Laser-mediated cartilage reshaping with feedback-controlled cryogen spray cooling: biophysical properties and viability.

BACKGROUND AND OBJECTIVE: Recent studies have indicated that chondrocyte viability decreases with prolonged or repeated laser irradiation. To optimize laser-mediated cartilage reshaping, the heating process must be finely controlled. In this study, we use high-power Nd:YAG laser irradiation (lambda = 1.32 microm) combined with cryogen spray cooling (CSC) in an attempt to reshape porcine septal cartilage while enhancing chondrocyte viability. STUDY DESIGN/MATERIALS AND METHODS: Chondrocyte viability was determined after high-power (50 W/cm2) Nd:YAG-mediated cartilage reshaping with and without cryogen spray cooling (CSC) and correlated with dynamic measurements of tissue optical and thermal properties. RESULTS: After 1.5 to 2.0 seconds of laser exposure, characteristic changes in diffuse reflectance (indicating the onset of accelerated stress relaxation) was observed in both laser only and laser with CSC specimens. After 2 seconds of laser exposure, specimens in both groups retained the curved shape for up to 14 days. After one laser exposure, chondrocyte viability was 94.35 +/- 6.1% with CSC and 68.77 +/- 20.1% (P < 0.05) without CSC. After two laser exposures, a similar trend was observed with CSC (70.18 +/- 16.44%) opposed to without CSC (28 +/- 45%; P < 0.05). CONCLUSION: CSC during high-power laser irradiation allows rapid heating while minimizing extreme front surface temperature elevations and axial thermal gradients. Laser irradiation with CSC can be used to effectively reshape cartilage tissue with the additional advantage of increasing chondrocyte viability.

Theramal, mechanical, optical, and morphologic changes in bovine nucleus pulposus induced by Nd:YAG (lambda = 1.32 microm) laser irradiation.

UNLABELLED: BACKGROUND AND OBJECTIVE To examine the biophysical effects of photothermal heating on herniated intervertebral discs during laser decompression surgery. STUDY DESIGN/MATERIALS AND METHODS: Ex vivo bovine nucleus pulposus specimens were irradiated with a Nd: YAG laser (lambda = 1.32 microm, 100 seconds exposure time, 9-31 W/cm(2), 4.8 mm spot diameter), whereas changes in tissue thermal, mechanical, and optical properties were monitored by using, respectively, infrared radiometry, tissue tension measurements, and diffuse reflectance from a HeNe probe laser. Morphologic changes and mass reduction were monitored by recording shape changes on video and weighing specimens before and after laser exposure. RESULTS: At power densities below 20 W/cm(2), evaporation of water and specimen volume reduction (shrinking) were consistently observed on video during irradiation. In contrast, above 20 W/cm(2), vapor bubbles formed within the specimen matrix and subsequently ruptured (releasing heated vapors). When radiometric surface temperature approaches approximately 60 to 70 degrees C (denaturation threshold for tissue), tissue tension begins to increase, which is consistent with observations of specimen length reduction. The onset of this change in tissue tension is also reflected in characteristic alterations in diffuse reflectance. With cessation of laser irradiation, a sustained increase in tissue tension is observed, which is consistent with changes in specimen length and volume. Higher laser power results in a faster heating rate and subsequently an accelerated tension change. Specimen mass reduction increased with irradiance from 19 to 72% of the initial mass for 9--31 W/cm(2), respectively. Irradiated specimens did not return to their original shape after immersion in saline (48 hours) in contrast to air-dried specimens (24 hours), which returned to their original shape and size. CONCLUSION: These observations suggest that photothermal heating results in irreversible matrix alteration causing shape change and volume reduction (observed on video and evidenced by the increase in tissue tension) taking place at approximately 65 degrees C. Inasmuch as high laser power results in vapor bubble formation and specimen tearing, the heating process must be controlled. Diffuse reflectance measurements provide a noncontact, highly sensitive means to monitor dynamically changes in tension of nucleus purposus.

Optimal cryogen spray cooling parameters for pulsed laser treatment of port wine stains.

BACKGROUND AND OBJECTIVE: In dermatologic laser therapy, cryogen spray cooling (CSC) is a means to protect the epidermis while leaving dermal structures susceptible to thermal damage. The purpose of this study was to determine optimal spurt duration, tau(s), and optimal delay, tau(d), between the cryogen spurt and laser pulse when using CSC in treatment of port wine stain birthmarks. STUDY DESIGN/MATERIALS AND METHODS: A finite difference method is used to compute temperature distributions in human skin in response to CSC. Optimal tau(s) and tau(d) are determined by maximizing the temperature difference between a modeled basal layer and an imaginary target chromophore. RESULTS: The model predicts an optimal tau(s) of 170-300 msec and approximately 400 msec for shallow (150 microm) and deeper (400 microm) targets, respectively. Spraying for longer than the optimal tau(s) does not critically impair cooling selectivity. For a spurt duration of 100 msec, optimal delays are 5-10 msec and 25-70 msec for a shallow and deep basal layer, respectively. CONCLUSION: In the absence of knowledge about the lesion anatomy, using a tau(s) of 100-200 msec and no delay is a good compromise. A delay is justified only when basal layer and target chromophore are relatively deep and the optimal spurt duration cannot be applied, e.g., to avoid frostbite.

Combining two excitation wavelengths for pulsed photothermal profiling of hypervascular lesions in human skin.

When pulsed photothermal radiometry (PPTR) is used for depth profiling of hypervascular lesions in human skin, melanin absorption also heats the most superficial skin layer (epidermis). Determination of lesion depth may be difficult when it lies close to the epidermal dermal junction, due to PPTR's limited spatial resolution. To overcome this problem, we have developed an approximation technique, which uses two excitation wavelengths (585 and 600 nm) to separate the vascular and epidermal components of the PPTR signal. This technique permits a noninvasive determination of lesion depth and epidermal thickness in vivo, even when the two layers are in close physical proximity to each other. Such information provides the physician with guidance in selecting the optimal parameters for laser therapy on an individual patient basis.

Accuracy of subsurface temperature distributions computed from pulsed photothermal radiometry.

Pulsed photothermal radiometry (PPTR) is a non-contact method for determining the temperature increase in subsurface chromophore layers immediately following pulsed laser irradiation. In this paper the inherent limitations of PPTR are identified. A time record of infrared emission from a test material due to laser heating of a subsurface chromophore layer is calculated and used as input data for a non-negatively constrained conjugate gradient algorithm. Position and magnitude of temperature increase in a model chromophore layer immediately following pulsed laser irradiation are computed. Differences between simulated and computed temperature increase are reported as a function of thickness, depth and signal-to-noise ratio (SNR). The average depth of the chromophore layer and integral of temperature increase in the test material are accurately predicted by the algorithm. When the thickness/depth ratio is less than 25%, the computed peak temperature increase is always significantly less than the true value. Moreover, the computed thickness of the chromophore layer is much larger than the true value. The accuracy of the computed subsurface temperature distribution is investigated with the singular value decomposition of the kernel matrix. The relatively small number of right singular vectors that may be used (8% of the rank of the kernel matrix) to represent the simulated temperature increase in the test material limits the accuracy of PPTR. We show that relative error between simulated and computed temperature increase is essentially constant for a particular thickness/depth ratio.

A comparative study of human skin thermal response to sapphire contact and cryogen spray cooling.

Surface cooling, in conjunction with various thermally mediated therapeutic procedures, can provide a means to protect superficial tissues from injury while achieving destruction of deeper targeted structures. We have investigated the thermal response of in-vivo human skin to: 1) contact cooling with a sapphire window (6-12 degrees C); and 2) spray cooling with a freon substitute cryogen [tetrafluoroethane; boiling point approximately -26 degrees C at 1 atmospheric pressure (atm)]. Measurements utilizing infrared radiometry show surface temperature reductions from 30 degrees C to 14-19 degrees C are obtained within approximately 1 s in response to sapphire contact cooling. Surface temperature reductions to values between 5 degrees C and -9 degrees C are obtained in response to 20-100-ms cryogen spurts. Computational results, based on fitting the measured radiometric surface temperature to estimate heat transfer parameters, show: 1) temperature reductions remain localized to approximately 200 microns of superficial tissue; and 2) values of heat flux and total energy removed per unit skin surface area at least doubled when using cryogen spray cooling.

Infrared imaging of in vivo microvasculature following pulsed laser irradiation.

Infrared emission images of the chick chorioallantoic membrane (CAM) microvasculature following pulsed laser irradiation were recorded using a high speed infrared focal plane array camera. A three-dimensional tomographic reconstruction algorithm was applied to compute the initial space-dependent temperature increase in discrete CAM blood vessels caused by light absorption. The proposed method may provide consistent estimates of the physical dimensions of subsurface blood vessels and may be useful in understanding a variety of biomedical engineering problems involving laser-tissue interaction. © 1998 Society of Photo-Optical Instrumentation Engineers.

Cryogen spray cooling during Nd:YAG laser treatment of hemangiomas. A preliminary animal model study.

BACKGROUND: Successful laser treatment of hemangiomas requires selective photothermal destruction of dilated cutaneous vessels without damaging the overlying epidermis. Delivering a short cryogen spurt, on the order of milliseconds, has been shown to result in localized cooling of the superficial skin structures during laser irradiation. OBJECTIVE: The purpose of this study was to examine the effectiveness of cryogen spray cooling (CSC) in protecting superficial tissue structures during continuous Nd:YAG laser irradiation of an in vivo model hemangioma. METHODS: The highly vascularized chicken comb was selected as the animal model for hemangiomas. The Nd:YAG laser irradiation ranged from 2.6 to 35.1 J/mm2. A feedback system utilizing infrared radiometry monitored the comb surface temperature and controlled delivery time of the cryogen spurt. When comb surface temperature during laser irradiation reached 36-42 degrees C, a 30-100 msec cryogen spurt was delivered. Animals were euthanized 1 hour to 21 days following each experiment. Gross and histologic analyses were performed. RESULTS: Nd:YAG laser irradiation resulted in deep (up to 6.1 mm) tissue photocoagulation, while CSC preserved the overlying epidermis and papillary dermis. CONCLUSION: The results demonstrate that CSC is effective in protecting the epidermis and papillary dermis, while achieving deep tissue photocoagulation during Nd:YAG laser irradiation. Further pilot studies in humans appear warranted.

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.

Nd:YAG laser irradiation in conjunction with cryogen spray cooling induces deep and spatially selective photocoagulation in animal models.

Successful laser treatment of haemangiomas requires selective photocoagulation of subsurface targeted blood vessels without thermal damage to the overlying epidermis. We present an in vivo experimental procedure, using a chicken comb animal model, and an infrared feedback system to deliver repetitive cryogen spurts (of the order of milliseconds) during continuous Nd:YAG laser irradiation. Gross and histologic observations show deep-tissue photocoagulation is achieved, while superficial structures are protected from thermal injury due to cryogen spray cooling. Experimental observation of epidermis protection in chicken comb animal models suggests selective photocoagulation of subsurface targeted blood vessels for successful treatment of haemangiomas can be achieved by repetitive applications of a cryogen spurt during continuous Nd:YAG laser irradiation.

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.

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.

Spatially selective photocoagulation of biological tissues: feasibility study utilizing cryogen spray cooling.

Successful laser treatment of selected dermatoses such as hemangiomas requires thermally induced damage to blood vessels while protecting the epidermis. We present and test a procedure in a rabbit liver tissue model that utilizes cryogen spray cooling during continuous Nd:YAG laser irradiation to induce deep photocoagulation necrosis while protecting superficial tissues from thermal injury. Gross and histologic observations are consistent with calculated thicknesses of protected and photocoagulated tissues and demonstrate the feasibility of inducing spatially selective photocoagulation when cryogen spray cooling is used in conjunction with laser irradiation. This procedure may be useful in the thermal treatment of some pathological conditions for which it is desired that deep photocoagulation be induced while protecting superficial tissues.

A theoretical study of the thermal response of skin to cryogen spray cooling and pulsed laser irradiation: implications for treatment of port wine stain birthmarks.

The successful treatment of port wine stain (PWS) patients undergoing laser therapy is based on selective thermal coagulation of blood vessels without damaging the normal overlying epidermis. Cryogen spray cooling of skin may offer an effective method for minimizing epidermal thermal injury. Inasmuch as the density of melanosomes and depth of PWS blood vessels can vary considerably, an optimum cooling strategy is required on an individual patient basis. We present a theoretical study of the thermal response of various pigmented PWS lesions to spray cooling in conjunction with flashlamp-pumped pulsed dye laser irradiation (585 nm). Results of our model indicate that precooling of skin using tetrafluoroethane as the cryogen spray is sufficient to eliminate epidermal thermal injury when using incident fluences less than 10 J cm-2 and 8 J cm-2 on patients with intermediate and high epidermal melanin content, respectively. Cryogens that have lower boiling points than tetrafluoroethane may allow successful treatment when using fluences equal to or greater than those indicated.

Depth profiling of laser-heated chromophores in biological tissues by pulsed photothermal radiometry.

A solution method is proposed to the inverse problem of determining the unknown initial temperature distribution in a laser-exposed test material from measurements provided by infrared radiometry. A Fredholm integral equation of the first kind is derived that relates the temporal evolution of the infrared signal amplitude to the unknown initial temperature distribution in the exposed test material. The singular-value decomposition is used to demonstrate the severely ill-posed nature of the derived inverse problem. Three inversion methods are used to estimate solutions for the initial temperature distribution. A nonnegatively constrained conjugate-gradient algorithm using early termination is found superior to unconstrained inversion methods and is applied to image the depth of laser-heated chromophores in human skin.

Dynamic epidermal cooling during pulsed laser treatment of port-wine stain. A new methodology with preliminary clinical evaluation.

BACKGROUND AND DESIGN: The clinical objective in the treatment of a patient with port-wine stain (PWS) undergoing laser therapy is to maximize thermal damage to the PWS, while at the same time minimizing nonspecific injury to the normal overlying epidermis. With dynamic cooling, the epidermis can be cooled selectively. 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 cooling remains localized in the epidermis, while leaving the temperature of the deeper PWS vessels unchanged. RESULTS: Comparative measurements obtained by a fast infrared imaging detector demonstrated that the surface temperature prior to laser exposure could be reduced by as much as 40 degrees C using the dynamic cooling technique. No skin surface textural changes were noted on PWS test sites cooled with a 20- to 80-millisecond cryogen spurt after flashlamp-pumped pulsed dye laser (FLPPDL) exposure (lambda = 585 nm; tau p = 450 microseconds) at the maximum light dosage possible (10 J/cm2). In contrast, epidermal necrosis occurred on the uncooled sites after such exposure. Six months after laser exposure, clinically significant blanching on the cooled sites indicates laser photothermolysis of PWS blood vessels did occur. CONCLUSIONS: Our preliminary experiments demonstrate the feasibility of selectively cooling the normal overlying epidermis without affecting the temperature of the deeper PWS vessels. Furthermore, protection of the epidermis from thermal injury, produced by melanin light absorption at clinically relevant wavelengths, can be achieved effectively. An additional advantage of dynamic epidermal cooling is reduction of patient discomfort associated with FLPPDL therapy. Further studies are under way to determine an optimum strategy for applying this dynamic cooling technique during pulsed laser treatment of patients with PWS and others with selected dermatoses (dermal melanocytic lesions and tattoos).

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.

Parameters of the plasma affecting the radiation of pulsar 1.

Analysis of the relation between time delay and frequency for pulses from Pulsar 1 shows that the dispersive region of the ray path must exceed 300 astronomical units and have an average electron number density less than 8000 per cubic centimeter and average magnetic field strength less than 2 x 10(-3) gauss. These requirements almost guarantee that the observed dispersion takes place in the interstellar medium.