Patent ID: 12226650

DESCRIPTION

Exemplary embodiments of the present disclosure are illustrated in the drawings, which are illustrative rather than restrictive. No limitation on the scope of the technology, or on the claims that follow, is to be implied or inferred from the examples shown in the drawings and discussed herein.

Treatment of many dermatological conditions involve using laser light to heat a target skin area to thermally damage a selected structure within the target skin area and promote a healing response. Consistently accurate delivery of energy to targeted structures to achieve a desired level of damage to the target structure, while minimizing the delivery of energy and corresponding damage to non-targeted structures, has remained an unrealized goal. The present disclosure is directed to providing systems and methods to achieve these objectives.

As used herein “target skin area” refers to the skin receiving the energy of a laser pulse. The target skin area may include the surface skin area illuminated by the laser pulse, as well as deeper structures beneath the surface skin area that receive at least a portion of the energy from the laser pulse. As such, “target skin areas” treated by a laser pulse may refer to a volume of skin as opposed to a true area of an outer surface of the epidermis.

As used herein, “surface temperature” in reference to a target skin area refers to the temperature of the target skin area as determined or measured at or above the surface of the skin. In particular, where infrared (IR) energy radiated from a target skin area is used to measure the temperature of the skin surface, the surface temperature determination includes energy radiated from deeper in the epidermis in addition to the outermost layer of cells. Without being bound by theory, the strong scattering effects of IR wavelengths within the epidermis limit the energy emitted and detected to the upper 100 microns, and primarily the upper portions thereof. Consequently, “determining a surface temperature” based on detection of radiated IR energy refers to the determination of a composite or average temperature of the upper portions (e.g., tens of microns in depth) of the epidermis, and not merely the outermost layer of skin cells. In embodiments of the present invention, IR-based temperature measurements or determinations provides a reliable and precise determination of the temperature of the uppermost portion of the epidermis.

As used herein in connection with optical elements and optical energy, “engages” refers to optical contact between optical energy (e.g., a laser pulse or IR energy) and an optical element such as a lens or a mirror. A laser pulse or IR energy may engage a lens by passing through it, and engages a reflective element by being reflected of its surface.

In one aspect, the present invention comprises systems and methods having a handpiece for improved temperature control of a target skin area during the delivery of one or more therapeutic laser pulses in the treatment of a medical condition. The handpiece is configured to facilitate the delivery of laser pulses traveling in a first direction to a target skin area, and to allow IR energy radiated from the target skin area to travel in a second direction generally opposite (“counterdirectional”) to the first direction to detect skin temperature. The handpiece is optically coupled to a laser source adapted to generate at least one, and preferably a plurality, of therapeutic laser pulses for application to the target skin area. The handpiece receives therapeutic laser pulses from the laser source, and includes a cooling window for contacting and cooling a first skin area that includes the target skin area. The cooling window is transmissive to the laser pulses and to IR energy radiated from the target skin area. The laser pulses travel through the handpiece along a first optical path in the first direction, and pass through the cooling window to a target skin area within the first skin area. The system further includes a temperature determination unit that includes a temperature sensing element and a processor for determining a surface temperature of the target skin area based on IR energy radiated from the target skin area through the cooling window along a second optical path travelling along a second optical path generally opposite or counterdirectional to the first optical path. In a preferred embodiment, the first optical path and the second optical path share a common optical axis for at least a portion of their length. The handpiece includes a reflective optical element located in the first optical path and having one of a slot and an aperture through which the laser pulses pass while traveling along the first optical path. The reflective optical element is oriented to receive the IR energy radiated from the target skin area along the second optical path, and to reflect it onto the temperature sensing element. The temperature sensing element generates a signal that is processed by the processor to determine the surface temperature of the target skin area. In a preferred embodiment, the reflective optical element is precisely oriented to receive IR energy from substantially only the target skin area, and not from other adjacent tissue within the larger skin area cooled by the cooling window. The handpiece further comprises at least one second optical element within the first optical path, and the laser pulses engage the at least one second optical element. In a preferred embodiment, the at least one second optical element comprises a plurality of optical elements, including at least one lens and at least one reflective element (e.g., a mirror). In a still more preferred embodiment, the IR energy radiated from the target skin area along the second optical path also engages the plurality of optical elements. In various embodiments, the at least one second optical element may comprise elements for focusing, splitting, redirecting, collimating, or performing other operations on the laser pulses and/or IR energy.

In some embodiments, the present invention comprises systems and methods for determining or measuring a surface temperature of a target skin area of a patient during a laser treatment using a handpiece that provides contact cooling of the skin and surface temperature sensing of substantially only a target skin area receiving laser energy. In some embodiments, the present invention provides improved temperature control of a target non-surface (i.e., deeper) structure in the target skin area of a patient during the laser treatment. By providing accurate temperature control of a target skin area during the delivery of laser pulses, the invention provides systems and methods with improved efficacy, safety and/or comfort to patients being treated for a range of dermatological conditions.

In some embodiments, the present invention comprises systems and methods for treating the skin of a patient with therapeutic laser pulses with a handpiece that provides contact cooling of the skin and contact sensing to ensure proper contact between the contact cooling element and skin of the patient. In some embodiments, the handpiece further includes temperature sensing based on IR energy radiated from the target skin area receiving the laser pulse(s) and traveling counterdirectionally to the laser pulses.

In one aspect, the invention provides systems and methods of controlling a temperature of a target skin area during a laser treatment to avoid one or more of overheating or excessively damaging the target area, underheating the target structure, or causing undesired damage to overlying non-targeted structures.

In one aspect, the present invention discloses systems and methods for minimizing the temperature increase of non-target structures overlying a target structure within a target skin area during the delivery of a laser one or a plurality of laser treatment pulses to raise the target structure from a first temperature to a second temperature (e.g., a damage threshold temperature).

In various embodiments, systems of the present invention may determine the temperature of a target skin area one or a plurality of times before, during, or after treatment of the target skin area using IR energy radiated from the skin. The laser treatment may comprise comprises one pulse, or a plurality of pulses comprising a single heating episode of the target skin area. As used herein, a “single heating episode” involves a plurality of pulses where the first pulse raises the temperature of the target skin area from a first or baseline temperature immediately prior to the first pulse, and each successive pulse in the heating episode is applied before the target skin area returns to the first or baseline temperature. Where a plurality of pulses is used to heat the target skin area in a single heating episode, the temperature of the target skin area may be determined during a pulse, between pulses, or a combination of during and between pulses of the single heating episode.

As used in connection with temperature determinations, “real-time” refers to temperature determinations (e.g., temperature measurements or calculations based on data from an IR temperature sensor) performed with little time delay (e.g., less than 100 msec, more preferably less than 5 msec, most preferably 1 msec or less) between the initiation and conclusion of temperature determination. Stated differently, real-time temperature determinations are those made very rapidly and capable of use by the system to perform one or more tasks, such as terminating a treatment of a target skin area, logging the skin temperature profile vs time to a memory, or providing a warning indication to a user.

In one aspect, the invention also comprises contact cooling applied to an external surface of a first skin area to enable heating of deeper structures (e.g., a sebaceous gland) to a damage threshold temperature, while minimizing the heating of overlying non-targeted tissue structures. Real-time temperature determinations may occur during before, during, or after the cooling of a first skin area, and may be used (e.g., by a processor executing a treatment algorithm) to perform a responsive action such as initiating, terminating or adjusting the cooling process, initiating or terminating the delivery of one or more laser pulses to a target skin area within the skin area being cooled, or adjusting a parameter of the laser therapy.

In one aspect, the invention comprises a method of treating a patient having one of more dermatological conditions including, without limitation, abnormal pigmentation conditions, acne vulgaris, dyschromia, hyperhidrosis i.e., excessive sweating), pigmented lesions, vascular lesions, and wrinkles and fine lines by controlled heating of a target skin area from a first surface temperature to a second surface temperature sufficient to cause thermal damage to one or more structures in the target skin area. In one embodiment, the duration of a laser treatment pulse is based on determining the surface temperature of the target skin area one or more times before, during, or after the delivery of laser treatment pulses. In one embodiment, a laser treatment pulse is terminated when the second surface temperature reaches a value indicative of a deeper target structure (e.g., a sweat gland) reaching a desired treatment temperature. The second surface temperature corresponding to the target structure reaching its treatment temperature may be determined prior to treatment, e.g., by thermal (mathematical) modeling of the heating of the target skin area as a function of skin depth based on the parameters of the treatment laser such as wavelength, energy flux, and thermal characteristics of the target skin area such as thermal conductivity, the absorption coefficients of various tissue structures and/or chromophores, etc.

In one aspect, the invention comprises a method of treating a patient having acne vulgaris by controlled heating of a target skin area from a first surface temperature to a second surface temperature, where the second surface temperature corresponds to a temperature resulting in thermal damage to one of sebum or a sebaceous gland within the target skin area. In one embodiment, the duration of the laser treatment pulse is based on determining the surface temperature of the target skin area a plurality of times during the delivery of one or more laser treatment pulses. In one embodiment, the laser treatment pulse is terminated when the second surface temperature reaches a value indicative of the deeper sebaceous gland reaching a sebaceous gland treatment temperature. The second surface temperature corresponding to the sebaceous gland reaching the sebaceous gland treatment temperature may be identified by thermal modeling as previously discussed.

FIG.1is a side view illustrating a cross-sectional view of a portion100of the skin of a patient, including the outermost epidermis102, the middle layer or dermis104, and the bottom layer or hypodermis106. The epidermis102has a thickness of about 80-100 μm, which may vary from patient to patient, and even for a single patient depending upon age, health status, and other factors. It includes up to five sub-layers (not shown) and acts as an outer barrier.

The dermis104has a thickness of about 1-5 mm (1000-5000 μm). It contains the blood vessels, nerves, hair follicles, collagen and sweat glands within the skin. Because skin conditions frequently involve structures in the dermis, many laser systems must include sufficient energy to penetrate into the dermis to reach those structures. Careful selection of a number of parameters must be made in the design and construction of laser systems to achieve a desired level of damage to a target structure while minimizing or avoiding damage to non-targeted (e.g., overlying) structures. For example, incorrect selection of the laser wavelength, pulse width, energy per pulse, the use (or nonuse) of a seed laser, or the pump energy of the laser source or amplifier may result in undesired damage and poor performance in treating a dermal structure. Numerous other system choices, such as the use or non-use of an articulating arm for delivery of the laser light to a handpiece for application to the skin, may also affect overall system performance.

The lowest layer of the skin is the hypodermis106, which includes adipose tissue and collagen. The hypodermis106helps control body temperature by insulating the structures of the body below the skin. In addition, the hypodermis protects the inner body tissues from damage by absorbing shock and impacts from outside the body. Because the hypodermis contains fat, its thickness varies widely from person to person based on diet, genetic makeup, and other factors.

FIG.1depicts a laser beam108applied to a target skin area110of the skin100. The target skin area110comprises a surface skin area112, as well as underlying skin tissue114that absorbs at least a portion of the energy of the laser beam108.

FIG.2is a side view of the skin of a patient illustrating in simplified form, a hair202including a hair shaft204extending beyond the exterior skin surface206. Hair shaft204includes a root208located below epidermis210in the dermis212. The base, or papilla, of root208is located about 4 mm below exterior skin surface206. Root208is housed within hair follicle214and is surrounded by tissues including connective tissue sheath216and blood vessels218. Follicle214includes a sebaceous gland219below an opening223. Sebaceous glands such as gland219are typically located at depths ranging from about 0.3 mm (300 μm) to about 2.0 mm (2000 μm) below exterior skin surface206, but their depth varies depending upon body location.

Epidermis210includes melanin (not shown), a dark pigment found in tissues of the hair, skin and eyes. Melanin, the primary determinant of skin color, is located within globular structures known as melanosomes, which are produced by skin cells called melanocytes. Darker skin has more melanosomes (and thus more melanin) per unit skin area compared to lighter skin. Laser systems targeting deeper structures such as sebaceous gland219in the dermis may present a higher risk of patient discomfort where wavelengths having a relatively high absorption coefficient in melanin are used. Without being bound by theory, when laser light at wavelengths readily absorbed by melanin is applied to darker skin (or dark tattoos having ink particles that absorb laser light at similar wavelengths to melanin), the energy absorbed by the melanin (or tattoo ink particles) attenuates part of the laser energy that otherwise would reach deeper structures, heating the skin of the epidermis and/or upper dermis to a greater degree than lighter/un-tattooed skin. Additional energy—e.g., using higher fluences, higher energy per pulse, or longer treatment times—must be applied to reach and heat deeper structures to a target treatment temperature. However, higher pulse fluences and pulse energy may compound the problem, since the additional energy delivered in a shorter time period will cause the overlying skin temperature to rise even faster than using lower fluences or energies. In addition, longer treatment times can only deliver more energy to the target if the energy is delivered within the TRT of the target tissue—otherwise, the additional energy largely leaks from the target tissue into adjacent non-target tissue.

Accordingly, in one aspect, the present invention provides laser treatment systems to minimize discomfort by adjusting one or more treatment parameters based on the patient's skin type. In one embodiment, the invention provides systems and methods comprising a handpiece for determining a skin type of a patient and automatically adjusting one or more treatment parameters based on the skin type of the patient. This may involve, for patients having darker skin types, one or more of: providing additional cooling of the patient's skin prior to applying a laser therapy to the patient's skin; lowering a first skin temperature at which a therapy pulse is initiated and applied to the patient's skin; lowering a fluence of a laser therapy; lowering a peak power of the laser pulses of a laser therapy; providing a longer pulse width of a pulsed laser therapy; and providing a larger beam diameter for a pulsed laser therapy.

Successful treatment of acne involves damaging sebocytes, sebum and/or sebaceous glands. This involves heating these structures to damage the gland and/or kill bacteria resident therein. Accordingly, in one embodiment the invention provides laser light at a wavelength that is highly absorbed by sebum, compared to competing skin chromophores (e.g., water), to limit the damage to non-targeted tissue and concentrate the laser energy delivered into the targeted sebaceous gland. Because sebaceous glands are relatively deep structures located in the dermis at depths of 300-2000 μm (0.3-2.0 mm), it is desirable to select a wavelength of light capable of non-ablative penetration to these depths.

FIGS.3A and3Bare graphs illustrating the absorption curves for several chromophores of interest (water, sebum, and melanosomes) at wavelengths of light for portions of the near-infrared spectrum (about 750 nm-1400 nm) and the short-wavelength IR spectrum (about 1400-3000 nm). The figures highlight the problem of targeting tissues having a target chromophore with poor selectivity relative to a non-target chromophore in a nontarget tissue.FIG.3Aillustrates the absorption curve310for sebum, the water absorption curve320, and the absorption curve330for melanosomes. It will be appreciated that in laser treatment systems directed toward conditions other than acne, e.g., tattoo removal or pigmented lesions, the absorption of other chromophores (e.g., inks of various colors, hemoglobin, etc.) will be important considerations in selecting laser treatment system parameters such as wavelength, fluence, peak power, etc.

For much of the wavelength range ofFIG.3A, the water absorbs light more strongly that sebum, as illustrated by the absorption curve for water320lying above the sebum absorption curve310for most of the wavelength range. However, the sebum absorption curve310has a peak at about 1727.5 nm (point335), meaning that sebum absorbs laser light at this wavelength more strongly than light at other nearby wavelengths, e.g., 1650 nm or 1800 nm. Although the absorption coefficient for sebum in this wavelength range is greater than that of water, the ratio of the two curves in this region has a maximum value of about two. As previously noted, ratios less than ten are one characteristic of poor chromophore selectivity. The other characteristic of tissues with poor chromophore selectivity is that the target chromophore absorption coefficient only exceeds that of the non-target chromophore for a narrow range. The absorption coefficient of water (curve320) is less than that of sebum in a range of from about 1693 nm to about 1742 nm. Since this range is less than 6000 GHz, the sebum curve in this wavelength is an example of poor chromophore selectivity. Note that there are no areas of the sebum curve320exceeding the absorption curve for water at which the ratio of the sebum and water coefficients is 10 or greater. Accordingly, treating acne with laser light is characterized by poor chromophore selectivity even at the most advantageous wavelength.

The absorption coefficient of melanosomes exceeds that of sebum at all wavelengths less than about 2225 nm, although only by a small amount at the 1727.5 nm peak for sebum, as demonstrated at point335ofFIG.3A, where the two absorptions curves approach one another. It will be appreciated by persons of skill in the art that the concentration of sebum, water, and melanin may vary from patient to patient for a given area, and even within a particular patient depending upon the target tissue structure(s), the hydration status of the patient, and the skin type or area of the patient.

As shown more clearly inFIG.3B, which is a more detailed illustration of the absorption curves ofFIG.3Afor the 1600-1800 nm wavelength region using like numbers for like absorption curves and peaks, the absorption coefficient for sebum (curve310) at a peak of about 1727.5 nm (point335) is approximately twice that of water (curve320), and is only slightly less than that of melanosomes (curve330). Specifically, the absorption coefficient for melanosomes at 1727.5 is about 11.0 cm−1, and that of sebum is about 10.3 cm−1. As can be seen from steep drop in curve310on either side of the peak, the ratio of the sebum and water coefficients declines relatively rapidly on either side of the peak. For typical diode lasers having a relatively broad linewidth, much of the laser energy will be provided at ratios significantly less than the maximum value, further contributing to heating of non-target tissues overlying the sebaceous gland. There is a need for laser treatment systems incorporating laser sources with reduced linewidth to treat tissues (such as sebum inFIGS.3A and3B) having poor chromophore selectivity.FIGS.12-15discuss structures and methods to achieve a narrower linewidth, preferably less than 500 GHz, more preferably less than 300 GHz, more preferably still less than 200 GHz. Accordingly, in one embodiment, the invention comprises a laser providing pulsed laser light at a wavelength of between 1693-1742 nm, more preferably at about 1720-1730 nm, and more preferably still at about 1727.5 nm.

Referring again toFIG.3A, the sebum absorption curve310has a further absorption peak (340) of about 2305 nm, exceeding that of both water and melanosomes at the same wavelength. In one embodiment, the invention comprises a laser providing pulsed laser light at a wavelength of between about 2287-2318 nm. Although sebum strongly absorbs light at 2305 nm, light at this wavelength is less suitable because its penetration depth into skin is much less than that of light at 1727.5 nm. In general, at wavelengths shown inFIGS.3A and3B, the penetration of light decreases with increasing wavelength. Treatment of acne and other conditions with laser light involves multiple tradeoffs, including the relative absorption coefficients of target and non-target tissues/structures, penetration depth of the wavelength of interest into skin, laser power, laser pulse fluence, pulse duration, pulse frequency, etc.

FIGS.4A and4Billustrate exemplary temperature profiles of the surface of a target skin area (FIG.4A) and a sebaceous gland (FIG.4B) located below the surface of the target skin area during a laser pulse according to a mathematical model. The laser pulse is intended to raise the temperature of the sebaceous gland to a temperature to achieve a desired cell population death for sebocytes. In this embodiment, the laser pulse is a tophat pulse (i.e., having a uniform intensity profile over the covered area) with a wavelength of 1727.5 nm, a pulse duration of 30 msec, a beam diameter of 2.8 mm, a power of 75 W, a pulse energy of 2.25 J, and a fluence of 37 J/cm2. For purposes of illustration, the skin is depicted as remaining at body temperature for 2 seconds prior to the application of the pulse, although it will be appreciated that any arbitrary time period could be shown.

Referring toFIG.4A, at time t=2 seconds, a single pulse of laser light having the parameters noted above is initiated and applied to a target skin area, depicted at point420. The surface temperature of the skin rises during the pulse, as shown by line430, to slightly above 100° C. as shown by peak440. After the pulse is terminated, the skin surface temperature of the target area cools rapidly over the next several seconds, as indicated by curve450, falling to below 60° C. within 4 seconds (t=6 seconds) after the termination of the pulse.

FIG.4Billustrates the temperature profile of a sebaceous gland located at a depth of 650 μm below the skin surface in the laser pulse model ofFIG.4A. As inFIG.4A, the skin remains at body temperature for 2 seconds (410) prior to the initiation of a single pulse (421) applied to the target skin area. The temperature of the gland rises during the pulse (430) to a maximum temperature440of about 92° C.—less than the surface skin temperature illustrated inFIG.4Adue to scattering and the energy absorbed by the overlying tissue. Because the pulse energy at 1727.5 nm is preferentially absorbed by the sebaceous gland (as discussed in connection withFIGS.3A and3B), comparatively more energy from the laser pulse that reaches the gland is absorbed by the oily tissue therein compared to overlying tissue containing a higher water content. Consequently, the temperature profile (450) of the sebaceous gland after termination of the pulse at440differs significantly from that of the skin surface temperature depicted inFIG.4A. Although the temperature initially falls rapidly to about 85° C., the temperature thereafter falls more slowly than the surface temperature shown inFIG.4A.

The pulse modeled inFIGS.4A and4Bhas energy levels below those necessary to ablate skin tissue. Although the pulse will result in thermal damage to the sebaceous gland and could be used to treat acne, temperatures above 45-50° C. are likely to result in significant discomfort when they persist, as illustrated inFIG.4A, for 4 seconds or longer. Accordingly, the pulse depicted inFIG.4Awould have limited application as a viable treatment to most patients. In one embodiment, the laser pulses described in connection withFIGS.4A and4Bresult in temperatures too high to be used for treatment, although they could be modified (e.g., by lowering pulse fluences, shortening pulse treatment times, etc.) to result in skin temperatures more suitable for treatment. In one embodiment, temperatures may be lowered by skin cooling, as described in connection withFIGS.5A and5B.

FIGS.5A and5Billustrate exemplary temperature profiles of a target skin area during a laser pulse according to a different mathematical model than those ofFIGS.4A-B. In the embodiment ofFIGS.5A and5B, the laser pulse has the same parameters as those ofFIGS.4A-B(wavelength λ=1727.5 nm; pulse duration=30 msec; beam diameter=2.8 mm, power=75 W; pulse energy=2.25 J; fluence=37 J/cm2). However, inFIGS.5A and5Bthe target skin area is cooled prior to, during, and after the application of the laser pulse.

Although many known methods and modes of precooling the skin may be used, the embodiment ofFIGS.5A and5Bare modeled on a system having a contact cooling element applied to a first skin area that includes a target skin area to be treated by the laser pulse. The contact cooling element includes a cooling window that, in some embodiments, directly contacts the first skin area, and the target skin area actually irradiated by the laser pulse is wholly located within the first skin area. Although a variety of materials may be used as the contact cooling window, in the embodiment ofFIGS.5A and5B, the cooling system includes a sapphire cooling window cooled by a thermoelectrical cooler (TEC) coupled to the window. The sapphire cooling window has a thickness of 3 mm and a diameter of 1 inch (25.4 mm), although many different sizes, shapes, thicknesses, and materials may be used different embodiments. For example, although the cooling window modeled in the embodiment ofFIGS.5A and5Bwas circular, other cooling window shapes such as square, rectangular, or other polygonal or nonpolygonal shapes could be used in different embodiments and for different tissue types. The cooling window was modeled as being cooled to a temperature of 5° C.

In alternative embodiments, non-contact cooling systems (e.g., cold air or other fluid circulated onto or across the surface of a target skin area) may be used to cool the skin. However, it is believed that the thermal resistivity of the skin, and the thermal coupling between the skin and gases such as air, typically preclude non-contact systems from providing adequate cooling capacity during the delivery of laser pulses to both effectively treat deeper target structures and prevent the skin surface from reaching temperatures likely to result in significant discomfort. Accordingly, contact cooling systems are preferred. In other embodiments, evaporative cooling systems (e.g., sprayed coolant evaporating from the skin) may be used.

InFIG.5A, the contact cooling element at 5° C. is applied to the skin at time t=0, and skin temperature falls rapidly along curve510to a target temperature of about 10° C. at time t=2 second, at which point (520) the laser pulse is applied to the skin. Delivery of the laser pulse to the target skin area is continued until a target surface temperature560of the target skin area is reached (540), at which point the laser pulse is terminated. Because the contact cooling element continues to cool the skin both during and after the laser pulse, the surface temperature falls rapidly along curve550after laser pulse termination.

FIG.5Billustrates the temperature profile of a sebaceous gland located at a depth of 650 μm below the skin surface in the cooling and laser pulse delivery process ofFIG.5A. When contact cooling is applied to the skin at time t=0, the temperature of the gland declines (curve510), but much less rapidly than the surface temperature, depicted inFIG.5A. The laser pulse is initiated at point520, and the temperature of the gland rises along line530until the laser pulse is terminated (540). The gland temperature thereafter falls along line550, but less rapidly than the surface temperature decline following the pulse termination inFIG.5A.

Because direct measurement of the gland temperature is difficult or impossible given its depth within the skin, in embodiments of the present invention, surface skin temperature may be monitored as an indirect indication of the gland temperature. Because the goal of the laser treatment is to heat the sebaceous gland to a damage threshold temperature, cooling the gland (as opposed to the skin surface) shown by curve510inFIG.5Bis undesired, but is an unavoidable consequence of the protective precooling of the overlying skin tissue. Precooling the overlying skin tissue to a desired surface temperature of about 10° C., as shown inFIG.5A, generates a downward cooling wave in the target skin area, propagating from the skin surface toward the deeper tissues in the dermis and hypodermis. The precooling process may be controlled such that, for a sebaceous gland in a known depth range, when the laser pulse is delivered to heat the target skin area, the precooled overlying skin remains below a damage threshold temperature while the target sebaceous gland reaches (or exceeds) a damage threshold temperature. This is facilitated by selecting a laser wavelength for which the absorption coefficient of sebum/sebaceous gland tissue exceeds that of water, the primary chromophore of most of the overlying dermal and epidermal tissue.

ComparingFIGS.5A and5B, precooling the skin allows the sebaceous gland to reach a temperature of about 78° C. at the termination of the laser pulse—about 13° C. above the surface temperature of target skin area at the surface (about 62° C.). Although the overlying tissue is unavoidably heated during pulse delivery, careful precooling before initiating the laser pulse allows the surface temperature to be precooled to a temperature well below the sebaceous gland at pulse initiation (about 10° C. for the skin surface vs. about 22° C. for the sebaceous gland as shown byFIGS.5A and5Bat point520). This temperature difference occurs because the cooling window creates a thermal gradient between the skin surface and deeper structures as heat is removed. In addition, the pulse energy at a wavelength of 1727.5 nm is more highly absorbed by the sebaceous gland than overlying tissue. Because of the selective precooling and differential absorption between the surface and the sebaceous gland, the non-targeted overlying tissue is heated by the laser pulse to a lower temperature (about 63° C.,FIG.5Aat point540) than the targeted sebaceous gland (about 81° C.,FIG.5Bat point540), minimizing damage to the non-targeted tissue and patient discomfort.

In some embodiments, the present invention includes a method of controlling the duration of a pulse to limit the surface temperature of a target skin area to a desired or target threshold using a handpiece capable of contact cooling and rapid, real-time temperature measurement of the skin during the delivery of one or more laser pulses.FIG.5Cdemonstrates a method of achieving such control by monitoring the temperature of a pulse during the delivery of a single pulse. The surface temperature of the skin may be determined one or more times during pulse delivery, and the pulse may be terminated based on one or more of the skin temperatures. In one embodiment, the skin temperature is periodically determined during the pulse delivery, and the pulse is terminated when the surface skin temperature reaches (or is within a desired interval of) a threshold temperature.

FIG.5C, illustrates a surface temperature profile during the delivery of the laser pulse ofFIG.5A. From time t=1.99 to t=2.00 seconds, the temperature of the skin near the surface (modeled inFIG.5Cat a depth of 100 μm) is relatively constant at about 10° C. (line510). At time t=2.00 seconds (520), the pulse is initiated and applied to the skin through the cooling window. Simultaneously, the first of a plurality of surface temperature determinations of the target skin area570is made. Pulse delivery continues along line530, and the surface temperature rises until the pulse is terminated at540. After pulse termination, the surface temperature falls as indicated by line550. During pulse delivery, multiple temperature determinations570are made at equal intervals, although the frequency of temperature sampling may vary based on a variety of factors such as the time frame desired for heating the tissue, thermal relaxation time of the target structure, pulse fluence, pulse power, pulse wavelength, and exogenous factors such as the target structure damage threshold, and other factors. Temperature determinations may be performed at a desired sampling interval, e.g., 100 msec or less (i.e., 10 or more temperature determinations per second) and may occur at uniform or non-uniform time intervals, e.g., varying based on the difference between a measured temperature and a desired threshold, or on other exogenous factors. In one embodiment, the temperature sampling interval is increased as the surface skin temperature approaches a desired temperature. Depending upon the sensing element and processor used, the surface temperature may be determined at a sampling or time interval of 0.001-100.0 msec (i.e., 1-100,000 psec, or performing 10 to 1 million temperature determinations per second).

FIGS.5A and5Billustrate methods of treating a sebaceous gland according to one embodiment of the present invention. Additional details of treating a sebaceous glans may be found in U.S. Pat. No. 10,864,380, which is incorporated herein by reference. However, embodiments of the present invention may be used to treat other structures in the dermis or hypodermis (e.g., sweat glands, hair follicles, etc.) by facilitating precise control of surface and deeper temperatures within a target skin area.

FIG.6is a schematic illustration, in block diagram form, of an embodiment of a therapeutic laser system600having a handpiece with contact cooling and temperature sensing for providing therapeutic laser pulses along a first optical path that is coaxial with a second optical path for sensing skin temperature for at least a portion of the first and second optical paths. A laser610, which is preferably a semiconductor laser, provides laser pulses having a wavelength with a high absorption coefficient in a target tissue. The target tissue may be sebaceous gland tissue, sweat gland tissue, fat, or other tissue. Laser610is optically coupled, e.g., by an optical fiber, articulating arm, or other optical coupling elements known in the art, to a handpiece620for delivery of one or more laser pulses to a target skin area. Although semiconductor (e.g., diode) lasers are preferred, it will be appreciated that other laser types (e.g., fiber lasers, dye lasers, etc.) may be used in different embodiments.

In a preferred embodiment, the laser source incorporates a grating element to reduce linewidth by amplifying only photons at a desired wavelength.FIGS.8A-Dillustrate laser sources that may be used in systems of the present invention.

Handpiece620includes a cooling system622for cooling a first skin area that includes a target skin area within the first skin area. Cooling system622includes a contact cooling element comprising a cooling window628maintained in a fixed position in contact with a heatsink portion of a thermoelectric cooler (TEC)630by a window frame626. Cooling window628may comprise any of a variety of IR-transmissive materials, including sapphire, ZnS, diamond, ZnSe, and other thermally conductive material that are transmissive to infrared light. In alternative embodiments (not shown), the contact cooling element may comprise components or structures in addition to cooling window628, such as a copper (or other material having a high thermal conductivity) cooling element that is not light-transmissive to provide additional cooling capacity.

TEC630may be a Peltier-type cooler and has a warm side and a cold side (not shown). The heatsink portion of the TEC630is part of the cold side and is used to remove heat from the cooling window628to maintain the cooling window at desired temperature as it contacts the first skin area. A cooling medium632removes heat from the hot side of the TEC630to prevent heat buildup in handpiece620. In one embodiment, the cooling medium comprises circulating cold water, although other thermally conductive fluids or other materials may be used in different embodiments. In preferred embodiments, the cooling medium is circulated to and from TEC630from a reservoir (not shown) that is not part of the handpiece.

To ensure efficient skin cooling, it is necessary to maintain good contact between the skin and the cooling window628during treatment. In one embodiment, the invention comprises a laser treatment system including a handpiece having one or more contact sensing elements to detect when the cooling window628is properly in contact with the first skin area. The contact sensing elements may determine one or more contact parameters such as contact, force, or pressure. In one embodiment, a safety interlock may be provided to prevent the delivery of laser pulses to the skin of the patient unless one or more contact parameter conditions are fulfilled (e.g., all contact elements in contact with the skin, and/or a threshold force such as 0.5 pounds is being applied to the skin, and the conditions must be satisfied during the delivery of each laser pulse). The contact sensing element(s) may be coupled to, or separate from, cooling window628and/or frame626(e.g., a heatsink surrounding the cooling window periphery), and may comprise, e.g., one or more electrical contacts capable of sensing electrical activity, conductivity, or resistance of the skin indicative of adequate contact between the skin and the handpiece (e.g., cooling window). Other contact sensing elements (e.g., ultrasonic sensors) detecting different skin parameters associated with proper contact (e.g., force, vibration, pressure, temperature, the presence of sweat or skin oils) may also be used.

One or more skin contact indicators (not shown) may alert a user to the contact status between the skin and cooling window628. The skin contact indicator may indicate when the contact element(s) are—or are not—in good contact with the first skin area and may prompt the user to manipulate the handpiece to restore good contact when necessary. The skin contact indicator(s) may comprise, e.g., an LED indicator on handpiece620that displays a first color when good skin contact exists and a second color when the window628is not in proper contact with the skin. Other indicators, such as an audible sound or alarm, may also be provided, and the system may be interlocked such that the system will not apply (or will terminate) a laser pulse if good contact between the cooling window268and the skin is absent.

Handpiece620may in some embodiments further includes a temperature determination unit (TDU) for determining a surface temperature of the target skin area. The TDU may, in various embodiments, sense the temperature of the target skin area one or more times before (e.g., during a precooling step), during, or after (e.g., during a postcooling step) laser pulse delivery. During delivery laser pulse(s) to a target skin area, the skin surface temperature may be influenced by two different heating mechanisms, including energy absorbed directly from the laser, and thermal bloom resulting from energy conducted from deeper skin tissue as the thermal energy absorbed by deeper structures relaxes into the environment. Thermal bloom from deeper structures back to the skin surface may be a significant cause of epidermal damage in laser systems targeting relatively deep structures such as sebaceous or sweat glands. Therapeutic laser systems such as system600enable improved treatment outcomes by ensuring that the surface temperature of a target skin area remains below a desired surface temperature even while heating deeper structures to higher temperatures, minimizing both skin damage and patient discomfort.

The TDU may comprise a temperature sensing element for generating a first signal indicative of skin surface temperature, and a processor for processing the first signal to determine the surface temperature. The TDU may sense the surface temperature of the target skin area one or more times before, during, or after delivery of laser pulse(s) from laser610. The TDU may be capable of sensing the surface temperature of the target skin area at from 10 to 1 million times per second. In one embodiment, the temperature sensing element of TDU comprises an infrared (IR) radiation detector to detect IR energy radiating from the surface of the target skin area through the cooling window628, and a processor (e.g., controller640as discussed below) to determine the surface temperature of the target skin area based on data received from the TDU. It will be appreciated that non-IR temperature sensors (e.g., an electrical temperature sensor) may also be used. In the embodiment ofFIG.6, the TDU may be a part of the handpiece620, while in other embodiments, the temperature sensing element, the processor, or the entire TDU may be located outside the handpiece. In preferred embodiments, an IR temperature sensing element is provided as part of the handpiece620. Additional details about the TDU may be found in co-pending application U.S. application Ser. No. 17/120,237, filed 13 Dec. 2020, which is hereby incorporated by reference in its entirety.

Handpiece620also includes a plurality of optical elements634to sequentially direct laser pulses along a first optical path within the handpiece to a target skin area, and to direct IR energy from the target skin area along a second optical path that is coaxial with and generally counterdirectional to the first optical path for at least a portion of both optical paths. Additional details on embodiments of the optical elements are provided in connection withFIGS.7A-Band in the aforementioned '237 application. To facilitate the counterdirectional flow of laser and IR energy, the handpiece comprises a first optical element (not shown) having a first open area through which the first optical path passes, i.e., the laser pulses do not engage the first optical element, and pass through the first open area. In contrast to the laser pulses, however, the IR energy does engage the first optical element, which is preferably a reflective optical element (e.g., a mirror). The first optical element directs the IR energy from the target skin area to the temperature sensing element in the TDU. The signal from the temperature sensing element is processed to determine skin surface temperature at a desired rate of from 10 to 1 million times per second.

The plurality of optical elements634in handpiece620also includes at least one second optical element (not shown), and more preferably a plurality of second optical elements, that are engaged by the laser pulses and/or IR energy from the target skin area. In one embodiment, shown in more detail inFIGS.7A-7B, the at least one second optical element comprises eight (8) optical elements, with the first optical path (i.e., the laser pulse path) engaging all eight optical elements, and the second optical path engaging five of the optical elements in addition to the first optical element. The optical elements may include one or more of lenses (e.g., plano-convex lenses, turning mirrors, meniscus lenses, aspherical lenses, flat lenses, etc.), mirrors (e.g., aspherical mirrors), or other optical elements (e.g., optical parametric oscillators) to direct the laser pulses received from the optical laser source (e.g., via an optical fiber cable) to a target skin area. In preferred embodiments, the at least one second optical element comprises a plurality of lenses (e.g., at least three lenses) and at least one mirror, and the first and second optical paths engage at least two lenses and the last least one mirror. The optical elements634may in various embodiments concentrate the laser energy to a single target skin area, or may include beam-splitting elements to split each pulse beam into multiple beams to treat a plurality of target skin areas simultaneously.

In one embodiment, the plurality of optical elements634includes a movable scanning mirror capable of movement to direct laser pulses to different target skin areas within a first skin area cooled by cooling window628. The movable scanning mirror also limits IR energy received by the TDU to IR energy from substantially only the target skin area to which the laser is directed at any given time, i.e., it eliminates IR light from other skin areas within the larger first skin area cooled by cooling window628, which is significantly larger than a single target skin area. In embodiments including a movable scanning mirror, after a first target skin area is treated by one or more laser pulses, the scanning mirror is repositioned to direct subsequent pulses to a new (i.e., second, third, etc.) target skin area within the larger first skin area cooled by the cooling window628. When a desired number of target skin areas have been treated at a single cooling window position, the user may reposition the cooling window628to a new position covering a new skin area, and a different group of target skin areas within the new skin area may be treated by laser610using scanner in handpiece620. In one embodiment, the position of the movable scanning mirror may be adjusted on two or more axes, e.g., by one or more motors, thereby directing succeeding pulses to different target skin areas within the first skin area, enabling treatment of a relatively high proportion of the total area in contact with the cooling window. In alternative embodiments, the plurality of optical elements634may not include a scanner. Additional details on the use of a scanning mirror may be found in the '237 application previously noted.

Referring again toFIG.6, system600further includes a controller640, which may comprise one or more processing elements such as microprocessors, microcontrollers, field programmable gate arrays (FPGAs), etc. to control the operations of the laser treatment system. Controller640includes a pulse timing control unit642that controls the timing of the laser pulses from laser610, including initiating the pulse at a first timepoint and terminating the pulse at a second timepoint. The pulse timing control unit642may receive data from temperature sensor624, and may initiate the therapeutic laser pulse at a first timepoint based on, e.g., a manual signal from a user or a determination that target skin area has been cooled to a desired surface temperature (e.g., 15° C., 10° C., 5° C., 0° C., −5° C., −10° C., etc.). Pulse timing control unit642may also terminate the therapeutic laser pulse at a second timepoint based on, e.g., a predetermined pulsewidth or a determination that the surface temperature of the target skin area has reached a threshold surface temperature (e.g., indicating that a deeper target structure such as a sebaceous gland has reached a damage threshold temperature, e.g., 60° C.-75° C.).

Controller640also includes a temperature sensing control unit644that controls the operation of the TDU. Temperature sensing control unit644ensures that the TDU determines the surface temperature of a target skin area at a desired (e.g., programmed or predetermined) sampling rate such as 10 or more times per second. Controller640may synchronize the operations of the temperature sensing control unit644with the pulse timing control unit642. In one embodiment, the pulse timing control unit642and the temperature sensing control unit644may comprise one or more of software, firmware, or other programming code operating in the controller640. In one embodiment, the pulse timing control unit642and the temperature sensing control unit644may comprise separate processors or sub-processors, and/or separate executable code programs comprising one or more of software, firmware, etc., within controller640. A wide variety of hardware and software designs may be used to achieve the functions described herein, and all are considered as within the scope of the present disclosure.

Controller640may also control other operations within the therapeutic laser treatment system600(e.g., software and firmware units and subunits, timers, mechanical or electrical elements or subsystems, etc.). These functions may also include, without limitation, control of the positioning of a movable scanning mirror for determining a target skin area, as discussed above and in greater detail in connection withFIGS.7and9A-9F. Controller640also controls the operation of cooling system622, including without limitation the temperature at which the cooling window is maintained (which may be determined by a user or by the patient's skin type as described in connection withFIG.6B), the cooling capacity (i.e., the thermal energy removal rate of the TEC), status alarms, etc.

A user interface650is preferably provided to allow a system user to select or program one or more parameters (e.g., beam diameter or spot size, fluence, wavelength, target temperature of the surface of the target skin area, cooling temperature of the target skin area at which a pulse may be delivered, etc.) to control the operation of therapeutic laser system600. User interface650may also display various status indicators and data associated with the system and/or a treatment session, such as the current laser parameters, duration of treatment, number of pulses delivered, etc. Controller640may also receive and process inputs from the user interface650, and provide outputs to the user interface. In alternative embodiments, the user interface may be omitted.

Finally, the system600includes a power supply660for providing power to one or more of the foregoing portions of the system. In one embodiment, power supply660may comprise a power supply coupled to a standard NC power outlet to convert AC to DC power at one or more voltages, and may include a battery (e.g., for backup in the event of a power outage), a supercapacitor, etc. Power supply660also provides power to controller640, which in turn includes a current-controlled power supply for driving the laser610and/or other system components and subassemblies at rapid switching rates based on inputs from pulse timing control unit642, temperature sensing control unit644, cooling system622, temperature sensor24, and scanner634.

FIG.6illustrates a system according to certain embodiments of the invention involving cooling the skin before, during, or after pulse delivery. Alternative embodiments of the invention include systems with no cooling of the skin, or without cooling of the skin during one or more of the periods before, during, or after delivery of the therapeutic laser pulse. Additional alternative embodiments include systems in which different cooling capacities (i.e., rate of heat removal from the skin) are used in the periods before, during, or after delivery of the laser pulse, and during portions of these periods.

FIGS.7A and7Bare perspective views, respectively, of one embodiment of a handpiece700for providing laser therapy to a patient's skin as part of a laser treatment system. The handpiece700provides contact cooling of the skin, at one or more timepoints before, during, or after application of therapeutic laser energy to the patient's skin.

Handpiece700includes a proximal end702and a distal end704, and comprises a housing710having a shape adapted for holding by a user (e.g., a physician or technician), and having an inner volume shielding a plurality of optical elements. An optical cable705, which comprises an optical fiber core (not shown), is coupled to the proximal end702of the handpiece700. Optical cable705is coupled to a laser source (not shown) which generates and delivers laser pulses to the handpiece900through the cable. Optical cable705, and specifically the optical fiber therein, terminates inside the proximal end702of handpiece700in a standard optical coupler (not shown) such as an SMA coupler, although other standard optical couplings may be used.

At the distal end704of the handpiece700, a contact cooling unit715includes a cooling window720to cool, by direct contact, a first skin area equal in size to the cooling window. In addition to the cooling window720, contact cooling unit715also comprises other optical elements, including a cooling window heatsink716that surrounds the cooling window720and a thermoelectric cooler (TEC) (not shown). Laser pulses from optical cable705pass through handpiece700along a first optical path and are applied to a target skin area, which comprises a smaller skin area within the first skin area cooled by the cooling window.

As shown inFIG.7B, housing710of handpiece700includes an optical aperture or port714through which laser pulses exit the housing and travel along the first optical path through the cooling window720to the target skin area. Cooling window720is spaced a desired distance from housing710by cooling unit715, which also functions as a spacing member to allow a user to visualize the area being cooled and treated by the handpiece900.

As noted in the discussion ofFIG.6, in some embodiments a contact sensing element or system may be provided to ensure good contact between the skin of the patient and the cooling window during treatment. In various embodiments, contact may be sensed by electrical contacts (e.g., electrodes capable of sensing changes in electrical conductivity or resistivity of the skin), or by detecting other skin parameters associated with contact such as force, pressure, vibration, temperature, sweat, etc. In a particular embodiment, the invention comprises systems and methods for laser treatment using a handpiece capable of sensing one or more of contact, pressure, or force on the external periphery of the cooling window. By sensing the pressure or force between the contact sensor and the skin, the system can determine when contact between the skin and cooling window is sufficient to enable effective treatment to be achieved.

Poor contact may result in non-uniform cooling such that one or more target skin areas within the first skin area (i.e., the skin area in contact with the cooling window) are not cooled to a sufficiently low temperature to avoid pain, discomfort, or damage to overlying a target during laser pulse(s), especially for deeper target structures such as a sebaceous gland. Poor contact may involve a failure to fully contact the skin with the cooling window; failure to maintain even pressure of the cooling window across the first skin area; maintaining excessive pressure on the skin; or maintaining too little pressure. For example, if part of the cooling window is not in contact with the skin, or pressure is not evenly maintained, cooling may be uneven. Where cooling is uneven, some target skin areas may be overheated, while others may be underheated, resulting in poor efficacy. Additional details on contact, force, and pressure sensing may be found in related U.S. Provisional Application Ser. No. 63/125,354, filed Dec. 14, 2020, entitled “Dermatological Laser Systems and Methods with Pressure Sensing Handpiece,” incorporated by reference herein in its entirety.

In alternative embodiments (not shown) a contact cooling unit may be omitted, and the handpiece may comprise a pulse delivery region to deliver the laser pulses through a pulse delivery aperture that does not comprise a contact cooling unit.

In preferred embodiments, a contact indicator may be provided, which may comprise a user interface similar to user interface755(FIG.7A). The contact indicator may provide one of a contact feedback parameter, a force feedback parameter, and a pressure feedback parameter to a user. The feedback parameter may indicate to a system user, based on contact, force, and/or pressure, one or more of the following feedback parameters: an indication of whether or not the handpiece (e.g., as confirmed by each of the plurality of contact sensing elements) is in contact with the patient's skin; an indication of the force exerted by the handpiece against the patient's skin; an indication of the pressure exerted by the handpiece against the patient's skin; an indication of one of the variation in pressure and the variation in force at one or more of the different locations of the contact sensing elements; an indication one of the variation in pressure and the variation in force between two or more of the contact sensing element locations; an indication that the pressure exerted by the handpiece against the skin exceeds a minimum pressure threshold; an indication that the pressure exerted by the handpiece against the skin is less than a maximum pressure threshold; an indication of the force at each of the different locations; an indication of the variation in force between two or more of the different locations; an indication that the force exerted by the handpiece against the skin exceeds a minimum force threshold; and an indication that the force exerted by the handpiece against the skin is less than a maximum force threshold.

FIGS.8A-8Dillustrate exemplary laser sources usable in laser treatment systems of the present invention (e.g., the system ofFIG.6) that, when coupled with a handpiece (e.g., the handpiece ofFIGS.7A and7B) having one or both of a skin cooling system and a temperature determination unit (TDU), provides improved temperature control for treating tissues with poor chromophore selectivity. Each of the lasers incorporates a grating element to reduce the amplification of longitudinal modes outside of a desired center wavelength (e.g., a wavelength ranging from about 1725-1728 nm near the peak ratio of the absorption coefficients of sebum and water, such as about 1725.5, 1726, 1726.5, 1727, or 1727.5 nm). Use of such a laser helps ensure that substantially all of the available laser energy is within a desired tolerance value of the wavelength having the maximum absorption coefficient ratio of sebum to water, which helps to reduce discomfort associated with applying laser pulses to sebaceous gland tissue. When used in a system that also provides contact cooling of the skin, the laser sources illustrated inFIGS.8A-8Dcan reduce laser energy absorbed by non-target tissues above a sebaceous gland.

FIG.8Aillustrates a distributed feedback (DFB) laser800, which provides a continuous Bragg grating reflector810disposed along (and generally parallel to) the entire gain medium808of the laser.

If sufficient gain is present within gain medium808, no additional outcoupling mirror is required for the DFB laser, and the continuous Bragg grating reflector810is responsible for all optical feedback to dampen out undesired modes during generation of laser light, resulting in laser emission having a narrow linewidth that is less than half of the linewidth that would be present in the absence of the continuous Bragg grating reflector element810. In one embodiment, the gain medium808is such that it would have a linewidth of 1000 GHz or more in the absence of the continuous Bragg grating reflector element810, and the Bragg reflector is selected and incorporated into substrate802so as to reduce the linewidth of the emitted light818to 500 GHz or less, and preferably 300 GHz or less. The frequency selection of the continuous Bragg grating reflector810may be much narrower than that provided by a broad band mirror and as such a DFB laser will operate in a single longitudinal mode.

FIG.8Billustrates a distributed Bragg reflector (DBR) laser850, which may also be used in embodiments of the present disclosure to reduce the linewidth of the laser light applied to the patient's skin. The DBR laser includes many of the elements of the DFB laser800ofFIG.8A, and like numerals are used to refer to like structures inFIG.8B. However, in DBR laser850, the fully reflective mirror814ofFIG.8Ais replaced by a distributed Bragg grating851along the longitudinal direction (i.e., generally parallel to gain medium808) and outside of the gain region characterized by the presence of gain medium808. Such a distributed continuous grating reflector tends to reflect a narrower band of wavelengths, increasing the wavelength stability of the diode laser.

Referring again toFIG.8B, DBR laser850includes a gain region820in which the gain medium808is pumped to generate laser light, and a feedback region822coupled to the gain region that provides feedback to reduce the amplification of undesired modes of laser light in the gain region. DBR laser850also includes a semiconductor substrate802that includes the gain medium808, which may be pumped by an electrode pair (e.g., anode803and cathode805) to produce laser light. Substrate802may be fabricated in layers using known processes, and may include a p-type layer804, an n-type layer806, or additional layers (not shown). DBR laser850includes a partially reflective mirror816at one end, and laser light emitted from the mirror may be directed to skin tissue of a patient via a handpiece coupled to the DBR laser. As previously noted, fully reflective mirror814(FIG.8A) is replaced by distributed Bragg grating reflector element851disposed in a feedback region822that is outside—but optically coupled to—the gain region820. Distributed Bragg grating reflector element851is selected to reflect back into the gain region820a desired mode (e.g., a first order mode) of laser light, which results in amplification by the gain medium808of the selected wavelength reflected by the distributed Bragg grating851and the suppression of all other wavelengths.

The net result, with proper selection of distributed Bragg grating reflector851, is an optical feedback from the distributed Bragg grating that dampens out undesired modes of laser light in the gain region820, and a narrow linewidth of the output light818that is less than half of the linewidth that would be present in the absence of the distributed Bragg grating reflector element. In one embodiment, the gain medium808is such that it would have a linewidth of 1000 GHz or more in the absence of the continuous Bragg grating reflector element851, and the Bragg reflector is selected and coupled to the gain medium808so as to reduce the linewidth of the emitted light818to 500 GHz or less, preferably 300 GHz or less, and more preferably 200 GHz or less.

FIG.8Cillustrates a volume holographic grating (VHG) laser system860that may be used in embodiments of the present disclosure. In the embodiment ofFIG.8C, a volume holographic grating Bragg reflector is located externally to a semiconductor laser substrate802and optically coupled thereto to dampen out undesired modes. In particular, a VHG Bragg grating861is placed as a separate element in front of the diode laser. This implementation has the advantage of thermally decoupling the reflector from the diode laser itself, further improving thermal wavelength stability.

In the VHG system860, a semiconductor laser substrate802includes a gain medium808pumped by an electrode pair (803,805) to produce laser light. Substrate802may include a p-type layer804, an n-type layer806, or additional layers (not shown). Laser substrate802further includes a fully reflective mirror814at one end and partially reflective mirror816at another end. Laser light817emitted from partially reflected mirror816exits the semiconductor laser substate802and engages volume holographic grating (VHG) Bragg element861, which reflects a portion of the light back along path817, and transmits a portion of the light818for application to the skin of the patient via a handpiece coupled to the VHG laser system860.

While the distributed Bragg grating reflector element851ofFIG.8Bis located outside the gain region but within the semiconductor laser substrate802, the VHG Bragg element861ofFIG.8Cis located entirely outside of the diode laser substrate802. In addition to thermally decoupling the VHG Bragg element from the diode laser substrate802as noted above, the VHG Bragg element is selected to reflect back into the gain medium808a desired mode (e.g., a first order mode) of laser light817received from the substrate via mirror816. Like the distributed Bragg grating851ofFIG.8B, VHG Bragg element861results in a feedback amplification of a selected wavelength reflected back into the gain medium808from the VHG, and the suppression of all other wavelengths.

By selecting the VHG Bragg element861to provide a feedback amplification of only a desired mode, undesired modes of laser light in the gain medium808are eliminated, and the output light818has a linewidth that is less than half of the linewidth that would be present in the absence of the VHG Bragg element861. In one embodiment, gain medium808would have a linewidth of 1000 GHz or more in the absence of the VHG861, and the VHG is selected and coupled to the gain medium808so as to reduce the linewidth of the emitted light818to 500 GHz or less, and preferably 300 GHz or less.

FIG.8Dillustrates an external cavity diode laser (ECDL) system870. In an ECDL, the output light815from a gain medium808of a diode laser substrate802is first collimated by a lens819(or other optical elements), and then sent along path817onto an external cavity diode laser (ECDL) Bragg grating871which reflects a narrow longitudinal mode back into the diode laser along path817, through collimating lens819, and the path taken by the output light815from the diode laser. Due to the typically larger cavity length in the ECDL configuration870, extremely narrow linewidths of <1 MHz can be achieved.

The ECDL system870functions similarly to VHG system860, in that the grating element871(or861in the VHG system) is located entirely outside the semiconductor laser substrate802. Referring toFIG.8D, the ECDL diode laser substrate802includes a gain medium808pumped by an electrode pair (803,805) to produce laser light, and may include a p-type layer804, an n-type layer806, or additional layers. A fully reflective mirror814is provided at one end of the substrate802, and partially reflective mirror816is provided at the other end. Laser light815is emitted from partially reflected mirror816and passes through collimating optics819(e.g., a lens) before engaging the ECDL Bragg grating871, which is selected to reflect a desired mode of the light back along path817, and to transmit a portion of the light818for application to the skin of the patient via a handpiece coupled to the ECDL system870.

Because it is positioned entirely outside the diode laser substrate802, the ECDL grating871is thermally decoupled from the substrate, and by reflecting back a desired mode into the gain medium808, ECDL Bragg grating871results in a feedback amplification of a selected wavelength and the suppression of all other wavelengths.

As with the VHG861, ECDL Bragg grating871is selected to provide a feedback amplification of only a desired mode, eliminating undesired wavelengths of light in the gain medium808, and resulting in output light818having a linewidth that is less than half of the linewidth that would be present in the absence of ECDL Bragg grating871. In one embodiment, gain medium808would have a linewidth of 1000 GHz or more in the absence of the ECDL Bragg grating871, and the ECDK Bragg grating is selected and coupled to the gain medium808so as to reduce the linewidth of the emitted light818to 500 GHz or less, and preferably 300 GHz or less.

Laser sources as shown inFIGS.8A-8Dhave not been utilized in dermatological applications because it has been thought that the increase in complexity of such systems, and the added expense, fabrication time, and failure modes exceed any benefit from their use. Moreover, instances of poor chromophore selectivity can in some cases be avoided by simply selecting a different wavelength for which the target chromophore has relatively good selectivity over a non-target chromophore. Consequently, instances of poor chromophore selectivity such as discussed in connection with the treatment of acne have been largely dismissed. Moreover, solid-state lasers can typically provide sufficient power to heat target structures in a much narrower timeframe, which is advantageous for small target structures with short TRTs. However, such lasers are only available for a small selection of wavelengths.

FIGS.9-11are graphs illustrating the improved control of heating sebum tissue using systems of the present disclosure.FIG.9is a graph showing wavelengths for which sebum absorption is higher compared to the absorption in water (curve910), displayed on the left-hand side y-axis as the ratio of the absorption coefficients of sebum and water. A value of curve910above 0 shows preferential absorption in sebum compared to the water. The three gaussian profiles920,930,940are abstracted output spectra of three typical unstabilized diode lasers used in prior art systems, with a target wavelength of 1725 nm. A typical unstabilized diode laser as used in prior art approaches has multiple effects influencing its center wavelength and linewidth. The width of the gaussian profile as a whole (i.e., from the left side of curve930to the right side of curve940), incorporating all three gaussian provides, illustrates the expected linewidth of an unstabilized diode laser for one center frequency with manufacturing variances taken into account. During manufacturing, the center wavelength of a diode laser varies from unit to unit within a certain wavelength range. The two outer gaussian spectral profiles illustrate the expected upper and lower ranges in a typical manufacturing environment. While the diode laser920that is in the center of the range matches the absorption profile of the sebaceous gland for the wavelength range with maximal preferred absorption (having a center wavelength peak at just over 1720 nm), it will be noted that both of the other curves930,940represent lasers that would typically be received from a manufacturer, but which would provide poor performance, as indicated by the negative absorption values for the ends of curve910—indicating that water would more strongly absorb light at those wavelengths than sebum, resulting in overtreatment and pain of the tissue above the sebaceous gland, and likely undertreatment of the sebaceous gland.

FIG.10is a graph illustrating the improvement in wavelength stabilization and control of thermal damage to tissue for systems of the present invention compared to prior art systems at wavelengths discussed in connection withFIG.3regarding the region of poor chromophore selectivity for sebum compared to water (e.g., about 1700-1740 nm).FIG.10shows that thermal effects of lasers contribute to wavelength instability. Curves1010and1020demonstrate how the output of an example prior art laser (e.g., without grating stabilization of wavelength as disclosed herein) would shift if the operational conditions changed from 20° C. to 30° C. These curves illustrate the need for controlling the laser operating temperature, which can be challenging. A change in operating temperature of 10° C. can easily result in a shift of 7 nm in the output wavelength, which could result in a significant increase in pain to the patient, undertreatment of the target chromophore (sebum) and overtreatment (e.g., burning) of the overlying tissue, for which water is the dominant chromophore. Especially in pulsed operation, the temperature of the laser diodes can easily change by 20-40° C. when switched on, adding additional difficulty to controlling the output spectrum of the laser.

Curves1030and1040illustrate the narrowing of the linewidth that is expected when designing a laser with the same target center wavelength in a system using a distributed feedback (DFB) laser source (e.g., the laser ofFIG.8A) to narrow the linewidth of laser pulses in the treatment of tissues at wavelengths of about 1725-1728 nm. The linewidth—illustrated by the width of curves1030and1040—is significantly narrower than that of curves1010and1020of prior art lasers with unstabilized wavelengths. Without being bound by theory, it is believed that a linewidth reduction of about a factor of 10 can typically achieved using embodiments of the present invention.FIG.10also illustrates the reduction of the wavelength change caused by a temperature shift of a DFB laser. Curves1030and1040show that a shift in the output wavelength of systems according to the present disclosure limited to about 1-2 nm can be achieved despite an operating temperature change from 20° C. to 30° C. In the example ofFIG.10, a reduction in wavelength shift by a factor of 6 is achieved compared to the prior art systems. The increased temperature stability directly translates into less spectral (wavelength) shift during pulsed operation of the laser. The laser diodes still heat up by a significant amount, but the resultant shift of the output spectrum is significantly reduced.

Accordingly, in some embodiments of the present invention, a cooling system is provided to cool a grating-stabilized laser source to minimize the thermal wavelength shifts occurring as the laser heats up during operation. In one embodiment, the cooling system comprises a thermoelectric cooler (TEC) coupled to a baseplate to which the laser modules are mounted. In one embodiment, the cooling system comprises circulating water through channels in the baseplate.

FIG.11is a graph overlaying the output spectrum of idealized diode laser modules according to both the prior art (curves1110and1120) and embodiments of the present disclosure (curves1130and1140) with the absorption spectrum of sebum relative to water (curve1105). Ideally, the output spectrum of the laser should overlap with the absorption spectrum in the region of the maximum absorption coefficient ratio to preferentially heat the sebum instead of the surrounding tissue. When creating a train of multiple pulses of therapeutic fluence, the accumulation of thermal energy inside the diode lasers results in a temperature increase of the laser diodes of roughly 30° C. As shown inFIG.11, even for a perfectly selected diode laser of the prior art (curves1110and1120) this temperature change will result in a shift of the output spectrum of the laser into a region for which the laser light is more strongly absorbed by water rather than sebum, meaning that the system fails to provide laser energy in the desired range to treat acne and causing significant pain, overtreatment of tissue overlying the sebaceous gland, and undertreatment of the sebum tissue. This would translate into a larger temperature rise in the tissue above the sebaceous gland rather than the gland itself, and as a result the damage to the overlying tissue would be greater than the damage to the sebaceous gland. This effect can be mitigated by limiting the number of consecutive pulses to limit the increase in the temperature rise of the laser (reducing the amount of the shift), or by firing the laser into a beam dump before directing the laser onto the target tissue. Both options, however, require a more complex design. In addition to the described thermal effect, manufacturing variation between diode laser modules (e.g., as discussed inFIG.9) can result in an additional shift of the center wavelength of +/−20 nm which would necessitate additional controls or lower yield as the output spectrum might further shift outside of the wavelength range of preferential absorption by sebum.

FIG.11further illustrates that, for a DFB laser according to one embodiment of the present disclosure (curves1130and1140), the reduction in spectral shift with temperature results in an output spectrum that is still favorably absorbed by the sebum even after a 30° C. temperature increase of the laser. Consequently, the output spectrum still results in a preferential heating of the sebaceous gland compared to overlying tissue comprising water as the primary chromophore, even after a long pulse train.

FIG.12Aillustrates a flowchart depiction of a method for treating a patient using a laser, in accordance with embodiments herein. A target tissue of a patient to be treated using a laser is selected (1210).FIG.12Billustrates a flowchart depiction of a more detailed description for selecting the target tissue of the patient to be treated, in accordance with embodiments herein.

Turning now toFIG.12B, the target tissue to be treated includes a first tissue structure that has a target chromophore as well as a second tissue structure having a non-target chromophore (1212). That is, the target tissue includes both a structure having a target chromophore to be thermally damaged by absorption of laser light, and a structure having a non-target chromophore for which absorption of light is not intended or desired.FIG.12Balso illustrates that the target tissue has poor chromophore selectivity, as indicated at1216and1218. In particular, the absorption coefficient of the target chromophore (CTarget) exceeds the absorption coefficient of the non-target chromophore (CNon-Target) over a first frequency range from which a laser wavelength may be selected (1216). However, while the target chromophore has higher absorption than the non-target chromophore over the first laser frequency (or wavelength) range, it does not substantially exceed that of the non-target chromophore so as to enable thermal damage to the target chromophore structure while providing little or no damage to the non-target chromophore. In particular, the maximum value of the ratio of CTargetto CNon-Targetis less than 10 over the entire first frequency range. Thus, the target chromophore does not, for any laser frequency within the first frequency range, absorb 10 times or more of the energy compared to the non-target chromophore (1218). Only when both conditions1216and1218are satisfied is the target tissue structure considered one having poor chromophore selectivity, to which the embodiment ofFIGS.12A-12Cis directed.

Returning toFIG.12A, upon selecting a target tissue having poor chromophore selectivity for providing treatment, a laser, such as a semiconductor or diode laser is provided (1220).FIG.12Cillustrates a flowchart depiction of a more detailed description for providing a laser comprising a semiconductor or a diode laser system, in accordance with embodiments herein.

InFIG.12C, a laser system is provided, wherein the laser system includes a laser gain medium that, in the absence of a grating filter element, is adapted to provide laser light having a center frequency within the first frequency range and a first frequency linewidth of at least 1000 GHz (1222). Providing the laser system also includes using a grating filter element that is capable of providing feedback to the light in the laser gain medium, and also capable of reducing the first frequency linewidth to a second frequency linewidth that is no more than half of the first frequency linewidth (1224). Further, using the laser system also includes using a system that includes an output coupling capable of providing a predetermined fraction of light from the laser gain medium (1226). The method then continues to block1230ofFIG.12A

Returning toFIG.12A, upon providing a laser (1220), a laser light is generated in a resonant cavity of the laser system (1230). The generated laser light may then be filtered using the grating filter element (described in block1224ofFIG.12C) of the laser system (1240). Using the output coupling (described in block1226ofFIG.12C), a laser light output is provided (1250). In some embodiments, the laser light output may have a center frequency and a second frequency linewidth of no more than 500 GHz.

The laser light output may be applied to the target tissue (1260). This application enables the selective heating of the target chromophore to be performed, relative to the non-target chromophore. As such, treatment of the first tissue structure having the target chromophore may be heated to the maximum extent relative to the second tissue structure having the non-target chromophore.

In some embodiments, the system may also include a safety interlock preventing the laser source from generating the therapeutic laser pulse unless a desired force and/or pressure feedback parameter is provided by the contact indicator. In addition to the foregoing feedback parameters, the safety interlock may prevent the laser source from operating unless one of the following is provided: an indication that the pressure difference between the highest and lowest pressures among the different locations is less than a maximum pressure difference threshold, an indication that the difference between the highest and lowest applied forces among the different locations is less than a maximum force difference threshold; and an indication that desired cooling time has elapsed; and indication that a laser pulse has not exceeded a maximum pulse duration.

In various embodiments, the present invention relates to the subject matter of the following numbered paragraphs.

201. A system for treating a target tissue having poor chromophore selectivity, the target tissue comprising a first tissue structure comprising a target chromophore and a second tissue structure comprising a non-target chromophore, wherein the absorption coefficient of the target chromophore continuously exceeds the absorption coefficient of the at least one non-target chromophore over a first frequency range of less than 6000 GHz, and the maximum value of the ratio of the absorption coefficient of the target chromophore to the absorption coefficient of the non-target chromophore over the first frequency range is less than 10, the system comprising:a) a diode laser system having at least one semiconductor laser generating pulsed laser light, the at least one semiconductor laser comprising:1) a semiconductor laser gain medium that, in the absence of a grating filter element, produces laser light having a center frequency within the first frequency range and a first frequency linewidth of at least 1000 GHz;2) a grating filter element capable of providing feedback to the light in the laser gain medium, wherein the grating element is adapted to reduce the first frequency linewidth to a second frequency linewidth that is no more than one-half of the first frequency linewidth; and3) an output coupling adapted to output a desired fraction of light from the semiconductor laser gain medium as laser pulses;b) a handpiece to receive the laser pulses output from the diode laser system and to direct the laser pulses to the target tissue along a first optical path, the handpiece comprising:1) an optical connector to receive the laser light output from the output coupling of the diode laser system;2) a contact cooling element comprising a cooling window adapted to contact and cool a first skin area of the patient, wherein the cooling window comprises a thermally conductive material and wherein the target tissue comprises a volume of tissue having an external skin surface within the first skin area; and3) at least one optical element located in the first optical path and adapted to direct the laser light along the first optical path from the optical connector through the cooling window into the target tissue; andc) a temperature determination unit that determines a surface temperature of the target tissue one or more times before, during, or after the application of each laser pulse.

202. The system of numbered paragraph 201, wherein the cooling window comprises a thermally conductive material that is transmissive to infrared energy, and the temperature determination unit determines a surface temperature of the target tissue based on infrared energy radiated from the target tissue through the cooling window along a second optical path.

203. The system of claim 202, wherein the handpiece comprises at least one reflective optical element located in the second optical path, and wherein the temperature determination unit comprises:1) a temperature sensing element for sensing infrared energy radiated from substantially only the target tissue through the cooling window along the second optical path, the temperature sensing element generating a first signal indicative of the infrared energy radiating along the second optical path, wherein the infrared energy radiating along the second optical path engages the at least one reflective optical element before being directed onto the temperature sensing element; and2) a processor adapted to determine the surface temperature of the target tissue one or more times during or after the application of each therapeutic laser pulse based on the first signal.

204. The system of claim 201, wherein the diode laser system further comprises:4) a cooling system that cools the at least one semiconductor laser to maintain the at least one semiconductor laser at a temperature that varies by no more than 40° C. during operation of the at least one semiconductor laser to generate laser pulses for application to the target tissue.

205. The system of claim 204, wherein the cooling system is a dynamic cooling system that adjusts the cooling capacity based on the power applied to the at least one semiconductor laser.

206. The system of claim 204, wherein the cooling system comprisesA) a thermoelectrical cooler; andB) a heat sink comprising a base plate thermally coupled to the thermoelectric cooler and to the at least one semiconductor laser, wherein the thermoelectric cooler controls the temperature of the base plate to a desired temperature within the range of 10-40° C. during the operation of the at least one semiconductor laser to generate laser pulses for application to the target tissue.

207. The system of claim 201, wherein the grating filter element provides feedback to the light in the laser gain medium to reduce the first frequency linewidth to a second frequency linewidth that is no more than 25% of the first frequency linewidth.

208. The system of claim 201, wherein the grating filter element provides feedback to the light in the laser gain medium to reduce the first frequency linewidth to a second frequency linewidth that is no more than 300 GHz.

209. The system of claim 201, wherein the grating filter element provides feedback to the light in the laser gain medium to reduce the first frequency linewidth to a second frequency linewidth for which at least 75% of the energy of the laser pulses is at a frequency for which the ratio of the absorption coefficient of the target chromophore to the non-target chromophore is at least 90% of the maximum value of the absorption coefficient ratio over the first frequency range.

210. The system of claim 201, wherein the diode laser system comprises a plurality of semiconductor lasers, each laser in the plurality of semiconductor lasers comprising:1) a semiconductor laser gain medium that, in the absence of a grating filter element, produces laser light having a center frequency within the first frequency range and a first frequency linewidth of at least 1000 GHz;2) a grating filter element capable of providing feedback to the light in the laser gain medium, wherein the grating element is adapted to reduce the first frequency linewidth to a second frequency linewidth that is no more than one-half of the first frequency linewidth; and3) an output coupling adapted to output a desired fraction of light from the semiconductor laser gain medium as laser pulses;
wherein the diode laser system further comprises:4) at least one beam combining optical element; and5) at least one collimating optical element,
wherein the at least one beam combining optical element and the at least one collimating optical element combine the output of the plurality of semiconductor lasers into a single laser light output having a common optical axis.

301. A system for treating a target tissue having poor chromophore selectivity, the target tissue comprising a first tissue structure comprising a target chromophore and a second tissue structure comprising a non-target chromophore, wherein the absorption coefficient of the target chromophore continuously exceeds the absorption coefficient of the at least one non-target chromophore over a first frequency range of less than 6000 GHz, and the maximum value of the ratio of the absorption coefficient of the target chromophore to the absorption coefficient of the non-target chromophore over the first frequency range is less than 10, the system comprising:a) a diode laser system having at least one semiconductor laser generating pulsed laser light, the at least one semiconductor laser comprising:1) a semiconductor laser gain medium that, in the absence of a grating filter element, produces laser light having a center frequency within the first frequency range and a first frequency linewidth of at least 1000 GHz;2) a grating filter element capable of providing feedback to the light in the laser gain medium, wherein the grating element is adapted to reduce the first frequency linewidth to a second frequency linewidth that is no more than one-half of the first frequency linewidth; and3) an output coupling adapted to output a desired fraction of light from the semiconductor laser gain medium as laser pulses;b) a handpiece to receive the laser pulses output from the diode laser system and to direct the laser pulses to the target tissue along a first optical path.

302. The system of claim 301, wherein the handpiece comprises:1) an optical connector to receive the laser light output from the output coupling of the diode laser system;2) a contact cooling element comprising a cooling window adapted to contact and cool a first skin area of the patient, wherein the cooling window comprises a thermally conductive material and wherein the target tissue comprises a volume of tissue having an external skin surface within the first skin area; and3) at least one optical element located in the first optical path and adapted to direct the laser light along the first optical path from the optical connector through the cooling window into the target tissue;
the system further comprising:c) a temperature determination unit that determines a surface temperature of the target tissue one or more times before, during, or after the application of each laser pulse.

303. The system of claim 302, wherein the cooling window comprises a thermally conductive material that is transmissive to infrared energy, and the temperature determination unit determines the surface temperature of the target tissue based on infrared energy radiated from the target tissue through the cooling window along a second optical path.

304. The system of claim 303, wherein the handpiece comprises at least one reflective element located in the second optical path, and wherein the temperature determination unit comprises:1) a temperature sensing element for sensing infrared energy radiated from substantially only the target tissue through the cooling window along the second optical path, the temperature sensing element generating a first signal indicative of the infrared energy radiating along the second optical path, wherein the infrared energy radiating along the second optical path engages the at least one reflective optical element before being directed onto the temperature sensing element; and2) a processor adapted to determine the surface temperature of the target tissue one or more times during or after the application of each therapeutic laser pulse based on the first signal.

305. The method of claim20, wherein the target chromophore is sebum or sebaceous gland tissue and the non-target chromophore is water.

306. The system of claim 301, wherein the at least one semiconductor laser comprises one of a distributed feedback laser (DFB), a distributed Bragg reflector (DBR) laser, a volume holographic grating (VHG) stabilized laser, and an extended cavity diode laser (ECDL).

The particular embodiments disclosed and discussed above are illustrative only, as the invention may be modified and practiced in different but equivalent manners apparent to those skilled in the art having the benefit of the teachings herein. Embodiments of the present invention disclosed and claimed herein may be made and executed without undue experimentation with the benefit of the present disclosure. While the invention has been described in terms of particular embodiments, it will be apparent to those of skill in the art that variations may be applied to systems and apparatus described herein without departing from the concept and scope of the invention. Examples are all intended to be non-limiting. It is therefore evident that the particular embodiments disclosed above may be altered or modified and all such variations are considered within the scope of the invention, which are limited only by the scope of the claims.