System and method for thermal gradient preconditioning for selective photothermal targeting

Abstract

To provide systems and methods for providing a controlled thermal treatment to a target medium.SOLUTION: A preconditioning process 402 is performed to establish a thermal gradient within the target medium. Following the establishment of the thermal gradient, a phototreatment 404 is performed within the target medium. The target medium can contain a chromophore of interest, such as sebum.SELECTED DRAWING: Figure 5

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims priority to U.S. Provisional Patent Application No. 62 / 411,149, filed October 21, 2016, which is incorporated herein by reference.

[0002] (Statement Regarding Federally Funded Research) Not applicable.

[0003] The present disclosure relates generally to improved systems and methods for targeting specific chromophores embedded in a medium, and more particularly to systems and methods for targeting and initiating damage in sebaceous glands without exceeding a given damage threshold for adjacent tissue. [Background technology]

[0004] The concept of targeting sebaceous glands using photoexcitation of sebum to initiate thermal damage is known in the art. However, to achieve thermal damage, a significant amount of light must be applied, which is absorbed by both the sebaceous glands and the higher layers of the skin, resulting in a significant increase in temperature. This temperature increase can cause pain to the subject and undesirable damage to the epidermis covering the target glands. Summary of the Invention [Problem to be solved by the invention]

[0005] Various attempts have been made to apply surface cooling to counteract pain. However, surface cooling is insufficient to overcome the pain caused by thermal damage to some chromophores, such as sebum. In the case of induced damage to sebum and sebaceous glands, surface cooling failed to prevent pain.

[0006] There is a clear need for improvements to enable the induction of thermal damage in various chromophores, such as sebum, while remaining below threshold pain and unwanted damage to the subject. [Means for solving the problem]

[0007] The present invention overcomes the shortcomings of the prior art by providing a system and method for providing controlled thermal treatment to a target.

[0008] In one aspect, the present disclosure provides a method for providing controlled thermal treatment to a target medium, which may include one or more of the following steps: preconditioning the target medium to establish a temperature gradient having a peak temperature at a predetermined depth from the surface of the target medium; and phototreating the target medium.

[0009] In another aspect, the present disclosure provides a system comprising a pre-processing subsystem, a light processing subsystem, a processor, and a memory storing computer-executable instructions that, when executed by the processor, cause the processor to perform a method described herein, wherein the processor is configured to execute the computer-executable instructions.

[0010] These and other advantages of the present disclosure will become apparent from the following description. Reference is made to the accompanying drawings, which form a part of the specification and which show, by way of example, certain aspects of the present disclosure. However, these aspects do not necessarily represent the full scope of the disclosure, and reference is therefore made to the claims and this specification for interpreting the scope of the disclosure.

[0011] The present disclosure is described below with reference to the accompanying drawings, in which like reference numerals indicate like elements. [Brief explanation of the drawings]

[0012] [Figure 1] FIG. 1 is a schematic diagram of a system according to one aspect of the present disclosure. [Figure 2] FIG. 1 is a schematic diagram of a system according to one aspect of the present disclosure. [Figure 3] 1 is a plot illustrating a temperature gradient according to one aspect of the present disclosure. [Figure 4] FIG. 1 is a schematic diagram of a scanning strategy according to an aspect of the present disclosure. [Figure 5] 1 is a flowchart illustrating a method according to one aspect of the present disclosure. [Figure 6] 1 is a flowchart illustrating a method according to one aspect of the present disclosure. [Figure 7] FIG. 1 is a schematic diagram of the experimental setup used in Experimental Example 12 and other cases. DETAILED DESCRIPTION OF THE INVENTION

[0013] Before describing the present invention in further detail, it is to be understood that the present invention is not limited to the particular embodiments described. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting. The scope of the present invention will be limited only by the claims. As used herein, the singular forms "a," "an," and "the" include plural embodiments unless the context clearly dictates otherwise.

[0014] Those skilled in the art will recognize that many additional modifications beyond those already described are possible without departing from the inventive concept. In interpreting this disclosure, all terms should be interpreted in the broadest manner consistent with the context. Variations of the terms "comprises," "comprises," or "having" should be interpreted as referring non-exclusively to elements, components, or steps. As such, a referenced element, component, or step may be combined with other elements, components, or steps not expressly referenced. Embodiments referred to as "comprising," "comprising," or "having" particular elements are also considered to "consist essentially of" and "consist of" those elements, unless the context clearly dictates otherwise. It should be understood that aspects of the present disclosure described with respect to systems are applicable to methods, and vice versa, unless the context clearly dictates otherwise.

[0015] Numerical ranges disclosed herein are inclusive of their endpoints. For example, a numerical range from 1 to 10 includes the values ​​1 and 10. When a series of numerical ranges is disclosed for a given value, the disclosure expressly contemplates ranges including all combinations of the upper and lower limits of those ranges. For example, a numerical range between 1 and 10 or between 2 and 9 is intended to include the numerical ranges between 1 and 9 and between 2 and 10.

[0016] The present disclosure provides systems and methods for providing controlled thermal treatment to a target. As described above, existing systems and methods apply thermal treatment with electromagnetic radiation, which in some cases has selective absorption at the target chromophore. Furthermore, surface cooling has been applied to help reduce the amount of pain caused by non-selective absorption of electromagnetic radiation. However, none of these approaches have produced a treatment that effectively damages the chromophore or the material surrounding the chromophore while remaining below a pain threshold acceptable to the patient. The present disclosure provides systems and methods that may include pretreatment utilizing surface cooling in combination with preheating (e.g., light-induced preheating) to target and / or heat the target chromophore of interest. A temperature gradient is established with a peak temperature at the depth where the chromophore is expected to be located. The temperature of the tissue above and below the depth of the chromophore remains low enough so that the subject does not suffer unwanted damage and / or experience extreme pain, while subsequent phototreatment can be introduced to raise the temperature of the chromophore to a level at which targeted damage is induced. The degree of selectivity in inducing damage and the degree to which pain to the subject is reduced by the systems and methods described herein is surprising and represents a substantial improvement over the current state of the art.

[0017] (system) 1, the present disclosure provides a system 10. System 10 may include a pre-treatment subsystem 12, a light treatment system 14, and a computer 16. As discussed in more detail below, system 10 is configured to provide treatment to a target medium 18 having a target surface 20.

[0018] The pre-treatment subsystem 12 may include a pre-treatment cooling device 22 and a pre-treatment heating device 24 .

[0019] The pre-cooling device 22 may be any device recognized by those skilled in the art as suitable for applying cooling to the target medium 18. In certain embodiments, the pre-cooling device 22 may be a conductive or convective cooling device. Examples of suitable pre-cooling devices 22 include, but are not limited to, thermally conductive materials coupled to a cooling circuit (e.g., metal, glass, ceramic, sapphire window, gaseous fluid such as air, liquid fluid such as heavy water, pulsed spray of liquid or gaseous fluid, etc.). One specific, non-limiting example of a suitable pre-cooling device 22 includes two windows (e.g., two sapphire windows) with a fluid, such as a gaseous or liquid fluid, between them, which is circulated by a cooling circuit. The cooling circuit may be configured according to the knowledge of those skilled in the art of thermal circuits. In certain embodiments, the pre-cooling device 22 may include a surface contact 26 configured to contact the target surface 20 to apply cooling. In certain embodiments, the surface contact 24 may be transparent to various portions of the electromagnetic spectrum. In certain embodiments, surface contact portion 26 is configured to provide a via for the transfer of one or more heat sources from pretreatment heating device 24. The catheter may include one or more openings configured to allow passage of electrodes, ultrasonic energy, electromagnetic radiation, etc.

[0020] The pretreatment heating device 24 may be one or more electrodes, an ultrasonic probe configured to impart a thermal effect to the target medium 18, a pretreatment microwave source, or a radio frequency source including a pretreatment light source.

[0021] In certain embodiments, the pretreatment heating device 24 can be a pretreatment light source, which can be a laser (e.g., a fiber laser, a diode laser, or other suitable laser), a light emitting diode, an incandescent light source, an arc lamp (also known as a discharge lamp), a flash lamp (e.g., a Xe flash lamp), or the like.

[0022] Pre-processing subsystem 12 may include various electronics, power supplies, controls, circuitry, optics, etc. to provide appropriate functionality according to the performance described herein.

[0023] The light treatment subsystem 14 can include a light treatment light source 30. The light treatment light source 30 can be a laser (e.g., a fiber laser, a diode laser, or other suitable laser), a flash lamp (e.g., a Xe flash lamp), or the like.

[0024] The light processing subsystem 14 may include various electronics, power supplies, controllers, circuitry, optics, etc. to provide appropriate functionality according to the performance described herein.

[0025] In certain embodiments, the pre-treatment light source and the photo-treatment light source 30 can be the same device. When the pre-treatment light source and the photo-treatment light source 30 are the same device, the device can be a laser (e.g., a fiber laser, a diode laser, or other suitable laser), a flash lamp (e.g., a Xe flash lamp), or the like.

[0026] The pretreatment light source and / or phototreatment light source 30 can be configured to emit light having a wavelength or wavelength range that penetrates the target medium 18 to a desired depth, including, but not limited to, wavelengths or wavelength ranges between 350 nm and 2000 nm, 600 nm to 1100 nm, 610 nm to 700 nm, 1600 nm to 1800 nm, 1000 nm to 1500 nm, 450 nm to 650 nm, or other wavelengths or wavelength ranges suitable for achieving the desired effects described herein. In certain embodiments, the pretreatment light source and / or phototreatment light source 30 can be configured to emit light having a wavelength tuned to the absorption peak of the chromophore of interest. In certain embodiments, the pretreatment light source and / or phototreatment light source 30 can be configured to emit light having a wavelength of 760 nm, 920 nm, 1064 nm, 1210 nm, 1726 nm, or other wavelengths suitable for achieving the desired effects described herein. Of course, when wavelengths are defined, the nominal wavelength of the absorption band is also contemplated.

[0027] Those skilled in the art will appreciate that wavelength selection can involve a host of variables, including the location, intensity, and shape of the absorption band for the target chromophore and the location, intensity, and shape of the absorption band for the competing chromophore. Thus, in some cases, a wavelength can be selected for the peak absorption of the target chromophore, as long as the competing chromophore does not significantly interfere with the absorption at the peak absorption wavelength of the target chromophore. In other cases, a wavelength can be selected that has significant, but weaker, absorption than the peak absorption, such that the competing chromophore interferes at the wavelength of the peak absorption but not at the selected wavelength. In the case of pretreatment, wavelengths are selected to appropriately achieve the spatial temperature gradient and pretreatment effects described herein. In the case of phototreatment, wavelengths are selected to appropriately achieve the phototreatment effects described herein.

[0028] The pre-treatment light source and / or light processing light source 30 can be configured to emit continuous wave light, light pulses, or both. The pre-treatment light source and / or light processing light source 30 can be configured to be switchable between continuous wave light and light pulses. In certain situations, the pre-treatment light source and / or light processing light source 30 can have a shaped beam in which the emitted energy is larger in diameter at the surface and more focused at the desired depth. One means of achieving this would be through the use of a high numerical aperture objective lens. In these situations, it may be beneficial to scan the shaped beam, for example, using methods described elsewhere herein.

[0029] The pretreatment light source and / or light treatment light source 30 can be configured to emit light pulses with pulse widths between 10 fs and continuous wave, including, but not limited to, pulse widths between 100 fs and 1 s, 1 ps and 750 ms, 10 ps and 500 ms, 100 ps and 250 ms, 1 ns and 100 ms, 10 ns and 50 ms, 100 ns and 10 ms, 1 μs and 750 ms, 10 μs and 500 ms, 50 μs and 250 ms, 100 μs and 100 ms, 500 μs and 50 ms, or 1 ms and 25 ms. The depth of penetration of the pretreatment source into tissue is such that the tissue layer containing the subsurface target can be warmed before the arrival of the treatment pulse. The average absorbed power density of the pretreatment source is such that cooling at the tissue surface maintains a non-damaging temperature substantially lower than cooling in the target tissue layer before the arrival of the treatment pulse. Pulses for either the pretreatment source or the phototreatment source can be provided by a pulsed source, such as a pulsed laser, or by spatially scanning a continuous or quasi-continuous source to achieve the desired average absorbed power density. The pulse width is measured as a full width at half maximum using methods known to those skilled in the art. The pre-treatment light source and / or photo-treatment light source 30 can be configured to emit pulses of light having pulse intervals (measured as the peak-to-peak spacing of the pulses using methods known to those skilled in the art) between 100 fs and 1 s, including, but not limited to, pulse intervals between 1 ps and 750 ms, 10 ps and 500 ms, 100 ps and 250 ms, 1 ns and 100 ms, 10 ns and 50 ms, 100 ns and 10 ms, 1 μs and 750 ms, 10 μs and 500 ms, 50 μs and 250 ms, 100 μs and 100 ms, 500 μs and 50 ms, or 1 ms and 25 ms. It will be appreciated by those skilled in the art that the use of pulse sources for pre-treatment and photo-treatment will remain within the desired effect of the pre-treatment and photo-treatment. For example, a pulsed source for pre-treatment can be configured to provide a desired average power density to establish a temperature gradient as described elsewhere herein without causing thermal effects in other ways (e.g., phototreatment). As another example, a pulsed source for phototreatment can be configured to perform photothermolysis according to the mechanism of selective photothermolysis using one (or more in certain cases) pulses of light. This allows for the desired thermal results to be achieved.

[0030] In certain embodiments, the light processing light source 30 can be configured to emit pulses of light having pulse widths between 1 μs and 750 ms, which can include, but are not limited to, pulse widths between 10 μs and 500 ms, 50 μs and 250 ms, 100 μs and 100 ms, 500 μs and 50 ms, or 1 ms and 25 ms.

[0031] Computer 16 may take the form of a general-purpose computer, tablet, smartphone, or other computing device that can be configured to control the devices described herein and that can run computer-executable programs that perform the methods described herein. Computer 24 may include various components known to those skilled in the art, such as a processor and / or CPU, various types of memory, interfaces, etc. Computer 24 may be a single computing device or may be multiple computing devices operating in coordination.

[0032] The processor and / or CPU may be configured to read and execute computer-executable instructions stored in memory, which may include all or part of the methods described herein.

[0033] The memory may include one or more computer-readable and / or writable media, such as a magnetic disk (e.g., a hard disk), an optical disk (e.g., a DVD, Blu-ray, CD), such as a magneto-optical disk, a semiconductor memory (e.g., a non-volatile memory card, flash memory, solid-state drive, SRAM, DRAM), an EPROM, an EEPROM, etc. The memory may store computer-executable instructions for all or part of the methods described herein.

[0034] The interface may provide a communication interface to input / output devices, which may include a keyboard, a display, a mouse, a printing device, a touch screen, a light pen, an optical storage device, a scanner, a microphone, a camera, a drive, a communication cable, or a network (wired or wireless). The interface may also provide a communication interface to other components included in system 10 and / or used in the methods described herein.

[0035] The system 10 may include one or more power supplies (not shown) for providing power to the various components of the system 10 .

[0036] Referring to FIG. 2, an example of the system 10 is shown in a particular configuration, i.e., the pre-treatment heating device 26 and the photo-treatment light source 30 are a single light source, and in a particular situation, i.e., for sebaceous gland treatment.

[0037] 2, the target medium 18 may be a layered system, such as human skin. The target medium 18 may include a first layer or stratum corneum 32, a second layer or epidermal layer 34, a third layer or dermal layer 36, and a fourth layer or subcutaneous layer 38. The dermal layer 36 may include multiple target chromophores or sebaceous glands 40. Of course, the target chromophores 40 are not limited to the third layer or dermal layer 36, but may be located in various other layers and / or at various different depths.

[0038] The system 10 may include a light conversion element (not shown) for lateral translation of light emitted from one or more of the light sources described herein. The light conversion element may be a one-dimensional, two-dimensional, or three-dimensional translation stage mounted on the light source, whereby the entire light source is moved to convert the emitted light. The light conversion element may also be an optical configuration that allows the light itself to be converted without requiring movement of the light source. Those skilled in the art will recognize suitable light conversion elements, including, but not limited to, a single mirror, a pair of mirrors, one or more mirrors coupled to a motor that changes the angle and / or position of the emitted light, etc.

[0039] In certain embodiments, the target chromophore 40 can be sebum, melanin, hemoglobin, oxyhemoglobin, reduced hemoglobin, water, etc. In certain embodiments, the target chromophore 40 is sebum.

[0040] Aspects of the disclosure described elsewhere herein with respect to methods may be used where the context clearly indicates otherwise. Unless otherwise indicated, all references to a method are applicable to system 10. For example, if a given wavelength or pulse width is described with respect to a method, system 10 should be construed as providing that given wavelength or pulse width.

[0041] (method) The present disclosure also provides a method for thermal gradient pretreatment of a selective target. In some embodiments, referring to FIG. 5, method 400 can include one or more of the following steps: In process block 402, a temperature gradient is established by pretreatment of a target medium; and in process block 404, the target medium is phototreated. The temperature gradient can have a peak temperature at a predetermined depth from the surface of the target medium. Pretreatment can include applying conductive or convective cooling to the surface of the target medium and applying thermal energy to the target medium that propagates through the surface of the target medium.

[0042] 6, method 500 can include one or more of the following steps: performing pre-cooling on the surface of the target medium at process block 502; performing photothermal pre-heating on the target medium at process block 504; and photo-treating the target medium at process block 506.

[0043] In certain aspects, pre-treating the target medium can include simultaneously performing pre-cooling on the surface of the target medium and performing photothermal pre-heating on the target medium.

[0044] The methods described herein may be useful in the treatment of a variety of clinical indications, including, but not limited to, acne, benign skin tumors (e.g., xanthomas / xanthomas, syringomas), granulomas, subcutaneous fat and cellulite, angiokeratoma, ganglion cysts, calcinosis cutis, and other similar conditions. Without being limited to these, in certain cases, the methods described herein may be useful in treating acne.

[0045] The methods described herein are configured to provide a subject with a treatment that induces pain in the subject that is below a predefined pain threshold for the subject. As known in the art, there are various methods for determining a subject's pain level (e.g., a 1-10 point scale, etc.). The predefined pain threshold can be defined based on the situation, with a higher pain threshold being used for emergency treatments and a lower pain threshold being used for purely cosmetic treatments. Calibrating a treatment for a given user can be done by testing a series of known treatments on the user. This can be achieved by establishing a pain threshold calibration plot. Calibration of treatment for a given user can utilize real-time pain feedback from the subject. Pain thresholds can be determined for the user in the presence or absence of analgesics. A statistical distribution of pain thresholds can be determined for a selected group of subjects, and the method can be configured to be less than a given percentile pain threshold for the selected group, such as less than the 99th percentile pain threshold, less than the 95th percentile pain threshold, less than the 90th percentile pain threshold, less than the 80th percentile pain threshold, or less than the 75th percentile pain threshold. In certain embodiments, the pain threshold for pretreatment can be the same as or different from the pain threshold for light treatment.

[0046] The step of performing pre-cooling on the surface of the target medium, or performing conductive or convective cooling on the surface, may include contacting the surface of the target medium with a temperature control device, such as the surface contact portion 26 of the pre-cooling device.

[0047] In certain aspects, administering pre-cooling to the surface can include applying pre-cooling for a length of time between 1 second and 5 minutes, including, but not limited to, between 2 seconds and 2 minutes, 3 seconds and 1 minute, 4 seconds and 50 seconds, 5 seconds and 45 seconds, 6 seconds and 40 seconds, 7 seconds and 30 seconds, 8 seconds and 25 seconds, 9 seconds and 20 seconds, 10 seconds and 15 seconds, or 15 seconds and 30 seconds. One skilled in the art will recognize that the length of time for applying pre-cooling can depend on several factors, such as the desired penetration depth of the pre-cooling.

[0048] In certain embodiments involving contacting the surface of the target medium with a temperature control device, the temperature control device can have a temperature between -10°C and 20°C, including, but not limited to, temperatures between -5°C and 10°C, -2.5°C and 5°C, and 0°C and 2.5°C. In certain embodiments, the step of pre-cooling the surface comprises applying a temperature of 0.1 W / cm 2 ~10W / cm 2 In amounts between and extracting thermal power, W / cm 2 ~9.0W / cm 2 , 1W / cm 2 ~8.0W / cm 2 , 2.5W / cm 2 ~7.5W / cm 2 , or 4 W / cm 2 ~6W / cm 2 Including but not limited to amounts between Not determined.

[0049] The step of applying propagating thermal energy to the target medium through the surface of the target medium includes the steps of applying radio frequency energy to the target medium through the surface of the target medium, applying ultrasonic energy to the target medium through the surface of the target medium, and applying propagating thermal energy to the target medium through the surface of the target medium. applying electromagnetic radiation, or a combination thereof.

[0050] Applying electromagnetic radiation to the target medium or performing photothermal preheating on the target medium can include transmitting light having a preheating absorbed average power density or absorbed average irradiance for a preheating time. In certain aspects, the preheating absorbed average power density or absorbed average irradiance is greater than the photoprocessing absorbed average power density or absorbed average irradiance of the light used for photoprocessing. or the absorbed average irradiance, and / or the preheating time can be shorter than the light treatment time during which the light treatment is carried out.

[0051] In certain embodiments, the preheating absorbed average power density or absorbed average irradiance is 0.1 W / cm 2 ~10W / cm 2 0.25 W / cm 2 ~9W / cm 2 , 0.5W / c m 2 ~7.5W / cm 2 , 0.75W / cm 2 ~5W / cm 2 , 1W / cm 2 ~4W / cm 2 , or 2 W / cm 2 ~3W / cm 2 Preheating absorbed average power density during In certain embodiments, the preheat time can be between 1 second and 5 minutes, including, but not limited to, between 2 seconds and 2 minutes, 3 seconds and 1 minute, 4 seconds and 50 seconds, 5 seconds and 45 seconds, 6 seconds and 40 seconds, 7 seconds and 30 seconds, 8 seconds and 25 seconds, 9 seconds and 20 seconds, 10 seconds and 15 seconds, or 15 seconds and 30 seconds. As used herein, the absorbed average irradiance, assuming perfect absorption, refers to the irradiance of the light source times 1 minus the reflectance.

[0052] In certain embodiments, the steps of performing pre-cooling on the surface of the target medium and performing photothermal pre-heating on the target medium can be simultaneous or sequential. In simultaneous embodiments, the steps of performing pre-cooling and performing photothermal pre-heating can overlap completely in time, or can overlap partially in time with either step. As an example of complete overlap, both the steps of performing pre-cooling and performing pre-heating can be performed together for 20 seconds. As an example of partial overlap, the step of performing pre-cooling can be performed alone for 10 seconds, and the steps of performing pre-cooling and performing pre-heating can both be performed together for 10 seconds. Of course, simultaneous or sequential application of pre-cooling and / or photothermal pre-heating to achieve a desired temperature gradient is contemplated without limitation.

[0053] As discussed elsewhere, a temperature gradient can be established by combining a cooling component of the temperature gradient (e.g., the portion of the temperature gradient caused by pre-cooling) with a heating component of the temperature gradient (e.g., the portion of the temperature gradient caused by pre-heating). Referring to FIG. 3, an exemplary temperature gradient 302 is plotted. The units are arbitrary, and the plot is intended to generally illustrate the concept without limiting how the temperature gradient may be applied. The temperature gradient 302 is a combination of a cooling component 304 and a heating component 306. In the illustrated example, the cooling component 304 and the heating component 306 have the same maximum magnitude, although it should be understood that either the cooling component 304 or the heating component 306 can have a larger absolute magnitude. In the illustrated example, the cooling component 304 and the heating component 306 are exponentially decaying functions. The cooling component 304 and / or the heating component 306 can take on various functional forms depending on the absorption and conduction characteristics of the target medium. In the illustrated example, the cooling component 304 has a decay rate that is twice the decay rate of the heating component 306. Of course, the decay rates of the cooling component 304 and the heating component 306 may be the same or different, and one may be greater or less than the other. Those skilled in the art will understand how to combine various cooling components 304 and heating components 306 to achieve a temperature gradient 302 that has a maximum temperature at a desired depth. Those skilled in the art will also recognize that due to scattering, the components of the temperature gradient may not be exponential as shown in FIG. 3.

[0054] In certain embodiments, the desired depth for the maximum temperature of the temperature gradient 302 may be between 1 μm and 100 mm, including, but not limited to, depths between 10 μm and 75 mm, 50 μm and 50 mm, 100 μm and 40 mm, 250 μm and 30 mm, 500 μm and 25 mm, 750 μm and 20 mm, 1 mm and 10 mm, 2 mm and 5 mm, or 1 mm and 2 mm. In certain cases, the desired depth can be selected based on the known location of the chromophore of interest. For example, sebaceous glands (and the sebum contained therein) are known to be generally located at a known depth range below the skin surface between 1 mm and 2 mm.

[0055] In certain embodiments, the light treatment is at 1 W / cm 2 ~100W / cm 2 Light processing can be performed at absorbed average power densities or absorbed average irradiances between 2 W / cm 2 ~90W / cm 2 , 3W / cm 2 ~80W / cm 2 , 4W / cm 2 ~75W / cm 2 , 5W / cm 2 ~70W / cm 2 , 6W / cm 2 ~60W / cm 2 , 7W / cm 2 ~50W / cm 2 , 8W / cm 2 ~40W / cm 2 , 9W / cm 2 ~30W / cm 2 , 10W / cm 2 ~25W / cm 2 , 15W / cm 2 ~20W / cm 2 , 20W / cm 2 ~35W / cm 2 , 25W / cm 2 ~45W / cm 2 , 30W / cm 2 ~55W / cm 2 , 35W / cm 2 ~65W / cm 2 , or 40W / cm 2 ~85W / cm 2Phototreatments may be applied over a time period between 10 fs and 1 s, including, but not limited to, 100 fs to 900 ms, 1 ps to 800 ms, 10 ps to 750 ms, 100 ps to 700 ms, 1 μs to 600 ms, 10 μs to 500 ms, 100 μs to 400 ms, 1 ms to 300 ms, 5 ms to 250 ms, 10 ms to 200 ms, 25 ms to 100 ms, 50 ms to 75 ms, 100 ms to 350 ms, 200 ms to 450 ms, 250 ms to 550 ms, or 300 ms to 650 ms. In certain embodiments, phototreatments may be performed with a single pulse or multiple pulses. In the case of a single pulse, the time scale of the single pulse should be on the order of the relaxation time of the target chromophore. In the case of multiple pulses, the timing between pulses must be shorter than the relaxation time of the target chromophore.

[0056] Of course, the parameters for the phototreatment depend on the chromophore of interest, the properties of the surrounding medium, and the properties of the temperature gradient 302 .

[0057] In certain embodiments, the methods described herein can be achieved using a single light source. In certain embodiments, the methods described herein can be achieved without changing the output of the single light source. However, even with a single light source and constant power output, when compared with light treatment, the method can still utilize lower power application and / or shorter time for pretreatment. One way to achieve this effect is to scan light across the target medium at a relatively fast speed to establish pretreatment (fast speed means lower exposure at a given point), and then scan light across the target medium at a relatively slow speed. This includes pausing at a given point (slowing down and / or pausing at a particular point results in higher exposure at a particular point).

[0058] In certain embodiments, scanning can include raster scanning. Referring to Figure 4, one possible scanning pattern is shown, with sequential numbers indicating the sequence of positions for scanning the light (i.e., point P1 is illuminated first, followed by points P2, P3, ..., etc., until point P30 is illuminated, after which point P1 is illuminated again). Note: Pre-cooling can be performed on all points simultaneously or scanned in the same way.

[0059] A non-limiting example of a scanning protocol includes a pretreatment of scanning a 60 W laser in the pattern shown in FIG. 4 at a rate such that the light illuminates each location for 1 / 30 seconds, thus providing an effective light power of 2 W at each location. This pretreatment scan can be performed for a time period described herein, e.g., 20 seconds, thereby providing a pretreatment laser treatment of 2 W effective power for 20 seconds at each point. Following this pretreatment scan, a non-limiting example of a scanning protocol can include a light treatment of scanning a 60 W laser in the pattern shown in FIG. 4, pausing for 0.2 seconds at each point to provide a 60 W light treatment for 0.2 seconds at each point. Again, this example is not intended to be limiting, and it will be apparent to those skilled in the art in light of this disclosure that many other scanning protocols are contemplated. This description of the pretreatment scan explains the concepts of instantaneous power density (the power density of the laser regardless of the scanning rate) and average power density (the power density received for a given location). It should be understood that the average power density favors heating of the bulk tissue, balanced by the rejection of power density due to the cooling effect of the surrounding tissue.

[0060] The methods described herein can selectively target a target chromophore embedded in a surrounding medium. The target chromophore can be any of the chromophores described above. In certain aspects, the target chromophore can be sebum, melanin, hemoglobin, oxyhemoglobin, reduced hemoglobin, water, or the like. In certain aspects, the target chromophore can be sebum. The surrounding medium can be tissue, including, but not limited to, layers of the skin such as the epidermis or dermis, subcutaneous tissue, muscle tissue, adipose tissue, brain tissue, organ tissue, or biological fluid, including, but not limited to, blood, plasma, lymph, urine, bile, or the like.

[0061] In certain embodiments, the target chromophore can have selectivity for photoprocessing relative to the surrounding medium. In certain embodiments, the selectivity (as the ratio of target light absorption or chromophore to surrounding medium) can be between 2 and 1 relative to the surrounding medium, including, but not limited to, between 1.95 and 1.1, 1.9 and 1.2, 1.85 and 1.3, 1.8 and 1.4, 1.75 and 1.5, 1.7 and 1.6, 1.6 and 1.05, 1.5 and 1.15, or 1.4 and 1.25. Of course, the heat capacity of the target chromophore and surrounding medium can affect the resulting temperature achieved by selectivity. For example, a target chromophore with a selectivity of 1 relative to the surrounding medium and a higher heat capacity than the surrounding medium can be used to achieve a higher temperature at the target chromophore.

[0062] In certain aspects, the methods described herein may be useful for targeting red hair for photothermolytic removal. In other aspects, the methods described herein may be useful for speeding the healing of contusions or bruises.

[0063] Aspects of the disclosure described elsewhere herein with respect to system 10 are applicable to the method unless the context clearly dictates otherwise. For example, if a given wavelength or pulse width is described with respect to system 10, the method should be construed as utilizing that given wavelength or pulse width.

[0064] [Experimental Example] (Experimental Example 1) In this and subsequent experiments, a custom-built laser operating at a wavelength of 1726 nm and having a 5 mm spot size with a substantially uniform intensity distribution was used.

[0065] To determine the damage threshold, porcine skin tissue target media were preheated with 1 W for various durations. Irradiation with 1 W of 1726 nm light for 15 to 30 seconds produced no damage. Irradiation with the same light for 40 seconds produced damage over a volume 2 mm wide and 1.5 mm deep. Irradiation with the same light for 60 seconds produced damage over a volume 3.5 mm wide and 2 mm deep.

[0066] (Experimental Example 2) The laser of Example 1 was used in human subject testing to determine pain thresholds for single light pulses of various intensities. The light pulses had a pulse width of 100 ms. No surface cooling was performed. Irradiation with light pulses of 25-40 W output caused only mild symptoms in the subjects. Irradiation with light pulses of 45 W output was uncomfortable for the subjects. Irradiation with light pulses of 55 W output was painful for the subjects and resulted in whitening of the subjects' skin.

[0067] (Experimental Example 3) Using the laser from Experiment 1, a single pulse was used to damage an ex vivo pig skin sample. Thresholds were determined. A single 100-ms pulse of 45–55 W at 1726 nm without Zimmer cooling produced nonselective damage. A single 100-ms pulse of 45–55 W at 1726 nm with Zimmer cooling produced no damage. Preheating light at 1 W output power at 1726 nm was applied for 15 seconds with Zimmer cooling to -5.5°C to generate a temperature gradient in a pig skin sample. Following preheating, a single 200-ms pulse of 30 W at 1726 nm (Zimmer cooling is still effective, but similar results would be expected if Zimmer cooling was discontinued immediately before application of the single pulse) was applied, resulting in a 1.5 mm deep skin injury.

[0068] (Experimental Example 4) The laser from Example 1 and the Zimmer cooler from Example 3 were utilized in this example. Pre-cooling Zimmer cooling to -5.5°C was performed for 15-20 seconds, followed by varying numbers of 100 ms pulses of 15 W light at 1726 nm.

[0069] In this and all subsequent examples, images were taken with purple staining, purple representing areas of undamaged tissue and white representing areas of damaged tissue.

[0070] The application of three pulses resulted in a partially damaged area extending deep into the skin sample that was not completely free of purple staining across the width of the sample. The depth of the partially damaged area extended into the thickness of the undamaged sample with the epidermis extending across the width of the sample. The partially damaged area was approximately uniform in damage across the entire width of the sample, and the damaged area did not show complete removal of the purple staining. The partially damaged area was characterized by scattered areas that remained undamaged and resulted in non-selective damage of the sample.

[0071] Irradiation of the sample with another three pulses produced similar results, in that the epidermis was spared and showed non-selective damage below the epidermis. A small hemispherical region in the dermis of the sample, located at the surface of the sample, showed damage extending from the surface to a small depth within the sample.

[0072] After seven pulses, the epidermis was spared, and the sample was characterized by nonselective damage below the epidermis. The nonselective damage area in the dermis of the sample was located centrally on the sample and extended from the surface of the sample in a hemispherical shape toward the epidermis but not into the epidermis. The damaged area was characterized by scattered areas that remained undamaged, resulting in nonselective damage of the sample. The partially damaged area surrounded the hemispherical damaged area and was characterized by scattered areas that remained undamaged, resulting in nonselective damage of the sample below the epidermis.

[0073] The application of eight pulses produced similar results to the application of three pulses. The depth of the partially damaged region extended into the thickness of the undamaged sample with a cuticle extending across the width of the sample. The partially damaged region had nearly uniform damage across the entire width of the sample, and the damaged region was not characterized by complete removal of the purple coloration. The partially damaged region was characterized by scattered areas that remained undamaged and resulted in non-selective damage of the sample.

[0074] The damage obtained in Example 4 was inconsistent with some samples showing minimal or no damage and others showing non-selective damage.

[0075] (Experimental Example 5) The laser of Example 1 and the Zimmer cooler of Example 3 were utilized in this example. Various lengths of Zimmer pre-cooling at -5.5°C and various numbers of 100W of 1726nm 30W light were used. A 0 ms pulse was applied to determine the minimum damage threshold.

[0076] Pre-cooling the tissue sample for 1 second before applying the first pulse resulted in no damage to the tissue sample. The purple stain remained throughout the sample, indicating that the entire sample was intact.

[0077] Zimmer pre-cooling for 1 second before applying the three pulses resulted in non-selective damage of the tissue sample, characterized by a partially damaged region of the sample between the surface of the sample and the epidermis of the sample. The partially damaged region resulted in a spherical faded region of the sample that was partially damaged at its center and faded into the undamaged region surrounding the partially damaged region. This partially damaged region resulted in a non-selective damaged region of the sample.

[0078] When Zimmer pre-cooling was performed for 1 second before applying the six pulses, the epidermis remained intact, but the non-selective damage area extended from the surface of the sample to the epidermis of the sample. The non-selective damage area in the dermis of the sample was characterized by a purple-stained damage area extending from a first area on the surface of the sample to a second area on the surface of the sample. The damage area extended in an approximately U-shape from the first area on the surface to the second area on the surface, with the intermediate area on the surface between the first and second areas undamaged. The U-shaped damage area tapered near the first and second areas on the surface, with a thickness similar to the thickness of the sample between the epidermis and the surface of the sample. This resulted in non-selective damage of the tissue sample.

[0079] Performing Zimmer pre-cooling for 10–30 seconds before applying the six pulses resulted in either no damage to the sample or non-selective damage to the sample. Non-selective damage resulted in an oval damaged area near the sample's surface surrounded by an undamaged area between the surface and the epidermis. In each of these samples, the epidermis was also undamaged.

[0080] The results of Experiment 5 showed conflicting results, with some settings showing no damage and others showing non-selective damage.

[0081] (Experimental Example 6) The laser of Example 1 and the Zimmer cooler of Example 3 were utilized in this example.

[0082] A temperature gradient was established in ex vivo porcine skin by performing Zimmer precooling for 20 seconds at -5.5°C in combination with preheating with 1726 nm light of various power outputs. After establishment of the temperature gradient, a single 100 ms pulse of 35 W light at 1726 nm was applied.

[0083] Applying 6.5 W preheating resulted in non-selective damage of the majority of the tissue sample, with the surface of the sample and the surface of the epidermis located away from the surface of the sample remaining undamaged, while the remainder of the sample was non-selectively damaged and lost the previously applied purple coloring.

[0084] Preheating to 2.5 W caused little to no damage to the tissue samples: the epidermis was spared and there was little to no damage between the surface of the sample and the epidermis.

[0085] Preheating at 3.0 W resulted in deep dermal damage, with the epidermis spared. The deep dermal damage was spherical and had an area extending between the epidermis and the dermal surface of the sample. This was due to a partially damaged area surrounding the damaged area between the epidermis and the dermal surface of the sample. This resulted in semi-selective damaged areas of the sample, while the other areas were damaged.

[0086] The results of Experiment 6 showed non-selective damage with 6.5 W preheating, little or no damage with 2.5 W preheating, and deep dermal damage with epidermal sparing with 3.0 W preheating.

[0087] (Experimental Example 7) The laser of Example 1 and the Zimmer cooler of Example 3 were utilized in this example.

[0088] A temperature gradient was established by applying a 20-second Dimmer precooling at -5.5°C in combination with an identical 20-second preheating period using 2.5W of 1726nm light. After the temperature gradient was established, a single 100ms pulse of 35W of 1726nm light was applied. The pulse was followed by a 20-second Dimmer postcooling at -5.5°C. Selective damage was achieved, including damage to the sebaceous glands, while sparing the epidermis. The selective damage was spherical, resulting in selective damage with the surrounding areas of the damaged or partially damaged samples spared.

[0089] (Experimental Example 8) The laser of Example 1 and the Zimmer cooler of Example 3 were utilized in this example.

[0090] To determine pain thresholds, 1726 nm light of various power levels was applied to the skin of healthy volunteers at -5.5°C with or without Zimmer cooling. With 2.0 W of 1726 nm light, the pain threshold was reached in 7 seconds without Zimmer cooling and 8 seconds with Zimmer cooling. With 1.5 W of 1726 nm light, the pain threshold was reached in 5–8 seconds without Zimmer cooling and 20 seconds with Zimmer cooling. With 1.0 W of 1726 nm light, the pain threshold was reached in 15 seconds without Zimmer cooling and 40–57 seconds with Zimmer cooling.

[0091] (Experimental Example 9) The laser of Example 1 and the Zimmer cooler of Example 3 were utilized in this example.

[0092] A temperature gradient was established in the skin of healthy volunteers by performing 20 seconds of Zimmer precooling at -6°C in combination with preheating with 1.5 W of 1726 nm light. After the temperature gradient was established, the skin was irradiated with single 150 ms pulses of various power levels of 1726 nm light. Single 150 ms pulses of 15-30 W light at 1726 nm caused mild to moderate pain. Single 150 ms pulses of 35-50 W light at 1726 nm caused moderate to sharp pain. Clinical papules were observed with 45 W pulses.

[0093] (Experimental Example 10) The laser of Example 1 and the Zimmer cooler of Example 3 were utilized in this example.

[0094] A temperature gradient was established in ex vivo porcine skin by preheating with 1726 nm light at 1.5 W for 20 seconds, with or without 20 seconds of Zimmer precooling at -5.5°C. After the temperature gradient was established, a single 150 ms pulse of 50 W light at 1726 nm was applied. Without Zimmer precooling, the epidermis was spared while a 1 mm lesion was created within the sample. The lesion area was characterized by an oval oriented horizontally across the sample at a depth of 1 mm.

[0095] With Zimmer precooling, the epidermis was spared from injury at a depth of 1 mm, similar to that without Zimmer precooling. The area of ​​the injury was slightly smaller with Zimmer precooling. Therefore, the damage area was slightly more selective than without Zimmer pre-cooling.

[0096] (Experimental Example 11) The laser of Example 1 and the Zimmer cooler of Example 3 were utilized in this example.

[0097] A temperature gradient was established in ex vivo porcine skin by preheating for 20 seconds with 1726 nm light at various power outputs. Preheating at 4.0 W resulted in non-selective damage of the majority of the tissue sample; the surface of the sample and the surface of the epidermis located away from the sample surface remained undamaged, while the remainder of the sample was non-selectively damaged and the previously applied purple coloring was lost.

[0098] A temperature gradient was also established in ex vivo porcine skin by preheating with 1726 nm light at 1.5 W for 40 seconds when preheating was performed at 2.0 W. This resulted in a nonselective skin lesion of the sample that was cylindrical in shape and extended between the epidermis and the dermal surface of the sample. The lesion was surrounded by an area of ​​undamaged dermis, and the epidermis remained undamaged.

[0099] Preheating at 1.5 W for 40 seconds similarly resulted in non-selective skin damage in samples that were cylindrical in shape and located between the epidermis and the dermal surface of the sample, with the damage surrounded by an area of ​​undamaged dermis and an undamaged or partially damaged epidermis.

[0100] (Experimental Example 12) The laser from Example 1 and the Zimmer refrigerator from Example 3 were utilized in this example. The results of this example were achieved using the experimental setup shown in Figure 7. The skin sample was positioned so that the cut edge of the skin was halfway through the laser beam. The heating plate was maintained at 37°C to simulate body temperature. The Zimmer refrigerator was maintained at -5°C.

[0101] In addition to Zimmer precooling, preheating was performed with 1726 nm light at 0.5 W for 20 seconds, followed by a single pulse of 1726 nm light at powers ranging from 3 W to 30 W and pulse widths ranging from 100 ms to 175 ms. The maximum temperature measured in the epidermis was 18°C. The maximum temperature measured in the dermis was 53°C, obtained with a 150 ms pulse at 30 W. Temperatures of 5–17°C in the epidermis and 44°C in the dermis were obtained with a 150 ms pulse at 20 W. Temperatures of 9–11°C in the epidermis and 37°C in the dermis were obtained with a 150 ms pulse at 20 W.

[0102] In addition to Zimmer precooling, after 20 seconds of preheating with 1726 nm light at 0.5 W, various pulses of 1726 nm light were applied at 10 W power and 150 ms pulse width. Three pulses resulted in temperatures of 3-10°C in the epidermis and 28°C in the dermis. Six pulses resulted in temperatures of 6°C in the epidermis and 37°C in the dermis. Nine pulses resulted in temperatures of 23°C in the epidermis and 37°C in the dermis. Fifteen pulses, with a 700 ms delay between pulses, resulted in temperatures of 32°C in the epidermis and 57°C in the dermis. For the 15 pulses, the dermal temperature was measured after each pulse, and the results are as follows: The notation is pulse number = temperature, with 1 = 29°C; 2 = 36°C; 3 = 40°C; 4 = 43°C; 5 = 46°C; 6 = 48°C; 7 = 49.7°C; 8 = 51°C; 9 = 52.3°C; 10 = 53.2°C; 11 = 53.6°C; 12 = 55°C; 13 = 55.7°C; 14 = 57°C; and 15 = 57°C.

[0103] (Experimental Example 13) The laser of Example 1 and the Zimmer cooler of Example 3 were utilized in this example. Measurements were taken using the experimental setup of Example 12.

[0104] In addition to Zimmer precooling, 20 seconds of preheating with 1726 nm light at 0.5 W was applied, followed by single or multiple 150 ms pulses of 1726 nm light at 10 W. With Zimmer precooling alone (i.e., without preheating or 150 ms pulses at 10 W), the dermal temperature was 15°C. With preheating alone (i.e., without 150 ms pulses at 10 W), the dermal temperature was 24°C. When one pulse was applied with Zimmer precooling but without preheating, the dermal temperature was 32°C. When three pulses were applied with Zimmer precooling and preheating, the dermal temperature was 29°C. When four pulses were applied with Zimmer precooling and preheating, the dermal temperature was 40°C. When five pulses were applied with Zimmer precooling and preheating, the dermal temperature was 54–56°C. When eight pulses were applied with Zimmer precooling and preheating, the dermal temperature was 48°C. Nitroblue tetrazolium chloride (NBTZ) staining was performed on all samples and showed no epidermal damage.

[0105] (Experimental Example 14) The laser of Example 1 and the Zimmer refrigerator of Example 3 were utilized in this example. A control sample of human cadaver skin had epidermis (Ep), hair follicles (HF), and sebaceous glands (SG). The human cadaver skin was placed between the cooling window of the Zimmer refrigerator and a heating plate maintained at 37°C to simulate body temperature.

[0106] Treatment of human cadaver skin samples with two 150 ms pulses of 35 W light with a 1000 ms pulse delay and no preheating resulted in selective damage to some sebaceous glands, with some non-selective damage observed around the glands.

[0107] Treatment of human cadaver skin samples with two 150 ms pulses of 40 W light with a 1000 ms pulse delay and no preheating resulted in selective damage of some sebaceous glands. Some non-selective damage was observed around the sebaceous glands, particularly between the sebaceous glands and the epidermis.

[0108] Human cadaver skin samples treated with two 150 ms pulses of 35 W light with a 1000 ms pulse delay and preheated for 20 s at 0.5 W resulted in selective damage of some sebaceous glands, with minimal amounts of non-selective damage observed around the sebaceous glands.

[0109] While the above detailed description illustrates, describes, and points out novel features as applied to various embodiments, it will be understood that various omissions, substitutions, and changes in the form and details of the illustrated devices or algorithms are possible without departing from the spirit of the disclosure. As will be recognized, some features may be used or performed separately from others, and therefore particular embodiments of the disclosures described herein may be embodied in a form that does not provide all of the features and benefits set forth herein. The scope of the particular disclosures disclosed herein is indicated by the appended claims, rather than the foregoing description. All changes that come within the meaning and range of equivalency of the claims are to be embraced within their scope.

Claims

1. 1. A method for providing controlled thermal treatment to a target medium, comprising: a) preparing a target medium to establish a temperature gradient having a peak temperature at a predetermined depth from the surface of the target medium; b) phototreating the target medium; A method comprising:

2. 10. The method of claim 1, wherein the pre-conditioning of step a) comprises applying conductive or convective cooling to the surface of the target medium, thereby establishing an exponential cooling component of the temperature gradient.

3. The method of claim 2 , wherein the step of applying conductive or convective cooling comprises contacting the surface of the target medium with a cooling medium.

4. 4. The method of claim 1, wherein the pre-treatment of step a) comprises applying thermal energy that propagates through the surface of the target medium to the target medium, thereby establishing an exponential thermal component of a temperature gradient.

5. 5. The method of claim 4, wherein applying the propagating thermal energy comprises radio frequency heating, ultrasonic heating, photothermal heating, or a combination thereof.

6. 5. The method of claim 4, wherein the step of applying propagating thermal energy comprises photothermal heating.

7. 7. The method of claim 5 or 6, wherein the photothermal heating step comprises irradiating the target medium with a first light at a first power for a first length of time, and the phototreatment in step b) comprises irradiating the target medium with a second light at a second power for a second length of time, wherein the first power is less than the second power or the first length of time is greater than the second length of time.

8. 7. The method of claim 5 or 6, wherein the photothermal heating step comprises scanning a light source across a surface area of ​​the target medium at a first speed.

9. 10. The method of claim 8, wherein phototreating the target medium in step b) comprises scanning the light source or a second light source across the surface area of ​​the target medium at a second speed that is slower than the first speed.

10. The step of phototreating the target medium in step b) comprises: 1 W / cm ２ ~100 W / cm ２ Light processing light having an average power density of light processing absorption between and, optical treatment light having a wavelength between 350 nm and 2000 nm; an optical processing light irradiated at a predetermined location within the target medium for a time period between 10 fs and 1 s; The combination of these and 10. The method of claim 1, comprising applying the light treatment light to a surface of the target medium under conditions selected from the group consisting of:

11. The optical treatment light is 1 W / cm ２ ~100 W / cm ２ The average power density absorbed during the optical process 11. The method of claim 10, comprising:

12. 12. The method according to claim 10 or 11, wherein the optical treatment light has a wavelength of 1210 nm or 1726 nm.

13. 13. The method of any one of claims 10 to 12, wherein the optical treatment light is applied to a predetermined location within the target medium for a period of time between 50 ms and 250 ms.

14. 14. The method of any one of claims 1 to 13, wherein the target medium is inside or on a subject, and the pre-treatment of step a) and / or the light treatment of step b) are configured to be less than the pain threshold of the subject.

15. 15. The method of claim 14, wherein the pain threshold for the subject is determined in the absence of an analgesic.

16. 16. The method of claim 1, wherein both the pretreatment in step a) and the light treatment in step b) are configured to reduce the pain threshold to below the 95th percentile for a given subject group.

17. 17. The method of claim 16, wherein the 95th percentile pain threshold for the given subject group is determined in the absence of analgesic medication.

18. 18. The method of any one of claims 1 to 17, wherein the target medium comprises a chromophore of interest embedded in a surrounding medium.

19. 20. The method of claim 18, wherein the chromophores of interest are within a predetermined depth from the surface of the target medium.

20. 20. The method of claim 19, wherein the predetermined depth falls within a known range of depths.

21. 21. The method of any one of claims 18 to 20, wherein the chromophore of interest has a selectivity for phototreatment of at least 1% to 100% relative to the surrounding medium.

22. 22. The method of any one of claims 18 to 21, wherein the chromophore of interest is sebum.

23. a pre-processing subsystem; a light processing subsystem; a processor; a memory storing computer executable instructions that, when executed by the processor, cause the processor to perform a method for providing a controlled thermal treatment to a target medium; A system comprising: The method comprises: a) preparing a target medium to establish a temperature gradient having a peak temperature at a predetermined depth from the surface of the target medium; b) phototreating the target medium; Equipped with The system, wherein the processor is configured to execute computer-executable instructions.

24. 24. The system of claim 23, wherein the pre-conditioning of step a) comprises applying conductive or convective cooling to the surface of the target medium, thereby establishing an exponential cooling component of the temperature gradient.

25. The system of claim 24, wherein the step of applying conductive or convective cooling comprises contacting the surface of the target medium with a cooling medium.

26. 26. The system of any one of claims 23 to 25, wherein the pre-treatment of step a) includes applying thermal energy that propagates through the surface of the target medium to the target medium, thereby establishing an exponential thermal component of a temperature gradient.

27. 27. The system of claim 26, wherein applying the propagating thermal energy comprises radiofrequency heating, ultrasonic heating, photothermal heating, or a combination thereof.

28. 27. The system of claim 26, wherein the step of applying propagating thermal energy comprises photothermal heating.

29. 29. The system of claim 27 or 28, wherein the photothermal heating step comprises irradiating the target medium with a first light at a first power for a first length of time, and wherein the light treatment in step b) comprises irradiating the target medium with a second light at a second power for a second length of time, wherein the first power is less than the second power or the first length of time is greater than the second length of time.

30. 29. The system of claim 27 or 28, wherein the photothermal heating step comprises scanning a light source across a surface area of ​​the target medium at a first speed.

31. 31. The system of claim 30, wherein phototreating the target medium in step b) comprises scanning the light source or a second light source across the surface area of ​​the target medium at a second speed that is slower than the first speed.

32. The step of phototreating the target medium in step b) comprises: 1 W / cm ２ ~100 W / cm ２ Light processing light having an average power density of light processing absorption between and, optical treatment light having a wavelength between 350 nm and 2000 nm; an optical processing light irradiated at a predetermined location within the target medium for a time period between 10 fs and 1 s; The combination of these and 24. The system of claim 23, further comprising applying the light treatment light to a surface of the target medium under conditions selected from the group consisting of:

33. The optical treatment light is 1 W / cm ２ ~100 W / cm ２ The average power density absorbed during the optical process 33. The system of claim 32, comprising:

34. 34. The system of claim 32 or 33, wherein the optical treatment light has a wavelength of 1210 nm or 1726 nm.

35. 35. The system of any one of claims 32 to 34, wherein the optical treatment light is irradiated onto a predetermined location within the target medium for a period of time between 50 ms and 250 ms.

36. 36. The system of any one of claims 23 to 35, wherein the target medium is inside or on a subject, and the pre-treatment of step a) and / or the light treatment of step b) are configured to be less than the pain threshold of the subject.

37. 37. The system of claim 36, wherein the pain threshold for the subject is determined in the absence of analgesic medication.

38. 38. The system of any one of claims 23 to 37, wherein both the pre-treatment in step a) and the light treatment in step b) are configured to reduce the pain threshold below the 95th percentile for a given subject group.

39. 39. The system of claim 38, wherein the 95th percentile pain threshold for the given subject group is determined in the absence of analgesic medication.

40. 40. The system of any one of claims 23 to 39, wherein the target medium comprises a chromophore of interest embedded in a surrounding medium.

41. 41. The system of claim 40, wherein the chromophores of interest are within a predetermined depth from the surface of the target medium.

42. 42. The system of claim 41, wherein the predetermined depth falls within a known range of depths.

43. 43. The system of any one of claims 40 to 42, wherein the chromophore of interest has a selectivity for light treatment of at least 1% to 100% relative to the surrounding medium.

44. 44. The system of any one of claims 40 to 43, wherein the chromophore of interest is sebum.

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