System and method for thermal gradient pre-treatment for selective photo-thermal aiming

Abstract

The present disclosure provides systems and methods for providing controlled thermal processing to a target medium. A pre-processing process is performed to establish a thermal gradient within a target medium. After establishing the thermal gradient, light processing is performed within the target medium. The target medium may contain a chromophore of interest, such as sebum.

Description

This application is a divisional application of PCT international application number PCT / US2017 / 057893, international application date October 23, 2017, Chinese national application number 201780077591.4, and entitled “System and method for thermal gradient pretreatment for selective photothermal targeting”. Cross-references to related applications

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 62 / 411,149, filed on October 21, 2016, and is incorporated herein by reference. A note about federally funded research

[0002] not applicable Background Art

[0003] The present disclosure generally relates to improvements in systems and methods for targeting specific chromophores embedded in a medium. Specifically, the present disclosure relates to systems and methods for targeting sebaceous glands and inducing damage in sebaceous glands without exceeding a given damage threshold of adjacent tissue.

[0004] The concept of targeting sebaceous glands using optical excitation of sebum to induce thermal damage is known in the art. However, in order to achieve thermal damage, a large amount of light must be applied, which is absorbed by the sebaceous glands and higher skin layers and causes a significant increase in temperature. This increased temperature can cause pain to the subject and may cause unnecessary damage to the epidermis covering the target glands.

[0005] To counteract the pain, various attempts have been made to apply surface cooling. However, surface cooling is not sufficient to overcome the pain caused by thermal damage to some chromophores, such as sebum. In the case of sebum and sebaceous gland damage, surface cooling does not prevent pain.

[0006] There is a clear need for improvements that allow thermal damage to be induced in various chromophores, such as sebum, while remaining below the subject's threshold for pain and unwanted damage. Summary of the invention

[0007] The present invention overcomes the shortcomings of the prior art by providing systems and methods 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. The method may include one or more of the following steps: preconditioning the target medium to establish a thermal gradient having a peak temperature at a predefined depth from the surface of the target medium; and phototreating the target medium.

[0009] In another aspect, the present disclosure provides a system. The system may include a pre-processing subsystem, a light processing subsystem, a processor, and a memory having computer-executable instructions stored thereon, wherein when the instructions are executed by the processor, the processor performs the method as described herein, and the processor is configured to execute the computer-executable instructions.

[0010] The foregoing and other advantages of the present disclosure will become apparent from the following description. In the specification, reference is made to the accompanying drawings which form a part hereof and in which certain aspects of the present disclosure are shown by way of illustration. However, these aspects do not necessarily represent the full scope of the present disclosure, and therefore reference is made to the claims and are used herein to interpret the scope of the present disclosure. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] The present disclosure will now be described with reference to the drawings, wherein like reference numerals refer to like elements.

[0012] Figure 1 is a schematic diagram of a system according to aspects of the present disclosure.

[0013] Figure 2 is a schematic diagram of a system according to aspects of the present disclosure.

[0014] Figure 3 is a graph illustrating thermal gradients according to aspects of the present disclosure.

[0015] Figure 4 is a schematic diagram of a scanning scheme according to aspects of the present disclosure.

[0016] Figure 5 is a flow chart illustrating a method according to aspects of the present disclosure.

[0017] Figure 6 is a flow chart illustrating a method according to aspects of the present disclosure.

[0018] Figure 7 is a schematic diagram of the experimental setup used in Example 12 and elsewhere. DETAILED DESCRIPTION

[0019] Before describing the present invention in further detail, it should be understood that the present invention is not limited to the specific embodiments described. It should also be understood that the terms used herein are only for the purpose of describing specific embodiments and are 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 indicates otherwise.

[0020] It should be apparent to those skilled in the art that many additional modifications other than those described are possible, and do not deviate from the inventive concept herein. When interpreting the present disclosure, all terms should be interpreted in the broadest possible manner consistent with the context. The variation of the term "comprising / including" or "having" should be interpreted as quoting elements, parts or steps in a non-exclusive manner, so the quoted elements, parts or steps can be combined with other elements, parts or steps that are not clearly quoted. The embodiments cited as "comprising", "including" or "having" certain elements are also considered to be "essentially composed of those elements" and "composed of those elements", unless the context clearly indicates otherwise. It should be recognized that the various aspects of the present disclosure described about the system can be applied to the method, and vice versa, unless the context clearly indicates otherwise.

[0021] Numerical ranges disclosed herein include their endpoints. For example, a numerical range between 1 and 10 includes values ​​1 and 10. When a series of numerical ranges are disclosed for a given value, the disclosure explicitly contemplates the 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 a numerical range between 1 and 9 and between 2 and 10.

[0022] The present disclosure provides systems and methods for providing controlled thermal treatment to a target. As described above, existing systems and methods have applied thermal treatment by electromagnetic radiation, which, in some cases, has selective absorption in the chromophore of interest. In addition, surface cooling has been applied to help reduce the amount of pain introduced by the non-selective absorption of electromagnetic radiation. However, none of these methods produces a treatment that effectively damages the chromophore or the material around the chromophore while maintaining a pain threshold that is lower than that tolerable to the patient. The present disclosure provides systems and methods that may involve pretreatment, which utilizes surface cooling in combination with preheating (e.g., light-induced preheating) to establish a thermal gradient having a peak temperature at a depth where the target chromophore of interest is located and / or expected to be located. Subsequent light treatment can then be introduced to raise the temperature of the chromophore to a level that induces target damage, while keeping the temperature of the tissue above and below the depth of the chromophore low enough so that the subject does not suffer undesirable damage and / or experience extreme pain. The degree of selectivity in introducing damage and the degree of pain reduction to the subject by the systems and methods described herein are surprising and mark a substantial improvement over the prior art. system

[0023] refer to Figure 1, the present disclosure provides a system 10. The system 10 may include a pre-processing subsystem 12, a light processing system 14, and a computer 16. As discussed in more detail below, the system 10 is configured to provide processing to a target medium 18 having a target surface 20.

[0024] The pre-processing subsystem 12 may include a pre-processing cooling device 22 and a pre-processing heating device 24 .

[0025] The pre-processing cooling device 22 can be a device that a person of ordinary skill in the art considers suitable for applying cooling to the target medium 18. In some aspects, the pre-processing cooling device 22 can be a conduction cooling device or a convection cooling device. Examples of suitable pre-processing cooling devices 22 include, but are not limited to, heat-conducting materials (e.g., metals, glass, ceramics, sapphire windows, gaseous fluids (such as air), liquid fluids (such as heavy water), pulse sprays of liquid or gaseous fluids, etc.) coupled to a cooling circuit. A specific non-limiting example of a suitable pre-processing cooling device 22 includes two windows (such as two sapphire windows) with a fluid, such as a gaseous or liquid fluid, between which the fluid circulates through the cooling circuit. The cooling circuit can be constructed according to the knowledge of a person of ordinary skill in the art of thermal circuits. In some aspects, the pre-processing cooling device 22 may include a surface contact portion 26, which is configured to contact the target surface 20 for application cooling. In some aspects, the surface contact portion 24 may be transparent to various parts of the electromagnetic spectrum. In certain aspects, surface contact portion 26 may include one or more holes configured to provide through-holes for transmitting one or more heat sources from pretreatment heating device 24 (e.g., the holes may allow passage of electrodes, ultrasonic energy, electromagnetic radiation, etc.).

[0026] The pre-treatment heating device 24 may be a radio frequency source including one or more electrodes, an ultrasound probe configured to provide a thermal effect to the target medium 18 , a pre-treatment microwave source, or a pre-treatment light source.

[0027] In some aspects, the pre-treatment heating device 24 can be a pre-treatment light source. The pre-treatment light source 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), etc.

[0028] Pre-processing subsystem 12 may include various electronics, power supplies, controls, circuits, optics, etc., to provide appropriate functionality according to the performance described herein.

[0029] The light processing subsystem 14 may include a light processing light source 30. The light processing light source 30 may be a laser (eg, a fiber laser, a diode laser, or other suitable laser), a flash lamp (eg, a Xe flash lamp), or the like.

[0030] Light processing subsystem 14 may include various electronics, power supplies, controls, circuits, optics, etc., to provide appropriate functionality according to the performance described herein.

[0031] In some aspects, the pre-treatment light source and the light treatment light source 30 can be the same device. When the pre-treatment light source and the light 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), etc.

[0032] Pretreatment light source and / or light treatment light source 30 can be configured to emit light with a wavelength or wavelength range of the desired depth penetrating into target medium 18, including a wavelength or wavelength range between 350nm and 2000nm, including but not limited to a wavelength or wavelength range between 600nm and 1100nm, between 610nm and 700nm, between 1600nm and 1800nm, between 1000nm and 1500nm, between 450nm and 650nm, or other wavelengths or wavelength ranges suitable for achieving the desired effect described herein. In some aspects, pretreatment light source and / or light treatment light source 30 can be configured to emit light with a wavelength tuned to the absorption peak of the chromophore of interest. In some aspects, pretreatment light source and / or light treatment light source 30 can be configured to emit light with a wavelength of 760nm, 920nm, 1064nm, 1210nm, 1726nm, or other wavelengths suitable for achieving the desired effect described herein. It should be understood that in the case of defining wavelengths, the nominal wavelength of the absorption band is also expected.

[0033] Those of ordinary skill in the art will appreciate that the selection of wavelengths may involve many variables, including the location, intensity, and shape of the absorption bands of the target chromophore, as well as the location, intensity, and shape of the absorption bands of the competing chromophores. Thus, in some cases, the wavelength may 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. In other cases, the wavelength may be selected to maintain a significant but weaker absorption than the peak absorption, but the competing chromophore may interfere with the peak absorption wavelength and not interfere with the selected wavelength. In the case of pretreatment, the wavelength is selected to appropriately achieve the spatial temperature gradient as described herein, as well as the pretreatment effects described herein. In the case of light treatment, the wavelength is selected to appropriately achieve the light treatment effects described herein.

[0034] Pre-treatment light source and / or light treatment light source 30 can be configured to emit continuous wave light, light pulse or continuous wave light and light pulse.Pre-treatment light source and / or light treatment light source 30 can be configured to switch between continuous wave light and light pulse.In some cases, pre-treatment light source and / or light treatment light source 30 can have shaped light beam, and the energy of wherein emission is larger in diameter at the surface and more concentrated in the desired depth.A kind of means realizing it is by using high numerical aperture objective lens.In these cases, scanning shaped light beam may be useful, for example by using the method described elsewhere herein.

[0035] The pretreatment light source and / or light treatment light source 30 can be configured to emit light pulses having a pulse width between 10 fs and a continuous wave, including but not limited to pulse widths between 100 fs and 1 second, between 1 ps and 750 ms, between 10 ps and 500 ms, between 100 ps and 250 ms, between 1 ns and 100 ms, between 10 ns and 50 ms, between 100 ns and 10 ms, between 1 μs and 750 ms, between 10 μs and 500 ms, between 50 μs and 250 ms, between 100 μs and 100 ms, between 500 μs and 50 ms, or between 1 ms and 25 ms. The depth of penetration of the pretreatment source into the tissue allows the tissue layer containing the subsurface target to be warmed before the arrival of the treatment pulse. The absorbed average power density of the pretreatment source allows the cooling at the tissue surface to maintain a non-damaging temperature significantly lower than the temperature at the target tissue layer before the arrival of the treatment pulse. Pulses for the pretreatment source or treatment source can be provided by a pulsed source (such as a pulsed laser), or by a spatially scanned continuous or quasi-continuous source to achieve the desired average absorbed power density. The pulse width as described herein is measured as the full-width at half maximum using methods known to those of ordinary skill in the art. The pre-treatment light source and / or the light treatment light source 30 can be configured to emit light pulses having a pulse spacing (measured as the peak-to-peak spacing of the pulses by methods known to those skilled in the art) between 100 fs and 1 second, including but not limited to between 1 ps and 750 ms, between 10 ps and 500 ms, between 100 ps and 250 ms, between 1 ns and 100 ms, between 10 ns and 50 ms, between 100 ns and 10 ms, between 1 μs and 750 ms, between 10 μs and 500 ms, between 50 μs and 250 ms, between 100 μs and 100 ms, between 500 μs and 50 ms, or between 1 ms and 25 ms. It should be understood by those skilled in the art that the use of pulsed sources for pre-treatment and light treatment is still within the limits of the desired effects of the pre-treatment and light treatment. For example, a pulse source for pretreatment can be configured to provide a desired average power density to establish a thermal gradient as described elsewhere herein without otherwise causing thermal consequences (such as phototreatment). As another example, a pulse source for phototreatment can use one light pulse (or in some cases multiple) to provide the desired thermal consequences, which follows the mechanism of selective photolysis.

[0036] In some aspects, the light treatment light source 30 can be configured to emit light pulses having a pulse width between 1 μs and 750 ms, including but not limited to pulse widths between 10 μs and 500 ms, between 50 μs and 250 ms, between 100 μs and 100 ms, between 500 μs and 50 ms, or between 1 ms and 25 ms.

[0037] The computer 16 may take the form of a general purpose computer, tablet computer, smart phone or other computing device that may be configured to control the measurement device described herein and may execute a computer executable program for performing the methods described herein. The computer 24 may include various components known to those of ordinary skill in the art, such as a processor and / or CPU 24, various types of memory, interfaces, etc. The computer 24 may be a single computing device or may be multiple computing devices operating in a coordinated manner.

[0038] The processor and / or CPU may be configured to read and execute computer executable instructions stored in the memory. The computer executable instructions may include all or part of the methods described herein.

[0039] The memory may include one or more computer-readable and / or writable media, and may include, for example, a magnetic disk (e.g., hard disk), an optical disk (e.g., DVD, Blu-ray, CD), a magneto-optical disk, a semiconductor memory (e.g., non-volatile memory card, flash memory, solid-state drive, SRAM, DRAM), EPROM, EEPROM, etc. The memory may store computer-executable instructions for all or part of the methods described herein.

[0040] The interface may provide a communication interface to input and output devices, which may include a keyboard, display, mouse, printing device, touch screen, light pen, optical storage device, scanner, microphone, camera, drive, communication cable, or network (wired or wireless). The interface may also provide a communication interface to other components included in the system 10 and / or used in the methods described herein.

[0041] System 10 may include one or more power supplies (not shown) for providing power to the various components of system 10 .

[0042] refer to Figure 2 , one example of the system 10 is shown deployed in a particular arrangement, namely where the pre-treatment heating device 26 and the light treatment light source 30 are a single light source, and in a particular context, namely for treating sebaceous glands.

[0043] exist Figure 2In the specific context of the present invention, the target medium 18 can be a layered system (such as human skin). The target medium 18 can include a first layer or stratum corneum 32, a second layer or epidermis 34, a third layer or dermis 36, and a fourth layer or subcutaneous layer 38. The dermis 36 can contain a plurality of target chromophores or sebaceous glands 40. It should be understood that the target chromophores 40 are not limited to the third layer or dermis 36 and can be located in various other layers and / or at various depths.

[0044] The system 10 may include an optical translation element (not shown) for laterally translating light emitted from one or more light sources described herein. The optical translation element may be a 1-, 2-, or 3-dimensional translation stage to which the light source is mounted, thereby moving the entire light source to translate the emitted light. The optical translation element may also be a light source arrangement that allows the light itself to be translated without requiring movement of the light source. One of ordinary skill in the art will recognize suitable optical translation 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, and the like.

[0045] In certain aspects, the target chromophore 40 can be sebum, melanin, hemoglobin, oxyhemoglobin, reduced hemoglobin, water, etc. In certain aspects, the target chromophore 40 is sebum.

[0046] Unless the context clearly dictates otherwise, aspects of the disclosure described elsewhere herein with respect to methods apply to system 10. For example, if a given wavelength or pulse width is described with respect to a method, system 10 should be interpreted as providing that given wavelength or pulse width. method

[0047] The present disclosure also provides methods for selectively targeting thermal gradient pretreatment. Figure 5 , method 400 may include one or more of the following steps: at process block 402, pre-treating the target medium to establish a thermal gradient; and at process block 404, light-treating the target medium. The thermal gradient may have a peak temperature at a predefined depth from the surface of the target medium. Pre-treating may include applying conductive cooling or convective cooling to the surface of the target medium and applying propagated heating energy into the target medium via the surface of the target medium.

[0048] In some respects, reference Figure 6 , method 500 may include one or more of the following steps: at process block 502, applying pre-cooling to the surface of the target medium; at process block 504, applying photothermal preheating to the target medium; and at process block 506, phototreating the target medium.

[0049] In certain aspects, pre-treating the target medium can include simultaneously applying pre-cooling to a surface of the target medium and applying photothermal pre-heating to the target medium.

[0050] The methods described herein can be used to treat various clinical indications, including but not limited to acne, benign skin tumors (e.g., xanthomas / chloasmas, syringomas), granulomas, subcutaneous fat and fat masses, angiokeratoma, ganglion cysts, calcinosis cutis and other similar conditions. In some cases, the methods described herein can be used to treat acne.

[0051] Methods described herein are configured to provide a process of inducing pain in a subject to a subject, and the pain is less than a predefined pain threshold of the subject. As known in the art, there are multiple methods for determining the pain level of a subject (e.g., 1 to 10 scales, etc.). Predefined pain thresholds can be defined based on context, so that a higher pain threshold can be used for emergency treatment, or a lower pain threshold can be used for pure cosmetic treatment. Via a series of known treatments tested on a user, a given user calibration treatment can be achieved by establishing a pain threshold calibration map for a given user. Real-time feedback from the pain of the subject can be used to calibrate treatment for a given user. Pain thresholds can be determined for a user in the presence or absence of analgesics. The statistical distribution of pain thresholds can be determined for a selected subject group, and the method can be configured to be less than a given percentile pain threshold of a 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 some aspects, the pain threshold of pretreatment can be the same or different from the pain threshold of light treatment.

[0052] Applying pre-cooling to the surface or applying conduction cooling or convection cooling to the surface of the target medium may include contacting the surface of the target medium with a temperature control device, such as a surface contact portion 26 of a pre-process cooling device.

[0053] In certain aspects, applying pre-cooling to the surface may include applying the pre-cooling for a length of time between 1 second and 5 minutes, including but not limited to between 2 seconds and 2 minutes, between 3 seconds and 1 minute, between 4 seconds and 50 seconds, between 5 seconds and 45 seconds, between 6 seconds and 40 seconds, between 7 seconds and 30 seconds, between 8 seconds and 25 seconds, between 9 seconds and 20 seconds, between 10 seconds and 15 seconds, or between 15 seconds and 30 seconds. One of ordinary skill in the art will recognize that the length of time the pre-cooling is applied may depend on many factors, such as the desired penetration depth of the pre-cooling.

[0054] In certain aspects 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, between -5°C and 10°C, between -2.5°C and 5°C, or between 0°C and 2.5°C. In certain aspects, applying pre-cooling to the surface can include extracting 0.1 W / cm 2 With 10W / cm 2 The thermal power of the amount between, including but not limited to, 0.5W / cm 2 and 9.0W / cm 2 Between 1W / cm 2 and 8.0W / cm 2 Between 2.5W / cm 2 and 7.5W / cm 2 Between or at 4W / cm 2 With 6W / cm 2 The amount between.

[0055] Applying propagated heating energy into the target medium through the surface of the target medium may include applying radio frequency energy into the target medium through the surface of the target medium, applying ultrasonic energy into the target medium through the surface of the target medium, applying electromagnetic radiation into the target medium through the surface of the target medium, or a combination thereof.

[0056] Applying electromagnetic radiation to the target medium or applying photothermal preheating to the target medium can include transmitting light having a preheating absorption average power density or absorption average irradiance for a preheating time length. In some aspects, the preheating absorption average power density or absorption average irradiance can be less than the phototreatment absorption average power density or absorption average irradiance of the light used in the phototreatment and / or the preheating time length can be less than the phototreatment time length of applying the phototreatment.

[0057] In some aspects, the preheating absorbed average power density or absorbed average irradiance can be 0.1 W / cm 2 With 10W / cm 2 Between, including but not limited to, 0.25W / cm 2 With 9W / cm 2 Between 0.5W / cm 2 With 7.5W / cm 2 Between 0.75W / cm 2 With 5W / cm 2 Between 1W / cm 2 With 4W / cm 2 Between or at 2W / cm 2 With 3W / cm 2In some aspects, the preheating time length can be between 1 second and 5 minutes, including but not limited to, between 2 seconds and 2 minutes, between 3 seconds and 1 minute, between 4 seconds and 50 seconds, between 5 seconds and 45 seconds, between 6 seconds and 40 seconds, between 7 seconds and 30 seconds, between 8 seconds and 25 seconds, between 9 seconds and 20 seconds, between 10 seconds and 15 seconds, or the time length between 15 seconds and 30 seconds. As used herein and assuming complete absorption, the absorption average irradiance refers to the irradiance of the light source multiplied by the quantity 1 minus the reflectivity.

[0058] In some aspects, the steps of applying precooling to the surface of the target medium and applying photothermal preheating to the target medium can be simultaneous or sequential. In terms of simultaneous, applying precooling and applying photothermal preheating can overlap completely in time, or can overlap in time in a portion of either application step. As an example of complete overlap, applying precooling and applying preheating can be applied together for 20 seconds. As an example of partial overlap, precooling can be applied separately for a period of 10 seconds, and applying precooling and applying preheating can be applied together for a period of 10 seconds. It should be understood that, without limitation, simultaneous or sequential application of precooling and / or photothermal preheating to achieve a desired thermal gradient can be expected.

[0059] As discussed elsewhere, the thermal gradient may be established by combining a cooling component of the thermal gradient (e.g., a portion of the thermal gradient generated by pre-cooling) and a heating component of the thermal gradient (e.g., a portion of the thermal gradient generated by pre-heating). Figure 3 , an exemplary thermal gradient 302 is plotted. The units are arbitrary, and the plot is intended to represent the concept generally without limiting the way in which the thermal gradient can be applied. The thermal gradient 302 is a combination of a cooling component 304 and a heating component 306. In the example shown, the cooling component 304 and the heating component 306 have the same maximum magnitude, but it should be understood that the cooling component 304 or the heating component 306 may have a larger absolute magnitude. In the example shown, the cooling component 304 and the heating component 306 are exponential decay functions. Depending on the absorption and conduction properties of the target medium, the cooling component 304 and / or the heating component 306 may take on various functional forms. In the example shown, the cooling component 304 has a decay rate that is twice the decay rate of the heating component 306. It should be understood that the decay rates of the cooling component 304 and the heating component 306 may be the same or different, and either may be larger or smaller than the other. One of ordinary skill in the art will recognize how to combine various cooling components 304 and heating components 306 to achieve a thermal gradient 302 with a maximum temperature at a desired depth. One of ordinary skill in the art will also recognize that due to scattering, the components of the thermal gradient may not be as Figure 3 The index shown.

[0060] In some aspects, the desired depth of the maximum temperature of the thermal gradient 302 can be a depth between 1 μm and 100 mm, including but not limited to between 10 μm and 75 mm, between 50 μm and 50 mm, between 100 μm and 40 mm, between 250 μm and 30 mm, between 500 μm and 25 mm, between 750 μm and 20 mm, between 1 mm and 10 mm, between 2 mm and 5 mm, or between 1 mm and 2 mm. In some cases, the desired depth can be selected based on the known location of the chromophore of interest. For example, it is known that sebaceous glands (and the sebum contained therein) are typically located at a known depth range between 1 mm and 2 mm below the skin surface.

[0061] In some aspects, light treatment can be performed at 1W / cm 2 With 100W / cm 2 The light treatment average power density or average irradiance is applied between, including but not limited to, 2W / cm 2 With 90W / cm 2 Between 3W / cm 2 With 80W / cm 2 Between 4W / cm 2 With 75W / cm 2 Between 5W / cm 2 With 70W / cm 2 Between 6W / cm 2 With 60W / cm 2 Between 7W / cm 2 With 50W / cm 2 Between 8W / cm 2 With 40W / cm 2 Between 9W / cm 2 With 30W / cm 2 Between 10W / cm 2 With 25W / cm 2 Between 15W / cm 2 With 20W / cm 2 Between 20W / cm 2 With 35W / cm 2 Between 25W / cm 2 With 45W / cm 2 Between 30W / cm 2 With 55W / cm 2 Between 35W / cm 2 With 65W / cm 2 Between or at 40W / cm 2 With 85W / cm2 In some aspects, the light treatment may be applied for a time length between 10 fs and 1 s, including but not limited to, between 100 fs and 900 ms, between 1 ps and 800 ms, between 10 ps and 750 ms, between 100 ps and 700 ms, between 1 μs and 600 ms, between 10 μs and 500 ms, between 100 μs and 400 ms, between 1 ms and 300 ms, between 5 ms and 250 ms, between 10 ms and 200 ms, between 25 ms and 100 ms, between 50 ms and 75 ms, between 100 ms and 350 ms, between 200 ms and 450 ms, between 250 ms and 550 ms, or between 300 ms and 650 ms. In some aspects, the light treatment may be applied for a single pulse or multiple pulses. In the case of a single pulse, the time scale of the single pulse should be of the order of the relaxation time of the target chromophore. In the case of multiple pulses, the timing between pulses should be shorter than the relaxation time of the target chromophore.

[0062] It will be appreciated that the parameters of the light treatment will depend on the chromophore of interest, the properties of the surrounding medium, and the properties of the thermal gradient 302 .

[0063] In some aspects, the methods described herein can be implemented using a single light source. In some aspects, the methods described herein can be implemented without changing the power output of the single light source. However, even with a single light source and constant power output, the method can still utilize lower power applications and / or shorter lengths of time for pre-treatment compared to light treatment. One way to achieve this effect is by scanning light across the target medium at a relatively fast speed to establish pre-treatment (fast speed means lower exposure of a given point), and then scanning light across the target medium at a relatively slow speed, which can include pausing above a given point (slow speed and / or pausing above a given point means higher exposure of a given point).

[0064] In some aspects, scanning may include raster scanning. Figure 4 , shows one possible scanning pattern, where the sequence number identifies the sequence of positions of the scanning light (in other words, point P1 is illuminated first, followed by point P2, point P3, ..., etc., until point P30 is illuminated, after which point P1 is illuminated again). Note: Pre-cooling can be applied to all points simultaneously, or can be scanned in a similar manner.

[0065] Non-limiting examples of scanning protocols may include: Figure 4The pattern shown in FIG. 1 is pre-processed with a 60W laser at a rate such that light illuminates each location for 1 / 30 second, thereby providing 2W of effective power light to each location. The pre-processing scan can be performed for a period of time as described herein (such as 20 seconds), thereby providing an effective 2W pre-processing laser treatment for 20 seconds at each point. After the pre-processing scan, a non-limiting example of a scanning protocol may include Figure 4 The pattern light treatment shown in scans a 60W laser, pausing for 0.2 seconds at each point, thereby providing 60W light treatment for 0.2 seconds at each point. Again, this example is not intended to be limiting, and many other scanning protocols are contemplated and will be apparent to one of ordinary skill in the art in view of this disclosure. This description of a pretreatment scan should be understood as describing the concepts of instantaneous power density (the power density of the laser, regardless of the scan speed) and average power density (the power density experienced at a given location). The average power density drives body tissue heating and is balanced by the resulting power density removal from the cooling effect of the surrounding tissue.

[0066] The methods described herein can selectively target a chromophore of interest embedded in a surrounding medium. The chromophore of interest can be any of the chromophores described above. In some aspects, the chromophore of interest can be sebum, melanin, hemoglobin, oxyhemoglobin, reduced hemoglobin, water, etc. In some aspects, the chromophore of interest can be sebum. The surrounding medium can be a tissue, including but not limited to skin layers such as the epidermis or dermis, subcutaneous tissue, muscle tissue, adipose tissue, brain tissue, organ tissue, etc.; a biological fluid, including but not limited to blood, plasma, lymph, urine, bile, etc.; and the like.

[0067] In some aspects, the chromophore of interest can have selectivity for phototreatment when compared to the surrounding medium. In some aspects, the selectivity (as the ratio of optical absorption or chromophore of interest relative to the surrounding medium) can be between 2 and 1, including but not limited to, between 1.95 and 1.1, between 1.9 and 1.2, between 1.85 and 1.3, between 1.8 and 1.4, between 1.75 and 1.5, between 1.7 and 1.6, between 1.6 and 1.05, between 1.5 and 1.15, or between 1.4 and 1.25 relative to the surrounding medium. It should be understood that the heat capacity of the chromophore of interest and the surrounding medium can affect the final temperature achieved by the selectivity. For example, when the chromophore of interest has a selectivity of 1 relative to the surrounding medium and a heat capacity higher than the surrounding medium, the temperature in the chromophore of interest can reach higher.

[0068] In certain aspects, the methods described herein can be used to target red hair for photothermolytic removal. In other aspects, the methods described herein can be used to accelerate the recovery of contusions or bruises.

[0069] Unless the context clearly dictates otherwise, aspects of the disclosure described elsewhere herein with respect to system 10 apply to the method. For example, if a given wavelength or pulse width is described with respect to system 10, the method should be interpreted as utilizing that given wavelength or pulse width. Example

[0070] Example 1.

[0071] A custom laser operating at a wavelength of 1726 nm and having a 5 mm spot size with a substantially uniform intensity distribution was used in this example and others that follow.

[0072] A 1W preheat application was performed on the target medium of porcine skin tissue for varying periods of time to determine the damage threshold. Application of 1W of 1726nm light for 15-30 seconds did not cause damage. Application of the same light for 40 seconds caused damage to a volume 2mm wide and 1.5mm deep. Application of the same light for 60 seconds caused damage to a volume 3.5mm wide and 2mm deep.

[0073] Example 2.

[0074] The laser of Example 1 was used in human subject tests to determine the pain threshold of single light pulses of various intensities. The light pulses had a pulse width of 100 ms. No surface cooling was applied. Light pulses applied at a power of 25-40 W showed only mild symptoms in the subject. Light pulses applied at a power of 45 W were uncomfortable for the subject. Light pulses applied at a power of 55 W were painful for the subject and were accompanied by blanching of the subject's skin.

[0075] Example 3.

[0076] An ex vivo porcine skin sample was used with the laser of Example 1 to determine the damage threshold of a single pulse. A single 100ms pulse of 45-55W light at 1726nm produced non-selective damage without Zimmer cooling. A single 100ms pulse of 45-55W light at 1726nm produced no damage with Zimmer cooling. Preheated 1726nm light at 1W power was applied together with -5.5°C Zimmer cooling for 15 seconds to produce a temperature gradient in the porcine skin sample. After preheating, a single 200ms pulse of 30W light at 1726nm was applied (with Zimmer cooling still in effect, but similar results would be expected if Zimmer cooling was stopped immediately before the single pulse was applied), resulting in skin damage 1.5 mm deep.

[0077] Example 4.

[0078] In this example the laser of Example 1 was used and the Zimmer cooling device of Example 3. A pre-cooling -5.5°C Zimmer cooling was applied for 15-20 seconds followed by varying numbers of 100ms pulses of 15W light at 1726nm.

[0079] In all cases of this and the following examples, images were taken with purple staining, where purple represents undamaged tissue areas and white represents damaged tissue areas.

[0080] Application of 3 pulses resulted in a partially damaged area extending to a depth in the skin sample that was not completely free of purple dye across the width of the sample. The depth of the partially damaged area extended to the thickness of the sample, which was undamaged at the epidermis extending across the width of the sample. The partially damaged area was roughly uniformly damaged across the width of the sample, and the damaged area did not completely remove the purple dye. The partially damaged area was characterized by dispersed areas of undamaged residue remaining and resulted in non-selective damage to the sample.

[0081] In applying another 3 pulses to the sample, similar results were achieved, namely the epidermis was spared and the sample featured non-selective lesions beneath the epidermis.A small hemispherical area in the sample dermis located at the sample surface showed lesions extending from the surface to a smaller depth within the sample.

[0082] The application of 7 pulses left the epidermis free of damage, and the sample was characterized by non-selective damage below the epidermis. The non-selective damaged area in the sample dermis was located in the center of the sample and extended from the surface of the sample in a hemispherical shape toward the epidermis, but did not extend into the epidermis. The damaged area was characterized by dispersed areas that remained undamaged, and resulted in non-selective damage to the sample. The partially damaged area surrounded the hemispherical damaged area and was characterized by dispersed areas that remained undamaged, and resulted in non-selective damage to the sample below the epidermis.

[0083] Application of 8 pulses resulted in similar results to application of 3 pulses. The depth of the partially damaged area extended to the thickness of the sample, which was undamaged at the epidermis extending across the width of the sample. The partially damaged area was generally uniformly damaged across the width of the sample, and the damaged area did not completely remove the purple dye. The partially damaged area was characterized by scattered areas that remained undamaged and resulted in non-selective damage to the sample.

[0084] The resulting damage in Example 4 was inconsistent, with some samples showing little to no damage and other samples showing non-selective damage.

[0085] Example 5.

[0086] This example utilized the laser of Example 1 and the Zimmer cooling device of Example 3. Various lengths of -5.5°C Zimmer pre-cooling and various numbers of 100 ms pulses of 30 W light (at 1726 nm) were applied to determine the minimum damage threshold.

[0087] Applying Zimmer pre-cooling for 1 second before applying 1 pulse resulted in no damage to the tissue sample. The purple stain was retained throughout the sample and showed no damage throughout the sample.

[0088] Applying Zimmer precooling for 1 second before applying 3 pulses resulted in non-selective damage to the tissue sample characterized by a partially damaged area of ​​the sample between the surface of the sample and the epidermis of the sample. The partially damaged area resulted in a discolored spherical area of ​​the sample that was damaged in its center and faded to an undamaged area surrounding the partially damaged area. The partially damaged area resulted in a non-selective damaged area of ​​the sample.

[0089] Applying Zimmer precooling for 1 second before applying 6 pulses causes the epidermis to remain intact, while the non-selective injury area extends from the sample surface to the epidermis of the sample. The non-selective injury area in the sample dermis is characterized by an injury area without purple dye, which extends from a first area on the sample surface to a second area on the sample surface. The injury area extends from a first area on the surface to a second area on the sample surface in a roughly U-shaped manner, so that the middle area of ​​the surface between the first area and the second area remains undamaged. The U-shaped injury area is characterized by a thickness near the sample thickness between the epidermis and the surface of the sample, which gradually narrows near the first area and the second area on the surface. This results in non-selective damage to the tissue sample.

[0090] Applying Zimmer precooling for 10 to 30 seconds before applying 6 pulses resulted in no damage to the sample or non-selective damage to the sample. Non-selective damage to the sample resulted in an elliptical damaged area near the sample surface, which was surrounded by an undamaged area between the surface and the epidermis. In each of these samples, the epidermis was also undamaged.

[0091] The results for Example 5 showed inconsistent results, with some settings showing no damage and other settings showing non-selective damage.

[0092] Example 6.

[0093] The laser of Example 1 and the Zimmer cooling device of Example 3 were utilized in this example.

[0094] A thermal gradient was established in ex vivo porcine skin by applying Zimmer precooling at -5.5°C for 20 seconds combined with preheating with 1726 nm light at various powers. After the thermal gradient was established, a single 100 ms pulse of 35 W light at 1726 nm was applied.

[0095] Applying 6.5 W preheating resulted in non-selective damage to the majority of the tissue sample, such that the surface of the sample and the epidermal surface located away from the sample surface remained undamaged, while the remainder of the sample was non-selectively damaged and free of the previously applied purple stain.

[0096] Applying 2.5 W preheating resulted in almost no damage to the tissue samples. The epidermis was spared from damage and there was little evidence of damage between the sample surface and the epidermis.

[0097] Applying 3.0W preheating resulted in deep dermal damage that spared the epidermis. The deep dermal damage had a spherical shaped area and extended between the epidermal and dermal surfaces of the sample. This resulted in a semi-selective damaged area of ​​the sample while having a partial damaged area around the damaged area between the epidermal and dermal surfaces of the sample.

[0098] The results of Example 6 show non-selective damage for 6.5 W preheating, almost no damage for 2.5 W preheating, and deep dermal damage that spared the epidermis for 3.0 W preheating.

[0099] Example 7.

[0100] The laser of Example 1 and the Zimmer cooling device of Example 3 were utilized in this example.

[0101] A thermal gradient was established by applying Zimmer pre-cooling at -5.5°C for 20 seconds combined with pre-heating with 1726nm light at 2.5W for the same 20 seconds. After the thermal gradient was established, a single 100ms pulse of 35W light at 1726nm was applied. After the pulse, Zimmer post-cooling was applied at -5.5°C for 20 seconds. Selective damage was achieved, including damage to the sebaceous glands, and the epidermis was spared. The selective damage was spherical and lacked the surrounding area of ​​the damaged or partially damaged sample, resulting in selective damage.

[0102] Example 8.

[0103] The laser of Example 1 and the Zimmer cooling device of Example 3 were utilized in this example.

[0104] 1726 nm light at various powers was applied to the skin of healthy human volunteers with and without Zimmer cooling at -5.5°C to determine pain thresholds. When 2.0 W of 1726 nm light was applied, the pain threshold was reached in 7 seconds without Zimmer cooling and in 8 seconds with Zimmer cooling. When 1.5 W of 1726 nm light was applied, the pain threshold was reached in 5-8 seconds without Zimmer cooling and in 20 seconds with Zimmer cooling. When 1.0 W of 1726 nm light was applied, the pain threshold was reached in 15 seconds without Zimmer cooling and in 40-57 seconds with Zimmer cooling.

[0105] Example 9.

[0106] The laser of Example 1 and the Zimmer cooling device of Example 3 were utilized in this example.

[0107] A thermal gradient was established in the skin of healthy human volunteers by applying Zimmer precooling for 20 seconds at -6°C combined with preheating with 1726nm light at 1.5W. After the thermal gradient was established, a single 150ms pulse of light at different powers at 1726nm was applied. The pain was mild to moderate for a single 150ms pulse of 15-30W light at 1726nm. The pain was moderate to sharp for a single 150ms pulse of 35-50W light at 1726nm. Clinical papules were observed with a 45W pulse.

[0108] Example 10.

[0109] The laser of Example 1 and the Zimmer cooling device of Example 3 were utilized in this example.

[0110] A thermal gradient was established in ex vivo porcine skin by applying preheating with 1726nm light at 1.5W for 20 seconds, with and without Zimmer precooling at -5.5°C for 20 seconds. After the thermal gradient was established, a single 150ms pulse of 50W light at 1726nm was applied. No Zimmer precooling resulted in 1mm of damage in the sample, while the epidermis was spared. The damaged area was oval in shape, oriented horizontally across the sample at a depth of 1mm into the sample.

[0111] The presence of Zimmer precooling was similar to the absence of Zimmer precooling, resulting in a lesion depth of 1 mm and no damage to the epidermis. In the presence of Zimmer precooling, the lesion area was slightly smaller, thus resulting in a slightly more selective lesion area compared to the absence of Zimmer precooling.

[0112] Example 11.

[0113] The laser of Example 1 and the Zimmer cooling device of Example 3 were utilized in this example.

[0114] A thermal gradient was established in ex vivo porcine skin by applying preheating for 20 seconds with 1726 nm light at different powers. Preheating at 4.0 W resulted in non-selective damage to the majority of the tissue sample, leaving the surface of the sample and the epidermal surface located away from the sample surface undamaged, while the remainder of the sample was non-selectively damaged and free of the previously applied purple stain.

[0115] A thermal gradient was also established in ex vivo porcine skin by applying preheating with 1726 nm light at 1.5 W for 40 seconds when preheating was applied at 2.0 W. This resulted in non-selective skin lesions of the specimens that were cylindrical and extended between the epidermis and dermis surfaces of the specimens. The lesions were surrounded by undamaged dermis areas, and the epidermis remained undamaged.

[0116] When preheating was applied for 40 seconds at 1.5 W, r similarly resulted in non-selective skin lesions of the specimens that were cylindrical and located between the epidermis and dermis surfaces of the specimens. The lesions were surrounded by undamaged dermis areas, and the epidermis remained undamaged or partially damaged.

[0117] Example 12.

[0118] In this example, the laser of Example 1 and the Zimmer cooling device of Example 3 are used. Figure 7 The experimental setup shown in achieved the results in this example. The skin sample was placed so that the cut edge of the skin was in the middle of the laser beam. The heating plate was maintained at 37°C to simulate body temperature. The Zimmer cooling device was maintained at -5°C.

[0119] In addition to Zimmer pre-cooling, pre-heating was applied using 1726nm light at 0.5W for 20 seconds, followed by a single pulse of 1726nm light with a power range from 3W to 30W and a pulse width range from 100ms to 175ms. The maximum temperature measured at the epidermis was 18°C. The maximum temperature measured at the dermis was 53°C achieved at 30W by a 150ms pulse. The temperature at the epidermis was 5-17°C at 20W achieved by a 150ms pulse, and the temperature at the dermis was 44°C. The temperature at the epidermis was 9-11°C at 150ms achieved by a 150ms pulse, and the temperature at the dermis was 37°C.

[0120] In addition to Zimmer pre-cooling, pre-heating was applied with 1726 nm light at 0.5 W for 20 seconds, followed by different numbers of pulses of 1726 nm light at a power of 10 W and a pulse width of 150 ms. When 3 pulses were applied, a temperature of 3-10°C was achieved at the epidermis, and a temperature of 28°C was achieved at the dermis. When 6 pulses were applied, a temperature of 6°C was achieved at the epidermis, and a temperature of 37°C was achieved at the dermis. When 9 pulses were applied, a temperature of 23°C was achieved at the epidermis, and a temperature of 37°C was achieved at the dermis. When 15 pulses were applied with a 700 ms delay between pulses, a temperature of 32°C was achieved at the epidermis, and a temperature of 57°C was achieved at the dermis. In the application of 15 pulses, the temperature of the dermis was measured after each pulse, and the results were as follows (nomenclature is pulse number = temperature: 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.

[0121] Example 13.

[0122] In this example the laser of Example 1 and the Zimmer cooling device of Example 3 were utilized. The experimental setup of Example 12 was used to obtain the measurements.

[0123] In addition to Zimmer pre-cooling, pre-heating was applied with 1726nm light at 0.5W for 20 seconds, followed by single or multiple 150ms pulses of 1726nm light at 10W. Using only Zimmer pre-cooling (i.e., no pre-heating or 150ms pulses at 10W), the temperature of the dermis was 15°C. Using only pre-heating (i.e., no 150ms pulses at 10W), the temperature of the dermis was 24°C. When 1 pulse was applied with Zimmer pre-cooling but no pre-heating, the temperature of the dermis was 32°C. When 3 pulses were applied with Zimmer pre-cooling and pre-heating, the temperature of the dermis was 29°C. When 4 pulses were applied with Zimmer pre-cooling and pre-heating, the temperature of the dermis was 40°C. When 5 pulses were applied with Zimmer pre-cooling and pre-heating, the temperature of the dermis was 54-56°C. When 8 pulses were applied with Zimmer pre-cooling and pre-heating, the temperature of the dermis was 48°C. Nitro blue tetrazolium chloride (NBTZ) staining was applied to all samples and no epidermal damage was found.

[0124] Example 14.

[0125] In this example, the laser of Example 1 and the Zimmer cooling device of Example 3 were used. A control sample of human cadaver skin had epidermis (Ep), hair follicles (HF) and sebaceous glands (SG). The human ex vivo skin was positioned between the cooling window of the Zimmer cooling device and a heating plate maintained at 37° C. to simulate body temperature.

[0126] A human ex vivo skin sample was treated with two 150 ms pulses of 35 W light with a pulse delay of 1000 ms and without preheating, which resulted in selective damage to parts of the sebaceous glands. Some non-selective damage was shown around the sebaceous glands.

[0127] Human ex vivo skin samples were treated with two 150 ms pulses of 40 W light with a pulse delay of 1000 ms and without preheating, which resulted in selective damage to parts of the sebaceous glands. Some non-selective damage was shown around the sebaceous glands, especially between the sebaceous glands and the epidermis.

[0128] A human ex vivo skin sample was treated with two 150 ms pulses of 35 W light, with a pulse delay of 1000 ms and preheating for 20 seconds at 0.5 W, which resulted in selective damage to parts of the sebaceous glands. Very little non-selective damage was shown around the sebaceous glands.

[0129] Although the above detailed description has shown, described and pointed out the novel features applied to various embodiments, it will be understood that various omissions, substitutions and changes can be made to the form and details of the devices or algorithms shown without departing from the spirit of the present disclosure. As will be appreciated, certain embodiments of the present disclosure described herein can be implemented in a form that does not provide all the features and benefits set forth herein, because some features can be used or practiced separately from other features. The scope of certain disclosures disclosed in this article is indicated by the attached claims rather than the foregoing description. All changes within the meaning and scope of the equivalent schemes of the claims should be covered by the scope of the claims.

Claims

1. A system for controlled thermal treatment of a target comprising a chromophore of interest embedded in a surrounding medium, the system comprising: a pre-process cooling device configured to apply cooling to a surface of the surrounding medium; a pre-treatment light source configured to transmit light into the surrounding medium, the target, and the chromophore of interest; a light processing light source configured to transmit light into the surrounding medium, the target, and the chromophore of interest; a processor in communication with the pre-processing cooling device, the pre-processing light source, and the light-processing light source, and configured to control the pre-processing cooling device, the pre-processing light source, and the light-processing light source; as well as a memory having stored thereon instructions which, when executed by the processor, cause the processor to execute a pre-processing routine and a light processing routine, wherein the processor controls the pre-treatment cooling device and the pre-treatment light source to establish a thermal gradient in the surrounding medium during the pre-treatment routine, the thermal gradient having a peak temperature within a desired depth below the surface of the surrounding medium, wherein the desired depth is selected based on the known depths of the target and the chromophore of interest, wherein the thermal gradient can be established by combining a cooling component and a heating component in various functional forms during the pre-treatment routine, wherein the processor, during the pre-treatment routine, controls the pre-treatment cooling device and the pre-treatment light source to simultaneously apply cooling from the pre-treatment cooling device to the surface of the surrounding medium and transmit light from the pre-treatment light source into the surrounding medium, and wherein simultaneously applying includes full or partial overlap in time; wherein the processor controls the light treatment light source to selectively heat the chromophore of interest during the light treatment routine in an amount sufficient to exceed a damage threshold of the target at the desired depth while not exceeding a damage threshold of the surrounding medium at the desired depth, wherein the pre-treatment light source and the light treatment light source are a single light source, wherein the single light source is a laser, wherein the single light source is configured to provide pulsed light during the pre-treatment routine and the light treatment routine, wherein the single light source is configured to provide light having a wavelength between 1000 nm and 1500 nm or between 1600 nm and 1800 nm or a wavelength of 1210 nm or 1726 nm, and wherein the chromophore of interest is sebum and the target is the sebaceous gland.

2. The system according to claim 1, characterized in that The single light source is configured to provide light having a wavelength tuned to a peak absorption of the chromophore of interest.

3. The system according to claim 2, characterized in that The pre-treatment routine selectively heats the chromophore of interest to a higher temperature than the surrounding medium.

4. The system according to any one of claims 1 to 3, characterized in that: The processor controls the pre-processing cooling device during the light processing routine.

5. The system according to any one of claims 1 to 3, characterized in that: The pre-processing cooling device includes a thermally conductive material coupled to a cooling loop.

6. The system according to any one of claims 1 to 3, characterized in that: The desired depth is between 1 μm and 100 mm.

7. The system according to any one of claims 1 to 3, characterized in that: The surrounding medium is located on or in the subject.

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