Biomedical subjects
Publications and source records attributed to S L Jacques.
An overview of laser-tissue interactions is presented in terms of the physical mechanisms of interaction, the time course of tissue response, and the level of biologic structure affected. The factors that affect dosimetry of photodynamic therapy are presented. Laser dosimetry for photothermal and photomechanical interactions is outlined.
Argon-fluoride (ArF) excimer laser-induced acoustic injury was confirmed by ablating the stratum corneum (s.c.) inertially confined by water in vivo. Hairless rats were irradiated through a quartz chamber with flowing distilled water or air and a 2.5 mm aperture. The laser was adjusted to deliver 150 mJ/cm2 at the skin surface for both conditions. Partial and complete ablation of the s.c. was achieved with 12 and 24 pulses, respectively. Immediate damage was assessed by the transmission electron microscopy. Partial ablation of the s.c. through air produced no damage, whereas partial ablation through water damaged skin to a mean depth of 114.5 +/- 8.8 microns (+/- SD). Full thickness ablation of the s.c. through air and water produced damage zones measuring 192.2 +/- 16.2 and 293.0 +/- 71.6 microns, respectively (P less than 0.05). The increased depth of damage in the presence of inertial confinement provided by the layer of water strongly supports a photoacoustic mechanism of damage. The damage induced by partial ablation of the s.c. provides evidence that photochemical injury is not a significant factor in the damage at a depth because the retained s.c. acts as a partial barrier to diffusion of photochemical products. Combined with our previous studies, these experiments demonstrate that pressure transients are responsible for the deep damage seen with 193 nm ablation and that photoacoustic effects must be considered when using short-pulse, high-peak power lasers.
The precise removal of stratum corneum from cadaveric swine skin by a mid-infrared erbium:yttrium scandium gallium garnet laser (lambda = 2.79 microns; 250 microseconds pulse width) was assessed by electrical resistance measurements and documented by histology. The effects of stratum corneum removal by laser ablation and by adhesive tape-stripping on the in vitro penetration of 3H-hydrocortisone and 125I-gamma-interferon were determined. Excised swine skin was irradiated with laser (1 J/cm2; 31 mJ/pulse; 1 Hz; 2 mm spot diameter). For skin penetration studies, laser pulses were delivered to discrete 2-mm areas to ablate up to 12.6% of the total 3-cm2 stratum corneum diffusional area. Franz in vitro skin penetration chambers were used to measure the cumulative 48-h penetration of 3H-hydrocortisone and 125I-gamma-interferon in laser-treated and tape-stripped skin. Electrical resistance measurements and histologic studies demonstrated that 10-14 laser pulses at the above energy density were required to abolish skin resistance and selectively ablate stratum corneum without damage to adjacent dermal structures. Laser ablation of 12.6% of the surface area of stratum corneum produced a 2.8 and 2.1-times increase in permeability constant (kp) for 3H-hydrocortisone and 125I-gamma-interferon, respectively. These studies demonstrate that a pulsed mid-infrared laser can reliably and precisely remove the stratum corneum, facilitating penetration of large molecules such as 125I-gamma-interferon that cannot penetrate intact skin. This new technique may be useful for basic and clinical investigation of skin barrier properties.
The explosive vaporization of melanosomes in situ in skin during pulsed laser irradiation (pulse duration less than 1 microsecond) is observed as a visible whitening of the superficial epidermal layer due to stratum corneum disruption. In this study, the ruby laser (694 nm) was used to determine the threshold radiant exposure, H0 (J/cm2), required to elicit whitening for in vitro black (Negroid) human skin samples which were pre-equilibrated at an initial temperature, Ti, of 0, 20, or 50 degrees C. A plot of H0 vs Ti yields a straight line whose x-intercept indicates the threshold temperature of explosive vaporization to be 112 +/- 7 degrees C (SD, N = 3). The slope, delta H0/delta Ti, specifies the internal absorption coefficient, mua, within the melanosome: mua = -rho C/(slope(1 + 7.1 Rd)), where rho C is the product of density and specific heat, and Rd is the total diffuse reflectance from the skin. A summary of the absorption spectrum (mua) for the melanosome interior (351-1064 nm) is presented based on H0 data from this study and the literature. The in vivo absorption spectrum (380-820 nm) for human epidermal melanin was measured by an optical fiber spectrophotometer and is compared with the melanosome spectrum.
Immediate pigment darkening (IPD) occurs in human skin upon exposure to ultraviolet-A and visible radiation. The spectral changes that occur during IPD were measured with a rapid scanning reflectance spectrophotometer (RS) which employs optical fiber bundles for delivery and detection of light between 400 and 750 nm. The radiation dose dependence and wavelength dependence (334-549 nm irradiation) of IPD were studied by both the classical visual grading method and by spectrophotometric scoring using the RS system. The spectral changes that occur at long wavelengths with IPD mimic the natural absorption spectrum of melanin. Therefore, the IPD was scored in terms of the apparent change in melanin optical density, using the method Kollias and Baqer [Photochem. Photobiol. 43, 49-54 (1986)], based on reflectance in the 620-720 nm range. The nonlinearity of the visual grading method is demonstrated. The degree of IPD is first-order with respect to delivered dose and saturates after high doses. The maximum amount of IPD attained at saturation is greater for shorter wavelengths. Extrapolation of the reflectance data suggests the longest wavelength capable of eliciting IPD is about 470 nm.
Finite-width light distributions in arterial tissue during Argon laser irradiation (476 nm) are simulated using the Monte Carlo method. Edge effects caused by radial diffusion of the light extend +/- 1.5 mm inward from the perimeter of a uniform incident beam. For beam diameters exceeding 3 mm the light distribution along the central axis can be described by the one-dimensional solution for an infinitely wide beam. The overlapping edge effects for beam diameters smaller than 3 mm reduce the penetration of the irradiance in the tissue. The beam profile influences the light distribution significantly. The fluence rates near the surface for a Gaussian beam are two times higher on the central axis and decrease faster radially than for a flat profile. The diverging light from a fiber penetrates tissue in a manner similar to collimated light.
Quantitative dosimetry in the treatment of skin disorders with (laser) light requires information on propagation of light in the skin related to the optical properties of the individual skin layers. This involves the solution of the integro-differential equation of radiative transfer in a model representing skin geometry, as well as experimental methods to determine the optical properties of each skin layer. These activities are unified under the name skin optics. This paper first reviews the current status of tissue optics, distinguishing between the cases of: dominant absorption, dominant scattering, and scattering about equal to absorption. Then, previously published data as well as some current unpublished data on (human) stratum corneum, epidermis and dermis, have been collected and/or (re)analyzed in terms of absorption coefficient, scattering coefficient, and anisotropy factor of scattering. The results are that the individual skin layers show strongly forward scattering (anisotropy factors between 0.7 and 0.9). The absorption and scattering data show that for all wavelengths considered scattering is much more important than absorption. Under such circumstances, solutions to the transport equation for a multilayer skin model and finite beam laser irradiation are currently not yet available. Hence, any quantitative dosimetry for skin treated with (laser) light is currently lacking.
Monte Carlo simulations illustrate how various absorption mu a and scattering mu s coefficients influence time-dependent reflectance R (t) from a semi-infinite homogeneous turbid tissue following an impulse of narrow-beam irradiation. The tissue absorption coefficient mu a in cm -1 can be obtained from measurements of R (t) after the first 20-200 ps (depends on mu s) following an impulse by the expression: mu a = -(n/c) d In [R(t)]/dt - 3n/2ct where n is the tissue-refractive index and c is the in vacuo speed of light. Early data in the first 20-200 ps do not conform to this expression or to diffusion theory. Monte Carlo simulations allow study of the early R(t) behavior. The volume of tissue involved in a measurement is specified by a volume radius r that approximately equals (6Dtc/n)1/2 where t is the time of measurement and D is the optical diffusion constant D = (3 mu s (1 - g]-1. At 50 ps and typical values of mu s = 100 cm-1 and anisotropy equal to 0.9, r equals 5 mm. The upper limit for measurable mu a values is limited by how quickly the reflectance signal is attenuated, and is estimated for current streak camera technology to be mu a less than or equal to 21 cm-1, assuming several measurements are taken over a dynamic range of two orders of magnitude within a 10 ps period.
The ability of gamma interferon (IFN-gamma) to affect cutaneous collagen synthesis in vivo was examined in a murine wounding model. Reproducible areas of full-thickness skin necrosis were produced by argon laser radiation. Mice received recombinant murine IFN-gamma (rMuIFN-gamma) (8.7 X 10(3) units/hr) over 14 d via osmotic pumps implanted subcutaneously or intraperitoneally. At 14 and 21 d after wounding, there was less fibrous tissue in healing scars of treated animals as determined by light and transmission electron microscopy. Associated with the decrease in connective tissue was an increase in the acid mucopolysaccharide content of healing scars, which was largely hyaluronate. Quantitative image analysis of electron micrographs confirmed that less collagen was present in healing scars of animals receiving rMuIFN-gamma. The mean cross-sectional area of collagen fibers was smaller in specimens from treated mice, but no difference was seen in the size of collagen fibrils. The time required to obtain full skin closure was also delayed 23%-27% in treated animals. Using this injury model, we also found that rMuIFN-gamma significantly reduced the degree of perilesional erythema surrounding the laser injury sites and, in the first 6 d after wounding, the degree of polymorphonuclear infiltrate present histologically at lesional sites. Indeed, rMuIFN-gamma also decreased the cutaneous accumulation of neutrophils induced by known proinflammatory mediators, such as interleukin 1 and activated serum. Thus, systemically administered IFN-gamma not only down-regulates collagen synthesis in the skin but also modulates in a previously unrecognized manner: neutrophil accumulation at sites of tissue injury in vivo.
The application of lasers in gastrointestinal endoscopy is rapidly expanding. Because of the tubular configuration of the gastrointestinal tract, endoscopists often deliver laser energy at large angles of incidence. As incident angle affects the fraction of radiation reflected from the tissue surface, we measured the transmittance and reflectance of laser light from in vitro esophagus as a function of incident angle, using integrating sphere and goniometric techniques. At a wavelength of 633 nm and angles of incidence less than 50 degrees, the total transmittance of the esophagus is approximately 25% and the total reflectance is approximately 45%; both are isotropically distributed. At larger angles of incidence, a specularly reflected component becomes evident and the total reflectance increases. The absorbed light per unit area illuminated decreases with increasing angle, because the area illuminated by the laser beam is proportional to the secant of the incident angle. The data suggest that during endoscopic laser procedures the incident laser beam should be directed within 50 degrees of normal for optimal performance and safety.
Argon-fluoride excimer laser ablation of guinea pig stratum corneum causes deeper tissue damage than expected for thermal or photochemical mechanisms, suggesting that photoacoustic waves have a role in tissue damage. Laser irradiation (193 nm, 14-ns pulse) at two different radiant exposures, 62 and 156 mJ/cm2 per pulse, was used to ablate the 15-microns-thick stratum corneum of the skin. Light and electron microscopy of immediate biopsies demonstrated damage to fibroblasts as deep as 88 and 220 microns, respectively, below the ablation site. These depths are far in excess of the optical penetration depth of 193-nm light (1/e depth = 1.5 micron). The damage is unlikely to be due to a photochemical mechanism because (a) the photons will not penetrate to these depths, (b) it is a long distance for toxic photoproducts to diffuse, and (c) damage is proportional to laser pulse intensity and not the total dose that accumulates in the residual tissue; therefore, reciprocity does not hold. Damage due to a thermal mechanism is not expected because there is not sufficient energy deposited in the tissue to cause significant heating at such depths. The damage is most likely due to a photoacoustic mechanism because (a) photoacoustic waves can propagate deep into tissue, (b) the depth of damage increases with increasing laser pulse intensity rather than with increasing total residual energy, and (c) the effects are immediate. These effects should be considered in the evaluation of short pulse, high peak power laser-tissue interactions.
The propagation of light energy in tissues is an important problem in phototherapy, especially with the increased use of lasers as light sources. Often a slight difference in delivered energy separates a useless, efficacious, or disastrous treatment. Methods are presented for experimental characterization of the optical properties of a tissue and computational prediction of the distribution of light energy within a tissue. A standard integrating sphere spectrophotometer measured the total transmission, Tt, total reflectance, Rt, and the on-axis transmission, Ta, for incident collimated light that propagated through the dermis of albino mouse skin, over the visible spectrum. The diffusion approximation solution to the one-dimensional (1-D) optical transport equation computed the expected Tt and Rt for different combinations of absorbance, k, scattering, s, and anisotropy, g, and by iterative comparison of the measured and computed Tt and Rt values converged to the intrinsic tissue parameters. For example, mouse dermis presented optical parameters of 2.8 cm-1, 239 cm-1, and 0.74 for k, s, and g, respectively, at 488 nm wavelength. These values were used in the model to simulate the optical propagation of the 488-nm line of an argon laser through mouse skin in vivo. A 1-D Green's function thermal diffusion model computed the temperature distribution within the tissue at different times during laser irradiation. In vitro experiments showed that the threshold temperature range for coagulation was 60 degrees-70 degrees C, and the kinetics were first order, with a temperature-dependent rate constant that obeyed an Arrhenius relation (molar entropy 276 cal/mol-degrees K, molar enthalpy 102 kcal/mol). The model simulation agreed with the corresponding in vivo experiment that a 2-s pulse at 55 W/cm2 irradiance will achieve coagulation of the skin.
A new method is presented for controlled removal of the stratum corneum of human skin. An excimer laser (193 nm wavelength, 14 ns pulsewidth) was used to remove stratum corneum from in vitro human skin samples by an ablative process. The tritiated water (3H2O) permeability constant and electrical resistance of skin samples were measured in a diffusion chamber apparatus to quantify the enhancement of skin permeability. Each laser pulse ablates about a micrometer of stratum corneum, which allows controlled removal of tissue. The maximum specific enhancement of the 3H2O permeability constant obtained after complete stratum corneum removal depends on the laser pulse energy used. The most gentle laser ablation, achieved with a radiant exposure of 70 mJ/cm2 per pulse, produced a 124-fold enhancement, which is comparable to that achieved after stratum corneum removal by tape-stripping or removal of epidermis by mild heat treatment. Rapid tissue ablation occurred at higher radiant exposures of 170-480 mJ/cm2 per pulse, but only a 45-fold enhancement of permeability was achieved. The precision with which stratum corneum can be ablated using excimer laser pulses may allow further basic research on the internal structure of stratum corneum and on the re-epithelization in controlled wounds. The technique may prove useful clinically to enhance percutaneous transport in applications such as topical delivery of drugs, patch testing, and percutaneous blood gas monitoring.
The specific targeting of melanosomes may allow for laser therapy of pigmented cutaneous lesions. The mechanism of selective destruction of pigmented cells by various lasers, however, has not been fully clarified. Black, brown, and albino guinea pigs were exposed to optical pulses at various radiant exposure doses from a Q-switched, 40 nsec, 694 nm ruby laser. Biopsies were analyzed by light and electron microscopy (EM). Albino animals failed to develop clinical or microscopic evidence of cutaneous injury after irradiation. In both black and brown animals, the clinical threshold for gross change was 0.4 J/cm2, which produced an ash-white spot. By light microscopy, alterations appeared at 0.3 J/cm2 and included separation at the dermoepidermal junction, and the formation of vacuolated epidermal cells with a peripheral cytoplasmic condensation of pigment. By EM, enlarged melanosomes with a central lucent zone were observed within affected epidermal cells at 0.3 J/cm2. At 0.8 and 1.2 J/cm2, individual melanosomes were more intensely damaged and disruption of melanosomes deep in the hair papillae was observed. Dermal-epidermal blisters were formed precisely at the lamina lucida, leaving basal cell membranes and hemidesmosomes intact. Possible mechanisms for melanosomal injury are discussed. These observations show that the effects of the Q-switched ruby laser are melanin-specific and melanin-dependent, and may be useful in the selective destruction of pigmented as well as superficial cutaneous lesions.
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Since 1962, lasers have been used in dermatology and have become the first choice in the treatment of superficial, vascular ectasia. Lasers are unique sources of light; they are coherent, monochromatic, collimated and intense. By careful selection of wavelength, pulse duration, and intensity, it is often possible to selectively confine a laser effect to a specific histologic structure in tissue, depending upon the tissue properties. The ideal treatment of Port Wine Stains (PWS) should irreversibly damage the ectatic vessels but minimize heating of the epidermis and superficial dermis. A theory, called selective photothermolysis, predicts the optimal combination of laser parameters of achieving this ideal treatment of PWS to be a wavelength of 577 nm, a pulse duration of 0.35-10 msec, and an energy per surface area of about 7-8 J/cm2. Laser wavelength: The wavelength of 577 nm is preferred because it: maximizes the selective absorption by hemoglobin, minimizes absorption by epidermal melanin, provides sufficient depth of penetration in the blood to coagulate 0.1 mm vessels allows penetration of light into dermis up to 1 mm. Laser pulse duration: A pulse-width in the range of 0.35-10 msec allows the temperature elevation to be uniform inside the vessel and to be confined to the vessel area. Shorter pulses superheat the red blood cells causing explosive boiling and hemorrhage. Longer pulses allow heat to diffuse away from vessels, requiring greater energies per pulse to achieve vessel damage. An increased energy per pulse increases the risk of excessive damage to surrounding tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
Determination of tissue optical properties is fundamental for application of light in either therapeutical or diagnostics procedures. In the present work we implemented a spatially resolved steady-state diffuse reflectance method where only two fibers (one source and one detector) spaced 2.5 mm apart are used for the determination of the optical properties. The method relies on the spectral characteristics of the tissue chromophores (water, dry tissue, and blood) and the assumption of a simple wavelength dependent expression for the determination of the reduced scattering coefficient. Because of the probe dimensions the method is suited for endoscopic measurements. The method was validated against more traditional models, such as the diffusion theory combined with adding doubling for in vitro measurements of bovine muscle. Mean and standard deviation of the absorption coefficient and the reduced scattering coefficient at 630 nm for normal mucosa were 0.87+/-0.22 cm(-1) and 7.8+/-2.3 cm(-1), respectively. Cancerous mucosa had values 1.87+/-1.10 cm(-1) and 8.4+/-2.3 cm(-1), respectively. These values are similar to data presented by other authors. Blood perfusion was the main variable accounting for differences in the absorption coefficient between the studied tissues.