Measurement of tissue absorption coefficients by use of interferometric photothermal spectroscopy

We describe a spectroscopic technique called interferometric photothermal spectroscopy (IPTS) that can measure the absorption coefficient of pulsed laser radiation in nonscattering tissue samples. The technique is suitable for measuring effective absorption coefficients from 10(3) to 10(5) cm(-1). IPTS is particularly attractive because it requires minimal disturbance of the sample. These features indicate potential use for in vivo measurements of tissue absorption coefficients. To validate the technique, the absorption coefficient of pulsed Q-switched Er:YSGG (2.79-microm) radiation in pure water was measured to be 5200 (+/-500) cm(-1) when IPTS was used, in agreement with other published values. IPTS was also used to measure the absorption coefficient of pulsed ArF excimer laser radiation (193 nm) in bovine corneal stroma (in vitro), giving a value of 1.9 (+/-0.4) x 10(4) cm(-1).     

Measurement of small-signal absorption coefficient and absorption cross section of collagen for 193-nm excimer laser light and the role of collagen in tissue ablation

A 193-nm ArF excimer laser transmission was measured at subablative fluence through varying strength solutions of dissolved collagen, yielding an absorption cross section of 1.14 x 10(-17) cm2 for the peptide bond, which accounts for 96% of the total collagen attenuation that is based on additional transmission measurements through solutions of isolated constituent amino acids. The measured absorption cross sections, in combination with typical corneal tissue composition, yield a predicted corneal tissue absorption coefficient of 16,000 cm(-1). In addition, dry collagen films were prepared and ablation-rate data were recorded as a function of laser fluence. Ablation rates were modeled by use of a Beer-Lambert blow-off model, incorporating a measured ablation threshold and an absorption coefficient that are based on the measured collagen absorption cross section and the film bond density. The measured ablation rates and those predicted by the model were in very good agreement. The experiments suggest that collagen-based absorption coefficients are consistent with predicted corneal tissue ablation rates and previously observed dynamic changes in tissue properties under ablative conditions.     

Development of a fiber-optic laser delivery system capable of delivering 213 and 266 nm pulsed Nd:YAG laser radiation for tissue ablation in a fluid environment

Ultraviolet (UV) lasers have the capability to precisely remove tissue via ablation; however, due to strong absorption of the applicable portion the UV spectrum, their surgical use is currently limited to extraocular applications at the air/tissue boundary. Here we report the development and characterization of a fiber-optic laser delivery system capable of outputting high-fluence UV laser pulses to internal tissue surfaces. The system has been developed with a view to intraocular surgical applications and has been demonstrated to ablate ocular tissue at the fluid/tissue boundary. The fifth (213?nm) and fourth(266?nm) harmonics of a Nd:YAG laser were launched into optical fibers using a hollow glass taper to concentrate the beam. Standard and modified silica/silica optical fibers were used, all commercially available. The available energy and fluence as a function of optical fiber length was evaluated and maximized. The maximum fluence available to ablate tissue was affected by the wavelength dependence of the fiber transmission; this maximum fluence was greater for 266?nm pulses (8.4?J/cm2) than for 213?nm pulses (1.4?J/cm2). The type of silica/silica optical fiber used did not affect the transmission efficiency of 266?nm pulses, but transmission of 213?nm pulses was significantly greater through modified silica/silica optical fiber. The optical fiber transmission efficiency of 213?nm pulses decreased as a function of number of pulses transmitted, whereas the transmission efficiency of 266?nm radiation was unchanged. Single pulses have been used to ablate fresh porcine ocular tissue. In summary, we report a method for delivering the fifth (213?nm) and fourth (266?nm) harmonics of a Nd:YAG laser to the surface of immersed tissue, the reliability and stability of the system has been characterized, and proof of concept via tissue ablation of porcine ocular tissue demonstrates the potential for the intraocular surgical application of this technique.     

Comparison of spatially and temporally resolved diffuse-reflectance measurement systems for determination of biomedical optical properties

Time-resolved and spatially resolved measurements of the diffuse reflectance from biological tissue are two well-established techniques for extracting the reduced scattering and absorption coefficients. We have performed a comparison study of the performance of a spatially resolved and a time-resolved instrument at wavelengths 660 and 786 nm and also of an integrating-sphere setup at 550-800 nm. The first system records the diffuse reflectance from a diode laser by means of a fiber bundle probe in contact with the sample. The time-resolved system utilizes picosecond laser pulses and a single-photon-counting detection scheme. We extracted the optical properties by calibration using known standards for the spatially resolved system, by fitting to the diffusion equation for the time-resolved system, and by using an inverse Monte Carlo model for the integrating sphere. The measurements were performed on a set of solid epoxy tissue phantoms. The results showed less than 10% difference in the evaluation of the reduced scattering coefficient among the systems for the phantoms in the range 9-20 cm(-1), and absolute differences of less than 0.05 cm(-1) for the absorption coefficient in the interval 0.05-0.30 cm(-1).     

Tunable diode-laser absorption measurements of NO(2) near 670 and 395 nm

Two single-mode diode lasers were used to record high-resolution absorption spectra of NO(2) (dilute in Ar) near 670.2 and 394.5 nm over a range of temperatures (296 to 774 K) and total pressures (2.4 × 10(-2) to 1 atm). A commercial InGaAsP laser was tuned 1.3 cm(-1) at a repetition rate of 1 kHz to record the absorption spectra near 670.2 nm. In separate experiments with a prototype system, an external-cavity GaAlAs laser was frequency doubled with a quasi-phase-matched LiNbO(3) waveguide and tuned 3.5 cm(-1) to record absorption spectra near 394.5 nm. Variations of the spectral absorption coefficients with temperature and pressure were determined from measured spectra.     

Changes in optical properties of rat cerebral cortical slices during oxygen glucose deprivation

We simultaneously measured the diffuse reflectance spectra and transmittance spectra of in vitro rat cerebral cortical tissue slices perfused with artificial cerebrospinal fluid (aCSF) in the wavelength range from 500 to 900 nm. An ischemia-like condition in the cortical tissue was induced by oxygen/glucose deprivation (OGD) of the aCSF. Diffuse reflectance and transmittance of the cortical slices were decreased and increased, respectively, during OGD. Spectral data of reduced scattering coefficients and absorption coefficients were estimated by the inverse Monte Carlo simulation for light transport in tissue. As with OGD, significant decrease of the reduced scattering coefficients and alteration of the absorption coefficient spectrum were observed over the measured wavelength range. The mean maximum amplitudes of change in the absorption coefficient at 520, 550, 605, and 830 nm were 0.33 ± 0.14, 0.30 ± 0.12, 0.30 ± 0.14, and -0.04 ± 0.16, respectively, whereas those in the reduced scattering coefficient at 520, 550, 605, and 830 nm were -0.37 ± 0.08, -0.38 ± 0.08, -0.38 ± 0.08, and -0.39 ± 0.08. Variations in the reduced scattering coefficients implied cell deformation mainly due to cell swelling, whereas those in the absorption spectra indicated reductions in heme aa(3) and CuA in cytochrome c oxidase and cytochrome c.     

Nonlinear absorption of thin Al2O3 films at 193 nm

Absorption of thin Al(2)O(3) films was measured at 193 nm with an ArF-laser calorimeter. In addition to the expected high linear absorption coefficient, we found, for the first time to our knowledge, that two-photon absorption and transient color-center formation are nonnegligible loss channels in thin films at 193 nm. The nonlinear absorption coefficient is of the order of several times 10(-4) cm/W.     

Dynamic 193-nm optical properties of water

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.     

Temperature Dependence of Absorption in Ice at 532 nm

A YAG laser was used to emit nanosecond pulses of light at 532 nm at depths from 1185 to 2200 m in Antarctic ice, corresponding to temperatures increasing from 229 to 249 K. From the timing distributions of photons arriving at phototubes at distances up to 100 m and at similar depths, the scattering and absorption coefficients were measured, and the temperature dependence of absorptivity at 532 nm was determined. Despite the absorptivity being many orders of magnitude lower at 532 nm than in the near ultraviolet and near infrared, the fractional increase of absorptivity, a(-1)da/dT = 0.01 K(-1), was the same in the visible, ultraviolet, and infrared. Analysis of published data at other wavelengths shows that a(-1)da/dT is ~0.01 K(-1) from 175 nm to ~1 cm, above which it increases strongly from 1 cm to 10 m. That temperature dependence applies only in regions not close to absorption bands.     

808-nm diode-pumped continuous-wave Tm:GdVO4 laser at room temperature

A high-quality gadolinium vanadate (GdVO4) crystal with 7-at. % thulium as the starting material was grown by the Czochralski technique. The measured absorption spectra exhibited sufficient absorption coefficients for laser diodes (LDs) for neodymium laser pumping: 6.0 cm(-1) for pi polarization and 6.2 cm(-1) for sigma polarization at 808 nm. Laser oscillation was carried out with single-stripe 808-nm LDs in an end-pumping configuration. A slope efficiency of 28% and a threshold of 750 mW were exhibited with respect to the absorbed pump power. An output power of 420 mW was achieved at an absorbed power of 2.4 W. It was demonstrated that Tm:GdVO4 is a useful material for 2-microm lasers, particularly in a compact LD-pumped system.     

Ultrasensitive, visible tunable diode laser detection of NO(2)

Recent advances in room-temperature visible diode lasers and ultrasensitive detection techniques have been exploited to create a highly sensitive tunable diode laser absorption technique for in situ monitoring of NO(2) in the lower troposphere. High sensitivity to NO(2) is achieved by probing the visible absorption band of NO(2) with an AlGalnP diode laser at 640 or 670 nm combined with a balanced ratiometric electronic detection technique. We have demonstrated a sensitivity of 3.5 × 10(10) cm(-3) for neat NO(2) in a 1-m path at 640 nm and have estimated a sensitivity for ambient operation of 5 ppbv m (l0 ppbv m at 670 nm), where ppbvm is parts in 10(9) by volume per meter of absorption path length, from measured pressure-broadening coefficients.     

Injection-seeded pulsed alexandrite laser for differential absorption lidar application

We describe a Q-switched alexandrite laser injection seeded with a cw single-mode titanium-sapphire laser. The reported experimental results show that this system meets the frequency stabilization required for differential absorption lidar measurement of humidity, pressure, and temperature. The emission of the cw titanium-sapphire master oscillator is locked to an atmospheric absorption line by means of a servoloop with derivative spectroscopy. The spectral position is stabilized within ±3.5 × 10(-4) cm(-1) (10 MHz) of the peak of the line over 1 hr. The alexandrite laser emits pulses of 30 mJ in 500 ns, with a spectral linewidth of ≈ 3.3 × 10(-3) cm(-1) (100 MHz). The position of the centroid of the emitted spectrum has a standard deviation of 6 × 10(-4) cm(-1) (18 MHz) and is held within ±1.3 × 10(-3) cm(-1) (40 MHz) of the peak of the absorption line over 1 h.     

Visible single-shot autocorrelator in BaF(2) for subpicosecond KrF laser pulses

A single-shot autocorrelator based on the two-photon excited fluorescence of BaF(2) in the visible region at 400 nm has been developed for ultrashort KrF laser pulses at 248 nm. Operation in the visible region offers simplification in the required optical components as compared with previously reported systems, which used ultraviolet fluorescence emission. The fluorescence intensity is also used to measure the two-photon absorption coefficient of BaF(2), yielding a value of β = 1.3 ± 0.4 × 10(-10) cm/W.     

Spatially resolved absolute diffuse reflectance measurements for noninvasive determination of the optical scattering and absorption coefficients of biological tissue

The absorption and transport scattering coefficients of biological tissues determine the radial dependence of the diffuse reflectance that is due to a point source. A system is described for making remote measurements of spatially resolved absolute diffuse reflectance and hence noninvasive, noncontact estimates of the tissue optical properties. The system incorporated a laser source and a CCD camera. Deflection of the incident beam into the camera allowed characterization of the source for absolute reflectance measurements. It is shown that an often used solution of the diffusion equation cannot be applied for these measurements. Instead, a neural network, trained on the results of Monte Carlo simulations, was used to estimate the absorption and scattering coefficients from the reflectance data. Tests on tissue-simulating phantoms with transport scattering coefficients between 0.5 and 2.0 mm(-1) and absorption coefficients between 0.002 and 0.1 mm(-1) showed the rms errors of this technique to be 2.6% for the transport scattering coefficient and 14% for the absorption coefficients. The optical properties of bovine muscle, adipose, and liver tissue, as well as chicken muscle (breast), were also measured ex vivo at 633 and 751 nm. For muscle tissue it was found that the Monte Carlo simulation did not agree with experimental measurements of reflectance at distances less than 2 mm from the incident beam.     

Intracavity absorption spectroscopy with a tunable multimode traveling-wave ring Ti:sapphire laser

A tunable multimode unidirectional traveling-wave Ti:sapphire laser was developed to measure in situ the atmospheric absorption spectra using intracavity absorption spectroscopy. The effective absorption path length was 2100 km. O2 and H2O vapor lines in atmosphere with absorption coefficients of 10(-6)-10(-8) cm(-1) were measured with uncertainties <5%, and the absorption coefficients were in agreement with those estimated from the HITRAN database. By tuning the wavelength, a weak absorption line with an absorption coefficient of 10(-9) cm(-1) was measured with a sensitivity of 2×10(-10) cm(-1). The sensitivity was limited by the residual parasitic variation that appeared in the spectrum.     

Photothermal detection of trace optical absorption in water by use of visible-light-emitting diodes

Visible-light-emitting diodes of three different colors have been used to detect an absorbing compound (potassium permanganate) in trace quantities in aqueous solution. Photothermal absorption in a closed cell caused deflection of a water meniscus held at a small pinhole. The displacement was monitored with optical-fiber interferometry. The technique was limited by LED emission intensities and environmental acoustic noise, giving minimum detectable absorption coefficients of 2 x 10(-4) cm(-1) at 478 and 658 nm and 3 x 10(-4) cm(-1) at 524 nm. The magnitude and form of meniscus deflection signals were shown to be in good agreement with theory.     

Excimer laser chemical ammonia patterning on PET film

Laser is a promising technique used for biopolymer surface modification with micro and/or nano features. In this work, a 193 nm excimer laser was used for poly (ethylene terephthalate) (PET) surfaces chemical patterning. The ablation threshold of the PET film used in the experiments was 62 mJ/cm(2) measured before surface modification. Surface chemical patterning was performed by irradiating PET film in a vacuum chamber filled with ammonia at the flux of 10, 15, 20, 25 ml/min. Roughness of the surface characterized by profilometry showed that there were no significant observed change after modification comparing original film. But the hydrophilicity of the surface increased after patterning and a minimum water contact angle was obtained at the gas flux of 20 ml/min. FT-IR/ATR results showed the distinct amino absorption bands presented at 3352 cm(-1)and 1613 cm(-1) after modification and XPS binding energies of C(1s) at 285.5 eV and N(1s) at 399.0 eV verified the existence of C-N bond formation on the PET film surface. Tof-SIMS ions mapping used to identify the amine containing fragments corroborates that amino grafting mainly happened inside the laser irradiation area of the PET surface. A hypothesized radical reaction mechanism proposes that the collision between radicals in ammonia and on the PET surface caused by the incident laser provokes the grafting of amino groups.     

Wavelength-modulation laser hygrometer for ultrasensitive detection of water vapor in semiconductor gases

Water vapor is measured by use of a near-infrared diode laser and wavelength-modulation absorption spectroscopy. Humidity levels as low as 5 nmol/mol [1 nmol/mol = 1 ppb (1 ppb equals 1 part in 10(9))] of water vapor in air are measured with a sensitivity of better than 0.2 nmol/mol (3varsigma). The sensitivity, linearity, and stability of the technique are determined in experiments conducted at the National Institute of Standards and Technology, Gaithersburg, Maryland, by use of the low frost-point humidity generator over the range from 5 nmol/mol to 2.5 mumol/mol of water vapor in air. The pressure-broadening coefficients for water broadened by helium [0.0199(6) cm(-1) atm(-1) HWHM] and by hydrogen chloride [0.268(6) cm(-1) atm(-1) HWHM] are reported for the water line at 1392.5 nm.     

Measurement of the absorption coefficient of CO2 laser windows with hysteresis in the power-tuning curve of a single-mode continuous-wave CO2 laser

We report a new method for the measurement of the absorption coefficient of CO(2) laser windows. The method exploits the hysteresis in the power-tuning curve of a single-mode continuous-wave CO(2) laser and allows measurements of absorption coefficients of the order of ~10(-3) cm(-1) in CO(2) laser windows a few millimeters thick.     

Gold nanoshell photomodification under a single-nanosecond laser pulse accompanied by color-shifting and bubble formation phenomena

Laser-nanoparticle interaction is crucial for biomedical applications of lasers and nanotechnology to the treatment of cancer or pathogenic microorganisms. We report on the first observation of laser-induced coloring of gold nanoshell solution after a one nanosecond pulse and an unprecedentedly low bubble formation (as the main mechanism of cancer cell killing) threshold at a laser fluence of about 4?mJ?cm(-2), which is safe for normal tissue. Specifically, silica/gold nanoshell (140/15?nm) suspensions were irradiated with a single 4?ns (1064?nm) or 8?ns (900?nm) laser pulse at fluences ranging from 0.1?mJ?cm(-2) to 50?J?cm(-2). Solution red coloring was observed by the naked eye confirmed by blue-shifting of the absorption spectrum maximum from the initial 900?nm for nanoshells to 530?nm for conventional colloidal gold nanospheres. TEM images revealed significant photomodification of nanoparticles including complete fragmentation of gold shells, changes in silica core structure, formation of small 20-30?nm isolated spherical gold nanoparticles, gold nanoshells with central holes, and large and small spherical gold particles attached to a silica core. The time-resolved monitoring of bubble formation phenomena with the photothermal (PT) thermolens technique demonstrated that after application of a single 8?ns pulse at fluences 5-10?mJ?cm(-2) and higher the next pulse did not produce any PT response, indicating a dramatic decrease in absorption because of gold shell modification. We also observed a dependence of the bubble expansion time on the laser energy with unusually very fast PT signal rising (～3.5?ns scale at 0.2?J?cm(-2)). Application of the observed phenomena to medical applications is discussed, including a simple visual color test for laser-nanoparticle interaction.