Patent Application
20240225731
The present invention relates to photo-thermal targeted treatment systems and, more specifically, systems and methods for controlling the safety operations of a photo-thermal targeted treatment system for improved efficacy, consistency, and pain minimization in providing photo-induced thermal treatment targeting specific chromophores embedded in a medium.
Chromophores embedded in a medium such as the dermis, can be thermally damaged by heating the chromophore with a targeted light source, such as a laser. However, the application of enough thermal energy to damage the chromophore can also be damaging to the surrounding dermis and the overlying epidermis, thus leading to epidermis and dermis damage as well as pain to the subject. This problem also applies to targets, such as sebaceous glands, where a chromophore such as sebum is used to heat the target to a high enough temperature to cause damage to the target.
Previous approaches to prevent epidermis and dermis damage, as well as subject pain include:
More recent approaches have involved, for example, determination and predictive closed-loop control of dosimetry using measurement of skin surface temperature, as discussed in the above mentioned related disclosures. Additionally, there has been a shift in such photo-thermal treatment systems to provide more efficient and consistent treatment results while considering patient comfort.
Thus, there is a need for an improved photo-thermal targeted treatment system and methods for providing effective, consistent treatment results and minimizing the pain felt by patients during the course of treatment.
The following presents a simplified summary relating to one or more aspects and/or embodiments disclosed herein. As such, the following summary should not be considered an extensive overview relating to all contemplated aspects and/or embodiments, nor should the following summary be regarded to identify key or critical elements relating to all contemplated aspects and/or embodiments or to delineate the scope associated with any particular aspect and/or embodiment. Accordingly, the following summary has the sole purpose to present certain concepts relating to one or more aspects and/or embodiments relating to the mechanisms disclosed herein in a simplified form to precede the detailed description presented below.
In accordance with the embodiments described herein, there is disclosed a method for determining a suitable set of parameters for operating a light source within a photo-thermal targeted treatment system for targeting a chromophore embedded in a medium. The method includes, prior to administering a treatment protocol to a first subject, 1) administering at least one laser pulse at a preset power level to a first treatment location, where the preset power level is below a known damage threshold. The method also includes 2) measuring a skin surface temperature at the first treatment location, following administration of the at least one laser pulse. The method further includes 3) estimating a relationship between the parameters for operating the light source and the skin surface temperature at the first treatment location, and 4) defining a safe operating range for the parameters for operating the light source in order to avoid thermal damage to the medium at the first treatment location while still effectively targeting the chromophore in administering the treatment protocol.
In an embodiment, steps 1) through 4) are repeated at a second treatment location on the first subject prior to administering the treatment protocol at the second treatment location. In another embodiment, steps 1) through 4) are repeated at the first treatment location on a second subject prior to administering the treatment protocol on the second subject. In still another embodiment, the method further includes 5) storing in a memory of the photo-thermal targeted treatment system the safe operating range for the parameters for operating the light source for the first subject at the first treatment location, and 6) when administering the treatment protocol on the first subject at a later time, taking into consideration the parameters so stored in the memory.
In another embodiment, a photo-thermal targeted treatment system for targeting a chromophore embedded in a medium is disclosed. The system includes a light source configured for providing laser pulses over a range of power levels when operated using a set of parameters, the range of power levels including a known damage threshold for the chromophore and a treatment location. The system also includes a temperature measurement apparatus for measuring a skin surface temperature at the treatment location, and a controller for controlling the light source and the temperature measurement apparatus. The controller is configured for estimating a relationship between the parameters of the light source and the skin surface temperature at the treatment location, defining a safe operating range for the set of parameters of the light source in order to avoid thermal damage to the medium at the treatment location while still effectively targeting the chromophore in administering the treatment protocol, and setting the light source to administer the laser pulses within the safe operating range.
In yet another embodiment, a method for adjusting a suitable set of parameters for operating a light source within a photo-thermal targeted treatment system for targeting a chromophore embedded in a medium during administration of a treatment protocol to a first subject at a first treatment location is disclosed. The method includes: 1) measuring the skin surface temperature at the first treatment location at least once; 2) predicting skin temperature as the treatment protocol is administered to the first subject at the first treatment location; and 3) adjusting at least one of the parameters for operating the light source such that a future measurement of the skin surface temperature at the first treatment location will not exceed a specified value. Predicting skin temperature considers at least one of a heat transfer model and a series of experimental results.
In another embodiment, a method for determining a suitable set of parameters for operating a light source within a photo-thermal targeted treatment system for targeting a chromophore embedded in a medium is disclosed. The method includes:
In still another embodiment, a method for determining a suitable set of parameters for operating a light source within a photo-thermal targeted treatment system for targeting a chromophore embedded in a medium is disclosed. The method includes, prior to administration of a treatment protocol to a first subject:
In a further embodiment, a method for treating a subject with a photo-thermal targeted treatment system including a light source for targeting a chromophore embedded in a medium is disclosed. The method includes:
In a further embodiment, a photo-thermal targeted treatment system for targeting a chromophore embedded in a medium is disclosed. The system includes a cooling unit for providing cooling at a treatment location, a light source for providing laser pulses at the treatment location, a temperature monitoring unit for monitoring a skin surface temperature at the location, and a controller for receiving the skin surface temperature as monitored by the temperature monitoring unit and accordingly controlling operating parameters of the cooling unit and the light source. In embodiments, the controller is configured for directing the light source to administer at least one laser pulse at a preset power to the treatment location, the preset power level being blow a known pain and damage threshold, directing the temperature monitoring unit to measure a skin surface temperature at the treatment location, correlation fitting a relationship between the operating parameters of the light source and the skin surface temperature so measured, defining a safe operating range for the operating parameters of the light source in order to avoid pain and thermal damage to the medium at the treatment location, modifying the operating parameters of at least one of the cooling unit and the light source to administer at least one higher-level laser pulse from the light source to maintain the skin surface temperature below the known pain and damage threshold while simultaneously increasing a peak temperature and depth of a thermal gradient until the peak temperature and depth of the thermal gradient reaches a desired depth within the medium at the treatment location, and directing the light source to administer at least one treatment laser pulse from the light source with a power above the at least one initial laser pulse to raise a temperature of the targeted chromophore to its required damage temperature.
These and other features, and characteristics of the present technology, as well as the methods of operation and functions of the related elements of structure and the combination of parts and economies of manufacture, will become more apparent upon consideration of the following description and the appended claims with reference to the accompanying drawings, all of which form a part of this specification, wherein like reference numerals designate corresponding parts in the various figures. It is to be expressly understood, however, that the drawings are for the purpose of illustration and description only and are not intended as a definition of the limits of the invention. As used in the specification and in the claims, the singular form of ‘a’, ‘an’, and ‘the’ include plural referents unless the context clearly dictates otherwise.
For simplicity and clarity of illustration, the drawing figures illustrate the general manner of construction, and descriptions and details of well-known features and techniques may be omitted to avoid unnecessarily obscuring the embodiments detailed herein. Additionally, elements in the drawing figures are not necessarily drawn to scale. For example, the dimensions of some of the elements in the figures may be exaggerated relative to other elements to help improve understanding of the described embodiments. The same reference numerals in different figures denote the same elements.
The word “exemplary” is used herein to mean “serving as an example, instance, or illustration.” Any embodiment described herein as “exemplary” is not necessarily to be construed as preferred or advantageous over other embodiments. In the following detailed description, references are made to the accompanying drawings that form a part hereof, and in which are shown by way of illustrations or specific examples. These aspects may be combined, other aspects may be utilized, and structural changes may be made without departing from the present disclosure. Example aspects may be practiced as methods, systems, or apparatuses. The following detailed description is therefore not to be taken in a limiting sense, and the scope of the present disclosure is defined by the appended claims and their equivalents.
The present invention is described more fully hereinafter with reference to the accompanying drawings, in which embodiments of the invention are shown. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. In the drawings, the size and relative sizes of layers and regions may be exaggerated for clarity. Like numbers refer to like elements throughout.
It will be understood that, although the terms first, second, third etc. may be used herein to describe various elements, components, regions, layers and/or sections, these elements, components, regions, layers and/or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, layer or section from another region, layer or section. Thus, a first element, component, region, layer or section discussed below could be termed a second element, component, region, layer or section without departing from the teachings of the present invention.
Spatially relative terms, such as “beneath,” “below,” “lower,” “under,” “above,” “upper,” and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is turned over, elements described as “below” or “beneath” or “under” other elements or features would then be oriented “above” the other elements or features. Thus, the exemplary terms “below” and “under” can encompass both an orientation of above and below. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly. In addition, it will also be understood that when a layer is referred to as being “between” two layers, it can be the only layer between the two layers, or one or more intervening layers may also be present.
The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the singular forms “a,” “an,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. As used herein, the term “and/or” includes any and all combinations of one or more of the associated listed items and may be abbreviated as “/”.
It will be understood that when an element or layer is referred to as being “on,” “connected to,” “coupled to,” or “adjacent to” another element or layer, it can be directly on, connected, coupled, or adjacent to the other element or layer, or intervening elements or layers may be present. In contrast, when an element is referred to as being “directly on,” “directly connected to,” “directly coupled to,” or “immediately adjacent to” another element or layer, there are no intervening elements or layers present. Likewise, when light is received or provided “from” one element, it can be received or provided directly from that element or from an intervening element. On the other hand, when light is received or provided “directly from” one element, there are no intervening elements present.
Embodiments of the invention are described herein with reference to cross-section illustrations that are schematic illustrations of idealized embodiments (and intermediate structures) of the invention. As such, variations from the shapes of the illustrations as a result, for example, of manufacturing techniques and/or tolerances, are to be expected. Thus, embodiments of the invention should not be construed as limited to the particular shapes of regions illustrated herein but are to include deviations in shapes that result, for example, from manufacturing. Accordingly, the regions illustrated in the figures are schematic in nature and their shapes are not intended to illustrate the actual shape of a region of a device and are not intended to limit the scope of the invention.
Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and/or the present specification and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.
Still referring to
Controller 122 further controls other components within photo-treatment unit 120, such as a laser 124, a display 126, a temperature monitoring unit, a foot switch 130, a door interlock 132, and an emergency on/off switch. Laser 124 provides the laser power for the photo-treatment protocol, and controller 122 regulates the specific settings for the laser, such as the output power and pulse time settings. Laser 124 can be a single laser or a combination of two or more lasers. If there more than one laser is used, the laser outputs are combined optically to function as one more powerful laser. Display 126 can include information such as the operating conditions of cooling unit 110, laser 124, and other system status. Temperature monitoring unit 128 is used to monitor the temperature of the skin surface in the treatment area, for example, and the measured skin surface temperature at the treatment area is used by controller 122 to adjust the photo-treatment protocol. Controller 122 also interfaces with footswitch 130 for remotely turning on or off laser 124 and/or cooling unit 110. Additionally, door interlock 132 can be used as an additional safety measure such that, when the door to the treatment room is ajar, door interlock 132 detects the condition and instructs controller 122 to not allow photo-treatment unit 120, or at least laser 124, to operate. Furthermore, emergency on/off switch 134 can be provided to quickly shut down photo-thermal targeted treatment system 100 in case of an emergency. In another modification, additional photodiodes or other sensors can be added to monitor the power level of the energy emitted from laser 124.
Continuing to refer to
Finally, temperature connection 166 is connected with a temperature sensor 206, which measures the temperature at the treatment area for feedback to controller 122. Additionally, scanner 160 includes an on/off switch 210 (such as a trigger switch to turn on/off laser 124) and, optionally, a status indicator 212, which indicates the operational status of scanner 160, such as if the laser is being operated. While scanner 160 is schematically shown as a box in
In an exemplary usage scenario, the full treatment area overlying the sebaceous glands to be treated is cooled. The cooling protocol can include, for example, the application of a cold airstream across the treatment area for a prescribed time period, such as 10 seconds. In embodiments, the cooling may be adjusted according to the detection of the skin surface temperature reaching a specified temperature (e.g., −1° C.). Following pre-cooling, the cooling mechanism (e.g., cold airstream or contact-cooling) remains active and a photo-treatment protocol is applied to the treatment area. In one embodiment, pulses of a square, “flat-top” beam are used in combination with a scanner apparatus to sequentially apply a laser pulse to the treatment area. For example, the photo-treatment protocol can include the application of a set number of light pulses onto each segment of the treatment area, with the segments being sequentially illuminated by the laser pulses. In another embodiment, the segments are illuminated in a random order.
An example of a set of pulses suitable for a conditioning/photo-treatment protocol is illustrated in
The resulting changes in skin surface temperature are shown in a graph 400, where a peak 422 corresponds to the application light pulse 322 as shown in
The requirements for successful photo-thermal targeted treatment of specific chromophores with minimum subject discomfort include: 1) Epidermis sparing, namely making sure that the peak temperature value at the skin surface is less than around 49° C.; 2) Dermis sparing, namely avoiding overheating the dermis by balancing the peak and average power of the treatment pulses with the heat extraction of the cooling system; and 3) Selective heating of the chromophore, and the target containing the chromophore, such as a peak temperature greater than 55° C. for sebaceous gland treatments. It is noted that the peak temperature value of 55° C. is highly dependent on the specific treatment protocol and is adjustable to other temperatures to stay within a safe operating range to avoid damaging the surrounding dermis and epidermis.
It is known in the literature that tissue parameters, such as the thickness of the epidermis and dermis, vary among individuals, according to factors such as age, gender, and ethnicity, as well as between different skin locations on the body. For example, the forehead has different tissue properties than the back, even for the same individual, thus necessitating different treatment parameter settings for the different treatment locations. Consideration of such variations in tissue properties in determining the specific treatment protocol is significant for laser-based treatment of acne. Additionally, there may be variations in, for instance, the exact laser power, spot size, and cooling capacity between specific laser systems due to manufacturing variability and operating conditions. In fact, manufacturing variations from system to system can result in fluence variation of 15% or more among different laser treatment systems. Furthermore, the individual technique used by the user delivering the treatment can also affect the treatment, e.g., by different pressures applied to the skin surface which in turn affects, for instance, blood perfusion at the treatment site.
In laser treatment of acne, the operating thermal range is generally bound on the upper end at the epidermis and dermis damage threshold temperature, and at the lower end by the temperature required to bring the sebaceous gland to its damage threshold temperature. While there is currently not a good way to directly measure the temperature of the sebaceous gland being targeted by the treatment protocol, the skin surface temperature can be an indicator of the sebaceous gland temperature. A correlation model providing the correspondence between sebaceous gland temperature and skin surface temperature can then be used to tailor the actual treatment protocol using skin surface temperature measurements for effectively targeting sebaceous gland damage while staying below the damage threshold for the epidermis. The correlation model can be developed using, for example, an analytical heat transfer model, or by using clinical data (e.g., via biopsies) correlating skin surface temperature to sebaceous gland damage given the application of a specific treatment protocol.
Based on clinical data, the operating temperature range for acne treatment expressed in terminal skin surface temperature, using for example the treatment protocol illustrated in
However, clinical data also indicates that terminal skin surface temperature has a strong dependence on tissue parameters at the specific treatment area for a particular individual. While existing treatment protocols have been based on a “one treatment fits all” type of an approach, an innovative analysis protocol can be incorporated into the treatment method so as to directly determine individually tailored treatment parameters extrapolating from measurements of terminal skin temperature at lower laser powers and/or the skin surface temperature reached during an initial part of a treatment and/or the terminal skin surface temperatures reached during previous treatments, to avoid epidermis damage while efficaciously causing sebaceous gland damage. In this way, the treatment protocol can be customized for a specific treatment area for a particular individual, and also mitigates treatment variations that can be caused by variations in the laser power output of a specific machine, as well as variations in treatment conditions, such as ambient humidity and temperature. Therefore, it would be desirable to optimize the treatment protocol for different subjects and even different tissue locations for the same subject so as to not cause unwanted tissue damage, while still effectively treating the target tissue component (e.g., the sebaceous gland).
For instance, by directly measuring the skin surface temperature during the first four pulses of
This analysis protocol can be performed by incorporating temperature measurements using, for example, a commercial, off-the-shelf, low-cost cameras that can be built into the scanner (e.g., see temperature sensor 206 of
Turning to
As shown in
If the answer to decision 516 is yes, then analysis protocol 500 proceeds to fit the measured skin surface temperature data to the established correlation model in a step 518. Next, the appropriate laser parameters for the specific treatment area for the particular individual are determined in a step 520. Finally, in a step 522, the exact treatment protocol to be used for the specific treatment area for the particular individual is modified according to the appropriate laser parameters found in step 520.
Continuing to refer to
In other words, until the treatment protocol is complete, analysis protocol 500 can implement optional steps 530 through 540 to continue adjusting the laser parameters even during the actual treatment protocol. In fact, if other relevant data regarding the subject, such as laser settings from prior treatments in the same treatment area for the same subject, exist, they can also be fed into the model calculations for further refinement of the laser parameters.
Turning now to
Continuing to refer to
The analysis protocol can be performed in advance of the actual treatment session, for example, as the subject is being checked in at an appointment or in a pre-treatment session. As low powers are used, the analysis protocol can be performed without the need for local anesthesia, with virtually no epidermal or dermal damage occurring during the application of the analysis protocol. For instance, in preparation for treatment, a trained operator can quickly pre-measure the various treatment locations and, with one scan per skin location, develop an individualized treatment protocol. Alternatively, the temperature adjustment, including adjustment of laser power and/or cooling mechanism, may be performed in real time, during the actual treatment protocol.
Once a relationship between laser power and the resulting skin surface temperature has been established for a particular subject, and/or a particular skin location, and/or a particular laser device, this relationship, indicated by the slope of the line connecting dots 612, 614, 616, 622, 624, and 626 in
The concept of the analysis protocol described above can be extended to real-time adjustment of the treatment protocol using a closed-loop control process. The surface temperature of the skin can be measured using, for example, an infrared (IR) camera or other temperature measurement mechanisms. By fitting the measured temperature to a mathematical model of the skin tissue, for instance, the measured skin surface temperature can be correlated to the temperature of the target component, such as the sebaceous gland, which cannot be directly measured.
That is, in accordance with another embodiment, a system whereby temperature measurements of a skin surface during initial parts of a treatment for a specific location are used to predict future temperatures of the skin surface at this specific location. The future temperatures, so predicted, are used to adjust a thermal energy delivered by a laser, or lasers, by adjusting one or more parameters, such as laser power, pulse width, number of pulses, and others that affect the thermal energy delivered by the laser, or by adjusting one or more parameters of a cooling system, such as air flow, such that the future temperature of the skin surface for the specific location, and thereby the temperature of the underlying regions and components of the tissue, which cannot be readily measured in a direct manner, reaches a desired value or does not exceed a specified value.
In other words, the dosimetry (e.g., the settings of the light treatment including, for example, power settings for the laser light source) administered to the subject) can be adjusted in real-time by using a predictive control process. For instance, by directly measuring the skin temperature during pulses 322, 324, and 326 shown in
The analysis for use in the predictive control process can be performed using a temperature measurement device, for example, a commercial, off-the-shelf, low-cost camera incorporated into the scanner (e.g., temperature sensor 206 of
For instance, the Arhenius damage function yields that target damage is exponentially related to peak temperature; subsequently, the peak temperature of the skin surface is correlated to the peak temperature of the target component. In an example, the temperature rise is approximately 180° C./second for irradiation with a 22 W laser over a 5 mm-by-5 mm spot with a 100 ms pulse; in this case, the skin surface measurement should be updated approximately every 2.5 ms, or at 400 Hz, in order for the temperature measurement is to be used as a control input for the treatment protocol. With such a fast temperature measurement method, the laser can be shut off when the measured skin surface temperature reaches a preset threshold value.
Alternatively, a slower temperature measurement device can be used to predict the peak temperature by measuring the temperature rise and fall behavior during the early pulse application in the treatment protocol. The skin surface temperature can be measured during the first few laser pulses applied at the treatment area, and the temperature measurements are used to extrapolate the expected skin surface temperature during subsequent pulse applications such that the energy profile of the subsequent pulses can be adjusted accordingly. For instance, laser parameters such as the laser pulse duration, power, and pulse interval can be adjusted in order to deliver the appropriate amount of energy to the target chromophore while avoiding damage to the surrounding medium.
A flow chart shown in
Continuing to refer to
Then a determination is made in a decision 716 whether enough skin surface temperature data has been gathered for curve-fitting purposes. If the answer to decision 716 is NO, then the process returns to step 712 for the application of another laser pulse. If the answer to decision 716 is YES, then the measured skin surface temperature data are fitted to a predictive model in a step 718. Curve-fits of the maximum and, optionally, minimum skin surface temperatures are generated during step 718. The predictive model can be generated, for instance, by compiling a large number of temperature measurements corresponding to the application of laser pulses to test subjects in clinical settings, or by analytical modeling of the tissue.
Based on the curve-fits generated in step 718, a determination is made in a step 720 for the appropriate laser parameters for the specific treatment area on the individual being treated. In certain embodiments, step 720 may include determining the appropriate laser parameters for the next pulse. For example, if the curve-fits predict the skin surface temperature will rise above a predetermined threshold temperature, such as 45° C., then the laser parameters are adjusted to reduce the laser power. In this case, the skin surface temperature measurements can indicate that the specific treatment area on the subject is particularly sensitive to laser pulse energy absorption. Alternatively, if the curve-fits predict the desired temperature, such as 55° C. for target chromophore damage, will not be reached with the current laser pulse power settings, then the laser parameters can be adjusted to provide the necessary treatment power. Such a situation can occur if the epidermis and dermis characteristics are such that the specific treatment area does not readily absorb the laser pulse energy.
Continuing to refer to
Starting at time zero, the first temperature measurements after the first four pulses (indicated by circular dots) are fitted to a predictive model. Specifically, in the example shown in
The skin surface temperatures are measured during subsequent laser pulse applications, as shown in curve 812. It can be seen that the maximum and minimum temperature curves 830 and 832 accurately track the measured skin surface temperatures (i.e., peaks 842, 844, 846, and 848 and nadirs 843, 845, and 847 of curve 812). It is noted that the predicted temperature rise (i.e., dashed curve 830) and the actual measured temperatures (specifically peaks 846 and 848) indicate the desired temperature of 45.5° C. has been achieved by the application of pulses 6 and 7, thus the laser treatment protocol is halted without the application of an eighth pulse.
Even with a relatively slow temperature measurement device, such as a 25 Hz refresh IR camera, fitting the temperature data during the cooling down periods between laser pulse applications allows for a good estimation of the rapid temperature rise achieved with each pulse application. If a faster temperature measurement device (e.g., 400 Hz refresh rate or faster) is used, then the temperature profiles can be directly measured in real time.
The foregoing is illustrative of the present invention and is not to be construed as limiting thereof. Although a few exemplary embodiments of this invention have been described, those skilled in the art will readily appreciate that many modifications are possible in the exemplary embodiments without materially departing from the novel teachings and advantages of this invention. For example, lasers with other wavelengths, such as around 1210 nm, can be used. Alternatively, the pre-treatment analysis method described above can be used with other treatment protocols, such as those described in WIPO Patent Application WO/2018/076011 to Sakamoto et al. and WIPO Patent Application WO/2003/017824 to McDaniel. In fact, the method is applicable to any thermal treatment protocol involving equipment that may be subject to system, user, atmospheric conditions, and other variability from treatment to treatment.
Accordingly, many different embodiments stem from the above description and the drawings. It will be understood that it would be unduly repetitious and obfuscating to literally describe and illustrate every combination and subcombination of these embodiments. As such, the present specification, including the drawings, shall be construed to constitute a complete written description of all combinations and subcombinations of the embodiments described herein, and of the manner and process of making and using them, and shall support claims to any such combination or subcombination.
For example, embodiments such as the below are contemplated:
An improved approach to defining and adjusting the parameters of the photo-thermal treatment system involves the establishment and manipulation of a thermal gradient below the skin surface in the treatment area. Previous discussions of the establishment of a thermal gradient with photo-thermal targeted treatments involve the simultaneous application of a skin surface cooling with a laser pulse to effect damage to a chromophore at a particular depth below the skin surface (see, for example, U.S. Pat. App. Pub. No. 2109-0262072 A1 to Sakamoto, et al., which is incorporated herein by reference). Others have discussed the monitoring of skin surface temperature while applying laser pulses of varying pulse durations and powers in pre-set application protocols, while extrapolating the temperature profile in, for instance, the dermal layer of the treatment area (see, for example, U.S. Pat. No. 8,974,443 B2 to Dunleavy, et al., and U.S. Pat. No. 9,333,371 B2 to Bean, et al.).
In contrast, the embodiments disclosed herein provides systems and methods for controlling the peak of the thermal gradient (TG) established below the skin surface in the treatment area with closed-loop control of the heating and cooling systems. In embodiments, the present disclosure provides for a combination of active cooling and heating, adjustable prior to and during the application of a treatment protocol, to build a desired TG profile below the skin surface. By controlling the TG profile in a closed-loop manner, embodiments of the present disclosure provides consistent management of the photo-thermal energy delivery by the photo-thermal treatment system. In this way, the TG profile at the treatment area may be accurately controlled before and during the treatment, thus providing consistent, efficacious treatment experience for the patient while minimizing the sensation of pain.
In particular, it is recognized herein that the TG profile changes over time at any given location, such that the correlation between a measured surface temperature and the peak TG temperature also changes over time. Thus, it is insufficient to simply monitor the skin surface temperature as an indicator of subcutaneous TG. The relationships between the skin surface temperature, peak TG temperature, TG profile below the skin surface, and time of photo-thermal energy application must be considered to achieve consistent and effective energy delivery while ensuring patient comfort.
The embodiments described herein provide closed-loop control of the TG profile established below the skin surface at the treatment area, including the peak TG temperature during the photo-thermal energy application. As the TG profile at the treatment area changes over time, certain embodiments establish correlations between the skin surface temperature and the peak TG temperature over time, thus enabling active control of the cooling and heating mechanisms of the system to ensure the depth and peak temperature of the TG profile remains below a pain threshold of the patient being treated. In certain embodiments, a pre-treatment TG profile is established at the treatment area prior to any treatment protocol such that, when a treatment pulse is applied at the treatment area, the pain sensation felt by the patient is minimized. For example, the pre-treatment TG profile may be established such that the temperature at the desired target depth below the skin surface is less than 52° C. during the pre-conditioning phase. In embodiments, the method of establishing the TG profile at the treatment area includes using correlation functions to relate the expected heating and/or cooling response to measured variations in the heating and/or cooling response from previously applied photo-thermal energy pulses at a given treatment location.
A key factor differentiating the approaches described in the present disclosure is the recognition that correlation functions are universal for a given heating/cooling protocol, independent of the treatment area location and patient. Prior closed-loop approaches to controlling the photo-thermal energy delivery required adjustments to the cooling and heating parameters between different patients as well as different treatment locations on the same patient. In contrast, the present disclosure describes systems and methods that enable the definition and implementation of correlation functions derived as empirical relationships that allow for accurate predictions of heating and cooling responses across different treatment areas and patients. The correlation functions may be derived from a priori information obtained via laboratory and/or clinical testing, then applied for all subsequent treatments on actual patients.
Particularly, the correlation models implemented in the systems and methods described herein enable the estimation of a temperature drop at a given treatment location as measured between the end of a first heating pulse and just prior to the application of a second heating pulse immediately following the first heating pulse. That is, whereas previous approaches focused on the predictive closed-loop control of the temperature rise measurable at a particular treatment location by application of photo-thermal energy, such as a laser pulse, embodiments of the present disclosure also takes into consideration the cooling drop between the laser pulses to improve the control over the TG established by the laser pulses.
By accurately estimating this cooling drop, the starting temperature at the given treatment location prior to the second heating pulse may be predicted, thus enabling the adjustment of the parameters of this second heating pulse (e.g., power, pulse duration) to ensure that the skin temperature after the application of this second heating pulse may be within an acceptable range of a pre-determined target temperature. This estimation of the cooling drop may be based on the cooling measurements (i.e., the cooling temperature delta) prior to the first laser pulse along with the heating measurements (i.e., the heating temperature delta) of the prior pulse as inputs for the correlation model. That is, the input into the correlation model may also consider any laser pulses applied at the given treatment location prior to the first laser pulse (e.g., any pre-conditioning pulses or prior treatment pulses). In this way, the real time adjustment of the photo-thermal energy delivery based on the correlation model may consider both the cooling and heating temperature deltas at the treatment site, enabling more consistent and accurate control of the photo-thermal energy delivery to the patient than previously possible.
In certain embodiments, the heating properties of the second pulse (e.g., temperature increase per unit power and/or pulse duration) may be estimated from the heating properties any previously applied pulses (e.g., the first pulse and/or any pre-conditioning pulses applied to the given treatment location prior to the second pulse). By incorporating this heating property estimate, the photo-thermal energy source parameters to achieve a target peak temperature may be determined. Additionally, the cooling mechanism may be adjusted during treatment such that the cumulative effects of both the cooling and heating provided at the treatment location may be considered and adjusted as necessary, in real time during the application of the treatment protocol.
In other words, the methods described herein enable the closed loop control of any and all heating pulses (i.e., photo-thermal energy delivery) at a given treatment location. Thus, the described method and systems allow accurate control of the TG and treatment temperatures at different depths. In this way, embodiments of the systems and methods described herein allow more consistent and effective application of photo-thermal energy delivery at a given treatment location than possible using previously disclosed approaches.
As an example, the control of the TG profile by correlation with measured surface temperature may be performed as follows. The TG profile is defined as the profile of temperature as a function of depth in the tissue at a specific point in time. To target specific chromophores at different depths, the TG profile should be controlled to selectively heat those specific chromophores above a damage threshold, while maintaining the surrounding tissue below the damage threshold. Additionally, the pain experienced by the patient during the application of photo-thermal energy may be minimized by maintaining the overall tissue temperature below a predetermined pain threshold for as long as possible.
In order to achieve a desired thermal gradient profile, one may begin with a particular thermal profile in the tissue then apply sufficient photo-thermal energy to provide damage at a desired location within the tissue. Additionally, a cooling mechanism may be provided prior to and/or during the application of the photo-thermal energy. Due to the different mechanisms and efficiency rates of the heating (e.g., application of energy from a pulsed laser) and cooling (e.g., air cooling with the application of cooled air), the heating and cooling must be carefully balanced in order to achieve efficacious treatment results while avoiding tissue damage and patient discomfort. For instance, in order to create a thermal gradient peaked deeper into the tissue, the surface heat extraction and deposition of energy must be balanced near the skin surface while controlling the energy deposition at the desired depth over a sufficient amount of time to achieve the desired effects.
It is also recognized that the TG profile at a given treatment location changes over time. That is, the TG is a function of time, heat extraction rate (i.e., cooling effect produced by any cooling mechanism applied at the tissue surface), heat injection rate (i.e., the tissue heating produced by application of photo-thermal energy at the tissue surface), and tissue depth. Furthermore, for a given heating and cooling protocol, it is recognized that the TG profile as a function of time (i.e., tissue temperature as a function of depth and time) may be estimated using numerical heat transfer modeling using, for example, finite element analysis.
In a generalized three-dimensional case, numerical modeling is generally the only accurate method for estimating the spatial and temporal evolution of the TG profile at a given treatment location. However, the accuracy of such numerical modeling is only as good as the accuracy of the assumed optical and thermal parameters of the tissue used in the simulation. That is, the numerical modeling results may not accurately predict the TG profile in a patient if the actual tissue parameters significantly differ from the assumed optical and thermal parameters used in the simulation. While the numerical simulation results may be validated against clinical and/or experimental results, the simulation results may not accurately predict the TG profile for all patients.
The approaches described in the present disclosure overcomes the shortcomings of the previously described methods by combining the predicted TG profile from photo-thermal heat injection with a refined model of the extraction rate of cooling and real time temperature measurements. In an example, the heat extraction rate of cooling may be described by a known thermodynamic relationship:
where q is the heat extraction rate (in Watts), h is the heat transfer coefficient (in units of W per m2×x° C.), A is the area being cooled (in m2), and ΔT is the temperature differential between the tissue surface and the cooling medium (in ° C.). Thus, the heat extraction rate may be controlled by changing the heat transfer coefficient (e.g., by changing the cooling air speed, when using air cooling) or the temperature of the cooling medium (e.g., the cooling air temperature, when using air cooling, or the temperature of a contact surface, when using contact cooling).
The depth profile of photo-thermal heat injection may be expressed as a function of the optical absorption and scattering coefficients of the tissue onto which the photo-thermal energy is applied. That is, upon application of photo-thermal energy, the tissue at the applied location will be heated from the surface and into the tissue, where the TG profile depends on the energy and time of the heat application as well as the specific absorption efficient at each tissue layer. In order to provide efficient photo-thermal targeted treatment, it is recognized herein that the damage caused to tissue or a specific structure in the tissue (e.g., the sebaceous gland) generally follows the Arrhenius damage equation with dependence on temperature and time, namely that greater damage may be caused with the application of higher temperatures for a longer time. Therefore, to selectively damage a structure residing at a specific depth without causing damage to the surrounding tissue, the peak temperature of the TG profile should ideally be achieved at the depth of interest where the object to be damaged is located. Further, the sharper the temperature peak, the more selective the intended damage may be provided.
For short optical pulses (e.g., laser pulses with duration less than approximately 0.5 second), the resulting temperature profile of injected heat is generally independent of the temperature of the surrounding tissue if the tissue temperature is above freezing (0° C.) and below the tissue damage temperature (approximately 60-65° C. for pulses less than 0.2 seconds in duration). In such situations, the deposited heat from the short optical pulse has not had time to diffuse into the surrounding tissue prior to the end of the optical heating pulse, and the TG profile of the tissue remains generally unchanged.
Referring now to
Then, after the first optical pulse has been applied, the second from the bottom curve of
In other words, the TG profiles of the given location continues to fluctuate between a higher peak temperature at a depth of between 0.5 mm and 1 mm immediately after the application of each optical pulse as shown in
In previous approaches, as referenced above, the parameter changes were predicated on the peak temperature measurements taken immediately after the optical pulse application, without consideration of the subsequent cooling temperature delta that takes place between the optical pulses. Therefore, while the resulting adjustment of the laser parameters led to providing inconsistent treatment results since the photo-thermal energy provided may not have been sufficient to achieve efficacious treatment results.
However, the embodiments described herein considers both the heating temperature delta provided by the optical pulses as well as the cooling temperature delta provided by the continuous application of cooling at the skin surface. It is recognized herein that the time it takes to cool a given location to a certain depth and a given temperature is a function of the cooling power and the heat diffusion time of the tissue, which is a generally fixed property of the tissue determined by its thermal conductivity, specific heat capacity, and density. While decreasing the temperature of the cooling mechanism and increasing the heat transfer coefficient at the surface of the tissue will speed up the cooling at depths below the skin surface, the upper layers of tissue may freeze with excessive cooling. Therefore, there is a limit to the amount of cooling that may be provided at the skin surface, and it is important to balance the cooling provided and the heating due to the photo-thermal energy application. Taking all of these factors into consideration, the result is a more accurate prediction of the required photo-thermal energy for sufficient heating of the target chromophore and, consequently, more reliable and efficacious photo-thermal targeted treatment results.
For instance, using the thermal model estimations, such as exemplified in the graphs shown in
It is also recognized herein that both excessive heating and excessive cooling may lead to heightened perception of pain by the patient during the pre-conditioning and treatment protocols. Commonly provided pain mitigation procedures include providing sufficient cooling of the skin, the use of a topical anesthetic cream or gel, and the injection of an anesthetic such as those containing lidocaine, the application of a gaseous analgesic such as PRO-NOX™ analgesia, and the like. A combination of the various pain mitigation procedures may also help to reduce the sensation of pain (see, for example, co-pending U.S. patent application Ser. No. 17/564,836 filed Dec. 29, 2021, which is incorporated herein by reference). While the various pain management techniques listed above are effective for most photo-thermal targeted treatment procedures, the injection process of injectable anesthetics is itself painful, various other anesthetics require prescription, and typically requires a physician specialist to perform or supervise the procedures. Thus, it would be beneficial if the pain associated with the photo-thermal targeted therapy itself may be fundamentally reduced.
Specifically taking the example of photo-thermal targeted treatment of acne, the sebaceous glands located 0.5 mm to 1.5 mm below the skin surface are required to be heated to a temperature above 65° C. with a 100 ms laser pulse (for example) to achieve efficacious results. In general, the perception of pain is driven by excess temperature (i.e., temperature above a pain threshold), the time duration of the elevated temperature, and the volume of tissue at these elevated temperature. That is, the pain receptors for elevated temperatures are different depending on the temperature profile. For instance, exceeding the pain threshold at the skin surface will lead to a sensation of heat, whereas exceeding the pain threshold at a depth of approximately 1 mm below the skin surface will lead to a sensation of “needle sticks” at that location. In general, a person will perceive pain based on factors such as: 1) the temperature profile in the tissue, such as the volume of tissue exposed to temperatures above the threshold temperature associated with the pain receptor residing at the applicable depth; and 2) the duration of time spent above the pain threshold. At the depth of the typical sebaceous gland, the pain threshold of an average person is approximately 52° C. (see, for example, Basbaum, et al., “Cellular and Molecular Mechanisms of Pain,” Cell 139, Oct. 16, 2009), and generally no pain is perceived at this depth if the temperature spike is less than 52° C. and the duration is less than 250 milliseconds. As 52° C. is below the damage threshold of the sebaceous gland, additional pain remediation is generally needed with photo-thermal targeted treatment protocols for acne treatment.
As a specific example, consider a photo-thermal treatment protocol targeting a sebaceous gland that resides at a depth of 0.8 mm, without damaging the overlying or underlying dermis. The Arrhenius model shows that sebaceous gland damage is dependent on temperature and time, as is damage to the dermis. Using a time period of 100 milliseconds as an example, the required temperature to damage the target sebaceous gland is 65° C. However, the surrounding dermis must be kept below 60° C. over the same 100 milliseconds.
Ideally, the maximum sebaceous gland damage may be achieved without damaging the surrounding tissue by creating a TG profile with a peak temperature above 65° C. at approximately 0.8 mm, taking advantage of the difference in absorption between the sebaceous gland and the surrounding dermis, thus getting the sebaceous gland to reach a temperature above 65° C. while maintaining a dermis temperature below 60° C. Such a TG profile may be achieved by cooling the skin surface using a cooling source with a constant heat transfer coefficient, combined with a photo-thermal energy source such as a laser that deposits energy in a constant fashion, either pulsed or continuous wave. Using a 1726 nm laser, tissue pre-cooling at the skin surface to 1° C. and continuous cooling during the application of laser energy, the peak temperature of the TG profile may be achieved at a depth of 0.8 mm in approximately seven seconds.
It may be noted upon examination of graph 1200 of
It is noted that the laser parameters of the pulsing sequence exemplified in
In certain embodiments, cooling may be provided at the skin surface prior to and/or during the application of the pulses shown in
In an alternative approach, the combination of the cooling and photo-thermal heating pulses may be adjusted to quickly achieve the peak of the thermal gradient to just below the 52° C. pain threshold at the desired depth early in the seven second laser application period, then reduce the heating (e.g., by reducing the power and/or pulse duration of subsequent pulses) to maintain the peak temperature at the desired depth while allowing time for heat to diffuse, thus heating deeper tissue. In still another approach, the pre-cooling and treatment time may be further reduced by increasing the cooling power by decreasing the temperature of the cooling mechanism or increasing the heat transfer coefficient (e.g., increase cooling airspeed in an air-cooled system). If the skin surface temperate can be maintained just above the freezing temperature during the application of the photo-thermal energy, the additional cooling may more quickly reduce the temperature at depth, thus pushing the peak of the TG profile deeper below the skin surface. Such an effect would allow the application of greater heating power (e.g., increased laser pulse power or duration), effectively resulting in deeper penetration of the heating power into the tissue in a given pulse application sequency while preventing damage at the shallower tissue.
In embodiments, the aim of the processes described herein is to keep the dermis temperature below the generally accepted pain threshold temperature of 52° C. The skin surface temperature and its correlation to the dermis temperature may be determined using the processes described herein and used as a proxy for the temperature at a depth below the skin surface (e.g., at the dermis).
As shown in
A CW laser source may be applied at the treatment location, as indicated by a dashed curve in
As the CW power is decreased, the wavelength of the CW light source may be selected to promote heating of the deeper dermis while keeping the skin surface temperature at a tolerable level for the subject. This time period is indicated as tETG in
In embodiments, rather than an initial spike of the CW laser power as shown in
At a time to, when the peak CW power is applied as shown in
The use of CW power may be advantageous as the steady state temperature at the depth of the target chromophore may be maintained at a higher temperature than with a pulsed pre-heating scheme. Further, the CW power may be applied over a larger surface area at and around the target treatment location, thus enabling the broader heating and earlier establishment of the thermal gradient over a larger surface area.
In addition to the embodiments enumerated above, additional embodiments such as below are contemplated:
As used herein, the recitation of “at least one of A, B and C” is intended to mean “either A, B, C or any combination of A, B and C.” The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present disclosure. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the disclosure. Thus, the present disclosure is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
The terms and expressions employed herein are used as terms and expressions of description and not of limitation, and there is no intention, in the use of such terms and expressions, of excluding any equivalents of the features shown and described or portions thereof. Each of the various elements disclosed herein may be achieved in a variety of manners. This disclosure should be understood to encompass each such variation, be it a variation of an embodiment of any apparatus embodiment, a method or process embodiment, or even merely a variation of any element of these. Particularly, it should be understood that the words for each element may be expressed by equivalent apparatus terms or method terms-even if only the function or result is the same. Such equivalent, broader, or even more generic terms should be considered to be encompassed in the description of each element or action. Such terms can be substituted where desired to make explicit the implicitly broad coverage to which this invention is entitled.
As but one example, it should be understood that all action may be expressed as a means for taking that action or as an element which causes that action. Similarly, each physical element disclosed should be understood to encompass a disclosure of the action which that physical element facilitates. Regarding this last aspect, by way of example only, the disclosure of a “protrusion” should be understood to encompass disclosure of the act of “protruding”—whether explicitly discussed or not—and, conversely, were there only disclosure of the act of “protruding”, such a disclosure should be understood to encompass disclosure of a “protrusion”. Such changes and alternative terms are to be understood to be explicitly included in the description.
In the specification, there have been disclosed embodiments of the invention and, although specific terms are employed, they are used in a generic and descriptive sense only and not for purposes of limitation. Although a few exemplary embodiments of this invention have been described, those skilled in the art will readily appreciate that many modifications are possible in the exemplary embodiments without materially departing from the novel teachings and advantages of this invention. Therefore, it is to be understood that the foregoing is illustrative of the present invention and is not to be construed as limited to the specific embodiments disclosed, and that modifications to the disclosed embodiments, as well as other embodiments, are intended to be included within the scope of the present disclosure.
The present application claims the benefit of U.S. Provisional Application Ser. No. 63/451,991, filed 2023 Mar. 14 and titled “Photo-Thermal Targeted Treatment System and Associated Methods for Efficacy, Consistency, and Pain Minimization.” The present application is a continuation-in-part of co-pending U.S. patent application Ser. No. 17/735,056, filed 2022 May 3 and titled “Determination Process and Predictive Closed-Loop Control of Dosimetry Using Measurement of Skin Surface Temperature and Associated Methods.” The above application is in turn a continuation of U.S. patent application Ser. No. 16/658,818, now U.S. Pat. No. 11,317,969, filed 2019 Oct. 21 and titled “Dosimetry Determination Process via Measurement of Skin Surface Temperature and Associated Methods,” which claims the benefit of U.S. Provisional Patent Application Ser. No. 62/749,104, filed 2018 Oct. 22 and titled “Dosimetry Determination Process via Measurement of Skin Surface Temperature and Associated Methods,” as well as U.S. Provisional patent Application Ser. No. 62/771,523, filed 2018 Nov. 26 and titled “Predictive Closed-Loop Control of Dosimetry Using Measurement of Skin Surface Temperature and Associated Methods.” All of the above-referenced applications are incorporated herein by reference in their entirety.
| Number | Date | Country | |
|---|---|---|---|
| 63451991 | Mar 2023 | US | |
| 62771523 | Nov 2018 | US | |
| 62749104 | Oct 2018 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 16658818 | Oct 2019 | US |
| Child | 17735056 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 17735056 | May 2022 | US |
| Child | 18605707 | US |
