Modelling multiple laser pulses for port wine stain treatment.

Many port wine stains (PWS) are still resistant to pulsed dye laser treatment. However, anecdotal information suggests that multiple-pulse laser irradiation improves patient outcome. Our aims in this note are to explain the underlying mechanism and estimate the possible thermal effects of multiple pulses in vascular structures typical of PWS. Based on linear response theory, the linear combination of two thermal contributions is responsible for the total increase in temperature in laser irradiated blood vessels: direct light absorption by blood and direct bilateral thermal heat conduction from adjacent blood vessels. The latter contribution to the increase in temperature in the targeted vessel can be significant, particularly if some adjacent vessels are in close proximity, such as in cases of optical shielding of the targeted vessel, or if the vessels are relatively distant but many in number. We present evidence that multiple-pulse laser irradiation targets blood vessels that are optically shielded by other vessels. Therefore, it may be a means of enhancing PWS therapy for lesions that fail to respond to single-pulse dye laser treatment.

Bioheat transfer analysis of cryogen spray cooling during laser treatment of port wine stains.

BACKGROUND AND OBJECTIVE: The thermal response of port wine stain (PWS) skin to a combined treatment of pulsed laser irradiation and cryogen spray cooling (CSC) was analyzed through a series of simulations performed with a novel optical-thermal model that incorporates realistic tissue morphology. STUDY DESIGN/MATERIALS AND METHODS: The model consisted of (1) a three-dimensional reconstruction of a PWS biopsy, (2) a Monte Carlo optical model, (3) a finite difference heat transfer model, and (4) an Arrhenius thermal damage calculation. Simulations were performed for laser pulses of 0.5, 2, and 10 ms and a wavelength of 585 nm. Simulated cryogen precooling spurts had durations of 0, 20, or 60 ms and terminated at laser onset. Continuous spray cooling, which commenced 60 ms before laser onset and continued through the heating and relaxation phases, was also investigated. RESULTS: The predicted response to CSC included maximal pre-irradiation temperature reductions of 27 degrees C at the superficial surface and 12 degrees C at the dermoepidermal junction. For shorter laser pulses (0.5, 2 ms), precooling significantly reduced temperatures in superficial regions, yet did not effect superficial vessel coagulation. Continuous cooling was required to reduce significantly thermal effects for the 10-ms laser pulse. CONCLUSIONS: For the PWS morphology and treatment parameters studied, optimal damage distributions were obtained for a 2-ms laser pulse with a 60-ms precooling spurt. Epidermal and vascular morphology as well as laser pulse duration should be taken into account when planning CSC/laser treatment of PWS. Our novel, realistic-morphology modeling technique has significant potential as a tool for optimizing PWS treatment parameters.

Modeling laser treatment of port wine stains with a computer-reconstructed biopsy.

BACKGROUND AND OBJECTIVE: The efficacy of laser treatment of port wine stains (PWS) has been shown to be highly dependent on patient-specific vasculature. The effect of tissue structure on optical and thermal mechanisms was investigated for different pulse durations by using a novel theoretical model that incorporates tissue morphology reconstructed tomographically from a PWS biopsy. STUDY DESIGN/MATERIALS AND METHODS: An optical-thermal numerical model capable of simulating arbitrarily complex, three-dimensional tissue geometries was developed. The model is comprised of (1) a voxel-based Monte Carlo optical model, (2) a finite difference thermal model, and (3) an Arrhenius rate process calculation to predict the distribution of thermal damage. Simulations based on previous computer-based reconstruction of a series of 6 microm sections from a PWS biopsy were performed for laser pulse durations (taup) of 0.5, 5.0, and 10.0 ms at a wavelength of 585 nm. RESULTS: Energy deposition rate in the blood vessels was primarily a function of vessel depth in skin, although shading effects were evident. Thermal confinement and selectivity of damage were seen to be inversely proportional to pulse duration. The model predicted blood-specific damage for taup = 0.5 ms, vascular and perivascular damage for taup = 5 ms, and widespread damage in superficial regions for taup = 10 ms. The effect of energy deposition in the epidermis was most pronounced for longer pulse durations, resulting in increased temperature and extent of damage. CONCLUSION: Pulse durations between 0.5 and 5 ms are likely optimal for the PWS analyzed. The incorporation of a tomographically reconstructed PWS biopsy into an optical-thermal model represents a significant advance in numerical modeling of laser-tissue interaction.

Signal attenuation and localization in optical coherence tomography studied by Monte Carlo simulation.

A Monte Carlo model has been developed for optical coherence tomography (OCT). A geometrical optics implementation of the OCT probe with low-coherence interferometric detection was combined with three-dimensional stochastic Monte Carlo modelling of photon propagation in the homogeneous sample medium. Optical properties of the sample were selected to simulate intralipid and blood, representing moderately (g = 0.7) and highly (g = 0.99) anisotropic scattering respectively. For shallow optical depths in simulated intralipid (<3 scattering mean free path (mfp) units), the number of detected backscattered photons followed the extinction-single-backscatter model, and OCT was found to detect only minimally scattered photons. Within this depth range the backscatter positions of detected photons corresponded well with the nominal focus position of the probe. For propagation to deeper positions in intralipid, localization of backscattering was quickly lost due to detection of stray photons, and the number of detected photons remained constant with increasing depth in the non-absorbing medium. For strongly forward-directed scattering in simulated blood, the number of detected photons approached the extinction-single-backscatter model only for very shallow depths (<2 mfp units). However, backscattering positions for detected photons correlated well with the nominal focus position of the probe even for optical depths greater than 40 mfp units.

Accuracy and noise in optical Doppler tomography studied by Monte Carlo simulation.

A Monte Carlo model has been developed for optical Doppler tomography (ODT) within the framework of a model for optical coherence tomography (OCT). A phantom situation represented by blood flowing in a horizontal 100 microm diameter vessel placed at 250 microm axial depth in 2% intralipid solution was implemented for the Monte Carlo simulation, and a similar configuration used for experimental ODT measurements in the laboratory. Simulated depth profiles through the centre of the vessel of average Doppler frequency demonstrated an accuracy of 3-4% deviation in frequency values and position localization of flow borders, compared with true values. Stochastic Doppler frequency noise was experimentally observed as a shadowing in regions underneath the vessel and also seen in simulated Doppler frequency depth profiles. By Monte Carlo simulation, this Doppler noise was shown to represent a nearly constant level over an investigated 100 microm interval of depth underneath the vessel. The noise level was essentially independent of the numerical aperture of the detector and angle between the flow velocity and the direction of observation, as long as this angle was larger than 60 degrees. Since this angle determines the magnitude of the Doppler frequency for backscattering from the flow region, this means that the signal-to-noise ratio between Doppler signal from the flow region to Doppler noise from regions underneath the flow is improved by decreasing the angle between the flow direction and direction of observation. Doppler noise values from Monte Carlo simulations were compared with values from statistical analysis.

Accuracy of subsurface temperature distributions computed from pulsed photothermal radiometry.

Pulsed photothermal radiometry (PPTR) is a non-contact method for determining the temperature increase in subsurface chromophore layers immediately following pulsed laser irradiation. In this paper the inherent limitations of PPTR are identified. A time record of infrared emission from a test material due to laser heating of a subsurface chromophore layer is calculated and used as input data for a non-negatively constrained conjugate gradient algorithm. Position and magnitude of temperature increase in a model chromophore layer immediately following pulsed laser irradiation are computed. Differences between simulated and computed temperature increase are reported as a function of thickness, depth and signal-to-noise ratio (SNR). The average depth of the chromophore layer and integral of temperature increase in the test material are accurately predicted by the algorithm. When the thickness/depth ratio is less than 25%, the computed peak temperature increase is always significantly less than the true value. Moreover, the computed thickness of the chromophore layer is much larger than the true value. The accuracy of the computed subsurface temperature distribution is investigated with the singular value decomposition of the kernel matrix. The relatively small number of right singular vectors that may be used (8% of the rank of the kernel matrix) to represent the simulated temperature increase in the test material limits the accuracy of PPTR. We show that relative error between simulated and computed temperature increase is essentially constant for a particular thickness/depth ratio.

Infrared imaging of in vivo microvasculature following pulsed laser irradiation.

Infrared emission images of the chick chorioallantoic membrane (CAM) microvasculature following pulsed laser irradiation were recorded using a high speed infrared focal plane array camera. A three-dimensional tomographic reconstruction algorithm was applied to compute the initial space-dependent temperature increase in discrete CAM blood vessels caused by light absorption. The proposed method may provide consistent estimates of the physical dimensions of subsurface blood vessels and may be useful in understanding a variety of biomedical engineering problems involving laser-tissue interaction. © 1998 Society of Photo-Optical Instrumentation Engineers.

Three-dimensional reconstruction of port wine stain vascular anatomy from serial histological sections.

Port wine stains (PWSs) treated with a flashlamp-pumped pulsed dye laser show a variability in clinical response that is incompletely understood. To identify any vascular structure that might adversely affect treatment response, we obtained a three-dimensional reconstruction of the vascular anatomy of a non-responsive, light-purple superficial PWS on the forearm. The reconstructed PWS consisted of multiple clusters of small diameter (10-50 microns) blood vessels. We propose that this and similar structures, which have not been identified in the literature, have limited the efficacy of laser therapy. Further study is required to clarify the role of vessel clusters for laser treatment of PWSs, and the corresponding dosimetry necessary to clear non-responsive lesions. We expect that three-dimensional reconstruction of PWS vascular anatomy will provide the basis for (i) accurate PWS classification, (ii) guidance for selection of more effective laser dosimetry, and (iii) a standard against which to assess non-invasive diagnostic imaging techniques.

The blanching process due to copper vapour laser treatment of port-wine stains.

We describe the causes and speed of transient blanching during copper vapour laser treatment of port-wine stains. Five watts of yellow (578 nm) light from a copper vapour laser was scanned over the lesion using a computer controlled scanning system. The clinical response of the lesion to treatment is transient blanching, followed immediately by erythema. The clinical response of sclerosed vessels is different in that an intravascular coagulum is observed. We measure the time taken for the lesion to blanch using two methods. First, high-speed photography is used to photograph the treatment process. Second, a photodiode measures the light re-emitted from the skin. Using illumination times of 3 to 5 ms and fluences of approximately 10 J cm-2, blanching times varied between 0 and 33 ms. We conclude that the cause of the transient blanching is not thermal denaturation of either collagen or epidermal melanin. Rather it is the rapid expulsion of red blood cells from the treated vessels. Our results have caused us to commence clinical trials using a new treatment protocol aimed at further improving the response of port-wine stains to copper vapour laser treatment.

Non-invasive determination of port wine stain anatomy and physiology for optimal laser treatment strategies.

The treatment of port wine stains (PWSs) using a flashlamp-pumped pulsed dye laser is often performed using virtually identical irradiation parameters. Although encouraging clinical results have been reported, we propose that lasers will only reach their full potential provided treatment parameters match individual PWS anatomy and physiology. The purpose of this paper is to review the progress made on the technical development and clinical implementation of (i) infrared tomography (IRT), optical reflectance spectroscopy (ORS) and optical low-coherence reflectometry (OLCR) to obtain in vivo diagnostic data on individual PWS anatomy and physiology and (ii) models of light and heat propagation, predicting irreversible vascular injury in human skin, to select optimal laser wavelength, pulse duration, spot size and radiant exposure for complete PWS blanching in the fewest possible treatment sessions. Although non-invasive optical sensing techniques may provide significant diagnostic data, development of a realistic model will require a better understanding of relevant mechanisms for irreversible vascular injury.

Wavelengths for port wine stain laser treatment: influence of vessel radius and skin anatomy.

Recent Monte Carlo computations in realistic port wine stain (PWS) models containing numerous uniformly distributed vessels suggest equal depth of vascular injury at wavelengths of 577 and 585 nm. This finding contradicts clinical experience and previous theory. From a skin model containing normal and PWS vessels in separate dermal layers, we estimate analytically the average volumetric heat production in the deepest targeted PWS vessel. The fluence rate distribution is approximated by Beer's law, which depends upon the tissue's effective attenuation coefficient, and includes a homogeneous fractional volumetric blood concentration corrected for finite-size blood vessels. The model predicts 585-587 nm wavelengths are optimal in adult PWSs containing at least one layer of small-radius blood vessels. In superficial PWSs, typically in young children with small-radius vessels, 577-580 nm wavelengths are optimal. Wavelength-independent results similar to those from Monte Carlo models are valid in single-layered PWSs of large-radius vessels. In conclusion, the volumetric heat production in the deepest targeted PWS blood vessel can be maximized on an individual patient basis. However, absorption of 585-587 nm wavelengths is sufficiently high in superficial lesions, so we hypothesize that these wavelengths may be considered adequate for the treatment of any PWS.

Modelling light distributions of homogeneous versus discrete absorbers in light irradiated turbid media.

Laser treatment of port wine stains has often been modelled assuming that blood is distributed homogeneously over the dermal volume, instead of enclosed within discrete vessels. The purpose of this paper is to analyse the consequences of this assumption. Due to strong light absorption by blood, fluence rate near the centre of the vessel is much lower than at the periphery. Red blood cells near the centre of the vessel therefore absorb less light than those at the periphery. Effectively, when distributed homogeneously over the dermis, fewer red blood cells would produce the same absorption as the actual number of red blood cells distributed in discrete vessels. We quantified this effect by defining a correction factor for the effective absorbing blood volume of a single vessel. For a dermis with multiple vessels, we used this factor to define an effective homogeneous blood concentration. This was used in Monte Carlo computations of the fluence rate in a homogeneous skin model, and compared with fluence rate distributions using discrete blood vessels with equal dermal blood concentration. For realistic values of skin parameters the homogeneous model with corrected blood concentration accurately represents fluence rates in the model with discrete blood vessels. In conclusion, the correction procedure simplifies the calculation of fluence rate distributions in turbid media with discrete absorbers. This will allow future Monte Carlo computations of, for example, colour perception and optimization of vascular damage by laser treatment of port wine stain models with realistic vessel anatomy.

Depth determination of chromophores in human skin by pulsed photothermal radiometry.

We report on the application of pulsed photothermal radiometry (PPTR) to determine the depth of in-vitro and in-vivo subsurface chromophores in biological materials. Measurements provided by PPTR in combination with a nonnegative constrained conjugate-gradient algorithm are used to determine the initial temperature distribution in a biological material immediately following pulsed laser irradiation. Within the experimental error, chromophore depths (50-450 µm) in 55 in-vitro collagen phantoms determined by PPTR and optical low-coherence reflectometry are equivalent. The depths of port-wine-stain blood vessels determined by PPTR correlate very well with their locations found by computer-assisted microscopic observation of histologic sections. The mean blood-vessel depth deduced from PPTR and histologic observation is statistically indistinguishable (p > 0.94).

Modelling the distribution of laser light in port-wine stains with the Monte Carlo method.

Using the Monte Carlo method, we have calculated the distribution of absorbed light in skin during the laser treatment of port-wine stains. Our model includes the effect that the blood capillaries and epidermis have on the propagation of light through skin. It is more complete than those used by previous workers. In this paper, we change the number of scattering dimensions, the spot diameter, and the capillary separation and diameter, and we use the wavelengths 577 nm and 585 nm. One-dimensional scattering calculations are misleading but two-dimensional results suffice for large spot diameters. The model shows that changing the position or diameter of the capillaries has a larger effect on the distribution of absorbed light in the skin than changing the wavelength of the laser beam from 577 nm to 585 nm. Changing the wavelength does increase absorption in the deeper capillaries, but this is not significant. From our results, we discuss the optimal treatment of port-wine stains.

A computer controlled scanner for the laser treatment of vascular lesions and hyperpigmentation.

A computer controlled scanner has been used with a copper vapour laser for the treatment of vascular lesions and hyperpigmented lesions. The computer controls the position and speed of travel of the laser spot during treatment. The illumination time is adjustable with a minimum of 1 ms. The light from the laser is scanned over the lesion so that the lesion is 'painted in' in a raster-like scan of arbitrary shape and produces a series of parallel lines 0.6 mm apart.