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.

Background and objectives

The objective of this study was to compare the efficacy and safety of cryogen spray cooled laser treatment (CSC-LT) at wavelengths of 585 nm vs. 595 nm for port wine stain (PWS) birthmarks in a large series of patients.

Study design/materials and methods

A retrospective review was conducted of 64 patients with PWS treated with the ScleroPLUS [Candela (Wayland, MA)] pulsed dye laser (lambda = 585 or 595 nm wavelength; spot size 7 mm, tau(p) = 1,500 microseconds) over a 3-year period. Subjects' ages ranged between 3 months and 64 years; there were 42 females and 22 males, all of whom were Asian. Number of treatments ranged from 1 to 6. Duration of treatment ranged from 6 months to 2 years 11 months, with a mean of 12 months. Patients (n = 32) received CSC-LT (585 nm) using radiant exposures of 7-10 J/cm(2). A second group of patients (n = 32) received CSC-LT (595 nm) using radiant exposures of 7-10 J/cm(2). The primary efficacy measurement was the quantitative assessment of blanching response scores for CSC-LT (585 nm) versus CSC-LT (595 nm). Patients were monitored for adverse effects.

Results

Based on chi-squared analysis, there were clinical, and statistically significant, differences in blanching response scores favoring PWS receiving CSC-LT (585 nm) as compared to CSC-LT (595 nm) (P <.001). Transient hyperpigmentation was noted in 43.7% (n = 14) and 37.5% (n = 12) of patients in the CSC-LT (585 nm) and CSC-LT (595 nm) groups, respectively. In both groups, transient hyperpigmentation resolved in all patients within 1 year. Permanent hypopigmentation or scarring was not observed in either group.

Conclusions

CSC-LT (585 nm) resulted in superior blanching as compared to CSC-LT (595 nm). Further study is required to optimize wavelength selection on an individual patient basis during PWS therapy in order to improve treatment results.

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.

Using a low-coherence Michelson interferometer, we measure two-dimensional images of optical birefringence in bovine tendon as a function of depth. Polarization-sensitive detection of the signal formed by interference of backscattered light from the sample and a mirror in the reference arm give the optical phase delay between light that is propagating along the fast and slow axes of the birefringent tendon. Images showing the change in birefringence in response to laser irradiation are presented. The technique permits rapid noncontact investigation of tissue structural properties through two-dimensional imaging of birefringence.

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.

We report the development of an optical technique for noninvasive imaging of in vivo blood flow dynamics and tissue structures with high spatial resolution (2-10 microm) in biological systems. The technique is based on optical Doppler tomography (ODT), which combines Doppler velocimetry with optical coherence tomography to measure blood flow velocity at discrete spatial locations. The exceptionally high resolution of ODT permits noninvasive in vivo imaging of both blood microcirculation and tissue structures surrounding the vessel, which has significance for biomedical research and clinical applications. Tomographic imaging of in vivo blood flow velocity in the chick chorioallantoic membrane and in rodent skin is demonstrated.

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.

Using a polarization sensitive Michelson interferometer, we measure two-dimensional images of optical birefringence in bovine tendon as a function of depth with a technique known as Optical Coherence Tomography (OCT). Detection of the polarization state of the signal, formed by interference of backscattered light from the sample and a mirror in the reference arm, gives the optical phase delay between light that has propagated along the fast and slow axes of the birefringent tendon. Images showing the change in birefringence in response to laser irradiation are presented. The technique allows rapid non-contact investigation of tissue structural properties through two-dimensional imaging of birefringence.

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.

Photothermal tomography (PU) is applied to characterize diameter and depth of subcutaneous chromophores such as blood vessels that comprise port wine stain (PWS) birthmarks. PU uses a fast infrared detector array to measure temperature rises in a PWS induced by pulsed laser radiation. A FIT record of PWS in response to pulsed laser exposure is composed of a sequence of infrared emission frames, each consisting of elevated temperature regions indicative of subcutaneous blood vessel heating. An analytic expression for recorded infrared emission frames is derived as a convolution integral of a PTF point spread function and the three dimensional temperature distribution in the PWS immediately following laser exposure. Diameters of blood vessels comprising the PWS are best resolved in early infrared emission frames when radial heat diffusion is relatively small. Blood vessel images in subsequent frames increase in amplitude due to heat generated in the subsurface PWS diffusing to the skin surface indicative of a "delayed thermal wave". Influence of diameter and depth of blood vessels on the FVF record is analyzed using an in-vitro PWS model consisting of multilayered collagen films.