Although thermal relaxation times of cutaneous port-wine stain microvessels have been calculated and used to formulate laser selective photothermolysis, they have never been measured. A scheme to do so was devised by measuring the skin response to pairs of 585-nm dye laser pulses (250-360 microseconds each) as a function of the time interval between the two pulses, in five volunteers with port-wine stains. After a pump pulse delivering 80% of the fluence necessary for causing purpura, the fluence of a second probe pulse necessary to cause purpura was determined and was found to increase with the interval between the two pulses, in a manner consistent with thermal diffusion theory. Biopsy specimens were obtained from four of the five subjects to examine the nature and extent of vessel damage and to measure the port-wine stain vessel diameters. Using diffusion theory, the thermal relaxation time was calculated based on the measured vessel diameters. These calculated values are consistent with the increase in radiant exposure (fluence) of the probe pulse necessary to induce purpura for longer time delays. Two simple models for thermal relaxation of port-wine stain vessels are presented and compared with the data. The data and histologic assessment of the vessel injury strongly suggest that pulse durations for ideal laser treatment are in the 1-10-millisecond region and depend on vessel diameter. No dermatologic lasers presently used for port-wine stain treatment operate in this pulse width domain.

The broad, long term objective of this work is the development of Photodynamic Therapy (PDT) for application in the clinical management of patients with port wine stain (PWS). PDT involves the use of an exogenous drug which is concentrated in a targeted tissue. When irradiated at wavelengths specifically absorbed by the drug, selective destruction of the targeted tissue, without the production of heat, occurs. The results of this preliminary study demonstrate in human PWS patients that a photosensitizer, such as PHOTOFRINR, activated by red light at the appropriate therapeutic wavelength, can cause destruction of subsurface blood vessels in the skin with a high degree of specificity, and further study appears warranted.

Despite widespread government and public interest, there are significant barriers to translating basic science discoveries into clinical practice. Biophotonics and biomedical optics technologies can be used to overcome many of these hurdles, due, in part, to offering new portable, bedside, and accessible devices. The current JBO special issue highlights promising activities and examples of translational biophotonics from leading laboratories around the world. We identify common essential features of successful clinical translation by examining the origins and activities of three major international academic affiliated centers with beginnings traceable to the mid-late 1970s: The Wellman Center for Photomedicine (Mass General Hospital, USA), the Beckman Laser Institute and Medical Clinic (University of California, Irvine, USA), and the Medical Laser Center Lübeck at the University of Lübeck, Germany. Major factors driving the success of these programs include visionary founders and leadership, multidisciplinary research and training activities in light-based therapies and diagnostics, diverse funding portfolios, and a thriving entrepreneurial culture that tolerates risk. We provide a brief review of how these three programs emerged and highlight critical phases and lessons learned. Based on these observations, we identify pathways for encouraging the growth and formation of similar programs in order to more rapidly and effectively expand the impact of biophotonics and biomedical optics on human health.

Radiation injury to the skin is a major source of dysfunction, disfigurement, and complications for thousands of patients undergoing adjunctive treatment for internal cancers. Despite the great potential for affecting quality of life, radiation injury has received little attention from dermatologists and is primarily being managed by radiation oncologists. During our volunteer work in Vietnam, we encountered numerous children with significant scarring and depigmentation of skin from the outdated use of radioactive phosphorus P32 in the treatment of hemangiomas. This dangerous practice has left thousands of children with significant fibrosis and disfigurement. Currently, there is no treatment for radiation dermatitis. Here, we report a case series using the combination of laser treatment, including pulsed-dye laser, fractional CO2 laser, and epidermal grafting to improve the appearance and function of the radiation scars in these young patients. We hope that by improving the appearance and function of these scars, we can improve the quality of life for these young patients and potentially open up a new avenue of treatment for cancer patients affected with chronic radiation dermatitis, potentially improving their range of motion, cosmesis, and reducing their risk of secondary skin malignancies.

The application of pulsed photothermal radiometry (PPTR) diagnostics to characterize port wine stain (PWS) lesions is discussed. A PPTR signal of a PWS in response to pulsed laser exposure is shown to consist of an initial `T-jump' due to epidermal melanin absorption and a `delayed thermal wave' resulting from laser generated heat in subsurface blood vessels diffusing to the skin surface. A prototype PPTR instrument incorporating an infrared fiber is constructed which facilitates convenient skin-site accessibility. Laser heating of the infrared collection optics results in an artifactual signal which overestimates the initial `T-jump.' Magnitude of the error is measured and a method to eliminate it is suggested.

Heat transfer rate at the skin-air interface is of critical importance for the benefits of cryogen spray cooling in combination with laser therapy of shallow subsurface skin lesions, such as port-wine stain birthmarks. With some cryogen spray devices, a layer of liquid cryogen builds up on the skin surface during the spurt, which may impair heat transfer across the skin surface due to relatively low thermal conductivity and potentially higher temperature of the liquid cryogen layer as compared to the spray droplets. While the mass flux of cryogen delivery can be adjusted by varying the atomizing nozzle geometry, this may strongly affect other spray properties, such as lateral spread (cone), droplet size, velocity, and temperature distribution. We present here first experiments with sequential cryogen spraying, which may enable accurate mass flux control through variation of spray duty cycle, while minimally affecting other spray characteristics. The observed increase of cooling rate and efficiency at moderate duty cycle levels supports the above described hypothesis of "isolating" liquid layer, and demonstrates a novel approach to optimization of cryogen spray devices for individual laser dermatological applications.

Cryogen spray cooling (CSC) can protect the epidermis from non-specific thermal injury during laser treatment of port wine stains and other hypervascular cutaneous malformations. Knowledge of skin internal temperatures in response to CSC is essential for optimization of this technique. We used an epoxy resin compound to construct a skin phantom and measured its internal temperatures in response to cooling with different cryogens at various spurt durations, spraying distances, and ambient humidity levels. The measured temperature distributions during CSC were fitted by a mathematical model based on thermal diffusion theory. For spurt durations up to 100 ms, temperature reduction within the phantom remained confined to the upper 200 μm, and was affected by spraying distance. Depending on the cryogen used, temperature reductions up to 45 °C could be measured 20 μm below the surface at the end of a 100 ms spurt. However, the cryogen film temperature on the epoxy resin surface was up to 35 °C lower, indicating lack of perfect thermal contact at the cryogen film-phantom interface. Theoretical predictions were within 10% of measured temperatures. Ice formation occurred following termination of the spurt and was influenced by the ambient humidity level.

Goal is to investigate how delivery nozzle design influences the cooling rate of cryogen spray as used in skin laser treatments. Cryogen was sprayed through nozzles that consist of metal tubes with either a narrow or wide diameter and two different lengths. Fast-flashlamp photography showed that the wide nozzles, in particular the long wide one, produced a cryogen jet (very small spray cone angle) rather than a spray (cone angles of about 15° or higher) and appeared to atomize the cryogen less finely than the narrow nozzles. We measured the cooling rate by spraying some cryogen on an epoxy-block with thermocouples embedded. The heat extraction rate of the wide nozzles was higher than that of the narrow nozzles. The results suggest that finely atomized droplets produced by the narrow nozzles do not have enough kinetic energy to break through a layer of liquid cryogen accumulated on the object, which may act as a thermal barrier and, thus, slow down heat extraction. Presumably, larger droplets or non-broken jets ensure a more violent impact on this layer and therefore ensure an enhanced thermal contact. The margin of error for the heat extraction estimate is analyzed when using the epoxy-block. We introduce a complementary method for estimating heat extraction rate of cryogen sprays.

Optical coherence tomography (OCT) was used to image the internal structure of a rat cochlea (ex vivo). Immediately following sacrifice, the temporal bone of a Sprague-Dawley rat was harvested. Axial OCT cross sectional images (over regions of interest, 1×1 mm to 2×8 mm) were obtained with a spatial resolution of 10-15 μm. The osseous borders of the lateral membranous labyrinth overlying the cochlea and the scala vestibuli, media, and tympani which were well demarcated by the modiolus, Reissner's and the basilar membranes were clearly identified. OCT can be used to image internal structures in the cochlea without violating the osseous labyrinth, and may potentially be used to diagnose inner ear pathology in vivo in both animal and human subjects.