WO2021126858A1

WO2021126858A1 - Coincident feedback and irradiation for a treatment device

Info

Publication number: WO2021126858A1
Application number: PCT/US2020/065130
Authority: WO
Inventors: Jayant Bhawalkar; Jason Karp; Daniel Gray; Patrick Shaughnessy; Charles Holland DRESSER
Original assignee: Avava, Inc.
Priority date: 2019-12-20
Filing date: 2020-12-15
Publication date: 2021-06-24

Abstract

Systems and methods for providing image feedback and therapeutic irradiation are described. Some embodiments include: a laser source configured to generate a laser beam having a transverse ring mode, an optical element configured to converge the laser beam and direct the laser beam toward a tissue, and an optical arrangement configured to collect light from the tissue through the aperture of the optical element.

Description

COINCIDENT FEEDBACK AND IRRADIATION FOR A TREATMENT DEVICE

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application No.

62/951,726, filed on December 20, 2019, entitled “Coincident Feedback And Irradiation For A Treatment Device,” the entirety of which is incorporated by reference herein.

BACKGROUND

[0002] Melasma or chloasma faciei (the mask of pregnancy) is a common skin condition characterized by tan to dark gray-brown, irregular, well-demarcated macules and patches on the face. The macules are believed to be due to overproduction of melanin, which is taken up by the keratinocytes (epidermal melanosis) or deposited in the dermis (dermal melanosis, melanophages). The pigmented appearance of melasma can be aggravated by certain conditions such as pregnancy, sun exposure, certain medications (e.g., oral contraceptives), hormonal levels, and genetics. The condition can be classified as epidermal, dermal, or mixed depending on the location of excess melanin. Exemplary symptoms of melasma primarily include the dark, irregularly-shaped patches or macules, which are commonly found on the upper cheek, nose, upper lip, and forehead. These patches often develop gradually over time.

[0003] Melasma can cause considerable embarrassment and distress. It is especially problematic for darker skin tones and women, impacting up to 30% of Southeastern Asian women, as well as many Latin American women. Only l-in-4 to 1 -in-20 affected individuals are male, depending on the population study. Approximately 6 million women in the US cope with melasma, according to the American Academy of Dermatology. Worldwide, numbers of those with melasma are estimated at 157 million people in Asia/Pacific, 58 million in Latin America, and 3 million in Europe. Melasma generally appears between ages 20-40. As no cure exists for melasma, US patients undergoing treatment for melasma currently try many different types of treatment. 79% of US patient’s topical medications; while, 37% use oral treatment; and, 25% use a laser.

[0004] Unlike other pigmented structures that are typically present in the epidermal region of skin (i.e., at or near the tissue surface), dermal (or deep) melasma is often characterized by widespread presence of melanin and melanophages in portions of the underlying dermis. Accordingly, treatment of dermal melasma (e.g., lightening of the appearance of darkened pigmented regions) can be particularly challenging because of the greater difficulty in accessing and affecting such pigmented cells and structures located deeper within the skin. Accordingly, conventional skin rejuvenation treatments such as facial peels (laser or chemical), dermabrasion, topical agents, and the like, which primarily affect the overlying epidermis (and are often the first course of treatment for melasma), may not be effective in treating dermal melasma.

[0005] Additionally, up to 50% of melasma patients also experience other hyperpigmentation problems. Among all pigmentary disorders, melasma is the one for which the largest proportion of patients are likely to visit a dermatologist. The management of this disorder remains challenging given the incomplete understanding of the pathogenesis, its chronicity, and recurrence rates. After treatment, the melasma may recur, often worse than prior to treatment. Moreover, topical treatments which may work in treating epidermal melasma fail to effectively treat dermal or mixed melasma.

SUMMARY

[0006] It has been observed that application of light or optical energy of certain wavelengths can be strongly absorbed by pigmented cells, thereby damaging them. However, an effective treatment of dermal melasma using optical energy introduces several obstacles. For example, pigmented cells in the dermis must be targeted with sufficient optical energy of appropriate wavelength(s) to disrupt or damage them, which may release or destroy some of the pigmentation and reduce the pigmented appearance. However, such energy can be absorbed by pigment (e.g., melanin) in the overlying skin tissue, such as the epidermis and upper dermis.

This near-surface absorption can lead to excessive damage of the outer portion of the skin, and insufficient delivery of energy to the deeper dermis to affect the pigmented cells therein. Moreover, moderate thermal injury to melanin containing melanocytes located in the basal layer of the epidermis can trigger an increase in the production of melanin (e.g., hyperpigmentation) and severe thermal damage to the melanocytes can trigger a decrease in the production of melanin (e.g., hypopigmentation). [0007] The Pigmentary Disorders Academy (PDA) evaluated the clinical efficacy of different types of melasma treatment in an attempt to gain a consensus opinion on treatment. Their efforts were published in a paper titled “Treatment of Melasma” by M. Rendon et al. published in The Journal of the American Academy of Dermatology in May 2006. Rendon et al. reviewed literature related to melasma treatment for the 20 years prior and made determinations based upon their review. Rendon et al. determined that “The consensus of the group was that first line therapy for melasma should consist of effective topical therapies, mainly fixed triple combinations.” And, that “[ljasers should rarely be used in the treatment of melasma and, if applied, skin type should be taken into account.”

[0008] A criticism of Rendon et al.’s comprehensive report on melasma treatment could be that it is dated, having been published in 2006. A more recent article by M. Sadeghpour et al. published in 2018 in Advances in Cosmetic Surgery entitled “Advances in the Treatment of Melasma” attempts to review current melasma treatment modalities. Sadeghpour et al. likewise conclude that “Topical therapy remains the gold standard for first-line therapy for melasma using broad- spectrum sunscreens and either hydroquinone 4% cream, tretinoin, or triple-combination creams.” Sadeghpour et al. note that dermal melasma is more difficult to treat “because destruction of these melanosomes is often accompanied by significant inflammation that in turn stimulates further melanogenesis.”

[0009] Therefore there is still a large, unmet need for a more efficacious and safe treatment for melasma and other hard to treat pigmentary disorders.

[0010] Approaches have been developed that involve application of optical energy to small, discrete treatment locations in the skin that are separated by healthy tissue to facilitate healing. Accurately targeting the treatment locations (e.g., located in dermal layer) with desirable specificity while avoiding damage to healthy tissue around the treatment location (e.g., in the epidermal layer) can be challenging. This requires, for example, an optical system with high numerical aperture (NA) for focusing a laser beam to a treatment location. The high NA optical system delivers a sufficiently high in-focus 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” has shown this technique to be advantageous for treatment of dermal pigmentation including Melasma in research settings.

[0011] However, this technique requires that a focal region formed by the high NA optical system be located precisely (e.g., within a tolerance of about +/- 25 pm) at a depth within a target tissue. For example, melanocytes are typically located within a basal layer of the epidermis at a depth of about lOOpm. Dermal melanophages responsible for deep melasma can be present in the upper dermis just beneath the basal layer of the epidermis (e.g., 50pm below). Therefore, a difference in focal region depth of a few-tens of micrometers can become the difference between effectively treating dermal pigmentation and inadvertently damaging melanocytes thereby potentially causing debilitating cosmetic results (e.g., hypopigmentation). In part for this reason, an EMR-based system that effectively treats dermal pigmentation has yet to be made commercially available.

[0012] Therefore, it is desirable to develop an EMR-based treatment system that reliably locates a focal region to a prescribed depth within a tolerance of tens of micrometers (e.g., about ±100pm, about ±10pm, about ±lpm, etc.) Further, it can be desirable that the EMR-based treatment systems achieve this performance in part through calibration, for example by periodically placing the focal region at a reference having a known depth. Furthermore, it can be desirable that the reference used during calibration be used during treatment. For example, the reference can comprise an interface that establishes a robust contact with the treatment region and stabilizes the treatment region.

[0013] Some developed approaches for dermal pigment treatment, like those outlined by Anderson et ak, can employ selective thermionic plasma generation as a means of treatment. In these cases, laser fluence at a focal region within the dermis is above a thermionic plasma threshold (e.g., 10⁹ W/cm²), but below an optical breakdown threshold (e.g., 10¹² W/cm²). This causes plasma formation selectively when the focal region is located at a pigmented tissue (e.g., melanin) within the dermis without generating a plasma in unpigmented tissue in the dermis or pigmented epidermal tissue above the focal region. The selectively formed thermionic plasma disrupts or damages the pigment and surrounding tissue. This disruption ultimately leads to clearing of the dermal pigment. Therefore, presence of plasma during treatment within a tissue being treated can be indicative of efficacious treatment in some embodiments. As parameter selection for laser-based skin treatments often depends on skin type and is therefore dependent upon each individual patient, the presence of plasma may be used as an indication that correct treatment parameters have been achieved. This feedback is therefore desirable for successful treatment of a condition, such as melasma, in populations that are generally underserved by laser-based treatment (e.g., those with darker skin types).

[0014] Alternatively, in some cases, properties of a detected plasma may indicate that the treatment is having an adverse effect. For example, in some embodiments a transmissive window is placed onto a skin being treated to reference the skin and keep it from moving during treatment. It is possible for treatment to fail when the laser beam etches the window. Etching of the window prevents further efficient transmission of the laser to the tissue and often coincides with very bright plasma formation in the window itself. If treatment continues with an etched window it is likely that heat accumulation within the window will cause damage to the epidermis of the skin (e.g., burning and blistering). It is therefore advantageous to employ feedback to detect plasma formation within the window and stop treatment when it occurs.

[0015] From the foregoing, it can be understood that plasma formation during treatment can be both advantageous and deleterious to treatment. Thus, systems and methods that provide plasma detection can detect properties of the plasma and distinguish between plasma beneficial to tissue treatment and plasma detrimental to tissue treatment continuously in real-time.

[0016] It can be desirable in some embodiments to image the tissue being treated from the perspective of the treatment device and project this view onto a screen for viewing by the practitioner. In one aspect, placement of a treatment device typically occludes a practitioner’s view of the tissue being treated. Thus, tissue imaging can facilitate accurate placement of the treatment device for targeting affected tissue. Additionally, as the goal of treatment of many pigmentary conditions is aesthetic (e.g., improve the appearance of the skin) it images of the skin can be consistently acquired under repeatable imaging conditions (e.g., lighting and distance) during imaging so that results of treatment may be ascertained. Attempts to address some of the foregoing issues can be found in co-owned and co-pending patent application number 16/447,937 entitled “Feedback Detection for a Treatment Device” by J. Bhawalkar et al, incorporated herein by reference.

[0017] It has long been the hope of those suffering with pigmentary conditions, such as melasma, that an EMR-based treatment for their condition be made widely available. Accordingly, as discussed in greater detail below, an EMR-based treatment system is provided that provides repeatable depth positioning of the focal region within a target tissue. The disclosed systems and methods can also detect and record plasma events in order to document and track treatment safety and effectiveness and image the treated tissue to accurately deliver EMR to the treatment region. These capabilities address a number of technical problems currently preventing widespread successful treatment of dermal pigmentation and other hard to treat skin conditions with EMR-based systems.

[0018] An embodiment of a system for providing image feedback and therapeutic irradiation includes: a laser source configured to generate a laser beam having a transverse ring mode, an optical element configured to converge the laser beam and direct the laser beam toward a tissue, a first optical arrangement configured to direct the laser beam incident the optical element, such that the transverse ring mode of the laser beam circumscribes an aperture of the optical element, a second optical arrangement configured to collect light from the tissue through the aperture of the optical element, and a sensor configured to sense light from the tissue.

[0019] In some embodiments of the system, the laser source additionally includes a beam shaper configured to shape the laser beam.

[0020] In some embodiments of the system, the optical element comprises at least one of a converging lens and an axicon.

[0021] In some embodiments of the system, the optical element has a first optical axis and the second optical arrangement has a second optical axis that is substantially coaxial with the first optical axis. In some versions, the system also includes a beam splitter disposed along the first optical axis, which is configured to separate the laser beam and the light from the tissue. [0022] In some embodiments of the system, the system additionally includes a third optical arrangement configured to accept the light from the tissue and form an image of the tissue incident the sensor. In some versions, the sensor comprises at least one of a charge coupled device (CCD) sensor and a capacitive metal-oxide semiconductor (CMOS) sensor.

[0023] In some embodiments of the system, the second optical arrangement comprises at least one of a lens assembly and an endoscope.

[0024] In some embodiments of the system, the system additionally includes an illumination system configured to direct an illuminating light toward the tissue.

[0025] An embodiment of a method of providing imaging feedback and therapeutic irradiation includes: generating, using a laser source, a laser beam having a transverse ring mode; directing, using a first optical arrangement, the laser beam towards an optical element having an aperture, such that the transverse ring mode circumscribes the aperture; converging, using the optical element, the laser beam; directing, using the optical element, the laser beam toward a tissue; collecting, using a second optical arrangement, light from the tissue through the aperture of the optical element; and, sensing, using a sensor, the light from the tissue.

[0026] In some embodiments of the method, generating the laser beam having the transverse ring mode additionally includes shaping, using a beam shaper, the laser beam.

[0027] In some embodiments of the method, the optical element comprises at least one of a converging lens and an axicon.

[0028] In some embodiments of the method, the optical element has a first optical axis and the second optical arrangement has a second optical axis that is substantially coaxial with the first optical axis. In some versions, the method additionally includes separating, using a beam splitter, the laser beam from the light from the tissue.

[0029] In some embodiments of the method, the method additionally includes accepting, using a third optical arrangement, the light from the tissue; and, forming, using the third optical arrangement, an image of the tissue incident the sensor. In some versions, the sensor comprises at least one of a charge coupled device (CCD) sensor and a capacitive metal-oxide semiconductor (CMOS) sensor.

[0030] In some embodiments of the method, the second optical arrangement comprises at least one of a lens assembly and an endoscope.

[0031] In some embodiments of the method, the method additionally includes directing, using an illumination system, an illuminating light toward the tissue.

BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Embodiments of the disclosure will be more fully understood from the following detailed description taken in conjunction with the accompanying drawings, in which:

[0033] FIG. 1 schematically illustrates an exemplary apparatus for electromagnetic radiation (EMR) treatment and visualization of treated tissue;

[0034] FIG. 2 is a flowchart that illustrates an exemplary method for electromagnetic radiation (EMR) treatment and visualization of treated tissue;

[0035] FIG. 3 illustrates an exemplary ray trace for an EMR treatment apparatus;

[0036] FIG. 4 graphs modulation transfer function of an embodiment compared to a currently available dermatoscope;

[0037] FIG. 5 is an image of an exemplary test setup for an endoscope imaging system;

[0038] FIG. 6A is a first exemplary image taken with an endoscope imaging system;

[0039] FIG. 6B is a second exemplary image taken with an endoscope imaging system;

[0040] FIG. 6C is a third exemplary image taken with an endoscope imaging system; and

[0041] FIG. 7 is an exemplary ray trace of another EMR treatment apparatus.

[0042] It is 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 therefore should not be considered as limiting the scope of the disclosure. The systems, devices, and methods specifically described herein and illustrated in the accompanying drawings are non-limiting exemplary embodiments.

DETAILED DESCRIPTION

[0043] Certain exemplary embodiments will now be described to provide an overall understanding of the principles of the 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 and methods specifically described herein and illustrated in the accompanying drawings are non-limiting exemplary embodiments and that the scope of the present invention is defined solely by the claims. The features illustrated or described in connection with one exemplary embodiment may be combined with the features of other embodiments. Such modifications and variations are intended to be included within the scope of the present invention.

[0044] Embodiments of the disclosure are discussed in detail below with respect to treatment of pigmentary conditions of the skin, such as melasma, to improve the appearance of such a pigmentary condition. However, the disclosed embodiments can be employed for treatment of other pigmentary and non-pigmentary conditions and other tissue and non-tissue targets without limit. Examples of pigmentary conditions can 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 pigmented tissues and structures that can be treated 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 targets for the treatment of non-pigmented structures, tissues and conditions can include, but are not limited to, hair follicles, hair shafts, vascular lesions, infectious conditions, sebaceous glands, acne, and the like.

[0045] Methods of treating various skin conditions, such as for cosmetic purposes, can be carried out using the systems described herein. It is understood that, although such methods can be conducted by a physician, non-physicians, such as aestheticians and other suitably trained personnel may use the systems described herein to treat various skin conditions with and without the supervision of a physician.

[0046] Further, in the present disclosure, like-named components of the embodiments generally have similar features, and thus within a particular embodiment each feature of each like-named component is not necessarily fully elaborated upon. Additionally, to the extent that linear or circular dimensions are used in the description of the disclosed systems, devices, and methods, such dimensions are not intended to limit the types of shapes that can be used in conjunction with such systems, devices, and methods. A person skilled in the art will recognize that an equivalent to such linear and circular dimensions can easily be determined for any geometric shape. Sizes and shapes of the systems and devices, and the components thereof, can depend at least on the anatomy of the subject in which the systems and devices will be used, the size and shape of components with which the systems and devices will be used, and the methods and procedures in which the systems and devices will be used.

[0047] In general, high numerical aperture (NA) optical treatment systems are described that can focus electromagnetic radiation (EMR) (e.g., a laser beam) to a treatment region in a tissue. Unless otherwise noted, the terms EMR, EMR beam, and laser beam are employed interchangeably herein. The focused laser beam can deliver optical energy to the treatment region without harming the surrounding tissue. The delivered optical energy can, for example, disrupt pigmented chromophores and/or targets in a treatment region of the dermal layer of the skin, without affecting the surrounding regions (e.g., overlying epidermal layer, other portions of the dermal layer, and the like). In other implementations, the delivered optical energy can cause tattoo removal or alteration, or hemoglobin-related treatment.

[0048] Exemplary methods and devices for treating skin conditions with light or optical energy are disclosed in U.S. Patent Application Publication No. 2016/0199132, entitled “Method and Apparatus for Treating Dermal Melasma,” and U.S. Provisional Application No. 62/438,818, entitled “Method and Apparatus for Selective Treatment of Dermal Melasma,” each of which is hereby incorporated by reference herein in their entirety.

[0049] In general, systems and corresponding methods are provided for treatment of pigmentary conditions in tissues. As discussed in greater detail below, the disclosed systems and methods employ electromagnetic radiation (EMR), such as laser beams, to deliver predetermined amounts of energy to a target tissue. The EMR can be focused to a focal region and the focal region can be translated or rotated in any direction with respect to the target tissue. The predetermined amount of radiation can be configured to thermally disrupt or otherwise damage portions of the tissue exhibiting the pigmentary condition. In this manner, the predetermined amount of energy can be delivered to any position within the target tissue for treatment of the pigmentary condition such as to improve the appearance thereof.

[0050] Referring now to FIG. 1, an electromagnetic radiation (EMR) source (e.g., laser source) 110 generates an EMR beam (e.g., laser beam) 112. According to some embodiments, the EMR beam 112 has a transverse ring mode (e.g., TEM 01*) natively from the EMR source 110. According to other embodiments, a beam shaper 114 shapes the EMR beam to produce a transverse ring mode. FIG. 1 illustrates the beam shaper 114 that employs two axicons. A first axicon 116 having a first wedge angle accepts the EMR beam 112 and produces a quasi-Bessel beam 118 As the quasi -Bessel beam 118 propagates to produce a diverging ring mode. The diverging ring mode 120 is collimated by a second axicon 122 into an EMR beam having a transverse ring mode 124. According to some embodiments, the ring mode 124 is reflected by a beam splitter 126 and directed toward a focus optic 128. Some examples of the focus optic 128 include converging optics (e.g., plano-convex lenses) and axicons. The focus optic 128 converges the EMR beam and directs it toward a tissue 130 (e.g., skin). According to some embodiments, a window 132 is located between the focus optic 128 and the tissue 130. The window is transparent at multiple wavelengths, for example at visible wavelengths and at an EMR wavelength of the EMR beam 124. Exemplary window materials can include glass, quartz and sapphire. In some embodiments, the window 132 can be cooled and used to cool the tissue 130 during treatment. The window 132 can be placed in contact with an outer surface of the tissue during operation of the apparatus 100. The focus optic 128 is manufactured with an aperture through its center. According to some embodiments, an optical assembly 134 is located within the aperture of the focus optic 128. The optical assembly 134 affects light 136 from the tissue 130. In some embodiments, the optical assembly 134 has an optical axis that is substantially coaxial with an optical axis of the focus optic 128. According to some embodiments, the light 136 is transmitted through the beam splitter 126 and focused by a camera lens 138 onto a sensor 140. For example, the sensor 140 in some implementations is a camera sensor (e.g., a charge-coupled device [CCD] or Complementary metal-oxide-semiconductor [CMOS] camera). According to some embodiments, the tissue 130 is illuminated by an illuminator source 142, which directs an illuminating light 144 toward the tissue 130.

[0051] FIG. 2 illustrates a flow chart for a method 200 involving treatment and visualization according to some embodiments. Treatment and visualization may occur sequentially, coincidently, or independent of one another. For this reason, the treatment method 204 and the visualization method 206 are shown in parallel.

[0052] Referring first to treatment method 204, an electromagnetic radiation (EMR) beam having a transverse ring mode is generated 210. An exemplary EMR beam is a laser beam, for example a 1064nm wavelength laser beam. An example transverse ring mode is a transverse electromagnetic mode (TEM) 01* or doughnut mode. Next, the EMR beam is directed at an EMR optic having an aperture, such that the transverse ring mode circumscribes the aperture 220. In some versions, the EMR optic comprises at least one of a converging lens and an axicon. As the EMR beam has a transverse ring mode, a center portion of the EMR beam has negligible radiative power. The EMR beam is directed at the EMR optic so that this center portion of the EMR beam overlaps with the aperture of the EMR optic. This way substantially all the radiative power of the EMR beam is affected by the EMR optic, despite the optical element having an aperture through its middle portion. The EMR beam is then converged 230 and directed toward a tissue 240 by the EMR optic. In some embodiments, the converging EMR beam performs a therapy on the tissue (e.g., photothermolysis). In some embodiments, the treatment method 204 additionally includes shaping the EMR beam in order to produce the transverse ring mode, for example with a beam shaper.

[0053] Referring now to the visualization method 206, light from the tissue is collected through the aperture of the EMR optic 250. In some embodiments, the light from the tissue is directed through the aperture using one or more optical elements. For example, in some embodiments at least one of a lens assembly and an endoscope is used to collect light through the aperture. In some versions, the one or more optical elements have an optical axis that is substantially collinear with an optical axis of the EMR optic. According to some embodiments, the method 200 additionally includes separating the light from the tissue from the beam path of the EMR beam, for example by using a beam splitter. Next, the collected light is sensed 260. According to some embodiments, the collected light is focused to an image, which is then sensed by a camera sensor (e.g., a charge-coupled device [CCD] or Complementary metal-oxide-semiconductor [CMOS] camera). Finally, the camera sensor produces a digital image of the tissue. This digital image can be used by the operating clinician in order to view and monitor the treatment procedure. In alternative embodiments, the light is sensed by alternative means, for example at least one of a photosensor, a photodiode, and a photovoltaic. In some additional embodiments, the method includes directing an illumination light toward the tissue, in order to illuminate the tissue for visualization.

[0054] FIG. 3 shows a ray-trace 300, according to some embodiments. A focus optic 310 has an aperture 312 through its center. An endoscope 314 can be located in the aperture 312. A beam splitter 316 is placed after the endoscope 314 (e.g., downbeam from the endoscope 314 for light coming from a target tissue). The beam splitter 316 is configured to reflect a laser beam wavelength (e.g., 1064nm) and pass light wavelengths for sensing (e.g., visible wavelengths). Two ray paths are shown in FIG. 3. A laser ray trace 318 illustrates a path of rays associated with a treatment laser. An imaging ray trace 320 illustrates a path of rays associated with the endoscope 314. An object plane 322 and an image plane 324 are shown in FIG. 3.

[0055] FIG. 4 illustrates modulation transfer function (MTF) graph 400 for diffraction limited endoscope imaging systems compared with a DermLite Foto II Pro photographic dermatoscope lens assembly 402. The DermLite Foto II Pro is currently available to the market from 3Gen, Inc. of San Juan Capistrano, California, U.S.A. The graph 400 depicts MTF contrast on a vertical axis 404 and spatial frequency along a horizontal axis 406. A cutoff frequency 408 has been arbitrarily selected to be at an MTF contrast value of 10%. An F/14.1 diffraction limited endoscope 412 and an F/9 diffraction limited endoscope 414 have best case MTF curves plotted on the graph 400. As the endoscope MTF curves in the graph 400 are diffraction limited, and therefore the performance of an actual endoscope system will be less than that shown in the graph. For this reason, a test was performed in order to quantify actual performance achievable with an exemplary endoscope-based imaging system. [0056] FIG. 5 is an image showing a test setup 510 for an exemplary endoscope imaging system. The system comprises an endoscope 512, a coupler optical assembly (e.g., a camera lens) 514, and a camera 516. The endoscope can be a Hawkeye ProSlim from Gradient Lens Corporation of Rochester, New York, U.S.A. The Hawkeye ProSlim used in the tests had a length of 7”, an outside diameter of 4.2mm, a field of view (FOV) of 42°, and a small illuminated ring light. The coupler optical assembly 514 is attached to the endoscope 512. Examples of coupler optical assemblies 514 include: 18mm, 20mm, and 30mm focal length assemblies. The coupler optical assembly 514 is attached to the camera 516. A specific example of a camera includes a Basler ACA2500-14UC from Basler of Ahrensburg, Germany.

[0057] FIGS. 6A-C illustrate images from the test setup 510. A first exemplary image 610 is shown in FIG. 6 A. The first exemplary image 610 was taken with a 30mm focal length coupler lens and the Basler ACA2500-14UC camera. The first exemplary image shows a 1952 Air Force target taken at focus. A second exemplary image 620 is shown in FIG. 6B. The second exemplary image 620 was taken with a 20mm focal length coupler and a PixeLink PL-D755 camera from PixeLink of Ottawa, Ontario, Canada. The second exemplary image shows a skin region treated with a fractionated pattern at a first magnification. A third exemplary image 630 is shown in FIG. 6C. The third exemplary image 630 was taken with a 20mm focal length coupler and a PixeLink PL-D755 camera from PixeLink of Ottawa, Ontario, Canada. The third exemplary image shows a skin region treated with a fractionated pattern at a second magnification.

Additional Embodiments.

[0058] Additional embodiments include alternative imaging technologies used in conjunction with EMR-based treatment. These alternative imaging technologies can 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.

[0059] A ray trace 700 for an additional embodiment is shown in FIG. 7. Annular laser beam rays 710 are shown reflected from a beam splitter 712. The laser beam rays 710 are then focused to a tissue plane 714 by an aspherical focus optic 716. The focus optic 716 has an aperture 718 through its center. Through the aperture 718 image rays 720 that extend from a point source at the tissue plane 714 can pass. The image rays 720 transmit through the beamsplitter 712. After the beamsplitter 712 (e.g., downbeam from the beamsplitter 712) an extra-long working distance microscope objective brings the image rays 720 to focus at an image plane 722. An exemplary extra-long working distance microscope objective is InfmiMini from Photo-Optical Company of Boulder, Colorado, U.S.A. In some embodiments, the InfmiMini is coupled to a standard converter and an LDS amplifier (both also from Photo-Optical Company) to provide a 2.4mm field of view (FOV), a 110mm working distance (WD), and 106 line pair per mm (lpmm) resolution with an f-number of about f-14. In the additional embodiment, the image rays 720 can pass through the aperture 718 of the focus optic 716, but without an optical arrangement (e.g., endoscope) located within the aperture 718. Instead, the extra-long working distance objective can obviate the need for imaging optics on the object side of the beam splitter 712.

[0060] One skilled in the art will appreciate further features and advantages of the invention based on the above-described embodiments. Accordingly, the invention 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.

[0061] The subject matter described herein can be implemented in digital electronic circuitry, or in computer software, firmware, or hardware, including the structural means disclosed in this specification and structural equivalents thereof, or in combinations of them. The subject matter described herein can be implemented as one or more computer program products, such as one or more computer programs tangibly embodied in an information carrier (e.g., in a machine readable storage device), or embodied in a propagated signal, for execution by, or to control the operation of, data processing apparatus (e.g., a programmable processor, a computer, or multiple computers). A computer program (also known as a program, software, software application, or code) can be written in any form of programming language, including compiled or interpreted languages, and it can be deployed in any form, including as a stand-alone program or as a module, component, subroutine, or other unit suitable for use in a computing environment. A computer program does not necessarily correspond to a file. A program can be stored in a portion of a file that holds other programs or data, in a single file dedicated to the program in question, or in multiple coordinated files (e.g., files that store one or more modules, sub programs, or portions of code). 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 communication network.

[0062] The processes and logic flows described in this specification, including the method steps of the subject matter described herein, can be performed by one or more programmable processors executing one or more computer programs to perform functions of the subject matter described herein by operating on input data and generating output. The processes and logic flows can also be performed by, and apparatus of the subject matter described herein can be implemented as, special purpose logic circuitry, e.g., an FPGA (field programmable gate array) or an ASIC (application specific integrated circuit).

[0063] Processors suitable for the execution of a computer program include, by way of example, both general and special purpose microprocessors, and any one or more processor of any kind of digital computer. Generally, a processor will receive instructions and data from a read only memory or a random access memory or both. The essential elements of a computer are a processor for executing instructions and one or more memory devices for storing instructions and data. Generally, a computer will also include, or be operatively coupled to receive data from or transfer data to, or both, one or more mass storage devices for storing data, e.g., magnetic, magneto optical disks, or optical disks. Information carriers suitable for embodying computer program instructions and data include all forms of non-volatile memory, including by way of example semiconductor memory devices, (e.g., EPROM, EEPROM, and flash memory devices); magnetic disks, (e.g., internal hard disks or removable disks); magneto optical disks; and optical disks (e.g., CD and DVD disks). The processor and the memory can be supplemented by, or incorporated in, special purpose logic circuitry.

[0064] To provide for interaction with a user, the subject matter described herein can be implemented on a computer having a display device, e.g., a CRT (cathode ray tube) or LCD (liquid crystal display) monitor, for displaying information to the user and a keyboard and a pointing device, (e.g., a mouse or a trackball), by which the user can provide input to the computer. Other kinds of devices can be used to provide for interaction with a user as well. For example, feedback provided to the user can be any form of sensory feedback, (e.g., visual feedback, auditory feedback, or tactile feedback), and input from the user can be received in any form, including acoustic, speech, or tactile input.

[0065] The techniques described herein can be implemented using one or more modules. As used herein, the term “module” refers to computing software, firmware, hardware, and/or various combinations thereof. At a minimum, however, modules are not to be interpreted as software that is not implemented on hardware, firmware, or recorded on a non-transitory processor readable recordable storage medium (i.e., modules are not software per se). Indeed “module” is to be interpreted to always include at least some physical, non-transitory hardware such as a part of a processor or computer. Two different modules can share the same physical hardware (e.g., two different modules can use the same processor and network interface). The modules described herein can be combined, integrated, separated, and/or duplicated to support various applications. Also, a function described herein as being performed at a particular module can be performed at one or more other modules and/or by one or more other devices instead of or in addition to the function performed at the particular module. Further, the modules can be implemented across multiple devices and/or other components local or remote to one another. Additionally, the modules can be moved from one device and added to another device, and/or can be included in both devices.

[0066] The subject matter described herein can be implemented in a computing system that includes a back end component (e.g., a data server), a middleware component (e.g., an application server), or a front end component (e.g., a client computer having a graphical user interface or a 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 can be interconnected by any form or medium of digital data communication, e.g., a communication network. Examples of communication networks include a local area network (“LAN”) and a wide area network (“WAN”), e.g., the Internet.

[0067] Approximating language, as used herein throughout the specification and claims, may be applied to modify any quantitative representation that could permissibly vary without resulting in a change in the basic function to which it is related. “Approximately,” “substantially,” or “about” can include numbers that fall within a range of 1%, or in some embodiments within a range of 5% of a number, or in some embodiments within a range of 10% of a number in either direction (greater than or less than the number) unless otherwise stated or otherwise evident from the context (except where such number would impermissibly exceed 100% of a possible value). Accordingly, a value modified by a term or terms, such as “about,” “approximately,” or “substantially,” are not to be limited to the precise value specified. In at least some instances, the approximating language may correspond to the precision of an instrument for measuring the value. Here and throughout the specification and claims, range limitations may be combined and/or interchanged, such ranges are identified and include all the sub-ranges contained therein unless context or language indicates otherwise.

[0068] The articles “a” and “an” as used herein in the specification and in the claims, unless clearly indicated to the contrary, should be understood to include the plural referents. Claims or descriptions that include “or” between one or more members of a group are considered satisfied if one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process unless indicated to the contrary or otherwise evident from the context. The disclosure includes embodiments in which exactly one member of the group is present in, employed in, or otherwise relevant to a given product or process. The disclosure also includes embodiments in which more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process. Furthermore, it is to be understood that the disclosed embodiments provide all variations, combinations, and permutations in which one or more limitations, elements, clauses, descriptive terms, etc., from one or more of the listed claims is introduced into another claim dependent on the same base claim (or, as relevant, any other claim) unless otherwise indicated or unless it would be evident to one of ordinary skill in the art that a contradiction or inconsistency would arise. It is contemplated that all embodiments described herein are applicable to all different aspects of the disclosed embodiments where appropriate. It is also contemplated that any of the embodiments or aspects can be freely combined with one or more other such embodiments or aspects whenever appropriate. Where elements are presented as lists, e.g., in Markush group or similar format, it is to be understood that each subgroup of the elements is also disclosed, and any element(s) can be removed from the group. It should be understood that, in general, where the disclosed embodiments, or aspects of the disclosed embodiments, is/are referred to as comprising particular elements, features, etc., certain embodiments of the disclosure or aspects of the disclosure consist, or consist essentially of, such elements, features, etc. For purposes of simplicity those embodiments have not in every case been specifically set forth in so many words herein. It should also be understood that any embodiment or aspect of the disclosure can be explicitly excluded from the claims, regardless of whether the specific exclusion is recited in the specification. For example, any one or more active agents, additives, ingredients, optional agents, types of organism, disorders, subjects, or combinations thereof, can be excluded.

[0069] Where ranges are given herein, embodiments of the disclosure include embodiments in which the endpoints are included, embodiments in which both endpoints are excluded, and embodiments in which one endpoint is included and the other is excluded. It should be assumed that both endpoints are included unless indicated otherwise. Furthermore, it is to be understood that unless otherwise indicated or otherwise evident from the context and understanding of one of ordinary skill in the art, values that are expressed as ranges can assume any specific value or subrange within the stated ranges in different embodiments of the disclosure, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise. It is also understood that where a series of numerical values is stated herein, the disclosure includes embodiments that relate analogously to any intervening value or range defined by any two values in the series, and that the lowest value may be taken as a minimum and the greatest value may be taken as a maximum. Numerical values, as used herein, include values expressed as percentages.

[0070] It should be understood that, unless clearly indicated to the contrary, in any methods claimed herein that include more than one act, the order of the acts of the method is not necessarily limited to the order in which the acts of the method are recited, but the disclosure includes embodiments in which the order is so limited. It should also be understood that unless otherwise indicated or evident from the context, any product or composition described herein may be considered “isolated”.

[0071] As used herein the term "comprising" or "comprises" is used in reference to compositions, methods, and respective component(s) thereof, that are essential to the disclosed embodiments, yet open to the inclusion of unspecified elements, whether essential or not. [0072] As used herein the term "consisting essentially of refers to those elements required for a given embodiment. The term permits the presence of additional elements that do not materially affect the basic and novel or functional characteristic(s) of that embodiment of the disclosure.

[0073] The term "consisting of refers to compositions, methods, and respective components thereof as described herein, which are exclusive of any element not recited in that description of the embodiment.

[0074] Although a few variations have been described in detail above, other modifications or additions are possible.

[0075] In the descriptions above and in the claims, phrases such as “at least one of’ or “one or more of’ may occur followed by a conjunctive list of elements or features. The term “and/or” may also occur in a list of two or more elements or features. Unless otherwise implicitly or explicitly contradicted by the context in which it is used, such a phrase is intended to mean any of the listed elements or features individually or any of the recited elements or features in combination with any of the other recited elements or features. For example, the phrases “at least one of A and B;” “one or more of A and B;” and “A and/or B” are each intended to mean “A alone, B alone, or A and B together.” A similar interpretation is also intended for lists including three or more items. For example, the phrases “at least one of A, B, and C;” “one or more of A, B, and C;” and “A, B, and/or C” are each intended to mean “A alone, B alone, C alone, A and B together, A and C together, B and C together, or A and B and C together.” In addition, use of the term “based on,” above and in the claims is intended to mean, “based at least in part on,” such that an unrecited feature or element is also permissible.

[0076] The subject matter described herein can be embodied in systems, apparatus, methods, and/or articles depending on the desired configuration. The implementations set forth 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. Although a few variations have been described in detail above, other modifications or additions are possible. In particular, further features and/or variations can be provided in addition to those set forth herein. For example, the implementations described above can be directed to various combinations and sub-combinations of the disclosed features and/or combinations and sub-combinations of several further features disclosed above. In addition, the logic flows depicted in the accompanying figures and/or described herein do not necessarily require the particular order shown, or sequential order, to achieve desirable results. Other implementations may be within the scope of the following claims.

Claims

What is claimed is:

1. A system comprising: a laser source configured to generate a laser beam having a transverse ring mode; an optical element configured to converge the laser beam and direct the laser beam toward a tissue, the optical element having an aperture; a first optical arrangement configured to direct the laser beam towards the optical element, such that the transverse ring mode of the laser beam circumscribes the aperture of the optical element; a second optical arrangement configured to collect light from the tissue through the aperture of the optical element; and, a sensor configured to sense the light from the tissue and transmitted by the second optical arrangement.

2. The system of claim 1, wherein the laser source further comprises a beam shaper configured to shape the laser beam;

3. The system of claim 1, wherein the optical element comprises at least one of a converging lens and an axicon.

4. The system of claim 1, wherein the optical element has a first optical axis; and the second optical arrangement has a second optical axis that is substantially coaxial with the first optical axis.

5. The system of claim 4, further comprising: a beam splitter, disposed along the first optical axis and configured to separate the laser beam and the light from the tissue.

6. The system of claim 1, further comprising: a third optical arrangement configured to accept the light from the tissue and form an image of the tissue directed at the sensor.

7. The system of claim 6, wherein the sensor comprises at least one of a charge coupled device (CCD) sensor and a capacitive metal-oxide semiconductor (CMOS) sensor.

8. The system of claim 1, wherein the second optical arrangement comprises at least one of a lens assembly and an endoscope.

9. The system of claim 1, further comprising: an illumination system configured to direct an illuminating light toward the tissue.

10. A method comprising: generating, using a laser source, a laser beam having a transverse ring mode; directing, using a first optical arrangement, the laser beam towards an optical element having an aperture, such that the transverse ring mode circumscribes the aperture; converging, using the optical element, the laser beam; directing, using the optical element, the laser beam toward a tissue; collecting, using a second optical arrangement, light from the tissue through the aperture of the optical element; and, sensing, using a sensor, the light from the tissue.

11. The method of claim 10, wherein generating the laser beam having the transverse ring mode further comprises: shaping, using a beam shaper, the laser beam.

12. The method of claim 10, wherein the optical element comprises at least one of a converging lens and an axicon.

13. The method of claim 10, wherein the optical element has a first optical axis; and the second optical arrangement has a second optical axis that is substantially coaxial with the first optical axis.

14. The method of claim 13, further comprising: separating, using a beam splitter, the laser beam and the light from tissue.

15. The method of claim 10, further comprising: accepting, using a third optical arrangement, the light from the tissue; and forming, using the third optical arrangement, an image of the tissue incident the sensor.

16. The method of claim 15, wherein the sensor comprises at least one of a charge coupled device (CCD) and a capacitive metal-oxide semiconductor (CMOS).

17. The method of claim 10, wherein the second optical arrangement comprises at least one of a lens assembly and an endoscope.

18. The method of claim 10, further comprising: directing, using an illumination system, an illuminating light toward the tissue.