Feedback detection for therapy devices

Abstract

To provide an EMR base system effectively treating pigmentation of the skin.SOLUTION: A system includes a focus optic system configured to converge an electromagnetic radiation (EMR) beam to a focal region located along an optical axis. The system also includes a detector configured to detect a signal radiation emanating from a predetermined location along the optical axis. The system additionally includes a controller configured to adjust a parameter of the EMR beam based in part on the signal radiation detected by the detector. The system also includes a window located a predetermined depth away from the focal region between the focal region and the focus optic system along the optical axis, wherein the window is configured to make contact with a surface of a tissue.SELECTED DRAWING: Figure 5

Description

[Technical field]

[0001] [CROSS REFERENCE TO RELATED APPLICATIONS] This application is a joint venture of "Pigment Detection for Treatment Devices" filed on June 22, 2018. Detection for a Therapeutic Device) No. 62 / 688,940, filed June 22, 2018, entitled “E Diffractive Optics for MR-Based Tissue Treatment The present application is filed in the United States Provisional Patent Application No. 2010 / 023666 entitled "EmrEMR-Based Tissue Treatment." No. 62 / 688,913, filed June 22, 2018, entitled "Selective Tissue Treatment Device for the Treatment of Tissues" Selective Plasma Generation for T The benefit of U.S. Provisional Application No. 62 / 688,855, entitled "International Patent Application No. 62 / 688,855 (International Patent Application No. 62 / 688,855)" is hereby incorporated by reference in its entirety. No. 6,399,423, filed on Oct. 23, 2007. Each of these applications is incorporated by reference in its entirety. [Background technology]

[0002] Chloasma or chloasma (melasma of pregnancy) is an irregular, poorly-circumscribed patch of yellow-brown to deep gray-brown color on the face. A common skin condition characterized by sharp spots and patches The spots are caused by the formation of keratinocytes (epidermal melanosis )) or penetrates the dermis (dermal melanosis, melanoma) It is believed that the cause is the overproduction of melanin that is deposited in melanophages. Melasma pigmentation may be caused by pregnancy, sun exposure, certain medications (e.g., oral contraceptives), It can be further exacerbated by several conditions, including hormone levels and genetic factors. The condition can be classified as epidermal, dermal, or mixed, depending on the location of the excess melanin. Typical symptoms of melasma include dark, blemished areas that are mainly found on the upper cheeks, nose, upper lip, and forehead. It includes irregularly shaped spots or blotches. These spots gradually develop over time. appears.

[0003] Melasma can cause considerable embarrassment and distress, especially in dark-skinned women. This is a particular problem for up to 30% of women in Southeast Asia and many women in Latin America. Affects both sexes. Population studies have shown that between 1 in 4 and 1 in 20 affected individuals are male. According to the American Academy of Dermatology, approximately six million women in the United States deal with melasma. Globally, the number of people affected by melasma is estimated at 157 million in the Asia / Pacific region and 100 million in the Latin America region. Melasma is generally diagnosed in people between the ages of 20 and 30. It appears between the ages of 40 and 50. There is no cure for melasma, so the number of people in the U.S. who are being treated for melasma is increasing. Patients are currently trying a variety of different treatments: 79% of patients in the United States use topical medications, 37% use oral treatments, and 25% use lasers.

[0004] Unlike other pigmented structures normally present in the epidermal region of the skin (i.e., at or near the tissue surface), Dermal (or deep) melasma is often caused by the accumulation of melanin and melanophages in parts of the lower dermis. It is characterized by being widespread. Therefore, it is important to treat dermal melasma (e.g., dark pigmented areas). The lightening of the appearance of pigmented areas is due to the loss of such pigmented cells and structures located deeper within the skin. This can be particularly challenging as the structure is very difficult to access and influence. It mainly affects the upper epidermis (often the first stage of melasma treatment) Conventional skin rejuvenation treatments such as lasers (or chemicals), dermabrasion, topical agents, etc. It may not be effective in treating dermal melasma.

[0005] Additionally, up to 50% of melasma sufferers also experience other hyperpigmentation problems. Among the deposition conditions, melasma is the disease that most patients are likely to visit a dermatologist. Given the incomplete understanding of the causes, chronicity, and recurrence rate, management of this disorder remains It is difficult. Melasma may come back after treatment, often worse than before treatment. And topical treatments that may be effective in treating epidermal melasma may not be effective in treating dermal or mixed melasma. It is not possible to treat. Summary of the Invention [Means for solving the problem]

[0006] The application of light or light energy of specific wavelengths stimulates pigmented cells. It has been observed that the cellulose is strongly absorbed by the cellulose membranes (Cu, Cu ... However, the effective treatment of dermal melasma using light energy presents several obstacles. For example, pigmented cells in the dermis receive enough light energy of the appropriate wavelength to destroy or damage the cells. The targeting of the globules is essential, as this is part of the pigmentation process. However, such energy can damage the epidermis and It can be absorbed by pigments (e.g., chromophores) in overlying skin tissues, such as the upper dermis. Such superficial absorption can lead to excessive damage to the outer portion of the skin and ultimately to the deeper dermis. In addition, the energy transfer to the pigmented cells in the epidermis is insufficient. Moderate thermal damage to melanin-containing melanocytes located in the stratum basale leads to melanin production. may induce increased growth (e.g. hyperpigmentation) and have serious adverse effects on melanocytes. Severe thermal damage can induce a decrease in melanin production (e.g., hypopigmentation).

[0007] Pigmentary Disorders Academy (P The DA conducted a study to evaluate the clinical effectiveness of various types of melasma treatments to reach a consensus on treatment. Their efforts were published in a paper entitled "Treatment of Melasma" by M. Rendon et al. , published in the Journal of the American Academy of Dermatology in May 2006. We reviewed the literature on melasma treatment and based our decision on that review. reported that the first-line treatment for melasma is mainly a fixed triple combination. The consensus of the group is that treatment should consist of effective local therapy. "Lasers are rarely used to treat melasma, and when they are used, it depends on the skin type. must be taken into consideration."

[0008] A critique of Rendon et al.'s comprehensive report on melasma treatment was published in 2006. This may be the date of the recent publication of the article by M. Sadeghpour et al. The article was published in Advances in Cosmetic Surgery in 2018 under the title "Advances in the Treatment of Melasma." Sadeghpour et al. also argue that "local therapy is not a global treatment." Spectrum UV blocker and hydroquinone 4% cream, tretinoin, or triphosphatidylserine First-line treatment for melasma using either Gold or combination cream "These remain the standard," they concluded. The destruction of melanosomes is often accompanied by severe inflammation, which further stimulates melanogenesis. He pointed out that treating dermal melasma is even more difficult because the condition worsens due to the inflammation.

[0009] Therefore, it is possible to more effectively treat melasma and other difficult to treat pigment disorders. There is a large unmet need for effective and safe treatments.

[0010] Small, discrete treatment areas on the skin separated by healthy tissue to promote healing An approach to applying light energy has been developed. while avoiding damage to the surrounding healthy tissue (dermal layer). High specificity allows accurate targeting of treatment locations (e.g., dermal layer locations) This can be difficult, for example, to focus the laser beam on the treatment location. A high numerical aperture (NA) optical system is required to achieve this. The goal is to achieve a high enough focal fluence in the dermis while maintaining a low enough out-of-focus fluence in the epidermis. "Method and apparatus for treating dermal melasma" The U.S. Patent Application Publication No. 2016 / 0199132, entitled "Melasma Treatment for Liver Disease," describes how the technology can be used to treat melasma in a laboratory setting. The results have shown that nicotine is beneficial in treating skin pigmentation including psoriasis, ... and rheumatoid arthritis.

[0011] However, this technique is limited in that the focal region formed by the high NA optical system is not visible within the target tissue. The depth of the Laninocytes are generally located at a depth of about 100 μm within the basal layer of the epidermis. Dermal melanophages, which are responsible for the formation of melanocytes, are present in the upper dermis just below the basal layer of the epidermis (e.g., 50 μm below). Therefore, the difference in depth of the focal region of several tens of micrometers may be Effectively treating hyperpigmentation and preventing inadvertent damage and potentially debilitating melanocytes This could make the difference between inducing a desired cosmetic outcome (e.g., hyperpigmentation). For these reasons, the EMR core system that effectively treats skin pigmentation is also It is not commercially available.

[0012] Therefore, within a tolerance of several tens of micrometers (for example, about ±100 μm, about ±10 μm, about EMR-based treatment systems that reliably position the focal region at a given depth (e.g. ±1 μm) It is desirable to develop an EMR-based treatment system that can measure the depth of a known By periodically placing the focal region on a reference having a It may be desirable to achieve this performance in a timely manner. Also, it may be desirable to have the reference used during calibration be a therapeutic For example, a reference may be used to ensure strong contact with the treatment area. It can include an interface that establishes and stabilizes the treatment area.

[0013] Some methods for skin pigmentation treatments, such as those reviewed by Anderson et al. The developed approach involves the use of selective thermionic plasma generation as a means of treatment. In this case, the laser fluence at the focal region in the dermis is greater than the thermionic plasma threshold (e.g. For example, 10 9 W / cm 2 ), but not below the optical breakdown threshold (e.g., 10 12 W / cm 2 ) This is because, when located in pigmented tissue (e.g., melanin) within the dermis, the focal area Selectively, without plasma generation in non-pigmented tissue in the dermis or in pigmented epidermal tissue over focal areas The selectively formed thermoelectron plasma destroys the pigment and surrounding tissue. This destruction ultimately removes the dermal pigment. The presence of plasma during intravascular treatment may indicate effective treatment in some embodiments. Parameter selection for laser-based skin treatments often depends on skin type and can vary from individual to individual. As each patient is different, the presence of plasma is an indication that the correct treatment parameters have been achieved. Such feedback is therefore generally used in laser beam In populations where primary treatments do not work as well as primary steroids (e.g., those with darker skin types), This is desirable for successful treatment of conditions such as plaques.

[0014] Alternatively, in some cases, the detected plasma properties may indicate that the treatment has side effects. For example, in some embodiments, the transmissive window may be indicative of the skin. As a treatment aid, it is placed on the skin to be treated to prevent the skin from moving during treatment. If the laser beam etches the window, the treatment may fail. This prevents the laser from being delivered more efficiently to the tissue, and coincides with the formation of a very bright plasma in the window itself. If treatment continues with an etched window, the heat buildup in the window will be absorbed by the skin. May cause damage to the epidermis (e.g. burns and blisters). Therefore, feedback It is possible to detect plasma formation in the window and stop treatment when it occurs using It is beneficial.

[0015] From the above, plasma formation during treatment can be beneficial or detrimental to the treatment. It can be appreciated that the system and method for providing plasma detection may include The plasma characteristics are detected and the plasma that is beneficial for tissue treatment and the plasma that is harmful for tissue treatment are detected in real time. It can be divided into two categories:

[0016] In some embodiments, the tissue to be treated is imaged in terms of the treatment device to provide a view for the physician. It may be desirable to project this view onto a screen so that In one aspect, the placement of treatment devices typically blocks the physician's view of the tissue being treated. Thus, tissue imaging facilitates precise placement of therapeutic devices to target diseased tissue. In addition, the goal of treating many pigmentation conditions is cosmetic (e.g., improving skin appearance). Therefore, it is possible to obtain a skin image under repeatable imaging conditions (e.g., illumination and distance) during imaging. Images can be acquired continuously and the results of the treatment confirmed.

[0017] People who suffer from pigmentation conditions such as melasma are seeing widespread availability of EMR-based treatments for their condition. It has been our hope for a long time that the In addition, the EMR-based treatment system provides repeatable depth location of the focal region within the target tissue. The disclosed systems and methods also provide for documenting the safety and efficacy of treatments. To image the treated tissue and deliver EMR precisely to the treatment area, It is possible to detect and record plasma events. Such a feature is compatible with the current skin pigmentation. Successful treatment of a wide range of skin conditions that are difficult to treat with EMR-based systems, including psoriasis, ... and other skin conditions. This will solve many of the technical problems that currently prevent treatment from being completed.

[0018] In one embodiment, a system is provided, the system including a focus optics The focusing optics may include a focusing optical system, a detector, a controller, and a window. The electromagnetic radiation (EMR) beam may be configured to focus to a focal region disposed along the optical axis. The detector may be configured to detect signal radiation emanating from a predetermined position along the optical axis. The controller may generate EMR images based in part on the signal emissions detected by the detector. The window may be configured to adjust parameters of the focal region and the focal point along the optical axis. The window may be disposed at a predetermined depth away from the focal region between the optical system and the tissue surface. The control unit 10 may be configured to:

[0019] In another embodiment, the EMR beam is configured to generate a plasma at a predetermined location along the optical axis. The signal radiation may be emitted from the plasma.

[0020] In other embodiments, the signal radiation may originate from an interaction between the EMR beam and a window. can.

[0021] In another embodiment, the focusing optics is adapted to image the signal radiation detected by the detector. It may be further configured as follows.

[0022] In another embodiment, the system detects a focal region from a first region in the tissue to a second region in the tissue. The imaging system may further comprise a scanner configured to scan the imaging system.

[0023] In another embodiment, the EMR beam is further adapted to generate a thermionic plasma at the focal region. It may be configured as follows.

[0024] In other embodiments, the window may be further configured to transmit the EMR beam. In an embodiment, the focusing optics focuses the EMR beam to a numerical aperture (NA) of at least 0.3. The device may be further configured to:

[0025] In other embodiments, the parameters of the EMR beam include pulse energy, repetition rate, pulse At least one of the following: duration of the laser, position of the focal region, size of the focal region, wavelength, or power. It may include one.

[0026] In other embodiments, the signal radiation may be visible light, infrared light, an acoustic signal, an ultrasonic signal, a radio signal, or temperature.

[0027] In one embodiment, a method is provided that includes contacting a tissue surface using a window. The method may also include the step of: detecting electromagnetic radiation (EMR) using a focusing optical system. ) focusing the beam to a focal region disposed along the optical axis. The method includes the steps of detecting signal radiation emanating from positions along an optical axis using a detector. The method can further include using the controller to detect the detected signal emission. The method may further include adjusting parameters of the EMR beam based in part on the projection. The method also includes the step of positioning a focal region within the tissue at a predetermined distance from a tissue surface. It may include a group.

[0028] In another embodiment, the method includes using an EMR beam to generate a plasma at a location along the optical axis. The signal radiation may be emitted from the plasma. Cut.

[0029] In another embodiment, the method further comprises the step of directing a focused EMR beam incident on a window. The signal radiation may further include emanating from an interaction between the EMR beam and the window. can be done.

[0030] In another embodiment, the method further comprises using focusing optics to image the signal radiation incident on the detector. The method further includes the step of:

[0031] In another embodiment, the method includes using a scanner to measure from a first region in the tissue to a second region in the tissue. Further comprising the step of scanning the focal area to the area.

[0032] In another embodiment, the method includes using an EMR beam to generate a thermionic plasma at a focal region. The method further includes the step of generating a

[0033] In another embodiment, the method further comprises transmitting the EMR beam through a window. .

[0034] In another embodiment, the focusing optics focuses the EMR beam at a numerical aperture (NA) of at least 0.3. The optical fiber is further configured to focus the optical fiber.

[0035] In other embodiments, the parameters of the EMR beam include pulse energy, repetition rate, pulse At least one of the following: duration of the laser, position of the focal region, size of the focal region, wavelength, or power. It may include one.

[0036] In other embodiments, the signal radiation may be visible light, infrared light, an acoustic signal, an ultrasonic signal, a radio signal, or temperature.

[0037] In one embodiment, a system is provided, the system comprising: focusing optics, a window, an optical detector, The focusing optics may include an electromagnetic radiation (EMR) beam splitter, a controller, and a stage. The window may be configured to focus the beam to a focal region located along the optical axis. The optical detector may be configured to intersect with the EM The control unit may be configured to detect signal radiation emanating from the interaction of the R beam with the window. The scanner is configured to determine a reference position where a portion of the focal region substantially coincides with a surface of the window. The stage may translate the focal region to a treatment position located at a predetermined distance from the reference position. The control unit 10 may be configured to:

[0038] In another embodiment, the focusing optics and stage are configured to position the treatment location within the tissue. It may be possible to do so.

[0039] In other embodiments, the treatment location may be located within the dermal tissue.

[0040] In another embodiment, the EMR beam is configured to generate a thermionic plasma at a focal region. You may do so.

[0041] In another embodiment, the EMR beam is a pulse having a pulse duration of at least 1 picosecond. It may include luz.

[0042] In another embodiment, the focusing optics is further adapted to image the signal radiation incident on the detector. It may be configured as follows.

[0043] In another embodiment, the controller detects EMR beams incident on the surface of the window based on the signal radiation. by determining the width of the frame and translating the focal region until the width has a minimum value. , may be further configured to determine a reference position.

[0044] In other embodiments, the detector may be further configured to detect an intensity of the signal radiation. The controller causes the focal region to be transformed until the intensity of the signal radiation has a maximum value. The reference position may be determined by:

[0045] In another embodiment, the focusing optics is adapted to focus the second EMR beam to a second focal region. The second EMR beam may be of the same wavelength as the EMR beam or of the same wavelength as the EMR beam. The second EMR beam may have at least one of a wavelength different from the wavelength of the R beam. may be configured to effect a desired change in the tissue.

[0046] In other embodiments, the stage includes at least one of the focusing optics, the one or more optical elements, and the window. It may be configured to transform the focal region by transforming at least one of the focal regions.

[0047] In one embodiment, focusing optics are used to align the electromagnetic radiation (EMR) beam along an optical axis. The method also includes the step of detecting the light emitted from the target object by focusing the light onto a focal region located at the target object. The detector detects signal radiation emanating from the interaction of the EMR beam with a window crossing the optical axis. The method may include the steps of: using a controller to determine whether a signal is emitted from a detected source; The method may further include determining a reference position along the optical axis based on the reference position. In the embodiment, a portion of the focal region may substantially coincide with a surface of the window. to a treatment position located a predetermined distance away.

[0048] In another embodiment, the method includes assembling the tissue using a window so that a treatment site can be placed within the tissue. The method may further include contacting the woven surface.

[0049] In other embodiments, the predetermined distance may be configured to identify a treatment location within the dermal tissue. good.

[0050] In another embodiment, the EMR beam is configured to generate a thermionic plasma at a focal region. You may do so.

[0051] In another embodiment, the EMR beam is a pulse having a pulse duration of at least 1 picosecond. It may include luz.

[0052] In another embodiment, the step of detecting the signal radiation includes using focusing optics to focus the signal radiation onto the detector. The method may further include imaging the incident signal radiation.

[0053] In another embodiment, the step of determining the reference position comprises controlling the control based on the signal emission. determining a lateral width of the EMR beam incident on the surface of the window using a laser; The method may further include translating the focal region along the optical axis until the focal region has a minimum value. Cut.

[0054] In another embodiment, the step of determining the reference position comprises measuring the intensity of the signal radiation using a detector. and translating the focal region until the intensity of the signal radiation is at a maximum value. The steps may include:

[0055] In another embodiment, the method further comprises using focusing optics to focus the second EMR beam at a second focal region. The step of focusing the second EMR beam may further include focusing the second EMR beam. The wavelength of the EMR beam is at least one of the same wavelength as the wavelength of the EMR beam or different wavelength from the wavelength of the EMR beam. The second EMR beam may be configured to produce a desired change in the tissue.

[0056] In other embodiments, the step of transforming the focal region includes focusing optics, one or more optical elements The method may further include transforming at least one of the child and the window.

[0057] In one embodiment, a system is provided, comprising: a radiation source; a window; focusing optics; a scanner; and a detector. The radiation source may include a control circuit for controlling the radiation source to produce a desired change in tissue. The window may be configured to generate therapeutic radiation configured to contact the tissue surface. The focusing optics may be configured to generate a plasma at a focal region. The scanner can be configured to focus the therapeutic radiation at a point region. The detector may be configured to detect signal radiation emanating from the plasma. The controller may be configured to determine whether the plasma is present within the window based on the detected signal radiation. determining whether one or more of the therapeutic radiation beams are located at least in part on the target tissue; The parameter may be configured to be controlled.

[0058] In another embodiment, the controller is further configured to determine one or more characteristics of the plasma. In other embodiments, the one or more characteristics of the plasma may be determined by determining whether the plasma exists, At least one of the intensity of the plasma, the spectral content of the plasma, and the position of the plasma. In another embodiment, the controller may include determining whether to irradiate the therapeutic radiation based on the determination. It may further be configured to terminate the line.

[0059] In other embodiments, one or more parameters of the therapeutic radiation include energy per pulse. , a repetition rate, a position of the focal region, and a size of the focal region. In another embodiment, the desired change in tissue is induced by selective thermoelectric conversion in the presence of a chromophore. In another embodiment, the controller may include controlling the generation of a daughter plasma. It may further be configured to record the characteristics.

[0060] In another embodiment, the controller detects a first signal radiation emanating from the first plasma at the first location. and mapping the first characteristic to coordinates relative to the first location to generate a second signal. The apparatus may be further configured to record a second characteristic of the second plasma emanating from the second plasma at the second location. A signal emission is generated to map the second property to coordinates of the second location.

[0061] In another embodiment, the controller determines whether the plasma is at least partially present in the window based on the intensity of the signal emission. The device may be further configured to determine whether the at least partially located

[0062] In another embodiment, the controller controls the plasma The sensor may be further configured to determine whether the sensor is at least partially located within the window. Cut.

[0063] In one embodiment, a method is provided. The method includes using a radiation source to induce a desired change in tissue. The method may further include generating therapeutic radiation configured to provide The method may also include contacting the tissue surface using a window. The method may further include focusing the therapeutic radiation to a focal region using a The method may further include scanning the focal region with a scanner. The method may further include generating a plasma at the focal region using the radiation. Also, the method can include detecting signal radiation emanating from the plasma using a detector. The method may further comprise determining that the plasma is at least partially located within the window based on the detected signal emissions. The method may further include determining, using a controller, whether to The method includes using a controller to control one or more parameters of the therapeutic radiation based on the determination. The method may further include controlling the

[0064] In another embodiment, the method includes using a controller to determine one or more characteristics of the plasma. The method may further include the step of determining

[0065] In other embodiments, the one or more characteristics of the plasma include the presence of the plasma, the intensity of the plasma, and at least one of: a spectral content of the plasma; and a position of the plasma. can.

[0066] In another embodiment, the method includes using the controller to terminate the therapeutic radiation based on the determination. The method may further include the step of completing the process.

[0067] In other embodiments, one or more parameters of the therapeutic radiation include energy per pulse. , a repetition rate, a position of the focal region, and a size of the focal region. can be done.

[0068] In yet another embodiment, the desired change in tissue is achieved by selective thermoelectric plasma irradiation in the presence of a chromophore. It is also possible that a .ma. may be generated.

[0069] In another embodiment, the method includes using the controller to record a characteristic of the signal emission. It can include.

[0070] In another embodiment, the method further comprises using the controller to generate a first plasma at the first location. recording a first characteristic of a first signal radiation emanating from the first position in coordinates relative to the first location; Mapping the characteristic from the second plasma at the second location using the data acquisition device. and recording a second characteristic of the second signal radiation emanating from the second location and mapping the second characteristic to coordinates of the second location. In another embodiment, the plasma may further include detecting a plasma in the window. The step of determining whether the signal radiation is located partially on the substrate may be based on the intensity of the signal radiation. .

[0071] In another embodiment, determining whether the plasma is at least partially located within the window The steps may be based on the spectral content of the signal radiation.

[0072] In one embodiment, a system is provided, comprising a radiation source, focusing optics, a detector, and a therapeutic radiation source. The radiation source may be configured to irradiate tissue with imaging radiation. The focusing optics may be configured to image a field of view of the tissue. The therapeutic radiation may be focused into an image using focusing optics. and configuring the imaging system to focus on a focal region within a designated target treatment region based in part on the focal region. can be done.

[0073] The system further includes a scanner configured to scan the field of view to a second region of the tissue. The focusing optics can be adapted to image a second image of the field of view from a second region of the tissue. The detector may be further configured to detect a second image. In other embodiments, the scanner is further configured to scan a focal region within the target treatment region. It may be possible to do so.

[0074] In another embodiment, the system is configured to insert the image and the second image into the map. The map may further include a controller for determining whether a diagnostic, treatment planning, and treatment radiation are performed. The method may be configured to be used to determine at least one of the treatment parameters of do.

[0075] In another embodiment, the system may be configured to position the focal region at a predetermined depth from the tissue surface. In another embodiment, the tissue surface may further include a window configured to contact the tissue surface. The system may further include a controller configured to record the image. In another embodiment, the system controls parameters of the therapeutic radiation based in part on the image. The device may further include a controller configured to control the

[0076] In another embodiment, the therapeutic radiation selectively generates a plasma with chromophores proximate to the focal region. The present invention may be configured to achieve the above.

[0077] In other embodiments, the focusing optics is suitable for microscopic imaging, wide-field imaging, and reflective confocal imaging. and further configured to image a first image using at least one of the imaging modes S. good.

[0078] In another embodiment, the system further comprises a display configured to display the image. may be included in the

[0079] In one embodiment, a method is provided. The method includes: The method may also include illuminating the tissue using focusing optics. The method may include imaging an image of the field using a detector. The method may further include determining a target for tissue based in part on the image. The method may include the step of designating a target treatment area using focusing optics. The method can further include focusing the therapeutic radiation to a focal region within the target treatment region.

[0080] In another embodiment, the method includes scanning a field of view for a second region of tissue using a scanner. imaging a second image of the field of view at a second region of the tissue using focusing optics. The method may further include detecting the second image using the amplifier and the detector.

[0081] In another embodiment, the method includes scanning a focal region within the target treatment region using a scanner. The method may further include steps.

[0082] In another embodiment, the method further comprises inserting the image and the second image together into the map. can be included in.

[0083] In another embodiment, the method further comprises: determining the diagnosis, treatment planning, and treatment parameters of the therapeutic radiation; The method may further include determining at least one of from a map.

[0084] In another embodiment, the method further comprises: forming a window such that the focal region is located at a predetermined depth from the tissue surface. The method may further include contacting the tissue surface using a

[0085] In another embodiment, the method further comprises recording the image using the controller. It can include.

[0086] In another embodiment, the method includes using the controller to determine a therapy release based in part on the image. The method may further include controlling a parameter of the ray.

[0087] In another embodiment, the therapeutic radiation selectively generates a plasma with chromophores proximate to the focal region. The present invention may be configured to achieve the above.

[0088] In other embodiments, imaging the first image includes microscopic imaging, wide-field imaging, or reflectance confocal imaging.

[0089] In another embodiment, the method further comprises displaying the image using a display. It can include.

[0090] Embodiments of the present disclosure will be more fully understood from the following detailed description taken in conjunction with the accompanying drawings, in which: It will be. [Brief description of the drawings]

[0091] [Figure 1] 1 illustrates an exemplary embodiment of a treatment system, according to some embodiments. [Diagram 2] 1 is a schematic diagram of an electromagnetic radiation (EMR) beam focused on a pigmented region of the dermis layer of the skin. [Figure 3A] 1 is a graph of an exemplary absorbance spectrum of melanin. [Figure 3B] 1 is a graph of an exemplary absorbance spectrum of hemoglobin. [Figure 4] 1 shows a plot of the absorption coefficient of melanin and venous blood, and the scattering coefficient of light in skin versus wavelength. [Diagram 5]1 is a schematic diagram of a treatment system, according to some embodiments. [Figure 6] 1 is a schematic diagram of an optical system according to some embodiments. [Figure 7] FIG. 1 is a schematic diagram of an optical system with a microscope attachment, according to some embodiments. [Figure 8] 1 is a schematic diagram of an optical system having a fiber coupler attachment according to some embodiments. [Figure 9] 1 shows a flowchart of a method for plasma detection according to some embodiments. [Figure 10] 1 shows a schematic diagram of a plasma detection system according to some embodiments. [Figure 11A] 1 is a schematic diagram of a therapeutic optical system, according to some embodiments. [Figure 11B] 1 shows a histology image of a section of a skin sample bearing a melanin tattoo. [Figure 12] 1 shows spectra associated with radiation from a plasma generated in a melanin tattoo and non-plasma generated on bare skin, according to some embodiments. [Figure 13] 1 shows spectra associated with plasma generated radiation on a carbon tattoo and non-plasma generated radiation on bare skin, according to some embodiments. [Figure 14] 1 shows a spectrum of radiation generated by a plasma in a skin sample according to some embodiments. [Figure 15] 1 shows an emission spectrum from a plasma formed using a sapphire window, according to some embodiments. [Figure 16A] 1 shows a front view of an exemplary version of a plasma detection system according to some embodiments. [Figure 16B] 1 illustrates a cross-sectional view of an exemplary version of a plasma detection system according to some embodiments. [Figure 16C] 1 shows a detailed view of an exemplary version of a plasma detection system according to some embodiments. [Figure 17] 1 illustrates a flowchart for window referencing, according to some embodiments. [Figure 18A] 1 shows a schematic diagram of a window referencing system according to some embodiments. [Figure 18B] 1 illustrates the performance of a windowed reference system, according to some embodiments. [Figure 19] 1 illustrates an exemplary bench prototype for confocal imaging, according to some embodiments. [Figure 20] 1 illustrates maximum radiation intensity measurement according to some embodiments. [Figure 21A] 1 illustrates a front view of an exemplary version of a treatment system without a removable window reference system attached, according to some embodiments. [Figure 21B] 1 illustrates a front view of an exemplary version of a treatment system with a removable window reference system attached, according to some embodiments. [Figure 21C] 1 illustrates a cross-sectional view of an exemplary version of a treatment system fitted with a removable window reference system, according to some embodiments. [Figure 22A] 1 illustrates a front view of an exemplary version of a treatment system without a window referencing system attached, according to some embodiments. [Figure 22B] 1 illustrates a front view of an exemplary version of a treatment system with a window referencing system attached, according to some embodiments. [Figure 22C] 1 illustrates a cross-sectional view of an exemplary version of a treatment system equipped with a window referencing system, according to some embodiments. [Figure 23] 1 shows a flowchart of an imaging and radiation-based therapy method, according to some embodiments. [Figure 24] 1 shows a schematic diagram of an imaging and radiation-based therapy system, according to some embodiments. [Diagram 25] 1A-1C are schematic diagrams illustrating inset images according to some embodiments. [Figure 26A]FIG. 1 illustrates a front view of an exemplary version of an imaging and radiation-based therapy system, according to some embodiments. [Figure 26B] 1 illustrates an exemplary version of an imaging and radiation-based therapy system, according to some embodiments. [Figure 27A] 1 illustrates a black and white image taken using an exemplary version of an imaging and radiation-based therapy system, according to some embodiments. [Figure 27B] 1 illustrates an inset black and white image including multiple images taken using an exemplary version of an imaging and radiation-based therapy system, according to some embodiments. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0092] Please note that the drawings are not necessarily to scale. These and other aspects are intended to depict only exemplary aspects of the disclosed subject matter and are therefore not intended to limit the scope of the present disclosure. The present invention should not be construed as being limited to the above-mentioned embodiments as specifically described herein and shown in the accompanying drawings. The systems, devices and methods are non-limiting example embodiments.

[0093] A general understanding of the principles of structure, function, manufacture, and use of the devices and methods disclosed herein To provide a solution, certain exemplary embodiments are described herein. One or more examples are illustrated in the accompanying drawings. Those skilled in the art will understand the principles of the present invention as specifically described herein and in the accompanying drawings. The apparatus and methods illustrated in the accompanying drawings are non-limiting exemplary embodiments and are within the scope of the present invention. It will be understood that the scope of the present invention is defined solely by the claims. The features illustrated or described in the context 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.

[0094] An embodiment of the present invention is directed to treating such pigmentary conditions. ion) to improve the appearance of skin pigmentation conditions such as melasma. However, the disclosed embodiments may be used to treat other pigmented and non-pigmented conditions. , as well as other tissue and non-tissue targets, without limitation. Examples of hyperpigmentation include darkening around the eyes. Skin, black eyes, cafe au lait patches, Becker Becker's nevi, Nevus of Ota, congenital congenital melanocytic nevi, melanocytic nevi (ephelides) (freckles) and lentigo The pigmented tissues that can be treated include, but are not limited to, Additional examples of structures include hemosiderin-rich structures, pigment gallstones, tattoo-containing tissues, and Lutein, zeaxanthin, rhodopsin, carotenoids, biliverdin, bilirubin, and hemoglobin-rich structures. Non-pigmented structures, tissues and Examples of targets for the treatment of acne conditions include hair follicles, hair shafts, vascular lesions, infectious conditions, sebaceous glands, acne These may include, but are not limited to:

[0095] Methods for treating various skin conditions for cosmetic purposes include using the systems described herein. Such a method may be performed by a physician, but may also be performed by a beautician and Non-physicians, such as other appropriately trained personnel, may, with or without medical supervision, treat a variety of skin conditions. It will be appreciated that the systems described herein can be used to treat various conditions.

[0096] Furthermore, in this disclosure, like-named components of the embodiments generally have similar characteristics, Within a particular embodiment, each feature of each similarly named component is not necessarily fully described. In addition, in the description of the disclosed systems, devices, and methods, To the extent that rectilinear or circular dimensions are used, such dimensions shall apply to all such systems, devices, The present disclosure is not intended to limit the types of forms that can be used in conjunction with the methods and methods. Such linear and circular dimensions and equivalent dimensions can be easily determined for any geometric configuration. It will be appreciated that the size and construction of systems and devices and their components may vary. The shape refers to the size and shape of the components in which the system and device are used, The methods and procedures used should be at least partially adapted to the anatomy of the subject in which the system and device are to be used. may also depend.

[0097] Generally, electromagnetic radiation (EMR) (e.g., a laser beam) is focused onto a treatment area of ​​tissue. A high numerical aperture (NA) optical therapy system capable of performing the above-mentioned procedures is described. Therefore, the terms EMR, EMR beam, and laser beam are used interchangeably herein. The focused laser beam delivers light energy to the treatment area without damaging the surrounding tissue. The transmitted light energy can be delivered to unaffected non-target areas (e.g. , epidermis layer, other parts of the dermis layer, etc.) surrounding areas of skin or tissue with other pigmentation Without affecting the target area, for example in the dermis layer of the skin, the pigmentation chromophore (c In another embodiment, the chromophores and / or targets can be destroyed. The transmitted light energy induces tattoo removal or alteration, or hemoglobin-related treatment. It can be issued.

[0098] An exemplary method and device for treating a skin condition with light or light energy is described herein as “dermal melasma.” "Methods and Apparatus for Treating Acute Myocardial Infarction," U.S. Patent Application Publication No. 2016 / 0199132 No. 62 / 113,363, and U.S. Provisional Application No. 62 / 113,363, entitled "Method and Apparatus for the Selective Treatment of Dermal Melasma." No. 438,818, each of which is incorporated herein by reference in its entirety. It is built in.

[0099] Generally, systems and corresponding methods are provided for the treatment of pigmentation conditions in tissue. As discussed in more detail below, the disclosed systems and methods involve the use of a laser beam or the like. The device uses electromagnetic radiation (EMR) to deliver a predetermined amount of energy to the target tissue. The light can be focused to a focal region, which can be translated or moved in any direction relative to the target tissue. A given amount of radiation will thermally destroy or damage the portion of the tissue that exhibits the pigmentation condition. In this way, a predetermined amount of energy can be configured to improve the appearance. The compositions may be delivered to any location within the target tissue for the treatment of pigmentation conditions.

[0100] FIG. 1 illustrates an exemplary embodiment of a treatment system 10. As shown in the figure, the treatment system The system 10 includes a mounting platform 12, an emitter 14, and a controller 16. The mounting platform 12 may include one or more manipulators or arms 20. The arm 20 can emit radiation to perform various treatments on a target tissue 22 of a subject 24. The mounting platform 12 and the emitter 14 can be coupled to the mounting platform 12 and the emitter 14. , manually or using the controller 16 (e.g., via a user interface). ) may be indicated. In a particular embodiment (not shown), the emitter may be in a handheld form factor. 1 and the mounting platform 12 may be omitted.

[0101] The emitter 14 and controller 16 (and optionally the mounting platform 12) form a communication link. The communication can be performed over link 26 by any suitable communication protocol. Any suitable type of transmission signal (e.g., electrical, optical, infrared, etc.) may be used. The link may be of any type of wired and / or wireless communication.

[0102] An embodiment of the controller 16 may be configured to control the operation of the emitter 14. In one embodiment, the controller 16 can control the movement of the EMR 30. As will be described in more detail below, the emitter 14 includes a source 32 for emitting the EMR 30 and a For example, the scanning system 34 may include: The EMR 30 is focused at a focal region and the focal region is moved and / or rotated in space. The controller 16 may be configured to communicate with the source 32 via the communication link 26 the wavelength, the current power, repetition rate, pulse duration, pulse energy, focusing characteristics (e.g., focal volume, ray command the release of an EMR 30 having one or more selected characteristics (e.g., length of the In another embodiment, the controller 16 may transmit a signal to the source 32 to The scanning system 34 scans the target tissue via the communication link 26 with one or more translational and / or rotational movements. 22 to move the focal region of the EMR 30. A signal can be sent to

[0103] Embodiments of the treatment system 10 and method are directed to targets within skin tissue, such as the dermis layer. However, the disclosed embodiments are not intended to be limiting. It can be used for the treatment of any tissue anywhere. Examples of non-skin tissues include mucosal tissues, These may include reproductive tissue, visceral tissue, and gastrointestinal tissue surface and subsurface regions, Not limited to these.

[0104] FIG. 2 is an exemplary schematic diagram of a laser beam focused on a pigmented region of the dermis layer in skin tissue. The skin tissue includes a skin surface 100 and an upper epidermal layer 110, or epidermis, which For example, the epidermis 110 may be about 30 to 120 μm thick in the facial region. In other parts of the body, it may be slightly thicker. For example, the epidermis is generally about 30 cm thick. 1 μm (e.g., eyelids) to about 1500 μm (e.g., palms or soles). Such epidermis may be thinner than the above examples due to certain skin conditions, e.g., psoriasis. The lower dermal layer 120, or dermis, extends from below the epidermis 110 to the deeper subcutaneous layer. Skin exhibiting deep or dermal melasma contains excessive amounts of melanin. The pigmented cells or regions 130 may include a population of pigmented cells or regions 130 that include electromagnetic radiation (EMR) 150 The laser beam (e.g., a laser beam) may be focused at one or more focal points that may be located within the dermis 120 or the epidermis 110. The EMR 150 can be focused on the area 160, which is absorbed by melanin. The EMR wavelengths may be provided at any suitable wavelength, including those described below. The selection may be based on:

[0105] [Characteristics of therapeutic radiation] Determining the wavelengths that are desirable for treating specific skin conditions, such as pigmented and non-pigmented conditions, , e.g., various competing chromophores present in the skin (e.g., chromophores, hemoglobin, tattoos, etc.) The absorption coefficient of the dye (e.g., melanin) can be calculated by the wavelength-dependent absorption coefficient of the dye. 1 is a graph of a typical absorbance spectrum. The absorption of EMR by melanin is at about 350 nm. It has been observed that the optical transmission reaches a peak value at wavelengths of 100 nm and then decreases with increasing wavelength. Absorption of EMR by melanin promotes heating and / or destruction of melanin-containing regions 130 However, the very high melanin absorbance leads to high absorption by pigments in the epidermis 110, The penetration of EMR into the dermis 120 or epidermis 110 can be reduced. Thus, melanin absorption is relatively high at EMR wavelengths below about 500 nm. Wavelengths below 10 nm penetrate sufficiently into the dermis 120 to heat the pigmented areas 130 therein. and may not be suitable for damaging or destroying the smaller wavelengths. Such enhanced absorption can result in unwanted damage to the upper (superficial) portions of the epidermis 110 and dermis 120. This can result in unabsorbed EMR passing through the tissue and into the deeper dermis. It is relatively rare for them to enter the poor section.

[0106] FIG. 3B is a graph of an exemplary absorbance spectrum of oxygenated or deoxygenated hemoglobin. Hemoglobin is present in the blood vessels of the skin tissue and is either oxygenated (HbO2) or deoxygenated (Hb Each form of hemoglobin may exhibit slightly different EMR absorption. As shown in FIG. 3B, an exemplary absorption spectrum for both Hb and HbO2 is shown at approximately 600 nm. At EMR wavelengths below 100 nm, the absorption coefficients of both Hb and HbO2 are high, and at higher wavelengths, the absorption The results show that the degree of hemoglobin (Hb and / or HbO2) is significantly reduced. The strong absorption of EMR directed at skin tissue results in heating of blood vessels containing hemoglobin. If the desired treatment is in melanin-rich tissues or structures, then unnecessary exposure to these vascular structures may be This can cause significant damage and make less EMR available for absorption by melanin.

[0107] The selection of an appropriate wavelength for EMR depends on the wavelength-dependent scattering profile of the tissue that interacts with the EMR. Figure 4 shows the effect of melanin and venous (deoxygenated) blood on wavelength. Figure 4 shows a plot of the absorption coefficient of light in the skin versus wavelength. The absorption of melanin decreases monotonically with wavelength. When treating a skin condition, it is desirable to use a wavelength that is highly absorbed by melanin. This suggests that shorter time periods would increase the efficacy of the treatment. However, absorption by the blood is 800 At wavelengths shorter than nm, the risk of unintended vascular targeting increases. In addition, the intended target may be located below the skin surface (e.g., in the dermis layer). The role of scattering by light can be important. Scattering reduces the amount of light that reaches the intended target. The random coefficient decreases monotonically with increasing wavelength. Therefore, shorter wavelengths are dominated by melanin. Absorption can be favored, and longer wavelengths favor deeper penetration due to reduced scattering Similarly, longer wavelengths have lower absorption by blood, which helps preserve blood vessels. Suitable for.

[0108] With the above considerations in mind, the wavelength may range from about 400 nm to about 4000 nm, more specifically Typically, the wavelength can range from about 500 nm to about 2500 nm, and can be used to target specific structures in the dermis (e.g., Melanin) can be optionally targeted. In particular, A wavelength of 800 nm may be useful for such treatment. However, 1064 nm is attractive because diodes are cheap and readily available. There is less scattering at this wavelength, which may be useful for targeting deeper lesions. This wavelength may also be suitable for darker skin types with a large amount of epidermal melanin. In the body, the higher the absorption of low-wavelength EMR (e.g., around 800 nm) by melanin in the epidermis, the Therefore, 1064 nm may not be suitable for certain therapeutic purposes for some individuals. It may be furthermore a suitable wavelength of therapeutic radiation for treatment.

[0109] A variety of laser sources can be used for EMR generation. For example, 1064 nm E Neodymium (Nd)-containing laser sources that provide MR are readily available. The laser source should be operated in pulsed mode with a repetition rate ranging from approximately 1 Hz to 100 KHz. Q-switched Nd laser sources produce laser beams with pulse durations of less than 1 nanosecond. Other Nd laser sources can provide pulses with pulse durations longer than 1 ms. An exemplary laser source providing 1060 nm wavelength EMR is available from the NIH 2010 Electromagnetic Compatibility Testing Center (Electromagnetic Compatibility Testing Center) of the National Institute of Connecticut, Connecticut, USA. 20 of NUFERN Corporation, East Granby, UT The 20W NuQ fiber laser operates at about 20KHz. Provides pulses having pulse durations of approximately 100 ns at repetition rates in the range of approximately 100 KHz Other laser sources include Quantel, Les Ulis, France. The Nd:YAG Q-smart850 from Quantel. The 50 has a maximum pulse energy of about 850 mJ and a pulse duration of about 6 ns. Provide pulses with a repetition rate of 0 Hz.

[0110] The system described herein is designed to focus the EMR into a highly focused beam. For example, the system may be configured to have a ratio of about 0.3 to 1 (e.g., about 0.5 to The lens may include a focusing or converging lens array having a numerical aperture (NA) selected from about 0.9. The correspondingly large focusing angle of the EMR is high at the focal region of the lens (which can be placed inside the skin). It is possible to provide a high fluence and intensity in the focal region and a lower fluence in the overlying tissue above the focal region. Such a focal geometry can result in unwanted heating of the overlying tissue on pigmented skin areas and An exemplary optical array directs EMR from an emitting array to a focusing lens. The optical fiber may further include a collimating lens array configured to direct the optical fiber toward the lens array.

[0111] Exemplary optical therapy systems have a diameter of less than about 500 μm, e.g., less than about 100 μm, or less than about EM in a focal region having a width or spot size of less than 50 μm, e.g., about 1 μm For example, the spot size may be from about 1 μm to about 50 μm. m, about 50 μm to about 100 μm, and about 100 μm to about 500 μm. The spot size of the focal region may be determined, for example, in air. The spot size is large enough to provide a high fluence or intensity of EMR at the focal region. Small (to effectively irradiate pigmented structures in the dermis) and small enough to reduce the size of skin tissue within an appropriate treatment time The irradiance may be selected to be large enough to facilitate irradiation of a small area / volume.

[0112] High NA optical systems have different energy densities at different depths along the optical axis. For example, an optical system with an NA of about 0.5 would provide a focal spot of about 2 μm diameter at the focal point. The radiation is focused to the focal region width (i.e., waist). The focal region has a radiation density of approximately 1 J / cm 2 Impatience It has a fluence (i.e., energy density) at a point. High NA (i.e., fast) optical system Due to the beam size, at a position 10 μm outside the focus, the radiation energy density is 0.03 J / cm 2 or 3% of the focal energy density. The energy density of the radiation at 30 μm outside the focal point is 0.4% of the out-of-focus energy density (0.004 J / cm 2 ) along the optical axis. Such an abrupt change in energy density allows for depth selective tissue treatment. However, it also allows precise depth positioning of the focal region within the target tissue (e.g., within tens of microseconds). (within 200 meters) is required.

[0113] An exemplary optical arrangement may be used to position the focal region of the EMR to a depth below the skin surface, e.g., from about 30 μm. Within the dermis tissue in the range of about 2000 μm (e.g., between about 150 μm and about 500 μm) Such an exemplary depth range may be configured to target a location such as dermal melasma. or other target of interest. This focal depth can be determined by the focal area and the lower surface of the device configured to contact the skin surface. In addition, in some embodiments, The optical array can be configured to treat targets within the epidermis. For example, the optical array can be configured to The focal region of R is located within the epidermal tissue (e.g., from about 5 μm to about 2000 μm below the skin surface). Yet other embodiments may be configured to treat targets deep in the dermis. For example, a tattoo artist may typically adjust a tattoo gun to apply a The skin penetrates to a depth of about 1 mm to about 2 mm below the surface. The optical array is located in the dermis tissue, approximately 0.4 mm to 2 mm below the skin surface. The EMR may be configured to direct a focal region of the EMR to the

[0114] It is desirable for a treatment system for treating tissue to be able to identify treatment areas within a target tissue. (e.g., by imaging: dyes, the interface between the dermis and epidermis layers of the target tissue) , cell membranes, etc.) Interaction between EMR and target tissue (e.g. plasma generation within tissue) It may also be desirable to monitor / detect the following: The treatment process can be modified (e.g., intensity, size / In the following, various embodiments of the treatment system are described.

[0115] To further summarize, a table containing parameter ranges for some exemplary embodiments is provided below. is presented below. [Table 1]

[0116] Here, the focal region depth is the depth within the tissue (e.g., focal region depth = 0 is the depth within the tissue surface). surface), M2 is a parameter that characterizes the quality of the EMR beam.

[0117] [Feedback detection and EMR-based treatment] FIG. 5 is a schematic diagram of a treatment system 500. The treatment system 500 includes an optical system 5 502, an EMR detection system 504, and a controller 506. The stem 502 directs EMR 510 generated by a source (e.g., a laser) to a target tissue 55 0 focal region 552. The EMR 510 may include one or more of the following: The imaging radiation may include imaging radiation for imaging the dermis and / or epidermis layers of the skin. The MR 510 also treats a region of the target tissue (e.g., region 522 of the target tissue 550). In some implementations, the EMR 510 may include therapeutic radiation for providing A given period may include only one of imaging radiation and therapeutic radiation. For example, the EMR 510 can include a first period of therapeutic radiation and a second period of imaging radiation. In another embodiment, the EMR 510 can measure the amount of imaging and therapeutic radiation in a given period of time. According to some embodiments, the imaging radiation may include therapeutic radiation. The wavelength of the imaging radiation is approximately equal to the wavelength of the radiation, and the imaging radiation is less than the therapeutic radiation. According to another embodiment, the imaging radiation is provided by a source other than the source providing the therapeutic radiation. The imaging radiation is provided by a source of imaging radiation, the imaging radiation having a different wavelength than the therapeutic radiation. .

[0118] The EMR detection system 504 (e.g., a photodiode, a charge-coupled device (CCD), a spectrometer, a photomultiplier tube, etc.) can detect the signal emission 512 generated by the target tissue 550 due to the interaction with a part of the EMR 510 and / or the EMR 510 reflected by the target tissue. For example, the EMR 510 having an intensity above a threshold value (e.g., therapeutic radiation) may generate a plasma in the target tissue. The plasma can generate the signal emission 512, for example, by interacting with the EMR 510. The signal emission 512 can indicate the characteristics of the plasma (e.g., the presence of the plasma, the temperature of the plasma, the size of the plasma, the components of the plasma, etc.). In some implementations, the EMR 510 having an intensity below a threshold value (e.g., imaging radiation) can interact with the target tissue without significantly disturbing the target tissue (e.g., generating a plasma within the target tissue without damaging the target tissue 550). The signal emission 512 generated from such an interaction may be used to image the target tissue 550 (e.g., a part of the target tissue 550 in the focal region of the EMR 510). This signal emission 512 may also be used to detect a dye (e.g., a dye located in the focal region of the target tissue) in the target tissue 550. According to some embodiments, non-pigmented tissue is imaged. For example, when imaging radiation (e.g., the EMR 510) passes through cell structures having different refractive indices, the light is reflected as the signal emission 512.

[0119]

[0120] ​​​​​​​​​​​​​​​​The optical system 502 and the EMR detection system 504 can be in communication with a controller 506. A controller 506 (e.g., for controlling the operation of the optical system 502) may be coupled to By controlling the treatment system 500, the operating parameters of the treatment system 500 can be altered. For example, the controller 506 may shift the focal region 552 of the EMR 510 within the target tissue 550. As discussed in more detail below, this can be achieved, for example, by moving the focal region 5 Moving the optical system 502 relative to the target tissue 550 to change the position of 52 and / or by moving optical elements within the optical system 502 ( For example, this may be performed by controlling an actuator coupled to the optical element. The controller 506 controls the optical detection of signal emissions 512 from the EMR detection system 504. Data characterizing the.

[0121] The controller 506 may control the characteristics of the EMR 510. For example, the controller 506 is used to measure the characteristics of the EMR510 (e.g., intensity, repetition rate, energy per pulse, Instruct the EMR510's source (e.g., a laser source) to change its power (average power, etc.) In some implementations, the controller 506 may include an optical element ( For example, objective lenses, diffractive optical elements, etc.) can be positioned and controlled to The optical properties of the beam (e.g., position of the focal region, beam size, etc.) can be changed. For example, the controller 506 may place an objective lens in the path of the EMR 510 and / or Change the size of the focal area of ​​the EMR510 by moving the objective lens along the path of the MR510. can be changed.

[0122] The controller 506 detects the signal emission 512 from the EMR detection system 504. In this case, various characteristics of the target tissue 550 and / or the interaction between the EMR 510 and the target tissue 550 may be considered. The effect (e.g., plasma generation in the target tissue 550) can be determined. In one embodiment of the system 500, the controller 506 controls the concentration of dye in the target tissue 550. distribution of the dermal-epidermal layer junction, and / or histology of the dermal-epidermal layer junction. The controller 506 may be configured to detect one or more of the above-mentioned characteristics of the target tissue 550. The method may be configured to generate a map indicative of the distribution of the fabric. The generation of the map may be referred to herein as imaging.

[0123] In certain embodiments, a target tissue 550. For example, in a Cartesian coordinate system, a target may be one or more may be scanned along one axis (e.g., along the x-axis, y-axis, z-axis, or a combination thereof). In alternative embodiments, the scans may be calculated according to other coordinate systems (e.g., cylindrical, spherical, etc.). The scanning may be performed by using an imaging beam (e.g., EMR510 having an intensity below a threshold). 5, and various regions of the target tissue 550 in the path of the imaging beam may be imaged using the A signal emission 512 corresponding to the signal may be detected by the EMR detection system 504. The characteristics (e.g., intensity) of the signal radiation 512 may be determined by the intensity of the target tissue 550 interacting with the imaging beam. It may vary based on the dye of the portion (eg, the dye within the focal region 552 of the imaging beam). The controller 506 characterizes the detected characteristics (e.g., intensity) of the signal radiation 512. The signal may include data and may receive a signal from the EMR detection system 504 . The controller 506 analyzes the received data (e.g., finds the received data in a database 5. Compare the detected signal emission 512 to a predetermined characteristic value to determine the presence / characteristics of the pigment in the target tissue 550. It can be determined.

[0124] In some implementations, the controller 506 controls the treatment based on the signal emission 512. The location of the portion of the target tissue 550 that is to be treated (the "target treatment area") can be determined. For example, A layer (e.g., skin tissue) within the target tissue 550 located at a predetermined depth from the surface of the target tissue 550 In some cases, it may be desirable to treat the dermis layer within the tissue. 552 is incident on the surface of the target tissue 550 (e.g., optical system 502 is aligned with the target tissue The desired distance from the surface of the fabric 550 may be adjusted by, for example, For example, where signal radiation 512 indicates an interaction between EMR 510 and the surface of target tissue 550, This is performed by scanning the optical system 502 along the z direction until a certain characteristic is detected. For example, an interface material (e.g., an optical slab, gel, etc.) may be applied to the surface of the target tissue 550. When the focal region 552 transitions from the target tissue 550 to the interface material, The characteristics of the signal radiation 512 may change. This is because the EMR 510 at or near the tissue surface The position of the focal region 552 of the EMR 510 can be shown. When region 552 is positioned such that it is at or near the surface of target tissue 550, the optical system The microscope 502 is oriented such that the focal region 552 is at a predetermined depth (e.g., For example, it may move along the z direction.

[0125] The controller 506 receives an E Based on the signals received from the MR detection system 504, the operating parameters of the treatment system 500 are For example, some implementations of the EMR detection system 504 The state is the dermis-epidermal (DE) junction in the target tissue 550. The controller 506 can detect the depth of the is(DE) junction. The depth of the focal region 552 can be adjusted according to the depth of the DE junction. The DE junction may be used as a reference to determine the depth of the focal region 552 within the dermis. Additionally, some embodiments of the EMR detection system 540 may include a spectrophotometer (e.g., Using a spectrophotometer, the percentage of melanin present in the epidermal layer of the skin can be quantified. Based on this, the controller 506 may direct designated personnel (e.g., a clinician) to According to some embodiments, the system may propose modifications to one or more of the parameters. The change in this parameter is proportional to the energy per pulse, which is inversely proportional to the percentage of melanin detected. - Change, increase in focal angle with increasing melanin ratio, focal area based on melanin ratio 55 The depth change may include at least one of two.

[0126] In some implementations, the acoustic sensor 530 (e.g., an acoustic sensor) detects the target tissue 55 0, and the acoustic sensor 530 measures the correlation between the EMR 510 and the target tissue 550. For example, an acoustic sensor can detect the interaction properties of a target tissue 550 (e.g., The pressure waves 55 generated by the generation of plasma in the focal region 552 2. Examples of the acoustic sensor 530 include a piezoelectric transducer, a capacitive transducer, an ultrasonic transducer, and a Acoustic transducers, Fabry-Perot interferometers, and piezoelectric membranes may be included.

[0127] In one embodiment, the pressure wave 532 may be a shock wave, where a sudden change in pressure causes the medium ( In another embodiment, the pressure wave 532 propagates through the air (e.g., air) at a speed faster than the speed of sound. An acoustic wave propagates through a medium at a speed approximately equal to the speed of sound in that medium. ave).

[0128] Photoacoustic imaging is a biomedical imaging modality based on the photoacoustic effect. In photoacoustic imaging A non-ionizing laser pulse is delivered to the biological tissue (if radio frequency pulses are used). (When the energy is transmitted through the ion beam, the technique is called thermoacoustic imaging.) Part of the energy transmitted is absorbed and Converted to heat, it undergoes temporary thermoelastic expansion and emits broadband (i.e., MHz) ultrasound. .

[0129] The sensor measurement data from the acoustic sensor 530 can be transmitted to the controller 506. The controller 506 may then monitor this device for verification of dye detection via signal emission 512. According to some embodiments, the treatment can be performed by detecting the shock waves 532. The presence and / or strength of the pressure wave 532 is determined by the plasma and Correlating with the plasma mediated treatment being performed. Additionally, pressure waves 532 in the focal region are detected. By mapping, a comprehensive map of the treated tissue can be generated and documented.

[0130] FIG. 6 is a diagram illustrating an example embodiment of an optical system 600. 0 can direct the EMR beam 602 from the EMR source 605 to the target tissue 650. The MR source 605 is a laser (e.g., 450 mJ pulse energy, 6 nanosecond [nS] pulse Quantel with pulse duration and wavelength of 1064 nm or harmonics of 1064 nm In some embodiments, the laser may be a Quantel Q Smart 450 laser. According to the present invention, an EMR beam 602 is introduced into an optical system 600 via an adapter 610. The adapter may be attached to an EMR source generating the EMR beam 602 on an articulating arm, e.g. For example, it may be configured to be fixed to the arm 20 of the mounting platform 12 in FIG.

[0131] According to some embodiments, a diffractive optical element (DOE) 620 (e.g., a beam splitter) A DOE 6 (e.g., a multi-focus optical system) may be placed in the path of the EMR beam 602. 20 changes the characteristics of the EMR beam 602 to transmit a second EMR beam 604. For example, the DOE 620 can have multiple sub-beams that are focused to different focal regions. The implementation and use of DOE for the treatment of target tissues is Further details are provided in U.S. Provisional Application No. 62 / 656,639, entitled "Diffractive Optics for Tissue Treatment of Laser-Based Lasers." The disclosure of this document is incorporated herein by reference in its entirety. A transmitted second EMR beam 604 (e.g., a multiple sub-beam generated by the DOE 620) The beam is split into target groups by a beam splitter 640 (e.g., a dichroic beam splitter). An example of a dichroic beam splitter is a A cutoff wavelength, a transmission band between about 420 nm and about 900 nm, and a transmission band between about 990 and about 1600 A short-range dual-mode reflector with a reflection band between 100 nm and 200 nm (Thorlabs PN DMSP950R) The second EMR beam 604 may include a chromatic mirror / beam splitter. The light is reflected by the splitter 640 and directed towards the objective 660. The objective lens 660 can focus a focal region 652 of the target tissue 650 through the window 645. An example objective lens 662 can be a 25 mm objective lens having a diameter of approximately 1.5 mm. Millimeters (mm), numerical aperture (NA) approximately 0.83, near infrared (NIR) coating , and Edmunds Optics, which has an effective focal length of about 15 mm. The lens is a PN67-259 aspheric lens from Optics. The window 645 is a lens that faces the target tissue 650. may be used to hold the

[0132] In some implementations, the EMR beams 602, 604 are The beam may be expanded by a beam expander (not shown) disposed in the path of the fourth beam. The system expansion can allow for a desired NA value for the optical system 600. For example, The laser beam generated by the smart450 laser has a beam diameter of approximately 6.5 mm. This requires a beam expander that can expand the laser beam to twice its diameter. The expanded EMR beams 602, 604 may have a sufficiently high NA (e.g., 0. 3) to focus the EMR beams 602, 604, an EFL lens of about 15 mm can be used to focus the

[0133] The optical system 600 is configured to focus the EMR beam 604 at a focal region 652 adjacent the epidermis of the target tissue 650. This may be done, for example, to position the optical system 600 beneath a target structure. By moving the EMR 604 relative to the structure 650 and / or along the path of the beam of the EMR 604 This may be performed by moving the objective lens 660 along the optical axis. In the optical system 600, the position of the optical system 600 / optical elements is controlled by a controller (e.g. For example, the focal region 652 may be moved by the controller 506. For example, placement of the dermal epidermal (DE) junction can reduce hyperpigmentation or pigmentation in the epidermis. The present invention provides a method for reducing or substantially inhibiting unwanted heat production in the epidermis that can lead to reduced pigmentation. This can also be used to target areas within the dermis for heat and / or plasma generation. This makes it possible.

[0134] The interaction between the second EMR beam 604 and the target tissue 650 generates a signal emission 606. As explained above, the signal emission 606 may Radiation produced by plasma in the brain ("tissue radiation") The tissue radiation may be in the transmission band of the beam splitter 640. As a result, the tissue radiation can be split by the beam splitter 640. The signal radiation 606 may also be of a wavelength similar to that of the second EMR beam 604. Radiation with similar wavelengths ("system radiation") The wavelength of the system radiation may be within the reflection band of the beam splitter 640. As a result, a small fraction (e.g., 10%) of the system radiation is It is transmitted by splitter 640 .

[0135] The signal radiation 608 transmitted by the beam splitter 640 is the tissue radiation and the system The portion of the signal emission 608 may include both the EMR detection radiation and the The EMR detector 690 detects the signal radiation 608 (or a controller (e.g., controller 506) to transmit data characterizing the detection of the For example, the controller may detect (e.g., transmit) signal radiation 608 Based on the intensity of the received signal, the operation of the source 605 may be altered (e.g., turning the source 605 off). (to make it so).

[0136] In one embodiment, the optical system 600 may be used as a confocal microscope. can be achieved, for example, by placing a second objective lens (not shown) upstream from aperture 680. The aperture may be focused onto a focal plane that contains the aperture 680, thereby converging the signal radiation. The aperture 680 can be used to reimage the signal radiation 608. Such a configuration can filter (e.g., block) frequencies between the target Different regions of the tissue 650 (e.g., different depths of the target tissue relative to the tissue surface 654) The imaging aperture 6 may allow filtering of signal radiation associated with the imaging aperture 6. 80 and the target tissue 650 (e.g., along the path of the signal radiation 608 By moving the imaging aperture 680, different depths of the target tissue are imaged. In some implementations, a controller (e.g., controller 506) may By sending a command to the actuator, the imaging aperture 680 can be moved. The controller 506 analyzes the detection data to determine the presence of plasma in the target tissue 650, The optical system 600 can determine the distribution of dye in the target tissue, etc. Damage to the window 645 may be detected by the second EMR beam 60. 4 and the window 645 (e.g., when the intensity of the EMR beam is high, the EMR beam Detecting damage to the window 645 This may be accomplished by determining the change in intensity of the signal radiation due to damage to the window 645. This is done, for example, by dividing the focal region 652 incident on the window 645 (e.g., near the surface of the window 645). In particular, a sensor 606 is placed on the surface of the window 645 or inside the window 645 to detect the intensity of the signal radiation 606. This can be done by using a photodetector as the EMR detector 690. This intensity is comparable to that of the focal region 652 at the equivalent location of the undamaged window 645. The intensity of the window 645 may be compared to a previously measured intensity when the window 645 is opened. The damage may be determined.

[0137] FIG. 7 is an illustration of one embodiment of an optical system 700. The optical system 700 includes an eyepiece. It may include a microscope attachment 770 having an eyepiece 790. The microscope attachment 770 receives the signal radiation 6 transmitted by the beam splitter 640. 08 (or a portion thereof). The signal radiation 608 can be captured by a lens column 750 (e.g. , Edmund Optics PN49-665 25mm diameter x 50mm EFL Non The lens barrel 750 may be re-imaged by a spherical achromatic lens. The pupil plane 720 of the eyeglasses 790 (e.g., Edmund Optics The image can then be re-imaged onto a 10X DIN eyepiece (PN35-689 by Epson).

[0138] As mentioned above, the signal radiation 608 includes both tissue radiation and system radiation. Due to the difference in wavelength, the tissue radiation image and the system radiation image are captured at different positions ( As a result, the eyepiece 790 is generated by the system radiation. When the CT scanner is positioned to capture images generated by the CT scanner, it can accurately capture images related to tissue radiation. However, the eyepiece 790 may not capture the system radiation precisely in the focal region. The optical fiber may be calibrated to capture signal radiation having a different wavelength than the stem radiation. One method is to create a phantom (p The calibration of the eyepiece 790 is A second EMR beam 604 is focused (e.g., by objective lens 660) onto the phantom. ) to induce a breakdown (e.g., a laser-induced optical breakdown) in the focal region of the second EMR beam 604. This may include subsequently irradiating the phantom with a second EMR radiation having a predetermined wavelength. (e.g., at an oblique angle) and projecting EMR radiation having a predetermined wavelength at the eyepiece 790. The axial position of the eyepiece 790 can be measured using the intensity of the second EMR source. The intensity of the emitted radiation can be adjusted (e.g., along the z-axis) to maximize the intensity of the emitted radiation. In certain embodiments, a sensor may be used in place of the eyepiece 790. Examples of sensors include: There are CMOS and CCD imagers. The sensor detects the radiation in the sensor plane. The digital image shows an image of the focal region 652.

[0139] Figure 8 shows a fiber coupler attachment. FIG. 8 is a diagram of an embodiment of an optical system 800 having a fiber coupler 802. The attachment 802 is attached to the objective lens 660 and the beam splitter 640 as described above. The lens barrel 810 includes a pupil plane 815 (e.g., a plane parallel to the x- and y-axes) that can image the light from the lens barrel 810. 820) which is parallel to the collimating lens (collimating lens 820) The signal radiation 608 can be focused. The focused signal radiation 608 can be collimated. The lens 820 can be used to collimate the beam to the desired size, and the coupling lens 8 The coupling lens 830 is attached to a fiber connector 840. The signal radiation 608 can be focused at a desired NA for coupling into an attached fiber. The fibers may be optically connected to one or more EMR detectors (e.g., detector 504). According to some embodiments, the coupler attachment 802 is located at the pupil plane 815. The aperture may further include an imaging aperture 850 for capturing the light emanating from the focal region 652. The portion of the signal radiation 608 that is not transmitted can be filtered. According to an embodiment, the detection device (e.g., photodiode, spectrometer, etc.) may be optical fiber or The imaging aperture 850 may be located immediately behind the imaging aperture 850 without associated optics. Calibration of the optical aperture 850 is a similar process as described above in connection with calibration of the eyepiece 790. It may be achieved.

[0140] Feedback detection can be used in a variety of ways in conjunction with EMR-based therapy. It is possible to provide EMR treatment based on feedback information. To illustrate some of the methods that can be implemented, an exemplary application is described below. In other words, the example described below shows that EMR treatments are classified into three types based on feedback information. The three types are: 1) to detect the plasma, 2) to reference the position of the focal region, and 3) These three usage categories are based on feedback information and EMR The purpose of this article is to provide a comprehensive (or mutually exclusive) list of applications for the treatment of It's not something like that.

[0141] [Example of plasma feedback] Some treatments involve plasma formation during treatment (e.g., thermionic plasma or optical breakdown). In some embodiments, the detected plasma characteristic indicates a potential effect of the treatment. For example, in the treatment of skin pigmentation conditions, the focal area is located deep within the skin, The laser source is scanned over the skin to match the skin pigment that is scanned during treatment. A pulsed laser is irradiated and a thermoelectron plasma is formed where the focal area and the dermal pigment match. The formation of thermionic plasma occurs when 1) pigment is present in the skin and 2) the color changes at the moment of plasma formation. 3) the pixel is collocated with the focal region (e.g., XY coordinates and depth), and 3) the dye at this location is cured. This indicates that the pigment has been destroyed (e.g., the pigment has been destroyed).

[0142] In other situations, plasma formation may indicate the need for system maintenance. For example, some systems include a window that contacts the tissue being treated. Cools, stabilizes tissue, and provides a depth reference to tissue They serve many functions, including the evacuation of blood or other fluids from tissues by pressure. Radiation (e.g., laser beam) can also be directed through the window to treat the underlying treatment area. In some cases, the radiation can cause damage in or on the surface of the window, resulting in plasma This can lead to the generation of mercury and etching of the window. If the system continues to emit radiation, it can cause burning or thermal damage to tissue in direct contact with the window. This happens quite often.

[0143] FIG. 9 illustrates a method 90 for detecting plasma during radiation-based tissue treatment according to some embodiments. 9 shows a flow chart of the tissue surface contacting process using a window (906). , in contact with the outer surface of the tissue. The window is configured to be transparent to the therapeutic radiation. Typically, The window is referenced so that the tissue surface is in contact with the window to effectively reference the outer surface of the tissue. According to some embodiments, the window comprises: Preventing tissue movement during treatment, contact cooling of tissue during treatment, and blood (or other) in the tissue due to compression The fluorophore serves additional functions including, but not limited to, the ejection of competing chromophores (e.g., fluorophores that compete with one another for fluorophores).

[0144] Therapeutic radiation is then generated (908). Therapeutic radiation is typically generated by a radiation source. Therapeutic radiation is designed to produce an effect in tissue, which can range from improvement to In certain embodiments, the tissue effect is cosmetic and can result in a desired change in appearance. In other embodiments, the tissue effect may be therapeutic. According to some embodiments, The tissue effect involves the generation of selective thermionic plasma in the presence of chromophores. Parameter selection will depend on the procedure being performed, the tissue type, and the individual patient. Generation of therapeutic radiation 900 and associated power generation for producing an effect (e.g., a cosmetic effect) in tissue. The details regarding parameter selection are explained in detail above.

[0145] The therapeutic radiation is focused at a focal region 910. Typically, the therapeutic radiation is focused through focusing optics. According to some embodiments, the focal region is about 1 mm, The focal region has a width of less than about 0.1 mm, about 0.01 mm, or about 0.001 mm. The region may be located in a first region. In some embodiments, the first region is specifically treated. In some cases, the first region may be located outside the organization, e.g. The stencil may be intentionally or unintentionally placed within a window in contact with the

[0146] The focal region is typically scanned by a scanning system (e.g., a scanner) (9 12) Examples of scanning include tip / tilt of the focal area, rotation of the focal area, and shift of the focal area. Further description of the associated scanning means is incorporated herein by reference in its entirety. Also, Dresser et al., U.S. Patent Application Serial No. 16 / 219,809, entitled "Electromagnetic Radiation Beam Scanning" According to some embodiments, the therapeutic radiation is pulsed. The focal region is then scanned so that little to no therapeutic radiation is delivered (e.g., The focal area can be scanned continuously. In this case, The timing of the therapeutic radiation pulses and the scanning parameters control the location of the first and second regions. do.

[0147] The plasma is generated by the therapeutic radiation (914). The fluence is highest in the focal region. Because of the large size of the plasma, it is typically generated in or near the focal region. According to the embodiment, the plasma is generated by thermionic plasma generation, and optionally the pigmented region 914 is Alternatively, the plasma can be generated non-selectively (914).

[0148] The plasma is then detected (916). A detector typically detects signal radiation emanating from the plasma. Examples of signal radiation detection include optical detection, acoustic detection, and laser-induced breakdown. spectroscopic detection of (e.g., laser-induced breakdown spectroscopy), plasma generated shock waves (PGS) W) detection, plasma emission detection, plasma (plume) shielding detection e) shielding detection, and plasma photography. In some embodiments, a characteristic of the plasma is determined based on detecting (916) the plasma. Examples of plasma properties include the existence of plasma, the intensity of plasma, and the spectrum of plasma. According to some embodiments, the characteristics of the signal radiation include: , for example, recorded and stored by a controller.

[0149] In some embodiments, based on the detected plasma, the plasma is at least It is then determined whether the vertex is also partially positioned (918). For example, in some embodiments, The optical signal contains spectral components known to be representative of materials in the window but not tissue. Signal radiation can be detected as an indication that the plasma is partially within the window. In the embodiment, the intensity of the optical signal radiation indicates that the plasma is at least partially within the window. This may exceed known thresholds that

[0150] Therapeutic radiation-related parameters are controlled based in part on the detected plasma. 9. Determine (920) whether the plasma is partially located within the window (e.g., determine (918)). Examples of parameters related to therapeutic radiation include energy per pulse, repetition rate, focal length, and These may include, but are not limited to, the location of the point area, or the size of the focal area. These therapeutic radiation parameters may be controlled alone or in conjunction with each other or with other therapeutic radiation parameters. For example, if the plasma is partially located inside the window, This determination can be used as a trigger event to stop the therapeutic radiation.

[0151] In some embodiments, the property map is used to map a location, for example by a controller. A map is generated that can contain the following trix: A first characteristic of a first signal radiation emitted from the plasma is mapped to coordinates of a first position. and a second characteristic of a second signal radiation emanating from the second plasma at the second location. and mapping the focal region to coordinates of the focal region. A four-dimensional matrix with three orthogonal axes related to the lattice plane and a fourth axis related to one or more properties of the plasma. In some versions, the map can contain individual treatment effects. A system suitable for carrying out the above-described plasma detection method may be used as an indicator of The system is described in detail below.

[0152] Referring to FIG. 10, a plasma detection and treatment system 10 according to some embodiments. 10 is a schematic diagram of a tissue 1008. In some embodiments, the window 1006 is The window 1006 is configured to contact a surface, such as the exterior surface of tissue 1008. Optical materials configured to transmit the beam include, for example, glass, transparent polymers (e.g. For example, polycarbonate, quartz, sapphire, diamond, zinc selenide, or sulfide. Contains zinc.

[0153] The imaging and therapy system 1000 includes a focusing optical system 1010. (e.g., an objective lens) focuses the electromagnetic radiation (EMR) beam 1011 onto the tissue 10 The plasma is generated by thermionic power generation. In another embodiment, the plasma may be selectively generated at the chromophore in the tissue 1008. The EMR beam 1012 is generated non-selectively by optical breakdown. The EMR beam 1011 may be generated using a radiation source (not shown). Including light, either collimated or non-collimated, and either coherent or incoherent light. Good too.

[0154] The detector 1014 is configured to detect the plasma 1012. Examples of the 014 include optical sensors such as photodiodes and image sensors, and surface acoustic wave sensors. Acoustic sensors such as piezoelectric membranes, vibrometers, and etalons; spectrometers, spectrophotometers, and plasma and more specialized detectors such as bright (or obscured) optical probes.

[0155] In the illustrated embodiment, the plasma detector detects visible light 1016 emanating from the plasma 1012. The optical detector (e.g., a photodiode) detects the optical radiation (e.g., signal radiation). According to some embodiments, the lens column 1018 directs the visible light 1016 incident on the detector 1014. A detector 1014 is used in conjunction with focusing optics 1010 to focus the light. The controller 1015 is configured to input data related to the plasma generated. Communicate with La1015.

[0156] The scanner 1022 is configured to scan the focal region of the EMR beam 1011 . The scanner typically scans the focal region in one or more dimensions, and in some embodiments In this case, the scanner 1022 scans the focal area in all three dimensions. The scanner 1022 scans the tissue 1008 from a first region 1024 to a second region 1026 from left to right. It is shown scanning the focal region to the side.

[0157] As the scanner 1022 scans the focal region, a first plasma is generated in a first region 1024. A second plasma is then generated in the second region 1026 to pulse the EMR beam 1011. The first plasma and the second plasma can both be detected by detector 1014. In some embodiments, the first detected plasma and the second detected plasma are Data relating to Zuma is input to controller 1015. In some embodiments, The data relating to one or more plasma events is transmitted to the EMR beam 1011 and the scanner 1020. 1022 to the controller to control at least one of the related parameters Therefore, it is used.

[0158] In some embodiments, the controller 1015 may be configured to detect whether the plasma 1012 is within the window 1008. and controlling the EMR beam based on the determination of whether the EMR beam is at least partially located at the (e.g., terminating the EMR beam 1011). In this embodiment, the controller 1015 controls the signal radiation 1016 emanating from the plasma 1012. Based on the intensity of the plasma 1012, the plasma 1012 is at least partially located within the window 1006. The intensity of the signal radiation 1016 determines whether a light sensor (e.g., a photodiode) According to another version, the controller 1015 may detect the signal by using Based on the spectral content of the radiation 1016, it is possible to determine whether the plasma 1012 is at least partially formed within the window 1006. For example, according to some embodiments, the window 100 6 can include sapphire containing aluminum. The spectral peak is focused at about 396 nm. Skin normally contains aluminum. Therefore, the signal emission (taken at a precise time after the laser pulse [e.g., 10 μs]) If the plasma 1012 contains a spectral peak focused at about 396 nm, then the plasma 1012 is at least The spectrometer may also be partially located within the window 1006. Optical filters (e.g., notch filters) and optical sensors are used to determine the spectral content of the signal radiation. According to another embodiment, the spectrometer or spectrophotometer is used to detect the signal radiation. It is used to detect the spectral content of a morphism.

[0159] The controller 1015 is configured to record one or more detected characteristics of the plasma 1012. In some embodiments, the controller 1015 may be configured to The device is configured to record a matrix (or map) of the 12 detected characteristics. For example, the controller 1015 may be configured to generate a first plasma 1012 emanating from the first plasma 1012 at the first location 1024. A first characteristic of the signal emission is recorded and the first characteristic is mapped to coordinates relative to a first location 1024. and recording a second characteristic of a second signal radiation emanating from the second plasma at a second location 1026. The second characteristic may be configured to map to the coordinates of the second location 1026.

[0160] To further illustrate plasma detection in an EMR treatment device, specific embodiments are described below. will be provided.

[0161] [Plasma feedback example 1] An example of a first plasma feedback is the relative plasma light intensity, which indicates the presence of plasma. In vitro studies to quantify the changes are described. The in vitro studies were selected for dark skin. The study was carried out using the skin of selected female Yucatan pigs. A 2000W NUFERN fiber laser is used as the laser source in the in vitro studies.

[0162] FIG. 11A is a schematic diagram of a therapeutic optical system 1100 used for the in vitro studies. The therapeutic optical system 1100 is adapted to receive a collimated laser beam 1112. The beam combiner 1110 includes a beam combiner 1110 configured to combine the incident laser beams. The reflector 1114 reflects the laser beam 1112. The reflector 1114 reflects a predetermined wavelength range. In the current in vitro study, the laser beam 1 112 has a wavelength of 1060 nm, and the reflector has a wavelength range of 1047 to 1064 nm. The NB1-K14 from Thorlabs is 99.5% reflective. The emitted laser beam 1112 is imaged and focused by focusing optics 1116. The focusing optics 1116 used in the in vitro studies were manufactured by Thorlabs. The C240TME-C has an NA of 0.5 and an effective focal length of 8 mm. The laser beam 1112 strikes the skin sample 1114. The laser beam 1112 is focused to a waist (e.g., focal volume) within 118. In this study, a plasma plume (1120) was injected into a skin sample (111 8. Radiation 1124 generated from the plasma plume 1120 is focused The light is imaged by the optical system 1116 and passes through the reflector 1114. After that, the radiation 1124 is coupled to a first optical fiber (not shown) by a fiber coupler 1122 . The fiber couplers used in the in vitro studies were manufactured by Thorlabs (Thorlabs, TX). The second end of the optical fiber is an Ocean Waveguide (OWA) SMA-7-A. The spectrometer is the Ocean Optics HR2000+ES (Figure 1). In another embodiment of the in vitro study, a notch filter (not shown) is connected to the A reflector 1114 (not shown) is provided between the reflector 1114 and the fiber coupler 1122 to reflect the laser beam 1 112. The wavelength of the radiation 1124 is similar to that of the wavelength of the radiation 1124 ... The skin sample 1118 is mounted on a motorized stage 1130. The working distance between the lens 1118 and the focusing optics 1116 is set to the focal distance of the laser beam within the skin sample 1118. It is held to control the depth of the waist of the beam 1112.

[0163] In another embodiment of the in vitro study, a skin sample 11 having a melanin tattoo was 18 indicates that the waist of the laser beam 1112 is approximately 0.2 mm deep within the sample 1118. The laser is placed on a motorized stage 1130 so as to be positioned in the desired position. The melanin pigment used is from squid ink (e.g. sepia ink). The ranin tattoo is located approximately 1 / 4mm to 1mm deep in the dermis of the skin sample. The depth of the tattoo pigment is confirmed by skin histology samples.

[0164] FIG. 11B shows a histological sample of skin sample 1118 with a melanin tattoo. The skin surface 1150 is shown on top of the histology. The epidermis-dermis junction (1152) is the junction between the epidermis and the ulcerative collateral layer of the skin. The skin layer is divided. Melanin globules 1154 present in the dermis are what make up melanin tattoos. The laser was operated at 20 KHz, 100 ns pulse duration, and 0.5 mJ / pulse. The sample is scanned during laser irradiation at a speed of 100 mm / s. The light was captured over a 1000 ms period and the capture was adjusted to trigger in response to the laser illumination. It will be adjusted.

[0165] Figure 12 shows the spectra associated with radiation from a melanin tattoo and bare skin. The horizontal axis represents the wavelength of radiation from the sample skin 1118, and the vertical axis represents the relative intensity of the radiation. FIG. 12 shows a melanin tattoo spectrum (e.g., centered around 600 nm). and the bare skin spectrogram generated when skin 1118 is irradiated with laser beam 1112. spectrum (e.g., having a spectrum centered at about 1060 nm). The two spectra show measurements taken during irradiation of the sample at the melanin tattoo location. (e.g., the waist / focal volume of the input laser beam 1112 may be (When irradiating areas of skin that contain melanin tattoos.) The melanin tattoo spectrum shows measurements taken during irradiation of an area of ​​human skin 1118. , broad spectrum, including radiation in the visible spectrum (e.g., between 400 nm and 800 nm) Broad spectrum light stimulates plasma formation during irradiation of melanin tattoos. The bare skin spectrum generally has no or very little visible spectrum content. The absence of visible light in the tor generally indicates that no plasma was formed during irradiation of bare skin. It shows.

[0166] Other skin samples with carbon tattoos (e.g. India ink) The pull 1118 is performed such that the focal waist of the laser beam is approximately 0. The motorized stage 1130 is placed below the focusing optics 1116 so that it is positioned 2 mm below the focusing optics 1116. The carbon tattoo was placed in the dermis of skin sample 1118, approximately 1 / 4 mm to 1 mm deep. The laser operates at 20 KHz, 100 ns pulse duration, and 0.5 m The laser operates at 20 J / pulse. The sample is scanned during laser irradiation at a speed of 100 mm / s. The spectrometer captures light for a period of 5000 ms and triggers the capture in response to laser illumination. It is adjusted to match.

[0167] Figure 13 shows the spectra associated with radiation from a carbon tattoo and bare skin. The horizontal axis represents the wavelength of radiation from the sample skin 1118, and the vertical axis represents the relative intensity of the radiation. FIG. 13 shows the laser beam 1112 generated when the skin 1118 is irradiated with the laser beam 1112. Carbon tattoo spectrum and bare skin spectrum. Carbon tattoo spectrum , indicates measurements taken during irradiation of the sample at the location of the carbon tattoo (e.g., input The waist / focal volume of the laser beam 1112 is located at the area of ​​skin having the carbon tattoo. The bare skin spectrum was obtained by irradiating the sample skin without a carbon tattoo for 11 minutes. The measurements taken during the irradiation of 18 areas are shown. The carbon tattoo spectrum is The existence of broad spectrum light, including radiation in the 1000 nm to 800 nm wavelength range Broad spectrum light shows plasma formation during irradiation of carbon tattoo. Bare skin The spectrum generally has no visible spectral components. The lack of light is generally due to the exposure of bare skin. This indicates that no plasma is formed.

[0168] The broad spectrum captured in the above test is measured at a repetition rate of 2 Note that at a rate of 0 KHz, plasma was generated in many places. The integration time of the spectrometer is set to 1 ms or more. This is because the multiple It allows characterization of the spectral information of the plasma generated over the pulse. After the interaction between the pulse (of the laser beam 1112) and the plasma, the plasma cools. As electrons begin to move, they lower their energy level and are thus transported across a narrow spectral band. The spectrometer measurements above are integrated over multiple pulses, so It should be understood that these narrow bands are not observed in this example. A second example in which spectral bands are detected is described below.

[0169] [Plasma feedback example 2] In the second example, the radiation 1124 generated by the plasma of the skin sample 1118 A narrow spectral band is experimentally observed. The optical system used for this detection is shown in Figure 1. The optical system is described in detail in Ref. 1A. The optical system includes an optical system and an Ocean Optics Optical fiber that enables optical communication between the spectrometer model number HR2000+ES and the The optical system includes a Q-switched Nd:YAG laser with a 1000 GHz fiber optics. A Q-switched Nd:YAG laser ( It communicates optically with the Quantel Q-Smart 450.

[0170] The skin sample 1118 is positioned generally parallel to the focal region of the laser beam. The focal region is first positioned just below the surface of the skin sample 1118. A number of laser pulses was directed at the sample skin 1118, with spectrometer measurements taken immediately after each laser pulse. Each laser pulse produces a photon that leads to the generation of plasma in the skin sample 1118. The plasma has a peak power sufficient to produce chemical destruction. It is captured and transmitted to a spectrometer as described with reference to FIG. 11A.

[0171] FIG. 14 shows a scan of radiation 1124 generated by plasma in a skin sample 1118. The spectra shown are the results of the spectra captured from the plasma after each laser pulse. were averaged. The average spectrum is shown in chart 1400 shown in FIG. Chart 1400 has relative intensity in arbitrary units along the vertical axis and in nanometers along the horizontal axis. The average spectrum has wavelengths of about 589 nm and 766 nm. The average spectrum contains peaks at approximately 422 nm, 455 nm, 493 nm, Minor spectral peaks at approximately 521 nm, 553 nm, 614 nm, and 649 nm This also includes the work.

[0172] During testing, the sapphire window is positioned in the path of the laser beam 1112 and the skin sample 11 18 and focusing optics 1116. The laser beam 1112 is focused through a sapphire window via the suction tube to the waist / focal area located approximately 0.5 mm below the surface of the skin. The radiation spectrum from a plasma formed using a sapphire window in contact with tissue was The chart 1500 includes a chart 1500 showing relative velocity in arbitrary units along the vertical axis. 15 has the wavelength in nanometers along the horizontal axis. It can be seen that there is a major peak at 766 nm. In addition, there is an even larger peak at about 39 After the measurement, the sapphire window was aligned with the plasma formed inside. It was found to be damaged (e.g., etched). 396 nm peak occurs repeatedly with the sapphire window present and only when the sapphire window is present. And the sapphire window appears to be damaged by the plasma formation. The observations showed that this peak at about 396 nm was used as an indicator of plasma formation within the sapphire window. This shows that it can be used.

[0173] According to some embodiments, the material composition of the plasma is determined by spectral analysis. and one or more parameters of the laser beam are adjusted based on a material composition of the plasma. For example, according to some embodiments, the controller may determine a treatment from the spectral data. It was determined that materials other than the one being measured were being affected by the plasma, and the laser parameters were adjusted accordingly. The second example is to adjust the power supply or deactivate the laser source. Although a spectrometer is used to detect the amount of ions, some embodiments use alternative methods. For example, a photodiode measures 396 nm light to determine the spectral content of the plasma. Some versions have a narrow aperture that only passes light of about 396 nm so that only A bandpass filter is placed over the photodiode. The photodiode detects the EMR pulse. The controller is also triggered to collect a later time (e.g., 10 μS). , the relatively high values ​​occur only when the plasma impacts the sapphire window, so Configured to stop EMR source activation when the photodiode detects a relatively high value will be done.

[0174] [Plasma feedback example 3] The third example is an EMR-based treatment handpiece. A plasma detection system that detects plasma incorporated in a plasma hand piece Indicates the m.

[0175] 16A-16C show aspects of a third example of tissue treatment and plasma detection. and a plasma detection system 1600 is shown in Figures 16A-16C. FIG. 16B shows a front view of the system 1600 taken along section line BB of FIG. 16A. FIG. 16C shows a cross-sectional view of stem 1600. And FIG. 16C shows a detail taken within detail circle C of FIG. 16B. Detailed diagram is shown.

[0176] The fiber laser 1610 is configured to output therapeutic radiation. An example of the 1610 is from Fiber Laser Technology Co., Ltd. (Feibo) in Shanghai, China. Laser Technologies Co., Ltd.) fiber 1060 nm The therapeutic radiation is focused by an optical system. Towards point optics 1620. An example of a focusing optic is a part from Thorlabs Number: A240. The focusing optics 1620 focuses the tissue (not shown) through a window 1622. The optical system is configured to focus the therapeutic radiation at a focal region. 20 is configured to be scanned in all three dimensions. This allows the focal area of ​​the therapeutic radiation to be is scanned in all three dimensions within the tissue. The scan is performed in three separate steps, each responsible for a single axis. The X-stage 1625 scans the focusing optics in the X-axis. A Y-stage 1626 mounted on the X-stage 1625 scans the focusing optics in the Y-axis. And the Z stage 1627 attached to the Y stage 1626 moves the The X stage scans the focusing optical system (generally along the optical axis of the focusing optical system). Dover, Boxborough, Massachusetts A Dover MMX 50 manufactured by Motion was used at Petah Tikva in Israel. ELMO Motion Control, Petach-Tikva, Russia ELMO DC Whistle Goal by Motion Controller Ltd. Elmo DC whistle Gold controller An exemplary Y stage is manufactured by the Auburn, Massachusetts, USA Physik Instrumente, Inc. (Physik Inst Q545.140 steerer controlled by E873 controller from Rumente LP An exemplary Z stage is manufactured by Victor, NY, USA. New Scale Technology, Inc., located in es,Inc.'s New Scale 3M-FS.

[0177] A printed circuit board (PCB) 1640 is mounted on the Z stage 1627 and fitted to the window 16 22. PCB 1640 includes several electronic components and four photodiodes 1642. Exemplary photodiodes include those available from Osram AG, Munich, Germany. SRAM GmbH's Csram CHIPLED part number SFH 2711 Another example of a photodiode is from Roithne, Vienna, Austria. r Lasertechnik (Roithner Lasertechnik Gm) bH) gallium nitride-based sensor, GUVA-S12SD. Two exemplary Photodiodes emit light in the near infrared (NIR) through ultraviolet (UV) and visible light spectrum. For these reasons, it may be advantageous in some embodiments to more sensitively detect Therefore, these photodiode examples detect light from the plasma, but do not detect reflected or Therapeutic radiation that scatters less (eg, a 1060 nm laser beam) will be detected less. In another embodiment, the photodiode is protected with an optical coating to prevent detection of the therapeutic wavelength. The optical fiber may be coated with a coating (e.g., an interference notch filter coating). In another embodiment, the photodiode is spectrally polarized to prevent detection of the therapeutic wavelength. It may be placed behind a filter (eg, an interference notch filter membrane).

[0178] The light from the plasma is converted into a small electrical current by one or more photodiodes 1642. The current is converted to a voltage by a transimpedance amplifier. The pressure is amplified by one or more amplifiers and sampled by a microcontroller. The microcontroller includes an analog-to-digital converter (ADC) and a comparator. The voltage is sampled using one or more of:

[0179] In some versions, a comparator compares the voltage to a threshold and triggers the timer if the voltage exceeds the threshold. The microcontroller will trigger the synchronous synchronous oscillator (for example, 32678Hz). If the threshold is held above the threshold for a set period (e.g., 3 ticks of the timer), In some embodiments, the threshold is set to detect plasma generated during interstitial treatment. The threshold is set high so that the marker does not exceed the threshold, but the marker is closer and brighter in the optical window. In this case, the plasma detector may be damaged, possibly resulting in damage to the patient or the system. Used to detect unwanted plasma, such as plasma in surrounding tissue or optical windows that may be contaminated by plasma. When plasma is detected, a signal is sent to another controller (laser controller). controller) to log plasma detections and / or modify treatment based on detections (or stop the therapeutic radiation).

[0180] According to some embodiments, the ADCs are administered to plasma in tissue (e.g., in the presence of a therapeutic agent). The ADC can be used to detect the voltage from one or more photodetectors. In some cases, the digital value is assigned based on the X stage 1625, Y stage 1626, and Z stage 1627. In this case, the digital value for the position of the focal region is recorded together with the current position value. The logging may be formalized as a matrix (e.g., a map). The tricks may be used to indicate the efficacy of treatment or the presence of chromophores in tissue.

[0181] In some embodiments, the presence of the plasma at the first depth (e.g., relatively shallow) can include: This may indicate damage or side effects to the system, while the second depth (e.g., ratios within tissue The presence of plasma at relatively deep depths can indicate effective treatment. In the embodiment, it is possible to ensure that the focal region of the EMR beam is located at the desired focal depth. It is important that:

[0182] [Focus depth reference example] As mentioned above, in some embodiments, the depth of the focal region within the tissue is precisely controlled. For example, treatment of dermal pigmentation requires that focal areas are located within the tissue. The focal area must be placed at approximately the same depth as the dermal pigment. If the focal area is too shallow, the melanocytes in the basal layer is irradiated, potentially inducing adverse events (e.g., hyperpigmentation or hypopigmentation) It's possible.

[0183] Referring to FIG. 17, a flowchart for a depth of focus reference method 1700 according to some embodiments is shown. A flow chart 1700 is shown. First, an electromagnetic radiation (EMR) beam is directed along an optical axis. The EMR beam is focused to a focal region by a laser (1710). In many cases, the EMR beam is focused by a laser from an EMR source (e.g. The optical window is arranged to intersect with the optical axis. In some versions, the surface of the window is substantially perpendicular to the optical axis. Signal radiation is generated upon impact with at least one surface. The signal radiation includes a reflected portion of the EMR beam that is reflected off a surface of the window. The window is configured to contact tissue. The window surface is configured to contact the window material and the window surface. The optical interface between the material and the adjacent material (e.g., air or tissue) In some cases, the gap between the window material and the adjacent material may be optically understood as a thin, non-uniform surface. The difference in refractive index causes the reflected portion of the EMR beam to be reflected. The signal radiation is produced by scattering or transmitting a portion of the EMR beam at the window.

[0184] A signal emission is detected 1712. According to some embodiments, the signal emission is detected based on an image. In some cases, the image of the signal emission is imaged by an imaging system. Examples of sensors include optical sensors and image sensors. In some versions, a detector detects and measures the width of the image. Generally, the width of the image is determined by the window. The magnification of an imaging system is usually proportional to the beam width of the EMR beam incident on the surface of the Determine the proportionality of the image width to the width of the EMR beam incident on the window. According to an embodiment, the detector detects and measures the intensity of the signal radiation.

[0185] Based on the signal emission, a reference focal position is determined (1714). In this case, the beam width of the EMR beam incident on the window surface is measured. When the focus is shifted, the focal position of the focal region moves along the optical axis. The reference position is the position where the beam width is at its minimum. As another example, in some versions, the focus of the focus area The intensity of the signal radiation is detected as the position is moved along the optical axis. In this case, the reference position is found where the emitted signal strength is found to be maximum.

[0186] Once the reference focal position is determined, the focal region is transformed 1716 into a treatment focal position. Typically, the treatment focal position is a predetermined distance away from the reference focal position along the optical axis. According to some embodiments, the focal region is a region in which an optical element (e.g., an objective lens) is aligned along an optical axis. In another embodiment, the focal region is transformed by moving the The light is converted by adjusting the dispersion, for example by adjusting the optical power of an optical element. Finally, the window is placed in contact with the target tissue, resulting in a focal region within the target tissue. According to some embodiments, the target tissue is skin and the focal region is located on the skin. The precise depth positioning of the focal region within the tissue is achieved by thermionic plasma. Or through thermal destruction, it allows for the treatment of previously untreatable pigmentation conditions. For example, The EMR beam is focused on a focal area located within the dermis without risking harmful irradiation of the epidermis. To perform selective thermoelectron plasma-mediated treatment of dermal pigmentation conditions (e.g., dermal melasma) can be done.

[0187] Referring to FIG. 18B, in some embodiments, the second EMR beam 1816B is focused The point optics is configured to focus the light onto a second focal region 1818B located at the treatment location. In this case, the first EMR beam 1816A may be configured for reference purposes only. , (e.g., to extract a first focal region 1818A incident on the surface of the window 1810), and and the second EMR beam 1816B is used to achieve a desired effect (e.g., a cosmetic effect) in the tissue. This can be configured to achieve very high tissue effects (e.g., 10 12 W / cm 2 ), where the first EMR beam is used during referencing. If the window 1810 is damaged, the window 1810 may be damaged. The MR beam 1816B has a wavelength approximately equal to that of the first EMR beam 1816A. In an embodiment, the second EMR beam 1816B has a wavelength different from that of the first EMR beam 1816A. In this case, the treatment location is the focal optics at the two different wavelengths. Calibration based on different focal lengths may be required.

[0188] 18A-18b, a method for determining depth of focus and A schematic diagram of a treatment system 1800 is shown. The focal depth reference system 1800 is The optical system includes a window 1810 configured to contact tissue 1812. The objective lens or focusing optics focuses the electromagnetic radiation (EMR) beam 1816 along an optical axis 1820. The optical axis 1820 intersects the window 1810 and is configured to focus the light into a focal region 1818. The optical detector 1822 is configured to detect signal radiation 1824. According to this embodiment, the signal radiation 1824 is between the EMR beam 1820 and the window 1810. In some versions, the EMR beam 1820 and the window 1 The interaction between window 1810 is the interaction between the surface of window 1810 and the EMR beam. The interaction between the EMR beam 1820 and the window 1810 typically involves a number of processes, including reflection, transmission, and scattering. At least one of these.

[0189] The controller 1826 receives input from the optical detector 1822 and controls the optical axis 1820. The optical detector 1822 is configured to convert the focal position of the focal region 1818 along the Based at least in part on the feedback from the focus sensor 1826, the focus sensor 1826 determines the focus region. A reference location 1828 is determined in which a portion of 1818 substantially coincides with a surface of the window 1810 .

[0190] Signal radiation 1824 arises from the reflection of the EMR beam 1816 incident on the surface of the window 1810. The light is then (partially) focused onto the image sensor 1822 using focusing optics 1814. According to some embodiments, the controller 1826 may Determine the reference position by determining the lateral width of the EMR beam 1816 incident on the window surface Then, the focal region is transformed until the width reaches a minimum value. Radiation is emitted from the reflection of the EMR beam 1816 at the surface of the window 1810 and is incident on a detector 1822. is configured to detect the intensity of the signal radiation. In this case, the controller The reference position may be determined by translating the focal region until the intensity of .

[0191] Finally, the controller 1826 adjusts the focal region 1818 to a predetermined distance from the reference position 1828. 1830 to the treatment position. 8 in the positive direction along the optical axis 1820 (i.e., the optical system 1814 In some embodiments, the treatment location is located within the tissue. For example, the predetermined distance may be configured to identify a treatment location within a dermal tissue of the skin. The stage 1832 may be configured with one or more optical stages to transform the focal region. Transforming elements (e.g., focusing optics) may be used. The EMR beam 1816 Typically, the effect in tissue (e.g., aesthetic) is achieved at or near a focal region located at the treatment location. An example of a tissue effect is selective thermoelectric generation of tissue 1812. It is a plasma-mediated treatment.

[0192] In some embodiments, the second EMR beam is positioned at the treatment location by focusing optics. In this case, the first EMR beam is configured to be focused to a second focal region that is a reference and the second EMR beam may be configured to perform a tissue effect. This is because tissue effects occur at very high fluences (e.g., 10 12 W / cm 2 ) is required This may be advantageous in embodiments where the window 1810 is likely to be damaged during referencing. According to some embodiments, the second EMR beam may be the same as the first EMR beam. In other embodiments, the second EMR beam has a wavelength that is equal to or greater than the wavelength of the first EMR beam. have different wavelengths. In this case, the treatment location is the focal point of the focusing optics at the two different wavelengths. Calibration is required based on the difference in distance. In some embodiments, the window reference and treatment system The stem 1800 is used to measure one or more reference positions 1828 .

[0193] For example, according to some embodiments, the window reference and treatment system 1800 also includes a scanning The scanning system includes a focal region 1818 and an optical axis 1820 in at least one scanning axis. 1820. In some cases, the scan axis is generally configured to move the optical axis 182 It may be perpendicular to 0.

[0194] The parallelism measurement between the window and the scan axis is performed by measuring multiple reference positions 1828 at multiple scan positions. For example, the reference system 1800 may be initially determined by The first reference position is then determined by moving the optical axis 1818 to the first reference position. The reference system is then repositioned to a second scan position that is a distance along the scan axis away from the scan position. The system 1800 determines a second reference position. The difference between the first and second reference positions is calculated along the scan axis. Dividing the distance by the window distance indicates the slope of non-parallelism between the window and the scanning axis. To further illustrate the depth of focus references, specific embodiments are provided below.

[0195] [Focus depth reference example 1] An example of the first focal depth reference is described below. Such a configuration uses a feedback system such as In some embodiments, the surface can be used to reference surfaces within tissues, not just surfaces. For example, according to some embodiments, the focal region is the dermis-epidermis (DEP) of the skin. E) The junction between the epidermis (or the melanin in the basal layer of the epidermis) and the dermis. This can be achieved in some embodiments by the refractive index difference between

[0196] FIG. 19 illustrates a bench prototype 1900 for confocal imaging and plasma-mediated therapy. A collimated laser beam 1901 is directed through an entrance aperture 1902 into the The light enters the laser beam 1900 and is projected onto a reflector 1904. The beam 1901 is folded toward the objective lens 1906. The objective lens 1906 is The beam 1901 is focused to a focal region 1907. The sample holder 1908 has a window 1910 and a The sample shown in FIG. 19 includes a sample located optically downstream from the epidermis 19. 12 is located optically downstream from the epidermis 1912 and the dermis 1914. A conformable material such as window 1916 presses the sample against window 1910 and holds the window in the sample holder. The sample holder is used to press the sample against the landing point of the XY stage 1908. 18X and 1918Y. The prototype 1900 uses the laser beam as a reference. The Z stage 1920 is connected to the objective lens 1906 and the sample holder 19 08. The micrometer screw gauge allows you to adjust the distance between The movement of the Z stage 1920 can be precisely controlled. The light 1922 reflected from the area 1907 is collimated. 04. According to some embodiments, radiation 192 2 is a filter 1922 such that only a portion of the radiation 1922 having a particular wavelength range is accepted. The radiation 1922 passes through a filter 923 (e.g., a notch filter). The light is focused to aperture 1926 at focal point 1907 (e.g., less than 50 μm). Finally, the ray 1922 is sized to receive only rays originating from The light is projected onto a photodiode 1928.

[0197] In one embodiment, the optical system 1900 is used as a confocal microscope. For example, this may be accomplished by placing a second objective lens 1924 upstream from the aperture 1926. The aperture 1926 may be configured to focus the signal radiation onto a focal plane that contains the aperture 1926. Thus, the signal radiation 1922 can be re-imaged. 2. The unwanted spatial frequencies can be filtered (e.g., blocked). Such a configuration may be used to target tissues 1912 and 1914 in different regions (e.g., relative to the tissue surface). It allows filtering of signal emissions associated with different depths of the target tissue. The distance between the imaging aperture 1926 and the target tissues 1912 and 1914 can be changed ( For example, by moving the imaging aperture 1926 along the path of the signal radiation 1922 , commands can be sent to the actuator to image other depths of the target tissue ( 19 26). The controller 506 analyzes the detection data and applies the The presence of plasma in the target tissue, dye distribution in the target tissue, etc. may be determined.

[0198] To focus the laser beam to a given depth below the surface, a focal region 1907 is placed relative to the surface. Therefore, in some embodiments, the surface of the sample (e.g., For example, the position of the objective lens 1916 relative to the surface of the sample facing the objective lens 1906 This is advantageously done by referencing the focal region 1907 to the surface of the sample. Using the bench prototype described above, the focal region may be determined by the window 1910 to determine where the sample is located relative to the top and bottom of the skin and the top surface of the pig skin sample. Tests are performed to determine whether

[0199] The NUFERN 30W fiber laser, operating at a wavelength of 1060nm, has a diameter of approximately The reflector 1904 is used to provide a laser beam 1901 that is 7.5 mm in diameter. Reflects over 90% of the laser beam 1901 and transmits less than 10% at a wavelength of 1060 nm The effective focal length of the objective lens is about 8 mm. The tube 1924 is about The reflected light 1922 is focused with an effective focal length of 30 mm. The aperture 1926 is approximately 30 microns. The fiber laser operates at a power level of 0.1% (1 mJ / pulse) and It operates at a repetition rate of 30KHz. The signal from the photodiode 1928 is fed to the oscilloscope. When the fiber laser is turned on, the Z-Stage 1920 is The loop is slowly scanned until it captures the maximum signal.

[0200] Figure 20 shows maximum radiation intensity measurements. Intensity is displayed on the vertical axis in arbitrary units. Time is plotted along the horizontal axis. The maximum radiation intensity signal 2002 is the maximum radiation intensity signal 2002 when the focal region 1907 is The Z stage is 1920 micrometers in diameter. , reported a relative position of 0.487 mm where the maximum signal 2002 was observed. 0.458 mm and at a relative Z stage position of 0.519 mm, no detectable signal is observed.

[0201] In the above example, the focal region is located at the window interface where the reflection at the interface is maximum. The difference in refractive index between the two materials causes the Reflection occurs at interfaces between materials (e.g., air and a window) and is caused by a mismatch in refractive indices. Reflection is sometimes understood as Fresnel reflection, which varies with the angle of incidence and the polarization of the light. For simplicity, Fresnel reflection at general angles of incidence (polarization independent): The Fresnel reflection that occurs at the boundary between materials with different refractive indices is generally It works as follows:

number

[0202] where R is the reflectance (the proportion of light reflected), n1 is the refractive index of the first material, and n2 is the refractive index of the second material. A good example of Fresnel reflection is provided by diamond. The refractive index of the glass is very high (e.g., 2.42). Air has a unitary refractive index. (e.g. 1.00) Fresnel reflectance of normal light at the air-diamond interface is about 17%. Fresnel reflectance tends to be smallest at normal angles and is Therefore, in the case of diamond, almost 1 / 5 of the light is absorbed by at least the air The light is reflected at the boundary between the diamond and the glass. As a result, the diamond emits light.

[0203] In the skin, melanin has a different refractive index at optical wavelengths than the surrounding tissue (e.g., 106 At 4 nm, the refractive index of melanin is approximately 1.78, while that of the epidermis is approximately 1.35). Thus, the typical Fresnel reflectance is about 2% at the skin / melanin interface. The stratum basale of the skin contains melanocytes and is therefore very rich in melanin. Beneath the dermis, except in pathological cases (especially dermal melasma), the dermis usually does not contain melanin. Thus, in some embodiments, the focal region is the dermal-epidermal junction of the skin (e.g., For example, the basal layer.

[0204] [Focus depth reference example 2] In a second example of a depth of focus reference, the camera sensor is used instead of the imaging (e.g., confocal) aperture. 21A-21C show examples according to some embodiments. a treatment system configured to focus radiation (e.g., a laser) toward a target tissue; The radiation beam is provided by an optical fiber 2110 and collimated by a collimator 2120. The radiation beam is collimated by a collimator 2112. The focused radiation beam is focused and directed through the system 2100 by the stem. The system 2100 is then finally directed out of a window 2114 at the bottom of the system 2100. 4 is in contact with the treatment tissue so that the focal region of the focused radiation beam is located within the target tissue. The system 2100 also includes a port 2116. The port is configured to At least a portion of the radiation emanating from near the focal region is directed outward. , port 2116 is where signal radiation from near the focal region is "picked off" and detected. One application of the signal radiation is to pass it through a partially reflecting interface (e.g., a window 2114). is a depth of focus reference for determining a reference focus position corresponding to the surface of the

[0205] 21B-21C show a removable reference system 212 attached to a port 2116. 2 shows system 2100 having a removable The reference system 2120 is installed prior to treatment and measures a known reference (e.g., tissue surface or This can be used to accurately position the focal region relative to the window surface. See FIG. 21C. When the beam splitter 2 is turned on, the signal radiation 2129 propagates generally along the optical axis 2130. 132 is a window through which at least a portion of the signal radiation 2129 is transmitted toward the reference system 2120. According to some embodiments, the beam splitter is a collimator 21. 12. The signal radiation The projection is an imaging lens 2136 (e.g., Edmund Optics The camera sensor is manufactured by Edmund Optics (PN:33-020). The image is captured by the 2138 (Mightex PN: SCE-B013-U) system. Measurements taken on an exemplary system with a second focal depth reference to demonstrate the accuracy and usefulness of is shown below.

[0206] The measurement indicates the position of the objective lens along the optical axis and, therefore, the corresponding focal area of ​​the window. The alignment of the focal area and the window surface was determined by the participant taking the measurements. Participants are responsible for positioning the objective lens so that the image of the signal emission is of minimal size. The measurements were taken by two participants. The first participant took all measurements for numbers 1 to 3. The first participant took the measurements, and the second participant took all the measurements for numbers 4 through 6. The measurements were taken on the front of the window. This was done in all four corners of the face: top left (TL), top right (TR), bottom left (BL), and bottom right (BR). The table below summarizes the results.

[0207] Exemplary EMR-Based Treatment and Window Referencing System [Table 2]

[0208] The measurement results were consistent even when the minimum image size was subjectively determined by different participants. The reproducibility of an exemplary window reference system is shown. Such measurements are consistent with judgements from human participants. In some embodiments, the image size is determined using a focus A controller is used to automatically control the position of the region and inferences are made from the results. To allow for this, the parallelism of the window surface with respect to one or more scan axes is determined by a window reference system. It may be calculated from measurements taken, for example, using the following formula, which assumes small angles: Therefore, the angle between the scan axis and the surface of the window can be approximated.

number

[0209] where α is the angle (in radians) between the scan axis and the surface of the window. ref,1 teeth, is the depth measured at a first location (e.g., the first corner of the window surface) in micrometers Z ref,2 is the depth (in microseconds) measured at a second location (e.g., a second corner of the window surface). meters). d 1-2 is the optical distance between the first and second positions in micrometers The distance along one or more scan axes generally perpendicular to the feedforward axis. The imaging and treatment system 2100 may include a “ According to some embodiments, there is no "pickoff" .

[0210] [Focus depth reference example 3] 22A-22C are diagrams illustrating another exemplary focal depth referencing and treatment, according to some embodiments. FIG. 22A illustrates a system 2200 for focusing radiation (e.g., a laser) onto a target tissue. The treatment system 2200 is configured to bundle the radiation beam through the optical fiber 2. 210 and collimated by collimator 2212. The focused radiation is focused and directed through the system 2200 by the optical system. The radiation beam is ultimately directed out a window 2214 at the bottom of the system 2200. 2214 is adapted to contact the treatment tissue such that the focal region of the focal radiation beam is located within the target tissue. The system 2200 is configured to provide a port or “pick-up” to the optical system. Does not include "F".

[0211] 22B-22C show a system 22 with a removable reference system 2220 attached. 00. According to an exemplary use of the system 2200, a removable reference system 222 0 is installed prior to treatment to ensure focal area against a known reference (e.g., the surface of a window). The removable reference system 2220 can be used to position the collimator 221. 2. This aligns the optical axis 2222 of the reference system 2220 nominally It should be parallel to the optical axis 2224 of the treatment system. Radiation is reference radiation source 2226 (e.g., Thorlabs bs) diode laser PN: LPS-1064-APC-SP and collimating lens [For example, Edmund Optics PN 33 -020]). The reference radiation is generated by a beam splitter 2232 (e.g., Thorlabs 50-50 Beam Splitter PN:BSW4R-10 64) and is directed along the optical axis 2222 of the reference system. The illumination radiation is directed through a reference objective 2233 (e.g., a Thorlabs PN: The signal is focused by a 1000k-series ...

[0212] In some versions, the referencing object ive)2233 is a treatment objective lens (treatment objective) 22 The reference objective lens 2233 has a prescription approximately equal to that of the reference stage 223. 5, which translates the reference objective 2233 along the optical axis 2222. The objective lens 2233 brings the reference radiation to the reference focal region along the optical axis 2222. The reference stage 2235 translates the reference focal region and the reference objective lens 2233. If the focal region is near the surface of the window 2215, a portion of the reference radiation is reflected by the window 2215. A portion of the reflected reference radiation is collimated by the reference objective lens 2233. The light is then transmitted through the beam splitter 2232 and is then picked up by the imaging lens 2236 and incident on the camera sensor 22 38. Similarly, the transmitted radiation from the collimator 2212 is imaged by the treatment objective lens 2214. 2234 and passes through window 2215, where a portion of the transmitted radiation is directed toward the reference objective lens. The light is collimated by the lens 2233, transmitted through the beam splitter 2232, and then passed through the imaging lens 2234. An imaging lens 2236 captures an image on a camera sensor 2238. It will be turned into.

[0213] According to an exemplary embodiment of the system 2200, in use, the reference focal region is The camera 2235 is translated to a reference position that coincides with the outer surface of the window 2215. The reference image captured by 2238 is aligned so that the reference focal region coincides with the exterior surface of window 2215. The reference image size is used to determine the position where the reference focal region coincides with the window 2215. At this point, the reference objective lens 2233 is generally aligned with the outer surface of the window 2215. The therapeutic radiation source is then turned on and produces penetrating radiation. In some cases, the therapeutic radiation source operates at a lower power (e.g., 10%) than normal during treatment. do.

[0214] The transmitted radiation is focused by the treatment objective lens 2234 and transmitted through the window 2215. A portion of the transmitted radiation is collimated by the reference objective lens 2233 and The light is transmitted through the illuminator 2232 and imaged onto the camera sensor 2238 by the imaging lens 2236. The focal plane of the reference objective lens 2233 (e.g., outside a window) A transmission image showing the width of the transmitted radiation beam at the focal plane (plane) is detected by the camera sensor 2238. The treatment stage 2240 translates the treatment objective 2234 along the optical axis 2224. The transmission image is the smallest size where the position of the transmission focal region coincides with the focal plane of the reference objective lens 2233. The optical axis of the reference system 2222 and the optical axis of the treatment system 2224 are nominally aligned. In some versions, the two axes are slightly separated from each other. In some embodiments, a conversion stage 2242 can be used to convert the reference system light The axis 2222 is displaced. When the transmission focal region is aligned with the outer surface of the window, the treatment The stage can be zeroed to remove the reference system and perform treatment.

[0215] EMR-based treatment based on the feedback information mentioned above (e.g., harmful or useful information during treatment) The use cases for plasma detection and precise location of the focal region are generally safe and effective. The role of EMR-based treatment based on feedback is to provide An additional use would be to image tissue to aid in diagnostic decisions or to verify positive treatment outcomes. It may be relevant for additional purposes such as capture and documentation.

[0216] [Tissue imaging example] EMR-based treatments informed through tissue image feedback are being used in dermatological and cosmetic treatments. For example, in accordance with some embodiments, the present invention has a wide range of applications and advantages for tissue imaging. This allows users to precisely target the treatment site during EMR-based therapy. Another exemplary use of tissue imaging is to provide documentation of treatment outcomes over time (e.g., According to yet another embodiment, the tissue images are To confirm a diagnosis or treatment plan for a previous condition or to confirm an endpoint during treatment Many exemplary EMR-based skin treatment goals are cosmetic (e.g., skin rejuvenation, In these cases, images of the treated skin may be provided to interested parties (e.g., patients) Provide the most important feedback to the patient (patient and physician).

[0217] FIG. 23 illustrates an imaging and radiation based therapy method 2300 according to an embodiment of the present invention. 23 shows a flowchart of a method 2300 for detecting a tumor by irradiating tissue with imaging radiation. At 2306, illumination of the tissue is typically achieved in part using an illumination source. Illumination can be performed in a variety of ways, including: Bright field illumination provided substantially on-axis, and imaging radiation provided substantially on-axis relative to the imaging system. In some embodiments, the imaging radiation is substantially uniform. In other embodiments, the imaging radiation is substantially broadband (e.g., white light). ).

[0218] Next, the image of the field of view of the tissue is imaged (2310). The imaging may be performed using focusing optics (e.g., In some cases, the field of view is performed at least in part using a focusing lens. In some embodiments, the imaging of the image (2 310) includes the use of one or more additional optics in conjunction with the focusing optics. For example, The focusing optics can significantly collimate the light from the field of view, and the collimation can be achieved using a lens barrel. An image may be formed from the reflected light. The image may be formed at an image plane.

[0219] Next, the image is detected (2312). Typically, a detector is used to detect the image. Examples of detection include optical detection, confocal optical detection, interference detection, and spectroscopic detection. , an image may be detected at the image plane. The image may be detected by an image sensor. Examples of image sensors include semiconductor charge-coupled devices (CCDs), complementary metal oxide semiconductors (CMOs), There are two types of image sensors: active pixel sensors (S) and N-type metal oxide semiconductor (NMOS). Typically, the detected image is output as a two-dimensional (2D) matrix (e.g., a bitmap). do.

[0220] The image is then displayed (2314). Typically, the image is displayed by an electronic display device. Examples of displays include electroluminescent (EL) displays, liquid crystal (LC) displays, Light-emitting diode (LED) backlit liquid crystal (LC) displays, light-emitting diode (LE D) Displays (e.g., organic light-emitting diode (OLED) displays and active matrix displays) AMOLED displays, plasma displays, and quantum The displayed image can be viewed by a designated user (e.g., a clinician). ) or the like. In some cases, the images are displayed, for example, by the controller 2419. According to some embodiments, the displayed images are recorded and stored. The agent is used to target areas of tissue that are

[0221] Next, a target therapeutic area is designated within the tissue (2316). The target treatment area is designated based on a partial image. For example, the target treatment area may be designated based on a partial image. As shown, the lesions were based on apparent excess pigment (e.g., dermal melanin) in some parts of the tissue. In some cases, the clinician viewing the displayed image may Alternatively, in some embodiments, the controller may The target treatment region is automatically designated based on the target area. The target treatment region is typically defined as at least Partially present.

[0222] Finally, the therapeutic radiation is focused (2318) to a focal region within the treatment region. Typically, The therapeutic radiation is focused using focusing optics and configured to have an effect within the tissue ( (e.g., selectively generating thermoelectron plasma with chromophores to achieve cosmetic effects). In this embodiment, parameters affecting the therapeutic radiation are controlled in part based on the image. The parameters affected by therapeutic radiation treatment are described in detail above. In some embodiments, the focal region is scanned within the target treatment area.

[0223] In some embodiments, the field of view is scanned from a first region to a second region of the tissue. Examples of these include tip / tilt of the field of view, rotation of the field of view, and translation of the field of view. Further description of the screening procedures is provided in Dresser et al., US Pat. No. 6,349,313, incorporated herein by reference in its entirety. US Patent Application No. 16 / 219,809 entitled "Electromagnetic Radiation Beam Scanning System and Method" In some embodiments, the field of view located in the first region is a field of view located in the second region. In this case, some tissue is present in both the first and second regions. In another embodiment, the field of view located in the first region does not overlap with the field of view located in the second region. In some embodiments, scanning the field of view uses feedback related to the position of the field of view. For example, in some cases, this is achieved by moving the focusing optics with two linear stages. The field of view is scanned by the linear stage. Feedback from encoders on each linear stage is used to estimate the position of the field of view when located in the first and / or second regions. Good too.

[0224] A second image of the field of view from a second region can be imaged. Typically, imaging of the second image is performed using a The imaging of the image is performed in the same manner (2310), and only the position of the field of view differs between the two steps. The imaging is performed at least in part using focusing optics. , the field of view is the field of view of the focal region with respect to the focusing optics. A second image may be detected. Typically, the detection of the second image is performed in the same manner as the detection of the first image (2312), with only one The difference is that the second image is detected instead of the first image.

[0225] In some cases, both the first and second images have an inset image (or map) inserted. The inset image may contain additional images taken with fields of view located in additional areas. Inset images may be used to document pre-treatment images of tissue or post-treatment images of tissue. Any of the first image, second image, and inset image may be taken before treatment. and may be used, for example, to support diagnostic decisions by medical personnel. Similarly, the first, second and inset images may be used to demonstrate the efficacy of treatment. Photographs taken during or after treatment to identify endpoints during treatment that may indicate the end of treatment. You may also use the camera.

[0226] Referring to FIG. 24, a tissue imaging and treatment system 2400 according to some embodiments. A schematic diagram of an imaging and therapy system 2400 is shown. 10. Focusing optics 2410 (e.g., objective lens) focuses a field of view 241 of tissue 2413. 2. The detector 2414 is focused by focusing optics 2410. The detector 2414 is configured to detect at least a partially formed image 2416. , and a display 2417. The display may display the According to some embodiments, the tube 2418 is configured to display an image to a medical practitioner. , which are used in conjunction with focusing optics 2410 to form an image 2416. Detector 2414 In this case, data related to the image detected by the detector is input to the controller 2419. The focusing optics 2410 communicates with the controller 2419 in such a way that the focusing optics 2410 is capable of performing not only imaging but also treatment. The scanner 2422 is used to transmit radiation 2420. The scanner 2422 scans the field of view 2412. The scanner is typically configured to scan the field of view in one or more dimensions. In an embodiment, the scanner 2422 scans the field of view in all three dimensions. , the scanner 2422 scans the tissue 2413 from a first region 2424 to a second region 2426. 2412 is shown to be scanned.

[0227] As the scanner 2422 scans the field of view 2412, the focusing optics 2410 focus the first region 2 A first image is imaged at 424 and a second image is imaged at a second region 2426. The first detected image and the second image are both detected by detector 2414. Data relating to the two detected images is input to the controller 2419. In this example, data associated with multiple images is inserted together by the controller 2419. These are then stitched together to produce an inset image (or map). and / or one or more images are recorded and stored by the controller for later viewing. In some embodiments, data from one or more images may be used to treat According to some embodiments, the determination of the treatment area is performed by the controller. In another embodiment, the determination of the treatment area is performed automatically after viewing one or more images. Manually performed by a designated user.

[0228] The therapeutic radiation 2420 is focused to a focal region by focusing optics 2410. The dot area is directed toward the treatment area. According to some embodiments, the scanner 2422 The system 2400 includes a plurality of imaging devices 2404 configured to scan a focal region within the treatment region. The embodiment includes a window 2430 that is placed in contact with the surface of the tissue 2413. The window 2430 , are used for various purposes, one of which is to digitize the outer surface of tissue. 30 ensures that the focal region is positioned within the tissue 2413 at a predetermined depth from the surface of the tissue 2413. This enables it to be.

[0229] FIG. 25 illustrates a schematic of an inset image (or map) 2500, according to some embodiments. The inset image 2500 includes a number of (eg, nine) individual images 2510. Scan path 2520 shows the path taken by the field of view across the tissue. includes a raster pattern, but other patterns (e.g., spiral) are also possible. Each image 2510 is taken at a point along the scan path. 2500 can be formed from the individual images in a variety of ways. For example, the position of the field of view can be determined by the individual images. If it can be estimated for the image (e.g., via scanner feedback), Dead-reckoning calculation Alternatively, the inset image 2500 may be constructed by inset (sequence). The imaging system can be built using machine vision algorithms for image stitching. The first example of stitching software was Hugin-Panora. Hugin is a photo stitcher. n. Open source projects hosted on Sourceforge.net The second example of image stitching software is Adobe Photoshop. Photomerge in Adobe Photoshop Certain embodiments further enhance tissue imaging in EMR treatment devices. The following is provided to illustrate:

[0230] [Tissue imaging example 1] 26A-26B show a schematic diagram of an exemplary tissue imaging and treatment system 2600. FIG. 26A shows a front view of the system 2600. FIG. 26B shows a cross-sectional view taken along line BB of FIG. 2 shows a cross-sectional view of system 2600 taken along the line.

[0231] The system 2600 includes a fiber laser 2610. The fiber laser 2610 is An example of a fiber laser is available from Fiber Laser Technologies, Inc., located in Shanghai, China. Fiber 1060nm, 40W, 20Khz, Fiber Laser Technology The therapeutic radiation is delivered to the tissue through a window 2622 by an optical system. The therapeutic radiation is directed to focusing optics 2620 which focuses the therapeutic radiation to a focal region within the endoscopic cavity (not shown). The optical system is configured such that the focusing optics 2620 are scanned in all three dimensions. This allows the focal area of ​​therapeutic radiation to be scanned in all three dimensions within the tissue. This is achieved by three separate stages, each responsible for a single axis. X-Stage 2625 The Y-stage 2626 mounted on the X-stage 2625 scans the focusing optics in the X-axis. scans the focusing optics in the Y axis, and a Z stage mounted on the Y stage 2626 scans the focusing optics in the Z axis (i.e., generally along the optical axis of the focusing optics). The X Stage is located in Boxborough, Massachusetts, USA. The DoverMMX 50 was manufactured by Dover Motion, Inc., located in Israel. ELMO Motion Control, Petach-Tikva, Israel ELMO by Elmo Motion Controller Ltd. DC Whistle Gold Controller (Elmo DC whistle Gold controller An exemplary Y stage is manufactured by the NASA Aerospace Exploration Agency (NASA) in Boston, MA. Physik Instruments, Inc., Auburn, California Controlled by the E873 controller from hysik Instrumente LP An exemplary Z stage is the Q545.140 stage. New Scale Technologies, Inc., located in Victor, The new scale model is 3M-FS from Epson Technologies, Inc.

[0232] The optical system is designed to reflect the therapeutic radiation and allow other radiation (e.g. visible light) to pass through. Thus, imaging radiation (e.g., The light (e.g., visible light) is focused by focusing optics 2620 through beam splitter 2630 into an image. The down beam of the beam splitter 2630 is provided with a lens assembly 2632. An example of a lens assembly is provided by Corning NY, USA. Corning Inc., located at 1-800-850-5500, has a 10-year history of producing 100% chromatographic data. ioOptic Autofocus Lens Module Part Number: CC-39NO-2 The imaging radiation is further imaged by a lens assembly and finally The camera is detected by an image sensor in the camera, specifically the camera 2634. The PL-D755 was manufactured by PixelLink in Ontario. The PL-D755 is equipped with a Sony IMX25 with a global shutter. 0 CMOS image sensor. To image very small areas with a microscope, The imaging systems described above require illumination of the tissue.

[0233] Frame 2640 is shown with a number of holes 2642 therethrough. A number of optical fiber bundles (not shown) are disposed within the bore 2642. The ceremony consisted of 12 optical fiber bundles housed in a 0.06-inch diameter stainless steel tube. The optical fiber bundle is disposed in a hole 2642 located around the periphery of the frame 2640. The single bundle is placed in optical communication with the light source. Fiber Optics Technology, Pomfret, Connecticut Fiberoptics Technology Incorporated ) Daylight White 6500K 38W Light Engine Part Number FTIII24015 The holes 2642 are angled toward the windows 2622 so that the optical fibers The light from the bundle is directed towards the tissue when the bundle is present. The angle relative to the optical axis of the focusing optics In some embodiments, shining light in a dark field may be referred to as dark field illumination. Illumination is achieved by focusing optics where specular reflections from the window surface are not imaged (as glare) In other embodiments, the illumination is provided generally coaxially with the optical axis. Brightfield illumination is sometimes called brightfield illumination. Brightfield illumination focuses more light within the field of view of the focusing optics. This is advantageous in some embodiments because it provides a large illumination density. To that end, images taken with an exemplary imaging system will be described.

[0234] FIG. 27A is a photograph taken by the exemplary system 2600 shown in FIGS. Shown here is Image 2710, which was taken of an Air Force target in 1951. There are 18 images like this one, image 2710, taken (2 rows of 9). The images were then merged together into the inset image 2720 shown in FIG. "Fitting" is a photo editing program for Adobe Photoshop. This was done automatically using the Photomerge tool. Considering 20, we can see that element 6 of group 7 is decomposable. The line width of element 6 is about 2.2 μm. Microscopic imaging is therefore shown in Figures 26A and b. The exemplary system 2600 described above is useful and practical.

[0235] [Additional embodiment] In some embodiments, the repetition rate of the input laser beam is adjusted to account for the amount of light emitted by the laser beam within the target tissue / target material. This can be faster than the rate of plasma decay. The repetition rate of the laser beam can be increased to 100 times the normal rate of the plasma generation. By changing the intensity, the treatment area / target area (e.g. the area where plasma is generated) can be adjusted. The area can be controlled.

[0236] Additional embodiments include alternative imaging techniques used in combination with EMR-based therapy. Such alternative imaging techniques include electron microscopy imaging, wide-field imaging, and reflectance confocal imaging. Imaging, Optical Coherence Tomography Imaging, Optical Coherence Elastography Imaging, Coherent anti-Stokes Raman spectroscopic imaging, two-photon imaging, optical second harmonic imaging, phase These include conjugate imaging, photoacoustic imaging, infrared spectroscopic imaging, and hyperspectral imaging. .

[0237] One skilled in the art will appreciate further features and advantages of the present invention based on the above-described embodiments. Accordingly, the invention is not to be construed as particularly shown and described, except as indicated by the appended claims. All publications and references cited herein are to be construed as being in accordance with the principles of the present invention, without limitation to those disclosed herein. No. 6,399,313, which is expressly incorporated herein by reference in its entirety.

[0238] The subject matter described herein may be implemented as digital electronic circuitry, or as computer software, firmware, or a combination of both. The present invention may be implemented in software or hardware, and the configurations disclosed herein may be implemented in any suitable manner. The present invention includes any structural means and their structural equivalents, or any combination thereof. The subject matter described herein may be executed by or may be implemented in a data processing apparatus (e.g., a program To control the operation of any computer (a microprocessor, processor, or various computers) tangibly embodied in an information carrier (e.g., a machine-readable storage device) or propagated one or more computer programs embodied in transmitted signals The present invention can be realized by a computer program product. Software, software application or code) is compiled or It can be written in any form of programming language, including interpreted languages, and can be implemented independently. Modules and components suitable for use in a line-based program or computing environment The program may be distributed in any form, including as a program, subroutine, or other device. A program does not necessarily correspond to a file. A program can be a file that is accessed by other programs or devices. A part of the file that holds the program's data, a single file or multiple adjustment files dedicated to the program A file (e.g., a file that contains one or more modules, subprograms, or portions of code) A computer program may be stored on a computer or Distributed to run on multiple computers at multiple sites or distributed across multiple sites and may be interconnected by a communication network.

[0239] The process and logic described herein include steps of the subject method described herein. A flow is a process that converts input data into a and performing the functions of the subject matter described herein by operating on the generation of an output. The process and logic flow may be executed by one or more programmable processors. The subject matter described herein may also be implemented as follows: GA (Field Programmable Gate Array) or ASIC (Application Specific Integrated Circuit) The input signal may be implemented as a special purpose logic circuit such as

[0240] Processors suitable for the execution of a computer program include, for example, both general purpose and special purpose processors. Both microprocessors and any one or more of any kind of digital computer Typically, the processor includes a read-only memory or a random access memory. The essential elements of a computer are A processor for executing instructions and one or more memory devices for storing instructions and data. Typically, a computer also has one or more mass storage devices for storing data. A device, such as a magnetic, magneto-optical, or optical disk, receives data from or stores data or both. The information medium suitable for embodying the data includes, for example, a semiconductor memory device (e.g., PROM, EEPROM, and flash memory devices), non-volatile memory magnetic disks disks (e.g., internal hard disks or removable disks), magneto-optical disks, and optical All forms of non-volatile memory, including optical disks (e.g., CD and DVD disks) The processor and the memory may be supplemented by, or incorporated in, special purpose logic circuitry. .

[0241] To provide for interaction with a user, the subject matter described herein may, for example, provide information to a user. A CRT (cathode ray tube) or LCD (liquid crystal display) monitor for displaying information to the user. A keyboard and pointing device (e.g., a mouse or trackpad) through which the user can provide input. It can be implemented on a computer having a computer display device. Other types of devices may be used to provide interaction with the user. For example, The feedback provided may be any form of sensory feedback (e.g., visual feedback). feedback, auditory feedback, or haptic feedback) and is based on user input. The force may be received in any form, including acoustic, voice or tactile input.

[0242] The techniques described herein may be implemented using one or more modules. As used in this document, the term "Module" means computing software, This includes firmware, hardware, and / or various combinations thereof, but At least, the module is not implemented in hardware, firmware, or Software that is not recorded on a non-transitory processor-readable recordable storage medium The module itself is not software. In this context, a "module" refers to at least a portion of an object, such as a processor or part of a computer. This is interpreted as always including logical, non-transient hardware. Physical hardware can be shared (e.g. two different modules can run on the same processor) (The present specification may use a processor and a network interface.) Modules can be combined, integrated, separated, and reconfigured to support a variety of applications. and / or may be duplicated. The functions described may be functions that are performed by one or more other modules and / or by a particular module. The functions may be performed instead of or in addition to one or more other devices. The modules may be implemented locally or remotely across various devices and / or other components. Modules can also be moved from one device and added to another, or used in both devices. It can be included in the location.

[0243] The subject matter described herein includes back-end components (e.g., data servers), A hardware component (e.g., an application server) or a front-end Components (e.g., a user may interact with an implementation of the subject matter described herein) A client computer having a graphical user interface or web browser that can data), or such back-end, middleware, and front-end components The system may be implemented in a computing system including a combination of the following components: means any form or medium of digital data communication, e.g. by means of a communications network. Examples of communication networks include local area networks ("LANs"). ") and wide area networks ("WANs") (e.g., the Internet).

[0244] The language of approximation used throughout the specification and claims of this specification is intended to be understood as being consistent with the principles to which it pertains. To modify any quantitative expressions that may be permissibly varied without resulting in a change in function. "Approximately," "substantially," or "about" may be used unless expressly stated or stipulated otherwise. Unless otherwise clear from the context (if such figures exceed 100% of the acceptable values, ), within 1%, or in some embodiments, within 5%, in either direction. In one embodiment, the number can be within 10% of the range. " or "substantially" shall mean a value modified by one or more terms, e.g. In at least some instances, approximation language may be used to measure values. Throughout the specification and claims, limitations of scope may be set forth. can be combined and / or interchanged, and such scope will be identified and understood by context or Unless the language indicates otherwise, all subranges subsumed therein are included.

[0245] As used herein in the specification and claims, the articles "a" and "an" refer to Unless expressly indicated to the contrary, plural referents should be understood to be included. A claim or description containing "or" between one or more of the group constituents may be used to refer to one or more of the group constituents. is considered to be satisfied if any or all of the above features are present and in use, or Unless indicated to the contrary or apparent from the context, This disclosure provides evidence that exactly one member of the group is present in a given product or process. The present disclosure also includes embodiments in which one Are any of these or all group configurations present or used in a given product or process? Further, unless otherwise indicated or inconsistent, Unless otherwise apparent to one of ordinary skill in the art, the disclosed embodiments are not necessarily to be construed as limiting the scope of the invention as set forth herein. One or more limitations, elements, clauses, descriptive terms, etc. from one or more of the claims may be included in the same basic claim. All variations introduced in a different claim that depend on that claim (or on any other claim), It should be understood that combinations and permutations are provided. It should be understood that the embodiments are applicable to all different aspects of the disclosed embodiments where appropriate. It is also contemplated that any embodiment or aspect may incorporate one or more of the following features whenever appropriate: It is also contemplated that the present invention may be freely combined with any of the other embodiments or aspects. When elements are presented as lists (e.g., Markush groups), oup) or similar form), each subgroup of elements is also disclosed, and any element may be removed from the group. It should be understood that in general, the disclosed embodiments or the disclosed When aspects of an embodiment are referred to as including particular elements, features, etc., that particular An embodiment or aspect of the disclosure may consist of or essentially consist of such elements, features, etc. For simplicity, such an embodiment will be described in all cases as consisting of: Not specifically described in so many words herein. Specific exclusions are listed in the specification. Any embodiment or aspect of the present disclosure, whether or not expressly excluded from the claims, is expressly excluded from the claims. For example, any one or more of the active agents, additives, ingredients, or any Agents, organism types, disorders, subjects, or combinations thereof can be excluded.

[0246] To the extent provided herein, embodiments of the present disclosure include those that include an endpoint. The study included embodiments in which both endpoints were excluded altogether, and embodiments in which one endpoint was included. Unless otherwise specified, both endpoints are included in the It should be assumed that all endpoints are included. In addition, they may be displayed separately or Unless otherwise clear from the context and understanding of one of ordinary skill in the art, values ​​expressed as ranges are expressly intended to be within the scope of the present invention. Unless expressly stated otherwise, the ranges mentioned in other embodiments of this disclosure are to the tenth of the lower unit. It should be understood that any specific value or subrange within a range can be assumed. When numerical values ​​are recited herein, the present disclosure includes any number defined by any two values ​​in the range. The lowest value related similarly to any intermediate value or range will be considered the minimum value and the highest The numerical values ​​used herein are expressed as percentages, including embodiments in which a lower value may be considered a maximum value. Contains the value to be

[0247] Unless expressly indicated to the contrary, any method claimed herein may include one or more implementations. In law, the order of the acts of a method is not necessarily limited to the order in which the acts of the method are cited. However, it will be understood that the present disclosure may include embodiments in which the order is so limited. Unless otherwise indicated or clear from the context, It should also be understood that any product or composition that is prepared may be considered "separate." Must be.

[0248] As used herein, the term "comprises" refers to disclosed embodiments. Compositions, methods, and methods therefor are essential, but may include non-specified elements, whether or not essential. These are used in conjunction with each other.

[0249] As used herein, "consisting essentially of" The term "essentially of" refers to an element required for a given embodiment. does not materially affect the basic and novel or functional characteristics of the embodiments of the present invention. Allows for the presence of additional elements.

[0250] The term "consisting of" refers to a composition as described herein. The present invention refers to the method and respective components thereof, which are recited in the description of the embodiments. Excluding any elements that are not

[0251] Although a few variations have been described in detail above, other modifications or additions are possible.

[0252] In the above description and claims, "at least one A phrase such as "or" or "one or more of" refers to an element or feature. It may be followed by a list of conjunctions of signs. The term "and / or" also means two or more may appear in a list of elements or features of a Unless expressly contradicted, such phrases may refer to any of the listed elements or features individually. or any of the cited elements or features in combination with other cited elements or features. For example, in the sentence "at least one of A and B," "A and "One or more of" and "A and / or B" mean "A only, B only, or A and B," respectively. "together." A similar interpretation applies to lists containing three or more items. For example, "one or more of A, B, and C" or "one of A, B, and C" The phrases "one or more" and "A, B, and / or C" are to be interpreted as "A only, B only, C only, "A and B together, A and C together, B and C together, or A, B and C together" Moreover, use of the term "based on" above and in the claims is intended to "based at least in part on" is intended to allow for features or elements not included in the invention. It is intended that.

[0253] The subject matter described herein may be implemented as systems, apparatus, methods, and / or The implementations described in the above description may be embodied in any of the methods described herein. These are not intended to represent all implementations consistent with the subject matter described. Instead, they are intended to represent all implementations consistent with the subject matter described. These are just a few examples consistent with aspects related to the subject matter. However, other modifications or additions are possible, particularly to those described herein. Additionally, further features and / or variations may be provided. For example, the above implementations may be implemented in accordance with the disclosed Various combinations and subcombinations of the features described above and / or various other aspects of the present invention may be used. The present invention may relate to any combination or subcombination of features as set forth in the accompanying drawings. The logic flows shown and / or described herein are intended to accomplish desired results. The particular order or sequential order shown is not necessarily required. may be in the range.

Claims

1. 1. A system comprising: a focusing optic configured to focus the electromagnetic radiation (EMR) beam to a focal region disposed along an optical axis; a window intersecting the optical axis and configured to contact a surface of tissue; a stage configured to translate the focal region along the optical axis; an optical detector configured to detect a width of a signal radiation emanating from reflection of the EMR beam at a surface of the window, the width of the signal radiation being indicative of a lateral width of the EMR beam incident on the surface of the window; A controller, Using the stage to translate the focal region along the optical axis; determining a reference position where a portion of the focal region coincides with the surface of the window within a tolerance of 30 micrometers or less based on a position of the focal region corresponding to a minimum lateral width of the EMR beam incident on the surface of the window; a controller configured to translate the focal region using the stage to a treatment position, the treatment position being a predetermined distance from the reference position along the optical axis; Including, the system.

2. The system of claim 1 , wherein the treatment location is configured to be located within the tissue.

3. The system described in claim 2, wherein the predetermined distance is configured to identify the treatment location within dermal tissue.

4. The system of claim 2 , wherein the EMR beam is configured to perform selective thermionic plasma mediated treatment of the tissue.

5. The system of claim 1 , wherein the EMR beam includes pulses having a pulse duration of at least 1 picosecond.

6. The system of claim 1 , wherein the focusing optics is further configured to image the signal radiation incident on the optical detector.

7. The focusing optics further configured to focus the second EMR beam to a second focal region; The second EMR beam is the same wavelength as the wavelength of the EMR beam, or at least one of the wavelengths being different from the wavelength of the EMR beam; the second EMR beam is configured to produce a therapeutic effect on the tissue. The system of claim 1 .

8. The system of claim 1 , wherein the stage is configured to transform the focal region by transforming at least one of the focusing optics, one or more optical elements, and the window.

9. The system of claim 1, wherein the focusing optics are configured to focus the EMR beam to the focal region with a numerical aperture (NA) in the range of 0.2 to 1.

0.

10. The system described in claim 1, wherein the focusing optics are configured to focus the EMR beam into the focal region having a size that includes at least one of a width or a length extending in the direction of the optical axis.

11. The system of claim 1, wherein the optical detector includes at least one of a charge-coupled device (CCD) sensor or a complementary metal-oxide semiconductor (CMOS) sensor.

12. The optical fiber system according to claim 1, further comprising a beam scanning system configured to scan the focal region along a scanning axis to a second position; The controller: determining a second reference position relative to the second position, a portion of the focal region coinciding with the surface of the window; and further configured to calculate an angle between the window and the scan path based in part on the second reference position. The system of claim 1 .

Images