Optical clearing of skin using flash lamp-induced enhancement of epidermal permeability.

BACKGROUND AND OBJECTIVES: Strong light scattering in skin prevents precise targeting of optical energy in therapeutic and diagnostic applications. Optical immersion based on matching refractive index of scattering centers with that of surrounding matter through introduction of an exogenous index-matching agent can alleviate the problem. However, slow diffusion of the index-matching agent through skin barrier makes practical implementation of this approach difficult. We propose a method of accelerating penetration of the index-matching compounds by enhancing skin permeability through creating a lattice of micro-zones (islets) of limited thermal damage in the stratum corneum (SC). STUDY DESIGN/MATERIALS AND METHODS: A flash lamp (intense pulsed light) system and an island mask with a pattern of absorbing centers (center size approximately 75-120 microm, lattice pitch approximately 450-500 microm) were used to create the lattice of islets of damage (LID). Index-matching agents, such as glucose solution, propylene glycol solution, and glycerol solution, were applied. RESULTS: Experimental results of optical clearing ex vivo rat and pig skin, and ex vivo and in vivo human skin are presented. Optical transmission spectra of the skin samples with LID were measured during some 2 hours after application of index-matching chemical agents. In order to assess and compare the clearing rate under different treatment and clearing agents we calculated the quantity that we call "relative transmittance": T(rel) = I(t)(lambda)/I(0)(lambda), were I(t)(lambda) is the intensity measured at elapsed time t. The dynamics of relative transmittance of skin samples at 470 and 650 nm shows that the implementation of limited thermal damage technique leads to a 3-10-fold increase of optical clearing (rise of transmittance) rate compared to the results obtained when the samples were treated with high-intensity light pulses but without the use of island damage mask (IDM). It was observed from the plotted spectra of relative transmittance that the maximum increase of transmitted light intensity has been obtained with glucose solution as a clearing agent. Noteworthy is the difference in the trend of spectral curves: relative transmittance spectrum for glycerol reveals, on the whole, a greater slope which may be indicative of higher extent of index matching between the scattering centers and base material for this index-matching agent. Under the transillumination of the skin sample by the wide flat beam the more effective clearing (the increase of transmitted intensity) is attained within the hemoglobin absorption bands; with the narrow quasi-collimated beam the higher relative transmittance was observed over the intervals of minimum absorption. CONCLUSIONS: The use of specially designed island mask combined with non-laser intensive pulse irradiation produces a lattice of islands of limited thermal damage in SC that substantially enhances the penetration rate of topically applied index-matching agents. The suggested technique gave comparable magnitudes of clearing dynamics enhancement for glucose solution, glycerol solution, and propylene glycol solution applied to mammalian skin.

Design and evaluation of a novel portable erythema-melanin-meter.

BACKGROUND AND OBJECTIVES: Objective evaluation of the pigmentation index (PI) and the eythema index (EI) of human skin is a prerequisite for successful optimization of laser- and intense-pulsed-light (IPL)-based treatment modalities in dermatology. STUDY DESIGN/MATERIALS AND METHODS: We describe a three-wavelength technique for determining PI and EI as well as its particular implementation using LEDs operating at wavelengths of 560, 650, and 710 nm and a large-area photodiode. The instrument has been evaluated both in vitro and in vivo. RESULTS: In vitro, good correlation between the measured indices and results obtained with commercially available techniques has been observed. In addition, linearity of the PI with melanin concentration in the phantom medium up to 7 x 10(-3) nm(-1) (defined as a slope of the optical density spectrum) has been established. In vivo, feasibility of using the technique for predicting the minimal erythema dose (MED), minimal phototoxic dose (MPD), and the threshold of epidermal damage in a photothermal treatment has been demonstrated. CONCLUSIONS: The data suggest that the technique has a substantial potential as a method of pre-treatment diagnostics for photochemical and photothermal procedures.

Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range.

Medical laser applications require knowledge about the optical properties of target tissue. In this study, the optical properties of selected native and coagulated human brain structures were determined in vitro in the spectral range between 360 and 1100 nm. The tissues investigated included white brain matter, grey brain matter, cerebellum and brainstem tissues (pons, thalamus). In addition, the optical properties of two human tumours (meningioma, astrocytoma WHO grade II) were determined. Diffuse reflectance, total transmittance and collimated transmittance of the samples were measured using an integrating-sphere technique. From these experimental data, the absorption coefficients, the scattering coefficients and the anisotropy factors of the samples were determined employing an inverse Monte Carlo technique. The tissues investigated differed from each other predominantly in their scattering properties. Thermal coagulation reduced the optical penetration depth substantially. The highest penetration depths for all tissues investigated were found in the wavelength range between 1000 and 1100 nm. A comparison with data from the literature revealed the importance of the employed tissue preparation technique and the impact of the theoretical model used to extract the optical coefficients from the measured quantities.

Scattering delay time of Mie scatterers determined from steady-state and time-resolved optical spectroscopy.

We have determined the scattering delay time of Mie scatterers (r = 255 nm quartz spheres in polyester resin) from a combination of steady-state (integrating-sphere) and time-resolved (frequency-domain) measurements performed in the multiple-scattering regime. The effective transport velocity of light was derived from intensity and phase measurements at four different wavelengths by using the time-integrated microscopic Beer-Lambert law. We could demonstrate a systematic underestimation of the effective transport velocity compared with the phase velocity in the medium. Assuming that this discrepancy was caused entirely by the transient nature of a single-scattering process, the data presented resulted in time delays of between 18 fs (lambda = 678 nm) and 177 fs (lambda = 1,064 nm) per scattering event. For three out of four wavelengths investigated, the measured values are in excellent agreement with values predicted by a theoretical model for the scattering delay time based on Mie theory.

Quantitative microspectrophotometry in turbid media.

We present a new technique to determine the scattering coefficient, the absorption coefficient, and the anisotropy factor in turbid media on a microscopic level. To this end, a microspectrophotometer was used to obtain transmission measurements at different solid angles. To extract the optical properties from phantom materials (liquid and solid) and biological tissue (bovine liver) an inverse Monte Carlo algorithm was used. The results obtained with the new microspectrophotometric technique agreed within one standard deviation with the values from Mie theory and within less than 10% with the data derived from conventional spectroscopic measurements. The results suggest that this new method is a valid tool to determine the optical properties of turbid media on a microscopic level.

Influence of the scattering phase function approximation on the optical properties of blood determined from the integrating sphere measurements.

We investigated the impact of the scattering phase function approximation on the optical properties of whole human blood determined from integrating sphere measurements using an inverse Monte Carlo technique. The diffuse reflectance Rd and the total transmittance Tt(λ=633 nm) of whole blood samples (Hct=38%) were measured with double-integrating sphere equipment. The scattering phase functions of highly diluted blood samples (Hct=0.1%) were measured using a goniophotometer. We approximated the experimentally determined scattering phase functions with either Henyey-Greenstein (HGPF), Gegenbauer kernel (GKPF), or Mie (MPF) phase functions to preset the anisotropy factor µ¯ for the inverse problem. We have employed HGPF, GKPF, and MPF approximations in the inverse Monte Carlo procedure to derive the absorption coefficient µa and the scattering coefficient µs. To evaluate the obtained data, we calculated the angular distributions of scattered light for optically thick samples and compared the results with goniophotometric measurements. The data presented in this study demonstrate that the employed approximation of the scattering phase function can have a substantial impact on the derived values of µs and µ¯, while µa and the reduced scattering coefficient µs' are much less sensitive to the exact form of the scattering phase function. © 1999 Society of Photo-Optical Instrumentation Engineers.

Treatment planning for MRI-guided laser-induced interstitial thermotherapy of brain tumors--the role of blood perfusion.

MR techniques have been demonstrated to allow a reliable monitoring of laser-induced interstitial thermotherapy (LITT). However, an adequate on-line control of this coagulation technique requires an exact therapy planning. The latter is mandatory to interpret the MR-monitoring data correctly to guarantee a precise laser irradiation. Moreover, it is a prerequisite for on-line decisions if modifications of the therapeutic regimen are required. In this work, we present a new simulation technique for LITT planning. The model accounts for the specific geometry of the treatment site, the exact configuration of the applicator, and the optical and thermal properties of the tissue, including changes during the heating process. The simulation results were compared with MR scans of laser-induced lesions in three patients with World Health Organization (WHO) grade II astrocytoma. Special interest was directed toward the role of blood perfusion, which was studied parametrically. Good agreement between the simulation results and the MR data was found if the appropriate blood perfusion rates were taken into account. Thus, the model can generate valid therapy plans allowing a precise on-line control of laser irradiation using MR techniques. Neglecting adequate perfusion parameters resulted in substantial errors with respect to the prediction of the final laser lesion.

Effect of the scattering delay on time-dependent photon migration in turbid media.

We modified the diffusion approximation of the time-dependent radiative transfer equation to account for a finite scattering delay time. Under the usual assumptions of the diffusion approximation, the effect of the scattering delay leads to a simple renormalization of the light velocity that appears in the diffusion equation. Accuracy of the model was evaluated by comparison with Monte Carlo simulations in the frequency domain for a semi-infinite geometry. A good agreement is demonstrated for both matched and mismatched boundary conditions when the distance from the source is sufficiently large. The modified diffusion model predicts that the neglect of the scattering delay when the optical properties of the turbid material are derived from normalized frequency- or time-domain measurements should result in an underestimation of the absorption coefficient and an overestimation of the transport coefficient. These observations are consistent with the published experimental data.

Inverse hybrid technique for determining the optical properties of turbid media from integrating-sphere measurements.

We have combined the Monte Carlo method with the small-angle approximation of the radiative transfer theory to derive the optical properties (the absorption coefficient, the scattering coefficient, and the anisotropy factor) of turbid materials from integrating-sphere measurements (the total transmittance and the diffuse reflectance) and the collimated transmittance. Unlike one-dimensional models, the technique accounts for the side losses of light at the edges of the sample. In addition, it enables the correction of the measured collimated signal for the contribution of multiply scattered light. On the other hand, the hybrid technique allows a significant reduction in calculation time compared with inverse methods based on a pure Monte Carlo technique. Numerical tests and experimental results from a phantom material (milk) as well as samples of biological tissue (porcine myocardium) confirmed the feasibility of applying this technique to the determination of the optical properties of turbid media.

Combined elastic and Raman light scattering of human eye lenses.

The distribution of the scattering coefficient (as defined in the appendix) at a wavelength of 647.1 nm along the visual axis of human eye lenses was investigated using a specially designed set-up for spatially resolved measurements of the intensity of the scattered light. For the same lenses, the distribution of the protein content was measured using confocal Raman microspectroscopy. Data collected by both methods were processed in terms of a recently developed theory of short-range, liquid-like order of crystallin proteins that accounts for eye lens transparency. Seven fresh intact human lenses of varying age have been investigated. In addition, elastic and Raman scattering measurements have been performed on fixed lenses. The main results and conclusions are: (1) Fixation significantly affects the light scattering properties of the eye lens. The average level of scattering increases and a change in the distribution of scattered light intensity along the visual axis occurs. Protein content and average distribution were not altered by fixation. (2) There are significant differences between the distribution of the scattering coefficient for lenses of different ages. For young lenses (18 and 20 years) regions with a low protein content (anterior and posterior cortex) show a higher level of elastic light scattering, while for older lenses (42-78 years old) there is no obvious correlation between the scattering level and protein content. (3) Changes in the level of light scattering along the visual axis of the lens cannot be explained by protein concentration effects.(ABSTRACT TRUNCATED AT 250 WORDS)