System for feedback analysis and / or treatment of at least one patient using electromagnetic radiation treatment device, method, and computer accessible medium

Abstract

To provide a device and a method that facilitate treatment of at least one patient.SOLUTION: A data collection system that collects data of a patient, and a controller configured to authenticate access to a remote network, aggregate collected patient data, store aggregated patient data in a data storage device that communicates with the remote network, and access a service module that communicates with the remote network can be used. An EMR source configured to generate an electromagnetic radiation ("EMR") beam can be provided. A treatment system based on the EMR may include a convergence optical element configured to converge the EMR beam to a focal region located along an optical axis, and a window located between the focal region and the convergence optical element along the optical axis, away from the focal region by a predetermined depth. The window may be configured to allow the EMR beam to transmit therethrough and contact a tissue surface.SELECTED DRAWING: Figure 14

Description

[Technical Field]

[0001] [CROSS-REFERENCE TO RELATED APPLICATIONS] This application claims priority to U.S. Patent Application No. 62 / 952,793, filed December 23, 2019, the entire disclosure of which is incorporated herein by reference.

[0002] The present disclosure relates to feedback detection and / or treatment of at least one patient, and more particularly to systems, methods, and computer-accessible media for providing feedback detection and / or treatment of at least one patient, for example, using electromagnetic radiation therapy / utilization devices. [Background technology]

[0003] Dermatological and cosmetic treatments can utilize personalized treatment parameters to achieve desired results. Particularly challenging cases include patients with darker skin types (e.g., Fitzpatrick skin type II or higher) and those with dermal pigmentation conditions (e.g., melasma). To provide personalized treatment (e.g., for challenging cases), it may be advantageous to document treatment parameters, patient data, and images of lesions before and after treatment. This information can be used to later track progress and (if necessary) modify treatment. However, currently, this documentation requirement is not streamlined and requires the use of multiple systems that likely do not communicate with each other. For example, images of a patient's specific body parts are typically acquired using a camera system (e.g., a dermatoscope), patient data is usually stored in an electronic health record, and treatment is performed on a separate, stand-alone treatment electromagnetic radiation (EMR)-based system. Because of this, personalized tracking of specific patient outcomes and individualized treatment is available only to patients who visit the most vigilant clinicians.

[0004] Melasma or chloasma faciei (e.g., mask of pregnancy) is a common skin condition characterized by yellow-brown to dark gray-brown, irregular, well-demarcated spots and patches. The macules are thought to be due to the overproduction of melanin, which is either incorporated into keratinocytes (epidermal melanosis) or deposited in the dermis (dermal melanosis, melanophages). The pigmented appearance of melasma can be exacerbated by certain conditions, such as pregnancy, sun exposure, certain medications (e.g., oral contraceptives), hormonal levels, and genetics. Depending on the location of the excess melanin, the condition can be classified as an epidermal, dermal, or mixed condition. Exemplary symptoms of melasma include dark, irregularly shaped patches or blotches, often found primarily on the upper cheeks, nose, upper lip, and forehead, which often develop gradually over time.

[0005] Melasma can cause considerable embarrassment and distress. It can be particularly problematic for dark-skinned women, affecting up to 30% of women in Southeast Asia and many Latin American women. Population studies suggest that between one in four and one in 20 affected individuals are men. According to the American Academy of Dermatology, nearly 6 million women in the United States suffer from melasma. Globally, the number of people affected by melasma is estimated to be approximately 157 million in Asia-Pacific, 58 million in Latin America, and 3 million in Europe. Melasma typically appears between the ages of 20 and 40. Because there is currently no cure for melasma, patients in the United States currently attempt various types of treatment. 79% of patients in the United States use topical medications; for example, approximately 37% use oral treatments, and approximately 25% use lasers.

[0006] Unlike other pigmented structures typically present in the epidermal region of the skin (e.g., at or near the tissue surface), dermal (or deep) melasma is often characterized by the widespread presence of melanin and melanophages in parts of the underlying dermis. Therefore, treating dermal melasma (e.g., lightening the appearance of darkened pigmented areas) can be particularly challenging because it is more difficult to access and affect such pigmented cells and structures located deeper within the skin. Therefore, conventional skin rejuvenation treatments, such as facial peels (e.g., laser or chemical), dermabrasion, and topical agents, which primarily affect the upper epidermis (and are often the first course of treatment for melasma), may not be effective in treating dermal melasma.

[0007] Furthermore, up to 50% of melasma patients also experience other hyperpigmentation problems. Among pigmentary disorders, melasma is perhaps the one that causes the largest percentage of patients to visit a dermatologist. Managing this disorder remains challenging given our incomplete understanding of its etiology, its chronicity, and recurrence rate. After treatment, melasma may recur, often worse than before treatment. Furthermore, topical treatments that may be effective in treating epidermal melasma may not effectively treat dermal melasma or mixed melasma.

[0008] To successfully treat a challenging condition such as melasma, patient outcomes must be carefully tracked and treatment parameters rationally adjusted. Without feedback indicating treatment progress and patient response, melasma can only be successfully treated by the most skilled clinicians. Because so many people are affected by melasma and there are so few clinicians who can successfully treat the condition, many people suffering from such a disorder remain untreated.

[0009] It has been observed that applied light or light energy of a certain wavelength is strongly absorbed by pigmented cells, damaging them. However, effective treatment of dermal melasma using light energy can present several obstacles. For example, pigmented cells in the dermis must be targeted with sufficient light energy of an appropriate wavelength to destroy or damage them, which can partially depigment and / or destroy pigmentation and reduce the pigmented appearance. However, such energy can be absorbed by pigments (e.g., melanin) in upper skin tissues, such as the epidermis and upper dermis. This near-surface absorption can lead to excessive damage to the outer parts of the skin and insufficient energy delivered to the deeper dermis to affect the pigmented cells in the deeper dermis. Furthermore, moderate thermal injury to melanin-containing melanocytes located in the basal layer of the epidermis can cause increased melanin production (e.g., hyperpigmentation), while severe thermal damage to melanocytes can cause decreased melanin production (e.g., hypopigmentation).

[0010] The Pigmentation Disorders Association (PDA) evaluated the clinical effectiveness of different types of melasma treatments to reach a consensus on effective treatments. The PDA study results were published in a paper titled "Treatment of Melasma" by M. Rendon et al. in the Journal of the American Academy of Dermatology in May 2006. Rendon et al.'s paper reviewed literature on melasma treatments dating back 20 years and made their decision based on that review. The paper stated, "The group's consensus is that first-line therapy for melasma should consist of effective topical treatments, primarily fixed triple combinations," and "Lasers are rarely used to treat melasma, and when applied, skin type must be taken into consideration."

[0011] The most recent review of such literature on melasma treatment is dated to 2006. A recent editorial by M. Sadeghpour et al., titled "Advances in the Treatment of Melasma," published in Advances in Cosmetic Surgery in 2018, attempts to review current melasma treatments. The editorial by Sadeghpour et al. similarly concludes that "topical therapy remains the gold standard for first-line treatment of melasma, using broad-spectrum sunscreen and either hydroquinone 4% cream, tretinoin, or triple combination cream." The paper also notes that dermal melasma is more difficult to treat because "the destruction of these melanosomes is often accompanied by severe inflammation, which further stimulates melanogenesis."

[0012] Thus, there remains a significant unmet need for more effective and safer treatments for melasma and other difficult-to-treat pigmentary disorders.

[0013] An approach has been developed that involves applying light energy to small, discrete treatment locations within the skin separated by healthy tissue to facilitate healing. Accurately targeting treatment locations (e.g., located in the dermal layer) with the desired specificity while avoiding damage to surrounding healthy tissue (e.g., the epidermal layer) is challenging. This requires, for example, the use of an optical system with a high numerical aperture (NA) to focus the laser beam onto the treatment location. A high NA optical system delivers a sufficiently high focused fluence (i.e., energy density) to the dermis while maintaining a sufficiently low out-of-focus fluence in the epidermis. U.S. Patent Application Publication No. 2016 / 0199132, entitled "Method and Apparatus for Treating Dermal Melasma," demonstrates that this technique can be advantageous for treating dermal pigmentation, including melasma, in a research setting.

[0014] The techniques described in such publications generally favor a focal region formed by a high-NA optical system precisely positioned at a certain depth within the target tissue (e.g., within a tolerance of approximately ±25 μm). For example, melanocytes are typically located within the basal layer of the epidermis at a depth of approximately 100 μm from the top of the skin surface. Dermal melanophages, responsible for deep melasma, may reside in the upper dermis, just below the basal layer (e.g., 50 μm below). Thus, a difference in focal region depth of tens of micrometers can mean the difference between effectively treating dermal pigmentation and inadvertently damaging melanocytes and potentially causing debilitating cosmetic consequences (e.g., hypopigmentation). One reason for this is that EMR-based systems that effectively treat dermal pigmentation are not yet commercially available.

[0015] It is therefore desirable to provide an EMR-based treatment system that reliably positions the focal region to a predetermined depth within a tolerance of tens of micrometers (e.g., about ±100 μm, about ±10 μm, about ±1 μm, etc.). Furthermore, it may be desirable for such EMR-based treatment systems to achieve this performance in part through calibration, e.g., by periodically placing the focal region at a reference location having a known depth. Furthermore, it may be desirable for the reference location used during calibration to be used during treatment. For example, the reference location may include an interface that establishes firm contact with and stabilizes the treatment region.

[0016] Therefore, there is a need to address at least some of the deficiencies described herein above. Summary of the Invention [Problem to be solved by the invention]

[0017] [Illustrative Objectives and Potential Illustrative Benefits] Certain developed approaches for dermal pigmentation treatment, such as that outlined by U.S. Patent Application Publication No. 2016 / 0199132, can utilize selective thermionic plasma generation as a means of treatment. In these cases, the laser fluence at the focal region within the dermis is typically greater than the thermionic plasma threshold (e.g., 10 9 W / cm 2 ), but not above the optical breakdown threshold (e.g., 10 12 W / cm 2 ) below the target value. This causes selective plasma formation when the focal region is located in pigmented tissue (e.g., melanin) within the dermis without generating plasma in non-pigmented tissue within the dermis or in pigmented epidermal tissue above the focal region. The selectively formed thermionic plasma destroys or damages the pigment and surrounding tissue. This destruction ultimately leads to the removal of dermal pigment. Thus, according to certain exemplary embodiments, the presence of plasma during treatment within the tissue being treated can indicate effective treatment. Because parameter selection for laser-based skin treatments often depends on the patient's skin type and, indeed, other individual characteristics of the patient, the presence of plasma can be used as an indicator that the correct treatment parameters have been achieved. This feedback may therefore be desirable for successfully treating various conditions, including melasma, in populations typically underserved by various laser-based treatments (e.g., those with darker skin types).

[0018] Alternatively, in some cases, detected plasma characteristics may indicate that the treatment is having adverse effects. For example, in certain exemplary circumstances, a transmission window may be placed on the skin being treated to hold the skin stationary during treatment, using the skin as a reference position. If the laser beam etches the window, the treatment may fail. Window etching likely prevents further efficient penetration of the laser into the tissue and is often accompanied by very bright plasma formation in the window itself. Continuing treatment with an etched window can result in heat accumulation within the window, potentially damaging the epidermis of the skin (e.g., burning and blistering). Therefore, according to exemplary embodiments of the present disclosure, it may be advantageous to use feedback to detect plasma formation within the window and reduce and / or stop treatment when plasma formation occurs.

[0019] From the foregoing, it can be appreciated that plasma formation during treatment can be beneficial and detrimental to the treatment. Accordingly, systems and methods according to exemplary embodiments of the present disclosure that provide plasma detection can detect plasma characteristics and continuously distinguish between plasma that is beneficial to tissue treatment and plasma that may be detrimental to tissue treatment in real time.

[0020] According to certain exemplary embodiments of the present disclosure, it may be desirable to image the tissue being treated from the perspective of the treatment device and project this view onto a screen viewed by the practitioner. In one exemplary situation, the placement of the treatment device typically obstructs the practitioner's view of the tissue being treated. Thus, tissue imaging according to exemplary embodiments of the present disclosure can facilitate precise placement of the treatment device to target the affected tissue. Furthermore, because the goal of treatment for many pigmentation conditions is cosmetic (e.g., improving the appearance of the skin), it is desirable to be able to consistently obtain images of the skin under repeatable imaging conditions (e.g., illumination and distance) during imaging, allowing for confirmation of representative results of the treatment. An attempt to address some of the aforementioned issues can be found in pending U.S. patent application Ser. No. 16 / 447,937, entitled "Feedback Detection for a Treatment Device," by J. Bhawalkar et al., which is incorporated herein by reference in its entirety.

[0021] Furthermore, successful treatment of many dermatological and cosmetic conditions requires multiple treatments (often using EMR-based devices). Treatment parameters are largely patient-specific, and monitoring treatment progress over time can be difficult. For at least these reasons, it is desirable to capture, document, and analyze patient and treatment data to inform ongoing treatment. However, currently, no treatment platform is well-suited for performing these data-related activities.

[0022] People suffering from pigmentation conditions such as melasma have long anticipated the widespread availability of EMR-based treatments for their conditions. Accordingly, as described in more detail below, in accordance with exemplary embodiments of the present disclosure, an EMR-based treatment system can be provided that facilitates repeatable depth positioning of focal regions within target tissue.

[0023] It is an object of the present disclosure to provide feedback and analysis systems, methods, and computer-accessible media that can facilitate the treatment of dermatological and cosmetic conditions, including, but not limited to, conditions that are very difficult to treat (e.g., melasma). [Means for solving the problem]

[0024] To that end, certain exemplary embodiments of the present disclosure may provide systems, methods, and computer-accessible media for detecting and recording plasma events to document and track the safety and effectiveness of treatments, image treated tissue, and precisely deliver EMR to treatment areas and / or treatments in at least one patient. These capabilities may address many of the technical challenges that currently hinder the widespread and successful treatment of dermal pigmentation and other difficult-to-treat skin conditions using EMR-based systems.

[0025] In exemplary embodiments of the present disclosure, various systems, methods, and computer-accessible media can be provided to facilitate feedback detection and / or treatment of at least one patient. For example, a data collection system that collects patient data and a controller that authenticates access to a remote network, aggregates the collected patient data, stores the aggregated patient data in a data storage device in communication with the remote network, and (optionally) accesses a module (e.g., a service module) that can communicate with the remote network can be utilized. An electromagnetic radiation ("EMR") source configured to generate an EMR beam can be provided. An optics configuration (e.g., focus optics) can be provided that can be configured to converge or focus the EMR beam to a focal region located (i) along an optical axis and (ii) below the surface of at least one patient's tissue, and a window can be provided that is located a predetermined distance from the focal region and between the focal region and the optics configuration along the optical axis. The window can be configured to transmit the EMR beam and contact the tissue surface. The optical element configuration includes a folded Petzval lens.

[0026] In another exemplary embodiment of the present disclosure, access to a service module may be provided by authenticating access to the module. Access to the remote network may be provided by verifying that (i) a financial agreement (e.g., payment) has been executed, (ii) a financial transaction (e.g., payment) has been received, and / or (iii) a financial transaction is pending. For example, access to the remote network may be provided by facilitating payment for (i) a treatment, (ii) a patient, (iii) a subscription, (iv) an image, and / or (v) a service module. The service module may include an image recognition module, a computer vision module, an electronic health record module, and / or a clinical decision-making support module. The patient data may include an image of patient tissue, the age of the patient, treatment session information, a patient pain score, data collection parameters, and / or EMR-based treatment parameters. The data collection system may be configured to collect patient data from tissue in contact with the window. Both the data collection system and the optical element arrangement may be spatially registered to the window.

[0027] Exemplary embodiments of the present disclosure may implement drug-based therapies, including topical drugs, injectable drugs, and / or orally delivered drugs. An electromagnetic radiation (EMR) beam may be focused to a focal region, and such focusing may be performed with a numerical aperture (NA) of 0.3 or greater. Patient data may be collected, for example, by illuminating a tissue surface, directing light from the tissue surface to an image plane, and sensing the light at the image plane. Patient data may be collected by (i) entering patient data using a user interface or (ii) interfacing with another network that facilitates the device containing patient data. Patient data may be collected by a photoacoustic imaging device, a camera, a dermatoscope subsystem, a microscope subsystem, a confocal microscope subsystem, a plasma detection subsystem, and / or a window referencing subsystem.

[0028] These and other objects, features and advantages of exemplary embodiments of the present disclosure will become apparent from the following detailed description of exemplary embodiments of the present disclosure, taken in conjunction with the appended claims.

[0029] Further objects, features and advantages of the present disclosure will become apparent from the following detailed description taken in conjunction with the accompanying drawings illustrating exemplary embodiments of the present disclosure. [Brief explanation of the drawings]

[0030] [Figure 1] FIG. 1 is a block diagram of an apparatus for electromagnetic radiation (EMR) treatment and patient data collection, storage, and analysis, according to an exemplary embodiment of the present disclosure. [Figure 2]FIG. 2 is a flow chart illustrating a method for EMR treatment and patient data collection, storage, and analysis according to an exemplary embodiment of the present disclosure. [Figure 3] FIG. 3 is a block diagram of patient data storage according to an exemplary embodiment of the present disclosure. [Figure 4] FIG. 4 is a block diagram of a patient data analysis service module operating using the example device of FIG. 1 according to an example embodiment of the present disclosure. [Figure 5] FIG. 5 illustrates an exemplary embodiment of a treatment system according to the present disclosure. [Figure 6] FIG. 6 is an exemplary illustration of an EMR beam focused on a pigmented region of the dermis layer of skin using an exemplary method and system according to an exemplary embodiment of the present disclosure. [Figure 7A] FIG. 7A is an exemplary absorbance spectrum graph of melanin. [Figure 7B] FIG. 7B is an exemplary absorbance spectrum graph of hemoglobin. [Figure 8] FIG. 8 is a graph showing the absorption coefficients of melanin and venous blood and the scattering coefficient of light in skin versus wavelength. [Figure 9] FIG. 9 is a block diagram of a treatment system according to an exemplary embodiment of the present disclosure. [Figure 10] FIG. 10 is a schematic diagram of an optical system according to an exemplary embodiment of the present disclosure. [Figure 11] FIG. 11 is a schematic diagram of an optical system with a microscope attachment according to another exemplary embodiment of the present disclosure. [Figure 12] FIG. 12 is a schematic diagram of an optical system having a fiber coupler attachment according to yet another exemplary embodiment of the present disclosure. [Figure 13] FIG. 13 is a flow diagram for accomplishing an exemplary method for plasma detection, according to an exemplary embodiment of the present disclosure. [Figure 14] FIG. 14 is a diagram of a plasma detection system according to an exemplary embodiment of the present disclosure. [Figure 15] FIG. 15 is a flow diagram for implementing an exemplary window lookup procedure according to an exemplary embodiment of the present disclosure. [Figure 16A] FIG. 16A is a diagram of a window referencing system according to an exemplary embodiment of the present disclosure. [Figure 16B] FIG. 16B illustrates an exemplary performance of a window reference system according to an exemplary embodiment of the present disclosure. [Figure 17] FIG. 17 is a flow diagram of an exemplary imaging and radiation-based therapy method according to an exemplary embodiment of the present disclosure. [Figure 18] FIG. 18 is a diagram of an exemplary imaging and radiation-based therapy system according to an exemplary embodiment of the present disclosure. [Figure 19A] FIG. 19A is an exemplary stitched image according to an exemplary embodiment of the present disclosure. [Figure 19B] FIG. 19B is a flow diagram illustrating an exemplary method for stitching images together, according to an exemplary embodiment of the present disclosure. [Figure 19C] FIG. 19C illustrates two exemplary images of tissue subjected to a keypoint detection procedure, according to some exemplary embodiments of the present disclosure. [Figure 19D] FIG. 19D illustrates two exemplary images merged together highlighting inlier matches, according to some exemplary embodiments of the present disclosure. [Figure 19E] FIG. 19E illustrates an exemplary unfused mosaic of stitched images, according to some exemplary embodiments of the present disclosure. [Figure 19F] FIG. 19F illustrates an exemplary fused mosaic of stitched images, according to some exemplary embodiments of the present disclosure. [Figure 19G] FIG. 19G illustrates an exemplary final mosaic of stitched images, according to some exemplary embodiments of the present disclosure. [Figure 20] FIG. 20 is a diagram of an exemplary apparatus for EMR treatment and visualization of treated tissue, according to an exemplary embodiment of the present disclosure. [Figure 21] FIG. 21 is a flow diagram of a method for EMR treatment and visualization of treated tissue according to an exemplary embodiment of the present disclosure. [Figure 22] FIG. 22 is a diagram illustrating an exemplary ray trace according to an exemplary embodiment of the present disclosure. [Figure 23] FIG. 23 is an exemplary modulation transfer function (MTF) graph of a diffraction-limited endoscopic imaging system according to an exemplary embodiment of the present disclosure. [Figure 24] FIG. 24 is an exemplary image of an exemplary configuration of an exemplary endoscopic imaging system according to an exemplary embodiment of the present disclosure. [Figure 25A] FIG. 25A is an example image produced using the example configuration of FIG. [Figure 25B] FIG. 25B is an example image produced using the example configuration of FIG. [Figure 25C] FIG. 25C is an example image produced using the example configuration of FIG. [Figure 26] FIG. 26 is a diagram illustrating an exemplary ray trace according to yet another exemplary embodiment of the present disclosure. [Figure 27] FIG. 27 illustrates another exemplary embodiment of a data collection and treatment device / system according to an exemplary embodiment of the present disclosure. [Figure 28] FIG. 28 illustrates yet another exemplary embodiment of a data collection and treatment device / system according to an exemplary embodiment of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0031] It should be noted that the drawings are not necessarily to scale. The drawings are intended to depict only typical aspects of the subject matter disclosed herein and should not be considered as limiting the scope of the present disclosure. The systems, apparatus, and methods specifically described herein and shown in the accompanying drawings are non-limiting exemplary embodiments and the scope of the appended claims.

[0032] Certain exemplary embodiments are described below to provide a general understanding of the principles of structure, function, manufacture, and use of the devices and methods disclosed herein. One or more examples of these embodiments are illustrated in the accompanying drawings. Those skilled in the art will understand that the devices, systems, and methods specifically described herein and illustrated in the accompanying drawings are non-limiting exemplary embodiments, and the scope of the disclosure is defined only by the claims, which may be modified, supplemented, or otherwise altered as necessary. Exemplary features shown or described in connection with one exemplary embodiment may be combined with features of other embodiments. Such exemplary modifications and variations are intended to be included within the scope of the disclosure and not to limit the embodiments in any way.

[0033] Exemplary embodiments of the present disclosure are described in detail herein with respect to exemplary treatments of skin pigmentary conditions, such as melasma, to improve the appearance of such pigmentary conditions. However, exemplary embodiments of the present disclosure may be used or implemented without limitation for the treatment of a variety of other pigmentary and non-pigmentary conditions and / or other tissue and non-tissue targets. Examples of pigmentation conditions include, but are not limited to, post inflammatory hyperpigmentation (PIH), dark skin surrounding eyes, dark eyes, cafe au lait patches, Becker's nevi, Nevus of Ota, congenital melanocytic nevi, ephelides (freckles), and lentigo. Additional examples of treatable pigmented tissues and structures include, but are not limited to, hemosiderin-rich structures, pigmented gallstones, tattoo-containing tissues, and lutein-, zeaxanthin-, rhodopsin-, carotenoid-, biliverdin-, bilirubin-, and hemoglobin-rich structures. Examples of therapeutic targets for non-pigmented structures, tissues, and conditions include, but are not limited to, hair follicles, hair shafts, vascular lesions, infectious conditions, sebaceous glands, acne, and the like.

[0034] Exemplary methods or procedures for treating various skin conditions, such as for cosmetic purposes, may be performed using the exemplary systems, devices, etc. described herein. While such methods and / or procedures may be performed by a physician, it should be understood that non-physicians, such as aestheticians and other suitably trained personnel, may utilize the exemplary systems and / or devices described herein to treat various skin conditions, with or without the supervision of a physician or other medical professional.

[0035] Furthermore, in this disclosure, like-named components of exemplary embodiments may generally have similar characteristics, and therefore, in a particular exemplary embodiment, every feature of each like-named component need not necessarily be fully described. Furthermore, to the extent that linear or circular dimensions are used in describing the disclosed exemplary systems, devices, and methods, such dimensions are not intended to limit the types of shapes that may be used in conjunction with such systems, devices, and methods, but are intended to be exemplary. Those skilled in the art will recognize that equivalents of such linear and circular dimensions can be readily determined for any geometric shape. The sizes and shapes of the systems and devices and their components may depend, at a minimum, on the subject anatomy in which the systems and devices may be used, the sizes and shapes of components for use with the exemplary systems and devices, and the exemplary methods and procedures in which the systems and devices are used, and are intended to be exemplary.

[0036] For example, exemplary high numerical aperture (NA) optical treatment systems are described that can focus electromagnetic radiation (EMR) (e.g., a laser beam) to a treatment region within tissue. Unless otherwise specified, the terms EMR, EMR beam, and laser beam are used interchangeably herein. According to various exemplary embodiments of the present disclosure, the focused laser beam can deliver light energy to the treatment region without damaging surrounding tissue. The delivered light energy can, for example, destroy pigmented chromophores and / or targets in the treatment region in the dermis layer of the skin without affecting surrounding regions (e.g., the upper epidermis layer, other portions of the dermis layer, etc.). In other exemplary implementations, the delivered light energy can remove or alter tattoos or cause hemoglobin-related treatments.

[0037] Exemplary methods, systems, and devices for treating skin conditions with light or light energy are described in U.S. Patent Application Publication No. 2016 / 0199132, entitled "Method and Apparatus for Treating Dermal Melasma," and U.S. Provisional Application No. 62 / 438818, entitled "Method and Apparatus for Selective Treatment of Dermal Melasma," each of which is incorporated herein by reference in its entirety.

[0038] Generally, exemplary systems, devices, and methods are provided for treating pigmentation conditions in tissue. As described in more detail herein, the exemplary systems, devices, and methods can use electromagnetic radiation (EMR), such as a laser beam, to deliver a predetermined amount of energy to target tissue. The EMR can be focused to a focal region, which can be translated or rotated in any direction relative to the target tissue. The predetermined amount of radiation can be configured to thermally disrupt or otherwise damage portions of the tissue that exhibit the pigmentation condition. In this manner, a predetermined amount of energy can be delivered to any location within the target tissue to treat the pigmentation condition, e.g., improve its appearance.

[0039] Referring now to FIG. 1 , a system 100 for electromagnetic radiation (EMR) treatment and patient data collection, storage, and analysis is described and illustrated, according to an exemplary embodiment of the present disclosure. The exemplary system 100 illustrated in FIG. 1 may include an EMR-based treatment system 110. The exemplary EMR-based treatment system is described in detail below and may include a laser source (e.g., a fiber laser, a Q-switched Nd-YAG, a diode pumped solid state [DPSS] laser, etc.) that generates a laser beam. The laser beam may be in optical communication with a focus optic (e.g., an aspheric lens) configured to focus the laser beam with a high numerical aperture (NA) (e.g., greater than 0.2) to a focal region located a predetermined distance from a window below the beam (e.g., generally away from the laser source along the optical axis of the beam path). The window is configured to transmit the focused laser beam and contact the outer surface of the patient's tissue, allowing the focal region to be positioned within the tissue (often at a predetermined depth within the tissue). The exemplary system may also include a data collection system 112. The exemplary data collection system 112 is described in detail below. The data collection system may be configured to collect data regarding at least one patient, the treatment being performed, and / or the system. In some exemplary embodiments, the data collection system may include a sensor that senses patient data. For example, in some exemplary embodiments, the data collection system may include an illumination source configured to illuminate the surface of the tissue, an optical arrangement configured to direct light from the surface of the tissue through the window to a sensor plane, and a camera sensor configured to sense the light at the sensor plane. In other exemplary embodiments, the data collection system may collect non-sensing data. The collected patient data may include a plurality of images.The collected patient data may be aggregated (e.g., by the controller) by stitching together multiple images. For example, in some exemplary embodiments, the data collection system may include a user interface configured to receive patient data manually entered by a user. In another example, the data collection system includes a system interface configured to receive data from another network-enabled device (e.g., an electronic medical record).

[0040] Both the data acquisition system 112 and the treatment system 110 can communicate with a controller 114. The controller 114 can control the parameters performed by the treatment system 110 and the process data collected by the data acquisition system 112. In certain exemplary embodiments, data from the data acquisition system 112 can be used as a basis for controlling treatment parameters of the treatment system 110. Exemplary treatment parameters may include, for example, laser pulse duration, laser power, laser pulse energy, laser repetition rate, focal region location (e.g., depth within tissue), focal region scan speed, focal region scan path, etc. The controller 114 can be connected to one or more networks 116 and / or other communication systems and / or networks. For example, the controller 114, according to some exemplary embodiments, can be connected to a local area network (LAN) via a network interface card (NIC). In some other exemplary embodiments, the controller 114 may be connected to a wireless local area network (WLAN) (e.g., Wi-Fi) via a wireless adapter. Such a network 116 may ultimately be accessible by a remote network 118. The remote network 118 may provide communication to and / or from (e.g., between) a data store 120 (e.g., one or more hard drives, memory devices, etc.) and one or more service modules 122A-122C. In exemplary embodiments, the data store 120 may include non-volatile memory capable of securely storing data (e.g., patient data). The service modules 122A-122C may provide resources (e.g., applications) that can be used to perform services (e.g., analyze patient data).Remote network 118 (in some exemplary embodiments) may be a virtual network, so that data store 120 and one or more service modules 122A-C need not be co-located.

[0041] The controller 114 may access the remote network 118 after authentication by the access control system 124. In certain exemplary embodiments, the access control system 124 queries the controller 114 for credentials, such as a login, a password, etc. The access control system 124 (in some exemplary embodiments) may provide access to the remote network 118 only after a financial process has been performed or an assurance has been given that a financial process will be performed. For example, access to the remote network 118 (in certain exemplary embodiments) may be granted only after a user (or other party) of the system 100 has paid a fee. The fee structure (in certain exemplary embodiments) may include one or more of the following: a fee per treatment, a fee per patient, a fee per system user, a fee per system, a subscription fee (i.e., a fee for the access period), a fee for data storage, and a fee for a data module. In certain exemplary embodiments, the controller 114 may effect payment of the fee electronically using a payment structure maintained on file (either locally at the controller or remotely).

[0042] Referring now to FIG. 2 , such diagram illustrates a flow diagram 200 of a method for electromagnetic radiation (EMR) treatment and patient data collection, storage, and analysis, according to an exemplary embodiment of the present disclosure. As shown in FIG. 2 , in step 210, data can be collected. The data can relate to a patient receiving treatment. For example, the patient data (in some cases) can include a digital image of the patient tissue, the patient's age, treatment session information, a patient pain score, data collection parameters, and / or electromagnetic radiation (EMR)-based treatment parameters. The patient data can include one or more digital images of the tissue receiving treatment and other relevant information about the patient or treatment (e.g., treatment parameters, patient feedback, etc.). In some exemplary embodiments of the present disclosure, patient data can be aggregated for storage. An exemplary method of data aggregation can include, for example, steps including combining datasets, stitching images, and linking data with common variables (e.g., patient ID, treatment date, etc.).

[0043] In procedure 212, access to a remote network (e.g., remote network 118) may be authenticated. Authenticating access to the remote network 212 (in some exemplary embodiments) may include access control techniques. Examples of access control techniques may include attribute-based access control (ABAC), discretionary access control (DAC), identity-based access control (IBAC), mandatory access control (MAC), organization-based access control (OrBAC), role-based access control (RBAC), and responsibility-based access control. According to some exemplary embodiments of the present disclosure, authenticating access to the remote network may further include verifying that (i) a payment agreement has been established, (ii) payment has been made, and / or (iii) payment is outstanding. In some exemplary embodiments, authentication over the remote network may further include paying a fee. In some exemplary embodiments, paying the fee may involve a payment system. Exemplary payment systems may include electronic payment systems (which may facilitate payments, for example, from one bank account to another, using electronic methods without the direct intervention of a bank employee), e-commerce payment systems (e.g., PayPal, Google Wallet, etc.), and payment systems that use cash alternatives (e.g., debit cards, credit cards, electronic funds transfer, direct credit, direct debit, internet banking, e-commerce payment systems).In some exemplary embodiments, payment of fees may be made using one of a credit card payment system, an automated teller machine (ATM) system, an automated clearing house system, a real-time gross settlement (RTGS) system, and a SWIFT network system.

[0044] Once access to the remote network is achieved, the exemplary method continues by storing the data at step 214. For example, the data can be stored in a data storage device or system (e.g., data store 120) that can communicate with the remote network. In certain exemplary embodiments, the data storage device or system can be accessible over the remote network. An exemplary data storage device / system may include cloud storage, which stores data in a logical pool located across multiple servers. To prevent unauthorized access to patient data, data storage information can be generally organized by patient (e.g., unique patient identifier). Once stored, the patient data can be accessed by the controller and one or more service modules. In some exemplary cases, a picture archiving and communication system (PACS) can be used for physical storage, Digital Imaging and Communications in Medicine (DICOM) being the data format that can be used for feedback. DICOM is a standard maintained by the Health Level Seven (HL7) standards group. In some embodiments, data related to feedback is transferred to and from the cloud. Data exchange with remote data stores (in some example cases) can be performed via fast healthcare interoperability resources (FHIR) services implemented by multiple vendors, including Microsoft Azure cloud services and Google's Cloud Healthcare services.

[0045] In step 216, services can be accessed via a remote network (e.g., cloud computing). Services can be resources available to the controller. For example, services can access and process selected data in a data storage system. In certain exemplary embodiments, services can be processed locally at the controller. In other exemplary embodiments, services can be processed remotely on a device (e.g., a server) that can communicate with the remote network. In still other exemplary embodiments, services can be processed in a hybrid manner, both locally at the controller and remotely. In some exemplary cases, individual services can be accessed using additional authentication and payment. Exemplary services include image recognition, computer vision, electronic health records, and clinical decision support, although any module that supports treatment may be envisioned. For example, in some exemplary embodiments, remote services can facilitate a remote user (e.g., an expert clinician) to review and comment on patient data. The remote user (in some exemplary cases) can make a diagnosis, devise a treatment plan, and / or provide valuable insights (otherwise unavailable to the patient).

[0046] Additionally, in procedure 218, an electromagnetic radiation (EMR)-based treatment can be performed. In some exemplary embodiments, the EMR-based treatment utilizes collected data, remotely stored data, and / or remotely accessed services. For example, in an exemplary ongoing treatment of a pigmented lesion, a practitioner can first view images taken before and after a previous treatment and then adjust treatment parameters based on the clinical images. In another example, a practitioner can access an electronic health record, which may include images obtained of the pigmented lesion in addition to information related to previous treatments. Technical descriptions of systems, devices, and methods for EMR-based treatment according to various exemplary embodiments of the present disclosure are described in more detail herein.

[0047] Although the exemplary flow diagram of exemplary method 200 shows an exemplary treatment occurring after all other steps, the treatment may occur before, during, and / or after other steps shown therein or not shown therein. For example, according to another exemplary treatment of the present disclosure, a clinician may first perform a laser treatment on a pigmented lesion and then collect data regarding the treatment, including laser parameters and images of the tissue after treatment.

[0048] Referring now to FIG. 3 , a system 100 for remotely storing data (e.g., digital images of tissue) according to an exemplary embodiment of the present disclosure is shown. The system 100 is shown in FIG. 3 after capturing a recent image 310 of tissue having a lesion 312. The recent image 310 may then be uploaded to a data storage system 316 via one or more networks 116. In certain exemplary embodiments, access to the data storage system 316 may be controlled by an access control system 318. Within the data storage system, the recent image 310 may be grouped with previous images of the same lesion 312. A first (oldest) image 320, a second (second-oldest) image 322, and a third (third-oldest) image 324 are all shown grouped together within the data storage system 316. Each exemplary image of the lesion was taken at a different time prior to EMR-based treatment. For example, exemplary EMR-based treatments may be performed several weeks apart (e.g., six weeks). The pigmented lesions 312 may respond well to treatment, with a decrease in prevalence between sessions. In certain exemplary embodiments, the stored digital data may be used to provide a record of care. In certain exemplary embodiments, these exemplary images may be used as components of an electronic medical record. In accordance with exemplary embodiments of the present disclosure, in addition to the electronic medical record, any number of additional data services may be accessed via the platform.

[0049] FIG. 4 illustrates a system 100 (which may be the same as or similar to the system 100 of FIG. 1) configured to access an array of service modules 410A-410D, according to an exemplary embodiment of the present disclosure. The exemplary system 100 can access services via one or more networks 116. In some exemplary embodiments, access to the service modules 410A-410D can be controlled using an access control system 418 (which may be the same as or similar to the access control system 124 of FIG. 1). The first service module 410A can be or include a treatment parameter recommendation application. According to some exemplary embodiments, the treatment parameter recommendation application of the first service module 410A can provide recommended treatment parameters based on selected data using one or more procedures and / or algorithms. For example, in some cases, the treatment parameter recommendation application of the first service module 410A can receive as input pre-treatment images of the tissue to be treated and analyze those images to determine recommended treatment parameters. In certain exemplary embodiments, the treatment parameter recommendation application can use artificial intelligence to make its recommendations. Exemplary recommended treatment parameters are described in further detail below.

[0050] The second service module 410B may be or may include a machine vision module. This module can provide machine vision tools to the system 100. Exemplary machine vision resources may include, for example, image recognition, image registration, stitching, filtering, thresholding, pixel counting, segmentation, edge detection, color analysis, blob detection, neural net / deep learning, pattern recognition, and barcode reading. The computer vision service module according to some exemplary embodiments can be written using available software toolkits (e.g., OpenCV, TensorFlow, and CUDA). In some exemplary embodiments of the present disclosure, the machine vision-based service module can be used to detect the presence of a lesion in tissue and register the location of the lesion with the treatment system 110. In another exemplary embodiment, the machine vision based service module may be used to grade the progress of treatment by comparing before and after images. In yet another embodiment, the machine vision based service module may determine the skin type of the patient undergoing treatment from color analysis.

[0051] The third service module 410C may be or may include an electronic health record module. The electronic health record module can organize and provide some, most, or all stored data about an individual patient. Patients may respond differently to EMR-based treatments (e.g., a patient's skin may be more or less resistant to EMR). As a result, individualized treatments can be performed using ongoing EMR-based therapy. To create a treatment plan tailored to an individual patient, it may be important and / or beneficial for a practitioner to have access to most or all relevant patient data in a single location. The electronic health record module 410C can facilitate a practitioner's access and viewing of patient data (e.g., tissue images) from previous treatments.

[0052] The fourth service module 410D may be or may include a clinical decision support module. The clinical decision support module can help support clinical decisions using patient data. In certain exemplary embodiments, the exemplary clinical decision support module can predict likely outcomes of treatments. The exemplary clinical decision support system service module can calculate the area under a receiver operating characteristic curve to quantify the probability that a binary event occurs (e.g., a patient's pigmented lesion is successfully treated).

[0053] While the above service modules have been described in detail above, any number of additional service modules may be used depending on the needs of the clinician, patient, or clinic administrator. For example, additional service modules according to some exemplary embodiments may include remote access to a remote control that can be used by a medical professional (e.g., a specialized clinician) who can provide feedback on patient data without having to actually see the patient in person. Furthermore, in certain exemplary embodiments of the present disclosure, EMR-based therapy is augmented with medications (e.g., topical, oral, and injectable).

[0054] For example, exemplary systems, devices, and methods for electromagnetic radiation (EMR) treatment and patient data collection, storage, and analysis are described, according to exemplary embodiments of the present disclosure. Additional description of the exemplary EMR-based treatment system 110 and data collection system 112 is provided below.

[0055] In particular, Figure 5 illustrates an exemplary embodiment of a treatment system 510 according to another exemplary embodiment of the present disclosure. As shown in Figure 5, the treatment system 510 may include a mounting platform 512, an emitter 514, and a controller 516. The mounting platform 512 may include one or more manipulators or arms 520. The arms 520 may be coupled to the emitter 514 to perform various treatments on target tissue 522 of a subject 524. The exemplary operation of the mounting platform 512 and the emitter 514 may be directed manually by a user or using the controller 516 (e.g., via a user interface). In certain exemplary embodiments (not shown), the exemplary emitter has a handheld form factor, and the mounting platform 512 may be omitted.

[0056] Emitter 514 and controller 516 (and optionally mounting platform 512) can communicate with each other via communication link 526, which may be any suitable type of wired and / or wireless communication link that conveys any suitable type of signal (e.g., electrical, optical, infrared, etc.) according to any suitable communication protocol.

[0057] The controller 516, according to an exemplary embodiment, may be configured to control the operation of the emitter 514. In one exemplary embodiment, the controller 516 may control the movement of the EMR 530. As described in detail below, the emitter 514 may include a source 532 for emitting the EMR 530 and a scanning system 534 for steering the EMR 530. As an example, the scanning system 534 may be configured to focus the EMR 530 at a focal region and translate and / or rotate this focal region in space. The controller 516 may send signals to the source 532 via the communication link 526 to instruct the source 532 to emit the EMR 530 having one or more selected characteristics, such as wavelength, power, repetition rate, pulse duration, pulse energy, focusing characteristics (e.g., focal volume, Rayleigh length, etc.), etc. In another exemplary embodiment, the controller 516 can send a signal via the communication link 526 to the scanning system 534 to instruct the scanning system 534 to move the focal region of the EMR 530 relative to the target tissue 522 in one or more translational and / or rotational operations.

[0058] Exemplary embodiments of the treatment system 510 and exemplary methods are described herein in the context of targets within skin tissue, such as the dermis layer. However, the exemplary embodiments may be used to treat any tissue at any location on a subject, without limitation. Examples of non-skin tissue may include, but are not limited to, superficial and subsurface regions of mucosal tissues, genital tissues, internal organ tissues, and gastrointestinal tract tissues.

[0059] FIG. 6 illustrates a laser beam focused on a pigmented region of the dermis layer of skin tissue using an exemplary system, device, and method according to an exemplary embodiment of the present disclosure. The skin tissue may include a skin surface 600 and an overlying epidermal layer 610, or epidermis, which may be approximately 30-120 μm thick, for example, in the facial region. The epidermis 610 may be slightly thicker in other parts of the body. For example, the thickness of the epidermis may generally range from approximately 30 μm (e.g., in the eyelids) to approximately 1500 μm (e.g., in the palms of the hands or soles of the feet). Such epidermis may be thinner or thicker than the above example in certain exemplary skin conditions, such as psoriasis. The underlying dermal layer 620, or dermis, extends from below the epidermis 610 to a deeper subcutaneous fat layer (not shown). Skin exhibiting deep or dermal melasma may include clusters of pigmented cells or regions 630 containing excessive amounts of melanin. Electromagnetic radiation (EMR) 650 (e.g., a laser beam) can be focused to one or more focal regions 660 located within the dermis 620 or epidermis 610. The EMR 650 can be provided at one or more appropriate wavelengths that are absorbed by melanin. The EMR wavelengths can be selected based on one or more criteria described below.

[0060] [Example Characteristics of Therapeutic Radiation] Exemplary determinations of desirable wavelengths for treating specific skin conditions, such as pigmented and non-pigmented conditions, can depend, for example, on the wavelength-dependent absorption coefficients of various competing chromophores present in skin (e.g., chromophores, hemoglobin, tattoo ink, etc.). FIG. 7A shows an exemplary absorbance spectrograph of melanin. Absorption of EMR by melanin is observed to reach a peak value 700 at a wavelength of approximately 350 nm and then decrease with increasing wavelength. While absorption of EMR by melanin facilitates heating and / or destruction of melanin-containing regions 630, very high melanin absorbance can result in high absorption by pigment in the epidermis 610, reducing penetration of EMR into the dermis 620 or epidermis 610. As shown in FIG. 7A, absorption by melanin is higher at EMR wavelengths less than approximately 500 nm. Thus, wavelengths less than about 500 nm may not be suitable to penetrate sufficiently into the dermis 620 to heat, damage, and / or destroy the pigmented regions 630 therein. Such enhanced absorption at shorter wavelengths can result in undesirable damage to the upper (surface) portions of the epidermis 610 and dermis 620, with relatively little unabsorbed EMR passing through the tissue into deeper portions of the dermis 620.

[0061] FIG. 7B shows an exemplary absorbance spectrum of oxygenated or deoxygenated hemoglobin. Hemoglobin resides in blood vessels in skin tissue and can be oxygenated (HbCh) or deoxygenated (Hb). Each form of hemoglobin can exhibit slightly different EMR absorption characteristics. As shown in FIG. 7B, exemplary absorption spectra for both Hb and HbCh can show high absorption coefficients for both Hb and HbCh at EMR wavelengths less than about 600 nm (805), with a significant decrease in absorbance at higher wavelengths (810). The strong absorption of hemoglobin (Hb and / or HbCh) to EMR directed at skin tissue can heat the hemoglobin-containing blood vessels, which can result in undesirable damage to these vascular structures when treatment of melanin-rich tissues or structures is desired, potentially reducing the EMR available for melanin absorption.

[0062] The selection of an appropriate wavelength for EMR may also depend on the wavelength-dependent scattering profile of the tissue interacting with the EMR. Figure 8 shows an exemplary graph of the absorption coefficients of melanin and venous (deoxygenated) blood versus wavelength. Figure 8 also shows an exemplary graph of the scattering coefficient of light in skin versus wavelength. Absorption by melanin monotonically decreases with increasing wavelength. If melanin is the target for treating pigmentation conditions, wavelengths with high absorption by melanin are desirable. This may indicate that shorter wavelengths of light may result in more efficient treatment. However, absorption by blood increases at wavelengths shorter than approximately 800 nm, potentially increasing the risk of unintentionally targeting blood vessels. Furthermore, the role of scattering by the skin (e.g., the dermal layer) may be important because the intended target may be located below the skin surface. Scattering reduces the amount of light reaching the intended target. The scattering coefficient monotonically decreases with increasing wavelength. Therefore, shorter wavelengths may facilitate absorption by melanin, while longer wavelengths may provide deeper penetration due to reduced scattering. Similarly, longer wavelengths may be beneficial in sparing blood vessels due to lower absorption by blood at longer wavelengths.

[0063] Based on the above considerations, wavelengths ranging from about 400 nm to about 4000 nm, more specifically from about 500 nm to about 2500 nm, can be utilized to selectively target specific structures (e.g., melanin) within the dermis. For example, wavelengths of about 800 nm and about 1064 nm can be useful for such treatments. A wavelength of about 800 nm can be beneficial because laser diodes at such exemplary wavelengths are less expensive and more readily available for implementation. For about 1064 nm, such an exemplary wavelength can be useful for targeting deeper lesions due to the lower scattering at this wavelength. The 1064 nm wavelength is also more suitable for darker skin types with a high amount of epidermal melanin. In such individuals, the higher absorption of epidermal melanin with shorter wavelength EMR (e.g., about 800 nm) increases the likelihood of skin burns. Therefore, a wavelength of about 1064 nm may be more suitable for use as a therapeutic radiation wavelength for certain treatments and some individuals.

[0064] Various laser sources can be utilized for the generation and / or generation of EMR. For example, neodymium (Nd)-containing laser sources are available that provide EMR at a wavelength of approximately 1064 nm. These laser sources can operate in a pulsed mode, for example, with a repetition rate ranging from approximately 1 Hz to approximately 100 KHz. Q-switched Nd laser sources can provide laser pulses with pulse durations of less than 1 nanosecond. Other Nd laser sources can provide pulses with pulse durations greater than 1 millisecond. An exemplary laser source providing EMR at a wavelength of approximately 1060 nm is the 20 W NuQ fiber laser from Nufem, Inc., East Granby, Connecticut, USA. The 20 W NuQ fiber laser can provide pulses with a pulse duration of approximately 100 ns at a repetition rate ranging from approximately 20 KHz to approximately 10 KHz. Another exemplary laser source can be the Nd:YAG Q-smart 850 from Quantel, Les Ulis, France. The Q-smart850 can provide pulses having pulse energies of up to about 850 mJ and pulse durations of about 6 ns at repetition rates of up to about 10 Hz.

[0065] The exemplary systems described herein can be configured to focus the EMR into a highly focused beam. For example, exemplary systems may include a focusing and / or converging lens configuration having a numerical aperture (NA) selected from about 0.3 to about 1 (e.g., about 0.5 to about 0.9). The corresponding large convergence angle of the EMR can provide high fluence and intensity at the focal region of the lens (which may be located within the dermis) and low fluence in the overlying tissue above the focal region. Such a focusing geometry helps reduce undesired heating and thermal damage to the overlying tissue above the pigmented dermis region. The exemplary optical configuration may further include a collimating lens configuration configured to direct the EMR from the emitting configuration to the focusing lens configuration.

[0066] Exemplary optical therapy systems can be configured to focus EMR into a focal region having a width or spot size of less than about 500 μm, e.g., less than about 100 μm, or less than about 50 μm, e.g., about 1 μm. For example, the spot size can range from about 1 μm to about 50 μm, about 50 μm to about 100 μm, and about 100 μm to about 500 μm. The spot size of the focal region can be determined, for example, in air. Such spot size can be selected to balance being small enough to provide a high fluence or intensity of EMR at the focal region (to effectively irradiate pigmented structures in the dermis) and large enough to facilitate irradiation of a large area / volume of skin tissue in a reasonable treatment time.

[0067] High NA optical systems can deliver different energy densities at different depths along the optical axis. For example, an exemplary optical system with an NA of about 0.5 can focus radiation to a focal region width (i.e., waist) at the focal point that is about 2 μm in diameter. The focal region has a density of about 1 J / cm at the focal point. 2 Because of the high NA (e.g., high speed) optical system, just 10 μm out of focus, the radiation may have a fluence (i.e., energy density) of 0.03 J / cm 2 or 3% of the energy density at the focal point. Radiation just about 30 μm outside the focal point has an energy density of about 0.4% (0.004 J / cm) of the energy density at the focal point. 2 ) This rapid change in energy density along the optical axis can facilitate achieving depth-selective tissue treatment, which requires precise depth positioning (e.g., within tens of micrometers) of the focal region within the target tissue.

[0068] Exemplary optical configurations according to exemplary embodiments of the present disclosure may be configured to direct the focal region of EMR to a location within the dermal tissue at a depth below the skin surface, e.g., a depth ranging from about 30 μm to about 2000 μm (e.g., about 150 μm to about 500 μm). Such exemplary depth range may correspond to typical observed depths of pigmented areas of the skin indicative of dermal melasma or other targets of interest. Such exemplary focal depth may correspond to the distance along the optical axis between the lower surface of the device configured to contact the skin surface and the location of the focal region. Furthermore, according to some exemplary embodiments of the present disclosure, exemplary systems and methods may be configured to treat targets within the epidermis. For example, exemplary optical configurations may be configured to direct the focal region of EMR to a location within the epidermal tissue (e.g., about 5 μm to about 2000 μm below the skin surface). According to still other exemplary embodiments of the present disclosure, exemplary systems and methods may be configured to treat targets deep within the dermis. For example, tattoo artists typically calibrate the tattoo guns they use to penetrate the skin to a depth of about 1 mm to about 2 mm below the skin surface. Thus, in certain exemplary embodiments, exemplary optical configurations may be configured to direct the focal region of EMR to a location within the dermal tissue in a range of approximately 0.4 mm to 2 mm below the skin surface.

[0069] An exemplary treatment system for treating tissue may desirably be configured to identify specific exemplary treatment regions in the target tissue (e.g., by imaging pigments, the interface between the dermal and epidermal layers of the target tissue, cell membranes, etc.). It may also be desirable to monitor / detect interactions between the EMR and the target tissue (e.g., plasma generation within the tissue). Furthermore, based on detection, the exemplary treatment system may modify the treatment process (e.g., by varying intensity, size / location of the focal region within the target tissue, etc.).

[0070] Various exemplary parameters for use with exemplary embodiments of an exemplary treatment system according to the present disclosure are provided below.

[0071] [Table 1]

[0072] Here, the depth of the focal region may be a depth within the tissue (e.g., focal region depth=0 may be approximately at the surface of the tissue), and M 2 can be a parameter that characterizes the properties of the EMR beam.

[0073] Exemplary Feedback Detection and Exemplary EMR-Based Treatment 9 shows a block diagram of an exemplary treatment system 900 according to an exemplary embodiment of the present disclosure. The exemplary treatment system 900 may include an optical system 902, an EMR detection system 904, and a controller 906 (which may include one or more computers and / or processors). The optical system 902 may include optical components (e.g., one or more mirrors, beam splitters, objective lenses, etc.) that direct EMR 910 generated by a source (e.g., a laser) to a focal region 952 of a target tissue 950. The EMR 910 may include imaging radiation configured to image the dermal and / or epidermal layers of one or more portions of the target tissue 950 (e.g., skin). The EMR 910 may also include therapeutic radiation to treat a region within the target tissue (e.g., the region 952 of the target tissue 950). In some exemplary implementations, the EMR 910 may include only one of imaging radiation and / or treatment radiation within a given period of time. For example, the EMR 910 may include therapeutic radiation for a first period and imaging radiation for a second period. In other exemplary implementations, the EMR 910 may include both imaging radiation and therapeutic radiation simultaneously for a given period. According to certain exemplary embodiments, the imaging radiation may be provided at a wavelength generally equal to the wavelength of the therapeutic radiation and may have less power than the therapeutic radiation, for example. According to other exemplary embodiments, the imaging radiation may be provided by an imaging radiation source other than the source providing the therapeutic radiation and may have a different wavelength than the therapeutic radiation.

[0074] The EMR detection system 904 (e.g., a photodiode, a charge-coupled device (CCD), a spectrometer, a photomultiplier tube, etc.) can detect signal radiation 912 generated, emitted, and / or reflected by the interaction of the target tissue 950 with the EMR 910, and / or a portion of the EMR 910 reflected by the target tissue 950 that is signal radiation 912. For example, EMR 910 (e.g., therapeutic radiation) having an intensity above a threshold can generate plasma within the target tissue 950. The plasma can generate signal radiation 912, for example, due to interaction with the EMR 910. The signal radiation 912 can indicate characteristics of the plasma (e.g., the presence of plasma, the temperature of the plasma, the size of the plasma, the composition of the plasma, etc.).

[0075] In some exemplary implementations, EMR 910 (e.g., imaging radiation) having an intensity below a threshold can interact with the target tissue 950 without significantly disturbing the target tissue 950 (e.g., generating plasma within the target tissue 950 without damaging the target tissue 950). Signal radiation 912 generated from such an interaction can be used to image the target tissue 950 (e.g., a portion of the target tissue 950 at the focal region 952 of the EMR 910). This signal radiation 912 can be used to detect pigment within the target tissue 950 (e.g., a pigment located in the focal region 952 of the target tissue 950). According to some exemplary embodiments, non-pigmented tissue can be imaged. For example, when imaging radiation (e.g., EMR 910) passes through cellular structures with different refractive indices, light is reflected as signal radiation 912.

[0076] The exemplary optical system 902 and the exemplary EMR detection system 904 can be communicatively coupled to an exemplary controller 906. The controller 906 can alter operating parameters of the exemplary treatment system 900 (e.g., by controlling the operation of the optical system 902). For example, the controller 906 can control movement of a focal region 952 of the EMR 910 within the target tissue 950. As described in more detail herein, this can be done, for example, by moving the exemplary optical system 902 relative to the target tissue 950 and / or by moving optical components within the optical system 902 to change the position of the focal region 952 (e.g., by controlling actuators coupled to the optical components). The controller 906 can receive data characterizing the optical detection of the signal radiation 912 from the EMR detection system 904.

[0077] The controller 906 can control the characteristics of the EMR 910. For example, the controller 906 can instruct the source of the EMR 910 (e.g., a laser source) to change the characteristics of the EMR 910 (e.g., intensity, repetition rate, energy per pulse, average power, etc.). In certain exemplary implementations, the controller 906 can change the optical characteristics of the EMR 910 (e.g., focal region position, beam size, etc.) by placing / controlling optical components (e.g., objective lenses, diffractive optics, etc.) in the path of the EMR 910. For example, the controller 906 can change the size of the focal region 952 of the EMR 910 by placing an objective lens in the path of the EMR 910 and / or moving the objective lens along the path of the EMR 910.

[0078] The controller 906 can determine various characteristics of the target tissue 950 and / or interactions between the EMR 910 and the target tissue 950 (e.g., plasma generation within the target tissue 950) based on detection of the signal radiation 912 by the EMR detection system 904. In one exemplary implementation of the exemplary treatment system 900, the controller 906 can determine one or more of a distribution of pigment in the target tissue 950, a topography of the dermal-epidermal layer junction, etc. Additionally, the controller 906 can be configured to generate a map indicative of the detected distribution of one or more of the exemplary characteristics of the target tissue 950 described herein and exemplary characteristics of the target tissue 950 not specifically described. Such distribution determination and / or generation of the distribution map may be referred to herein, without limitation, as imaging.

[0079] In certain exemplary embodiments, the target tissue 950 can be scanned using a controller 906 that can control the EMR detection system 904 and / or the optical system 902. For example, in a Cartesian coordinate system, the target can be scanned along one or more axes (e.g., along the x-axis, y-axis, z-axis, or a combination thereof). In alternative embodiments, the scanning can be performed according to other coordinate systems (e.g., cylindrical coordinates, spherical coordinates, etc.). The scanning can be performed using an imaging beam (e.g., EMR 910 having an intensity below a threshold), and signal radiation 912 corresponding to various regions of the target tissue 950 in the path of the imaging beam can be detected by the EMR detection system 904. An exemplary characteristic (e.g., intensity) of the signal radiation 912 can vary based on a dye in a portion of the target tissue 950 that interacts with the imaging beam (e.g., a dye in the focal region 952 of the imaging beam). The controller 906 can receive a signal from the EMR detection system 904 that can include data characterizing a detected characteristic (e.g., intensity) of the signal radiation 912. The controller 906 can analyze the received data (e.g., compare the received data with predetermined characteristic values ​​of the detected signal radiation 912 in a database) to determine the presence / characteristics of the dye in the target tissue 950.

[0080] In some exemplary implementations, the controller 906 can determine the location of a portion of the target tissue 950 to be treated (the "target treatment region") based on the signal radiation 912. For example, it may be desirable to treat a layer of the target tissue 950 (e.g., the dermis layer of skin tissue) located at a predetermined depth from the surface of the target tissue 950. The optical system 902 can be adjusted (e.g., by positioning the optical system 902 a desired distance from the surface of the target tissue 950) so that the focal region 952 is incident on the surface of the target tissue 950. This can be done, for example, by scanning the optical system 902 along the z-direction until the signal radiation 912 exhibits a predetermined characteristic indicative of an interaction between the EMR 910 and the surface of the target tissue 950. For example, an interface material (e.g., an optical slab, gel, etc.) can be placed on the surface of the target tissue 950, and the characteristic of the signal radiation 912 can change as the focal region 952 transitions from the target tissue 950 to the interface material. This can indicate the location of the focal region 952 of the EMR 910 at or near the surface of the tissue. When the optical system 902 is positioned so that the focal region 952 of the EMR 910 is at or near the surface of the target tissue 950, it can be translated (e.g., along the z direction) so that the focal region 952 is at a predetermined depth below the surface of the target tissue 950.

[0081] The controller 906 can alter operating parameters of the exemplary treatment system 900 based on signals received from the EMR detection system 904, including data characterizing detected properties of the signal radiation 912. For example, some exemplary embodiments of the EMR detection system 904 can detect the depth of the dermal-epidermal (DE) junction of the target tissue 950, and the controller 906 can adjust the depth of the focal region 952 corresponding to the depth of the DE junction. In this exemplary method, the DE junction can be used as a reference position for determining the depth of the focal region 952 within the dermis. Furthermore, in some exemplary embodiments, the EMR detection system 904 can quantify (e.g., by using a spectrophotometer) the percentage of melanin present in the epidermal layer of the skin. Based on the percentage of melanin, the controller 906 can provide designated personnel (e.g., a clinician) the ability to implement one or more changes to the laser parameters. According to certain exemplary embodiments, varying the laser parameters may include, for example, changing the energy per pulse inversely proportional to the percentage of melanin detected, increasing the focus angle as the percentage of melanin increases, and / or modifying the depth of the focal region 952 based on the percentage of melanin.

[0082] In some exemplary implementations, an acoustic sensor 930 may be coupled to the target tissue 950, and the acoustic sensor 930 may detect characteristics of an interaction between the EMR 910 and the target tissue 950. For example, the acoustic sensor may detect pressure waves at or within the focal region 952 generated by, for example, the generation of plasma (e.g., plasma generated at the focal region 952) within the target tissue 950. Examples of the acoustic sensor 930 may include, for example, a piezoelectric transducer, a capacitive transducer, an ultrasonic transducer, a Fabry-Perot interferometer, and / or a piezoelectric film.

[0083] In one exemplary embodiment, the pressure waves in the focal region 952 may be or may include shock waves, abrupt changes in pressure propagating through a medium (e.g., air) at a velocity greater than the speed of sound in the medium. In another exemplary embodiment, for example, the pressure waves in the focal region 952 may be acoustic waves propagating through a medium at a velocity approximately equal to the speed of sound in the medium.

[0084] Photoacoustic imaging (also known as optoacoustic imaging) is a biomedical imaging modality based on the photoacoustic effect. In photoacoustic imaging, for example, non-ionizing laser pulses are delivered to biological tissue (when radio frequency pulses are used, the technique is called thermoacoustic imaging). A portion of the delivered energy is absorbed and converted to heat, causing transient thermoelastic expansion and resulting in broadband (i.e., MHz) ultrasound emission.

[0085] Sensor measurement data from acoustic sensor 930 can be transmitted to controller 906. Controller 906 can use this data to verify dye detection via signal radiation 912. According to some exemplary embodiments, treatment can be confirmed by detection of shock waves. The presence and / or strength of pressure waves can be correlated to the plasma generated and the plasma-mediated treatment performed. Additionally, by mapping, for example, pressure waves detected at or within focal region 952, a comprehensive map of the treated tissue can be generated and documented.

[0086] FIG. 10 shows a diagram of another exemplary embodiment of an optical system 1000. For example, the optical system 1000 can direct an EMR beam 1002 from an EMR source 1005 to a target tissue 1050. The EMR source 1005 can be a laser (e.g., a Q-smart450 laser from Quantel having a pulse energy of 450 mJ, a pulse duration of 6 nanoseconds [nS], and a wavelength of 1064 nm or a harmonic of about 1064 nm). According to certain exemplary embodiments, the EMR beam 1002 can be introduced into the exemplary optical system 1000 via an adapter 1010. The adapter can be configured to secure the EMR source generating the EMR beam 1002 to an articulated arm, such as arm 520 of the mounting platform 512 in FIG. 5.

[0087] According to certain exemplary embodiments, a diffractive optical element (DOE) 1020 (e.g., a beam splitter, multi-focus optics, etc.) can be positioned in the path of the EMR beam 1002. The DOE 1020 can modify the properties of the EMR beam 1002 and transmit a second EMR beam 1004. For example, the DOE 1020 can generate multiple sub-beams that focus to different focal regions. The implementation and use of the DOE 1020 for treatment of target tissue is described in more detail in U.S. Provisional Application No. 62 / 656,639, entitled "Diffractive Optics For EMR-Based Tissue Treatment," the disclosure of which is incorporated herein by reference in its entirety. The second EMR beam 1004 (e.g., multiple sub-beams) generated and / or transmitted by the DOE 1020 can be directed to the target tissue 1050 by a beam splitter 1040 (e.g., a dichroic beam splitter). An example of a dichroic beam splitter may include a short-pass dichroic mirror / beam splitter (Thorlabs PN DMSP950R) with a cutoff wavelength of about 950 nm, a transmission band from about 420 nm to about 900 nm, and a reflection band from about 990 to about 1600 nm. The second EMR beam 1004 may be reflected by the beam splitter 1040 and directed to an objective lens 1060. The objective lens 1060 may focus the second EMR beam 1004 to a focal region 1052 within the target tissue 1050 through a window 1045. An example of objective lens 1060 may be or may include an Edmund Optics PN67-259 aspheric lens having a diameter of approximately 25 millimeters (mm), a numerical aperture (NA) of approximately 0.83, a near-infrared (NIR) coating, and an effective focal length of approximately 15 mm. Window 1045 may be used to hold or otherwise maintain target tissue 1050 in place.

[0088] In certain exemplary implementations, the EMR beams 1002, 1004 may be expanded by a beam expander (not shown) positioned in the path of the EMR beams 1002, 1004. Beam expansion can enable a desired NA value for the optical system 1000. For example, the laser beam produced by a Q-smart450 laser has a beam diameter of approximately 6.5 mm, and a beam expander that can expand the laser beam by twice the diameter can be utilized. The expanded EMR beams 1002, 1004 can be focused with a sufficiently high NA (e.g., greater than 0.3) using an approximately 15 mm EFL lens.

[0089] The exemplary optical system 1000 may be positioned and / or configured to allow the focal region 1052 of the second EMR beam 1004 to be located below the epidermis of the target tissue 1050. This may be done, for example, by moving the exemplary optical system 1000 relative to the target tissue 1050 and / or by moving the objective lens 1060 along the beam path of the second EMR beam 1004. In one exemplary implementation, the position of the exemplary optical system 1000 and / or exemplary optical components in the optical system 1000 may be moved by the exemplary controller 905 of FIG. 9 . Locating the focal region 1052 below the epidermis (e.g., below the dermal-epidermal (DE) junction) can reduce or substantially prevent unwanted heating in the epidermis, which can lead to epidermal hyperpigmentation or hypopigmentation. This may also allow for targeting an area within the dermis for heat and / or plasma generation.

[0090] Interaction between the second EMR beam 1004 and the target tissue 1050 can lead to the generation of signal radiation 1006. As described above, the signal radiation 1006 may include radiation generated by plasma in the target tissue 1050 (“tissue radiation”). The tissue radiation 1050 may have a wavelength within the transmission band of the beam splitter 1040. As a result, most of the tissue radiation may be transmitted by the beam splitter 1040. The signal radiation 1006 may also include radiation (“system radiation”) having a wavelength similar to that of the second EMR beam 1004. The wavelength of the system radiation 1004 may be within the reflection band of the beam splitter 1040. As a result, only a small portion (e.g., 10%) of the system radiation may be transmitted by the beam splitter 1040.

[0091] The signal radiation 1008 transmitted by the beam splitter 1040 may include both tissue radiation and system radiation 1004 (or portions thereof). Portions of the signal radiation 1008 may be captured by the EMR detector 1090. The EMR detector 1090 can communicate data characterizing the detection of the signal radiation 1008 (or portions thereof) to the controller 906 of FIG. 9. The controller 906 can, for example, perform the detection (e.g., the intensity of the transmitted signal radiation 1008) and can, for example, alter the operation of the source 1005 (e.g., turn off the source 1005).

[0092] In one exemplary implementation, the exemplary optical system 1000 can be used as a confocal microscope. This can be done, for example, by placing a second objective lens (not shown) upstream of the aperture 1080. The aperture can re-image the signal radiation 1006 by focusing the signal radiation 1006 onto a focal plane that includes the aperture 1080. The aperture 1080 can filter (e.g., block) undesired spatial frequencies of the signal radiation 1008. This exemplary configuration can facilitate filtering of the signal radiation 1008 associated with different regions within the target tissue 1050 (e.g., regions of the target tissue at different depths relative to the tissue surface 1054). By varying the distance between the imaging aperture 1080 and the target tissue 1050 (e.g., by moving the imaging aperture 1080 along the path of the signal radiation 1008), locations at different depths of the target tissue 1050 can be imaged. 9 can move the imaging aperture 1080 by sending commands to the actuator. The controller 906 can analyze the detection data and / or determine the presence of plasma in the target tissue 1050, the distribution of dye in the target tissue, etc. The exemplary optical system 1000 can be used to detect damage at the window 1045. Damage to the window 1045 can be caused by an interaction between the second EMR beam 1004 and the window 1045 (e.g., if the intensity of the EMR beam is high, a long interaction with the second EMR beam 1004, etc.). Detection of damage at the window 1045 can be performed by determining a change in the intensity of the signal radiation 1006 (e.g., emanating from the window 1045) due to damage at the window 1045. This can be done, for example, by positioning the focal region 1052 incident on the window 1045 (e.g., near the surface of the window 1045, on the surface of the window 1045, within the window 1045) and detecting the intensity of the signal radiation 1006 (e.g., by using a photodetector as the EMR detector 1090).This intensity can be compared to the intensity previously measured when the focal region 1052 is located at an equivalent position in the undamaged window 1045. Based on this comparison, damage at the window 1045 can be determined.

[0093] FIG. 11 provides a diagram of an exemplary embodiment of an exemplary optical system 1100. The optical system 1100 may include a microscope attachment 1170 having an eyepiece 1190. The microscope attachment 1170 can capture the signal radiation 1008 (or a portion thereof) transmitted by the beamsplitter 1040 of FIG. 10. The signal radiation 1008 can be re-imaged by a tube lens 1150 (e.g., a 25 mm diameter Edmund Optics PN49-665 x 50 mm EFL aspheric achromatic lens). The tube lens 1150 can re-image the signal radiation 1008 at the pupil plane 1120 of the eyepiece 1190 (e.g., an Edmund Optics PN35-689 10X DIN eyepiece).

[0094] As described herein, signal radiation 1008 / 1108 may include both tissue radiation and system radiation. Due to differences in their wavelengths, images of the tissue radiation and the system radiation may be generated at different locations (e.g., different planes). As a result, when the eyepiece 1190 is positioned to capture an image generated by the system radiation, it may not accurately capture an image related to the tissue radiation. However, the eyepiece 1190 may be calibrated to capture signal radiation having a different wavelength than the system radiation at the focal region of the system radiation. One exemplary method for calibrating the eyepiece 1190 may be performed by using a material (e.g., acrylic) as a phantom with a refractive index similar to that of the target tissue 1050 / 1150. Calibrating the eyepiece 1190 may include, for example, focusing a second EMR (beam) 1004 / 1104 onto a phantom (e.g., with the objective 1060 / 1160) and inducing disruption (e.g., laser-induced optical disruption) at the focal region of the second EMR beam 1004 / 1104. This may be followed by impinging a second EMR radiation 1004 having a predetermined wavelength onto the phantom (e.g., at an oblique angle) and measuring the intensity of the EMR radiation having the predetermined wavelength with the eyepiece 1190. The axial position of the eyepiece 1190 may be adjusted (e.g., along the z-axis) to increase and / or maximize the intensity of the detected radiation from the second EMR source. In certain exemplary embodiments, a sensor may be used in place of the eyepiece 1190. Examples of such exemplary sensors may include, for example, CMOS and / or CCD imagers. The sensor may generate a digital image corresponding to the radiation at the sensor plane. The digital image may represent an image of the focal region 1052 / 1152.

[0095] FIG. 12 shows another exemplary embodiment of an exemplary optical system 1200 having a fiber coupler attachment 1202. The fiber coupler attachment 1202 may include a lens tube 1210 that can image light from the objective lens 1060 and beam splitter 1040 of FIG. 10 as described herein. The lens tube 1210 can focus the signal radiation 1008 / 1208 into a pupil plane 1215 (e.g., a plane parallel to the x- and y-axes and including a collimating lens 1220). The focused signal radiation 1008 / 1208 can be collimated to a desired size using the collimating lens 1220 and directed to a coupling lens 1230. The coupling lens 1230 can focus the signal radiation 1008 / 1208 with an NA that can be useful for coupling into a fiber attached to a fiber connector 1240. The fiber can be optically connected to one or more EMR detectors (e.g., detector 904 of FIG. 9). According to certain exemplary embodiments, the combiner attachment 1202 may further include an imaging aperture 1250 located at the pupil plane 1215. The aperture 1250 may filter out some portions of the signal radiation 1008 that do not emanate from the focal region 1052 / 1252. According to certain exemplary embodiments, the detection device (e.g., a photodiode, spectrometer, etc.) may be located immediately after the imaging aperture 1250 without optical fibers or associated optics. Alignment of the imaging aperture 1250 relative to the lens tube 1210 may be accomplished by a process similar to that described above with respect to calibrating the eyepiece 1190 of FIG. 11 .

[0096] Exemplary feedback detection can be used in conjunction with EMR-based therapy in many ways. Exemplary applications are described herein to demonstrate some ways in which feedback-information-based EMR therapy can be implemented. Broadly speaking, the examples described below can be categorized into three forms of feedback-information-based EMR therapy. These exemplary forms can include examples of a) detecting plasma, b) referencing the location of a focal region, and / or c) imaging tissue. Such exemplary use categories are not intended to be an exhaustive (or mutually exclusive) list of applications for feedback-information-based EMR-based therapy.

[0097] [Illustrative example of plasma feedback] Some exemplary treatments may include the formation of plasma (e.g., thermionic plasma or optical breakdown) during treatment. In certain exemplary embodiments, detected plasma characteristics indicate the potential effectiveness of the treatment. For example, in the treatment of a dermal pigmentation condition, the focal region is located deep within the skin and therefore overlaps with the dermal pigment when scanned during treatment. As the focal region is scanned over the skin, the laser source delivers pulsed laser light to form thermionic plasma at the location where the focal region and the dermal pigment overlap. The exemplary formation of thermionic plasma indicates that a) pigment is present within the skin, b) the pigment at the moment of plasma formation is located with the focal region (e.g., XY coordinates and depth), and / or c) the pigment at this location will be treated (e.g., the pigment will be destroyed).

[0098] In other exemplary circumstances, plasma formation can indicate the need / desirability of system maintenance. For example, some systems may include a window placed in contact with the tissue undergoing treatment. The window can perform many functions, including contact cooling, stabilizing the tissue, providing a depth reference for the tissue, evacuating blood or other fluids from the tissue through pressure, etc. Radiation (e.g., a laser beam) also passes through the window for application to the underlying treatment area. In some exemplary cases, the radiation can cause disruption within or at the surface of the window, resulting in plasma generation and window etching. If the system continues to deliver radiation after plasma is generated at the window, tissue in direct contact with the window often experiences burning or thermal damage.

[0099] FIG. 13 illustrates a flow diagram of a method 1300 for detecting plasma during radiation-based tissue treatment, according to certain exemplary embodiments of the present disclosure. Beginning in step 1306, a window is used to contact the surface of the tissue. The window is contacted to the outer surface of the tissue. The window is configured to transmit therapeutic radiation. For example, the window can be positioned against the outer surface of the tissue, effectively referencing the tissue by providing a reference plane. According to certain exemplary embodiments, the window can perform and / or facilitate the performance of additional functions, including, but not limited to, preventing movement of the tissue during treatment, contact cooling of the tissue being treated, and evacuation of blood (or other competing chromophores) within the tissue through compression.

[0100] Next, in procedure 1308, therapeutic radiation can be generated. Typically, the therapeutic radiation can be generated by a radiation source. The therapeutic radiation can be configured to affect tissue to improve appearance or produce a desired change in appearance. In certain exemplary embodiments, the tissue effect can be cosmetic. In other exemplary embodiments, the tissue effect can be therapeutic. According to certain exemplary embodiments of the present disclosure, the tissue effect can include selective thermionic plasma generation in the presence of a chromophore. Exemplary parameter selection for the therapeutic radiation can depend on the treatment being performed, as well as the tissue type and individual patient. Exemplary details regarding therapeutic radiation generation and associated parameter selection for affecting tissue (e.g., cosmetic effect) in exemplary method 1300 are described in detail herein.

[0101] In step 1310, the therapeutic radiation may be focused to a focal region. For example, in step 1310, the therapeutic radiation may be focused by focusing optics. According to certain exemplary embodiments, the focal region may have a width of less than about 1 mm, about 0.1 mm, about 0.01 mm, or about 0.001 mm. The focal region may be positioned in a first region. In certain exemplary embodiments, the first region may be located within the tissue, particularly at the location to be treated. In some exemplary cases, the first region may be located outside the tissue, for example, intentionally or unintentionally within a window that contacts the tissue.

[0102] In step 1312, the focal region may be scanned, typically by a scanning system (e.g., a scanner). Exemplary scanning procedures may include tilting / tilting the focal region, rotating the focal region, and / or translating the focal region. Further description of exemplary related scanning procedures and systems is provided in U.S. Patent Application No. 16 / 219,809, entitled "Electromagnetic Radiation Beam Scanning System and Method," by Dresser et al., the entire disclosure of which is incorporated herein by reference. According to certain exemplary embodiments, the therapeutic radiation may be pulsed to deliver little therapeutic radiation when scanning the focal region (e.g., moving from a first region to a second region). Alternatively, the focal region may be scanned continuously. In this exemplary case, different configurations of timing of therapeutic radiation pulses and scanning parameters for controlling the positions of the first and second regions may be implemented.

[0103] As shown in Figure 13, in step 1314, plasma can be generated by therapeutic radiation. Typically, the plasma can be generated in or near the focal region because the fluence is greatest in the focal region. According to certain exemplary embodiments, in step 1314, the plasma can be generated selectively in pigmented regions by thermionic plasma generation. Alternatively, in step 1314, the plasma can be generated non-selectively by laser-induced optical breakdown.

[0104] Further, in step 1316, the plasma may be detected. For example, a detector may detect signal radiation emitted from the plasma in such step 1316. Examples of signal radiation detection may include optical detection, acoustic detection, spectroscopic detection of laser induced breakdown (e.g., laser induced breakdown spectroscopy), plasma generated shockwave (PGSW) detection, plasma luminescence detection, plasma (plume) shielding detection, and plasma photography. In certain exemplary embodiments, a characteristic of the plasma is determined based on the detection of the plasma in step 1316. Specific examples of the characteristic of the plasma may include the presence of plasma, the intensity of plasma, the spectral content of plasma, and the position of plasma. According to certain exemplary embodiments, the characteristics of the signal radiation may be recorded and stored, for example, by a controller (eg, a computer processor).

[0105] In certain exemplary embodiments, procedure 1318 may determine, for example, based on the detected plasma, whether plasma is at least partially located within the window. For example, in certain exemplary embodiments, optical signal radiation may be detected that includes spectral components known to be indicative of material (but not tissue) within the window, indicating that plasma is partially within the window. In another version, the intensity of the optical signal radiation may exceed a known threshold, indicating that plasma is at least partially within the window.

[0106] In procedure 1320, exemplary parameters for the therapeutic radiation can be controlled based in part on the detected plasma (e.g., the determination in procedure 1318 that the plasma is partially or not located within the window). Examples of parameters for the therapeutic radiation can include, but are not limited to, energy per pulse, repetition rate, position of the focal region, or size of the focal region. These exemplary therapeutic radiation parameters can be used alone, in combination with each other, or in combination with other therapeutic radiation parameters without limitation. For example, the determination that the plasma is partially located within the window can be used as a trigger event for terminating the therapeutic radiation.

[0107] In certain exemplary embodiments, for example, a controller can generate an exemplary map including a matrix of properties mapped to locations. As an example, the map may include mapping a first property of a first signal radiation emitted from a first plasma at a first location to the coordinates of the first location, and mapping a second property of a second signal radiation emitted from a second plasma at a second location to the coordinates of the second location. The exemplary map may include, for example, a four-dimensional matrix with three orthogonal axes relating to the location of the focal region and a fourth axis relating to one or more properties of the plasma. In some versions, the map may be used as an indicator of individual treatment effectiveness. Exemplary systems suitable for implementing the plasma detection method described above are described in detail herein.

[0108] 14 illustrates a diagram of a plasma detection and treatment system 1400 according to certain exemplary embodiments of the present disclosure. For example, a window 1406 can be configured to contact a surface of tissue 1408, such as the outer surface of tissue 1408. The window 1406 can include an optical material configured to transmit the EMR beam, such as glass, a transparent polymer (e.g., polycarbonate), quartz, sapphire, diamond, zinc-selenide, or zinc-sulfide.

[0109] The exemplary imaging and therapy system 1400 of FIG. 14 may include focusing optics 1410. The focusing optics 1410 (e.g., an objective lens) may be configured to focus an electromagnetic radiation (EMR) beam 1411 and generate a plasma 1412 within the tissue 1408. The plasma 1412 may be selectively generated in chromophores within the tissue 1408 by thermoelectron generation. In other exemplary embodiments, the plasma 1412 may be non-selectively generated by optical breakdown. The EMR beam 1411 may be generated using a radiation source (not shown). The EMR beam 1411 may include either collimated or uncollimated light, as well as coherent and non-coherent light.

[0110] Detectors 1414 may be installed in example system 1400 configured to detect plasma 1412. Examples of such detectors 1414 may include photosensors such as photodiodes and image sensors, acoustic sensors such as surface acoustic wave sensors, piezoelectric films, vibrometers, and etalons, and more specialized detectors such as spectrometers, spectrophotometers, and plasma luminance (or shielding) optical probes.

[0111] As shown in the figures (including FIG. 14 ), the plasma detector may include a photodetector (e.g., a photodiode) that may be directed toward window 1406 (in one exemplary embodiment) and may sense visible light 1416 (e.g., signal radiation) emitted from plasma 1412. According to certain exemplary embodiments, a tube lens 1418 may be used in combination with focusing optics 1410 to direct and focus the visible light 1416 incident on detector 1414. Detector 1414 may be in communication with controller 1415 to input data related to the detected plasma to controller 1415.

[0112] The scanner 1422 of the exemplary system of FIG. 14 can be configured to scan the focal region of the EMR beam 1411. The scanner 1422 can scan the focal region in at least one dimension. In certain exemplary embodiments, the scanner 1422 can scan the focal region, for example, in all three dimensions. Referring to FIG. 14 , the installed scanner 1422 can scan the focal region from left to right from a first region 1424 to a second region 1426 of the tissue 1408, as shown. As the scanner 1422 scans the focal region, the EMR beam 1411 can be pulsed to generate a first plasma in the first region 1424 and then a second plasma in the second region 1426. Both the first plasma 1412 and the second plasma 1426 can be detected by the detector 1414. In certain exemplary embodiments, data related to the detected first plasma and the detected second plasma is input to the controller 1415. In certain exemplary embodiments, the controller 1415 uses data associated with one or more plasma events to control parameters associated with at least one of the EMR beam 1411 and the scanner 1422 .

[0113] According to certain exemplary embodiments, the controller 1415 may be configured to control the EMR beam 1411 (e.g., terminate the EMR beam 1411) based on a determination of whether the first plasma 1412 is at least partially located within the window 1408. In one example, the controller 1415 may determine whether the first plasma 1412 is at least partially located within the window 1406 based on the intensity of signal radiation 1416 emanating from the plasma 1412. The intensity of the signal radiation 1416 may be detected using a photodetector (e.g., a photodiode). According to another version, the controller 1415 may determine whether the plasma 1412 is at least partially located within the window 1406 based on the spectral content of the signal radiation 1416. For example, according to certain exemplary embodiments, the window 1406 may include sapphire containing aluminum. The spectral peak corresponding to aluminum is centered at approximately 396 nm. Skin typically does not contain aluminum. Thus, if the signal radiation (taken at a precise time after the laser pulse [e.g., 10 ps]) includes a spectral peak centered at about 396 nm, then the first plasma 1412 is likely located at least partially within the window 1406. According to certain exemplary embodiments, a spectral filter (e.g., a notch filter) and a photodetector are used to detect the spectral components of the signal radiation. According to other exemplary embodiments, a spectrometer or spectrophotometer is used to detect the spectral components of the signal radiation.

[0114] The controller 1415 may be configured to record one or more detected properties of the plasma 1412. In certain exemplary embodiments, the controller 1415 may be configured to record a matrix (or map) of detected properties of the plasma 1412. For example, the controller 1415 may be configured to record a first property of a first signal radiation emanating from the first plasma 1412 at a first location 1424 and map the first property to coordinates of the first location 1424, and to record a second property of a second signal radiation emanating from the second plasma at a second location 1426 and map the second property to coordinates of the second location 1426.

[0115] [Example of illustrative focal depth reference] As described in detail above, in certain exemplary embodiments, the depth of the focal region within the tissue must be tightly controlled (e.g., ±20 μm). For example, treatment of dermal pigmentation may require placing the focal region at approximately the same depth as the dermal pigment within the tissue. If the focal region is too deep, the dermal pigmentation treatment will be ineffective. If the focal region is too shallow, melanocytes in the stratum basale will be irradiated, potentially causing adverse events (e.g., hyperpigmentation or hypopigmentation).

[0116] FIG. 15 illustrates a flowchart of a focal depth referencing method 1500 according to certain exemplary embodiments of the present disclosure. Beginning with step 1510, an electromagnetic radiation (EMR) beam may be focused along an optical axis to a focal region. Often, the EMR beam may be generated by an EMR source (e.g., a laser). An optical window may be positioned to intersect the optical axis. In some exemplary embodiments, a surface of the window may be substantially perpendicular to the optical axis. The EMR beam may impinge on at least one surface of the optical window to generate signal radiation. According to certain exemplary embodiments, the signal radiation may include a reflected portion of the EMR beam that may be reflected by the surface of the window. In certain exemplary embodiments, the window may be configured to contact tissue. The surface of the window may be optically understood as an optical interface between the window material of the window and an adjacent material (e.g., air or tissue) proximate the surface of the window. According to various exemplary embodiments, differences in refractive index between the window material and the adjacent material may result in reflection of the reflected portion of the EMR beam. According to certain exemplary embodiments, the signal radiation may be generated by scattering or transmission of a portion of the EMR beam at the window.

[0117] Returning to FIG. 15 , in step 1512, signal radiation can be detected. According to certain exemplary embodiments, the signal radiation can be imaged by an imaging system. In some cases, an image of the signal radiation is formed by the imaging system with a sensor. Examples of sensors include a photodetector or an imaging sensor. In some exemplary versions, the detector detects and measures the width of the image. Generally, the width of the image is proportional to the beam width of the EMR beam incident on the surface of the window. The magnification of the imaging system typically determines the proportionality of the image width to the width of the EMR beam incident on the window. According to certain exemplary embodiments, the detector can detect and / or measure the intensity of the signal radiation.

[0118] In step 1514, a reference focal position may be determined based on the signal radiation. For example, in some exemplary embodiments, the beam width of the EMR beam incident on the surface of the window is measured, and the focal position of the focal region is translated along the optical axis as the beam width is measured. The reference position is found to be at the position where the beam width is determined to be smallest. As another example, in some exemplary versions, the intensity of the signal radiation is detected as the focal position of the focal region is translated along the optical axis. In this exemplary case, the reference position may be found to be at the position where the intensity of the emitted signal line is found to be largest.

[0119] Once the reference focal position is determined, in step 1516, the focal region can be translated to the treatment focal position. For example, the treatment focal position can be moved a predetermined distance along the optical axis from the reference focal position. According to certain exemplary embodiments, the focal region can be translated by moving an optical component (e.g., an objective lens) along the optical axis. In other exemplary embodiments, the focal region can be translated by adjusting the divergence of the EMR beam, e.g., adjusting the optical power of the optical component. Finally, a window is placed in contact with the target tissue to position the focal region within the target tissue. According to certain exemplary embodiments, the target tissue can be skin, and the focal region can be positioned within the dermal tissue of the skin. Precise depth positioning of the focal region within the tissue can facilitate treatment of pigmentation conditions that were previously untreatable by thermionic plasma or thermal destruction. For example, the EMR beam can perform selective thermionic plasma-mediated treatment of dermal pigmentation conditions (e.g., dermal melasma) with a focal region located within the dermis without risking harmful irradiation of the epidermis.

[0120] 16A and 16B show diagrams of a focal depth referencing and treatment system 1600 and exemplary methods, according to certain exemplary embodiments of the present disclosure.

[0121] For example, referring to FIG. 16B, a first EMR beam 1616A may be configured (for reference only), e.g., by having a first focal region 1618A incident on the surface of the window 1610, and a second EMR beam 1616B may be configured to achieve a desired effect on tissue (e.g., a cosmetic effect). In practice, the second EMR beam 1616B may be configured to converge with a focusing optic to a second focal region 1618B located at a treatment location. This may result in a very high fluence (e.g., 10 12 W / cm 2 ), which may be advantageous in various exemplary embodiments where the window 1610 is likely to be damaged if the first EMR beam is used during referencing. According to certain exemplary embodiments, the second EMR beam 1616B may have a wavelength approximately equal to that of the first EMR beam 1616A. In other exemplary embodiments, the second EMR beam 1616B may have a wavelength different from that of the first EMR beam 1616A. In this exemplary case, the treatment position may need to be calibrated based on the difference in focal length of the focusing optics at such different exemplary wavelengths.

[0122] The exemplary focal depth reference system 1600 shown in FIG. 16A includes a window 1610 configured to contact a target tissue 1612. An exemplary optical system (e.g., an objective lens or focusing optics) may be configured to focus an electromagnetic radiation (EMR) beam 1616 along an optical axis 1620 to a focal region 1618. The optical axis 1620 intersects the window 1610. A photodetector 1622 may be configured to detect signal radiation 1624. According to certain exemplary embodiments, the signal radiation 1624 may be generated by an interaction between the EMR beam 1616 and the window 1610. In some exemplary embodiments, the interaction between the EMR beam 1616 and the window 1610 may be an interaction between the surface of the window 1610 and the EMR beam 1616. The interaction between the EMR beam 1616 and the window 1610 is typically at least one of reflection, transmission, and scattering.

[0123] The controller 1626 may be configured to receive input from the photodetector 1622 and translate the focal position of the focal region 1618 along the optical axis 1620. Based at least in part on feedback from the photodetector 1622, the controller 1626 may determine a reference position 1628 where a portion of the focal region 1618 may substantially overlap the surface of the window 1610. The signal radiation 1624 originates from the reflection of the EMR beam 1616 incident on the surface of the window 1610 and may be incident on and imaged by the image sensor 1622 (in part) using the focusing optics 1614. According to certain exemplary embodiments, the controller 1626 may determine the reference position, for example, by determining a lateral width of the EMR beam 1616 incident on the surface of the window based on the signal radiation and translating the focal region until the lateral width is at a minimum. According to another exemplary embodiment, signal radiation originates from reflection of EMR beam 1616 off the surface of window 1610, and detector 1622 may be configured to detect the intensity of the signal radiation. In this exemplary case, controller 1626 may determine the reference position by translating the focal region until the intensity of signal radiation 1624 reaches a maximum value.

[0124] Additionally, the controller 1626 can translate the focal region 1618 to a treatment location a predetermined distance 1630 from the reference location 1628. Generally, translating the focal region 1618 away from the reference location 1628 can be performed in a positive direction along the optical axis 1620 (i.e., away from the optical system 1614). In certain exemplary embodiments, the treatment location can be configured to be located within tissue. For example, the predetermined distance can be configured to locate the treatment location within dermal tissue of the skin. The stage 1632 can be used to translate one or more optical components (e.g., focusing optics) to translate the focal region. The EMR beam 1616 can be configured to perform an effect (e.g., a cosmetic effect) on tissue at or near the focal region located at the treatment location. An example of a tissue effect is selective thermionic plasma-mediated treatment of the tissue 1612.

[0125] In certain exemplary embodiments, the second EMR beam can be configured to be focused by a focusing optic to a second focal region located at the treatment location. In this exemplary case, the first EMR beam can be configured for reference only, and the second EMR beam can be configured to perform the tissue effect. This is because the tissue effect can be achieved, for example, at very high fluences (e.g., 10 12 W / cm 2 ), which may be advantageous in embodiments where the window 1610 is likely to be damaged during referencing. According to certain exemplary embodiments, the second EMR beam may have the same wavelength as the first EMR beam. In other embodiments, the second EMR beam may have a wavelength different from that of the first EMR beam. In this case, the treatment position must be calibrated based on the difference in focal length of the focusing optics at the two different wavelengths. In certain exemplary embodiments, the exemplary window referencing and treatment system 1600 can be used to measure two or more reference positions 1628.

[0126] For example, according to certain exemplary embodiments, the exemplary window reference and treatment system 1600 may also include a scanning system. The scanning system may be configured to move the focal region 1618 and the optical axis 1620 in at least one scanning axis. In some exemplary cases, the scanning axis may be generally perpendicular to the optical axis 1620. The parallelism measurement between the window and the scanning axis may be determined by measuring multiple reference positions 1628 at multiple scanning positions. For example, the exemplary reference and treatment system 1600 may first determine a first reference position at a first scanning position. Then, the scanning system may reposition the optical axis 1618 to a second scanning position that is a certain distance along the scanning axis from the first scanning position. Then, the exemplary reference and treatment system 1600 may determine a second reference position. The difference between the first and second reference positions divided by the distance along the scanning axis may indicate the gradient of non-parallelism between the window and the scanning axis. To further explain focal depth referencing in an EMR treatment device, specific embodiments are provided below.

[0127] [Example of tissue imaging] Exemplary EMR-based treatments informed by tissue imaging feedback may have a wide range of applications and benefits in dermatological and aesthetic treatments. For example, according to certain exemplary embodiments, tissue imaging allows a user to precisely target a treatment site during an EMR-based treatment. Another exemplary use of tissue imaging may be to provide a written record of treatment results over time (e.g., pre-treatment and post-treatment images). According to yet other exemplary embodiments, tissue imaging is used to confirm a diagnosis or treatment plan for a pre-treatment condition or an endpoint during treatment. The goal of many exemplary EMR-based skin treatments is cosmetic (e.g., related to skin appearance). In these exemplary cases, imaging of the skin undergoing treatment provides some of the most important feedback to treatment stakeholders (patient and practitioner).

[0128] FIG. 17 illustrates a flow diagram of a method 1700 of imaging and radiation-based therapy according to certain exemplary embodiments of the present disclosure. In the exemplary method 1700, procedure 1706 irradiates the tissue with imaging radiation. For example, irradiation of the tissue can be achieved at least in part by using an illumination source. Exemplary illumination can be performed in many ways, including, for example, bright-field illumination, in which the imaging radiation is provided substantially on-axis relative to the imaging system, and dark-field illumination, in which the imaging radiation is provided substantially off-axis relative to the imaging system. In certain exemplary embodiments, the imaging radiation can be substantially monochromatic. In other exemplary embodiments, the imaging radiation can be substantially broadband (e.g., white light).

[0129] Additionally, procedure 1710 may capture an image of a view of the tissue. For example, imaging may be performed at least in part using a focusing optic (e.g., an objective lens). In some cases, the view may be a field of view of a focal region associated with the focusing optic. In certain exemplary embodiments, imaging procedure 1710 may include using one or more additional optical elements in combination with the focusing optic. For example, the focusing optic may significantly collimate light from the view, and a tube lens may be used to form an image from the collimated light. The image may be formed at an image plane.

[0130] In step 1712, the image can be detected. For example, the image can be detected using a detector. Examples of detection may include, for example, photodetection, confocal photodetection, interferometric detection, and spectroscopic detection. The detector can detect the image at an image plane. The image can be detected by an image sensor. Examples of image sensors include semiconductor charge-coupled devices (CCDs), complementary metal-oxide-semiconductor (CMOS) active pixel sensors, and N-type metal-oxides-semiconductor (NMOS) sensors. The image sensor can output the detected image as a two-dimensional (2D) matrix of data (e.g., a bitmap).

[0131] Additionally, in step 1714, the image can be displayed. For example, the image can be displayed by an electronic visual display. Examples of displays may include, for example, an electroluminescent (EL) display, a liquid crystal (LC) display, a light-emitting diode (LED)-backlit liquid crystal (LC) display, a light-emitting diode (LED) display (e.g., an organic LED (OLED) display and an active-matrix organic LED (AMOLED) display), a plasma display, or a quantum dot display. The displayed image can be viewed by a designated user (e.g., a clinician). In some exemplary cases, the image can be recorded and stored, for example, by controller 1819 of FIG. 18 or another controller described herein. According to certain exemplary embodiments, the displayed image can be used to target an area of ​​tissue requiring treatment.

[0132] Next, in step 1716, a target treatment region may be designated within the tissue. In certain exemplary embodiments, the target treatment region may be designated based in part on the image. For example, in step 1716, the target treatment region may be designated based on an apparent excess of pigment (e.g., dermal melanin) within a portion of the tissue, as displayed in the image. In some cases, a clinician viewing the displayed image designates the target treatment region. Alternatively, in certain exemplary embodiments, the controller may automatically designate the target treatment region based on the image. The target treatment region is typically at least partially present in the image.

[0133] Finally, in step 1718, the therapeutic radiation can be focused to a focal region within the treatment region. Typically, the therapeutic radiation is focused using focusing optics and configured to perform an effect within the tissue (e.g., selectively generate a thermionic plasma in a chromophore to achieve a cosmetic effect). In certain exemplary embodiments, parameters affecting the therapeutic radiation are controlled based in part on the image. Parameters affecting treatment with therapeutic radiation have been described in detail above. In certain exemplary embodiments, the focal region is scanned within the target treatment region.

[0134] In certain exemplary embodiments, a view is scanned from a first region of tissue to a second region. Examples of scanning include tilting / tilting the view, rotating the view, and translating the view. Further description of scanning configurations is provided in U.S. Patent Application No. 16 / 219,809, entitled "Electromagnetic Radiation Beam Scanning System and Method," by Dresser et al., the entire disclosure of which is incorporated herein by reference. In certain exemplary embodiments, a view located in a first region overlaps a view located in a second region. In this case, a portion of the tissue is present in both the first region and the second region. In some other embodiments, a view located in a first region does not overlap a view located in a second region. In certain exemplary embodiments, scanning of a view can be achieved using feedback regarding the view position. For example, in some exemplary cases, the view can be scanned by moving a focusing optic using two linear stages. When the view is located in the first region and / or the second region, feedback from encoders present on each linear stage can be used to infer the position of the view.

[0135] A second image of a view from a second region can be captured. For example, capturing the second image can be performed in the same manner as capturing the first image in step 1710, with only the location of the view differing between the two steps. The imaging is performed at least in part using focusing optics. In some cases, the view can be a field of view of a focal region associated with the focusing optics. The second image can be detected. Typically, detecting the second image is performed in the same manner as detecting the first image in step 1712, with only the difference being detecting the second image instead of the first image.

[0136] In some exemplary cases, the first image and the second image are stitched together to form a stitched image (or map). The stitched image may also include additional images taken at views located in additional regions. The stitched image may be used to document a pre-treatment image of the tissue or a post-treatment image of the tissue. Any of the first image, the second image, and the stitched image may be taken before treatment and used, for example, to assist a medical professional in making a diagnostic determination. Similarly, any of the first image, the second image, and the stitched image may be taken during or after treatment to look for endpoints during treatment that may demonstrate the effectiveness of the treatment or indicate the end of treatment.

[0137] FIG. 18 shows a diagram of an exemplary tissue imaging and treatment system 1800 in accordance with certain exemplary embodiments of the present disclosure. The exemplary imaging and treatment system 1800 may include a focusing optic 1810. The focusing optic 1810 (e.g., an objective lens) may be configured to image a view 1812 of tissue 1813. A detector 1814 may be configured to detect an image 1816 formed at least in part by the focusing optic 1810. The detector 1814 may be in communication with a display 1817. The display may be configured to display the image to a designated user (e.g., a clinician). According to certain exemplary embodiments, a tube lens 1818 may be used in combination with the focusing optic 1810 to form the image 1816. The detector 1814 may be in communication with a controller 1819 to input data related to the detected image from the detector to the controller 1819. The focusing optic 1810 is used to deliver and image therapeutic radiation 1820. The scanner 1822 may be configured to scan the view 1812. The scanner may scan the view in at least one dimension, and possibly more. In certain exemplary embodiments, the scanner 1822 may scan the view in all three dimensions. With reference to FIG. 18 , the scanner 1822 is shown, for example, scanning the view 1812 from a first region 1824 to a second region 1826 of the tissue 1813.

[0138] As the scanner 1822 scans the view 1812, the focusing optics 1810 can capture a first image in a first region 1824 and a second image in a second region 1826. Both the first image and the second image can be detected by the detector 1814. Further, for example, data associated with the detected first image and the detected second image can be input to the controller 1819. In certain exemplary embodiments, data associated with multiple images can be stitched together by the controller 1819 to generate a stitched image (or map). The stitched image and / or one or more images can be recorded and stored by the controller for future viewing. In certain exemplary embodiments, data from one or more images can be used to determine a treatment region. According to certain exemplary embodiments, the determination of the treatment region can be performed automatically by the controller. In other exemplary embodiments, the determination of the treatment region can be performed manually by a designated user after viewing one or more images.

[0139] The therapeutic radiation 1820 can be focused into a focal region by focusing optics 1810. The focal region can then be directed to the treatment region. According to certain exemplary embodiments, scanner 1822 can be configured to scan the focal region within the treatment region. Certain exemplary embodiments of exemplary system 1800 can include a window 1830 that can be placed in contact with the surface of tissue 1813. Window 1830 can serve several purposes, one being to digitize the outer surface of the tissue. Thus, window 1830 can facilitate reliably positioning the focal region within tissue 1813 at a predetermined depth from the surface of tissue 1813.

[0140] FIG. 19A illustrates an exemplary stitched image (or map) 1900 according to certain exemplary embodiments of the present disclosure. The exemplary stitched image 1900 may include several (e.g., nine) individual images 1910. An exemplary scan path 1920 illustrates an exemplary path taken by views as they traverse tissue. The scan path illustrated includes a raster pattern, although other patterns are possible (e.g., spiral). The individual images 1910 may be taken at points along the scan path. The stitched image 1900 may be formed from the individual images in several ways. For example, if the position of the views can be estimated for each individual image (e.g., via scanner feedback), the stitched image 1900 may be constructed using dead-reckoning calculations. Alternatively, the exemplary stitched image 1900 may be constructed using a machine vision algorithm for stitching. A first example of image stitching software is the Hugin-Panorama photo stitcher. Hugin is an open source project hosted at http: / / hugin.Sourceforge.net. A second example of image stitching software is the Photomerge tool in Adobe Photoshop. To further illustrate tissue imaging in an exemplary EMR therapy device, specific individual embodiments are provided below.

[0141] 19B is a flow diagram illustrating an exemplary method 1930 for stitching images according to various exemplary embodiments of the present disclosure, in which, for example, several images are used to perform image stitching. First, the method detects keypoints in the images in step 1932. An exemplary keypoint detection method / procedure may be or may include a scale-invariant feature transform (SIFT). For example, SIFT may apply a Gaussian blur to each image at various scales (e.g., various blur sizes), and may determine various exemplary features in each image that have the greatest amount of contrast relative to neighboring pixels, regardless of the amount of blur.

[0142] Once multiple keypoints are detected in each image, in step 1934, the keypoints may be compared between overlapping (e.g., consecutive) images to match inliers. An exemplary method for matching keypoints in step 1934 may be or may include random sampling consensus (RANSAC). RANSAC is an iterative method / procedure that may be used to estimate parameters of a mathematical model from a set of observed data that includes outliers. For example, RANSAC may iteratively determine inliers by removing outliers from a set of keypoints used to match the images. When inliers are determined in step 1934, the exemplary method 1930 may, in step 1936, derive a homography transform to align the images to each other based on the inliers. Homography transform matrices may be derived to associate each image with its overlapping partner. Although a homography transform is shown as an example, it should be understood that other transformation matrices may be used, including, but not limited to, affine transforms.

[0143] The exemplary method 1930 may proceed in step 1938 by applying a transformation matrix to transform (e.g., shifting, scaling, rotating, tilting, tipping, etc.) each image to fit its adjacent partner. The exemplary method 1930 may further continue in step 1940 by blending the images. For example, after the exemplary transformation, a clear juxtaposition can be seen between the edges of each image in the final stitched mosaic. To prevent this situation, the images may be blended in step 1940. The exemplary image blending step 1940 may include, for example, determining a boundary between adjacent images that has a minimum error (e.g., a minimal error boundary). For example, the minimal error boundary can be determined by analyzing the overlap of two or more images and determining where the overlap error is minimum within the overlap at the boundary (e.g., a non-linear). For example, the overlap error can be calculated using an overlap integral. Once the minimum error boundary is determined, the images can be cropped along the minimum error boundary. Further, the example method 1930 can construct a final mosaic in step 1942, for example, by digitally positioning all of the manipulated images together in the mosaic.

[0144] FIG. 19C illustrates two captured overlapping images 1944-A, 1944-B of skin, according to certain exemplary embodiments of the present disclosure. As shown in FIG. 19C, exemplary keypoint detection of procedure 1932 is performed on the two images, and detected keypoints are indicated therein. FIG. 19D illustrates the two overlapping images during inlier matching of procedure 1934. The two overlapping images are shown in FIG. 19D as merged image 1946, with inliers highlighted. FIG. 19E illustrates an initial unfused mosaic 1948 including the two images 1944-A, 1944-B of FIG. 19C. It can be seen that the unfused mosaic contains hard boundaries of high contrast between the overlapping images. FIG. 19F illustrates a fused mosaic 1950 after the unfused mosaic 1948 of FIG. 19E has undergone image fusion procedure 1940. The minimum error boundary is indicated in the fused mosaic 1950 of FIG. 19F.

[0145] 20 illustrates an exemplary electromagnetic radiation (EMR) source (e.g., laser source) 2010 that generates an EMR beam (e.g., laser beam) 2012, according to certain exemplary embodiments of the present disclosure. According to certain exemplary embodiments, the EMR beam 2012 is naturally emitted from the EMR source 2010 in a transverse ring mode (e.g., TEMO1). *) according to another exemplary embodiment, a beam shaper 2014 shapes the EMR beam to generate a transverse ring mode. As shown in FIG. 20 , a beam shaper 2014 using two axicons is provided. A first axicon 2016 having a first wedge angle can receive the EMR beam 2012 and generate a quasi-Bessel beam. The quasi-Bessel beam then propagates to generate a diverging ring mode. The diverging ring mode 2020 can be collimated by a second axicon 2022 into an EMR beam having a transverse ring mode 2024. According to a specific exemplary embodiment, the ring mode 2024 can be reflected by a beam splitter 2026 and directed to a focusing optic 2028. Some examples of the focus optic 2028 may include converging optics (e.g., plano-convex lenses) and an axicon. The focusing optic 2028 can focus the EMR beam and direct it to the tissue 2030 (e.g., skin). According to certain exemplary embodiments, a window 2032 can be positioned between the focusing optic 2028 and the tissue 2030. The window 2032 can be transparent at multiple wavelengths, for example, visible wavelengths and the EMR wavelength of the EMR beam 2024. Exemplary window materials may include glass, quartz, and sapphire. In certain exemplary embodiments, the window 2032 can be cooled and used to cool the tissue 2030 during treatment. Generally, the window 2032 can be placed in contact with the outer surface of the tissue during operation of the exemplary device 2000. The focusing optic 2028 can be fabricated with an opening through its center.

[0146] According to certain exemplary embodiments, optical assembly 2034 can be positioned within the opening of focusing optic 2028. Optical assembly 2034 can affect light 2036 from tissue 2030. In certain exemplary embodiments, optical assembly 2034 can have an optical axis that is substantially coaxial with the optical axis of focusing optic 2028. According to certain exemplary embodiments, light 2036 can be transmitted through beam splitter 2026 and focused by camera lens 2038 onto sensor 2040. For example, sensor 2040 (in some exemplary versions) can be or include a camera sensor (e.g., a charge-coupled device [CCD] or complementary metal-oxide semiconductor [CMOS] camera). According to certain exemplary embodiments, tissue 2030 can be illuminated by illumination source 2042, which can direct illumination light 2044 onto tissue 2030.

[0147] FIG. 21 illustrates a flow diagram of an exemplary combined method 2100 including treatment and visualization, according to certain exemplary embodiments. The exemplary treatment and visualization method 2100 and / or steps thereof may occur sequentially, simultaneously, and / or independently of one another. Thus, an exemplary treatment method 2104 and an exemplary visualization method 2106 are shown in parallel. Referring first to the exemplary treatment method 2104, step 2110 can generate an electromagnetic radiation (EMR) beam having a transverse ring mode. The exemplary EMR beam can be a laser beam, e.g., a laser with a wavelength of 1064 nm. The exemplary transverse ring mode can be a transverse electromagnetic mode (TEM) 01. *Alternatively, the EMR beam may be a donut mode. Furthermore, in step 2120, the EMR beam may be directed to be incident on an EMR optical element having an aperture, thereby forming a transverse ring mode surrounding the aperture. In some exemplary versions, the EMR optical element may include a focusing lens and / or an axicon. When the EMR beam has a transverse ring mode, a central portion of the EMR beam has negligible radiant power. The EMR beam may be directed to be incident on the EMR optical element such that this central portion of the EMR beam overlaps with the aperture of the EMR optical element. In this manner, substantially all of the radiant power of the EMR beam can be affected by the EMR optical element, regardless of the laser optical element having an aperture through the central portion. Next, in step 2130, the EMR beam is focused, and in step 2140, the EMR beam can be directed to tissue by the EMR optical element. In certain exemplary embodiments, focusing the EMR beam can perform therapy (e.g., photothermolysis) on tissue. In some additional exemplary embodiments, the exemplary treatment method 2104 may further include shaping the EMR beam, for example, to generate a transverse ring mode using a beam shaper.

[0148] Referring to exemplary visualization method 2106, light from the tissue is collected through an aperture in the EMR optics. In certain exemplary embodiments, the light from the tissue is directed through the aperture using one or more optical components. For example, in certain exemplary embodiments, a lens assembly and / or an endoscope is used to collect the light through the aperture. In some exemplary versions, the one or more optical components have an optical axis that is substantially collinear with the optical axis of the EMR optics. According to certain exemplary embodiments, exemplary combined method 2100 may further include separating the light from the tissue from the beam path of the EMR beam, for example, using a beam splitter. Further, in step 2160, the collected light can be sensed. According to certain exemplary embodiments, the collected light can be focused into an image that can be sensed by a camera sensor (e.g., a charge-coupled device [CCD] or a complementary metal-oxide semiconductor [CMOS] camera). The camera sensor can then generate a digital image of the tissue. In alternative embodiments, this digital image can be used by the operating clinician to sense the light in alternative ways, for example, with a photodetector, photodiode, and / or photovoltaic. In some additional exemplary embodiments, the exemplary method may include directing illumination light to the tissue to illuminate the tissue for visualization.

[0149] FIG. 22 shows a diagram of a ray trace 2200 using an exemplary system and / or method according to certain exemplary embodiments of the present disclosure. For example, as shown in FIG. 22 , a focusing optic 2210 may have an aperture 2212 through its center. An endoscope 2214 may be placed through the aperture 2212. A beam splitter 2216 may be positioned following the endoscope 2214 in the beam path. The beam splitter 2216 may be configured to reflect a laser beam of a certain wavelength (e.g., 1064 nm) and pass light of a certain wavelength (e.g., a visible wavelength) for sensing. Such exemplary paths of exemplary light rays 2218, 2220 are shown in FIG. 22 . The exemplary laser ray trace 2218 shows the path of a light ray associated with the therapeutic laser. The exemplary imaging ray trace 2220 shows the path of a light ray associated with the beam splitter 2216. An exemplary object plane 2222 and an exemplary image plane 2224 are shown in FIG. 22 .

[0150] FIG. 23 shows a modulation transfer function (MTF) graph 2300 of a diffraction-limited endoscopic imaging system according to an exemplary embodiment of the present disclosure compared to a DermLite Foto II Pro photographic dermatoscope lens assembly 2302. DermLite Foto II Pro is commercially available from 3Gen, Inc. of San Juan Capistrano, California, USA. Graph 2300 depicts MTF contrast on the vertical axis 2304 and spatial frequency along the horizontal axis 2306. A cutoff frequency 2308 is arbitrarily selected at an MTF contrast value of 10%. An F / 14.1 diffraction-limited endoscope 2312 and an F / 9 diffraction-limited endoscope 2314 have best-case MTF curves plotted in graph 2300. Because the endoscope MTF curve in graph 2300 is diffraction-limited, the performance of an actual endoscopic system will be lower than that shown in the graph. Therefore, tests were performed to quantify the actual performance achievable with exemplary endoscope-based imaging systems.

[0151] FIG. 24 shows an exemplary image 2400 of an exemplary configuration 2410 of an exemplary endoscopic imaging system according to an exemplary embodiment of the present disclosure. The exemplary system / configuration 2410 includes an endoscope 2412, a coupling lens 2414, and a camera 2416. The endoscope may be, for example, a Hawkeye ProSlim from Gradient Lens Corporation of Rochester, New York, USA. The Hawkeye ProSlim used in testing is 7 inches long, has an outer diameter of 4.2 mm, a 42° field of view (FOV), and has a small ring light for illumination. A coupler optical assembly 2414 may be attached to the endoscope 2412. Examples of coupler optical assemblies include assemblies with focal lengths of 18 mm, 20 mm, and 30 mm. Finally, the coupler optical assembly 2414 may be attached to a camera 2416. An example camera may include a Basler ACA2500-14UC from Basler of Ahrensburg, Germany.

[0152] 25A-25C show exemplary images from exemplary configuration 2410. A first exemplary image 2510 is shown in FIG. 25A and was taken with a 30 mm focal length combiner lens and a Basler ACA2500-14UC camera. The first exemplary image 2510 shows a 1952 Air Force target taken at focus. A second exemplary image 2520 is shown in FIG. 25B and was taken with a 20 mm focal length combiner and a PixeLink PL-D755 camera from PixeLink, Ottawa, Ontario, Canada. The second exemplary image 2520 shows a skin area treated with a segmented pattern at a first magnification. A third exemplary image 2530 is shown in FIG. 25C and was taken with a 20 mm focal length combiner and a PixeLink PL-D755 camera from PixeLink, Ottawa, Ontario, Canada. A third exemplary image 2530 shows an area of ​​skin treated with a split pattern at a second magnification.

[0153] Additional Exemplary Embodiments Additional exemplary embodiments include alternative imaging techniques used in combination with EMR-based therapy, which may include microscopic imaging, wide field of view imaging, reflectance confocal imaging, optical coherence tomography imaging, optical coherence elastography imaging, coherent anti-Stokes Raman spectroscopy imaging, two-photon imaging, second harmonic generation imaging, phase conjugate imaging, photoacoustic imaging, infrared spectral imaging, and hyperspectral imaging.

[0154] A diagram of an exemplary ray trace 2600 using an exemplary system and / or method according to an additional exemplary embodiment of the present disclosure is shown in FIG. 26 . For example, annular laser beam rays 2610 are shown there as being reflected from a beam splitter 2612. Laser beam rays 2610 are then focused by an aspheric focusing optic 2616 onto a tissue plane 2614. Focusing optic 2616 may have a hole 2618 through its center. Image rays 2620 pass through hole 2618 and extend from a point source at tissue plane 2614. Image rays 2620 are transmitted through beam splitter 2612. Following beam splitter 2612 in the beam path can be an extra long working distance microscope objective that can focus the image rays onto image plane 2622. Such an exemplary ultra-long working distance microscope objective may be, for example, the InfiniMini from Photo-Optical Company of Boulder, Colorado, USA. In certain exemplary embodiments of the present disclosure, the exemplary ultra-long working distance microscope objective may be coupled to a standard converter and LDS amplifier (e.g., both may be from Photo-Optical Company) to provide a 2.4 mm field of view (FOV), a 110 mm working distance (WD), and 106 line pairs per mm (lp / mm) resolution at an f-number of approximately f-14. According to yet another exemplary embodiment of the present disclosure, the image beam 2620 still passes through the central aperture 2618 of the focusing optics 2616 but does not use the exemplary optical configuration (e.g., endoscope) located within the aperture 2618. Instead, the ultra-long working distance objective may not require imaging optics on the object side of the beam splitter 2612.

[0155] 27 illustrates another exemplary embodiment of a data collection and treatment device / system 2700 according to the present disclosure and its exemplary operation. As shown in FIG. 27, the exemplary device / system 2700 can direct and focus a therapeutic electromagnetic radiation (EMR) beam 2710. The exemplary EMR beam can be, for example, a high quality laser (e.g., M 2 <1.5). For example, in some exemplary cases, the EMR beam 2710 can utilize a wavelength in the range of about 800 nm to about 1200 nm, a pulse energy in the range of about 10 mJ to about 10,000 mJ, and a pulse duration in the range of 5 nanoseconds to about 150 nanoseconds. First, the EMR beam 2710 can impinge on a first lens optical element group 2712. In some exemplary embodiments, the first optical element group 2712 can include a diffractive optical element (DOE) that splits the laser beam into multiple beamlets tilted / tipped at different angles that focus into a 2D patterned array. Examples of DOEs and their use in similar applications are described, for example, in U.S. Patent Application No. 16 / 381,736, which is incorporated herein by reference in its entirety. An exemplary DOE can be Holo / OR part number MS-429-IYA, from Holo / OR of Ness Ziona, Israel, which generates a 5 x 5 array of beamlets.

[0156] After passing through the first optical element group 2712, the EMR beam 2710 may be reflected by a beam splitter 2714. The beam splitter (in some exemplary cases) may be configured to reflect the EMR beam 2710 and transmit light 2715. Exemplary beam splitters may include, for example, a notch filter, a low-pass filter, and / or a high-pass filter. After being reflected by the beam splitter 2714, the EMR beam 2710 may pass through a second optical element group 2716. The second optical element group 2716 and the first optical element group 2712 are designed and / or configured to operate in concert to focus the EMR beam (or multiple EMR beamlets) 2710, for example, to a focal region located downstream from a contact window 2718 within the tissue, for example, a predetermined distance (e.g., approximately 0-1.5 mm ±0.02 mm). In some exemplary embodiments, first optical element group 2712 and second optical element group 2716 may both comprise a folded Petzval lens.

[0157] For example, light 2715 from the surface of the tissue may be directed upward through the contact window 2718, the second optical element group 2716, the beam splitter 2714, and imaged by the third optical element group 2720. The third optical element group 2720 and the second optical element group 2716 may work in concert to re-image the returning light 2715 to and / or at a sensor plane 2722 where a camera sensor (e.g., a CMOS or CDC sensor) may be located. The camera sensor may be configured to capture digital data (e.g., an image) representing the re-imaged light 2715. In some exemplary embodiments, light 2715 emanating from tissue in contact with the outer surface of the contact window 2718 may be focused at the sensor plane 2722. In this exemplary case, the light 2715 may typically have a wavelength in, for example, the visible range, because radiation in this range is less transparent (and therefore less penetrating) within tissue. Alternatively, or additionally, the light 2715 that is focused at the sensor plane 2722 may originate from a location that is a known distance (e.g., about 0-1.5 mm ±0.02 mm) away from the window 2718. In this exemplary alternative / additional case, the light 2715 may typically be selected to have a wavelength in the near-infrared range because, for example, tissue has a higher optical transparency in this wavelength range.

[0158] FIG. 28 illustrates another exemplary data acquisition and treatment system 2800 according to yet another exemplary embodiment of the present disclosure. As shown in FIG. 28 , the system 2800 can be configured to direct and focus an electromagnetic radiation (EMR) beam 2810 to a focal region. The EMR beam 2810 is shown in FIG. 28 as initially diverging and then collimated by a collimation optic 2812. The curvature of the collimation optic 2812 can be selected based on the divergence of the EMR beam 2810. The collimated EMR beam can then be reflected by a mirror 2814 and incident on a focusing optic 2816. The focusing optic 2816 can rapidly focus the EMR beam 2810 (e.g., with an NA greater than about 0.2). The converging EMR beam 2810 may then be selectively reflected by another beam splitter 2818, which may be configured to reflect the EMR beam 2810 and transmit light 2820 for subsequent detection. In some exemplary embodiments, the light 2820 for detection is in the visible range (e.g., about 350-750 nm), and the EMR beam 2810 may be outside the visible range.

[0159] The EMR beam 2810 may then ultimately be directed through a window 2822 configured to be placed in contact with tissue during treatment. The EMR beam 2810 (in various exemplary embodiments) may be configured to focus to a focal region located downstream (e.g., outside) the window 2822 a predetermined distance (e.g., approximately 0-1.5 mm ± 0.02 mm) from the window 2822. Light 2820 emanating from the tissue may pass through the window 2822 and then be imaged by an optical assembly 2824, which focuses the light onto a sensor plane 2826. A camera sensor may be disposed at the sensor plane 2826 and used to capture digital data related to or representative of the light 2820. In some exemplary embodiments, light 2820 emanating from tissue in contact with the outer surface of the window 2822 may be focused onto the sensor plane 2826 by the optical assembly 2824. In this exemplary case, the light 2820 may have a wavelength in the visible range because of the lower optical transparency of tissue at wavelengths in such exemplary range. Alternatively, or additionally, light emanating from a location a known distance (e.g., about 0-1.5 mm ±0.02 mm) from window 2822 can be focused by optical assembly 2824 onto sensor plane 2826. In this exemplary alternative or additional case, light 2820 can be selected to have a wavelength in the near-infrared range because of the higher optical transparency of tissue in this wavelength range.

[0160] Those skilled in the art will appreciate further features and advantages of the present disclosure based on the above-described embodiments. Accordingly, the present disclosure is not to be limited by what has been particularly shown and described, except as indicated by the appended claims. All publications and references cited herein are expressly incorporated herein by reference in their entirety.

[0161] The subject matter described herein may be implemented in digital electronic circuitry, or computer software, firmware, or hardware, including the structural means disclosed herein, their structural equivalents, or combinations thereof. The subject matter described herein may be implemented as one or more computer program products, such as one or more computer programs tangibly embodied in an information carrier (e.g., a machine-readable storage device) or embodied in a propagated signal, for execution by or to control the operation of a data processing device (e.g., a programmable processor, a computer, or multiple computers). Computer programs (also known as programs, software, software applications, or code) may be written in any form of programming language, including compiled or interpreted languages, and may be deployed in any form, including as stand-alone programs, or as modules, components, subroutines, or other units suitable for use in a computing environment. A computer program does not necessarily correspond to a file. A computer program may be stored or recorded as part of a file that holds other programs or data, in a single file dedicated to the program, or in multiple coordinated files (e.g., files storing one or more modules, subprograms, or code portions). A computer program can be deployed to be executed on one computer or on multiple computers at one site or distributed across multiple sites and interconnected by a communications network.

[0162] The example processes, methods, procedures, and logic flows described herein, including method steps of the subject matter described herein, may be performed by one or more programmable processors executing one or more computer programs to perform functions of the subject matter described herein by manipulating input data and generating output. The processes and logic flows may also be performed by, and example apparatus of the subject matter described herein may be implemented as, special purpose logic circuitry, such as an FPGA (field programmable gate array) or an ASIC (application-specific integrated circuit).

[0163] Processors suitable for the execution of a computer program include, by way of example, both general-purpose and special-purpose microprocessors, and any one or more processors of any kind of digital computer. Typically, a processor receives instructions and data from a read-only memory or a random-access memory, or both. The essential components of a computer are a processor for executing instructions and one or more memory devices for storing instructions and data. Typically, a computer also includes one or more mass storage devices for storing data, such as magnetic, magneto-optical, or optical disks, or is operatively coupled to receive data from, transmit data to, or receive data from / to such mass storage devices. Information carriers suitable for embodying computer program instructions and data include, by way of example, any form of non-volatile memory, including semiconductor memory devices (e.g., EPROM, EEPROM, and flash memory devices), magnetic disks (e.g., internal or removable hard disks), magneto-optical disks, and optical disks (e.g., CD and DVD disks). The processor and memory may be supplemented by, or incorporated in, special-purpose logic circuitry.

[0164] To provide for user interaction, the subject matter described herein may be implemented on a computer having a display device, such as a CRT (cathode ray tube) or LCD (liquid crystal display) monitor, for displaying information to the user, and a keyboard and pointing device (e.g., a mouse or trackball) by which the user can provide input to the computer. Other types of devices may also be used to provide for user interaction. For example, feedback provided to the user may be any form of sensory feedback (e.g., visual feedback, auditory feedback, or tactile feedback), and input from the user may be received in any form, including acoustic, speech, or tactile input.

[0165] The example techniques described herein may be implemented using one or more modules. As used herein, the term “module” refers to computing software, firmware, hardware, and / or various combinations thereof. However, at a minimum, a module should not be interpreted as software that is not embodied in hardware, firmware, or recorded on a non-transitory, processor-readable, recordable storage medium (i.e., a module itself is not software). Indeed, a “module” is always interpreted to include at least a portion of physical, non-transitory hardware, e.g., a processor or part of a computer. Two different modules may share the same physical hardware (e.g., two different modules may use the same processor and network interface). The modules described herein may be combined, integrated, separated, and / or replicated to support various applications. Also, functionality described herein as being performed by a particular module may be performed by one or more other modules and / or by one or more other devices instead of, or in addition to, the functionality performed by the particular module. Furthermore, modules may be implemented across multiple devices and / or other components, local or remote from each other. Additionally, modules may be moved from one device and added to another device and / or may be included in both devices.

[0166] The subject matter described herein may be implemented in a computing system that includes back-end components (e.g., data servers), middleware components (e.g., application servers), front-end components (e.g., client computers having a graphical user interface or web browser through which a user can interact with an implementation of the subject matter described herein), or any combination of such back-end, middleware, and front-end components. The components of the system may be interconnected by any form or medium of digital data communication, e.g., a communication network. Examples of communication networks include local area networks ("LANs") and wide area networks ("WANs"), e.g., the Internet.

[0167] Approximate language used throughout the specification and paragraphs herein may be applied to modify any quantitative expression that can be permissibly varied without resulting in a change in the basic function to which it pertains. Unless otherwise specified or clear from the context, "approximately," "substantially," or "about" may include numbers within a 1% range in either direction (more or less than the number), or, in certain exemplary embodiments, within a 5% range, or, in certain exemplary embodiments, within a 10% range (except where such numbers impermissibly exceed 100% of possible values). Thus, values ​​modified by one or more terms such as "about," "approximately," or "substantially" should not be limited to the exact value specified. In at least some instances, approximation language may correspond to the precision of an instrument measuring a value. Throughout the specification and paragraphs herein, unless the context or language dictates otherwise, range limitations may be combined and / or interchanged, and such ranges include all subranges identified and contained therein.

[0168] The articles "a" and "an," as used in the specifications and paragraphs herein, should be understood to include plural referents unless clearly indicated to the contrary. Unless indicated to the contrary or apparent from context, a paragraph or statement including "or" between one or more members of a group is deemed to be satisfied when one, more than one, or all group members are present in, employed in, or otherwise relevant to a given product or process. The present disclosure includes embodiments in which exactly one member of a group is present in, employed in, or otherwise relevant to a given product or process. The present disclosure also includes embodiments in which two or more, or all group members are present in, employed in, or otherwise relevant to a given product or process. Furthermore, it should be understood that the disclosed embodiments provide for all variations, combinations, and permutations in which one or more limitations, elements, clauses, descriptive terms, etc. from one or more listed paragraphs are introduced into other claims that depend from the same base claim (or other claims, if relevant), unless otherwise indicated or unless a contradiction or inconsistency would arise apparent to one of ordinary skill in the art. All embodiments described herein are contemplated as being applicable to all different aspects of the disclosed embodiments, where appropriate. It is contemplated that any of the embodiments or aspects may be freely combined with one or more other such embodiments or aspects, where appropriate, whenever appropriate. When elements are presented as lists, for example, in a Markush group or similar format, it should be understood that each subgroup of elements is also disclosed, and that any element can be removed from the group. In general, when a disclosed embodiment or aspect of a disclosed embodiment is referred to as including a particular element, feature, etc., it should be understood that the particular embodiment or aspect of the disclosure consists of or consists essentially of such element, feature, etc. For simplicity's sake, these embodiments will not be specifically described in so many words in every instance herein. It is also understood that any embodiment or aspect of the present disclosure may be expressly excluded from a paragraph, regardless of whether the specific exclusion is recited in the specification.For example, any one or more active agents, additives, ingredients, any drug, organism, disorder, subject, or combinations thereof can be excluded.

[0169] When ranges are given herein, embodiments of the present disclosure include those in which the endpoints are included, those in which both endpoints are excluded, and those in which one endpoint is included and the other is excluded. Unless otherwise specified, both endpoints should be assumed to be inclusive. Furthermore, unless otherwise indicated or otherwise apparent from the context and the understanding of one of ordinary skill in the art, values ​​expressed as ranges should be understood to mean that different embodiments of the present disclosure can assume any specific value or subrange within the stated range, down to the tenth of the unit of the lower limit of the range, unless clearly dictated by context. When a series of numerical values ​​is described herein, it is understood that the present disclosure includes embodiments related analogously to any intervening values ​​or ranges defined by any two values ​​in the series, and embodiments in which the lowest value may be considered a minimum and the highest value a maximum. Numerical values ​​used herein include values ​​expressed as percentages.

[0170] Unless expressly indicated to the contrary, in any method claimed herein including two or more acts, the order of the method acts is not necessarily limited to the order in which the method acts are recited, but it should be understood that the present disclosure includes embodiments in which the order is so limited. It should also be understood that, unless otherwise indicated or apparent from the context, any products or compositions described herein may be considered "separate."

[0171] As used herein, the terms "comprising" or "comprises" are used in reference to compositions, methods, and their respective components that are essential to the disclosed embodiments, and do not limit the inclusion of any unspecified element, whether essential or not.

[0172] As used herein, the term "consisting essentially of" refers to elements required for a given embodiment. The term allows for the presence of additional elements that do not materially affect the basic, novel, or functional characteristics of that embodiment of the present disclosure.

[0173] The term "consisting of" refers to compositions, methods, and their respective components described herein, excluding elements not recited in that description of an embodiment.

[0174] Although several variations have been described in detail above, other modifications or additions are possible.

[0175] In the above description and paragraphs, phrases such as "at least one of" or "one or more of" may appear followed by a conjunctive list of elements or features. The term "and / or" may also appear with a list of two or more elements or features. Such phrases are intended to mean any of the listed elements or features individually, or any of the listed elements or features in combination with any of the other listed elements or features, unless otherwise implicitly or explicitly contradicted by the context in which they are used. For example, the phrases "at least one of A and B," "one or more of A and B," and "A and / or B" are intended to mean "A only, B only, or A and B," respectively. A similar interpretation applies to lists containing more than two items. For example, "at least one of A, B, and C," "one or more of A, B, and C," and "A, B, and / or C" are intended to mean "A only, B only, C only, A and B, A and C, B and C, or A, B, and C," respectively. Additionally, use of the term "based on" above and in paragraphs is intended to mean "based at least in part on," such that unrecited features or elements are also allowed.

[0176] The subject matter described herein may be embodied in systems, devices, methods, and / or articles, depending on the desired configuration. The implementations described in the foregoing description do not represent all implementations consistent with the subject matter described herein. Instead, they are merely some examples consistent with aspects related to the described subject matter. While several variations have been described in detail above, other modifications or additions are possible. In particular, additional features and / or variations may be provided in addition to those described herein. For example, the implementations may be directed to various combinations and subcombinations of the disclosed features and / or combinations and subcombinations of several additional features disclosed above. Furthermore, the logic flow depicted in the accompanying figures and / or described herein does not necessarily require the particular order or sequence shown to achieve desirable results. Other implementations may be within the scope of the following claims.

Claims

1. 1. An apparatus for treating at least one patient, comprising: a data collection system configured to collect data for the at least one patient; Authenticating access to a remote network; aggregating the collected patient data; a controller configured to store the aggregated patient data in a data storage device in communication with the remote network; an electromagnetic radiation ("EMR") source configured to generate an EMR beam; an optical arrangement configured to converge or focus the EMR beam to a focal region located (i) along an optical axis within at least a portion of the at least one patient and (ii) below a surface of tissue of the at least one patient; a window located a predetermined distance from the focal region and positioned along the optical axis between the focal region and the optical element arrangement; The device, wherein the window is configured to transmit the EMR beam and contact a surface of the at least one patient tissue.

2. 10. The device of claim 1, wherein the controller is further configured to access modules in communication with the remote network, the modules including at least one of an image recognition module, a computer vision module, an electronic health record module, or a clinical decision support module.

3. 10. The device of claim 1, wherein the at least one patient data comprises at least one of patient tissue images, patient age, treatment session information, patient pain score, data collection parameters, or EMR-based treatment parameters.

4. 10. The apparatus of claim 1, wherein the data acquisition system is configured to acquire the patient data from tissue contacting the window, and the data acquisition system and the optical element arrangement are spatially aligned with the window.

5. 10. The apparatus of claim 1, further comprising a drug-based therapy system configured to be utilized in drug-based therapy of the at least one patient.

6. The device of claim 5 , wherein the drug-based therapeutic system comprises at least one of a topical drug, an injectable drug, or an orally delivered drug.

7. The apparatus of claim 1 , wherein the optical arrangement is configured to converge or focus the laser beam with a numerical aperture (NA) of at least 0.

3.

8. The data collection system includes: an illumination source configured to illuminate the surface of the tissue; a light directing arrangement configured to direct light from the tissue surface through the window to a sensor plane; a sensor arrangement configured to detect the light at the sensor plane; The apparatus of claim 1 , wherein the collected patient data includes a plurality of images.

9. The apparatus of claim 8 , wherein the controller is configured to aggregate the collected patient data by stitching the multiple images together.

10. 10. The device of claim 1, wherein the data collection system includes at least one of: (i) a user interface configured to receive data for the at least one patient from a user; or (ii) a system interface configured to receive data for the at least one patient from a further network connected to a storage device containing data for the at least one patient.

11. The apparatus of claim 1 , wherein the data acquisition system includes at least one of a photoacoustic imaging system, a camera, a dermoscope subsystem, a microscope subsystem, a confocal microscope subsystem, a plasma detection subsystem, or a window reference subsystem.

12. The apparatus of claim 1 , wherein the controller is further configured to access a module by performing authentication on the module in communication with the remote network.

13. 13. The apparatus of claim 12, wherein the authentication is performed by verifying at least one of: (i) a financial agreement has been executed; (ii) a financial distribution has been received; or (iii) the financial distribution is outstanding.

14. The apparatus of claim 12 , wherein the authentication is performed by achieving a financial share of the fee.

15. The device of claim 14 , wherein the fee is provided for at least one of a treatment, a patient, a subscription, an image, or a service module.

16. The apparatus of claim 1 , wherein the optical element arrangement comprises a folded Petzval lens.

17. 1. A method of treating at least one patient, comprising: collecting data for the at least one patient using a data collection system; aggregating the collected patient data; authenticating access to a remote network; storing the patient data in a data storage device in communication with the remote network; generating an electromagnetic ("EMR") beam using an EMR source; using an optical element arrangement to converge or focus the EMR beam to a focal region located (i) along an optical axis and (ii) below the surface of the at least one patient tissue; contacting a surface of the at least one patient tissue with a window located along the optical axis between the focal region and a focusing optic and a predetermined distance from the focal region; transmitting the EMR beam through the window; The method wherein the focal region is positioned within the tissue.

18. accessing a module in communication with the remote network; 20. The method of claim 17, wherein the module comprises at least one of an image recognition module, a computer vision module, an electronic health record module, or a clinical decision support module.

19. 20. The method of claim 17, wherein the at least one patient data comprises at least one of patient tissue images, patient age, treatment session information, patient pain score, data collection parameters, or EMR-based treatment parameters.

20. 20. The method of claim 17, wherein collecting the patient data includes sensing the patient data from tissue contacting the window, and wherein the data collection system and the optical element arrangement are spatially aligned with the window.

21. 20. The method of claim 17, further comprising administering a drug-based therapy to the at least one patient.

22. 22. The method of claim 21, wherein the drug-based treatment comprises at least one of a topical drug, an injectable drug, or an orally delivered drug.

23. 20. The method of claim 17, wherein converging or focusing the electromagnetic radiation (EMR) beam to the focal region is performed with a numerical aperture (NA) of at least 0.

3.

24. collecting the patient data includes: irradiating the surface of the at least one patient tissue; directing light from the tissue surface through the window to an image plane; sensing the light at the image plane using a sensor arrangement; The method of claim 17 , wherein the collected patient data includes a plurality of images.

25. 25. The method of claim 24, wherein aggregating the collected patient data comprises stitching the plurality of images together.

26. 20. The method of claim 17, wherein collecting the data further comprises at least one of: (i) entering the patient data using a user interface; or (ii) interfacing with a further network that facilitates storage containing data of the at least one patient.

27. 20. The method of claim 17, wherein collecting the data includes using at least one of an optoacoustic imager, a camera, a dermoscope subsystem, a microscope subsystem, a confocal microscope subsystem, a plasma detection subsystem, or a window reference subsystem.

28. 18. The method of claim 17, further comprising accessing a module that communicates with the remote network by authenticating access to the module.

29. 28. The method of claim 27, wherein the authentication is performed by verifying at least one of: (i) a financial agreement has been executed; (ii) a financial distribution has been received; or (iii) the financial distribution is outstanding.

30. 28. The method of claim 27, wherein the authentication is performed by effecting a financial share of the fee.

31. 30. The method of claim 29, wherein the fee is provided for at least one of a treatment, a patient, a subscription, an image, or a service module.

32. The method of claim 17 , wherein the optical element arrangement comprises a folded Petzval lens.

33. 1. A computer-accessible medium having computer software for facilitating treatment of at least one patient, the computer software, when executed by a computer processor, causing the computer processor to: collecting data for the at least one patient using a data collection system; aggregating the collected patient data; authenticating access to a remote network; storing the patient data in a data storage device in communication with the remote network; controlling an electromagnetic radiation ("EMR") source to generate an EMR beam; controlling an optical element configuration to converge or focus the EMR beam at a focal region located (i) along an optical axis and (ii) below the surface of the at least one patient tissue; controlling a surface of the at least one patient tissue to contact a window located along the optical axis between the focal region and a focusing optic at a predetermined distance from the focal region; and controlling the EMR beam to transmit through the window; The computer-accessible medium, wherein the data acquisition system and the optical element arrangement are aligned with the window and the focal region is positioned within the tissue.

Images