Abstract
.Pulsed dye laser irradiation in the wavelength range of 585 to 600 nm is currently the gold standard for treatment of port-wine stains (PWSs). However, this treatment method is often ineffective for deeply seated blood vessels and in individuals with moderate to heavy pigmentation. Use of optical particles doped with the FDA-approved near-infrared (NIR) absorber, indocyanine green (ICG), can potentially provide an effective method to overcome these limitations. Herein, we theoretically investigate the effectiveness of particles derived from erythrocytes, which contain ICG, in mediating photothermal destruction of PWS blood vessels. We refer to these particles as NIR erythrocyte-derived transducers (NETs). Our theoretical model consists of a Monte Carlo algorithm to estimate the volumetric energy deposition, a finite elements approach to solve the heat diffusion equation, and a damage integral based on an Arrhenius relationship to quantify tissue damage. The model geometries include simulated PWS blood vessels as well as actual human PWS blood vessels plexus obtained by the optical coherence tomography. Our simulation results indicate that blood vessels containing micron- or nano-sized NETs and irradiated at 755 nm have higher levels of photothermal damage as compared to blood vessels without NETs irradiated at 585 nm. Blood vessels containing micron-sized NETs also showed higher photothermal damage than blood vessels containing nano-sized NETs. The theoretical model presented can be used in guiding the fabrication of NETs with patient-specific optical properties to allow for personalized treatment based on the depth and size of blood vessels as well as the pigmentation of the individual’s skin.
Highlights
Port-wine stains (PWSs) are congenital and progressive malformations of dermal capillaries that occur in approximately three children per 1000 live births.[1]
As the depth of the blood vessel increased from 500 to 800 μm, there was a decrease in damage to the dermis, which was further reduced when using nano-sized NETs (nNETs) as compared to μNETs. These results suggest PWS patients with light pigmentation and blood vessels as deep as 500 to 800 μm could potentially benefit from the delivery of μNETs or nNETs that yield μa;BV 1⁄4 1 mm−1 to achieve photothermal injury to the blood vessels
For moderately pigmented skin, fraction of NETs (fNETs) 1⁄4 10%, and 755-nm laser irradiation at Dth 1⁄4 6 J∕cm[2], there was no damage to the blood vessels when using μNETs or nNETs that yielded μa;BV 1⁄4 1 mm−1 [Fig. 7(a)]
Summary
Port-wine stains (PWSs) are congenital and progressive malformations of dermal capillaries that occur in approximately three children per 1000 live births.[1]. It is reported that about 60% of patients receive reduction in redness and lesion size after 10 treatment sessions, but only 10% to 20% experience complete clearance of the stain.[4,6] In addition, PDL treatments within safe therapeutic radiant dosages of ≈7 to 16 J∕cm[2], when used in combination with cryogen spray cooling of skin,[7] do not provide the clinically desirable photothermal effects to completely destroy BVs located at depths greater than about 500 μm below skin surface Another challenge with the current approach is related to the treatment of patients with moderate to heavy skin pigmentation (Fitzpatrick types IV to VI).
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