Biomedical subjects

J Stuart Nelson

Publications and source records attributed to J Stuart Nelson.

At least 73 records · Page 4Linked to original sources

PubMed2002

Spectral variation of the infrared absorption coefficient in pulsed photothermal profiling of biological samples.

Pulsed photothermal radiometry can be used for non-invasive depth profiling of optically scattering samples, including biological tissues such as human skin. Computational reconstruction of the laser-induced temperature profile from recorded radiometric signals is sensitive to the value of the tissue absorption coefficient in the infrared detection band (muIR). While assumed constant in reported reconstruction algorithms, muIR of human skin varies by two orders of magnitude in the commonly used 3-5 microm detection band. We analyse the problem of selecting the effective absorption coefficient value to be used with such algorithms. In a numerical simulation of photothermal profiling we demonstrate that results can be markedly impaired, unless the reconstruction algorithm is augmented by accounting for spectral variation muIR(lambda). Alternatively, narrowing the detection band to 4.5-5 microm reduces the spectral variation muIR(lambda) to a level that permits the use of the simpler, unaugmented algorithm. Implementation of the latter approach for depth profiling of port wine stain birthmarks in vivo is presented and discussed.

Algorithms↗

PubMed2002

Coherent thermal wave imaging of subsurface chromophores in biological materials.

Thermal wave imaging of discrete subsurface chromophores in biological materials is reported using a phase sensitive coherent detection technique applied to recorded infrared (IR) images. We demonstrate that utilization of a periodically modulated laser source for thermal wave excitation and coherent detection applied to each pixel may be used to compute images of thermal wave amplitude and phase at the laser modulation frequency. In comparison to recorded IR images, the narrow-band detection technique significantly improves the quality of thermal wave amplitude images of subsurface chromophores in biological materials. Additionally, the technique provides phase information, which may be used to estimate chromophore depth in tissue. Application of the technique is demonstrated using tissue phantoms and in vivo biological models. We present a theoretical analysis and computer simulations that demonstrate the effect of tissue optical and thermal properties on thermal wave amplitude and phase. In comparison to the pulsed photothermal technique, coherent thermal wave imaging of subsurface chromophores in tissue for diagnostic applications allows reduction of peak incident laser fluence by as much as four orders of magnitude and is safer and more amenable to in vivo imaging.

Animals↗

PubMed2002

Clinical testing of a photoacoustic probe for port wine stain depth determination.

BACKGROUND AND OBJECTIVE: Successful laser treatment of port wine stain (PWS) birthmarks requires knowledge of lesion geometry. Laser parameters, such as pulse duration, wavelength, and radiant exposure, and other treatment parameters, such as cryogen spurt duration, need to be optimized according to epidermal melanin content and lesion depth. We designed, constructed, and clinically tested a photoacoustic probe for PWS depth determination. STUDY DESIGN/MATERIALS AND METHODS: Energy from a frequency-doubled, Nd:YAG laser (lambda=532 nm, tau(p)=4 nanoseconds) was coupled into two 1,500 mum optical fibers fitted into an acrylic handpiece containing a piezoelectric acoustic detector. Laser light induced photoacoustic waves in tissue phantoms and a patient's PWS. The photoacoustic propagation time was used to calculate the depth of the embedded absorbers and PWS lesion. RESULTS: Calculated chromophore depths in tissue phantoms were within 10% of the actual depths of the phantoms. PWS depths were calculated as the sum of the epidermal thickness, determined by optical coherence tomography (OCT), and the epidermal-to-PWS thickness, determined photoacoustically. PWS depths were all in the range of 310-570 microm. The experimentally determined PWS depths were within 20% of those measured by optical Doppler tomography (ODT). CONCLUSIONS: PWS lesion depth can be determined by a photoacoustic method that utilizes acoustic propagation time.

Dermatology↗

PubMed2002

Vascular response to laser photothermolysis as a function of pulse duration, vessel type, and diameter: implications for port wine stain laser therapy.

BACKGROUND AND OBJECTIVE: Treatment of port wine stains (PWS) by photothermolysis can be improved by optimizing laser parameters on an individual patient basis. We have studied the critical role of pulse duration (t(p)) on the treatment efficacy. STUDY DESIGN/MATERIALS AND METHODS: The V-beam laser (Candela) allowed changing t(p) over user-specified discrete values between 1.5 and 40 milliseconds by delivering a series of 100 microsecond spikes. For the 1.5 and 3 millisecond pulses, three spikes were observed at intervals t(p)/2 and for t(p)> or =6 milliseconds, four spikes separated by t(p)/3. The ScleroPlus laser (Candela) has a smooth output over its fixed 1.5 milliseconds duration. Blood vessels in the chick chorioallantoic membrane (CAM) were irradiated at fixed wavelength (595 nm), spot size (7 mm), radiant exposure (15 Jcm(-2)), and at variable t(p). The CAM contains an extensive microvascular network ranging from capillaries with diameter D<30 microm to blood vessels of D approximately 120 microm. The CAM assay allows real-time video documentation, and observation of blood flow in pre-capillary arterioles (A) and post-capillary venules (V). Vessel injury was graded from recorded videotapes. Mathematical modeling was developed to interpret results of vessel injury when varying t(p) and D. A modified thermal relaxation time was introduced to calculate vessel wall temperature following laser exposure. RESULTS: Arterioles. For increasing t(p), overall damage was found to decrease. For fixed t(p), damage decreased with vessel size. Venules. For all D, damage was smaller than for corresponding arterioles. There was no dependence of damage on t(p). For given t(p), no variation of damage with D was observed. Photothermolysis due to spiked (V-beam) vs. smooth (Scleroplus) delivery of laser energy at fixed t(p) (1.5 milliseconds), showed similar vessel injuries for al values of D (P>0.05). CONCLUSIONS: The difference between initial arteriole and venule damage could be explained by the threefold higher absorption coefficient at 595 nm in (oxygen-poor!) arterioles. In human patients, PWS consist of ectatic venules (characterized by higher absorption), so that these considerations favor the use of 595-nm irradiation for laser photothermolysis. For optimal treatment of PWS it is proposed that t(p) be between 0.1 and 1.5 milliseconds. This is based on a modified relaxation time tau'(d), defined as the time required for heat conduction into the full thickness of the vessel wall, which is assumed to have a thickness DeltaD approximately 0.1D. The corresponding tau'(d) will be a factor of about six smaller than given in the literature. For vessels with D between 30 and 300 mum, tau'(d) ranges from 0.1 to 1.5 milliseconds.

Humans↗

PubMed2002

Cryogen spray cooling efficiency: improvement of port wine stain laser therapy through multiple-intermittent cryogen spurts and laser pulses.

BACKGROUND AND OBJECTIVES: Cryogen spray cooling (CSC) is used to minimize the risk of epidermal damage during laser treatment of port wine stain (PWS) birthmarks. Unfortunately, CSC may not provide the necessary protection for patients with high concentrations of epidermal melanin. The objectives of this study are to: (1) provide a definition of cooling efficiency (eta) based on the amount of heat removed per unit area of skin for a given cooling time; (2) using this definition, establish the eta of previously reported spray nozzles; (3) identify the maximum benefit expected in PWS laser therapy based solely on improvement of eta; and (4) study the feasibility of using multiple-intermittent cryogen spurts and laser pulses to improve PWS laser therapy. STUDY DESIGN/MATERIALS AND METHODS: A theoretical definition to quantify eta is introduced. Subsequently, finite difference heat diffusion and Monte Carlo light distribution models are used to study the spatial and temporal temperature distributions in PWS skin considering: (1) the current approach to PWS laser therapy consisting of a single cryogen spurt followed by a single pulsed dye laser exposure (SCS-SLP approach); and (2) multiple cryogen spurts and laser pulses (MCS-MLP approach). At the same time, an Arrhenius-type kinetic model is used to compute the epidermal and PWS thermal damages (Omega(E) and Omega(PWS), respectively) for a high epidermal melanin concentration (20%), corresponding to skin types V-VI. RESULTS: The eta corresponding to a wide range of heat transfer coefficients (h) is quantified. For reported CSC nozzle devices eta varies from 40 to 98%. Using the SCS-SLP approach, it is shown that even eta = 100% cannot prevent excessive Omega(E) for a skin types V-VI. In contrast, the MCS-MLP approach provides adequate epidermal protection while permitting PWS photocoagulation for the same skin types. CONCLUSIONS: The new proposed definition allows to compute the cooling efficiency of CSC nozzle devices. Computer models have been developed and used to show that the SCS-SLP approach will not provide adequate epidermal protection for darker skin patients (skin types V-VI), even for eta = 100%. In contrast, the MCS-MLP approach may be a viable solution to improve PWS laser therapy for darker skin patients.

Burns↗

PubMed2002

Comparing the effectiveness of 585-nm vs 595-nm wavelength pulsed dye laser treatment of port wine stains in conjunction with cryogen spray cooling.

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.

Adolescent↗

PubMed2002

Treatment of port-wine stain birthmarks using the 1.5-msec pulsed dye laser at high fluences in conjunction with cryogen spray cooling.

BACKGROUND: The majority of port-wine stain (PWS) patients treated with the pulsed dye laser (PDL) do not achieve complete blanching. Safe administration of higher fluences has been proposed as a means of improving treatment efficacy. OBJECTIVE: To determine the safety and efficacy of PWS treatment with the 1.5-msec PDL at high fluences in conjunction with cryogen spray cooling. METHODS: Twenty PWS patients were treated with the PDL in combination with cryogen spray cooling utilizing a 7 or 10 mm spot size and fluences ranging from 6 to 15 J/cm2. Before and after treatment photographs were compared on a blinded basis. RESULTS: No scarring or skin textural changes occurred. Blanching scores were as follows: 20% of patients achieved 75% or greater blanching after an average of 3.3 treatments, 30% achieved 50-74% blanching, 20% achieved 25-49% blanching, and 30% achieved less than 25% blanching. CONCLUSION: In conjunction with cryogen spray cooling, the PDL can be safely used at high fluences. At this time it is not clear that the use of higher fluences improves treatment efficacy; however, as other aspects of PWS laser treatment are optimized, safe administration of higher fluences is likely to be advantageous.

Adolescent↗

PubMed2002

What is nonablative photorejuvenation of human skin?

Nonablative photorejuvenation has become an integral procedure in the emerging discipline of laser dermatologic surgery. The objective is to confine selectively, without any epidermal damage, thermal injury to the papillary, and upper reticular dermis leading to fibroblast activation and synthesis of new collagen and extracellular matrix material. The procedure results in minimal patient morbidity, no interference with lifestyle, and a low risk of complications, while providing a satisfying degree of rhytides reduction. Multiple devices have been studied and marketed for nonablative photorejuvenation of human skin. However, currently, nonablative photorejuvenation should not be considered an alternative to laser skin resurfacing. The skin surface is not removed or modified. What really occurs may be more accurately referred to as dermal "remodeling" or "toning" as a wound healing response is initiated and collagen regenerated. The narrow "therapeutic window" of laser-induced dermal heating and epidermal cooling must still be optimized so that effective treatments can be obtained routinely. Clinical verification of effective treatment parameters (irradiation wavelength, pulse structure, radiant exposure, cooling time) will be obtained through further human studies. Most importantly, understanding the relationship between the degree of dermal thermal injury and synthesis of new collagen and extracellular matrix material will be fundamental to predicting the clinical efficacy and limitations of nonablative photorejuvenation.

Humans↗

PubMedDate not supplied

Description and analysis of treatments for port-wine stain birthmarks.

Port-wine stain (PWS) birthmarks are congenital, low-flow vascular malformations of the skin. Lasers are the modality of choice for the treatment of PWS birthmarks, and for most patients the pulsed-dye laser in conjunction with epidermal cooling offers the greatest efficacy and safety. Other light devices, including the 532-nm frequency-doubled Nd:YAG laser, intense pulsed light, 1064-nm Nd:YAG laser, and combined 1064/532-nm system, may be useful during a treatment course for resistant PWS. Laser treatment results in blanching of most lesions, although complete resolution may not occur and some resistant PWS birthmarks respond minimally, if at all. Factors limiting laser treatment include variable vascular geometry, inadequate damage of some vessels, and lesional posttreatment recurrence as a result of neovascularization. Alternative or adjunct treatment options that address these limitations should be explored, including noninvasive real-time imaging to optimize the selection of treatment settings, photodynamic therapy, and perioperative use of antiangiogenic compounds.

Adolescent↗

PubMedDate not supplied

Determination of burn depth by polarization-sensitive optical coherence tomography.

An assessment of burn depth is a key step in guiding the treatment of patients who have sustained thermal injuries. Polarization-sensitive optical coherence tomography (PS-OCT) might eventually provide the physician with a quantitative estimate of actual burn depth. Burns of various depths were induced by contacting rat skin with a brass rod preheated to 75 degrees C for 5, 15, or 30 s. Thermal injury denatured the collagen in the skin, and PS-OCT imaged the resulting reduction of birefringence through the depth-resolved changes in the polarization state of light propagated and reflected from the sample. Stokes vectors were calculated for each point in the PS-OCT images and the reduction in the rate of phase retardation between two orthogonal polarizations of light (deg/microm) was found to show a consistent trend with burn exposure time. PS-OCT is a noninvasive technique with potential to give the physician the information needed to formulate an optimal treatment plan for burn patients.

Animals↗

PubMedDate not supplied

Computational model to evaluate port wine stain depth profiling using pulsed photothermal radiometry.

We report on development of an optical-thermal model to evaluate the use of pulsed photothermal radiometry (PPTR) for depth profiling of port wine stain (PWS) skin. In the model, digitized histology sections of a PWS biopsy were used as the input skin geometry. Laser induced temperature profiles were reconstructed from simulated PPTR signals by applying an iterative, non-negatively constrained conjugate gradient algorithm. Accuracy of the following PWS skin characteristics extracted from the reconstructed profiles was determined: (1) average epidermal thickness (z(epi)), (2) maximum epidermal temperature rise (DeltaT(epi,max)), (3) depth of PWS upper boundary (z(PWS)), and (4) depth of maximum PWS temperature rise (z(PWS,max)). Comparison of the actual and reconstructed profiles from PPTR data revealed a good match for all four PWS skin characteristics. Results of this study indicate that PPTR is a viable approach for depth profiling of PWS skin.

Algorithms↗

PubMedDate not supplied

On the physics of laser-induced selective photothermolysis of hair follicles: Influence of wavelength, pulse duration, and epidermal cooling.

The physical basis for optimization of wavelength, pulse duration, and cooling for laser-induced selective photothermolysis of hair follicles in human skin is discussed. The results indicate that the most important optimization parameter is the cooling efficiency of the technique utilized for epidermal protection. The optical penetration is approximately the same for lasers at 694, 755, and 800 nm. The penetration of radiation from Nd:yttrium-aluminum-garnet lasers at 1064 nm is, however, somewhat larger. Photothermal damage to the follicle is shown to be almost independent of laser pulse duration up to 100 ms. The results reveal that epidermal cooling by a 30-80-ms-long cryogen spurt immediately before laser exposure is the only efficient technique for laser pulse durations less than 10 ms. For longer pulse durations in the 30-100 ms range, protection can be done efficiently by skin cooling during laser exposure. For laser pulses of 100 ms, an extended precooling period, e.g., by bringing a cold object into good thermal contact with the skin for about 1 s, can be of value. Thermal quenching of laser induced epidermal temperature rise after pulsed exposure can most efficiently be done with a 20 ms cryogen spurt applied immediately after irradiation.

Cold Temperature↗

PubMedDate not supplied

Imaging wound healing using optical coherence tomography and multiphoton microscopy in an in vitro skin-equivalent tissue model.

Laser thermal injury and subsequent wound healing in organotypic, skin-equivalent tissue models were monitored using optical coherence tomography (OCT), multiphoton microscopy (MPM), and histopathology. The in vitro skin-equivalent raft tissue model was composed of dermis with type I collagen and fibroblast cells and epidermis of differentiated keratinocytes. Noninvasive optical imaging techniques were used for time-dependent, serial measurements of matrix destruction and reconstruction and compared with histopathology. The region of laser thermal injury was clearly delineated in OCT images by low signal intensity. High resolution MPM imaging using second-harmonic generation revealed alterations in collagen microstructure organization with subsequent matrix reconstruction. Fibroblast cell migration in response to injury was monitored by MPM using two-photon excited fluorescence. This study illustrates the complementary features of linear and nonlinear light-tissue interaction in intrinsic signal optical imaging and their use for noninvasive, serial monitoring of wound healing processes in biological tissues.

Burns↗

PubMedDate not supplied

Use of optical coherence tomography to monitor biological tissue freezing during cryosurgery.

The use of optical coherence tomography (OCT) for imaging skin during cryosurgery is evaluated. OCT provides high spatial resolution (5-10 microm) images of optical backscattering due to local variations in refractive index, such as the boundary between liquid and frozen water in tissue. Time resolved OCT images were acquired during freezing of water, Intralipid trade mark, and in vivo hamster skin. Subsurface morphological changes were evident only during freezing of Intralipid and skin. A simple thermal model was applied which predicted freezing times on the same order of magnitude as those observed in OCT images. OCT can be used as a feedback tool during cryosurgical procedures to monitor progression of the freezing front.

Animals↗

PubMedDate not supplied

Accurate measurement of blood vessel depth in port wine stained human skin in vivo using pulsed photothermal radiometry.

We report on application of pulsed photothermal radiometry (PPTR) to determine the depth of port wine stain (PWS) blood vessels in human skin. When blood vessels are deep in the PWS skin (>100 microm), conventional PPTR depth profiling can be used to determine PWS depth with sufficient accuracy. When blood vessels are close or partially overlap the epidermal melanin layer, a modified PPTR technique using two-wavelength (585 and 600 nm) excitation is a superior method to determine PWS depth. A direct difference approach in which PWS depth is determined from a weighted difference of temperature profiles reconstructed independently from two-wavelength excitation is demonstrated to be appropriate for a wider range of PWS patients with various blood volume fractions, blood vessel sizes, and depth distribution. The most superficial PWS depths determined in vivo by PPTR are in good agreement with those measured using optical Doppler tomography (ODT).

Algorithms↗

PubMedDate not supplied

Determination of human skin optical properties from spectrophotometric measurements based on optimization by genetic algorithms.

We present an initial study on applying genetic algorithms (GA) to retrieve human skin optical properties using visual reflectance spectroscopy (VRS). A three-layered skin model consisting of 13 parameters is first used to simulate skin and, through an analytical model based on optical diffusion theory, we study their independent effects on the reflectance spectra. Based on a preliminary analysis, nine skin parameters are chosen to be fitted by GA. The fitting procedure is applied first on simulated reflectance spectra with added white noise, and then on measured spectra from normal and port wine stain (PWS) human skin. A normalized residue of less than 0.005 is achieved for simulated spectra. In the case of measured spectra from human skin, the normalized residue is less than 0.01. Comparisons between applying GA and manual iteration (MI) fitting show that GA performed much better than the MI fitting method and can easily distinguish melanin concentrations for different skin types. Furthermore, the GA approach can lead to a reasonable understanding of the blood volume fraction and other skin properties, provided that the applicability of the diffusion approximation is satisfied.

Algorithms↗

PubMedDate not supplied

Determination of optimal view angles for quantitative facial image analysis.

In quantitative evaluation of facial skin chromophore content using color imaging, several factors such as view angle and facial curvature affect the accuracy of measured values. To determine the influence of view angle and facial curvature on the accuracy of quantitative image analysis, we acquire cross-polarized diffuse reflectance color images of a white-patched mannequin head model and human subjects while varying the angular position of the head with respect to the image acquisition system. With the mannequin head model, the coefficient of variance (CV) is determined to specify an optimal view angle resulting in a relatively uniform light distribution on the region of interest (ROI). Our results indicate that view angle and facial curvature influence the accuracy of the recorded color information and quantitative image analysis. Moreover, there exists an optimal view angle that minimizes the artifacts in color determination resulting from facial curvature. In a specific ROI, the CV is less in smaller regions than in larger regions, and in relatively flat regions. In clinical application, our results suggest that view angle affects the quantitative assessment of port wine stain (PWS) skin erythema, emphasizing the importance of using the optimal view angle to minimize artifacts caused by nonuniform light distribution on the ROI. From these results, we propose that optimal view angles can be identified using the mannequin head model to image specific regions of interest on the face of human subjects.

Computer Simulation↗

PubMedDate not supplied

Collagen solubility correlates with skin optical clearing.

Biomedical optics and photomedicine applications are challenged by the turbidity of most biological tissue systems. Nonreactive, biocompatible chemical agents can induce a reversible reduction in optical scattering of collagenous tissues such as human skin. Herein we show that a chemical agent's tissue optical clearing potential is directly related to its collagen solubility, providing a rational design basis for effective, percutaneous formulations.

Animals↗