Methods, devices, and systems for treating tissue with electromagnetic radiation

Abstract

Methods, devices, and systems for treating a region of interest (ROI) of skin of a subject or patient in need thereof are disclosed. Such a method of treating a ROI, in some embodiments, comprises irradiating a test region (TR) of the skin with a sub-therapeutic dose of electromagnetic radiation or with a series of sub -therapeutic doses, determining a tissue response of the TR, and generating one or more therapeutic dose parameters based at least in part on the tissue response of the TR. In some embodiments, the method further comprises irradiating the ROI with one or more therapeutic doses of electromagnetic radiation in accordance with the one or more therapeutic dose parameters.

Description

METHODS, DEVICES, AND SYSTEMS FOR TREATING TISSUE WITH ELECTROMAGNETIC RADIATIONCROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority pursuant to 35 U.S.C. §119 to U.S. Provisional Patent Application Ser. No. 63 / 650,201, filed on May 21, 2024, which is incorporated herein by reference in its entirety.FIELD

[0002] The present disclosure is generally related to methods, devices, and systems for treating biological tissue such as skin, including with electromagnetic radiation.BACKGROUND

[0003] Plastic and dermatologic therapies commonly incorporate treatments with light. In some previous methods, to perform a treatment the clinician holds a source of light close to the patient’s or subject’s skin and triggers the source to apply light, which treats an area on the patient’s skin. Currently, it is difficult to determine the dose of light provided to the treated area, particularly when the light source is moved across the treatment area. Therapeutic dosing is often based on guesswork by the clinician completing the treatment. This guesswork is highly subjective and time-consuming, and suffers under the learning curve of clinician training. Also, because of variations in the skin’s response to treatment among the patient population and even from region to region on a specific patient’s body, some current methods present one or more risks, such as safety risks. In some cases, for example, the clinician may overtreat the skin, which may produce adverse side effects, such as burning or discomfort. Overtreatment may also interfere with the desired therapeutic results of treatment or result in clinical inefficacy. It is also possible for a clinician to undertreat skin, which may require the patient to return for additional follow up treatments.

[0004] Thus, there exists a need for improved treatment methods, devices, and systems that can provide more successful and efficient treatment and / or reduce the risk of adverse events.SUMMARY

[0005] Some embodiments of the technology described herein can provide one or more advantages for treating biological tissue (such as skin) of a patient or subject in need of such treatment, as compared to some other technology. Such advantages may include, for instance, improved clinical efficiency, improved treatment efficiency, improved safety, reduced clinician error or guesswork, reduced adverse side effects or undesired outcomes, and / or the ability to more reliably adapt or tailor treatment protocols for a specific patient. In some cases, technology described herein may provide one or more of the foregoing advantages by more accurately determining and selecting therapeutic dose parameters of electromagnetic radiation for application to tissue such as skin. More particularly, the disclosed technology, in some embodiments, may provide customized or tailored therapeutic dose parameters specific to the patient or subject or specific to one or more particular regions of interest of the skin of the subject, without overburdening the clinician.

[0006] In one aspect, methods for treating a region of interest (ROI) of skin of a subject in need thereof, such as a human subject, are described herein. A method described herein, in some cases, comprises irradiating a test region (TR) of the skin with a sub -therapeutic dose of electromagnetic radiation or with a series of sub -therapeutic doses, and determining a tissue response of the TR. Moreover, in some embodiments, such a method further comprises generating one or more therapeutic dose parameters based at least in part on the tissue response of the TR. Additionally, in some embodiments, the method further comprises irradiating the ROI with one or more therapeutic doses of electromagnetic radiation in accordance with the one or more therapeutic dose parameters.

[0007] As described further herein, a method according to the present disclosure, in some implementations, can be carried out using a specific device or system or type of device or system. For example, in some embodiments, a method described herein comprises attaching a device to a handpiece, wherein the handpiece comprises a source of electromagnetic radiation that emits electromagnetic radiation along a path in a primary direction. For example, the handpiece may be a handpiece of a broadband light (or “BBL”) system, laser system, or other light-based system provided by Sciton, Inc. Moreover, in some cases, the device comprises a receiving space for the handpiece, and optionally a tissue response detector. In someembodiments, the method further comprises placing the attached device on or adjacent to the skin, and using the handpiece to irradiate at least one TR of the skin with a sub-therapeutic dose of electromagnetic radiation or a series of sub-therapeutic doses of electromagnetic radiation. Additionally, such a method, in some implementations, further comprises determining a tissue response of the TR using the tissue response detector, and generating one or more therapeutic dose parameters based at least in part on the tissue response of the TR. Further, in some such embodiments, the method further comprises removing the device from the handpiece and then using the handpiece (or some other source of light) to irradiate the ROI with one or more therapeutic doses of electromagnetic radiation in accordance with the one or more therapeutic dose parameters. Thus, in some embodiments of a method described herein, a removable or attachable / detachable device is used in conjunction with a separate handpiece, such as a handpiece of a separate light treatment system to provide treatment to a patient or subject. The attachable / detachable device may comprise one or more components configured to carry out or enable certain steps of a method described herein (such as providing a sub-therapeutic dose to skin), while the separate handpiece may comprise one or more components configured to carry out or enable other steps of the method (such as providing a therapeutic dose to skin).

[0008] Alternatively, in some other embodiments, a method described herein is carried out using an integrated device, rather than an attachable / detachable device such as described above. For example, in some such instances, a method described herein comprises placing a device on or adjacent to the skin, wherein the device itself comprises a source of electromagnetic radiation that emits electromagnetic radiation along a path in a primary direction. The device itself may also optionally (and preferably) comprise a tissue response detector. Further, in some embodiments, such a method can also comprise using the integrated device itself to irradiate at least one TR of the skin with a sub-therapeutic dose of electromagnetic radiation or a series of sub-therapeutic doses of electromagnetic radiation, and then determining a tissue response of the TR using the tissue response detector of the device itself. Moreover, in some such implementations, the method further comprises using the integrated device itself to irradiate the ROI with one or more therapeutic doses of electromagnetic radiation in accordance with the one or more therapeutic dose parameters generated as described above.

[0009] Various other methods of treating biological tissue are further described in the detailed description which follows.

[0010] In addition, in another aspect, devices for treating a ROI of skin of a subject in need thereof are described herein. In some embodiments, for example, a device described herein is an attachable / detachable device such as described above. In some such cases, the device comprises a receiving space for a handpiece, wherein the handpiece comprises a source of electromagnetic radiation that emits electromagnetic radiation along a path in a primary direction; an electromagnetic radiation manipulating element (such as a mirror) positioned in the path of the electromagnetic radiation; and a tissue response detector. Various other devices are further described in the detailed description which follows.

[0011] Moreover, in still another aspect, systems for treating a ROI of skin of a subject in need thereof are described herein. Such a system, in some implementations, may be used to carry out a method described herein. In some cases, for instance, a system comprises a source of electromagnetic radiation to irradiate a TR of the skin with a sub-therapeutic dose of electromagnetic radiation or a series of sub-therapeutic doses of electromagnetic radiation; a tissue response detector to determine a tissue response of the TR; a control unit to generate one or more therapeutic dose parameters based at least in part on the tissue response of the TR; and a source of electromagnetic radiation to irradiate the ROI of the skin with one or more therapeutic doses of electromagnetic radiation based on the one or more therapeutic dose parameters.

[0012] In still another aspect, improved computer devices and storage media are also described herein. For example, computer storage media storing computer-useable instructions are described herein. Such a computer storage medium can be used to carry out a method and / or use a system described herein. For instance, in some cases, a computer storage medium stores computer-useable instructions that, when used by one or more computing devices, cause the one or more computing devices to treat an ROI of skin, the operations comprising: irradiating a test region (TR) of the skin with a sub-therapeutic dose of electromagnetic radiation or with a series of sub -therapeutic doses, and determining a tissue response of the TR. Moreover, in some embodiments, the operations further comprise generating one or more therapeutic dose parameters based at least in part on the tissue response of the TR. Additionally, in some embodiments, the operations further comprise irradiating the ROI with one or more therapeuticdoses of electromagnetic radiation in accordance with the one or more therapeutic dose parameters. Various other systems are further described in the detailed description which follows.BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1A illustrates a perspective view of a handpiece that can be attached to a removable device according to one embodiment described herein.

[0014] Figure IB illustrates a perspective view of a removable device attached to the handpiece of Figure 1, according to one embodiment described herein.

[0015] Figure 2 illustrates a different perspective view of the removable device and handpiece of Figure IB.

[0016] Figure 3 illustrates a perspective view of a removable device, according to one embodiment described herein, without a handpiece in place and not attached to a handpiece.

[0017] Figure 4 illustrates a different perspective view of the removable device of Figure 3.

[0018] Figure 5 illustrates a perspective view of the device of Figure 3 and Figure 4.

[0019] Figure 6 illustrates a perspective view of a device according to one embodiment described herein, disposed on or adjacent to the skin of a patient or subject.

[0020] Figure 7 illustrates a perspective view of a device according to one embodiment described herein.

[0021] Figure 8 illustrates a block diagram of a system incorporating one device according to one embodiment described herein.

[0022] Figure 9 illustrates a block diagram of a system incorporating two devices according to one embodiment described herein.

[0023] Figure 10 illustrates images of a test region while carrying out a method according to one embodiment described herein.

[0024] Figure 11 illustrates a plot of the mean temperature of the images of Figure 10.

[0025] Figure 12 illustrates images of a test region while carrying out a method according to one embodiment described herein.

[0026] Figure 13 illustrates temperature rise plots of tissue of test regions irradiated at different fluences according to some embodiments of a method described herein.

[0027] Figure 14 illustrates a plot of the temperature maxima at the different fluences from Figure 13.

[0028] Figure 15 illustrates a flow chart of steps of a method according to one embodiment described herein.

[0029] Figure 16 illustrates a flow chart of steps of a method according to one embodiment described herein.

[0030] Figure 17 illustrates a flow chart of steps of a method according to one embodiment described herein.

[0031] Figure 18 illustrates an image captured with a visual camera of a test region of skin with overlays of predicted tissue temperatures based on treatment according to one embodiment of a method described herein.

[0032] Figure 19 illustrates an image captured with a visual camera of a test region of skin with overlays of predicted tissue temperatures based on treatment according to one embodiment of a method described herein.

[0033] Figure 20 illustrates an image captured with a visual camera of a test region of skin with overlays of predicted tissue temperatures based on treatment according to one embodiment of a method described herein.

[0034] Figure 21 illustrates a block diagram of a system according to one embodiment described herein.

[0035] Figure 22 illustrates a block diagram of a computer system in accordance with various embodiments described herein.DETAILED DESCRIPTION

[0036] Embodiments described herein can be understood more readily by reference to the following detailed description, examples, and figures. Elements, apparatus, and methods described herein, however, are not limited to the specific embodiments presented in the detailed description, examples, and figures. It should be recognized that these embodiments are merely illustrative of the principles of the present invention. Numerous modifications and adaptations will be readily apparent to those of skill in the art without departing from the spirit and scope of the invention.

[0037] In addition, all ranges disclosed herein are to be understood to encompass any and all subranges subsumed therein. For example, a stated range of “1.0 to 10.0” should be considered to include any and all subranges beginning with a minimum value of 1.0 or more and ending with a maximum value of 10.0 or less, e.g., 1.0 to 5.3, or 4.7 to 10.0, or 3.6 to 7.9. Similarly, a stated range of “1 to 10” should be considered to include any and all subranges beginning with a minimum value of 1 or more and ending with a maximum value of 10 or less, e.g., 1 to 5, or 4 to 10, or 3 to 7, or 5 to 8.

[0038] All ranges disclosed herein are also to be considered to include the end points of the range, unless expressly stated otherwise. For example, a range of “between 5 and 10” should generally be considered to include the end points 5 and 10.

[0039] Further, when the phrase “up to” is used in connection with an amount or quantity, it is to be understood that the amount is a non-zero amount or quantity.

[0040] Additionally, in any disclosed embodiment, the terms “substantially,” “approximately,” and “about” may be substituted with “within [a percentage] of’ what is specified, where the percentage could be 0.1, 1, 5, or 10 percent, unless the use of such a term in a given instance indicates otherwise.

[0041] It is also to be understood that the article “a” or “an” refers to “at least one,” unless the context of a particular use requires otherwise.

[0042] The present disclosure is generally related to methods, devices, and systems for treating biological tissue such as skin, including with electromagnetic radiation. More specifically, methods, devices, and systems described herein can, in some embodiments, provide various advantages by more accurately determining and selecting therapeutic dose parameters of electromagnetic radiation for application to tissue such as skin. More particularly, the disclosed technology, in some implementations, may provide customized or tailored therapeutic dose parameters specific to the patient or subject or specific to one or more particular regions of interest (ROI or ROIs) of the skin of the subject, without overburdening the clinician. Thus, in some cases, a method, device, or system described herein may provide successful and efficient treatment of the tissue (e.g., skin) with sources of electromagnetic radiation with a reduced safety risk.

[0043] Methods of treating an ROI described herein can be carried out using various steps or combinations of steps, and using various hardware and / or software components. Various devices or systems can also be used to carry out a method described herein, as further detailed below. For example, in some cases, a method described herein can be carried out using a single integrated treatment device or system. In other embodiments, a method described herein can be carried out using a combination of individual or discrete devices or systems.

[0044] In general, a method described herein, in some embodiments, comprises irradiating a test region (TR) of the skin with a sub-therapeutic dose of electromagnetic radiation or with a series of sub-therapeutic doses, and determining a tissue response of the TR. It is to be understood that the tissue response is in “response” to the sub-therapeutic dose or series of sub-therapeutic doses of light. In some instances, the method further comprises generating one or more therapeutic dose parameters based at least in part on the tissue response of the TR. Additionally, in some implementations, the method further comprises irradiating the ROI with one or more therapeutic doses of electromagnetic radiation in accordance with the one or more therapeutic dose parameters.

[0045] As mentioned above, in some embodiments described herein, a combination of individual devices can be used to carry out a method according to the present disclosure. Figures 1 and 2 illustrate aspects of one non-limiting example embodiment of a device (201) that can be used for treating an ROI of skin. The device (201) is a removable or attachable / detachable device that fastens or attaches to a handpiece (203), such as a handpiece of a separate, independently functional light treatment system, such as a BBL system or laser provided by Sciton, Inc. Figure 1A illustrates a perspective view of the handpiece (203), unattached to the device (201). Figure IB illustrates a perspective view of the device (201) when attached to the handpiece (203). In Figure IB, the device (201) comprises a receiving space (202) for the handpiece (203). As a visual aid, the handpiece (203) is depicted in Figure 1A, Figure IB, and Figure 2 with hatching. In the embodiment of Figure 1 and Figure 2, the handpiece (203) comprises a source of electromagnetic radiation (204) that emits electromagnetic radiation or light (not shown in Figure 1A-B). The radiation, in this embodiment, would initially be emitted by source (204) generally downward toward the bottom of the page in Figures 1A, IB, and 2, in the direction of arrow “D”. The electromagnetic radiation is not specifically illustrated in Figures 1 and 2. Additionally, theelectromagnetic radiation can be referred to as a “portion” of electromagnetic radiation or light. Further, in some cases, the portion of electromagnetic radiation can be a collimated portion of light, such as a beam of light. In other instances, the emitted portion of light may not have characteristics consistent with a “beam” of light, such as a collimated beam of light. Instead, in some such cases, the emitted light may be diffuse light.

[0046] In the embodiment of Figure IB and Figure 2, the device (201) also comprises a tissue response detector (205) and a visual camera (206). Figure 2 illustrates a rotated view of the device (201) of Figure IB, with the handpiece (203) in place. In this view, both the tissue response detector (205) and visual camera (206) are visible. The test region of skin (207) is positioned “below” the device (201), where, according to the perspective view of Figure 2, “below” is toward the right side of Figure 2. The test region of skin (207) is schematically depicted in Figure 2 as a wavy line or surface, indicating a possible topology of a surface of skin. As illustrated in Figure 2, a signal (209) is received from the test region (207) and detected by the tissue response detector (205) and / or visual camera (206). For example, the signal (209) may be infrared (IR) light emitted from the test region (207) and detected by the tissue response detector (205) as heat or thermal energy.

[0047] As illustrated in Figure 2, it will be appreciated that, in some embodiments, a device (201) coupled or attached to a handpiece (203) may be positioned, oriented, or applied to a surface of skin (such as test region (207)) in an orientation that is different than (e.g., substantially orthogonal to) the orientation the handpiece (203) might have during treatment if the device (201) were not attached to the handpiece (203). That is, the handpiece (203) coupled to device (201) may be laid on its side on the skin (207), instead of being held or positioned upright on the skin (207), with arrow D pointing toward the skin (207). Such an orientation of the handpiece (203) “on its side” may be suitable due to alteration of the pathway of light emitted by the light source (204) of the handpiece (203), as described further hereinbelow (e.g., with reference to Figure 5).

[0048] Figures 3-5 illustrate another non-limiting example embodiment of a removable or attachable / detachable handpiece (201), similar to the handpiece (201) illustrated in Figures 1 and 2. However, in Figures 3-5, the device (201) is illustrated without the handpiece (203) in place.Specifically, Figure 3 is a similar view of the device (201) as Figure 2. However, in Figure 3, the receiving space (202) where the handpiece can be clipped or fastened can be seen.

[0049] Figure 4 illustrates of the view of the device (201), where the view is “into” or toward the receiving space (202), orthogonal to the plane of the page of Figure 4 and parallel to axis of light emission from the source of the electromagnetic radiation of the handpiece (handpiece not shown). The view of Figure 4 is from “above” the source of electromagnetic radiation (or, more accurately, from above where the source would be, if the handpiece were attached to the device (201) in Figure 4, which it is not).

[0050] Figure 5 illustrates a different perspective view of the device (201), without the handpiece in place, showing an electromagnetic radiation manipulating element (208). In some cases, the electromagnetic radiation manipulating element (208) comprises a mirror. Moreover, in some embodiments, the electromagnetic radiation manipulating element (208) is positioned in the path of the electromagnetic radiation emitted by the handpiece, such as along primary direction (PD) in Figure 5.

[0051] Figure 6 is a zoomed in view of the tissue response detector (205) and visual camera (206) of the device (201). Figure 6 also illustrates the skin (207) and the electromagnetic radiation manipulating element (208). The handpiece itself is not shown in Figure 6.

[0052] Moreover, as mentioned previously, in some embodiments, a method described herein can be carried out using a single integrated device, rather than using a removable device such as illustrated in Figures 1-5. Figure 7 illustrates one non-limiting example embodiment of such an integrated device (301). In this non-limiting example, the device (301) comprises a tissue response detector (302), a visual camera (303), a first source of electromagnetic radiation (304), and a second source of electromagnetic radiation (305). As illustrated in Figure 7, the device comprises a spacer (306) that may contact the skin of the region of interest (ROI not shown in Figure 7; the plane or curved surface of the skin would be generally perpendicular to a line drawn toward the spacer (306) from the first and second sources of electromagnetic radiation (304, 305).

[0053] It is to be understood that the devices illustrated in Figures 1-7 are non-limiting examples of removable and integrated devices. Instead, these specific embodiments are provided for illustration purposes. Other removable devices and integrated devices are also contemplated bythe present disclosure, and the precise structure of a device used to carry out a method described herein is not necessarily limited.

[0054] Moreover, as described previously, in some implementations, systems for treating an ROI of skin are described herein, and such systems may incorporate one or more devices described herein and / or be used to implement one or more methods described herein. Further, it is to be understood that a system described herein may include a plurality of components. Figure 8 illustrates a block diagram of an example of a system (401) comprising a single device (402). In such a system, the device (402) comprises a source of electromagnetic radiation (403) to irradiate a test region (TR) of the skin with a sub-therapeutic dose of electromagnetic radiation (or series of sub -therapeutic doses) and a tissue response detector (404) to determine a tissue response of the TR. The device (402) of the system (401) also comprises a source of electromagnetic radiation (405) to irradiate the ROI of the skin with one or more therapeutic doses of electromagnetic radiation based on the one or more therapeutic dose parameters. However, in some embodiments of a system (401) with a single device (402), it may be that the source of electromagnetic radiation (403) used to irradiate the TR and the source of electromagnetic radiation (405) used to irradiate the ROI are the same. Additionally, as illustrated in Figure 8, the system (401) further comprises a visual camera (406). Moreover, the system further comprises a control unit (407) to generate one or more therapeutic dose parameters based at least in part on the tissue response of the TR. The control unit (407) may be co-localized with the device (402), in the sense that both the control unit (407) and the device (402) are close to one another, such as in the same room. Alternatively, in other instances, the control unit (407) may not be colocalized or co-located with the device (402), such as may occur, for instance, if the control unit (407) is in remote communication with the device (402), e.g., through cloud computing or otherwise.

[0055] Figure 9 illustrates a block diagram of a non-limiting example of a system (501) incorporating a first device (502) and a second device (503). The first device (502) comprises a source of electromagnetic radiation (504) to irradiate a TR, a tissue response detector (505), a visual camera (506), and a control unit (507) to generate the one or more therapeutic dose parameters. However, in some embodiments of a two device system, the control unit (507) may be located on or in the second device (503), or remote from both the first device (502) and thesecond device (503), such as may occur if the control unit (507) is in remote communication with the first device (502) and / or second device (503), e.g., through cloud computing or otherwise. In Figure 9, the second device (503) comprises a source of electromagnetic radiation (508) to irradiate the ROI. Thus, in this example of a system, the source of electromagnetic radiation (504) that irradiates the TR and the source of electromagnetic radiation (508) that irradiates the ROI are located on different devices. In some such instances, the first source of electromagnetic radiation (504) provides sub-therapeutic irradiation, whereas the second source of electromagnetic radiation (508) provide therapeutic irradiation.

[0056] Certain elements of methods, devices, and systems for treating skin will now be described in more detail.

[0057] It is to be understood that a method, device, and / or system described herein can be used to treat any portion of a subject or a patient, without particular limitation. For instance, in some cases, the region of interest (ROI) is located on the face of the subject. In other cases, the ROI is located on the neck, chest, back, or legs of the subject. Other areas of the body may also be treated as an ROI.

[0058] Moreover, the area of a ROI can be any size or of any magnitude not inconsistent with the technical objectives of this disclosure. For example, in some embodiments, the area of a specific ROI can be 10 mm2to 1,000 cm2; 20 mm2to 1,000 cm2; 30 mm2to 1,000 cm2; 40 mm2to 1,000 cm2; 40 mm2to 1,000 cm2; 50 mm2to 1,000 cm2; 60 mm2to 1,000 cm2; 70 mm2to 1,000 cm2; 80 mm2to 1,000 cm2; 90 mm2to 1,000 cm2; 100 mm2to 1,000 cm2; 200 mm2to 1,000 cm2; 300 mm2to 1,000 cm2; 400 mm2to 1,000 cm2; 500 mm2to 1,000 cm2; 600 mm2to 1,000 cm2; 700 mm2to 1,000 cm2; 800 mm2to 1,000 cm2; 900 mm2to 1,000 cm2; or 1 cm2to 1,000 cm2. Other sizes of ROI are also possible.

[0059] Similarly, the area of the test region (TR) of a method described herein can be any size not inconsistent with the technical objectives of this disclosure. For example, in some embodiments, the area of a TR can be 10 mm2to 1,000 cm2; 20 mm2to 1,000 cm2; 30 mm2to 1,000 cm2; 40 mm2to 1,000 cm2; 40 mm2to 1,000 cm2; 50 mm2to 1,000 cm2; 60 mm2to 1,000 cm2; 70 mm2to 1,000 cm2; 80 mm2to 1,000 cm2; 90 mm2to 1,000 cm2; 100 mm2to 1,000 cm2; 200 mm2to 1,000 cm2; 300 mm2to 1,000 cm2; 400 mm2to 1,000 cm2; 500 mm2to 1,000 cm2; 600 mm2to 1,000 cm2; 700 mm2to 1,000 cm2; 800 mm2to 1,000 cm2; 900 mm2to 1,000 cm2; or1 cm2to 1,000 cm2. Other sizes of a TR are also possible. Moreover, in some cases, an individual TR has an area that is smaller than the area of the ROI. In some such embodiments, the area of the ROI is at least 10 times, at least 50 times, at least 100 times, or at least 1000 times larger than the area of an individual TR or of the average size of all TRs (if more than one TR is used in the method). In some cases, the area of the ROI is 10 to 10,000 times, 10 to 5000 times, 10 to 1000 times, 50 to 10,000 times, 50 to 5000 times, 50 to 1000 times, 100 to 10,000 times, 100 to 5,000 times, or 100 to 1000 times larger than the area of an individual TR or of the average size of all TRs (if more than one TR is used in the method). In some implementations, an individual TR is the same size as the ROI. That is, in some embodiments, the ROI comprises a single TR, and the TR and ROI are co-extensive with or identical to one another.

[0060] Additionally, a TR may have any shape (e.g., in two dimensions, or within the plane of the outer surface of the skin) not inconsistent with the technical objectives of the present disclosure. For example, in some embodiments, the shape of a TR may be a circle, a square, a rectangle, a polygon, or some other geometric shape. However, in some implementations, the shape of a TR may also be amorphous and not correspond to a particular, well-defined geometric shape.

[0061] Moreover, it is to be understood that a sub-therapeutic dose of electromagnetic radiation can refer to any dose of electromagnetic radiation that is less than a therapeutic dose or that does not provide a therapeutic or clinical effect. For example, in some cases, a sub -therapeutic dose has a total duration, fluence (e g., optical energy delivered per unit area, such as in I / cm2), and / or power that is below a total needed to provide a specific therapeutic effect to the irradiated region of the patient or subject, such as a thermal ablation. In contrast, for reference purposes herein, a therapeutic dose of electromagnetic radiation does provide a therapeutic effect and generally has a total duration, fluence, and / or power that meets or exceeds the minimum needed to provide a specific therapeutic effect to the irradiated region of the patient or subject (such as thermal ablation). Thus, it is to be understood that, as used in the present disclosure, a “sub-therapeutic dose” by definition cannot also be a “therapeutic dose” in the context of a specific method, device, or system described herein.

[0062] Additionally, it is also to be understood that a sub -therapeutic irradiation step of a method described herein, in some embodiments, can include, comprise, or consist of only one sub-therapeutic dose. Alternatively, in other cases, it is also possible for a sub-therapeutic irradiation step of a method described herein to include, comprise, or consist of a series of sub-therapeutic doses (e.g., a series of two or more doses), instead of only one dose. Further, in such embodiments, each of the doses in the series can be a sub-therapeutic dose individually, as “sub- therapeutic” is described above. Moreover, the entire series in sum can be a sub-therapeutic dose, as described previously.

[0063] Further, any source of electromagnetic radiation not inconsistent with the objectives of the present disclosure may be used. Many suitable sources of electromagnetic radiation will be readily apparent to those of ordinary skill in the art. In some embodiments, the source of electromagnetic radiation comprises a laser. It is to be understood that a “laser” can refer to a single lasing device that produces a single beam of laser light from a single lasing medium. In some embodiments, a laser described herein can be a pulsed laser or a continuous wave (CW) laser. Moreover, when a pulsed laser is used, the laser can produce time-modulated pulses of the laser beam. For instance, in some cases, the laser beam comprises an ablative laser beam and the laser produces time-modulated pulses of the ablative laser beam. In other cases, the laser beam comprises a coagulative laser beam and the laser produces time-modulated pulses of the coagulative laser beam.

[0064] A laser or laser beam described herein can have any power and any peak or average emission wavelength not inconsistent with the objectives of this disclosure. For example, in some embodiments, a laser or laser beam of a device described herein has a peak or average emission wavelength in the infrared (IR) region of the electromagnetic spectrum. In some such cases, the laser or laser beam has a peak or average emission wavelength in the range of 1-4 pm, 1-3 pm, 2-4 pm, 2-3 pm, 8-12 pm, or 9-11 pm. For example, in some embodiments, the laser or laser beam comprises an erbium-doped yttrium aluminum garnet (Er:YAG) laser or laser beam or a neodymium-doped YAG (Nd:YAG) laser or laser beam having a peak or average emission wavelength of 2940 nm or 1064 nm. In other cases, the laser or laser beam comprises a carbon dioxide laser or laser beam. A laser beam described herein can also have a peak or average emission wavelength in the visible region of the electromagnetic spectrum. Non-limiting examples of peak or average emission wavelengths suitable for use in some embodiments described herein include 532 nm, 695 nm, 755 nm, 1064 nm, and 1470 nm, or 2940 nm. In someother embodiments, the laser beam can have an average wavelength X between 700 and 1500 nm. In some other instances, the laser beam can have an average wavelength between 900 and 1300 nm. Also, in some instances, a laser or laser beam of a device described herein has an average power of 1 to 10 W, 10 W to 50 W, or 50 to 200 W. Moreover, the spot size of a laser beam produced by a laser described herein may also vary. Any spot size not inconsistent with the technical objectives of the disclosure may be used. In some cases, for instance, the spot size is 0.1-10 mm, 0.1-1 mm, 0.1-0.5 mm, 0.5-5 mm, 1-10 mm, or 1-5 mm. Other spot sizes may also be used.

[0065] Additionally, in other embodiments, the source of electromagnetic radiation comprises a broadband light or “BBL” source or beam. As understood by one of ordinary skill in the art, the terms “BBL” source and “BBL beam” can refer to a source and beam, respectively, of intense, broad-spectrum pulses of light, including as defined and approved by the U.S. Food and Drug Administration. More particularly, in some embodiments, a BBL beam produced by a BBL source can comprise pulses of non-coherent or non-laser light having a wavelength from 500 nm to 1200 nm, as described, for instance, in Raulin et al., “IPL technology: a review,” Lasers Surg. Med. 2003, 32:78-87. Any laser, BBL source, laser beam, or BBL beam not inconsistent with the objectives of this disclosure can be used. Moreover, the choice of laser, BBL source, or laser or BBL beam can be based on a desired effect of the laser or BBL beam and / or on a desired target of the laser or BBL beam. A BBL source described herein generally produces a pulsed light output. In some cases, the BBL source comprises a xenon gas-filled chamber. In such instances, the BBL source can produce a BBL beam by the application of bursts or pulses of electrical current through the xenon-containing chamber.

[0066] Further, in other implementations, the source of electromagnetic radiation comprises a source of intense pulsed light (IPL). As understood by one of ordinary skill in the art, IPL sources are non-laser high intensity light sources that employ filtered flashlamps to produce noncoherent pulsed light across a broad wavelength spectrum of approximately 400 nm to 1400 nm.

[0067] The dose of electromagnetic radiation provided in accordance with a method described herein can have various properties, such as a determined intensity, fluence and / or duration. It is to be understood, for reference purposes herein, that a “dose” (or “application”) of electromagnetic radiation is generally not synonymous with a “pulse” of electromagneticradiation, particularly not with respect to the “pulses” of light inherently produced by a pulsed laser (as opposed to a continuous wave laser). Instead, a “dose” of electromagnetic radiation in the context of the present disclosure refers to light emitted by a source of electromagnetic radiation during a single, discrete “on” time of the source of electromagnetic radiation, during which the light is directed to the relevant TR (or ROI, as the case may be). Moreover, the “dose” of electromagnetic radiation can have a duration that is greater than the pulse duration of a pulsed laser or source (if a pulsed laser or source is used). For example, in some cases, a single “dose” of electromagnetic radiation is at least 1 ms, at least 5 ms, at least 10 ms, at least 100 ms, at least 0.5 seconds, or at least 1 second in duration. In some cases, a “dose” of electromagnetic radiation described herein has a duration of 1 ms to 10 seconds, 1 ms to 5 seconds, 1 ms to 1 second, 100 ms to 10 seconds, 100 ms to 5 seconds, or 100 ms to 1 second. Moreover, a “dose” of electromagnetic radiation is temporally bounded on both sides by an “off’ period of time during which the source of electromagnetic radiation is “off.” Further, this “off’ period of time is longer than (and different from) the time between pulses generated by a pulsed source in continuous operation (if a pulsed source is used).

[0068] Additionally, in some embodiments, it is also to be understood that a plurality of sources of electromagnetic radiation may be used, including in the case of methods, systems, and devices describing herein involving multiple irradiation steps. For example, in some instances, a sub- therapeutic irradiation step is carried out using a first laser, while a therapeutic irradiation step is carried out using a second laser, wherein the first laser and the second laser are different lasers. Similarly, in some cases, a sub-therapeutic irradiation step is carried out using a non-laser light source, while a therapeutic irradiation step is carried out using a laser. However, it is also possible, in some embodiments, for multiple irradiation steps or all irradiation steps of a method described herein to be carried out using only a single source of electromagnetic radiation. For example, in some implementations of a method, device, or system described herein, irradiating the TR and irradiating the ROI are both carried out using the same source of electromagnetic radiation (e.g., a laser).

[0069] Turning now in more detail to some other steps of a method described herein, in some implementations, a method described herein comprises imaging the TR (e.g., at the same time as determining the tissue response of the TR). In some embodiments, imaging the TR comprisescapturing an image of the TR with a visual camera. For reference purposes herein, a visual camera includes a camera that collects images in the visible spectrum. Many suitable visual cameras will be readily apparent to those of ordinary skill in the art. Non-limiting examples of a visual camera include RGB cameras, monocular cameras, stereo cameras, and fish eye cameras.

[0070] Moreover, in some cases, generating one or more therapeutic dose parameters is further based at least in part on the image of the TR. In some instances, the image of the TR is correlated to the tissue response of the TR. For reference purposes herein, a tissue response may comprise an observable change in the skin of the TR, including changes in temperature, color changes (e.g., color darkening, color lightening, etc.), or other spectral changes. In some implementations, the tissue response of the TR is detected using a tissue response detector. Moreover, in some embodiments, the tissue response of the TR corresponds to a sensed temperature, a detected color or color change, or another detected spectral change. It is to be understood that, in some embodiments, a tissue response detector may be a detector that can perceive, sense, detect, or measure an observable change in the skin, including a sensed temperature, a detected color or color change, or another detected spectral change. Many suitable tissue response detectors will be readily apparent to those of ordinary skill in the art. For example, in some embodiments, a tissue response detector comprises an infrared (IR) camera or a thermal camera.

[0071] Additionally, in some embodiments, the TR comprises one or more target features (TFs); and generating one or more therapeutic dose parameters is further based at least in part on a tissue response of the one or more TFs. In some embodiments, a target feature can be or refer to a visual “mark” on the skin that is the target for therapeutic treatment. That is, in such cases, the mark is the target for changing, lightening, or removal by therapeutic irradiation. In some implementations, a visual mark on the skin may include those marks that are visible to the unaided healthy eye of an average adult human observer. Non-limiting examples of a visual mark on the skin may include lesions, veins, capillaries, other blood vessels, redness, acne, acne scarring, skin scarring, moles, birthmarks, changes in skin texture, melasma, and hyperpigmentation. In some embodiments, the size of the target feature may be the same size in terms of area as the TR. In some cases, the size of the target feature may be substantially the same as the TR (i.e., at least 90% of the area of the TR). Moreover, in some implementations, aTF may be the same size or substantially the same size as the ROI (i.e., at least 90% of the area of the ROI). That is, in some cases, the entire ROI (or nearly the entire ROI) is intended to be treated as a “target”.

[0072] Moreover, in some cases, the TR comprises one or more non-target features (NTFs). Such NTFs, in some cases, are present in a TR along with one or more TFs. In other instances, a specific TR includes one or more NTFs, and does not include any TFs. In addition, in some embodiments in which a TR includes one or more NTFs, a method described herein can comprise generating one or more therapeutic dose parameters based at least in part on a tissue response of the one or more NTFs. It is to be understood that a non-target feature comprises a visual mark or a selected area on the skin that is not a target for therapeutic treatment. Moreover, in some implementations, a non-target feature can refer to a TR of skin that is substantially free or completely free of target features.

[0073] Additionally, in some implementations, the tissue response of a TR comprising one or more TFs and one or more NTFs may be correlated to the sub-therapeutic dose or series of sub- therapeutic doses of electromagnetic radiation to provide thermal dose parameters for treating a ROI. In some embodiments, determining the tissue response of such a TR (that is, a TR comprising both a TF (or more than one TF) and also an NTF (or more than one NTF)) comprises imaging one or more TFs and one or more NTFs at the same time. Moreover, in some implementations, imaging such a TR comprises capturing an image of the one or more TFs and one or more NTFs with a visual camera. Further, in some such cases, the image of the TR can be used to generate the one or more therapeutic dose parameters. That is, in some embodiments, capturing the image of the tissue response for the TFs and NTFs (e.g., in the same image or imaging step) can permit the selection of one or more therapeutic dose parameters that provide sufficient treatment of the TFs, but do not cause undue adverse effects (e.g., burning) of the NTFs. Moreover, in some such cases, the tissue response of the TFs and NTFs can be distinguished on a pixel-by-pixel basis. Similarly, in some embodiments, the one or more therapeutic dose parameters can be determined on a pixel-by-pixel basis, or by fitting a function to provide therapeutic dose parameters for treating a ROI, using both TF data and also NTF data (that is, using both the tissue response of the one or more TFs and also the tissue response of the one or more NTFs).

[0074] Further, it is to be understood that a method, device, or system described herein can use more than one TR, including more than one TR within the ROI. That is, in some implementations described herein, a plurality of TRs can be irradiated, probed, or tested. It is further to be understood that, in some such instances, the foregoing description of a method using one TR can be duplicated or expanded in an analogous way for a plurality of TRs. For example, in some cases, a method described herein comprises irradiating a plurality of test regions (TRs) of the skin with a sub-therapeutic dose of electromagnetic radiation (e.g., irradiating each of the plurality of TRs with a separate sub-therapeutic dose of electromagnetic radiation, or with a separate series of sub-therapeutic doses as described further herein), and determining a tissue response of each of the plurality of TRs. Additionally, in some such embodiments, the one or more therapeutic dose parameters can be generated based at least in part on the tissue responses of each of the plurality of TRs (e.g., by averaging the separate tissue response of the separate TRs).

[0075] Alternatively, in some implementations, a plurality of TRs may be irradiated, probed, or tested, but the therapeutic dose parameters may be based on the tissue response of only one of the TRs, or from some number of TRs less than all of the TRs irradiated, probed, or tested. In some example embodiments described herein, a method further comprises irradiating n additional TRs of the skin with n additional sub-therapeutic doses of electromagnetic radiation or n additional series of sub-therapeutic doses of electromagnetic radiation, determining H additional tissue responses of the n additional TRs, and generating one or more therapeutic dose parameters based at least in part on the n additional tissue responses of the n additional TRs. In some embodiments, n is an integer between 1 and 10,000, between 1 and 100,000, between 1 and 106, between 1 and 107, between 1 and 108, between 1 and 109, between 10,000 and 100,000, between 10,000 and 106, between 10,000 and 107, between 10,000 and 108, between 10,000 and 109, between 100,000 and 106, between 100,000 and 107, between 100,000 and 108, between 100,000 and 109, between 106and 107, between 106and 108, between 106and 109, between 107and 108, between 107and 109, or between 108and 109. Moreover, in some cases, ti is based on, or in some implementations, the same as, the resolution of the visual camera (if present) and / or the resolution of the tissue response detector (if present). For example, in some embodiments, if avisual camera or a tissue response detector, which is described below, has a resolution of two megapixels, then n may be 2 million.

[0076] Additionally, in some embodiments, irradiating the ROI in accordance with the one or more therapeutic dose parameters provides a therapeutic effect to the one or more TFs, and irradiating the ROI in accordance with the one or more therapeutic dose parameters does not damage the one or more TFs beyond a therapeutic damage threshold. It is to be understood that in some cases, a therapeutic damage threshold may include a level of skin damage, change, or treatment to the ROI caused by the intended therapeutic treatment (i.e., a total duration, fluence, and / or power that meets or exceeds the minimum needed to provide a specific therapeutic effect) and a minimum level of additional unintended damage, change, or treatment. In some embodiments, a therapeutic damage threshold may be reached when the ROI of skin develops symptoms that are considered by a clinician to be adverse side effects to the source of electromagnetic radiation used beyond the level typical of those side effects of a therapeutic dose. For example, in some instances, when a therapeutic damage threshold is reached, the skin of the ROI may experience burning, swelling, redness, and irritation beyond the typical level experienced with a therapeutic dose. In some cases, these adverse symptoms may develop immediately upon application of the ROI irradiating step. In other cases, these symptoms may develop after 1 hour, 2 hours, 6 hours, 12 hours, 24 hours, or 48 hours following the ROI irradiating step. In some instances, these symptoms development between 1 and 72 hours, between 1 and 48 hours, between 6 and 72 hours, between 6 and 48 hours, between 12 and 72 hours, between 12 and 48 hours, between 24 and 48 hours, or between 24 and 72 hours following the ROI irradiation step.

[0077] Further, in some embodiments, relationships among the tissue response of TRs and sub- therapeutic doses can be correlated to provide thermal dose parameters for treating an ROI. In some implementations, generating one or more therapeutic dose parameters is based on a regression function. In some such cases, the regression function comprises a linear function or one or more rate functions. In some instances, the rate function comprises an Arrhenius function, a bioheat function, and a light transport function. In some instances, the rate function comprises a derivative of a light transport function. The use of Arrhenius functions is described, for example, in W.C. Dewey, “Arrhenius relationships from the molecule and cell to the clinic,” Int. J.Hyperthermia, February 2009; 25(1): 3-20. Thermal dosing of tissue is described, for example, in Dewhirst et al., “Thermal Dose Requirement for Tissue Effect: Experimental and Clinical Findings,” Proc SPIE Int Soc Opt Eng. 2003 June 2; 4954:37.

[0078] Another embodiment of a method described herein will now be further discussed. In some implementations of a method for treating an ROI, the method comprises attaching a device to a handpiece, wherein the handpiece comprises a source of electromagnetic radiation that emits electromagnetic radiation (e.g., a portion or beam of electromagnetic radiation) along a path in a primary direction, and wherein the device comprises a receiving space for the handpiece, and a tissue response detector. In some cases, the method further comprises placing the attached device on or adjacent to the skin, and irradiating at least one TR of the skin with a sub-therapeutic dose of electromagnetic radiation or a series of sub-therapeutic doses of electromagnetic radiation, using the handpiece. Moreover, in some implementations, the method further comprises determining a tissue response of the TR using the tissue response detector, and generating one or more therapeutic dose parameters based at least in part on the tissue response of the TR. Additionally, in some embodiments, the method further comprises removing the device from the handpiece, then placing the handpiece on or adjacent to the skin, and irradiating the ROI with one or more therapeutic doses of electromagnetic radiation in accordance with the one or more therapeutic dose parameters. Moreover, in some cases, the receiving space may include an element to hold, retain, or restrain the handpiece in place within the receiving space. In some implementations, the receiving space comprises a fastener, clip, or bracket for retaining and / or restraining the handpiece. Thus, as discussed previously, it is to be understood that some embodiments of a method or system described herein may be implemented with a combination of devices or components (e.g., an attachment — the removable device — that is used in conjunction with the handpiece of a separate system).

[0079] Moreover, in some such implementations, irradiating the at least one TR with the sub- therapeutic dose of electromagnetic radiation or the series of sub-therapeutic doses of electromagnetic radiation, using the handpiece, comprises emitting a test portion (or beam) of electromagnetic radiation from the handpiece along the path in the primary direction, and irradiating the ROI with the one or more therapeutic doses of electromagnetic radiation comprises emitting a treatment portion (or beam) of electromagnetic radiation from thehandpiece. Moreover, in some such instances, the test portion (or beam) of electromagnetic radiation has a sub-therapeutic fluence, and the treatment portion (or beam) of electromagnetic radiation has a therapeutic fluence. That is, in some embodiments, the fluence of the electromagnetic radiation is selected by altering, manipulating, or changing the parameters of the source of the electromagnetic radiation of the handpiece, as compared to some other embodiments described herein, which may incorporate an electromagnetic radiation manipulating element to alter, manipulate, or change characteristics of the electromagnetic radiation, including fluence (but without altering the actual light generation step or light generation parameters at the light source).

[0080] Further, while it is to be understood that the therapeutic dose or doses of electromagnetic radiation may be applied with the same device as that which applies the sub-therapeutic dose or doses of electromagnetic radiation (as discussed previously), in some cases, it is possible that a separate device is used to apply the therapeutic dose or doses.

[0081] Thus, in some embodiments, a method for treating an ROI comprises placing a device on or adjacent to the skin, wherein the device comprises a source of electromagnetic radiation that emits electromagnetic radiation (e.g., a portion or beam of light) along a path in a primary direction and a tissue response detector. In some implementations, the method further comprises irradiating at least one TR of the skin with a sub-therapeutic dose of electromagnetic radiation or a series of sub-therapeutic doses of electromagnetic radiation, using the device, determining a tissue response of the TR using the tissue response detector, and generating one or more therapeutic dose parameters based at least in part on the tissue response of the TR.

[0082] Additionally, in some cases, the method further comprises placing the device on or adjacent to the skin, and irradiating the ROI with one or more therapeutic doses of electromagnetic radiation in accordance with the one or more therapeutic dose parameters. The foregoing steps can correspond to the situation in which the same device provides both therapeutic and sub-therapeutic doses.

[0083] In other cases, however, a method described herein can comprise placing a second device on or adjacent to the skin, instead of placing the “original” or “first” device on or adjacent to the skin after the sub -therapeutic irradiation. In such instances, the second device can comprise a source of electromagnetic radiation that emits electromagnetic radiation (e.g., a portion or beamof electromagnetic radiation), and the method can further comprise irradiating the ROI with one or more therapeutic doses of electromagnetic radiation in accordance with the one or more therapeutic dose parameters, using the second device. The foregoing steps can correspond to the situation in which different devices provide the therapeutic and sub-therapeutic doses.

[0084] Regarding the configuration and arrangement of the elements of embodiments comprising two devices described herein, many combinations may be contemplated. For example, in some implementations, the source of electromagnetic radiation to irradiate the TR is a component of a first device. In other implementations, the source of electromagnetic radiation to irradiate the TR is a component of a second device. In some cases, the tissue response detector is a component of the first device. In other cases, a visual camera may be a component of the first device. In some embodiments, a control unit may be a component of the first device of the system. In other embodiments, a control unit may be a component of the second device. In still other cases, a control unit may not be part of the first device or the second device, but instead may be in “the cloud” or otherwise remote from the first device and the second device.

[0085] It is further to be understood that certain elements or components may be used in multiple systems and devices described herein, regardless of how complex or integrated the system or device may be.

[0086] For example, in some implementations, a device described herein comprises an electromagnetic radiation manipulating element positioned in a path of electromagnetic radiation. It is to be understood that such an electromagnetic radiation manipulating element may refer to an element that alters, manipulates, or changes the characteristics of the electromagnetic radiation, such as the fluence, power, wavelength, path, or direction of the electromagnetic radiation. In one non-limiting example, an electromagnetic radiation manipulating element may reduce the power of the electromagnetic radiation. Moreover, in another non-limiting example, an electromagnetic radiation manipulating element may change the path of the electromagnetic radiation. In some embodiments, the electromagnetic radiation manipulating element comprises an optical element. For instance, in some such cases, the optical element comprises a mirror. Additionally, in some cases, the optical element reflects a sub-therapeutic portion of electromagnetic radiation of the handpiece away from the primary direction of travel and toward the TR along a reflected direction (e.g., as generally illustrated by example primary direction“PD” and example reflected direction “RD” in Figures 2 and 5). A device of a system described herein may also comprise a visual camera positioned to image the TR along the reflected direction. As discussed previously, many suitable visual cameras will be readily apparent to those of ordinary skill in the art, and the choice of visual camera is not particularly limited. Similarly, any suitable tissue response detector and source of electromagnetic radiation may be used in such a device or system, including a tissue response detector light source described hereinabove.

[0087] Devices or systems described herein, in some implementations, comprise a control unit that generates one or more therapeutic dose parameters based at least in part on the tissue response of the TR. In some cases, the control unit is further configured to direct a source of electromagnetic radiation to irradiate the ROI of the skin with the one or more therapeutic doses of electromagnetic radiation based on the one or more therapeutic dose parameters. Additionally, in some embodiments, the control unit is configured to direct irradiation of the ROI using machine learning and / or automation.

[0088] Moreover, embodiments of the disclosure can be described in the general context of computer code or machine-useable instructions, including computer-executable instructions such as program modules, being executed by a computer, FPGA, or other machine (virtual or otherwise), such as a smartphone or other handheld device. Generally, program modules, or engines, including routines, programs, objects, components, data structures etc., refer to code that performs particular tasks or implements particular abstract data types. Embodiments of the disclosure can be practiced in a variety of system configurations, including hand-held devices, consumer electronics, general-purpose computers, more specialized computing devices, etc. Embodiments of the disclosure can also be practiced in distributed computing environments where tasks are performed by remote-processing devices that are linked through a communications network.

[0089] In some such embodiments, a computer storage medium stores computer-useable instructions that, when used by one or more computing devices, cause the one or more computing devices to carry out a method described herein. For instance, in some cases, the computer-useable instructions cause the one or more computing devices to treat a region of interest of skin of a patient, the operations comprising the steps of: (1) irradiating a test region(TR) of the skin with a sub-therapeutic dose of electromagnetic radiation or with a series of sub- therapeutic doses; (2) determining a tissue response of the TR; (3) generating one or more therapeutic dose parameters based at least in part on the tissue response of the TR; and (4) irradiating the ROI with one or more therapeutic doses of electromagnetic radiation in accordance with the one or more therapeutic dose parameters.

[0090] Figure 22 shows an exemplary embodiment of a “User Interface & CPU” block within a system. With reference to Figure 22, computing device 2200 includes a bus 2210 that directly or indirectly couples the following devices: memory 2212, one or more processors 2214, one or more presentation components 2216, input / output ports 2218, input / output components 2220, and an illustrative power supply 2222. In some embodiments, devices or systems described herein utilize wired and rechargeable batteries and power supplies. Bus 2210 represents what can be one or more busses (such as an address bus, data bus or combination thereof). Although the various blocks of Figure 22 are shown with clearly delineated lines for the sake of clarity, in reality, such delineations are not necessarily so clear and these lines can overlap. For example, one can consider a presentation component such as a display device to be an VO component as well. Also, processors generally have memory in the form of cache. It is recognized that such is the nature of the art, and it is reiterated that the diagram of Figure 22 is merely illustrative of an example computing device that can be used in connection with one or more embodiments of the present disclosure. Distinction is not made between such categories as “workstation,” “server,” “laptop,” “hand-held device,” etc., as all are contemplated within the scope of Figure 22 and reference to “computing device.”

[0091] Computing device 2200 typically includes a variety of computer-readable media. Computer-readable media can be any available media that can be accessed by computing device 2200, and includes both volatile and non-volatile media, removable and non-removable media. By way of example, and not limitation, computer-readable media can comprise computer storage media and communication media.

[0092] Computer storage media include volatile and non-volatile, removable and nonremovable media implemented in any method or technology for storage of information such as computer-readable instructions, data structures, program modules, or other data. Computer storage media includes, but is not limited to, RAM, ROM, EEPROM, flash memory or othermemory technology, CD-ROM, digital versatile disks (DVD) or other optical disk storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium which can be used to store the desired information and which can be accessed by computing device 2200. Computer storage media excludes signals per se.

[0093] Communication media typically embodies computer-readable instructions, data structures, program modules or other data in a modulated data signal such as a carrier wave or other transport mechanism and includes any information delivery media. The term “modulated data signal” means a signal that has one or more of its characteristics set or changed in such a manner at to encode information in the signal. By way of example, and not limitation, communication media includes wired media such as a wired network or direct-wired connection, and wireless media such as acoustic, RF, infrared, NFC, Bluetooth and other wireless media. Combinations of any of the above should also be included within the scope of computer-readable media.

[0094] Memory 2212 includes computer storage media in the form of volatile and / or nonvolatile memory. As depicted, memory 2212 includes instructions 2224 that when executed by processor(s) 2214 are configured to cause the computing device to perform any of the operations described herein, in reference to the above discussed figures, or to implement any program modules described herein. The memory can be removable, non-removable, or a combination thereof. Illustrative hardware devices include solid-state memory, hard drives, optical-disc drives, etc. Computing device 2200 includes one or more processors that read data from various entities such as memory 2212 or I / O components 2220. Presentation component(s) 2216 present data indications to a user or other device. Illustrative presentation components include a display device, speaker, printing component, vibrating component, etc.

[0095] I / O ports 2218 allow computing device 2200 to be logically coupled to other devices including I / O components 2220, some of which can be built in. Illustrative components include a microphonejoystick, directional pad, monitor, scanner, printer, wireless device, battery, etc.

[0096] Some embodiments described herein are further illustrated in the following non-limiting Examples.EXAMPLE 1 Tissue Response Data

[0097] In this Example, tissue response data, specifically temperature data, are correlated to sub- therapeutic treatment parameters. Figure 10 shows images or frames of a test region captured with a tissue response detector, which is a thermal camera, while irradiating a test region of skin with an application of BBL radiation at a sub-therapeutic dose. Thus, the images display a sensed temperature for the test region. The individual frames captured by the tissue response detector can be analyzed to extract the mean temperature for the region of interest. Figure 11 shows a plot of the mean temperature of each frame plotted against the frame number. The larger circles indicate the minimum and maximum temperatures of the skin during treatment with BBL radiation.

[0098] Figure 12 shows frames from the treatment of a test region captured while irradiating the test region of skin with electromagnetic radiation at a sub-therapeutic dose. Images were taken with a thermal camera. Figure 13 shows three temperature rise plots of the tissue of the test region related to the frame number when electromagnetic radiation is applied at difference fluences (1.20 J / cm2, 1.44 J / cm2, or 1.68 J / cm2) to the test region of skin for 3.0 msec. These temperature maxima are plotted against fluence in Figure 14. As shown in Figure 14, with increased fluence, the maximum temperature increases. The maximum temperature rise can be related to each fluence applied and fit into a model, which is discussed in Example 2, that extrapolates the fluence that will achieve a certain temperature response from the tissue.EXAMPLE 2Models for Tissue Response Parameters

[0099] In this Example, models for generating therapeutic dose parameters are described for the methods, devices, and systems described herein, including a “forward” model and an “inverse” model. Each model is calibrated by exciting the skin (i.e., treating the skin) with known sub- therapeutic input parameters of the source of electromagnetic radiation. When treating the skin with these known input parameters, a resulting tissue response is observed, and the resulting tissue response is used to fit a “tissue response-light” model between the parameters applied and the tissue response.

[0100] An additional example of this model refinement is shown in Figure 16. In Figure 16, the source of electromagnetic radiation delivers the test pulse (i.e., the sub-therapeutic dose). Then, the device watches or observes the tissue response from the test pulse (i.e., the sub-therapeutic dose) and refines the model fit based on the results. Subsequently, based on this refinement, the device requests new parameters for the source, and then, the light parameters are adjusted for the electromagnetic radiation source. Several iterations of testing the skin with known input parameters and obtaining a tissue response can be completed to contribute to the fit of the model, personalizing the calibration of the model of the applied sub-therapeutic dose parameters of the methods, devices, and systems described herein. Thus, the subsequent cycle of applying an additional dose of sub-therapeutic treatment continues again, and with additional cycles, the model fit becomes more refined.

[0101] Turning now to prediction models, herein a “forward” model approach and an “inverse” model approach are described. A flow chart of the “forward” model approach and the “inverse” model approach is shown in Figure 17. In the “forward” model approach, the user sets the device parameters, and the model predicts the tissue response based on the model calibration. In the “inverse” model approach, the desired tissue response is set, and the model predicts the therapeutic parameters based on the model calibration.

[0102] In Figure 18, an example of “forward” model prediction is shown. In Figure 18, a visual camera image of a test region of skin is displayed, and an applied fluence of 5.5 J / cm2is shown on a sliding scale. In the visual image of the target region, areas of the skin are outlined in solid or dashed lines. The lines indicate 100.0°C or 150.0°C, which are the temperatures that the tissue drawn in by the lines are predicted to reach with the application of the indicated fluence of the source of electromagnetic radiation. That is, based on the prediction by the “forward” model, with the application of the source parameters, areas of the tissue that are outlined are predicted to heat to the indicated temperature upon the application of the selected fluence parameter.

[0103] Further, Figures 19 and 20 illustrate additional example images of a test region of skin. In these images, the fluence of the source of electromagnetic radiation is increased to 7 J / cm2and 9 J / cm2, respectively. In the images, areas of the skin are again outlined to indicate predicted temperatures upon treatment with the selected fluence. In both Figures 19 and 20, with increasedfluence, the area predicted to heat to 100.0°C has increased, and there is also an increase in the area predicted to heat to 150.0°C compared to Figure 18.EXAMPLE 3System for Treating Tissue with Electromagnetic Radiation

[0104] In this Example, an embodiment of a system (601) is described. As shown in Figure 21, the system (601) comprises an energy stimulus device or source of electromagnetic radiation (602) (a BBL source, in this instance) for treating a region of interest (RO I) of a patient, denoted in Figure 21 as the patient’s target tissue (603). The source of electromagnetic radiation (602) is attached to or in communication with a control unit or computer (604) that is configured to direct or control the radiation source (602) in real time. The system (601) also comprises a tissue response detector (605) (i.e., a thermal camera in the embodiment illustrated in Figure 21) and a visual camera (606). The tissue response detector (605) detects the response of one or more test regions (TRs, not specifically shown in Figure 21) of the ROI (603) while and / or after the one or more TRs of the ROI (603) is irradiated with a sub-therapeutic dose of the broadband light emitted by the source (602). Simultaneously, the visual camera (606) captures one or more images (not specifically shown in Figure 21) of the one or more TRs of the ROI (603). The captured image(s) and the detected tissue response(s) are then registered and processed (step 607), using a control unit or computer (609), which is in communication with one or more other components of the system (601). Additionally, as illustrated in Figure 21, the computer (609) has a user interface (not specifically labeled) for use by a practitioner / user (615).

[0105] The control unit or computer (609), optionally in conjunction with a data storage step (610), can also be used to overlay video capture of the captured images (step 608). In this overlay (step 608), the video-captured images of the one or more TRs are correlated to the tissue response of the one or more TRs. The tissue response of the one or more TRs is also correlated to the sub-therapeutic dose(s) of electromagnetic radiation. This correlation is used in a regression function or data model (step 612) for the tissue response. This regression function or data model can be used to calculate the predicted values of the tissue response (step 611) using initial recommended therapeutic dose parameters in a forward model prediction approach. With multiple treatments of one or more TRs with a sub-therapeutic dose of electromagnetic radiation(not specifically shown in Figure 21), the regression function or data model fit can, in some cases, become more refined. From the calculations (step 611), the recommended therapeutic dose parameters are then displayed on the user interface (step 613). A report of the parameters may be generated (step 614) for the practitioner (615).

[0106] Additional exemplary embodiments contemplated herein are as follows.

[0107] Embodiment 1. A method for treating a region of interest (ROI) of skin of a subject in need thereof, the method comprising: irradiating a test region (TR) of the skin with a sub-therapeutic dose of electromagnetic radiation or with a series of sub-therapeutic doses; determining a tissue response of the TR; and generating one or more therapeutic dose parameters based at least in part on the tissue response of the TR.

[0108] Embodiment 2. The method of Embodiment 1, further comprising irradiating the ROI with one or more therapeutic doses of electromagnetic radiation in accordance with the one or more therapeutic dose parameters.

[0109] Embodiment 3. The method of Embodiment 1, wherein irradiating the TR comprises irradiating the TR with a series of sub-therapeutic doses.

[0110] Embodiment 4. The method of any of the preceding Embodiments further comprising imaging the TR at the same time as determining the tissue response of the TR.

[0111] Embodiment 5. The method of Embodiment 4, wherein imaging the TR comprises capturing an image of the TR with a visual camera.

[0112] Embodiment 6. The method of Embodiment 5, wherein generating one or more therapeutic dose parameters is further based at least in part on the image of the TR.

[0113] Embodiment 7. The method of Embodiment 5, further comprising correlating the image of the TR to the tissue response of the TR.

[0114] Embodiment 8. The method of any of the preceding Embodiments, wherein: the TR comprises one or more target features (TFs); and generating one or more therapeutic dose parameters is further based at least in part on a tissue response of the one or more TFs.

[0115] Embodiment 9. The method of Embodiment 8, whereinthe TR further comprises one or more non-target features (NTFs); and generating one or more therapeutic dose parameters is further based at least in part on a tissue response of the one or more NTFs.

[0116] Embodiment 10. The method of Embodiment 8, wherein the method further comprises irradiating the ROI with one or more therapeutic doses of electromagnetic radiation in accordance with the one or more therapeutic dose parameters; wherein irradiating the ROI in accordance with the one or more therapeutic dose parameters provides a therapeutic effect to the one or more TFs; and wherein irradiating the ROI in accordance with the one or more therapeutic dose parameters does not damage the one or more TFs beyond a therapeutic damage threshold

[0117] Embodiment 11. The method of any of the preceding Embodiments, further comprising: irradiating n additional TRs of the skin with n additional sub-therapeutic doses of electromagnetic radiation or n additional series of sub-therapeutic doses of electromagnetic radiation; determining n additional tissue responses of the n additional TRs; generating one or more therapeutic dose parameters based at least in part on the n additional tissue responses of the n additional TRs.

[0118] Embodiment 12. The method of Embodiment 11, wherein n is an integer between 1 and 109.

[0119] Embodiment 13. The method of any of the preceding Embodiments, wherein the tissue response of the TR is detected using a tissue response detector.

[0120] Embodiment 14. The method of any of the preceding Embodiments, wherein the tissue response of the TR corresponds to a sensed temperature, a detected color or color change, or another detected spectral change.

[0121] Embodiment 15. The method of Embodiment 14, wherein the tissue response of the TR corresponds to a sensed temperature.

[0122] Embodiment 16. The method of any of the preceding Embodiments, wherein generating one or more therapeutic dose parameters is based on a regression function.

[0123] Embodiment 17. The method of Embodiment 16, wherein the regression function comprises a linear function or one or more rate functions.

[0124] Embodiment 18. The method of Embodiment 17, wherein: the regression function comprises one or more rate functions; and the one or more rate functions comprises at least one of an Arrhenius function, a bioheat function, and a light transport function.

[0125] Embodiment 19. The method of Embodiment 2, wherein irradiating the TR and irradiating the ROI are both carried out using the same source of electromagnetic radiation.

[0126] Embodiment 20. The method of Embodiment 19, wherein the source of electromagnetic radiation comprises a broadband light source.

[0127] Embodiment 21. A method for treating a region of interest (ROI) of skin of a subject in need thereof, the method comprising: attaching a device to a handpiece, wherein the handpiece comprises a source of electromagnetic radiation that emits electromagnetic radiation along a path in a primary direction, and wherein the device comprises a receiving space for the handpiece, and a tissue response detector; placing the attached device on or adjacent to the skin; irradiating at least one test region (TR) of the skin with a sub-therapeutic dose of electromagnetic radiation or a series of sub-therapeutic doses of electromagnetic radiation, using the handpiece; determining a tissue response of the TR using the tissue response detector; and generating one or more therapeutic dose parameters based at least in part on the tissue response of the TR.

[0128] Embodiment 22. The method of Embodiment 21, wherein the method further comprises: removing the device from the handpiece; placing the handpiece on or adjacent to the skin; and irradiating the ROI with one or more therapeutic doses of electromagnetic radiation in accordance with the one or more therapeutic dose parameters.

[0129] Embodiment 23. The method of Embodiment 21 or Embodiment 22, wherein the device further comprises an electromagnetic radiation manipulating element positioned in the path of the electromagnetic radiation.

[0130] Embodiment 24. The method of Embodiment 23, wherein the electromagnetic radiation manipulating element comprises an optical element.

[0131] Embodiment 25. The method of Embodiment 24, wherein the optical element comprises a mirror.

[0132] Embodiment 26. The method of Embodiment 24, wherein the optical element reflects a sub-therapeutic portion of electromagnetic radiation of the handpiece away from the primary direction and toward the TR along a reflected direction.

[0133] Embodiment 27. The method of any of Embodiments 21-26, wherein the device further comprises a visual camera positioned to image the TR along the reflected direction.

[0134] Embodiment 28. The method of any of Embodiment 22, wherein: irradiating the at least one TR with the sub -therapeutic dose of electromagnetic radiation or the series of sub-therapeutic doses of electromagnetic radiation, using the handpiece, comprises emitting a test portion of electromagnetic radiation from the handpiece along the path in the primary direction; irradiating the ROI with the one or more therapeutic doses of electromagnetic radiation comprises emitting a treatment portion of electromagnetic radiation from the handpiece; the test portion of electromagnetic radiation has a sub -therapeutic fluence; and the treatment portion of electromagnetic radiation has a therapeutic fluence.

[0135] Embodiment 29. The method of any of Embodiment 21-28, wherein the tissue response of the TR corresponds to a sensed temperature, a detected color or color change, or another detected spectral change.

[0136] Embodiment 30. The method of Embodiment 29, wherein the tissue response of the TR corresponds to a sensed temperature.

[0137] Embodiment 31. The method of any of Embodiments 21-30, wherein the source of electromagnetic radiation comprises a broadband light source.

[0138] Embodiment 32. A method for treating a region of interest (ROI) of skin of a subject in need thereof, the method comprising: placing a device on or adjacent to the skin, wherein the device comprises a source of electromagnetic radiation that emits electromagnetic radiation along a path in a primary direction and a tissue response detector;irradiating at least one test region (TR) of the skin with a sub-therapeutic dose of electromagnetic radiation or a series of sub-therapeutic doses of electromagnetic radiation, using the device; determining a tissue response of the TR using the tissue response detector; and generating one or more therapeutic dose parameters based at least in part on the tissue response of the TR.

[0139] Embodiment 33. The method of Embodiment 32, wherein the method further comprises: placing the device on or adjacent to the skin; and irradiating the ROI with one or more therapeutic doses of electromagnetic radiation in accordance with the one or more therapeutic dose parameters.

[0140] Embodiment 34. The method of Embodiment 32, wherein the method further comprises: placing a second device on or adjacent to the skin, wherein the second device comprises a source of electromagnetic radiation that emits electromagnetic radiation; and irradiating the ROI with one or more therapeutic doses of electromagnetic radiation in accordance with the one or more therapeutic dose parameters, using the second device.

[0141] Embodiment 35. The method of any of Embodiments 32-34, wherein the device further comprises an electromagnetic radiation manipulating element positioned in the path of the electromagnetic radiation.

[0142] Embodiment 36. The method of Embodiment 35, wherein the electromagnetic radiation manipulating element comprises an optical element.

[0143] Embodiment 37. The method of Embodiment 36, wherein the optical element comprises a mirror.

[0144] Embodiment 38. The method of Embodiment 36, wherein the optical element reflects a sub-therapeutic portion of electromagnetic radiation of the device away from the primary direction and toward the TR along a reflected direction.

[0145] Embodiment 39. The method of any of Embodiments 32-38, wherein the device further comprises a visual camera positioned to image the TR along the reflected direction.

[0146] Embodiment 40. The method of any of Embodiments 32-39, wherein the tissue response of the TR corresponds to a sensed temperature, a detected color or color change, or another detected spectral change.

[0147] Embodiment 41 . The method of Embodiment 40, wherein the tissue response of the TR corresponds to a sensed temperature.

[0148] Embodiment 42. The method of any of Embodiments 32-41, wherein the source of electromagnetic radiation comprises a broadband light source.

[0149] Embodiment 43. A device for treating a region of interest (ROI) of skin of a subject in need thereof, the device comprising: a receiving space for a handpiece, wherein the handpiece comprises a source of electromagnetic radiation that emits electromagnetic radiation along a path in a primary direction; an electromagnetic radiation manipulating element positioned in the path of the electromagnetic radiation; and a tissue response detector.

[0150] Embodiment 44. The device of Embodiment 43, wherein the electromagnetic radiation manipulating element comprises an optical element.

[0151] Embodiment 45. The device of Embodiment 44, wherein the optical element comprises a mirror.

[0152] Embodiment 46. The device of Embodiment 44, wherein the optical element reflects a sub-therapeutic portion of electromagnetic radiation away from the primary direction and toward a test region (TR) of skin, along a reflected direction; and wherein the tissue response detector is positioned to detect a tissue response of the TR along the reflected direction.

[0153] Embodiment 47. The device of any of Embodiments 43-46, wherein the tissue response detector is configured to detect a sensed temperature of a test region (TR) of skin.

[0154] Embodiment 48. The device of any of Embodiments 43-47 further comprising a visual camera positioned to image along the reflected direction.

[0155] Embodiment 49. The device of any of Embodiments 43-48, wherein the receiving space comprises a fastener, clip, or bracket for retaining and / or restraining the handpiece.

[0156] Embodiment 50. A system for treating a region of interest (ROI) of skin of a subject in need thereof, the system comprising:a source of electromagnetic radiation to irradiate a test region (TR) of the skin with a sub- therapeutic dose of electromagnetic radiation or a series of sub -therapeutic doses of electromagnetic radiation; a tissue response detector to determine a tissue response of the TR; and a control unit to generate one or more therapeutic dose parameters based at least in part on the tissue response of the TR.

[0157] Embodiment 51. The system of Embodiment 50 further comprising a source of electromagnetic radiation to irradiate the ROI of the skin with one or more therapeutic doses of electromagnetic radiation based on the one or more therapeutic dose parameters.

[0158] Embodiment 52. The system of Embodiment 50 further comprising a visual camera to capture an image of the TR.

[0159] Embodiment 53. The system of Embodiment 51, wherein: the source of electromagnetic radiation to irradiate the TR is a component of a first device of the system; and the tissue response detector is a component of the first device of the system.

[0160] Embodiment 54. The system of Embodiment 52, wherein the visual camera is a component of the first device of the system.

[0161] Embodiment 55. The system of Embodiment 53 or Embodiment 54, wherein the control unit is a component of the first device of the system.

[0162] Embodiment 56. The system of Embodiment 51, wherein the source of electromagnetic radiation to irradiate the ROI is a component of a second device of the system.

[0163] Embodiment 57. The system of Embodiment 56, wherein the control unit is a component of the second device of the system.

[0164] Embodiment 58. The system of Embodiment 51, wherein the source of electromagnetic radiation to irradiate the TR and the source of electromagnetic radiation to irradiate the ROI of the skin with one or more therapeutic doses of electromagnetic radiation are the same source of electromagnetic radiation.

[0165] Embodiment 59. The system of Embodiment 51, wherein the control unit is further configured to direct the source of electromagnetic radiation to irradiate the ROI of the skin withthe one or more therapeutic doses of electro agnetic radiation based on the one or more therapeutic dose parameters.

[0166] Embodiment 60. The system of Embodiment 59, wherein the control unit is configured to direct irradiation of the ROI using machine learning and / or automation.

[0167] Embodiment 61. A computer storage medium storing computer-useable instructions that, when used by one or more computing devices, cause the one or more computing devices to treat a region of interest of skin of a subject in need thereof, the operations comprising the steps of any of Embodiments 1-42.

[0168] Various embodiments of the invention have been described in fulfillment of the various objectives of the invention. It should be recognized that these embodiments are merely illustrative of the principles of the invention. Numerous modifications and adaptations thereof will be readily apparent to those skilled in the art without departing from the spirit and scope of the invention.

Claims

CLAIMS1. A method for treating a region of interest (ROI) of skin of a subject in need thereof, the method comprising: irradiating a test region (TR) of the skin with a sub-therapeutic dose of electromagnetic radiation or with a series of sub-therapeutic doses; determining a tissue response of the TR; and generating one or more therapeutic dose parameters based at least in part on the tissue response of the TR.

2. The method of claim 1, further comprising irradiating the ROI with one or more therapeutic doses of electromagnetic radiation in accordance with the one or more therapeutic dose parameters.

3. The method of claim 1, wherein irradiating the TR comprises irradiating the TR with a series of sub-therapeutic doses.

4. The method of claim 1 further comprising imaging the TR at the same time as determining the tissue response of the TR.

5. The method of claim 4, wherein imaging the TR comprises capturing an image of the TR with a visual camera.

6. The method of claim 5, wherein generating one or more therapeutic dose parameters is further based at least in part on the image of the TR.

7. The method of claim 5, further comprising correlating the image of the TR to the tissue response of the TR.

8. The method of claim 1, wherein:the TR comprises one or more target features (TFs); and generating one or more therapeutic dose parameters is further based at least in part on a tissue response of the one or more TFs.

9. The method of claim 8, wherein: the TR further comprises one or more non-target features (NTFs); and generating one or more therapeutic dose parameters is further based at least in part on a tissue response of the one or more NTFs.

10. The method of claim 8, wherein: the method further comprises irradiating the ROI with one or more therapeutic doses of electromagnetic radiation in accordance with the one or more therapeutic dose parameters; irradiating the ROI in accordance with the one or more therapeutic dose parameters provides a therapeutic effect to the one or more TFs; and irradiating the ROI in accordance with the one or more therapeutic dose parameters does not damage the one or more TFs beyond a therapeutic damage threshold.

11. The method of claim 1, further comprising: irradiating i additional TRs of the skin with n additional sub-therapeutic doses of electromagnetic radiation or n additional series of sub-therapeutic doses of electromagnetic radiation; determining n additional tissue responses of the n additional TRs; generating one or more therapeutic dose parameters based at least in part on the n additional tissue responses of the n additional TRs.

12. The method of claim 11, wherein n is an integer between 1 and 109.

13. The method of claim 1, wherein the tissue response of the TR is detected using a tissue response detector.

14. The method of claim 1, wherein the tissue response of the TR corresponds to a sensed temperature, a detected color or color change, or another detected spectral change.

15. The method of claim 14, wherein the tissue response of the TR corresponds to a sensed temperature.

16. The method of claim 1, wherein generating one or more therapeutic dose parameters is based on a regression function.

17. The method of claim 16, wherein the regression function comprises a linear function or one or more rate functions.

18. The method of claim 17, wherein: the regression function comprises one or more rate functions; and the one or more rate functions comprises at least one of an Arrhenius function, a bioheat function, and a light transport function.

19. The method of claim 2, wherein irradiating the TR and irradiating the ROI are both carried out using the same source of electromagnetic radiation.

20. The method of claim 19, wherein the source of electromagnetic radiation comprises a broadband light source.

21. A method for treating a region of interest (ROI) of skin of a subject in need thereof, the method comprising: attaching a device to a handpiece, wherein the handpiece comprises a source of electromagnetic radiation that emits electromagnetic radiation along a path in a primary direction, and wherein the device comprises a receiving space for the handpiece, and a tissue response detector;placing the attached device on or adjacent to the skin; irradiating at least one test region (TR) of the skin with a sub-therapeutic dose of electromagnetic radiation or a series of sub-therapeutic doses of electromagnetic radiation, using the handpiece; determining a tissue response of the TR using the tissue response detector; and generating one or more therapeutic dose parameters based at least in part on the tissue response of the TR.

22. The method of claim 21, wherein the method further comprises: removing the device from the handpiece; placing the handpiece on or adjacent to the skin; and irradiating the ROI with one or more therapeutic doses of electromagnetic radiation in accordance with the one or more therapeutic dose parameters.

23. The method of claim 21, wherein the device further comprises an electromagnetic radiation manipulating element positioned in the path of the electromagnetic radiation.

24. The method of claim 23, wherein the electromagnetic radiation manipulating element comprises an optical element.

25. The method of claim 24, wherein the optical element comprises a mirror.

26. The method of claim 24, wherein the optical element reflects a sub-therapeutic portion of electromagnetic radiation of the handpiece away from the primary direction and toward the TR along a reflected direction.

27. The method of claim 26, wherein the device further comprises a visual camera positioned to image the TR along the reflected direction.

28. The method of claim 21, wherein:irradiating the at least one TR with the sub-therapeutic dose of electromagnetic radiation or the series of sub -therapeutic doses of electromagnetic radiation, using the handpiece, comprises emitting a test portion of electromagnetic radiation from the handpiece along the path in the primary direction; irradiating the ROI with the one or more therapeutic doses of electromagnetic radiation comprises emitting a treatment portion of electromagnetic radiation from the handpiece; the test portion of electromagnetic radiation has a sub-therapeutic fluence; and the treatment portion of electromagnetic radiation has a therapeutic fluence.

29. The method of claim 21, wherein the tissue response of the TR corresponds to a sensed temperature, a detected color or color change, or another detected spectral change.

30. The method of claim 29, wherein the tissue response of the TR corresponds to a sensed temperature.

31. The method of claim 21, wherein the source of electromagnetic radiation comprises a broadband light source.

32. A method for treating a region of interest (ROI) of skin of a subject in need thereof, the method comprising: placing a device on or adjacent to the skin, wherein the device comprises a source of electromagnetic radiation that emits electromagnetic radiation along a path in a primary direction and a tissue response detector; irradiating at least one test region (TR) of the skin with a sub-therapeutic dose of electromagnetic radiation or a series of sub-therapeutic doses of electromagnetic radiation, using the device; determining a tissue response of the TR using the tissue response detector; and generating one or more therapeutic dose parameters based at least in part on the tissue response of the TR.

33. The method of claim 32, wherein the method further comprises: placing the device on or adjacent to the skin; and irradiating the ROI with one or more therapeutic doses of electromagnetic radiation in accordance with the one or more therapeutic dose parameters.

34. The method of claim 32, wherein the method further comprises: placing a second device on or adjacent to the skin, wherein the second device comprises a source of electromagnetic radiation that emits electromagnetic radiation; and irradiating the ROI with one or more therapeutic doses of electromagnetic radiation in accordance with the one or more therapeutic dose parameters, using the second device.

35. The method of claim 32, wherein the device further comprises an electromagnetic radiation manipulating element positioned in the path of the electromagnetic radiation.

36. The method of claim 35, wherein the electromagnetic radiation manipulating element comprises an optical element.

37. The method of claim 36, wherein the optical element comprises a mirror.

38. The method of claim 36, wherein the optical element reflects a sub-therapeutic portion of electromagnetic radiation of the device away from the primary direction and toward the TR along a reflected direction.

39. The method of claim 38, wherein the device further comprises a visual camera positioned to image the TR along the reflected direction.

40. The method of claim 32, wherein the tissue response of the TR corresponds to a sensed temperature, a detected color or color change, or another detected spectral change.41 . The method of claim 40, wherein the tissue response of the TR corresponds to a sensed temperature.

42. The method of claim 32, wherein the source of electromagnetic radiation comprises a broadband light source.

43. A device for treating a region of interest (RO I) of skin of a subject in need thereof, the device comprising: a receiving space for a handpiece, wherein the handpiece comprises a source of electromagnetic radiation that emits electromagnetic radiation along a path in a primary direction; an electromagnetic radiation manipulating element positioned in the path of the electromagnetic radiation; and a tissue response detector.

44. The device of claim 43, wherein the electromagnetic radiation manipulating element comprises an optical element.

45. The device of claim 44, wherein the optical element comprises a mirror.

46. The device of claim 44, wherein: the optical element reflects a sub-therapeutic portion of electromagnetic radiation away from the primary direction and toward a test region (TR) of skin, along a reflected direction; and the tissue response detector is positioned to detect a tissue response of the TR along the reflected direction.

47. The device of claim 43, wherein the tissue response detector is configured to detect a sensed temperature of a test region (TR) of skin.

48. The device of claim 46 further comprising a visual camera positioned to image along the reflected direction.

49. The device of claim 43, wherein the receiving space comprises a fastener, clip, or bracket for retaining and / or restraining the handpiece.

50. A system for treating a region of interest (ROI) of skin of a subject in need thereof, the system comprising: a source of electromagnetic radiation to irradiate a test region (TR) of the skin with a sub- therapeutic dose of electromagnetic radiation or a series of sub -therapeutic doses of electromagnetic radiation; a tissue response detector to determine a tissue response of the TR; and a control unit to generate one or more therapeutic dose parameters based at least in part on the tissue response of the TR.

51. The system of claim 50 further comprising a source of electromagnetic radiation to irradiate the ROI of the skin with one or more therapeutic doses of electromagnetic radiation based on the one or more therapeutic dose parameters.

52. The system of claim 50 further comprising a visual camera to capture an image of the TR.

53. The system of claim 50, wherein: the source of electromagnetic radiation to irradiate the TR is a component of a first device of the system; and the tissue response detector is a component of the first device of the system.

54. The system of claim 52, wherein the visual camera is a component of the first device of the system.

55. The system of claim 53, wherein the control unit is a component of the first device of the system.

56. The system of claim 51, wherein the source of electromagnetic radiation to irradiate the ROI is a component of a second device of the system.

57. The system of claim 56, wherein the control unit is a component of the second device of the system.

58. The system of claim 51, wherein the source of electromagnetic radiation to irradiate the TR and the source of electromagnetic radiation to irradiate the ROI of the skin with one or more therapeutic doses of electromagnetic radiation are the same source of electromagnetic radiation.

59. The system of claim 51, wherein the control unit is further configured to direct the source of electromagnetic radiation to irradiate the ROI of the skin with the one or more therapeutic doses of electromagnetic radiation based on the one or more therapeutic dose parameters.

60. The system of claim 59, wherein the control unit is configured to direct irradiation of the ROI using machine learning and / or automation.

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