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Biomedical subjects

J Stuart Nelson

Publications and source records attributed to J Stuart Nelson.

At least 19 recordsLinked to original sources

Hemoglobin contrast in magnetomotive optical Doppler tomography.

We introduce a novel contrast mechanism for imaging blood flow by use of magnetomotive optical Doppler tomography (MM-ODT), which combines an externally applied temporally oscillating high-strength magnetic field with ODT to detect erythrocytes moving according to the field gradient. Hemoglobin contrast was demonstrated in a capillary tube filled with moving blood by imaging the Doppler frequency shift, which was observed independently of blood flow rate and direction. Results suggest that MM-ODT may be a promising technique with which to image blood flow.

Blood Flow Velocity↗

Improvement of port wine stain laser therapy by skin preheating prior to cryogen spray cooling: a numerical simulation.

BACKGROUND AND OBJECTIVES: Although cryogen spray cooling (CSC) in conjunction with laser therapy has become the clinical standard for treatment of port wine stain (PWS) birthmarks, the current approach does not produce complete lesion blanching in the vast majority of patients. The objectives of this study are to: (1) experimentally determine the dynamic CSC heat flux when a skin phantom is preheated, and (2) numerically study the feasibility of using skin preheating prior to CSC to improve PWS laser therapeutic outcome. STUDY DESIGN/MATERIALS AND METHODS: A fast-response thin-foil thermocouple was used to measure the surface temperature and thus heat flux of an epoxy skin phantom during CSC. Using the heat flux as a boundary condition, PWS laser therapy was simulated with finite element heat diffusion and Monte Carlo light distribution models. Epidermal and PWS blood vessel thermal damage were calculated with an Arrhenius-type kinetic model. RESULTS: Experimental results show that the skin phantom surface can be cooled to a similar minimum temperature regardless of the initial temperature. Numerical simulation indicates that upon laser irradiation, the epidermal temperature increase is virtually unaffected by preheating, while higher PWS blood vessel temperatures can be achieved. Based on the damage criterion we assumed, the depth and maximum diameter of PWS vessels that can be destroyed irreversibly with skin preheating are greater than those without. CONCLUSIONS: Skin preheating prior to CSC can maintain epidermal cooling while increasing PWS blood vessel temperature before laser irradiation. Numerical models have been developed to show that patients may benefit from the skin preheating approach, depending on PWS vessel diameter and depth.

Cryotherapy↗

Thermal responses of ex vivo human skin during multiple cryogen spurts and 1,450 nm laser pulses.

BACKGROUND AND OBJECTIVE: Although cryogen spray cooling (CSC) is used to minimize the risk of epidermal damage during laser dermatologic surgery, concern has been expressed that CSC may induce cryo-injury. The objective of this study is to measure temperature variations at the epidermal-dermal junction in ex vivo human skin during three clinically relevant multiple cryogen spurt-laser pulse sequences (MCS-LPS). STUDY DESIGN/MATERIALS AND METHODS: The epidermis of ex vivo human skin was separated from the dermis and a thin-foil thermocouple (13 microm thickness) was inserted between the two layers. Thermocouple depth and epidermal thickness were measured using optical coherence tomography (OCT). Skin specimens were preheated to 30 degrees C before the MCS-LPS were initiated. Three MCS-LPS patterns, with total cryogen spray times of 38, 30, and 25 milliseconds respectively, were applied to the specimens in combination with laser fluences of 10 and 14 J/cm(2), while the thermocouple recorded the temperature changes at the epidermal-dermal junction. RESULTS: The thermocouple effectively recorded fast temperature changes during three MCS-LPS patterns. The lowest temperatures measured corresponded to the sequences with longer pre-cooling cryogen spurts. No sub-zero temperatures were measured for any of the MCS-LPS patterns under study. CONCLUSIONS: The three clinically relevant MCS-LPS patterns evaluated in this study do not cause sub-zero temperatures in ex vivo human skin at the epidermal-dermal junction and, therefore, are unlikely to cause significant cryogen induced epidermal injury.

Aerosols↗

Microvascular blood flow dynamics associated with photodynamic therapy, pulsed dye laser irradiation and combined regimens.

BACKGROUND AND OBJECTIVES: Previous in vitro studies demonstrated the potential utility of benzoporphyrin derivative monoacid ring A (BPD) photodynamic therapy (PDT) for vascular destruction. Moreover, the effects of PDT were enhanced when this intervention was followed immediately by pulsed dye laser (PDL) irradiation (PDT/PDL). We further evaluate vascular effects of PDT alone, PDL alone and PDT/PDL in an in vivo rodent dorsal skinfold model. STUDY DESIGN/MATERIALS AND METHODS: A dorsal skinfold window chamber was installed surgically on female Sprague-Dawley rats. One milligram per kilogram of BPD solution was administered intravenously via a jugular venous catheter. Evaluated interventions were: control (no BPD, no light), PDT alone (576 nm, 16 minutes exposure time, 15 minutes post-BPD injection, 10 mm spot), PDL alone at 7 J/cm2 (585 nm, 1.5 ms pulse duration, 7 mm spot), PDL alone at 10 J/cm2, PDT/PDL (PDL at 7 J/cm2), and PDT/PDL (PDL at 10 J/cm2). To assess changes in microvascular blood flow, laser speckle imaging was performed before, immediately after, and 18 hours post-intervention. RESULTS: Epidermal irradiation was accomplished without blistering, scabbing or ulceration. A reduction in perfusion was achieved in all intervention groups. PDT/PDL at 7 J/cm2 resulted in the greatest reduction in vascular perfusion (56%). CONCLUSIONS: BPD PDT can achieve safe and selective vascular flow reduction. PDT/PDL can enhance diminution of microvascular blood flow. Our results suggest that PDT and PDT/PDL should be evaluated as alternative therapeutic options for treatment of hypervascular skin lesions including port wine stain birthmarks.

Animals↗

Hand-held pulsed photothermal radiometry system to estimate epidermal temperature rise during laser therapy.

BACKGROUND/PURPOSE: During laser therapy of port wine stain (PWS) birthmarks in human skin, measurement of the epidermal temperature rise (DeltaT(epi)) is important to determine the maximal permissible light dose. In order to measure DeltaT(epi) on a specific PWS skin site, we developed an AC-coupled hand-held pulsed photothermal radiometry (PPTR) system, which overcomes the in vivo measurement limitations of bench-top systems. METHODS: The developed hand-held PPTR system consists of an infrared (IR) lens, AC-coupled thermoelectrically cooled IR detector, laser hand-piece holder, and positioning aperture. The raw AC-coupled signal was integrated to obtain a higher signal-to-noise ratio (SNR). The experimental temperature difference (DeltaT) calibration was compared with theoretical computations. In vitro and in vivo measurements of DeltaT were performed with a tissue phantom as a function of radiant exposure and human subject as a function of melanin concentration, respectively. RESULTS: The integrated AC-coupled signal provided higher SNR as compared with the raw AC-coupled signal. The experimental DeltaT calibration resulted in good agreements with the theoretical results. The in vitro and in vivo results also presented good agreements with theory. CONCLUSIONS: A fiber-free, hand-held AC-coupled PPTR system is capable of accurate epidermis temperature rise (DeltaT(epi)) measurements of human skin during pulsed laser exposure.

Calibration↗

Cutaneous effects of cryogen spray cooling on in vivo human skin.

BACKGROUND: Despite widespread clinical use of cryogen spray cooling (CSC) in conjunction with laser dermatologic surgery, in vivo cutaneous effects have not been systematically evaluated. OBJECTIVE: The authors characterize the in vivo cutaneous effects for Fitzpatrick skin types I through VI after CSC exposures of varying spurt durations and spurt delivery patterns (single vs. multiple spurts). MATERIALS AND METHODS: Twenty-seven normal human subjects were exposed to single cryogen spurts from 10 to 80 milliseconds, and multiple spurt patterns consisting of two 20-millisecond spurts, four 10-millisecond spurts, and eight 5-millisecond spurts. Subjects were evaluated by clinical observation and photography at 1 hour, 1 day, and 1, 4, 8, and 12 weeks after CSC exposure. RESULTS: Acute erythema and urticaria (1-24 hours) were noted in 14 of 27 and 3 of 27 subjects, respectively. Transient hyperpigmentation occurred in 4 of 27 subjects (skin types III-VI) but resolved spontaneously without medical intervention in all subjects by 8 weeks. No permanent skin changes were noted in any subjects. Skin reactions were more common with longer single-spurt durations (50 milliseconds or greater) and multiple spurt patterns. CONCLUSION: Acute erythema, urticaria, and, less commonly, transient hyperpigmentation were observed after CSC exposure. Permanent skin injury was not observed and is unlikely.

Administration, Topical↗

Effect of ambient humidity on light transmittance through skin phantoms during cryogen spray cooling.

Cryogen spray cooling (CSC) is a technique employed to reduce the risk of epidermal damage during dermatologic laser surgery. However, while CSC protects the epidermis from non-specific thermal damage, it might reduce the effective fluence reaching the target chromophore due to scattering of light by the spray droplets and subsequent water condensation/freezing on the skin surface. The objective of this work was to study the effect of ambient humidity (omega) on light transmittance during CSC. An integrating sphere was employed to measure the dynamics of light transmittance through a deformable agar phantom during CSC. The study included two representative CSC spurt patterns studied using four omega: 57, 40, 20 and 12%. Results show that during CSC, as omega increased, light transmittance decreased. For the highest humidity level (57%) studied, light transmittance reached a minimum of 55% approximately 30 ms after spurt termination. In a controlled environment with omega = 12%, light transmittance reached a minimum of 87% approximately 30 ms after spurt termination. The reduced light transmittance immediately after spurt termination was most likely because of scattering of light caused by condensation of water vapour due to aggressive cooling of ambient air in the wake of the cryogen spurt.

Aerosol Propellants↗

Evaluation of single versus multiple cryogen spray cooling spurts on in vitro model human skin.

Many commercially available dermatologic lasers utilize cryogen spray cooling for epidermal protection. A previous tissue culture study demonstrated that single cryogen spurts (SCS) of 80 ms or less were unlikely to cause cryo-injury in light-skinned individuals. More recently, multiple cryogen spurts (MCS) have been incorporated into commercial devices, but the effects of MCS have not been evaluated. The aim was to study an in vitro tissue culture model and the epidermal and dermal effects of SCS vs patterns of shorter MCS with the same preset total cryogen delivery time (Deltat(c)) and provide an explanation for noted differences. Four different spurt patterns were evaluated: SCS: one 40-ms cryogen spurt; MCS2: two 20-ms cryogen spurts; MCS4: four 10-ms cryogen spurts; MCS8: eight 5-ms cryogen spurts. Actual Deltat(c) and total cooling time (Deltat(Total)) were measured for each spurt pattern. RAFT tissue culture specimens were exposed to cryogen spurt patterns and biopsies were taken immediately and at days 3 and 7. Actual Deltat(c) was increased while Deltat(Total) remained relatively constant as the preset Deltat(c) of 40 ms was delivered as shorter MCS. Progressively more epidermal damage was noted with exposure to the MCS patterns. No dermal injury was noted with either SCS or MCS. For a constant preset Deltat(c) of 40 ms, delivering cryogen in patterns of shorter MCS increased the actual Deltat(c) and consequently the observed epidermal cryo-injury as compared to an SCS.

Apoptosis↗

Comparison of diffusion approximation and Monte Carlo based finite element models for simulating thermal responses to laser irradiation in discrete vessels.

Both diffusion approximation (DA) and Monte Carlo (MC) models have been used to simulate light distribution in multilayered human skin with or without discrete blood vessels. However, no detailed comparison of the light distribution, heat generation and induced thermal damage between these two models has been done for discrete vessels. Three models were constructed: (1) MC-based finite element method (FEM) model, referred to as MC-FEM; (2) DA-based FEM with simple scaling factors according to chromophore concentrations (SFCC) in the epidermis and vessels, referred to as DA-FEM-SFCC; and (3) DA-FEM with improved scaling factors (ISF) obtained by equalizing the total light energy depositions that are solved from the DA and MC models in the epidermis and vessels, respectively, referred to as DA-FEM-ISF. The results show that DA-FEM-SFCC underestimates the light energy deposition in the epidermis and vessels when compared to MC-FEM. The difference is nonlinearly dependent on wavelength, dermal blood volume fraction, vessel size and depth, etc. Thus, the temperature and damage profiles are also dramatically different. DA-FEM-ISF achieves much better results in calculating heat generation and induced thermal damage when compared to MC-FEM, and has the advantages of both calculation speed and accuracy. The disadvantage is that a multidimensional ISF table is needed for DA-FEM-ISF to be a practical modelling tool.

Blood Vessels↗

Radial and temporal variations in surface heat transfer during cryogen spray cooling.

Cryogen spray cooling (CSC) is a heat extraction process that protects the epidermis from thermal damage during dermatologic laser surgery. The objective of the present work is to investigate radial and temporal variations in the heat transferred through the surface of a skin phantom during CSC. A fast-response thermal sensor is used to measure surface temperatures every 1 mm across a 16 mm diameter of the sprayed surface of the phantom. An analytical expression based on Fourier's law and Duhamel's theorem is used to compute surface heat fluxes from temperature measurements. Results show that radial and temporal variations of the boundary conditions have a strong influence on the homogeneity of heat extraction from the skin phantom. However, there is a subregion of uniform cooling whose size is time dependent. It is also observed that the surface heat flux undergoes a marked dynamic variation, with a maximum heat flux occurring at the centre of the sprayed surface early in the spurt followed by a quick decrease. The study shows that radial and temporal variations of boundary conditions must be taken into account and ideally controlled to guarantee uniform protection during CSC of human skin.

Body Temperature↗

A library based fitting method for visual reflectance spectroscopy of human skin.

The diffuse reflectance spectrum of human skin in the visible region (400-800 nm) contains information on the concentrations of chromophores such as melanin and haemoglobin. This information may be extracted by fitting the reflectance spectrum with an optical diffusion based analytical expression applied to a layered skin model. With the use of the analytical expression, it is assumed that light transport is dominated by scattering. For port wine stain (PWS) and highly pigmented human skin, however, this assumption may not be valid resulting in a potentially large error in visual reflectance spectroscopy (VRS). Monte Carlo based techniques can overcome this problem but are currently too computationally intensive to be combined with previously used fitting procedures. The fitting procedure presented herein is based on a library search which enables the use of accurate reflectance spectra based on forward Monte Carlo simulations or diffusion theory. This allows for accurate VRS to characterize chromophore concentrations in PWS and highly pigmented human skin. The method is demonstrated using both simulated and measured reflectance spectra. An additional advantage of the method is that the fitting procedure is very fast.

Algorithms↗

Compensation of polarization-dependent loss in transmission fiber gratings by use of a Sagnac loop interferometer.

We analyze the transmission characteristics of a Sagnac loop interferometer containing a polarization-dependent loss element and lossless polarization-converting elements by use of Jones matrices. We show that polarization independence in the transmission mode can be achieved in such a configuration and that maximum transmittance occurs when a half-wave plate is used for the polarization-converting element. The result is verified experimentally for a fiber acousto-optic tunable filter and cascaded long-period fiber gratings with either intrinsic or process-induced polarization-dependent filtering characteristics.

Equipment Design↗

Determination of chemical agent optical clearing potential using in vitro human skin.

BACKGROUND AND OBJECTIVES: Optical clearing is a method that temporarily reduces the optical scattering of biological tissues. STUDY DESIGN/MATERIALS AND METHODS: To determine the optical clearing potential (OCP) of various chemical agents, we examined the change in reduced scattering coefficients of in vitro human skin after application directly to the dermal side. RESULTS/CONCLUSIONS: We found that the mean agent OCP did not correlate with refractive index or osmolality. Lipophilic hyperosmotic agents had a mean OCP less than unity, indicating increased optical scattering.

Culture Techniques↗

Skin model surface temperatures during single and multiple cryogen spurts used in laser dermatologic surgery.

BACKGROUND: Although cryogen spray cooling (CSC) is used to minimize the risk of epidermal damage during laser dermatologic surgery, concern has been expressed that CSC may induce cryo-injury. In order to address this concern, it is necessary to evaluate the effects of prolonged exposure of human skin phantoms (HSP) to CSC. OBJECTIVE: To measure the minimum surface temperature (T(min)) and the time at which it occurs (t(Tmin)) as well as determine the time the sprayed HSP surface remains below 0 degrees C (sub-zero time, Deltat(s)) and -26 degrees C (residence time, Deltat(r)) during the application of single (SCS) and multiple (MCS) cryogen spurts. Two initial HSP substrate temperatures were studied, T(i): 23 and 70 degrees C. STUDY DESIGN/MATERIALS AND METHODS: An epoxy-based HSP was constructed to measure T(min), t(Tmin), Deltat(s), and Deltat(r), for 17 spray patterns: 1 SCS with a total cryo-delivery time (Deltat(c)) of 40 milliseconds; 8 MCS patterns with identical Deltat(c), but with a total cooling time (Deltat(total)) varying from 50 to 280 milliseconds; and 8 SCS patterns that matched the Deltat(total) of the MCS patterns. RESULTS: For both T(i), our results show that it is possible to distinguish between two different cooling regimes. For Deltat(total) </= 110 milliseconds, the differences between SCS and MCS patterns with the same Deltat(total) for all variables (T(min), t(Tmin), Deltat(s), Deltat(r)) are negligible. Most importantly, all these variables show a remarkable linear dependence with Deltat(total). In the interval 110 milliseconds < Deltat(total) < 280 milliseconds, T(min) and t(Tmin) are similar for SCS and MCS, while Deltat(s) and Deltat(r) show more pronounced differences between the two spray patterns. In this interval, the values of T(min) and Deltat(s) for MCS remain invariant and similar to the corresponding values for Deltat(total) = 110 milliseconds. CONCLUSIONS: These results suggest that: (1) similar epidermal protection may be attained with SCS and MCS for Deltat(total) </= 110 milliseconds; and (2) for 110 milliseconds < Deltat(total) </= 280 milliseconds, MCS help to maintain Deltat(s) similar to that of SCS at Deltat(total) = 100 milliseconds, which may be beneficial to prevent cryo-injury.

Aerosols↗

Effects of hypobaric pressure on human skin: feasibility study for port wine stain laser therapy (part I).

BACKGROUND AND OBJECTIVES: Since the development of laser-induced photothermolysis for the therapy of port wine stain (PWS) birthmarks, clinical results have shown that dark purple lesions usually respond well to the first three to five treatments. However, for most PWS, complete blanching is never achieved, and the lesion stabilizes at a red-pink color. The aim of this feasibility study is to demonstrate that with the aid of a local vacuum applied to the lesion site prior to laser exposure, photocoagulation of the smaller PWS blood vessels may be successfully achieved. STUDY DESIGN/MATERIALS AND METHODS: Suction cups were designed to fit onto the hand pieces of commercial laser devices used for PWS laser therapy. One subject with normal skin and another with PWS skin were recruited for this study. Laser pulses of various fluences were applied at atmospheric pressure or shortly after (5-15 seconds) hypobaric pressures (17-51 kPa) were placed as test sites on the forearm of both subjects. The laser-induced purpura at the test sites was documented over the course of 1 week on both subjects and the resulting PWS blanching was optically quantified by visible reflectance spectrometry 7 months after therapy. RESULTS: For the subject with normal skin, the laser fluence needed with hypobaric pressure (51 kPa) to induce similar purpura intensity to that observed with atmospheric pressure was approximately 35% lower. For PWS skin, all suction application times (5-15 seconds) and hypobaric pressures (17-51 kPa) resulted in more intense purpura and the PWS blanching 7 months after treatment was clinically significant for test sites treated with hypobaric pressures ranging from 17 to 34 kPa. CONCLUSIONS: The temporary and controlled dilation of the targeted blood vessels achieved with a local vacuum can significantly reduce the "small-vessel-limitation" in the treatment of PWS without increasing the risk of epidermal damage.

Feasibility Studies↗

Comparison of 585 and 595 nm laser-induced vascular response of normal in vivo human skin.

BACKGROUND AND OBJECTIVES: Two wavelengths, 585 and 595 nm, are currently common options for treating vascular malformations such as port-wine stains (PWS). Controversy exists as to which wavelength induces greater photothermal damage to the blood vessels and subsequent resolution of the malformations. STUDY DESIGN/MATERIALS AND METHODS: We irradiated normal, human skin in vivo at 585 and 595 nm wavelengths using fluences of 10-30 J/cm(2) with a 1.5 millisecond laser pulse. The level of purpura, total vascular damage, maximum coagulation depth (MCD), and perivascular damage were quantified by gross observation and histological analysis. RESULTS: Results demonstrated that 585 nm light caused greater purpura, vascular damage, maximum coagulation depth, and perivascular damage than 595 nm. Purpura showed a positive correlation with total vascular damage to a certain extent beyond which the total vascular damage did not change. For equivalent purpura, 585 and 595 nm produced no statistically significant difference in vascular damage. The difference in the laser-induced vascular damage between 585 and 595 nm, although statistically significant, was no more than 50%. CONCLUSIONS: The bathochromic (red) shift and formation of met-hemoglobin, which reduces the 585 nm light absorption and increases that of 595 nm compared to native oxy-hemoglobin, play a considerable role in creating more parity in vascular damage between the two wavelengths than would be expected based on their respective "native" absorption coefficients alone.

Biopsy, Needle↗

Effects of hypobaric pressure on human skin: implications for cryogen spray cooling (part II).

BACKGROUND AND OBJECTIVES: Clinical results have demonstrated that dark purple port wine stain (PWS) birthmarks respond favorably to laser induced photothermolysis after the first three to five treatments. Nevertheless, complete blanching is rarely achieved and the lesions stabilize at a red-pink color. In a feasibility study (Part I), we showed that local hypobaric pressure on PWS human skin prior to laser irradiation induced significant lesion blanching. The objective of the present study (Part II) is to investigate the effects of hypobaric pressures on the efficiency of cryogen spray cooling (CSC), a technique that assists laser therapy of PWS and other dermatoses. STUDY DESIGN/MATERIALS AND METHODS: Experiments were carried out within a suction cup and vacuum chamber to study the effect of hypobaric pressure on the: (1) interaction of cryogen sprays with human skin; (2) spray atomization; and (3) thermal response of a model skin phantom. A high-speed camera was used to acquire digital images of spray impingement on in vivo human skin and spray cones generated at different hypobaric pressures. Subsequently, liquid cryogen was sprayed onto a skin phantom at atmospheric and 17, 34, 51, and 68 kPa (5, 10, 15, and 20 in Hg) hypobaric pressures. A fast-response temperature sensor measured sub-surface phantom temperature as a function of time. Measurements were used to solve an inverse heat conduction problem to calculate surface temperatures, heat flux, and overall heat extraction at the skin phantom surface. RESULTS: Under hypobaric pressures, cryogen spurts did not produce skin indentation and only minimal frost formation. Sprays also showed shorter jet lengths and better atomization. Lower minimum surface temperatures and higher overall heat extraction from skin phantoms were reached. CONCLUSIONS: The combined effects of hypobaric pressure result in more efficient cryogen evaporation that enhances heat extraction and, therefore, improves the epidermal protection provided by CSC.

Aerosols↗