WO2000071044A1

WO2000071044A1 - Method and apparatus for controlled and enhanced evaporation during cryogen spray cooling

Info

Publication number: WO2000071044A1
Application number: PCT/US2000/014002
Authority: WO
Inventors: Jorge H. Torres; Bahman Anvari
Original assignee: Wm. Marsh Rice University
Priority date: 1999-05-22
Filing date: 2000-05-19
Publication date: 2000-11-30
Also published as: AU5588500A

Abstract

Dermatological laser treatment methods, devices that employ air convection (air flow) enhanced cryogen spray cooling to reduce the risk of non-specific thermal injury of the epidermis, and underlying dermis during laser procedures such as wrinkle, hair or tattoo removal, or treatment of port wine stains are provided. A preferred device (10) comprises a directed airflow device (18) (air jet), a cryogen delivery device (16) and a laser delivery optics (14). A preferred method includes using the device to cool a designated outer surface portion of living skin by spraying a liquid cryogen onto the surface, to form a cooling film before or during laser actuation.

Description

METHOD AND APPARATUS FOR CONTROLLED AND ENHANCED EVAPORATION DURING CRYOGEN SPRAY COOLING

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 60/135,446 filed

May 22, 1999, the disclosure of which is incorporated herein by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Research leading to the present invention was supported in part by the federal government under a grant from the National Science Foundation (Grant No. BES-9896101).

The United States government may have certain rights in the invention.

BACKGROUND OF THE INVENTION

Field of the Invention

The present invention is generally related to apparatus and methods for applying laser light treatment to the body. More particularly, the invention pertains to such methods and apparatus employing cryogen spray cooling of the surface of the treatment site in conjunction with therapeutic laser treatment. Description of Related Art

Selective cooling of the epidermis and upper dermis is a well known technique aimed at protecting superficial skin structures from thermal injury during various dermatological laser procedures. The intended targets for laser-induced destruction are typically located deeper in the skin (e.g., abnormal capillaries, hair follicles, tattoo pigments). The risk of non-specific thermal injury of the epidermis and underlying dermis is a matter of great concern during various dermatological laser procedures such as wrinkle removal, hair removal, tattoo removal, and treatment of hypervascular lesions including port wine stains (PWS), telangiectasias, hemangiomas, and other cutaneous vascular malformations. The chance of thermal damage to the superficial tissue increases as higher radiant exposures are utilized. For example, in treating PWS, cooling is especially important as high radiant exposures (i.g., greater than 10 J/cm²) seem to be required to produce the desired irreversible damage of the abnormal blood vessels (S. Kimel, L. O. Svaasand, M. Hammer- Wilson, M. J. Schell, T. E. Milner, J. S. Nelson, and M. W. Berns, "Differential vascular response to laser photothermolysis," J. Invest. Dermatol, 103:693-700 (1994); J. S. Nelson, T. E. Milner, L. O. Svaasand, S. Kimel, "Laser pulse duration must match the estimated thermal relaxation time for successful photothermolysis of blood vessels," Lasers Med. Set, 10:9-12 (1995); and C. C. Dierickx, J. M. Casparian, V. Venugopalan, W. Farinelle, and R. R. Anderson, "Thermal relaxation of port-wine stain vessels probed in vivo: the need for 1-10-millisecond laser treatment," J. Invest. Dermatol, 105:709-714 (1995)). Since the cause of non-specific thermal injury of the epidermis is the absorption of laser radiation by melanin, patients with high melanin concentration (e.g., skin types III- VI) are particularly at risk. Epidermal injury may lead to complications such as dyspigmentation, hypertrophic scarring, atrophy, or induration.

Currently, protection of the epidermis during laser irradiation is usually achieved by cooling the skin surface through such methods as contact application of a cold sapphire window, or spraying the skin with a short cryogen spurt (on the order of milliseconds). Both methods, known as sapphire contact cooling (SCC) and cryogen spray cooling (CSC), respectively, have been utilized to protect the epidermis from non-specific thermal injury during laser treatment of cutaneous vascular malformations, and have been described in the literature (For example, E. A. Tanghetti, R. M. Adrian, "Long-pulsed 532 nm laser treatment of port wine stains," Lasers Med. Set, 22 (Suppl. 10):36 (1998); E. A. Tanghetti, R. M. Adrian, "Long-pulsed 532 nm laser treatment of facial telangiectasias," Lasers Med. Sci., 22 (Suppl. 10):45 (1998); J. S. Nelson, T. E. Milner, B. Anvari, B. S. Tanenbaum, S. Kimel, L. O. Svaasand, "Dynamic epidermal cooling during pulsed laser treatment of port wine stains: a new methodology with preliminary clinical evaluation," Arch. Dermatol, 131 :695-700 (1995); J. S. Nelson, T. E. Milner, B. Anvari, B. S. Tanenbaum, L. O. Svaasand, and S. Kimel, "Dynamic epidermal cooling in conjunction with laser-induced photothermolysis of port wine stain blood vessels," Lasers Surg. Med., 19:224-229 (1996); E. J. Fiskerstrand, L. T. Norvang, and L. O. Svaasand, "Laser treatment of port wine stains; reduced pain and shorter duration of purpura by epidermal cooling," SPIE Proc, 2922:20-28 (1996); and H. A. Waldorf, T. S. Alster, K. McMillan, A. N. B. Kauvar, R. G. Geronemus, and J. S. Nelson, "Effect of dynamic cooling on 585-nm pulse dye laser treatment of port-wine stain birthmarks," Derm. Surg., 23:657-662 (1997)). Currently, sapphire window temperature in commercially available devices is maintained at temperatures ranging from about -10 to 4^° C, and contact times of 1 second, or longer, may be required for adequate surface cooling. However, during that contact time significant cooling of deeper skin layers (> 400 μm) can take place. CSC is more often used in clinical practice because of the ability of this method to deliver cryogen spurts of very short duration (e.g., less than 100 milliseconds).

During cryogen spray cooling, the cryogen droplets form a cold liquid film on the substrate surface (e.g., skin) and cools it. For successful laser-mediated therapeutic outcomes, it is essential that the liquid cryogen film be sufficiently cold to rapidly reduce the temperature of the epidermis, and sufficiently short-lived to avoid cooling of deeper skin layers that are the target of the laser pulse applied immediately following the cryogen spurt. On the other hand, in order to improve the clinical outcome of some procedures such as PWS treatment, application of higher radiant exposures than those now typically used are required. As a result, these higher exposures increase the risk of epidermal injury. CSC parameters have to be properly adjusted to work with the higher laser radiant exposures in order to achieve the therapeutic goal.

U.S. Patent 5,814,040 describes a conventional CSC procedure in conjunction with laser irradiation. U.S. Patent 5,979,454 describes a method for achieving photocoagulation of deeper targets by laser irradiation of longer duration while protecting superficial tissue by CSC. Repetitive cryogen spurts are applied to the skin surface for short periods of time, on the order of tens of milliseconds, so that the cooling remains localized in epidermis. One problem encountered with conventional CSC methods, is that ice tends to form on the skin surface. The ice results from condensation or fast freezing of water vapor in ambient air (B. Anvari, et al. IEEE Trans. Biomed. Eng., 45:1-8 (1998); and B. Anvari, B. J. Ver Steeg, T. E. Milner, B. S. Tanenbaum, T. J. Klein, E. Gerstner, S. Kimel, and J. S. Nelson, "Cryogen spray cooling of human skin: effects of ambient humidity level, spraying distance, and cryogen boiling point," SPIE Proc, 3192:106-110 1997)). An ice layer prolongs the transmission of cold waves to the underlying tissue, and, additionally, interferes with or attenuates the laser pulse that is normally applied immediately after the cryogen spurt.

U.S. Patent 5,997,530 attempts to solve the problem of ice formation by controlling the atmospheric humidity of the treatment theatre. This patent describes flooding the theatre with a dry gas such as N , and/or employs a humidity controlled enclosure to maintain humidity at 5% or below during cryogen application. In many clinical situations, employing an enclosure around the treatment area is not a practical option.

Still needed is a way to more efficiently and selectively cool the skin surface while permitting use of a wide range of laser wavelengths and longer exposure times to treat a variety of dermatological problems. The need for additional temperature reductions for higher incident light exposure has not been adequately addressed by the known CSC devices. The problem of ice formation on the skin during conventional CSC laser treatment has not been adequately resolved by existing devices and techniques. The undesirable continuing propagation of cold waves into the skin occurs with many conventional devices as a result of the cryogen film residing on the skin surface for too long a time. Moreover, cryo-injury can occur when the film remains on the skin surface for a sufficient period of time. In none of the pre-existing methods does the instantaneous evaporation of cryogen droplets at the time of contact with the target surface occur. Thus, the conventional methods and devices do not fully exploit the cooling potential of CSC. The residence of liquid cryogen on the skin surface for a time longer than the spurt duration reduces cooling control, and promotes surface ice formation following spurt application.

SUMMARY OF THE INVENTION

Dermatological laser treatment methods and devices that employ air flow enhanced CSC are provided by the present invention. The new methods and devices offer an improvement over conventional laser treatment methods and CSC laser devices. Ice formation is reduced or eliminated when the methods and devices of the invention are used. The new methods and devices provide further reduction in the temperature of the cryogen film that forms over the skin surface, and significantly decrease the cryogen film's life-time on the skin surface by enhancing cryogen evaporation. These improvements are especially valuable when using high light dosage exposures. They also provide a way to control the cryogen evaporation rate and to improve skin cooling efficiency.

This enhanced and controlled evaporation is achieved by applying air flow preferably at the rate of 15-40 L/min onto the skin surface during and/or following cryogen spray. This is believed to be the first disclosure of the application of air flow in conjunction with CSC over the skin surface to enhance cryogen film evaporation.

In accordance with the present invention, an apparatus for laser treatment of biological tissue is provided. The apparatus generally comprises at least one directed air flow device or air jet, a cryogen delivery device and a laser delivery optics, which may be simply an optical fiber and an aperture. Directed air flow means that an air stream emerging from a device has a defined directional orientation (e.g., toward a designated target). Preferably the cryogen delivery device is located close to the laser delivery optics and the air jet is positioned at a defined distance away from the biological tissue surface and is aimed toward a predetermined or defined target on the tissue surface, when the apparatus is placed in position for treating the tissue. In preferred embodiments each air jet is aimed toward the target at an angle of about 20- 30 degrees to the normal to the target and provides the desired directed air flow.

In certain embodiments a distance guide, which may be adjustable or detachable, is also included on the apparatus. In some embodiments the apparatus comprises a hand piece that secures or retains the air jet, a cryogen delivery device, a laser delivery optics and a distance guide. In certain embodiments the apparatus includes separate laser delivery and air flow enhanced cryogen delivery units that are mutually attachable. The laser and air flow enhanced cryogen delivery units are attachable in such a way that the cryogen delivery device is preferably located close to the laser beam outlet on the laser delivery unit. In preferred embodiments the directed air flow device is disposed about 20-30 mm away from the skin surface and is oriented at about 20-30 degrees with the normal to the skin surface so that the air stream emitted by the directed air flow device (air jet) at least covers the area on the skin surface that is flooded by the cryogen spray.

Some embodiments of the apparatus of the present invention provide an improved apparatus for laser treating biological tissue such as skin, which has an overlying surface that is vulnerable to thermal injury. Such apparatus, which already include a cryogen delivery device, a laser delivery optics, and a distance guide, are improved by the addition of air flow directed onto the surface tissue. In preferred versions, the improvement includes means for applying directed air flow onto said surface in conjunction with operation of said cryogen delivery device. The means for applying directed air flow may include a source of 15-40 liters per minute air flow.

In another aspect of the invention, methods of laser treating dermatological conditions are provided. In one embodiment, the method includes cooling a designated outer surface portion of living skin that is initially at a first temperature (e.g., normal skin temperature). This cooling is accomplished by spraying a liquid cryogen onto the outer surface portion whereby a cooling film is formed on that portion of living skin. A stream of air is directed onto the film in cooperation with the application of liquid cryogen, whereby the temperature of the outer surface portion is reduced to a predetermined second temperature below the first temperature and the rate of evaporation of the film from the skin surface is enhanced or accelerated. The method also includes directing a laser beam onto the same portion of living skin sufficient to raise the temperature of an interior portion of skin located a predetermined depth below the outer surface up to a predetermined maximum temperature above the first temperature.

In preferred embodiments of the methods, the stream of air is directed onto the cryogen film at a 20-30° angle with the normal to the skin surface. In certain embodiments the method includes emitting a stream of air at a flow rate of about 15-40 L/min from an air jet having an approximately 3 mm internal diameter. In some embodiments, the method comprises directing a stream of air onto the outer surface portion of living skin for a sufficient time for the air stream to warm the outer surface portion back up to its approximate original temperature. In preferred embodiments the evaporation time of the cryogen film from the target area is approximately the same as the duration of the cryogen spurt.

In some embodiments, an existing apparatus (e.g., a conventional CSC dermatology laser) is provided with a new component that improves the efficiency and control of the underlying process. For example, an improvement is provided for a method of performing laser treatment of a biological tissue which includes applying a film of cryogenic liquid to a selected outer region of tissue such that a dynamic temperature gradient is established in the tissue. The method also includes directing a laser beam onto the region, whereby the outer region of tissue is protected from thermal damage while a selected region of interior tissue below the outer region is thermally treated by the laser beam. The improvement includes directing a stream of air onto the outer region in cooperation with the application of cryogenic liquid whereby a temperature lowering effect is obtained in the cryogen film on the selected outer region and whereby the evaporation time of the film from the outer region of tissue is shortened. By improving the cooling efficiency of a cryogen sprayed onto the skin surface via enhancement of evaporation of the liquid cryogen film that forms on the surface, more aggressive treatment protocols may be used. In addition to the improved cooling during cryogen spurt application, the method and device permits control of the total cooling time, which can be made to match the spurt duration. This control is important to avoid unwanted additional cooling by cryogen that would otherwise remain on the skin surface after the spurt. Advantageously, the added air flow allows the epidermal surface to quickly return to base temperature levels after the spurt, while minimizing or completely avoiding ice formation over the surface and without requiring a humidity controlled enclosure. Still another advantage of the present invention is that the risk of freeze injury (cryo-injury) to the treatment site is reduced compared to conventional methods and apparatus. These and other embodiments, features and advantages of the present invention will become apparent with reference to the following description and drawings.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 illustrates micro-thermocouple placement within an epoxy resin phantom which is used for making temperature measurements in response to CSC. Four 30 μm bead thermocouples were positioned at depths of 20, 90, 200, and 400 μm within the phantom. During CSC application, a fifth thermocouple was placed on the phantom surface to measure the cryogen film temperature. Figure 2 is a schematic of the instrumentation used for temperature measurements in the epoxy resin phantom in response to air flow enhanced CSC.

Figure 3 is a graph of one set of experimental results showing the measured internal temperatures in the phantom in response to a 100 ms cryogen spurt, without directed air flow. The initial temperature was about 25°C and the temperature history was monitored for up to 3 seconds.

Figure 4A is similar to the results shown in Figure 3. It shows the results of another experiment in which the internal temperatures in the epoxy resin phantom were measured following a 100 ms cryogen spurt without air flow applied to the phantom surface. The initial temperature was about 20°C and the monitoring time was up to about 1 second.

Figure 4B is similar to Figure 4A except that it shows the results obtained with air flow directed onto the phantom surface during cryogen application.

Figure 4C is a graph comparing predicted internal skin temperatures for CSC only and CSC plus air flow. Figure 5 A is a graph showing measured cryogen film temperatures at the surface of human skin resulting from the application of a 100 ms spurt at a spraying distance of 100 mm without air flow.

Figure 5B is similar to Figure 5 A except that it shows the results obtained when air flow is applied to the skin in combination with cryogen application. Figure 6 is a schematic of one embodiment of a device for laser treating a subject in conjunction with air flow enhanced CSC of the target site.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

Knowledge of the internal skin temperature distribution in response to any cooling method is essential for optimization of cooling and laser treatment parameters. Inasmuch as internal temperature measurements within human skin are not easily conducted, internal and external temperature measurements were obtained in an epoxy resin phantom, or experimental model, which is described below. Those measurements, in conjunction with a mathematical model, were used to predict the temperature distributions within human skin. In the present study external temperature measurements in human skin in response to CSC were also performed. During the course of these studies it was discovered that additional cooling was obtained with CSC by the application of air convection (air flow) at the skin surface. The epoxy resin phantom was also used to evaluate the cooling enhancement effects of simultaneous application of air flow and cryogen spray in conjunction with laser treatment. The skin phantom was constructed by creating a solid block of an epoxy resin (EP30, Master Bond Inc., Hackensack, NJ) with four micro-thermocouples embedded at known subsurface positions, as illustrated in Figure 1. Based on the manufacturer's reported values of

-7 2 -1 density, thermal conductivity, and specific heat, a value of 0.7x10 m -s was calculated for

-7 2 -1 the epoxy resin thermal diffusivity, which is within 36% of that for skin (1.1x10 m .s (F. A. Duck, Physical Properties of Tissue. A Comprehensive Reference Book. London: Academic Press, 1990)). The epoxy resin phantom was prepared as described by J. H. Torres et al. ("Estimation of Internal Skin Temperatures in Response to Cryogen Spray Cooling: Implications for Laser Therapy of Port Wine Stains" IEEE J. Sel. Topics Quant. Electron. 5:1058-1066 (1999)), the disclosure of which is incorporated herein by reference. As shown schematically in Figure 1, the four thermocouples were positioned at the following depths: 20, 90, 200, and 400 μm (as measured from the epoxy resin front surface to the bead centers). The error due to uncertainty in determining thermocouple positions with the microscope reticle was ±5 μm. In addition to the four embedded subsurface thermocouples, a fifth thermocouple (same type and size) was placed on the epoxy resin phantom surface to measure cryogen film temperature. When sprayed directly with a cryogen spurt, the response time of the thermocouples (to 67%) was 1.5 - 2 ms, with a nearly 100% response in 3 ms. Cryogen Spray Cooling of an Experimental Model

Figure 2 is a schematic showing the instrumentation used for thermocouple measurements in the epoxy resin phantom in response to CSC, with and without air flow enhancement. In the present studies 1,1,1,2-tetrafluoroethane (Refrigerant 134a; National Refrigerants, Inc., Rosenhayn, NJ) (boiling point about -26°C at 1 atm), an environmentally compatible, non-toxic, chlorofluorocarbon substitute (L. E. Manzer, "The CFC-ozone issue: progress on the development of alternatives to CFCs," Science, 249:31-35 (1990); D. J. Alexander, and S. E. Libretto, "An overview of the toxicology of HFA-134a (1,1,1,2- tetrafluoroethane)," Hum. Exp. Toxicol., 14:715-720 (1995); and W. Dekant, "Toxicology of chlorofluorocarbon replacements," Environ. Health Perspect, 104 (Supp. l):75-83 (1996)) was used for CSC. The cryogen, contained in a pressurized steel canister, was delivered by an electronically controlled standard automobile fuel injection valve. The cryogen was maintained in liquid phase inside the steel canister at room temperature by a pressure of about 6 atm and atomized into liquid droplets upon exiting from the injector nozzle. Upon release from the nozzle, droplet temperature was instantaneously reduced to the cryogen boiling point as the droplets were suddenly exposed to atmospheric pressure. On the phantom surface, a spot of approximately 1 cm in diameter was cooled by the spurt. The cryogen spurt duration, τ (20-100 milliseconds), was controlled by a programmable digital delay generator (DG535, Stanford Research Systems, Sunnyvale, CA). The spraying distance was varied between 5 and 100 mm. The phantom initial temperature was 25 °C (room temperature) for most experiments. Although 1,1,1,2-tetrafluoroethane was used in the present studies, different cryogens could be substituted, if desired. One cryogen might be preferred over another for a particular application because of differences in boiling points, for example, to achieve a specific film temperature. Surface and Internal Temperature Measurements in an Experimental Model An example of temperature measurements within the phantom in response to standard cryogen spray cooling is shown in Figure 3. A 100 ms spurt was delivered to the phantom surface from a distance of 60 mm. The cryogen film temperature on the epoxy resin surface was -44°C during the spurt, well below the cryogen boiling point (-26°C), indicating that the droplets cooled substantially as they traveled from the injector nozzle to the target. The temperature measured by the thermocouple located 20 μm below the epoxy surface was approximately -16°C at the end of the spurt, almost 30°C above the cryogen film temperature. Based on the temperature curve for 20 μm depth, liquid cryogen remains on the epoxy resin surface for about 335 ms following spurt termination (about 435 ms from beginning of the spurt). The longer cooling time (up to about 780 ms) measured by the thermocouple positioned on the surface is due to liquid cryogen that remains trapped by the thermocouple bead for additional time. CSC with Simultaneous Application of Air Flow to the Experimental Model

In order to evaluate the effect of air convection on the thermal response to CSC in an experimental model, an air jet, an air flow control valve and a source of pressurized air were included in the test assembly shown in Figure 2. Preferably the air source is a compressed air cylinder. A gas other than air, such as CO₂, O₂ or N₂, could also be used successfully, and it should be understood that the term "air" as used in this disclosure also refers to these gases. It is preferable to avoid using a source of pressurized air that contains tetrafluoroethane (TFE), since the inventors have observed that TFE saturated air is less efficient at taking in the additional cryogen vapor. The same may be true for other propellant-saturated air sources. The air is also preferably at ambient humidity, or it may be dry. Inclusion of water vapor is preferably avoided to minimize the chance of ice formation on the skin, however.

Figure 4A shows the internal temperature distribution in response to a 100 ms cryogen spurt without external air flow. The cryogen film temperature during spurt application is -42^° C and, immediately after the end of the spurt, the measured temperature at 20 μm depth drops to -17^°C (from an initial temperature of 20°C). The liquid cryogen remaining on the phantom surface for about 700 ms led to additional temperature reductions at depths of 90, 200 and 400 μm. Figure 4B shows the internal temperature distribution in response to a 100 ms cryogen spurt in conjunction with air flow applied to the phantom surface at a rate of 30 L/min in a direction forming a 20° angle with the normal to the surface. The air jet was positioned about 20-30 mm away from the surface. The air flow was turned on 2 seconds before the cryogen spurt and applied continuously to the phantom surface for 5 seconds. The cryogen outlet was positioned nearly vertically with respect to the plane of the surface, about 60 mm away. The cryogen film temperature dropped to -57^°C during the spurt and evaporated almost immediately after spurt termination. The temperature at 20 μm depth dropped to -22.5 °C at the end of the spurt, an additional 5°C temperature reduction when compared with no air flow. Due to the faster cryogen evaporation in the presence of air flow, temperature reductions at depths of 200 and 400 μm were limited to half the value of those measured after the spurt if no air flow is applied. Although the heat convection coefficient at the air-liquid cryogen interface was expected to increase considerably with the air flow application, the value obtained for the heat transfer coefficient hcsc at the cryogen-epoxy phantom interface was similar to that obtained without air flow, estimated using the mathematical model of Anvari, B., et al. (IEEE Trans. Biomed. Eng., 45:1-8 (1998)). In Figure 4C, predicted internal temperatures in the phantom in response to CSC alone are compared with those predicted in response to CSC in conjunction with air flow. For a 200 ms cryogen spurt, additional temperature reductions of 7 and 4°C were predicted at the surface and at a depth of 100 μm, respectively, without affecting the temperature profile at 400 μm. The epoxy resin phantom used in this study has allowed estimation of the surface heat transfer coefficients that are critical for any quantitative determination of skin internal temperatures in response to CSC. Cryogen Film Temperature and Duration on Human Skin

Referring now to Figures 5A-B, cryogen film temperature histories at the surface of human skin are shown. An assembly similar to that shown in Figure 2 was used, omitting the internal thermocouples. A 300 μm bead thermocouple (Omega Engineering) was placed over the surface of the cryogen sprayed area of the skin surface. The larger size thermocouple (instead of a 30 μm thermocouple like that used in the epoxy resin experimental model) was employed in this case because of the difficulty of securing the smaller thermocouple to the skin surface. Figure 5A shows the actual surface temperatures of the skin of a human volunteer obtained using a 100 ms cryogen spurt. The temperature history was followed for 3.5 seconds after the cryogen spurt. Figure 5B shows the results of an identical test conducted with simultaneous target-directed air flow in conjunction with CSC. In this test, air convection was induced by a high rate of air flow (e.g., about 15-40 L/min) directed onto the target area before, during and following the cryogen spurt. The cryogen delivery device, the air jet and the laser were positioned as in the tests using the experimental model. More specifically, the air flow tube outlet was placed approximately 25 mm from the skin (or phantom) surface. The distance may vary from 20 to 30 mm, and may be adjusted by the user according to the desired air flow rate and the diameter of the tube or air jet employed.

Cryogen film temperature at the surface of the phantom (Figures 3 and 4A-B) was compared to that measured over the skin of human volunteers during CSC application (Figures 5A-B). Although adhesion of cryogen droplets to the 300 μm thermocouple bead leads to an artifactual prolongation of the measured evaporation time, the cryogen film lifetime on the skin surface was about one half of that on the epoxy phantom surface. Nevertheless, the liquid cryogen film remained on the skin surface for a time longer than the spurt duration without the use of airflow.

Evaporative/convective cooling was assumed to be the heat transfer mechanism for CSC in earlier work (B. Anvari, et al. IEEE Trans. Biomed. Eng., 45:1-8 (1998)). The present findings challenge this assumption, however. Based on the estimated values of the surface heat transfer coefficient, i.e., <5,000 W/m²K (Torres, J.H., et al. IEEE J. Selected Topics Quant. Electron. 5:1058-1066 (1999)), which is at least an order of magnitude higher than the values obtained for CSC in the present studies. The inventors now conclude that the deposited cryogen progressively evaporates from the top of the liquid film, while no evaporation directly occurs at the film-skin interface. This scenario corresponds to the spray cooling mode described by Grissom and Wierum (W. M. Grissom, and F. A. Wierum, "Liquid spray cooling of a heated surface," Int. J. Heat Mass Transfer, 24:261-271 (1981)) as "flooded state" or "spray film cooling", as opposed to the "dry wall state" or "spray evaporative cooling" in which the surface instantaneously vaporizes all the impinging spray. The lifetime of the cryogen film can be limited to the spurt duration by accelerating film evaporation with the addition of air convection (i.e., air flow) (Figures 4B and 5B). Also, the temperature of the cryogen film can be varied by adjusting the spraying distance, as the cryogen droplets progressively cool in flight. A previous report (J. H. Torres, B. Anvari, B. S. Tanenbaum, T. E. Milner, J. C. Yu, and J. S. Nelson, "Internal temperature measurements in response to cryogen spray cooling of a skin phantom," SPIE Proc, 3590:11-19 (1999)) indicates that a cryogen spraying distance of about 60 mm results in maximum temperature reductions (at least for the cryogen delivery device utilized in those experiments). The inventors now report that, under similar conditions, additional cooling can be obtained when air flow is directly applied to the liquid film that has been deposited on the surface. This extra cooling of the liquid cryogen film is a result of the evaporation that occurs at the liquid surface by mass transfer of cryogen molecules to the air flowing over the film. The energy required for the evaporation comes from internal energy of the liquid film, whose temperature is hence reduced. The resulting heat flux can be expressed in terms of the heat and mass transfer analogy for evaporative cooling (see reference F. P. Incropera, D.P. De Witt, Fundamentals of Heat and Mass Transfer. New York: John Wiley and Sons, 1990, for details). Inasmuch as the estimated value of the heat transfer coefficient bcsc at the cryogen film-epoxy resin interface was found to be similar to that obtained in the case of no air flow, the heat transfer mechanism at this interface remains unaffected despite the fact that mass and heat convection occur at the liquid cryogen film-air interface.

On human skin, the addition of air flow to CSC has an effect similar to that in the epoxy resin phantom, except that the liquid cryogen normally evaporates faster on the skin surface (Figure 5A), probably due in most part to the higher thermal diffusivity of skin (36% higher than that for the epoxy resin).

With CSC, a temperature reduction of 31 °C at the surface is predicted for human skin at the end of a 100 ms spurt, with a temperature reduction of less than 4°C at a depth of 200 μm and no temperature reduction at 400 μm. In the case of PWS, some abnormal capillaries may be located at a depth of 200 μm (T. E. Milner, D. M. Goodman, B. S. Tanenbaum, and J. S. Nelson, "Depth profiling of laser heated chromophores in biological tissues by pulsed photothermal radiometry," J. Opt. Soc. Am., 12:1479-1488 (1995); and J. S. Nelson, T. E. Milner, B. S. Tanenbaum, D. M. Goodman, M. J. C. Van Gemert, "Infra-red tomography of port- wine-stain blood vessels in human skin," Lasers. Med. Sci.,11:199-204 (1996)) and a spurt duration < 100 ms is desirable to avoid cooling of these vessels prior to laser exposure. For deeper PWS blood vessels, i.e., 400 μm (S. H. Barsky, S. Rosen, D. E. Geer, and J. M. Noe,

"The nature and evolution of port wine stains: A computer assisted study," J. Invest. Dermatol.,

74:154-157 (1980)), a 200 ms spurt duration may be used since temperature reduction at this depth is not expected. Greater temperature reductions can be achieved with CSC by adding air convection at the skin surface, as shown in Figures 5A-B. For many applications the position of the outlet of the cryogen delivery device is preferably between about 5-100 mm, more preferably about 60 mm. For those applications, the position of the air jet is preferably between about 20-30 mm away from the surface and oriented at an angle of about 20-30 degrees with the normal to the surface. Optimum positioning of the cryogen delivery device and the air jet may be readily determined by adjusting their distance from the target and the orientation angle and force of the air flow. The air stream is preferably not so close to the target or the force of the flow so great that the cryogen pool or film is splashed or skewed from the target area, and the angle of the air stream is preferably so large that the air flow interferes with the cryogen droplets in flight. For spurt durations of 100 ms or less, freezing of water within the skin is not expected with CSC, as ice crystals may not have time to form before the laser pulse is applied. In addition, a temperature of only -1°C has been predicted by the inventors at the skin surface at the end of 100 ms using a thermal diffusion mathematical model (J. H. Torres, et.al. IEEE J. Special Topics Quant. Elect., in press). Although the predicted surface temperature drops to - 8°C at the end of a 200 ms spurt, the temperature throughout most of the epidermis is predicted to remain above 0°C, reaching a minimum of +9°C at a depth of 100 μm. For spurt durations greater than about 200 ms, water freezing within the skin may occur. Freezing of the skin is undesirable and must be avoided since it will damage the same epidermis for which thermal protection is sought. Although the laser pulse applied immediately after the cryogen spurt raises back the skin temperamre above 0°C ( data shown in J. H. Torres, et.al. IEEE J. Special Topics Quant. Elect., in press), the cryogen residence time on the skin surface must be controlled and limited to the desired spurt time for best results. This task is well accomplished with the utilization of airflow in conjunction with the CSC, as described herein. By providing air flow to ensure that the evaporation time of the cryogen film is not substantially longer than the duration of the cryogen spurt, the full cooling potential of CSC is more thoroughly exploited than was possible with previous methods or CSC devices.

In previous studies (B. Anvari, et al. IEEE Trans. Biomed. Eng., 45:1-8 (1998); and B. Anvari, B. J. Ver Steeg, T. E. Milner, B. S. Tanenbaum, T. J. Klein, E. Gerstner, S. Kimel, and J. S. Nelson, "Cryogen spray cooling of human skin: effects of ambient humidity level, spraying distance, and cryogen boiling point," SPIE Proc, 3192:106-110 (1997)), a mixture of cryogen and ice was believed to form over the skin surface during spurt application, the ice resulting from fast freezing of water vapor in ambient air. In recent experiments applying CSC to the epoxy phantom as well as to insulating foam materials, the inventors observed that ice forms over the surface only after the liquid cryogen film has completely evaporated. No ice deposited on the surface during the cryogen spurts in which air flow was continuously or intermittently applied.

Internal temperature measurements in an epoxy resin phantom have been used in conjunction with a thermal diffusion model to predict the thermal responses of human skin to CSC. The heat transfer mechanism for CSC appears to be conduction-limited heat transfer with a thermal resistance at the skin interface. A "flooded state" with rapid buildup of a liquid film occurs during the spurt, with evaporation taking place at the film surface but not at the film-skin interface. Cryogen film evaporation can be accelerated by addition of air convection at the film surface, further reducing the cryogen film temperature. Addition of a controlled and carefully aimed air flow capability, as described above, to any conventional laser treatment apparatus that is used in conjunction with application of a cryogenic coolant is expected to be similarly beneficial for enhancing the amount of surface temperature reduction, reducing ice formation, and controlling the residence time of the cryogen film on the surface of the treatment site, as well as reducing the risk of cryo-injury that may otherwise occur when the cryogen film resides on the surface for too long in the absence of convection inducing air flow.

The new convective air flow CSC method differs from the CSC methods of others, which are primarily directed at reducing or eliminating humidity effects by flooding a relatively larger area, or theatre, with a low humidity gas. None of the previous methods change the temperature or the residence time of the cryogen film. Air Flow Enhanced CSC Laser Device

Referring now to Figure 6, a preferred device 10 generally includes a hand piece 12, laser delivery optics 14, cryogen delivery device 16, and air flow jet 18. The device may also include a guide 20, which is preferably adjustable in length. Preferably all of these components are incorporated in an instrument that is hand held and easily manipulated by the physician during patient treatment. Cryogen delivery device 16 is connected to a liquid cryogen reservoir and includes a cryogen injector or delivery nozzle 24. The delivery nozzle 24 may be a conventional automobile fuel injector or a more specialized cryogenic injector, and is controlled by a relay circuit which in turn may be controlled by a programmable digital delay generator, substantially as described in U.S. Patent 5,997,530, which is incorporated herein by reference. Nozzle 24 may also be adjustable for orienting the path of emitted cryogen. Air jet 18, which is preferably a tube about 3-5 mm in diameter, is connected to a conventional source of pressurized air or other suitable gas. It is preferred if an air flow control valve 22 is positioned in line between the air source and air flow jet 18. Control valve 22 may be manually operable to allow continuous air flow from jet 18, or it may be electronically controlled to actuate intermittent releases of jets of air at a desired rate. Application time can also be controlled by the digital delay generator indicated above. Laser delivery optics 14, which may include an optical fiber 26. The laser source may be a conventional pulse or continuous wave light source for providing the desired heating of the target tissue. Although the laser, its power supply and control electronics are not shown in Figure 6, it should be understood that the device is intended to be used in combination with a conventional laser or other source of electromagnetic radiation. The particular shape of the hand piece 12 may be varied to accommodate the size and configuration of optics 14, delivery device 16, air valve 22 and guide 20, and for ease of handling by the user. Also, the arrangement of each component within or on the hand piece may be varied as long as the critical relative positioning of laser spot, cryogen film and air stream are maintained.

If desired, the apparatus could be formed from separate laser delivery and air flow enhanced CSC devices that are connected together in a single unit for use. The appearance and working arrangement would be similar to that of Figure 6. In this arrangement, the air flow enhanced CSC device is attached close to the laser delivery device and in such a way that the air stream emitted from the air jet has an incidence angle of about 20-30 degrees with the normal to the target surface. For some applications this design might be more desirable than a design having a single unit containing all of the components, or due to ease of manufacturing. Another alternative version of the device (not shown) is similar to that shown in Figure

6 but includes one or more additional air jets like jet 18, each of which is which is advantageously positioned with respect to the cryogen delivery device 16 and the target area 15 on the skin surface 30. For some treatment regimes, the additional air jets will be preferred to further enhance cryogen cooling and further shorten the cryogen film evaporation time. A suitable air enhanced CSC laser treatment device can also be produced by modifying a conventional hand held SCS laser unit such as the ScleroPlus™ manufactured by Candela Corporation to include a directed air flow capability as described above. Method of Laser Treating a Dermatological Condition

A focused or directed air flow capability is incorporated into a hand held cryogen spray- laser delivery system to enhance cryogen evaporation rate and epidermal cooling efficiency during laser treatment of a dermatological condition, such as PWS eradication, wrinkle removal, tattoo removal or hair removal, for example. Referring again to Figure 6, in operation, device 10 is positioned over the intended treatment area such that the laser spot 15 from optics 14 is directed at a target site on the skin surface 30. The distance between cryogen delivery nozzle 24 and surface 30 is adjusted to achieve the lowest cryogen temperature on the skin surface. For example, the outlet of the cryogen delivery device may be about 60 mm above the target. A guide 20 of suitable length is chosen and attached to hand piece 12; or alternatively, guide 20 is fixed to hand piece 12 and is adjustable such that it may be lengthened or shortened to establish the desired distance. Cryogen spray is delivered from nozzle 24 as perpendicularly to the skin surface as the size and placement of the laser optics allows. The cryogen nozzle 24 is positioned so that the resulting cryogen film at least covers the laser spot. In the present test, the cryogen outlet or nozzle 24 was about 60 mm above the skin surface and placed next to the laser aperture. It is preferred that the cryogen film also covers at least a 50% greater area surrounding the laser spot. The area covered by the cryogen is not necessarily circular. Usually the duration of the cryogen spurt will be up to about 200 milliseconds, more often 100 milliseconds or less. The optimum or desired duration and frequency of cryogen delivery device actuation can be readily determined and by the user, and the cryogen controls set accordingly. The outlet of the air tube or air jet 18 is preferably positioned as close to the target as possible, yet not so close that the air stream splashes or disrupts cryogen flooding of the target area at the selected air flow rate and angle. In this test, the air tube outlet was about 25 mm away from the target. The air stream is directed toward the area covered by the cryogen as it forms a film on the skin, and is applied at an angle that does not cause interference of the air flow with the cryogen mist or droplet spray in flight. Preferably the air jet is oriented at about a 20-30° angle with the normal to the skin surface. In any case, the angle should not be so great or the force of the air flow so great that the air stream interferes with the cryogen droplets in flight. In this test, a manual air flow control valve was employed and the stream of air was applied continuously from shortly before, during and after commencement of the 100 ms cryogen spurt. Alternatively, the stream of air could be applied in electronically controlled bursts whose duration and time of application can be readily established by the user. For many procedures, a suitable air flow rate is about 15-40 L/min using a 3-5 mm I.D. tubing outlet or air jet placed about 20-30 mm away from the target surface. Since excessive air flow can mechanically disrupt the formation of a liquid cryogen film on the skin surface, such occurrence is avoided by properly adjusting the air flow rate. Timing of air flow application relative to the onset of CSC and its application rate are easily adjusted by the user to achieving the desired optimal cooling effect. Additionally, the user can vary the temperature of the air flowing over the surface, if desired, so as to further adjust the residence time of the cryogen film on the skin. Preferably care is taken to avoid increasing the temperature so much that the cryogen evaporates prematurely, for example, before reaching the surface of the skin. Likewise, excessive reduction of the temperature is preferably also avoided because colder air may not hold as much cryogen vapor. For ease of operation, it is preferred to use ambient temperature air (i.e., about 20-25°C).

As with a conventional hand held CSC laser treatment device, the laser is electronically operated in concert with electronic actuation of the cryogen delivery device. The air flow system is operated manually or electronically in concert with the cryogen dispensing system to enhance the surface temperature reduction, to reduce or eliminate ice formation, and to control the residence time of the cryogen film on the surface of the treatment site. The device is repositioned on the skin surface, as the user deems necessary, to effect the desired treatment.

While the preferred embodiments of the invention have been shown and described, modifications thereof can be made by one skilled in the art without departing from the spirit and teachings of the invention. The embodiments described herein are exemplary only, and are not intended to be limiting. For example, although laser light application is a preferred treatment method and is described in detail herein, it should be understood that other types of electromagnetic radiation could be similarly used with air flow enhanced CSC, such as microwave, infrared or visible light. Many variations and modifications of the invention disclosed herein are possible and are within the scope of the invention. Accordingly, the scope of protection is not limited by the description set out above, but is only limited by the claims which follow, that scope including all equivalents of the subject matter of the claims. The disclosures of all patents and publications cited herein are incorporated by reference to the extent that they describe pertinent materials and techniques not explicitly set forth herein.

Claims

CLAIMS What is claimed is:

1. An apparatus for laser treatment of biological tissue comprising: a laser delivery optics; a cryogen delivery device; and at least one directed air flow device.

2. The apparatus of claim 1 wherein each said directed air flow device is disposed a defined distance away from a biological tissue surface and aimed toward a defined target on said surface when said apparatus is positioned for laser treating a biological tissue.

3. The apparatus of claim 1 wherein each said directed air flow device is aimed toward said target at an angle of about 20-30 degrees to the normal to said target.

4. The apparatus of claim 3 wherein said cryogen delivery device is disposed a defined distance away from a biological tissue surface such that a cryogen spray emitted by said device at least covers a laser spot emitted from said laser optics onto said target when said apparatus is operated for laser treating a biological tissue.

5. The apparatus of claim 4 wherein said cryogen delivery device is disposed adjacent said laser optics and about 60 mm away from said surface.

6. The apparatus of claim 4 wherein said directed air flow device is disposed about 20-30 mm away from said surface and oriented at about 20-30 degrees with the normal to said surface such that such that an air stream emitted by said directed air flow device at least covers an area covered by said cryogen spray on said surface, when said apparatus is operated for laser treating a biological tissue.

7. The apparatus of claim 1 further comprising a hand piece retaining said directed air flow device, cryogen delivery device and laser delivery optics.

8. The apparatus of claim 1 further comprising a distance guide.

9. The apparatus of claim 1 further comprising an air flow controller and a cryogen delivery controller.

10. In an apparatus for laser treating biological tissue having an overlying surface that is vulnerable to thermal injury, said apparatus comprising a cryogen delivery device and a laser delivery optics, the improvement comprising means for applying directed air flow onto said surface in conjunction with operation of said cryogen delivery device.

11. The apparatus of claim 10 wherein said means further comprises a source of 15-40 liters per minute air flow.

12. An apparatus for cryogen spray cooling a biological tissue, said apparatus comprising: a cryogen delivery device having a cryogen outlet; and at least one directed air flow device disposed a defined distance away from a biological tissue surface and aimed toward a defined target on said surface when said apparatus is positioned for air flow enhanced cryogen spray cooling said tissue.

13. An apparatus for laser treatment of biological tissue comprising: a laser delivery device; and a cryogen spray cooling device disposed adjacent said laser delivery device, said cryogen spray cooling device comprising a cryogen delivery device having an outlet and at least one directed air flow device disposed such that a stream of air emitted from said jet has an incidence angle of about 20-30 degrees with the normal to a target surface on a biological tissue when said device is operated for cooling said target surface in conjunction with operation of said laser for treating said biological tissue.

14. A method of treating a dermatological condition comprising: cooling a designated outer surface area of living skin which is initially at a first temperature by spraying a liquid cryogen onto said outer surface area such that a cooling film is formed on said area of living skin, and directing a stream of air onto said outer surface area simultaneously with said applying of liquid cryogen, whereby the temperature of said outer surface area is reduced to a predetermined second temperature below said first temperature and the rate of evaporation of said film from said area is enhanced; and while cooling said outer surface area, directing a laser beam onto a portion of said area sufficient to increase the temperature of a portion of interior tissue that is located a predetermined depth below said outer surface to a predetermined maximum temperature above said first temperature.

15. The method of claim 14 wherein said step of directing a stream of air onto said film comprises orienting said stream of air toward said film at a 20-30° angle with the normal to said surface.

16. The method of claim 14 wherein said step of directing a stream of air onto said film comprises emitting a stream of air from a directed air flow device having an approximately 3-5 mm internal diameter a stream of air at a flow rate of about 15-40 L/min.

17. The method of claim 14 wherein said step of directing a stream of air onto said film comprises intermittently emitting a stream of air from said directed air flow device.

18. The method of claim 14 wherein said step of directing a stream of air onto said film comprises continuously emitting a stream of air from said directed air flow device.

19. The method of claim 14 wherein said step of directing a stream of air onto said outer surface area simultaneously with said applying of liquid cryogen comprises establishing an air flow rate of said air stream onto said outer surface area such that the evaporation time of said cryogen film from said area is approximately the same as the duration of cryogen delivery onto said area.

20. The method of claim 14 wherein said step of directing a stream of air onto said film includes directing a stream of air onto said outer surface area for a sufficient time for said air stream to warm said outer surface portion to approximately said first temperature.

21. The method of claim 20 wherein said step of directing a stream of air onto said outer surface area comprises at least substantially evaporating said liquid cryogen film.

22. In a method of performing laser treatment of a biological tissue which includes applying a film of cryogenic liquid to a selected outer region of tissue such that a dynamic temperature gradient is established in the tissue, and directing a laser beam onto said region, such that said outer region of tissue is protected from thermal damage while a selected region of interior tissue lying below said outer region is thermally treated by said laser beam, the improvement comprising directing a stream of air onto said outer region in cooperation with applying a cryogenic liquid onto said outer region such that the temperature of said film of cryogenic liquid on said selected outer region is reduced and such that the evaporation time of said film from said outer region of tissue is less than the evaporation time of an identical film for which no air stream is directed onto said outer region.