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Biomedical subjects

L O Svaasand

Publications and source records attributed to L O Svaasand.

At least 19 recordsLinked to original sources

In vivo spectroscopy of jaundiced newborn skin reveals more than a bilirubin index.

AIM: The aims of this study were to improve the algorithms for calculating a transcutaneous bilirubin index (TcB), to follow the bilirubin concentrations during phototherapy and to evaluate possible changes in skin optical parameters such as pigmentation and erythema during phototherapy. METHOD: Reflectance measurements were performed on 51 jaundiced newborns, of which 10 were subjected to phototherapy. The measurements were collected with a diode array spectrophotometer with an integrating sphere accessory, and a TcB was calculated from the measured spectra using algorithms based on diffusion theory. The newborns' birthweights were > or = 2000 g and their gestational age was > or = 35.5 wk. They had no substantial illnesses, and no newborns were submitted to the study until their second day. Heel prick blood samples were analysed for total serum bilirubin (Sbr) by the diazo reaction method. Phototherapy equipment was either an overhead lamp or lightbed. RESULTS: Measurements from the forehead gave the best correlation between TcB and Sbr (r = 0.81, p < 0.05). However, during phototherapy no significant correlation between TcB and Sbr was observed. A correlation (r = 0.45, p < 0.05) was found between phototherapy and melanin index obtained from the patients' back. CONCLUSIONS: Reflectance spectroscopy is useful in assessing bilirubin concentrations before phototherapy, and can also reveal changes in skin parameters such as pigmentation occurring as a result of phototherapy.

Algorithms↗

Methemoglobin formation during laser induced photothermolysis of vascular skin lesions.

BACKGROUND AND OBJECTIVE: Monitoring dynamic changes during laser induced photothermolysis of vascular skin lesions is essential for obtaining an optimal therapeutic result. Rapid photoinduced thermal damage occurs at a threshold temperature of about 70 degrees C. It is therefore, relevant to identify markers to indicate if this threshold temperature has been reached. Methemoglobin, which is formed by a photo-induced oxidation of hemoglobin, indicates that the temperature has reached this threshold value. This study presents a proof of concept of a method for monitoring the in vivo presence of methemoglobin immediately after laser exposure. STUDY DESIGN/MATERIALS AND METHODS: The present study was designed to investigate the in vivo temperature dependence of hemoglobin absorption in the 450-800 nm spectrum range. In vivo diffuse reflectance measurements of port-wine stain (PWS) and telangiectasia were performed prior to, and immediately after, laser treatment with a pulsed dye laser (PDL) at 585 nm wavelength. RESULTS: In vivo measurements following laser treatment of vascular skin lesions showed an immediate increase in the optical absorption of blood. This effect, caused by thermal stress, is a result of an increased dermal blood volume fraction and methemoglobin formation. The effect is light dose dependent, and reflectance spectra revealed methemoglobin formation in patients treated with fluences above 5 J/cm2 at 585 nm wavelength. CONCLUSIONS: It was proved that methemoglobin can be measured in vivo by reflectance spectroscopy. Measurements of the average methemoglobin concentrations immediately after laser exposure may be a valuable diagnostic tool to verify that the blood temperature has been sufficiently high to induce thermal damage to the vessel wall.

Adolescent↗

Cooling efficiency of cryogen spray during laser therapy of skin.

BACKGROUND AND OBJECTIVES: Cryogen spray cooling (CSC) is used extensively for epidermal protection during laser-induced photothermolysis of port wine stains and other vascular skin lesions. The efficacy of CSC depends critically on the heat transfer coefficient (H) at the skin surface for which, however, no reliable values exist. Reported values for H, based on tissue phantoms, vary from 1,600 to 60,000 W/m(2) K. STUDY DESIGN/MATERIALS AND METHODS: A simple experimental model was designed and constructed, consisting of a pure silver-measuring disk (diameter 10 mm, thickness approximately 1 mm), embedded in a thermal insulator. The disk was covered with a 10 microm thick stratum corneum layer, detached from in vivo human skin. The heat transfer coefficient of the stratum corneum/cryogen interface was measured during CSC with short spurts of atomized tetrafluoroethane. RESULTS: H was found to be dependent on the specific design of the cryogen valve and nozzle. With nozzles used in typical clinical settings, H was 11,500 W/m(2) K, when averaged over a 100 ms spurt, and 8,000 W/m(2) K when averaged over a 200 ms spurt. CONCLUSIONS: The presented model enables accurate prediction of H and thus improve control over temperature depth profile and cooling efficiency during laser therapy. Thereby, it may contribute to improvement of therapeutic outcome.

Cryotherapy↗

Influence of nozzle-to-skin distance in cryogen spray cooling for dermatologic laser surgery.

BACKGROUND AND OBJECTIVE: Cryogen sprays are used for cooling human skin during various laser treatments. Since characteristics of such sprays have not been completely understood, the optimal atomizing nozzle design and operating conditions for cooling human skin remain to be determined. MATERIALS AND METHODS: Two commercial cryogenic spray nozzles are characterized by imaging the sprays and the resulting areas on a substrate, as well as by measurements of the average spray droplet diameters, velocities, temperatures, and heat transfer coefficients at the cryogen-substrate interface; all as a function of distance from the nozzle tip. RESULTS: Size of spray cones and sprayed areas vary with distance and nozzle. Average droplet diameter and velocity increase with distance in the vicinity of the nozzle, slowly decreasing after a certain maximum is reached. Spray temperature decreases with distance due to the extraction of latent heat of vaporization. At larger distances, temperature increases due to complete evaporation of spray droplets. These three variables combined determine the heat transfer coefficient, which may also initially increase with distance, but eventually decreases as nozzles are moved far from the target. CONCLUSIONS: Sprayed areas and heat extraction efficiencies produced by current commercial nozzles may be significantly modified by varying the distance between the nozzle and the sprayed surface.

Cryotherapy↗

Cryogen spray cooling in laser dermatology: effects of ambient humidity and frost formation.

BACKGROUND AND OBJECTIVE: Dynamics of cryogen spray deposition, water condensation and frost formation is studied in relationship to cooling rate and efficiency of cryogen spray cooling (CSC) in combination with laser dermatologic surgery. STUDY DESIGN/MATERIALS AND METHODS: A high-speed video camera was used to image the surface of human skin during and after CSC using a commercial device. The influence of ambient humidity on heat extraction dynamics was measured in an atmosphere-controlled chamber using an epoxy block with embedded thermocouples. RESULTS: A layer of liquid cryogen may remain on the skin after the spurt termination and prolong the cooling time well beyond that selected by the user. A layer of frost starts forming only after the liquid cryogen retracts. Condensation of ambient water vapor and subsequent frost formation deposit latent heat to the target site and may significantly impair the CSC cooling rate. CONCLUSIONS: Frost formation following CSC does not usually affect laser dosage delivered for therapy of subsurface targets. Moreover, frost formation may reduce the risk of cryo-injury associated with prolonged cooling. The epidermal protection during CSC assisted laser dermatologic surgery can be further improved by eliminating the adverse influence of ambient humidity.

Aerosol Propellants↗

Reflectance measurements of layered media with diffuse photon-density waves: a potential tool for evaluating deep burns and subcutaneous lesions.

The basic principles of a non-contact, near-infrared technique for the mapping of layered tissues are discussed theoretically and verified experimentally. The propagation properties of diffuse photon-density waves in tissues depend on the optical properties of the tissue. When a layered medium is irradiated by amplitude modulated light, the difference in optical properties between the layers is evident in the phase and amplitude of the diffuse reflection coefficient, which is a result of the interference of the partial waves propagating in the different layers. Thus, diffuse photon-density waves are applicable to the analysis of the structure of layered tissue. The probing depth is determined by the modulation frequency of the incident light. For modulation frequencies between several hundred megahertz and a few gigahertz, this allows us to analyse the properties of muscle tissue of up to 4-8 mm below the surface. Experimental results based on chicken breast muscle are given. As an example, the technique might be of use for evaluating the depth of necrosis and the blood volume fraction in deep burns.

Animals↗

Pigmentary changes after pulsed dye laser treatment in 125 northern European patients with port wine stains.

We investigated the occurrence of pigmentary changes after flash lamp pumped dye laser treatment in 125 Norwegian patients. Post-treatment hyperpigmentation occurred with equal frequency during summer and winter (23%), and the facial regions did not exhibit higher occurrence than lesions located elsewhere. The patients that achieved hyperpigmented skin were not exposed to any higher fluence than those without this complication. On the contrary, we found that during the summer period from April to September the patients with post-treatment hyperpigmentation had been exposed to a significantly lower dose than those without pigmentary changes. These results indicate that the epidermal melanin content is not the only criterion for obtaining post-treatment hyperpigmentation. There might also be a constitutional disposition. In predisposed individuals the threshold dose for hyperpigmentation might be reduced in summer when the skin is more pigmented.

Adolescent↗

The origin and role of erythema after carbon dioxide laser resurfacing. A clinical and histological study.

BACKGROUND: Transient erythema, which can last up to 3 months after carbon dioxide (CO2) laser skin resurfacing, is a usual side effect with pulsed or rapidly scanned CO2 lasers. OBJECTIVE: We evaluated the cause of erythema in the clinical setting and by histology in order to determine if and how we may decrease it, or even eliminate it. METHODS: Ten patients who underwent resurfacing were recruited to this study. Skin punch biopsies were taken at 0, 7, 21, and 90 days and analyzed by light microscopy. RESULTS: Erythema was noticed from about day 8, when the crusting on the skin surface was exfoliated. It reached its maximum intensity after 14 days, and had disappeared by 60-90 days. Histology showed an early inflammatory response, with an immature neopithelium, and rich vascularization. The normal epidermis had returned by 90 days, and during this period there was reduced optical scattering and absorption in melanin. CONCLUSION: Although the erythema is an unwanted side effect in the patient's eyes, it is to be expected and thus represents the effects of a combination of epidermal immaturity, reduced melanin absorption of light, reduced dermal optical scattering, and increased blood flow secondary to the surgically induced inflammatory response.

Aged↗

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.

Blood Vessels↗

Dosimetry model for photodynamic therapy with topically administered photosensitizers.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) based on topical application of photosensitizers has been under development over the last years. Typical applications are treatment of basal cell carcinoma of the skin and photoablation of the endometrium. The dosimetry for topically administered photosensitizers must take a time-dependent inhomogenous drug distribution into account together with the conventional parameters such as optical scattering, absorption, and photobleaching. STUDY DESIGN/MATERIALS AND METHODS: This study presents a dosimetry model where the cytotoxic dose is calculated in a stepwise procedure. The first step calculates the time-dependent distribution of 5-aminolevulinic acid (5-ALA) from diffusion theory. In skin this distribution is dependent on drug permeability through the stratum corneum, on the diffusivity of dermis and epidermis, on the drug clearance time, and on the conversion rate from 5-ALA to protoporphyrin IX (PpIX). In the second step the distribution of PpIX is calculated from the 5-ALA distribution found in the first step taking the dynamics of the biosynthesis of 5-ALA to PpIX and the clearance time of PpIX into account. In the third step the generation of cytotoxic singlet oxygen is calculated from the optical distribution during irradiation, taking a photobleaching mechanism into account. RESULTS: The distribution of cytotoxic oxygen is predicted from the optical dose, the drug dose, and the time between the application of the drug and the irradiation. CONCLUSION: The presented dosimetry model is made as simple as possible, yet composite enough to enable all relevant parameters to be taken into account. The model that is based on a linear theory in a semi-infinite medium can, if required, be extended to take nonuniform and nonlinear phenomena into account.

Administration, Topical↗

Dynamic epidermal cooling in conjunction with laser-induced photothermolysis of port wine stain blood vessels.

When a cryogen spurt is applied to the skin surface for an appropriately short period of time (on the order of tens of milliseconds), the spatial distribution of cooling remains localized in the normal overlying epidermis, while leaving the temperature of the deeper port wine stain (PWS) blood vessels unchanged. Furthermore, cooling continues after pulsed laser exposure as cryogen remaining on the surface evaporates and removes heat deposited by light absorption in epidermal melanin. An additional advantage of dynamic cooling is a reduction in the level of pain and discomfort associated with flashlamp-pumped pulsed dye laser therapy of PWS. Preliminary clinical studies and supporting theoretical calculations demonstrate the feasibility of selective epidermal cooling while achieving photothermolysis of blood vessels during pulsed laser treatment of PWS.

Laser Therapy↗

Structural and functional effects of endometrial photodynamic therapy in a rat model.

OBJECTIVE: Our purpose was to determine the optical dose required for irreversible endometrial destruction and prevention of implantation by photodynamic therapy with topical 5-aminolevulinic acid. STUDY DESIGN: Three hours after drug application 74 female Sprague-Dawley rats received varying doses of 630 nm of light delivered by an intrauterine cylindric diffusing fiber. RESULTS: A 64 J/cm2 in situ optical dose resulted in long-term irreversible endometrial destruction; 43 J/cm2 damaged endometrial stroma and myometrium but not glandular epithelium 1 day after photodynamic therapy. At this lower light dose endometrium regenerated to full thickness within 3 weeks; however, implantation sacs were significantly reduced. CONCLUSIONS: Photodynamic destruction of glandular epithelium accompanies irreversible endometrial ablation, whereas isolated stromal damage leads to reproductive impairment only. The optical dose required for endometrial ablation is approximately 1.5-fold higher than for reproductive impairment (functional damage) because of differential cell photosensitivity.

Aminolevulinic Acid↗

Possible mechanisms for an irregular vessel coagulation when long laser pulses are used in the treatment of port-wine stains.

The laser treatment of port-wine stains (PWS) has as a main aim the irreversible damage of ectatic vessels. Blood content of the subcutaneous venous plexus in PWS can be increased by a factor of seven or more, compared to that of the normal skin. The venous blood velocity ranges from 0.1-1 mm/s in capillaries to approximately 22 mm/s in larger vessels of about 300 microns in diameter. A PWS, selected for study, was irradiated with a multiline argon laser 488/515 nm wavelength, 1.5 W power, 200 ms pulse duration, 0.5 mm beam diameter and repetition frequency up to 5 Hz. Laser shots were placed adjacently in an area of 1 cm2. Using these parameters, in the case of dilated PWS vessels with an optical penetration depth and thermal diffusion length less than the diameter of the vessel, together with a transit time of blood across the irradiated spot less than the pulse duration, and estimating that during a pulsed laser emission of 200 ms, the blood has travelled a distance of 3-4 mm, there is a strong indication that hemodynamics during irradiation may influence the pattern of coagulation and agglutination. Thrombosis should occur in the case of small vessels and, in larger vessels, the coagulated blood will only partly fill the lumen. The structure developed in the vessel interior may also change continuously with time, as the coagulated material is progressively replaced by fibrotic tissue and the irregular agglutination pattern may be due to inhomogeneity in the absorbed optical energy.

Biophysical Phenomena↗

Imaging laser heated subsurface chromophores in biological materials: determination of lateral physical dimensions.

We describe a non-contact method using infrared radiometry to determine lateral physical dimensions of laser heated subsurface chromophores in biological materials. An imaging equation is derived that relates measured radiometric temperature change to the reduced two-dimensional temperature increase of laser heated chromophores. From measured images of radiometric temperature change, the lateral physical dimensions of chromophores positioned in an in vitro model of human skin are determined by deconvolution of the derived imaging equation using a non-negative constrained conjugate gradient algorithm. Conditions for optimum spatial resolution are found by analysis of a derived radiometric transfer function and correspond to superficial chromophores and/or weak infrared absorption in a laser irradiated biological material. Analysis indicates that if the infrared attenuation coefficient is sufficiently small (i.e., less than 10mm-1), infrared radiometry in combination with a deconvolution algorithm allows estimation of lateral physical dimensions of laser heated subsurface chromophores in human skin.

Algorithms↗

A mathematical model for light dosimetry in photodynamic destruction of human endometrium.

We are involved in the development of photodynamic therapy (PDT) as a minimally invasive method for treating dysfunctional uterine bleeding, one of the primary clinical indications for hysterectomy. In this paper, we analyse light propagation through the uterus in order to specify the requirements for a light delivery system capable of effectively performing endometrial PDT. Our approach involves developing an analytical model based on diffusion theory to predict optical fluence rate distributions when cylindrical and spherical optical applicators are placed in the uterine cavity. We apply the results of our model calculations to estimate the thermal effects of optical irradiation and the effective photodynamic optical dose. Theoretical fluence rate calculations are compared to fluence rate measurements made in fresh, surgically removed human uteri. Our results show that a trifurcated cylindrical optical applicator inserted into the human uterus can provide a light dose that is sufficient to cause photodynamic destruction of the entire endometrium. When the optical power per unit length of each cylindrical applicator is 100 mW cm-1 (at 630 nm), a fluence rate of 40 mW cm-2 is delivered to the boundary layer between the endometrium and the myometrium (a depth of about 4-6 mm). The optical fluence delivered to the boundary layer after 20 min of exposure is 50 J cm-2, a level that is generally accepted to cause tissue damage throughout the endometrium in most patients.

Dose-Response Relationship, Radiation↗

Photothermally induced vessel-wall necrosis after pulsed dye laser treatment: lack of response in port-wine stains with small sized or deeply located vessels.

The optimal treatment of port-wine stains is laser-induced selective photothermolysis. Lesion color and location and the age of the patient are reported to influence the therapeutic outcome. This study was initiated to analyze the outcome not only by the clinical response of lightening, but also in terms of photothermally induced necrosis to the vessel wall. Punch biopsy specimens were taken from 51 patients before treatment. Post-treatment biopsies were taken after exposure to a pulsed dye laser (585-nm wavelength, 0.45-ms pulse length) with an irradiant fluence of 6.5 J/cm2. Vessel diameter, depth, and wall thickness were measured in all histologic slides. The viability of the vessel walls was evaluated using an enzyme histochemical method. Port-wine stains with good blanching had significantly more superficially located vessels than the moderate and poor responders (p < 0.000). The moderate and good responding lesions consisted of moderate-sized vessels with diameters of 38 +/- 17 micrometers and 38 +/- 19 micrometers (mean +/- SD), respectively. The lesions showing poor blanching had significantly smaller vessels, with a diameter of 19 +/- 6.5 micrometers < 0.000). Analyses of the post-treatment specimens showed that coagulated vessels were superficially located and of moderate size, whereas the viable vessels were small with a median diameter of 14 micrometers. The probability of coagulation correlated with the thickness of the vessel wall. These data indicate that the therapeutic outcome of port-wine stains can be improved by using the lesional vessel parameters to select the optimal laser wavelength, pulse duration, and dose.

Humans↗

Laser treatment of port wine stains: therapeutic outcome in relation to morphological parameters.

Thirty patients were treated with a flashlamp-pumped pulsed dye laser, with 0.45 ms pulse width and 585 nm wavelength. Punch biopsies were taken prior to treatment, and the biopsies were examined morphometrically. Three different test sites were exposed to laser light of fluence 5.25, 6.50 and 7.75 J/cm2. The degree of blanching was examined 6-8 weeks after treatment, and each site was retreated four times. Six patients (20%) achieved poor blanching, eight patients (27%) obtained moderate lightening and 16 patients (53%) showed good response. The vessels of the good responders were located significantly more superficially than the vessels of the moderate and poor responders (P < 0.05). The poor responders had significantly smaller vessels than the moderate and good responders (P < 0.01). The moderate responders had deeper, but larger vessels, than the poor responders. Hence, an increasing vessel diameter reduces the negative outcome of increasing vessel depth. The vessel diameter was correlated to the colour (P < 0.01), e.g. the mean vessel diameter was increasing from 16.5 microns in pink lesions to 51.2 microns in purple lesions. The vessel depth was partly reflected in the lesional colour, as the pink and purple lesions had significantly deeper vessels than the red ones (P = 0.02). These results indicate that pink lesions predict poor blanching due to deeply located small vessels, while red lesions predict a good therapeutic result because of more superficially located vessels.

Adolescent↗

Selective cooling of biological tissues: application for thermally mediated therapeutic procedures.

The ability to control the degree and spatial distribution of cooling in biological tissues during a thermally mediated therapeutic procedure would be useful for several biomedical applications of lasers. We present a theory based on the solution of the heat conduction equation that demonstrates the feasibility of selectively cooling biological tissues. Model predictions are compared with infrared thermal measurements of in vivo human skin in response to cooling by a cryogen spurt. The presence of a boundary layer, undergoing a liquid-vapour phase transition, is associated with a relatively large thermal convection coefficient (approximately 40 kW m-2 K-1), which gives rise to the observed surface temperature reductions (30-40 degrees C). The degree and the spatial-temporal distribution of cooling are shown to be directly related to the cryogen spurt duration.

Body Temperature↗