicate that thermal damage thresholds in LDPE are 120kW/cm². Dwell time and repetition characteristics were investigated and thermal damage thresholds for full-power single pulses was approximately 1ms, using 0.125 NA lens to the LDPE film. The higher-power 405 nm laser diodes are able to be directly modulated so that small regions of interest within the scanned sample can be irradiated for diagnosis (autofluorescence) and therapy (cutting and necrosis). Future studies will integrate the violet laser light with red, green, and blue light for frame-sequential imaging, diagnosis, and therapy.

For medical and analytical applications, step-index fibers based on synthetic silica are widely used. For special applications, high-OH all-silica fibers with excellent UV-transmission are commercially available, even at 180 nm. E'-centers with an absorption band around 215 nm, generated by the UV-light transported in these fibers, have to be taken into account. In addition to stable E'-centers, transient defects exist at room temperature, as well; therefore, the transmission at 215 nm wavelength depends on the operational conditions. The newly developed fibers with different diameters (from 100 μm to 600 μm core) will have a reduced defect concentration at 215 nm. In addition, the transient defect concentration has been reduced, too. The variation between the two power levels (dark, light) depends on the fiber diameter: the value is less than 0.3 dB/2m or 30 mAU/2m for large core fibers, one magnitude of order better than the comparable UVM-fiber described above. The hydrogen-content of the new fibers is negligible; therefore, the long-term behavior of these fibers, from 100 μm to 600 μm core diameter, is significantly better. In addition to low-power deuterium-lamps, the UV-damage of these fibers has been studied with high-power pulsed UV-lasers at 193 nm wavelength. Using the standard high-OH UV-fibers and UVM-fibers for comparison, the damage results will be discussed in detail. In addition, the established system for quality control of these UV-fibers will be described.

The precise analysis of potential hazardous components within gases and the detection of trace gases in exhaled breath for early and non invasive diagnosis of illnesses have a great influence on the well-being of human beings. Besides the existing analysis techniques, which mostly require sample preparation, costly consumables, huge space and skilled personal carrying out the measurement, a measurement system based on optical absorption in the UV wavelength region might offer alternatives to existing techniques. Within this work a feasibility study based on measurements of different test gases at lowest concentrations and requirements for trace gases in exhaled breath in respect to detection limits, signal-to-noise ratio and system drifts were analyzed. A spectral database including over 1000 UV vapor-phase spectra allows the identification of unknown compounds within a mixture, as well as expanding the use of the measurement technique into new areas of application, for example automobile application.

A bundled hollow waveguide, composed of 37 Ag-hollow fibers, was designed and fabricated to deliver high peak-power Q-Switched Nd:YAG laser pulses. The input end of the fibers are directly radiated by the laser beam without using a lens to remove an air-breakdown effect. Output peak-power up to 24 MW at the fundamental-mode was observed without any damages in the fibers. Output beam profiles from the waveguide were also examined and we observed no degradation in the beam quality at straight and bent positions.

A confocal Raman probe based on a silver hollow optical fiber is developed to apply in remote optical biopsy via a micro-endoscope. The probe consists of a single hollow optical fiber delivering both the excitation and the Raman scattered light, and a confocal end unit attached at the distal end of the fiber. We demonstrate a high spatial resolution remote Raman measurement with the present probe. The measured spectrum shows a depth-resolution of below 0.15 μm. In addition, we propose a ball lens coupled miniature high-resolution Raman probe and show that it operates as well as the confocal probe.

Recent advances in bio-optical methods for Medical Diagnostics, Optical Biopsy and Non-Invasive Imaging have the potential to prolong and improve the quality of life while significantly reducing medical costs for the diagnosis and tracking of diseases. Advances in the Genomics and pharmaceutical discovery using micro-array technology and High Throughput Screening permit to study thousands of compounds in short periods of time. This paper presents a new Si-based photonic sensors and sensor arrays with internal discrete amplification that offers the necessary qualities thus allowing development of a new generation of high gain, ultra low noise, universal analog and counting photodetectors for bio-optical sensing applications. The new photodetectors can operate in the linear detection mode with a gain-bandwidth product of up to 10¹⁵/sec and in the photon counting mode with count rates of up to 10⁹ counts/sec. Detectors based on this amplification mechanism could have performance parameters superior to those of conventional avalanche photodiodes and photomultiplier tubes. For tested silicon photodetector prototypes, measured excess noise factor is as low as 1.02 at gains greater than 100,000.

Recent progress in nanostructured optical fiber-based sensors for the noninvasive, fast and quantitative measurement of volatile organic compounds (VOC) in human breath is reported. The sensor array, which is constituted with multilayered, interleaved metal nanocluster and polymer thin films on the distal ends of optical fibers, is fabricated by the electrostatic self-assembly (ESA) process. Initial research and early sensor prototype demonstrations indicate that the specific detection of acetone, ethane and other molecular targets in exhaled human breath is achievable. Moreover, the selectivity and sensitivity of the system are significantly improved by incorporating an advanced data analysis model.

We present a novel sensing system consisting of an intravaginal probe and an optoelectronic measurement unit, which allows an easy, comfortable and quantitative dynamic evaluation of women pelvic floor muscle strength. The sensing probe is based on a silicone cylinder that transduces radial muscle pressure into axial load applied to a fiber Bragg grating strain sensor. The performance of a first sensor probe prototype with temperature referentiation and of the autonomous, portable optoelectronic measurement unit with data logging capabilities and graphical user interface is disclosed. The presented results refer to an ongoing collaboration work between researchers from the Medical, Optoelectronics and Mechanical areas, directed to the development of equipment that can assist in medical practice and help in the research of primary mechanisms responsible for several pelvic floor disorders, in particular urogenital prolapses.

We have proposed selective removal of cholesterol ester by infrared laser of wavelength with 5.75 μm irradiation; the wavelength of 5.75 μm correspond with the ester bond C=O stretching vibration. The flexible laser guiding line and a compact light source are required for our proposal. We used a compact mid-infrared tunable laser by difference frequency generation; DFG laser was developed for substitute light source of free electron laser. In the present work, first, we have developed hollow optical fiber with a diamond lens-tip to deliver DFG laser in the blood vessel and evaluated the transmission of DFG laser from 5.5 μm to 7.5 μm. The transmission of 5.75 μm is about 65%, the DFG beam was focused on the tip of fiber by diamond lens-tip. Secondly, we performed the selective removal experiment of cholesterol ester using the hollow optical fiber with diamond lens-tip and DFG laser. The sample used a two layer model, cholesterol oleate and gelatin. The cholesterol oleate was decomposed by 5.75 μm DFG irradiation with 3.8 W/cm².

A closed loop-coating method has been proposed in order to form a uniform polymer layer in the fabrication of cyclic olefin polymer-coated silver (COP/Ag) hollow optical fiber. A COP solution was flowed in a closed loop system, in which silver-coated tube was used as a part of it. Owing to the constant flowing speed of the solution and the airtight flowing environment, a uniform COP layer was formed, which is one of the most important parameters to improve the transmission properties of the hollow fiber. The method was successfully applied to the fabrication of hollow fibers with 2 meters length for near and mid-infrared lasers, such as Nd:YAG, Er:YAG and CO₂ lasers. Stable fabrication and better reproduction were also observed by using the new coating method.

All-fiber acousto-optic (AO) devices such as frequency shifters, phase, intensity and polarization modulators, tunable filters and multiplexers have been developed in the last decade mostly for their importance in fiber optic communication systems. However they can equally have potential uses in bio sensing and fiber based biomedical systems. We present the design, construction and performance of a number of all-fiber and fiber compatible acousto-optic modulators that particularly phase and polarization modulators and will address their potential uses in biomedicine. Among these components and devices, an all-fibre phase modulator acts on the phase of optical fields that propagate down the fibre core. To enhance the phase modulation, the acoustic energy is focused into the fiber core using an acoustic lens. Another high efficiency birefringence (or polarization) modulator was demonstrated that is designed to operate at the acoustic resonance frequency of the fiber. Fiber compatible devices were built using gradient index (GRIN) lenses that can couple the light into a fiber or between two fibers. Diffraction based and polarization GRIN modulators were demonstrated and AOMs of in-fiber gratings as well as ones made from glasses that exhibit large AO figure of merit. As a high frequency polarization, phase, intensity or wavelength modulators these devices have a great potential for use in polarimetric imaging, scanning of a fiber-optic OCT system, tuning the wavelengths in miniature hyperspectral imaging systems and sensors or for frequency-domain OCT.

Hollow glass waveguide is one from a few instruments favored in industrial and medical fields for the delivery of mid-infrared laser light. The article summarizes delivery of the Er:YAG laser radiation (λ = 2.94 μm) by the cyclic olefin polymer coated silver hollow glass waveguides with various inner diameters - 320 μm, 700 μm, and 1 mm, and with length of 0.1 - 1 m. For medical applications, the so called "contact mode" in which the end of the waveguide is in contact with the soft or hard tissues is discussed. For this treatment the special sealed caps were used for preventing the waveguide system damage. Delivery of long (free-running) and short (Q-switched) mid-infrared pulses was investigated. The delivery systems were investigated for the ophthalmic, urologic, and dental tissue treatments. The comparison of interaction effects caused by the laser pulses with various lengths was made.

In the field of fluorescent microscopy, neuronal activity, diabetes and drug treatment are a few of the wide ranging biomedical applications that can be monitored with the use of dye markers. Historically, in-vivo fluorescent detectors consist of implantable probes coupled by optical fibre to sophisticated bench-top instrumentation. These systems typically use laser light to excite the fluorescent marker dies and using sensors, such as the photo-multiplier tube (PMT) or charge coupled devices (CCD), detect the fluorescent light that is filtered from the total excitation. Such systems are large and expensive. In this paper we highlight the first steps toward a fully implantable in-vivo fluorescence detection system. The aim is to make the detector system small, low cost and disposable. The current prototype is a hybrid platform consisting of a vertical cavity surface emitting laser (VCSEL) to provide the excitation and a filtered solid state Geiger mode avalanche photo-diode (APD) to detect the emitted fluorescence. Fluorescence detection requires measurement of extremely low levels of light so the proposed APD detectors combine the ability to count individual photons with the added advantage of being small in size. At present the exciter and sensor are mounted on a hybrid PCB inside a 3mm diameter glass tube.This is wired to external electronics, which provide quenching, photon counting and a PC interface. In this configuration, the set-up can be used for in-vitro experimentation and in-vivo analysis conducted on animals such as mice.

The Erbium:YAG laser is currently being tested experimentally for endoscopic applications in urology, including more efficient laser lithotripsy and more precise incision of urethral strictures than the Holmium:YAG laser. While side-firing silica fibers are available for use with the Ho:YAG laser in urology, no such fibers exist for use with the Er:YAG laser. These applications may benefit from the availability of a side-firing, mid-infrared optical fiber capable of delivering the laser radiation at a 90-degree angle to the tissue. The objective of this study is to describe the simple construction and characterization of a side-firing germanium oxide fiber for potential use in endoscopic laser surgery. Side-firing fibers were constructed from 450-micron-core germanium oxide fibers of 1.45-m-length by polishing the distal tip at a 45-degree angle and placing a 1-cm-long protective quartz cap over the fiber tip. Er:YAG laser radiation with a wavelength of 2.94 microns, pulse duration of 300 microseconds, pulse repetition rate of 3 Hz, and pulse energies of from 5 to 550 mJ was coupled into the fibers. The fiber transmission rate and damage threshold measured 48 +/- 4 % and 149 +/- 37 mJ, respectively (n = 6 fibers). By comparison, fiber transmission through normal germanium oxide trunk fibers measured 66 +/- 3 %, with no observed damage (n = 5 fibers). Sufficient pulse energies were transmitted through the side-firing fibers for contact tissue ablation. Although these initial tests are promising, further studies will need to be conducted, focusing on assembly of more flexible, smaller diameter fibers, fiber bending transmission tests, long-term fiber reliability tests, and improvement of the fiber output spatial beam profile.

A set of long period grating devices have been fabricated in photosensitive single mode fibre coated with a series of copper rings (period of 380 μm, 50% duty cycle and length of 4cm). The long period gratings were inscribed with a uniform UV-laser exposure across the entire length of the copper ring patterned coating. The devices ranged in copper thickness from 0.5 μm to 1.5 μm. In addition, a control long period grating was fabricated in the same type of fibre with the same period for comparison. The refractive index and temperature spectral sensitivity of these devices were investigated and it was found that the index and temperature sensitivity is a function of the thickness of the copper rings, as supported by theoretical modelling. Furthermore, the index sensitivity of these devices in the 1.333 index region is greater than the control long period grating. The patterned 0.5 μm coated long period grating gave a sensitivity of Δλ/Δn =-74 nm leading to a resolution of 1.4x10^-3 compared to the control which had a sensitivity of Δλ/Δn = -32 nm with a resolution of 3.2x10^-3 in the index region of 1.320 to 1.380 (aqueous solution regime). This demonstrates a two fold increase in the sensitivity. This novel fibre long period grating device shows potential for increasing the resolution of measurements of the index of aqueous solutions.

For medical and analytical applications, thick-core fibers are widely spread. For special applications in the UV-A region, flexible and inexpensive fibers with high transmission in this wavelength region are required. On the other hand, new high-power UV-A light sources (LEDs, laser-diodes) are available in this wavelength region. Although silica-based UV-fibers are mainly used over the full UV-range, there are two additional candidates for the UV-A region: the Polymer Optical Fiber (POF) and the Polymer Clad Silica Fiber (PCSF). Especially, the higher flexibility of the thick-core POF is superior in comparison to silica fibers with the same outer diameter. However, UV-induced losses exist in these fibers, too, using UV-light sources with significant power below 350 nm wavelength. However, the UV-damage with UV-light above this wavelength is significantly reduced; test results with high-power 365 nm UV-LED and 375 nm laserdiodes will be shown and discussed. On the other hand, the entire fiber-optic system, including the light-source, will be characterized. Especially the coupling efficiency between the light-source and the fibers was studied theoretically and experimentally.

Acousto-optic (AO) technology is used to design compact, vibration-insensitive spectrometers with fairly high sensitivity and resolution. The design of such AO spectrometers (AOS's) is based on the phenomenon of an anisotropic Bragg diffraction in a birefringent crystal, i.e., quartz, lithium niobate, tellurium dioxide (TeO₂), etc. The fundamental building block of an AOS is an acousto-optic tunable filter (AOTF) cell used with a sensitive detector. There are two types of AOTF cells - (i) collinear where the incident and diffracted optical beams and the acoustic beam all propagate in the same direction and (ii) noncollinear where all these beams do not travel in the same direction - based on the design of the cell. We have developed a number of AOS's to cover wavelengths from the ultraviolet (UV) to the mid wave infrared (MWIR). Spectrometers using a collinear AOTF cell fabricated in a single crystal of quartz operate in the spectral range from 255 to 430 nm and from 400 to 800 nm and those fabricated in a single crystal of TeO₂ with a noncollinear design operate from 1100 to 2700 nm and from 2000 to 4500 nm. We have developed special accessories to couple optical fiber(s) to such spectrometers for efficient light collection. In our laboratory, we are using these AOS's to measure emission, absorption, fluorescence, and Raman spectra. The development of these AOS's is discussed and compact portable fiber-coupled spectrometers based on quartz AOTF operating in the 255 to 800 nm spectral region are described and sample results are presented. Such spectrometers should be useful for medical diagnostics applications.

Sencils^tm (sensory cilia) are chemical sensors that are minimally invasive, disposable and easily readable to make frequent measurements of various analytes in vivo over a period of 1-3 months. A percutaneous optical fiber permits precise, reliable photonic measurement of chemical reactions in a nano-engineered polymer matrix attached to the internal end of the fiber. The first Sencils sense interstitial glucose based on measurement of fluorescence resonance energy transfer (FRET) between fluorophores bound to betacyclodextrin and Concanavalin A (Con A) in a polyethylene glycol (PEG) matrix. In vitro experiments demonstrate a rapid and precise relationship between the ratio of the two fluorescent emissions and concentration of glucose in saline over the physiological range of 0-500mg/dl. Chronic implantation in pigs has demonstrated biocompatibility. The Sencil platform can be adapted to detect other analytes in interstitial fluids.

An optical bio-sensor is built based on an infrared chalcogenide fiber coated with live cells. The fiber is immersed in an aqueous media appropriate for cell viability. The response of the cells to small quantities of toxicant can be monitored spectroscopically. The properties of chalcogenide fibers used for cell-based biosensors are investigated. The chemical stability of Te-As-Se fibers in aqueous media is shown to depend on the previous storage time of the fiber. Older fibers are shown to generate an oxide layer during extended exposure to air. This layer readily dissolves in aqueous solution and causes the release of As in the cell environment. The release of As during dissolution of the oxide layer is measured with ICP-MS and is shown to be complete after a couple hours. Fresh fibers do not show any detectable oxide layer and show excellent stability in aqueous solution. The surface roughness of old and fresh fibers is investigated with AFM before and after dissolution in aqueous media. Old fibers immersed in solution show sizable roughness due to the oxide surface layer dissolution. Fresh fibers do not show any detectable changes even after extended immersion in aqueous solution. The toxicity of As to various types of vertebrate cells is quantified using a colorimetric assay. Old fibers are shown to be notably toxic due to As released during dissolution. The fiber toxicity is shown to decrease when the fibers are previously washed in solution. The toxicity of the resulting wash water is then shown to increase due to the increase in As concentration.

Applications involving fluorescence detection in point-of-care systems are both interesting and challenging in nature. The applications usually require a simple, compact, robust, highly sensitive yet affordable system. As a result, the system needs to be efficient in fluorescence detection by using practical and easily fabricated, hence inexpensive sensors. In this paper, a fluorescence sensor using an in-fiber microchannel has been developed and tested successfully. A blue LED, multimode PMMA or silica fiber, mini-PMT and fluorescein in PBS pH 7.4 buffer solution were used as the excitation source, light guide, fluorescence detector and sample, respectively. Microfluidic channels of 100μm width and 1cm length were fabricated in the optical fibers using a direct write CO₂ laser system. The channels in the fibers were examined using a SEM and an optical microscope. Experimental results show that the sensor is highly sensitive, being able to detect 0.1 μg/L of fluorescein in the PBS buffer solution, with good signal to noise ratio and the results are reproducible. The data obtained using silica fibers as sensors when compared with the results from PMMA fibers show that the silica fiber sensor has better sensitivity than the PMMA fiber sensor. This could be due to the fouling effect created by the frosty layer at the bottom of the microchannel made within the PMMA fiber. Our future work will integrate the fiber sensor into microfluidic chips for lab-on-a-chip applications.

Continues efforts to develop low loss flexible waveguides, to transmit mid IR laser energy for minimal invasive surgical and diagnostic procedures, have been carried out by us and other groups in this area. We have introduced sulfide dielectric films coated over an Ag reflecting layer as another potential solution. The metal sulfides used, have high transparency in the infra red spectrum and their thickness can be tailored to minimize the attenuation over a selected wavelength range. The high refractive index contrast of the two metal sulfide materials enable to produce multi layer hollow waveguides. These waveguide will have low attenuation in both straight and bent conditions, low sensitivity to coupling and to surface roughness and a broad wavelength range. The straight lowest loss measured at 1.55μm for a 1,000-μm bore Ag/CdS/PbS/CdS HGW was 0.06 dB/m. This loss is three times less than that measured for a single layer Ag/CdS coated HGW at 1.55μm. A theoretical simulation applying the same conditions showed the same pattern with a good potential for improvement.

The most important parameter that reflects the balance between oxygen supply and demand in tissues is the mitochondrial NADH redox state that could be monitored In vivo. Nevertheless single parameter monitoring is limited in the interpretation capacity of the very complicated pathophysiological events, therefore three more parameters were added to the NADH and the multiparametric monitoring system was used in experimental and clinical studies. In our previous paper¹ we described the CritiView (CRV1) including a fiber optic probe that monitor four physiological parameters in real time. In the new model (CRV3) several factors such as UV safety, size and price of the device were improved significantly. The CRV3 enable to monitor the various parameters in three different locations in the tissue thus increasing the reliability of the data due to the better statistics. The connection between the device and the monitored tissue could be done by various types of probes. The main probe that was tested also in clinical studies was a special 3 points probe that includes 9 optical fibers (3 in each point) that was embedded in a three way Foley catheter. This catheter enabled the monitoring of urethral wall vitality as an indicator of the development of body metabolic emergency state. The three point probe was tested in the brain exposed to the lack of oxygen (Anoxia, Hypoxia or Ischemia). A decrease in blood oxygenation and a large increase in mitochondrial NADH fluorescence were recorded. The microcirculatory blood flow increased during anoxia and hypoxia and decreased significantly under ischemia.

In our previous publication (Mayevsky et al SPIE 5326: 98-105, 2004) we described a multiparametric fiber optic system enabling the evaluation of 4 physiological parameters as indicators of tissue vitality. Since the correlation between the various parameters may differ in various pathophysiological conditions there is a need for an objective quantitative index that will integrate the relative changes measured in real time by the multiparametric monitoring system into a single number-vitality index. Such an approach to calculate tissue vitality index is critical for the possibility to use such an instrument in clinical environments. In the current presentation we are reporting our preliminary results indicating that calculation of an objective tissue vitality index is feasible. We used an intuitive empirical approach based on the comparison between the calculated index by the computer and the subjective evaluation made by an expert in the field of physiological monitoring. We used the in vivo brain of rats as an animal model in our current studies. The rats were exposed to anoxia, ischemia and cortical spreading depression and the responses were recorded in real time. At the end of the monitoring session the results were analyzed and the tissue vitality index was calculated offline. Mitochondrial NADH, tissue blood flow and oxy-hemoglobin were used to calculate the vitality index of the brain in vivo, where each parameter received a different weight, in each experiment type based on their significance. It was found that the mitochondrial NADH response was the main factor affected the calculated vitality index.