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Objectives/ Hypothesis: One sequela of skull base surgery is iatrogenic damage to cranial nerves, which can be prevented if the nerve is identified. Devices that stimulate nerves with electric current assist in nerve identification. Contemporary devices have two main limitations: 1) the physical contact of the stimulating electrode and (2) the spread of the current through the tissue. In contrast to electrical stimulation, pulsed infrared optical radiation can be used to safely and selectively stimulate neural tissue and might be valuable for screening.Methods: The gerbil facial nerve was exposed to 250 microsecond pulses of 2.12 microm radiation delivered via a 600-microm-diameter optical fiber at a repetition rate of 2 Hz. With use of 27 GA, 12-mm intradermal electrodes, muscle action potentials were recorded. Nerve samples were examined for possible tissue damage.Results: Eight facial nerves were stimulated with radiant exposures between 0.71 and 1.77 J/cm, resulting in compound muscle action potentials (CmAPs) that were simultaneously measured at the m. orbicularis oculi, m. levator nasolabialis, and m. orbicularis oris. Resulting CmAP amplitudes were 0.3 to 0.4 mV, 0.15 to 1.4 mV, and 0.3 to 2.3 mV, respectively, depending on the radial location of the optical fiber and the radiant exposure. Individual nerve branches were also stimulated, resulting in CmAP amplitudes between 0.2 and 1.6 mV. Histology revealed tissue damage at radiant exposures of 2.2 J/cm but no apparent damage at radiant exposures of 2.0 J/cm.Conclusions: The experiments showed that selective muscle action potentials can be evoked optically in the gerbil facial nerve without direct physical contact. [ABSTRACT FROM AUTHOR]

This paper presents the latest progress on quantitative, in vivo, transcutaneous glucose sensing using surface enhanced spatially offset Raman spectroscopy (SESORS). Silver film over nanosphere (AgFON) surfaces were functionalized with a mixed self-assembled monolayer (SAM) and implanted subcutaneously in Sprague-Dawley rats. The glucose concentration was monitored in the interstitial fluid of six separate rats. The results demonstrated excellent accuracy and consistency. Remarkably, the root-mean-square error of calibration (RMSEC) (3.6 mg/dL) and the root-mean-square error of prediction (RMSEP) (13.7 mg/dL) for low glucose concentration (<80 mg/dL) is lower than the current International Organization Standard (ISO/DIS 15197) requirements. Additionally, our sensor demonstrated functionality up 17 days after implantation, including 12 days under the laser safety level for human skin exposure with only one time calibration. Therefore, our SERS based sensor shows promise for the challenge of reliable continuous glucose sensing systems for optimal glycemic control.

Artificial neural stimulation is widely used in clinic, rehabilitation, and research. One of the limitations of electrical stimulation is the current spread in tissue. Recently, pulsed mid-infrared laser stimulation of nerves has been investigated as an alternative stimulation method. The likely benefits of infrared neural stimulation (INS) include spatial selectivity of stimulation, noncontact mode of operation, and the lack of stimulation artifact in simultaneous electrical recordings. The hypothesis for this study is that INS of the cochlear spiral ganglion at low pulse energy is as spatially selective as low-level tonal stimulation of the cochlea. Spatial selectivity was measured using a masking method. An optical pulse with fixed optical parameters was delivered through a 200-μm diameter optical fiber. An acoustic tone, variable in frequency and level, was presented simultaneously with the optical pulse. Tone-on-light masking in gerbils revealed tuning curves with best frequencies between 5.3 and 11.4 kHz. The width of the tone-on-light tuning curves was similar to the width of tone-on-tone tuning curves. The results indicate that the spatial area of INS in the gerbil cochlea is similar to the cochlear area excited by a low level acoustic tone, showing promising results for future use of INS in implantable cochlear prostheses.

This paper reviews the existing research on infrared neural stimulation, a means of artificially stimulating neurons that has been proposed as an alternative to electrical stimulation. Infrared neural stimulation (INS) is defined as the direct induction of an evoked potential in response to a transient targeted deposition of optical energy. The foremost advantage of using optical radiation for neural stimulation is its spatial resolution. Exogenously applied or trans-genetically synthesized fluorophores are not used to achieve stimulation. Here, current work on INS is presented for motor nerves, sensory nerves, central nervous system, and in vitro preparations. A discussion follows addressing the mechanism of INS and its potential use in neuroprostheses. A brief review of neural depolarization involving other optical methods is also presented. Topics covered include optical stimulation concurrent with electrical stimulation, optical stimulation using exogenous fluorophores, and optical stimulation by transgenic induction of light-gated ion channels.

This letter presents the first quantitative, in vivo, transcutaneous glucose measurements using surface enhanced Raman spectroscopy (SERS). Silver film over nanosphere (AgFON) surfaces were functionalized with a mixed self-assembled monolayer (SAM) and implanted subcutaneously in a Sprague-Dawley rat. The glucose concentration was monitored in the interstitial fluid. SER spectra were collected from the sensor chip through the skin using spatially offset Raman spectroscopy (SORS). The combination of SERS and SORS is a powerful new approach to the challenging problem of in vivo metabolite and drug sensing.

Background and Objective: Melanoma is the most serious form of skin cancer and often appears as an evolving multicolored skin growth. It is well documented that pre-existing atypical or dysplastic nevi can evolve into a melanoma. The development of an in vivo imaging system to characterize benign and malignant nevi has been emphasized to aid in early detection of melanoma. The goal of this study is to utilize a novel Stokes polarimetry imaging (SPI) system for the characterization of pigmented lesions, and to evaluate the SPI system in comparison to dermoscopy and histology images., Study Design/materials and Methods: Linearly polarized light with varying incident polarization angles (IPA) illuminated various types of pigmented lesions. The melanocytic nesting patterns of pigmented lesions were characterized by constructing the degree-of-linear-polarization (DOLP) image map with comparison to dermoscopy and histology. The incident polarized light was filtered by visible filters for spectral imaging and incident deeply penetrating red light was used to correlate the SPI image with histopathological examination., Results: The DOLP images with varying IPA at different visible wavelengths were used to characterize various kinds of pigmented lesions by showing subsurface melanocytic nesting distribution as well as morphological information with better resolution and contrast. In correlation with dermoscopy and histology, various defining features such as compound, junctional, lentiginous, reticular, globular patterns of melanocytic nests were identified., Conclusion: When imaging pigmented melanocytic lesions, the SPI system with varying IPA at the red light wavelength can better define the melanocytic nesting patterns in both the dermal epidermal junction and the dermis. The SPI system has the potential to be an effective in vivo method of detecting pre-malignant nevi and melanoma.

In developing neural prostheses, particular success has been realized with cochlear implants. These devices bypass damaged hair cells in the auditory system and electrically stimulate the auditory nerve directly. In contemporary cochlear implants, however, the injected electric current spreads widely along the scala tympani and across turns. Consequently, stimulation of spatially discrete spiral ganglion cell populations is difficult. In contrast to electrical stimulation, it has been shown that extremely spatially selective stimulation is possible using infrared radiation (e.g. [Izzo, A.D., Su, H.S., Pathria, J., Walsh Jr., J.T., Whitlon, D.S., Richter, C.-P., 2007a. Selectivity of neural stimulation in the auditory system: a comparison of optic and electric stimuli. J. Biomed. Opt. 12, 1-7]). Here, we explore the correlation between surviving spiral ganglion cells, following acute and chronic deafness induced by neomycin application into the middle ear, and neural stimulation using optical radiation and electrical current. In vivo experiments were conducted in gerbils. Before the animals were deafened, acoustic thresholds were obtained and neurons were stimulated with optical radiation at various pulse durations, radiation exposures, and pulse repetition rates. In one group of animals, measurements were made immediately after deafening, while the other group was tested at least four weeks after deafening. Deafness was confirmed by measuring acoustically evoked compound action potentials. Optically and electrically evoked compound action potentials and auditory brainstem responses were determined for different radiation exposures and for different electrical current amplitudes, respectively. After completion of the experiments, the animals were euthanized and the cochleae were harvested for histology. Acoustically evoked compound action potential thresholds were elevated by more than 40 dB after neomycin application in acutely deaf and more than 60 dB in chronically deaf animals. Compound action potential thresholds, which were determined with optical radiation pulses, were not significantly elevated in acutely deaf animals. However, in chronically deaf animals optically evoked CAP thresholds were elevated. Changes correlated with the number of surviving spiral ganglion cells and the optical parameters that were used for stimulation.

We have pioneered what we believe is a novel method of stimulating cochlear neurons, using pulsed infrared radiation, based on the hypothesis that optical radiation can provide more spatially selective stimulation of the cochlea than electric current. Very little of the available optical parameter space has been used for optical stimulation of neurons. Here, we use a pulsed diode laser (1.94 microm) to stimulate auditory neurons of the gerbil. Radiant exposures measured at CAP threshold are similar for pulse durations of 5, 10, 30, and 100 micros, but greater for 300-micros-long pulses. There is evidence that water absorption of optical radiation is a significant factor in optical stimulation. Heat-transfer-based analysis of the data indicates that potential structures involved in optical stimulation of cochlear neurons have a dimension on the order of approximately 10 microm. The implications of these data could direct further research and design of an optical cochlear implant.

Lactate production under anaerobic conditions is indicative of human performance levels, fatigue, and hydration. Elevated lactate levels result from several medical conditions including congestive heart failure, hypoxia, and diabetic ketoacidosis. Real-time detection of lactate can therefore be useful for monitoring these medical conditions, posttrauma situations, and in evaluating the physical condition of a person engaged in strenuous activity. This paper represents a proof-of-concept demonstration of a lactate sensor based on surface-enhanced Raman spectroscopy (SERS). Furthermore, it points the direction toward a multianalyte sensing platform. A mixed decanethiol/mercaptohexanol partition layer is used herein to demonstrate SERS lactate sensing. The reversibility of the sensor surface is characterized by exposing it alternately to aqueous lactate solutions and buffer without lactate. The partitioning and departitioning time constants were both found to be approximately 30 s. In addition, physiological lactate levels (i.e., 6-240 mg/dL) were quantified in phosphate-buffered saline medium using multivariate analysis with a root-mean-square error of prediction of 39.6 mg/dL. Finally, reversibility was tested for sequential glucose and lactate exposures. Complete partitioning and departitioning of both analytes was demonstrated.

Pulsed lasers can evoke neural activity from motor as well as sensory neurons in vivo. Lasers allow more selective spatial resolution of stimulation than the conventional electrical stimulation. To date, few studies have examined pulsed, mid-infrared laser stimulation of nerves and very little of the available optical parameter space has been studied. In this study, a pulsed diode laser, with wavelength between 1.844-1.873 microm, was used to elicit compound action potentials (CAPs) from the auditory system of the gerbil. We found that pulse durations as short as 35 micros elicit a CAP from the cochlea. In addition, repetition rates up to 13 Hz can continually stimulate cochlear spiral ganglion cells for extended periods of time. Varying the wavelength and, therefore, the optical penetration depth, allowed different populations of neurons to be stimulated. The technology of optical stimulation could significantly improve cochlear implants, which are hampered by a lack of spatial selectivity.

Background and Objectives: For centuries, electric current has been used to stimulate neurons. Shortcomings of electrical stimulation include the contact between the stimulating electrode and the tissue, and the non-selective stimulation of the tissue. In contrast to electric stimulation, optical radiation can provide spatially selective neural stimulation without tissue contact., Study Design/materials and Methods: Acute in vivo experiments using gerbils were conducted to record optically evoked compound action potentials (CAPs) from the cochlea., Results: Optical radiation evokes CAPs in normal hearing animals and in deafened animals, in which cochleae lack outer and inner hair cells. Stimulation threshold was measured as 0.018+/-0.003 J/cm(2) (mean+/-SE). Laser radiation could be increased by 30-40 dB until drastic changes were seen in cochlear function. Cochlear response amplitudes to optical radiation were stable over extended stimulation times., Conclusions: We have demonstrated that the auditory nerve can be stimulated by optical radiation. One potential clinical use of this technology would be for cochlear implants., ((c) 2006 Wiley-Liss, Inc.)

Illumination with incident linearly polarized light on tissue and polarization state measurements of the remitted light provide a means by which various tissue structures can be differentiated. A rat tail is embedded within a turbid gelatin such that there is a variable depth of medium above it. By varying the incident polarization angle (IPA) of the illuminating linearly polarized light, the geometry, and the orientation angle of the tissue, a series of 2-D degree of linear polarization image maps are created using our Stokes polarimetry imaging technique. The image maps show locations of the polarization-sensitive structures in the rat tail, including soft tissue, intervertebral disks, and tendons. The observed morphologies in the image maps indicate locations where the depolarization of light differs according to the tissue type and underlying layers. The data indicate the importance of varying the IPA, and that tissue dichroism and birefringence affect the degree of linear polarization image maps. Diagnostic information regarding subsurface tissue structures is obtained.

Background and Objectives: We describe a Stokes polarimetry imaging technique that quantifies the polarization properties of remitted light backscattered from a sample., Study Design/materials and Methods: Right- and left-circularly polarized near-infrared light was used to illuminate rat-tail tissue embedded in turbid gelatin., Results: The degree of linear polarization (DoLP) and degree of circular polarization (DoCP) image-maps indicate that increasing the depth of the rat tail within the turbid medium and varying the rat-tail geometry and orientation relative to the light source affected the contrast between structures and adjacent tissue layers., Conclusion: Stokes polarimetry imaging shows that the intervertebral discs and soft tissue regions of rat tails strongly depolarize incident circularly polarized light. Tendon regions remit light with a more linear form due to birefringence. Both DoLP and DoCP image-maps provide contrast between tissue structures. When differentiating between unpolarized light and light with low DoCP or DoLP, the polarization of backscattered light from the turbid medium must to be taken into consideration., ((c) 2005 Wiley-Liss, Inc)

A new, mixed decanethiol (DT)/mercaptohexanol (MH) partition layer with dramatically improved properties has been developed for glucose sensing by surface-enhanced Raman spectroscopy. This work represents significant progress toward our long-term goal of a minimally invasive, continuous, reusable glucose sensor. The DT/MH-functionalized surface has greater temporal stability, demonstrates rapid, reversible partitioning and departitioning, and is simpler to control compared to the tri(ethylene glycol) monolayer used previously. The data herein show that this DT/MH-functionalized surface is stable for at least 10 days in bovine plasma. Reversibility is demonstrated by exposing the sensor alternately to 0 and 100 mM aqueous glucose solutions (pH approximately 7). The difference spectra show that complete partitioning and departitioning occur. Furthermore, physiological levels of glucose in two complex media were quantified using multivariate analysis. In the first system, the sensor is exposed to a solution consisting of water with 1 mM lactate and 2.5 mM urea. The root-mean-squared error of prediction (RMSEP) is 92.17 mg/dL (5.12 mM) with 87% of the validation points falling within the A and B range of the Clarke error grid. In the second, more complex system, glucose is measured in the presence of bovine plasma. The RMSEP is 83.16 mg/dL (4.62 mM) with 85% of the validation points falling within the A and B range of the Clarke error grid. Finally, to evaluate the real-time response of the sensor, the 1/e time constant for glucose partitioning and departitioning in the bovine plasma environment was calculated. The time constant is 28 s for partitioning and 25 s for departitioning, indicating the rapid interaction between the SAM and glucose that is essential for continuous sensing.

This Addendum provides a revised set of figures containing converged numerical data for total scattering cross section (TSCS), replacing the figures in our recent publication [Opt. Lett. 29, 1393 (2004)]. Due to the use of an overly large time step, our original TSCS data exhibited a systematic, nonphysical diminution above 150 THz for all cases studied. We have determined that numerical convergence in the temporal sense for the pseudospectral time-domain (PSTD) algorithm employed previously requires limiting the time step to no more than 1/60th of the sinusoidal period at the maximum frequency of interest, which in the previous case was 300 THz. This is an important point that we hereby report to future users of PSTD simulations in electrodynamics and optics. Note that all our original conclusions remain valid.

We report what we believe to be the first rigorous numerical solution of the two-dimensional Maxwell equations for optical propagation within, and scattering by, a random medium of macroscopic dimensions. Our solution is based on the pseudospectral time-domain technique, which provides essentially exact results for electromagnetic field spatial modes sampled at the Nyquist rate or better. The results point toward the emerging feasibility of direct, exact Maxwell equations modeling of light propagation through many millimeters of biological tissues. More generally, our results have a wider implication: Namely, the study of electromagnetic wave propagation within random media is moving toward exact rather than approximate solutions of Maxwell's equations.

We report the effect of changes in the corneal hydration on the refractive index of the cornea. Using optical coherence tomography (OCT), the geometrical thickness and the group refractive index of the bovine cornea were derived simultaneously as the corneal hydration was varied. The corneal hydration was then calculated from the corneal thickness. The group refractive index of the cornea increased non-linearly as the cornea dehydrated. In addition, a simple mathematical model was developed, based on the assumption that changes in corneal hydration occur only in the interfibrilar space with constant water content within the collagen fibrils. Good agreement between the experimental results and the mathematical model supports the assumption. The results also demonstrate that the measurement of refractive index is a quantitative indicator of corneal hydration.

This work updates the recent progress made toward fabricating a real-time, quantitative, and biocompatible glucose sensor based on surface-enhanced Raman scattering (SERS). The sensor design relies on an alkanethiolate tri(ethylene glycol) monolayer that acts as a partition layer, preconcentrating glucose near a SERS-active surface. Chemometric analysis of the captured SERS spectra demonstrates that glucose is quantitatively detected in the physiological concentration range (0-450 mg/dL, 0-25 mM). In fact, 94% of the predicted glucose concentrations fall within regions A and B of the Clarke error grid, making acceptable predictions in a clinically relevant range. The data presented herein also demonstrate that the glucose sensor provides stable SERS spectra for at least 3 days, making the SERS substrate a candidate for implantable sensing. Glucose sensor reversibility and reusability is evaluated as the sensor is alternately exposed to glucose and saline solutions; after each cycle, difference spectra reveal that the partitioning process is largely reversible. Finally, the SERS glucose sensor successfully partitions glucose even when challenged with bovine serum albumin, a serum protein mimic.

We report a new method by which phase slope and group dispersion can be calculated with a simple optical low-coherence reflectometer to quantify physiological conditions. A discrete-time signal processing algorithm based on the first and second derivatives of the phase with respect to wave number was developed from discrete-time Fourier properties. The algorithm avoids the 2pi ambiguity associated with most phase unwrapping. Experimental data collected by use of well-characterized optical materials validated the algorithm, which was minimally sensitive to phase noise. The group dispersion of bovine cornea was measured at various hydrations and was significantly dependent on hydration. The results suggest that group dispersion is an indicator of corneal alterations.

We report the depolarization of light scattered by a variety of birefringent and nonbirefringent tissues. We used Stokes polarimetry to investigate how scatterer structures in each tissue contribute to the depolarization of linearly versus circularly polarized light propagating through that tissue. Experiments were performed on porcine blood, fat, tendon, artery, and myocardium. The results indicate that the two incident polarization states are depolarized differently depending on the structure of the sample. As seen in sphere suspensions, for tissues containing dilute Mie scatterers, circularly polarized light is maintained preferentially over linearly polarized light. For more dense tissues, however, the reverse is true. The results illustrate situations where polarized light will provide an improvement over unpolarized light imaging, information that is crucial to optimizing existing polarimetric imaging techniques.

Background and Objective: Both patients and dentists would like a replacement of the dental drill. During the last decade, lasers have been investigated as a possible replacement. For lasers to be accepted, studies must show that their effect on the dental pulpal tissues is equal to or less noxious than those effects caused by the dental handpiece (drill)., Study Design/materials and Methods: In this study, two laser systems were used; the first was a breadboard CO(2) laser and the second a prototype clinical CO(2) laser system both emitted 60-micros-long pulses of 9.6-microm radiation. On the delivery system of both lasers, a scanner moved the focussed beam in a circular pattern and a water spray system served to cool the ablation site. Both lasers were used to create holes of similar dimensions in canine teeth. The treated teeth were then restored and harvested at either 4 days or 4 weeks. The teeth were decalcified, sectioned, and stained for examination via light microscopy., Results: The histologic examination revealed normal pulpal tissues in the canine teeth treated with both CO(2) lasers. Some histologic sections showed an increase in the predentin layer, 28 days after laser treatment. While many histologic sections showed normal pulpal architecture following handpiece treatment, some sections showed total disruption of the normal pulpal histology., Conclusions: Histologic evaluation revealed that the lasers produced no noticeable damage to the dental pulpal tissue and appear to be a safe method for removing dental hard tissues. From this study, it appears that 9.6 microm CO(2) laser does not cause damage to the dental pulpal tissues in dogs., (Copyright 2002 Wiley-Liss, Inc.)

Cryogen cooling during laser tissue welding was explored as a means of reducing lateral thermal damage near the tissue surface and shortening operative time. Two centimetre long full-thickness incisions were made on the epilated backs of guinea pigs, in vivo. India ink was applied to the incision edges then clamps were used to appose the edges. A 4 mm diameter beam of 16 W, continuous-wave, 1.06 microm, Nd:YAG laser radiation was scanned over the incisions, producing approximately 100 ms pulses. There was a delay of 2 s between scans. The total irradiation time was varied from 1-2 min. Cryogen was delivered to the weld site through a solenoid valve in spurt durations of 20, 60 and 100 ms. The time between spurts was either 2 or 4 s, corresponding to one spurt every one or two laser scans. Histology and tensile strength measurements were used to evaluate laser welds. Total irradiation times were reduced from 10 min without surface cooling to under 1 min with surface cooling. The thermal denaturation profile showed less denaturation in the papillary dermis than in the mid-dermis. Welds created using optimized irradiation and cooling parameters had significantly higher tensile strengths (1.7 +/- 0.4 kg cm(-2)) than measured in the control studies without cryogen cooling (1.0 +/- 0.2 kg cm(-2)) (p < 0.05). Cryogen cooling of the tissue surface during laser welding results in increased weld strengths while reducing thermal damage and operative times. Long-term studies will be necessary to determine weld strengths and the amount of scarring during wound healing.

Background and Objective: The purpose of this study was to evaluate sealant shear bond strength on bovine enamel with standard acid etching compared with CO(2) laser etching., Study Design/materials and Methods: Bovine enamel was prepared either by acid or laser etching and divided into four experimental groups, either acid or laser-etched teeth with or without a primer. A gelatin capsule was used to place the sealant on the prepared enamel surface and the bond tested in shear. Also surface roughness was evaluated by using a surface analyzer and an atomic force microscope., Results: Shear bond strength results were the following: acid etch = 8.8 +/- 3.8 MPa, acid etch with primer = 10.3 +/- 5.5 MPa, laser etch = 4.0 +/- 1.1 MPa, and laser etch with primer = 6.2 +/- 2.3 MPa. Analysis of variance statistical analysis found no significant difference in bond strength between the acid-etched groups. However, the laser-etched groups had significantly lower bond strengths from the acid-etched teeth. In addition, a significant difference was observed between the laser-etched groups, where the use of the primer helped to increase the bond strength of the sealants. The surface roughness was significantly greater on the laser-etched teeth at the microm level (by using a surface analyzer) from the acid-etched and the control specimens. No difference in roughness (by using an atomic force microscope) was observed at the nanometer level between the laser and acid-etched teeth., Conclusion: For these particular settings, the laser-etched teeth resulted in lower bond strengths to enamel and the use of a primer increased the bond strength for laser-etched teeth only., (Copyright 2000 Wiley-Liss, Inc.)

Background and Objective: Laser skin welding was investigated as a general model for laser tissue closure. Scanned delivery of near-infrared laser radiation in combination with a dye can produce strong welds with limited thermal damage., Study Design/materials and Methods: Two-centimeter-long, full-thickness incisions were made on the backs of guinea pigs. Wounds were closed either by laser welding or sutures and then biopsied at 0, 3, 6, 10, 14, 21, and 28 days postoperatively. Welding was achieved by using continuous-wave, 1. 06-micrometer, Nd:YAG laser radiation scanned over the incisions to produce a dwell time of approximately 80 msec. The cooling time between scans was fixed at 8 seconds. A 4-mm-diameter laser spot was maintained during the experiments, and the power was kept constant at 10 W. The operation time was fixed at 10 minutes per incision. India ink was used as an absorber of the laser radiation at the weld site, and clamps were used temporarily to appose the incision edges., Results: Acute weld strengths of 2.1 +/- 0.7 kg/cm(2) were significantly higher than suture apposition strengths of 0.4 +/- 0.1 kg/cm(2) (P < 0.01), and weld strengths continued to increase over time. Lateral thermal damage in the laser welds was limited to 200 +/- 40 micrometer near the epidermal surface with less thermal damage deeper within the dermis., Conclusion: Our welding technique produced higher weld strengths and less thermal damage than reported in previous skin welding studies and may represent an alternative to sutures., (Copyright 2000 Wiley-Liss, Inc.)

We demonstrate significant differences in the propagation of polarized light through biological tissue compared with two common tissue phantoms. Depolarization of linearly and circularly polarized light was measured versus propagation distance by use of two independent measurement techniques. The measurements were performed on adipose and myocardial tissues and on tissue phantoms that consisted of polystyrene microsphere suspensions and Intralipid. The results indicate that, in contrast with results obtained in tissue phantoms, linearly polarized light survives through longer propagation distances than circularly polarized light in biological tissue.

We describe the use of degree of polarization to discriminate unscattered and weakly scattered light from multiply scattered light in an optically turbid material. We use spatially resolved measurements of the degree of polarization to compare how well linearly and circularly polarized light survives in a sample. Experiments were performed on common tissue phantoms consisting of polystyrene and Intralipid microsphere suspensions and on adipose and arterial tissue. The results indicate that polarization is maintained even after unpolarized irradiance through each sample has been extinguished by several orders of magnitude. The results also show that polarized light propagation in common tissue phantoms is distinctly different from polarized light propagation in the two tissues investigated. Further, these experiments illustrate when polarization is an effective discrimination criterion and when it is not. The potential of a polarization-based discrimination scheme to image through the biological and nonbiological samples investigated here is also discussed.

Spreading of a new surfactant in the presence of a pre-existing surfactant distribution is investigated both experimentally and theoretically for a thin viscous substrate. The experiments are designed to provide a better understanding of the fundamental interfacial and fluid dynamics for spreading of surfactants instilled into the lung. Quantitative measurements of spreading rates were conducted using a fluorescent new surfactant that was excited by argon laser light as it spread on an air-glycerin interface in a petri dish. It is found that pre-existing surfactant impedes surfactant spreading. However, fluorescent microspheres used as surface markers show that pre-existing surfactant facilitates the propagation of a surface-compression disturbance, which travels faster than the leading edge of the new surfactant. The experimental results compare well with the theory developed using lubrication approximations. An effective diffusivity of the thin film system is found to be Deff = (E*gamma)/(mu/H), which indicates that the surface-compression disturbance propagates faster for larger background surfactant concentration, gamma, larger constant slope of the sigma*-gamma* relation, -E*, and smaller viscous resistance, mu/H. Note that sigma* and gamma* are the dimensional surface tension and concentration, respectively, mu is fluid viscosity, and H is the unperturbed film thickness.

Background and Objective: A thermal camera was used to measure surface temperatures during laser skin welding to provide feedback for optimization of the laser parameters., Study Design/materials and Methods: Two-centimeter-long, full-thickness incisions were made in guinea pig skin in vitro and in vivo. India ink was applied to the incision edges, which were then mechanically apposed. Continuous-wave, 1.06-microm Nd:YAG laser radiation was scanned over the incisions, producing an effective pulse duration of approximately 100 msec. Cooling durations between scans of 1.6, 4.0, and 8.0 sec were studied in vitro. A 5-mm-diameter laser spot was used with the power kept constant at 10 W. Thermal images were obtained at 30 frames per second with a thermal camera detecting 3-5 microm radiation. Surface temperatures were recorded at 0, 1, and 6 mm from the center line of the incision., Results/conclusions: Cooling durations of 1.6 and 4.0 seconds in vitro resulted in temperatures at the weld site that remained above approximately 65 degrees C for prolonged periods of time. Cooling durations of 8.0 seconds were sufficient both in vitro and in vivo to prevent a significant rise in baseline temperatures at the weld site over time., (Copyright 1999 Wiley-Liss, Inc.)

Linear birefringence, an optical property that results from a material's structure and composition, can be used to study dynamic changes in tissue structure. Single, 200 microseconds-long pulses from a Ho:YAG laser emitting 2.1 microns radiation were used to induce changes in the linear birefringence of rat tail tendon. Such changes were measured on a millisecond timescale. The measured rate coefficients describing the denaturation are not predicted by previous studies of collagen denaturation induced by slower, lower-temperature heating. Two types of laser-induced collagen denaturation can be differentiated: thermal denaturation, which appears rate-limited, and thermomechanical denaturation, which is observed at higher laser radiant exposures. Neither process is described by standard Arrhenius-type kinetic models.

Background and Objective: Linear birefringence is an anisotropic property of rat tail tendon, which is largely composed of collagen. Our goal is to show that the dynamic range and sensitivity of the linear birefringence loss of collagen during heating are sufficient for kinetic modeling of the reaction., Study Design, Materials and Methods: The linear birefringence loss was quantified for tendon denatured via both a heated-isotonic-saline bath and a heated stage. All measurements were made with a polarizing transmission microscope equipped with a Berek compensator., Results: The data show that the loss of linear birefringence is a first-order kinetic reaction. The native rat tail tendon birefringence, delta n = 3.0 +/- 0.6 x 10(-3) (mean +/- std. err.), is lost after denaturation occurs (delta n = 0). Application of the Arrhenius equation to the linear birefringence data yields the activation energy (Ea = 89 +/- 1 kcal/mole), pre-exponential coefficient (A = e130 +/- 1 s-1), enthalpy (delta H = 88 +/- 1 kcal/mole) and entropy (delta S = 197 +/- 2 cal/degree K.mole)., Conclusion: This study shows that dynamic changes in linear birefringence can be used to monitor thermally induced changes in collagen.

Previous assumptions that water is not a 193-nm chromophore during ArF excimer laser tissue ablation are based on room-temperature data and ignore spectroscopic literature that suggests a strong temperature dependence of far-ultraviolet water absorption. By the use of a Q-switched Er:YAG laser as a pump source and an ArF excimer laser as a probe source, thermal generation and relaxation of 193-nm water absorption were characterized under nonequilibrium high-temperature and high-pressure conditions. At volumetric energy densities as small as 2 kJ/cm(3) relative to room temperature, the 193-nm absorption coefficient of water was measured to increase by more than 5 orders of magnitude. These results are consistent with the hypothesis that the absorption of 193-nm radiation by water may play a role in ArF excimer laser ablation of tissue.

Background and Objective: The clinical use of lasers to cut and coagulate tissue necessitates a better understanding of how the residual thermal damage affects healing. This study was designed to evaluate the effects of varying degrees of thermal damage on the healing process., Study Design, Materials and Methods: Partial-thickness lesions were created in guinea pig skin using an Er:YAG laser, a Ho:YAG laser, and a scalpel. To monitor recovery of the stratum corneum, water flux from the wound sites was quantified and histological data obtained for approximately one week., Results: The data indicate an exponential water loss pattern from all wounds. Water flux from the scalpel- and the Er:YAG laser-induced wounds was initially high but decreased rapidly with decay rates (mean +/- SE) of 0.46 +/- 0.01 day-1 and 0.38 +/- 0.01 day-1, respectively. The Ho:YAG laser-induced wounds demonstrated a different pattern of decay with lower water flux values initially and a decay rate of only 0.13 +/- 0.01 day-1., Conclusion: Histological and water flux data reveal that Er:YAG laser-induced wounds achieve epidermal integrity only slightly after scalpel-induced lesions, and Ho:YAG laser-induced wounds heal substantially slower and contain more granulation tissue.

Background and Objective: Several lasers have been explored for hard dental tissue applications; used alone they have resulted in potentially harmful temperature increases in the pulp chamber., Materials and Methods: An Er:YAG laser (lambda = 2.94 microns) was used to ablate hard dental tissues. Ablation rates with and without a water-cooling spray were measured. Subsequent experiments investigated the cooling effects of the water. Initially single channels were drilled into dentin; further studies involved ablating rectangular areas with repetition rates up to 10 Hz., Results: The water spray minimally reduced the ablation rates of dentin and did not affect the ablation rates of enamel. The water spray effectively cooled the teeth; while using the maximum average power investigated (10 Hz, 360 mJ/pulse), a water flow rate of 4.5 ml/min limited the temperature rise in the pulp chamber to less than 3 degrees C., Conclusion: The studies confirm the feasibility of using an Er:YAG laser in conjunction with a water spray to safely and effectively remove hard dental tissues.

An Er:YAG laser coupled with a cooling stream of water effectively removes dental hard tissues. However, before such a system can be deemed clinically viable, some safety and efficacy issues must be addressed. We compared the bonding of composite to dentin following the preparation of the dentinal surface with either an Er:YAG laser (lambda = 2.94 microns) or a standard dental bur and with and without a subsequent acid-etching treatment. The crowns of extracted human molars were removed, revealing the underlying dentin. We removed an additional thickness of material with either a dental handpiece or an Er:YAG laser (350 mJ/pulse at 6 Hz) by raster-scanning the samples under a fixed handpiece or laser. Comparable surface roughnesses were obtained. Several samples from each group received an acid-conditioning treatment. A cylinder of composite was bonded onto the prepared surfaces. The dentin-composite bond was then shear-stressed to failure on a universal testing apparatus. The results indicate that laser-irradiated samples had improved bond strengths compared with acid-etched and handpiece controls. SEM photographs of the surfaces show exposed tubules following the laser treatment: tubules could also be exposed with acid etching. We conclude that Er:YAG laser preparation of dentin leaves a suitable surface for strong bonding or an applied composite material.

Since the development of the ruby laser by Maiman in 1960, there has been great interest among dental practitioners, scientists, and patients to use this tool to make dental treatment more pleasant. Oral soft tissue uses are becoming more common in dental offices. The possible multiple uses of lasers in dentistry, beyond soft tissue surgery and dental composite curing, unfortunately, have not yet been realized clinically. These include replacement of the dental drill with a laser, laser dental decay prevention, and laser decay detection. The essential question is whether a laser can provide equal or improved treatment over conventional care. Safe use of lasers also must be the underlying goal of proposed or future laser therapy. With the availability and future development of different laser wavelengths and methods of pulsing, much interest is developing in this growing field. This article reviews the role of lasers in dentistry since the early 1960s, summarizes some research reports from the last few years, and proposes what the authors feel the future may hold for lasers in dentistry.

Water is a primary tissue chromophore in the midinfrared. Absorption of midinfrared radiation by water is a function of temperature and pressure, both of which rise rapidly during an ablative laser pulse. Data show that the absorption coefficient of water changes, by as much as two orders of magnitude, during a high-irradiance laser pulse. We present an ablation model that is fundamentally based upon Beer's Law but considers changes in the absorption coefficient. The model predicts that Er:YAG laser cuts will be deeper than Er:YSGG laser cuts; an opposite prediction would be made based upon the static, low-intensity absorption coefficient of water. The results of in vitro ablation of skin confirm that the dynamic optical properties of tissue need to be considered in the understanding of laser ablation as well as the design, manufacture, use, and regulation of clinical laser systems.

We hypothesized that laser ablation of gallbladder epithelium would prevent gallstone formation in prairie dogs. An Er:YAG laser (lambda = 2.94 microns) was used to ablate the gallbladder epithelium of 24 prairie dogs; 20 sham-irradiated and 12 non-operated prairie dogs served as controls. Prairie dogs were sacrificed at time periods of 4 days, 2 weeks, and 8-12 weeks and evaluated for the presence of gallstones and cholesterol crystals. Laser-irradiated gallbladders demonstrated a lower rate of gallstone formation at 8-12 weeks than the sham-irradiated gallbladders (39% vs. 79%: P < .02). Crystal formation, however, was not different between laser-irradiated (88%) and sham-irradiated (100%) animals. The laser-irradiated group had less epithelium than the non-operated group at all time periods (P < or = .002) and compared to the sham-irradiated group at 4 days and 8-12 weeks (P < or = .001). These data suggest that laser ablation of gallbladder epithelium can reduce the rate of gallstone formation although this effect may be temporary.

Pressure induced by ablative pulses of laser radiation is shown to correlate with the mechanical disruption of tissue. The ablation pressure induced during Er:YSGG laser irradiation of skin, liver, and aorta was calculated from a ballistic pendulum-based measurement of recoil momentum. The ejected material and ablation crater were examined grossly and microscopically after ablation. A gas-dynamic model of laser-induced vaporization was used to understand the measured pressures. The results show that mechanical disruption of tissue occurs when the ablation pressure exceeds the strength of the irradiated tissue at sites of intrinsic weakness.

There is a quest to find a method to remove diseased and healthy dental hard tissues without the negative stimuli associated with dental handpieces. Today, lasers are being considered as a potential replacement. This report evaluates effects of three lasers on dentin and pulpal tissues. The Er:YAG laser appears to have a lesser thermal effect.

Knowledge of the optical properties of biliary tract tissues is useful for aiding in the development and understanding of clinical applications of lasers in the biliary tract. Human gallbladder and bile specimens were obtained during laproscopic cholecystectomy. The diffuse remittance and transmission of the samples were determined from 350 to 2450 nm. Collimated transmission was determined at 633 and 2100 nm. Using one-dimensional diffusion theory, we calculated micro(s), micro(a), and g as a function of wavelength. Both gallbladder and bile show absorption peaks at 1.4 and 1.9 microm. Bile has a peak at 400 nm; gallbladder has peaks at 410 and 550 nm. The absorption peaks are correlated with known tissue chromophores. The effect of the sample preparation on the results is discussed.

Thermal damage produced by continuous wave (cw) CO2 laser ablation of tissue in vitro was measured for irradiances ranging from 360 W/cm2 to 740 kW/cm2 in order to investigate the extent to which ablative cooling can limit tissue damage. Damage zones thinner than 100 microns were readily produced using single pulses to cut guinea pig skin as well as bovine cornea, aorta, and myocardium. Multiple pulses can lead to increased damage. However, a systematic decrease in damage with irradiance, predicted theoretically by an evaporation model of ablation, was not observed. The damage-zone thickness was approximately constant around the periphery of the cut, consistent with the existence of a liquid layer which stores heat and leads to tissue damage, and with a model of damage and ablation recently proposed by Zweig et al.

Ablation of guinea pig skin using a CO2 laser emitting 2-mu sec-long pulses has been quantified by measuring the mass of tissue removed as a function of incident fluence per pulse. The mass-loss curves show three distinct regimes in which water evaporation, explosive tissue removal, and laser-induced plasma formation dominate. The data are fit to two models that predict that the mass removed depends either linearly or logarithmically on fluence. Although the data are best fit by a linear dependence upon fluence, plasma formation at high fluences prohibited obtaining data over a wide enough fluence range to differentiate unambiguously between the two models. Ablation efficiency, ablation thresholds, and the optical penetration depth at 10.6 micron were obtained from the measurements.

Lasers could come to occupy a highly important position in the armament of medicine. They are the brightest known sources of light, man-made or natural, and emit light having such properties as coherence and monochromaticity. Furthermore, lasers have the ability to deliver very brief pulses of light which can cause unique alterations in biological materials. The major obstacle to the increased use of lasers in medicine and surgery is not the availability of laser devices, but the dearth of basic information about laser-tissue interactions. We have recently demonstrated that, even in turbid tissue such as the dermis, it is possible simultaneously to induce microscopically selective thermal damage, localized to millions of selectively absorbing targets, while sparing surrounding tissues. These "targets" may be as small as organelles or as large as blood vessels. Such localized thermal damage is truly unique to pulsed laser exposures. The scope and medical utility of these lesions has yet to be fully understood. Thus, there is much research to be done in describing and characterizing laser-induced injury. There is, however, ample evidence that several laser therapies could be improved by using selectively absorbed, short pulses that lead to the spatial confinement of thermal injury. Treatment of port wine stains, pigmented lesions, atheromatous arterial plaques, and the fragmentation of kidney and gall stones are examples. It should also be possible to use a variety of systems to deliver exogenous laser targets on or within individual types of cells or organelles. Such chromophores may lead to new forms of cancer therapy, for example.

Tissue removal by infrared lasers is accompanied by thermal damage to nonablated tissue. The extent of thermal damage can be controlled by a choice of laser wavelength, irradiance, and exposure duration. The effect of exposure duration has been studied in vivo by using CO2 lasers with pulse widths that vary from 2 microseconds to 50 msec. Pulse widths of 50 msec, typical of a shuttered, continuous-wave CO2 laser, produce damage regions 750 micron wide in normal guinea pig skin; the use of a 2-microseconds-long pulse reduced this damage zone to as little as 50 micron. Using 2-microseconds-long pulses, in vitro studies showed that the minimum zone of thermal damage varied significantly with tissue type. The thermal denaturation of these tissues has been studied and correlated with damage. The effect of denaturation temperature and pulse duration on the width of the damage zone is explained by a simple model.

The ablation rate of guinea pig skin and bovine aorta, myocardium, and liver by a CO2 laser emitting 2-microseconds-long pulses was quantified. Ablation efficiency was found to be strongly dependent upon the ultimate tensile strength of the tissue; the ablation efficiency of liver is seven times that of skin. Gluteraldehyde cross linking of skin, which is known to greatly increase tissue stiffness but not significantly affect ultimate tensile strength, did not change the ablation rate. The water content of the tissues, which largely determines the optical and thermal properties, was measured and found to vary only slightly. The results demonstrate that tissue mechanical properties are important in the interpretation and modeling of pulsed laser ablation of tissue and that variations in these mechanical properties can lead to drastically different cutting rates for different tissues.

The thermal damage caused by 2.94-micron Er:YAG laser ablation of skin, cornea, aorta, and bone was quantified. The zone of residual thermal damage produced by normal-spiking-mode pulses (pulse duration approximately 200 microseconds) and Q-switched pulses (pulse duration approximately 90 ns) was compared. Normal-spiking-mode pulses typically leave 10-50 microns of collagen damage at the smooth wall of the incisions; however, at the highest fluences (approximately 80J/cm2) tears were produced in cornea and aorta and as much as 100 microns of damaged collagen is found at the incision edge. Q-switched pulses caused less thermal damage, typically 5-10 microns of damage in all tissues.

The ablation of both soft and hard tissue using the normal-spiking-mode Er:YAG laser has been quantified by measuring the number of pulses needed to perforate a measured thickness of tissue. Bone is readily ablated by 2.94 microns radiation; however, at per pulse fluences greater than 20 J/cm2, plasma formation decreases ablation efficiency. At low fluence, desiccation can prevent efficient ablation of bone. The ablation efficiency for aorta and skin is higher than for bone. The ablation efficiency, 540 micrograms/J, and the ablation depth per pulse, greater than 400 microns, for skin are too high to be readily explained by simple models of ablation and thus provide evidence for a more complex explosive removal process.