WO2008070851A2 - Utilisation de la technologie rem sur des incisions et des tissus internes - Google Patents

Utilisation de la technologie rem sur des incisions et des tissus internes Download PDF

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Publication number
WO2008070851A2
WO2008070851A2 PCT/US2007/086827 US2007086827W WO2008070851A2 WO 2008070851 A2 WO2008070851 A2 WO 2008070851A2 US 2007086827 W US2007086827 W US 2007086827W WO 2008070851 A2 WO2008070851 A2 WO 2008070851A2
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Prior art keywords
tissue
islets
treatment
emr
volume
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PCT/US2007/086827
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English (en)
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WO2008070851A3 (fr
Inventor
Richard Cohen
Michael H. Smotrich
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Palomar Medical Technologies, Inc.
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Publication of WO2008070851A2 publication Critical patent/WO2008070851A2/fr
Publication of WO2008070851A3 publication Critical patent/WO2008070851A3/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A61B18/20—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00017—Electrical control of surgical instruments
    • A61B2017/00022—Sensing or detecting at the treatment site
    • A61B2017/00039—Electric or electromagnetic phenomena other than conductivity, e.g. capacity, inductivity, Hall effect
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00743—Type of operation; Specification of treatment sites
    • A61B2017/00747—Dermatology
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00005—Cooling or heating of the probe or tissue immediately surrounding the probe
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A61B18/20—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
    • A61B2018/208—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser with multiple treatment beams not sharing a common path, e.g. non-axial or parallel

Definitions

  • the devices and methods disclosed herein relate to the treatment of soft and hard tissues with electromagnetic radiation (EMR) to produce lattices of EMR-treated islets in the tissue to stimulate and facilitate repair and healing in a controlled fashion.
  • EMR electromagnetic radiation
  • the devices and methods also relate to systems for producing such lattices of EMR-treated islets in tissue, and cosmetic, medical and other applications of such devices, methods and systems.
  • Electromagnetic radiation has been used in a variety of cosmetic and medical applications, including uses in dermatology, dentistry, ophthalmology, gynecology, otorhinolaryngology and internal medicine.
  • the EMR treatment can be performed with a device that delivers the EMR to the surface of the targeted tissues.
  • the EMR treatment is typically performed with a device that works in combination with an endoscope or catheter to deliver the EMR to internal surfaces and tissues
  • the EMR treatment is typically designed to (a) deliver one or more particular wavelengths (or a particular continuous range of wavelengths) of
  • EMR EMR to a tissue to induce a particular chemical reaction
  • EMR treatments of various tissues have some of the same limitations as similar cosmetic treatments that apply EMR to the surface of skin to perform, e g , resurfacing or other procedures
  • the wavelengths typically utilized for selective photothermo lysis may be highly scattered and/or highly absorbed, which limits the ability to selectively target body components and, in particular, limits the depths at which treatments can be effectively and efficiently performed
  • Much of the energy applied to a target region may be either scattered such that it does not reach the body component undergoing treatment, or may be absorbed by overlying or surrounding tissue
  • larger and more powerful EMR sources may be required m order to achieve a desired therapeutic result
  • increasing power may cause undesired and potentially dangerous heating of tissue
  • One aspect of the invention is a method of treating internal tissue that includes accessing an internal tissue volume to be treated, and irradiating portions of the internal tissue volume with electromagnetic radiation The electromagnetic radiation causes the heated portions to form islets of treated tissue surrounded by untreated tissue
  • the internal tissue is accessed by one of an incision, an open wound, and an orifice of a body cavity
  • the internal tissue is a tissue from the group muscle, cartilage, ligaments, bone, fat, dermis, blood vessels, nervous tissue, gastrointestinal, heart, lungs, kidney, gall bladder, and liver
  • the heated portions may be ablated, coagulated, and/or denatured
  • the heated portions may alternatively be heated without further damage to the tissue in the heated portions
  • the treated tissue may be welded
  • the treated tissue may be a surgical incision and/or be composed of two portions of tissue joined during surgery
  • the heated portions may be heated substantially simultaneously or may be scanned
  • the treated portions may be irradiated for a time that is greater than the thermal relaxation time of the tissue volume to be treated
  • Another aspect of the invention is a method of treating internal tissue that includes inserting a treatment device into the internal tissue to be treated, causing the treatment device to transmit electromagnetic radiation from the device to portions of the internal tissue, and forming subvolumes
  • Another aspect of the invention is a method of performing a treatment on a volume located at area and depth coordinates of an internal tissue of a patient, which includes providing a source of treatment radiation, and applying treatment radiation from the source to an optical system providing multiple foci for concentrating said radiation to at least one depth within said depth coordinate and to selected areas within said area coordinates of said volume such that following application of the treatment radiation three dimensionally located treatment portions are formed at the foci in said volume separated from one another by untreated portions of said volume
  • Another aspect of the invention is a method for performing a treatment on a volume located at area and depth coordinates of an internal tissue by irradiating portions of the volume including providing a source of treatment radiation, precoohng the internal tissue over at least part of the area coordinate to a selected temperature for a selected duration, the selected temperature and duration being sufficient to cool the internal tissue to a depth below the depth coordinate to a temperature below normal body temperature of the internal tissue, and applying the treatment radiation to an optical system having a plurality of foci which concentrates said radiation to at least one depth coordinate and to selected areas within said area coordinate to define treatment portions at said foci in said volume following application of the treatment radiation, said treatment portions being less than said volume, each said treatment portion being within untreated portions and being substantially surrounded by cooled internal tissue separating said treatment portion from other treatment portions
  • Another aspect of the invention is a device for performing a treatment on a volume of internal tissue located at area and depth coordinates of a patient's skin
  • the device may include a source of treatment radiation, an optical system to which treatment
  • the methods and devices described herein provide for the fractional treatment of various hard and soft tissues such as internal tissues, including without limitation, muscle (including smooth, cardiac and striated muscle), cartilage, ligaments, bone, blood vessels, nervous tissue, tissue of the gastrointestinal system (including the esophagus, stomach, small intestine, large intestine and colon) and tissue of various organs such as the heart, lungs, kidney, gall bladder, and liver
  • tissues may be treated, for example, during a surgical or medical procedure through an incision or using a catheter or other devices
  • Such tissues can also be treated using nonsurgical and non-medical procedures, for example, as during therapy or the treatment of post-operative and other wounds
  • FIGS IA- 1C are semi-schematic perspective and side views respectively of a section of muscle tissue and of equipment positioned thereon for practicing one embodiment
  • FIG 2 is a schematic diagram of a device for treating internal tissue
  • FIG 3 is a schematic diagram of an alternate embodiment of a device for treating internal tissue
  • FIG 4 is a side schematic view of some components that can be used m some aspects
  • FIGS 5 and 5 A are schematic views other embodiments of the invention in which an endoscope is used to create EMR-treated islets in the walls of a blood vessel
  • FIGS 6A and 6B are top views of various matrix arrays of cylindrical lenses, some of which are suitable for providing a line focus for a plurality of target portions
  • FIGS 7A-7C are top views of various matrix arrays of cylindrical lenses, some of which are suitable for providing a line focus for a plurality of target portions
  • FIGS 8A-8D are cross-sectional or side views of one layer of a matrix cylindrical lens system suitable for delivering radiation in parallel to a plurality of target portions
  • FIG 9A is a side view of yet another embodiment
  • FIGS 9B to 9E are enlarged, side views of the distal end of the embodiment of FIG 9A
  • FIG 1OA is a side view of yet another embodiment
  • FIGS 1OB and 1OC are enlarged, side views of the distal end of the embodiment of FIG 1OA
  • FIG 11 is a side view of yet another embodiment
  • FIG 12A is a side view of an embodiment using a diode laser bar
  • FIG 12B is a perspective view of a diode laser bar that can be used in the embodiment of FIG 12A
  • FIG 12C is a side view of yet another embodiment, which uses multiple diode laser bars
  • FIG 12D is a side view of yet another embodiment, which uses multiple diode laser bars
  • FIG 12E is a side view of yet another embodiment, which uses multiple optical fibers to couple optical energy
  • FIG 13 A is a side view of another embodiment
  • FIG 13B is a perspective view of a light source and optical fiber that can be used along with the embodiment of FIG 13A
  • FIG 13C is a side view of an embodiment using a fiber bundle
  • FIG 13D is a bottom view of the embodiment of FIG 13C
  • FIG 13E is an enlarged, side view of a distal end of one of the embodiments of 13A-13D
  • FIG 14A is a side view of another embodiment, which uses a fiber bundle
  • FIG 14B is a side view of another embodiment, which uses a phase mask
  • FIG 14C is a side view of another embodiment, which uses multiple laser rods
  • FIG 15 is a bottom view of another embodiment, which uses one or more capacitive imaging arrays
  • FIG 16 is a side view of another embodiment, which uses a motor capable of moving a diode laser bar withm a hand piece
  • FIG 17 is a top view of one embodiment of a diode laser bar
  • FIG 18 is a side cross-sectional view of the diode laser bar of FIG 17
  • FIGS 19A-19C are top views of three optical systems involving arrays of optical elements suitable for use in delivering radiation in parallel to a plurality of target portions
  • FIGS 20A-21D are side views of various lens arrays suitable for delivering radiation in parallel to a plurality of target portions
  • FIGS 22A-22D are side views of Fresnel lens arrays suitable for delivering radiation in parallel to a plurality of target portions
  • FIGS 23A-23C are side views of holographic lens arrays suitable for use m delivering radiation in parallel to a plurality of target portions
  • FIGS 24A-24B are side views of gradient lens arrays suitable for use in delivering radiation in parallel to a plurality of target portions
  • FIGS 25A-25C are a perspective view and cross-sectional side views, respectively, of a two layer cylindrical lens array suitable for delivering radiation in parallel to a plurality of target portions
  • FIGS 26-29 are side views of various optical objective arrays suitable for use in concentrating radiation to one or more target portions
  • FIGS 30A-35 are side views of va ⁇ ous deflector systems suitable for use with the arrays to move to successive target portions
  • FIGS 36 and 37 are side views of two different variable focus optical systems
  • FIG 38 is a perspective view of another embodiment for creating treatment islets
  • FIG 39 is a perspective view of another embodiment
  • FIG 40 is a perspective view of yet another embodiment
  • the lattices are periodic patterns of islets in one, two or three dimensions in which the islets correspond to local maxima of EMR- treatment of tissue
  • the islets are separated from each other by non-treated tissue (or differently- or less-treated tissue)
  • the EMR-treatment results in a lattice of EMR- treated islets which have been exposed to a particular wavelength or spectrum of EMR, and which is referred to herein as a lattice of "optical islets "
  • the lattice is referred to herein as a lattice of "thermal islets
  • an amount of energy is absorbed that is sufficient to significantly disrupt cellular or intercellular structures, the lattice is referred to herein as a lattice of "damage islets "
  • EMR-treated islets can also be formed within an area or volume of treated tissue, for example, where the entire tissue area and/or volume is treated with a relatively lower intensity of EMR having a same or different wavelength while the islets are formed by treating portions of the area and/or volume using EMR having a higher intensity
  • EMR-treated islets can also be formed within an area or volume of treated tissue, for example, where the entire tissue area and/or volume is treated with a relatively lower intensity of EMR having a same or different wavelength while the islets are formed by treating portions of the area and/or volume using EMR having a higher intensity
  • EMR- treated tissues can be any hard or soft tissues for which such treatment is useful and appropriate, including but not limited to dermal tissues, mucosal tissues (e g , oral mucosa, gastrointestinal mucosa), ophthalmic tissues (e g , retinal tissues), neuronal tissue, vaginal tissue, glandular tissues (e g , prostate tissue), internal organs, bones, teeth, muscle tissue, blood vessels, tendons and ligaments
  • the lattices are periodic patterns of islets in one, two or three dimensions in which the islets correspond to local maxima of EMR-treatment of tissue
  • the islets are separated from each other by non-treated tissue (or differently- or less-treated tissue)
  • the EMR-treatment results in a lattice of EMR-treated islets which have been exposed to a particular wavelength or spectrum of EMR, and which is referred to herein as a lattice of "optical islets "
  • the lattice is referred to herein as a lattice of "thermal islets "
  • an amount of energy is absorbed that is sufficient to significantly disrupt cellular or intercellular structures
  • the lattice is referred to herein as a lattice of "damage islets
  • the lattice is referred to herein as a lattice of "photo
  • untreated regions (or differently- or less-treated regions) surrounding the islets can act as thermal energy sinks, reducing the elevation of temperature within the EMR-treated islets and/or allowing more EMR energy to be delivered to an islet without producing a thermal islet or damage islet and/or lowering the risk of bulk tissue damage
  • the percentage of tissue volume which is EMR- treated versus untreated can determine whether optical islets become thermal islets, damage islets or photochemical islets
  • This percentage is referred to as the "fill factor”
  • untreated tissue volumes act as a thermal sink, these volumes can absorb energy from treated volumes without themselves becoming thermal or damage islets
  • a relatively low fill factor can allow for the delivery of high fluence energy to some volumes while preventing the development of bulk tissue damage
  • the untreated tissue volumes act as a thermal sink, as the fill factor decreases, the likelihood of optical islets reaching critical temperatures to produce thermal islets or damage islets also decreases (even if the EMR power density and total exposure remain constant for the islet areas)
  • the embodiments described below provide improved devices and systems for producing lattices of EMR-treated islets in tissues, and improved cosmetic and medical applications of such devices and systems in plastic surgery, physical medicine, orthopedic medicine, neurology, neurosurgery, dermatology, dentistry, ophthalmology, gynecology, otorhmolaryngology and internal medicine, for example, during a surgery in which an open incision exposes the tissue to be treated or in combination with endoscope and catheter procedures
  • the devices, systems and methods are described in detail for internal medical applications, they can be used for treatment of any tissue surface or subsurface areas to which EMR can be delivered
  • the embodiments described herein relate to the creation of a multiplicity of treated volumes of the tissue which are separated by untreated volumes
  • the multiplicity of volumes can be described as defining a "lattice,” and the treated volumes, because they are separated by untreated volumes, can be described as "islets" within the tissue
  • four different categories of lattices can be produced lattices of optical islets (LOI), lattices of thermal islets (LTI), lattices of damage islets (LDI), and lattices of photochemical islets (LPCI)
  • LOI optical islets
  • LTI lattices of thermal islets
  • LLI lattices of damage islets
  • LPCI lattices of photochemical islets
  • EMR-treatment of completely or partially isolated volumes or islets of tissue produces a lattice of EMR-treated islets surrounded by untreated volumes
  • the islets can be treated with any form of EMR, they are referred to herein as "optical" islets for convenience, as many embodiments include the use of EMR within the ultraviolet, visible and mfra-red spectrum
  • Other forms of EMR may be useful, including, without limitation, microwave, radio frequency, low frequency and EMR induced by direct current
  • the tissue of an optical islet will be heated, resulting in a thermal islet If the temperature increase is sufficiently high, the tissue of a thermal islet will be damaged, resulting in a damage islet
  • the fill factor can be decreased m order to provide a greater volume of untreated tissue to act as a thermal sink
  • EMR-treatment of isolated volumes or islets of tissue can produce a lattice of thermal islets with temperatures elevated relative to those of surrounding untreated volumes Thermal islets result when energy is absorbed by an EMR-treated optical islet significantly faster than it is dissipated and, therefore, significant heating occurs
  • Heating can result from the absorbance of EMR by water present throughout a volume of treated tissue, by endogenous chromophores present in selected cells or tissue(s) (e g , melanin, hemoglobin), by exogenous chromophores pre-administered or applied within the tissue (e g , tattoo ink, ALA) or, as described below, by exogenous chromophores applied to the tissue
  • a lattice of thermal islets is a time-dependent phenomenon If absorptive heating occurs at too great a rate or for too long a period, heat will begin to diffuse away from the EMR-treated islets and into the surrounding untreated tissue volumes As this occurs, the thermal islets will spread into the untreated volumes and, ultimately, the thermal islets will merge and result in bulk heating
  • EMR-treatment of isolated volumes or islets of tissue can produce a lattice of damage islets surrounded by volumes of undamaged tissue (or differently- or less- damaged tissue) Damage islets result when the temperature increase of an EMR-treated thermal islet is sufficient to result in protein coagulation, thermal injury, photodisruption, photo ablation, or water vaporization
  • damage islets with lesser degrees of damage (e g , protein coagulation, thermal injury) or greater degrees of damage (e g , photodisruption, photo ablation, or water vaporization) may be appropriate
  • damage can result from the absorbance of
  • the damage islets are thermal injuries with coagulation of structural proteins Such damage can result when, for example, the light pulse duration varies from several microseconds to about 1 sec, but the peak tissue temperature remains below the vaporization threshold of water in the tissue (Pearce et al (1995), in Optical- Thermal Response of Laser-Irradiated Tissue.
  • the degree of damage is a function of the tissue temperature and the duration of the thermal pulse, and can be quantified by any of several damage functions known in the art In the description below, for example, the damage function yielding the Arrhenius damage integral (Pearce et al (1995), in Optical-Thermal Response of Laser-Irradiated Tissue.
  • EMR-treatment of isolated volumes or islets of tissue can produce a lattice of photochemical islets surrounded by volumes of tissue in which a photochemical reaction has not been induced
  • the photochemical reaction can involve endogenous bio molecules or exogenous molecules
  • exposure of the tissue to certain wavelengths of EMR can result in increased melanin production and "tanning" through the activation of endogenous biomolecules and biological pathways
  • exogenous molecules can be administered in photodynamic therapy, and activation of these molecules by certain wavelengths of EMR can cause a systemic or localized therapeutic effect
  • Treatment Parameters In practice, a variety of different treatment parameters relating to the applied
  • EMR can be controlled and varied according to the particular cosmetic or medical application These parameters include, without limitation, the following
  • the optical islets can be formed in any shape which can be produced by the devices described below, limited only by the ability to control EMR beams within the tissue
  • the islets can be variously-shaped volumes extending from the surface of the tissue through one or more layers, or extending from beneath the surface of the tissue through one or more layers, or within a single layer If the beams are not convergent, such beams will define volumes of substantially constant cross-sectional areas in the plane orthogonal to the beam axis (e g , cylinders, rectanguloids) Alternatively, the
  • the lattice is a periodic structure of islets, and can be arranged in one, two, or three dimensions
  • a two-dimensional (2D) lattice is periodic in two dimensions and translation invariant or non-periodic in the third
  • the lattice dimensionality can be different from that of an individual islet
  • a single row of equally spaced cylinders is an example of a ID lattice of 3D islets
  • an "inverted" lattice can be employed, in which islets of intact tissue are separated by areas of EMR-treated tissue and the treatment area is a continuous cluster of treated tissue with non treated islands
  • each of the treated volumes can be a relatively thin disk, as shown, a relatively elongated cylinder (e g , extending from a first depth to a second depth), or a substantially linear volume having a length which substantially exceeds its width and depth, and which is oriented substantially parallel to the tissue surface
  • the orientation of the lines for the islets 214 in a given application need not all be the same, and some of the lines may, for example, be at right angles to other lines (see for example Figs 6A and 6B) Lines also can be oriented around a treatment target for greater efficacy For example, the lines can be perpendicular to a vessel or parallel to a wrinkle
  • islets 214 are subsurface cylindrical volumes However, many other configurations are possible, such as spheres, ellipsoids, cubes or rectanguloids of selected thickness and starting at or below the surface of the tissue being treated
  • the islets can also be substantially linear or planar volumes
  • the parameters for obtaining a particular islet shape can be determined empirically with only routine experimentation
  • a 1720 nm laser operating with a low conversion beam at approximately 0 005-2 J and a pulse width of 0 5-2 ms can produce a generally cylindrically shaped islet
  • the islets By suitable control of wavelength, focusing, incident beam size at the surface and other parameters, the islets, regardless of shape, can extend through a volume, can be formed m a single thin layer of a volume, or can be staggered such that adjacent islets are in different thin layers of volume
  • Most configurations of a lattice of islets can be formed either serially or simultaneously Lattices with islets in multiple thin layers in a volume can be easily formed serially, for example using a scanner or using multiple energy sources having different wavelengths Islets in the same or varying depths can be created, and when viewed top-down from the tissue surface, the islets at varying depths can be either spatially separated or overlapping
  • the geometry of the islets affects the thermal damage in the treatment region Since a sphere provides the greatest gradient, and is thus the most spatially confined, it provides the most localized biological damage, and can therefore be preferred for applications where this is desirable Other geometries that increase the surface to volume ratio of the islets may be preferred for other applications B. Size of EMR-Treated Islets
  • the size of the individual islets within the lattices of EMR-treated islets can vary widely depending upon the intended cosmetic or medical application As discussed more fully below, in some embodiments it is desirable to cause substantial tissue damage to destroy a structure or region of tissue ⁇ e g , vessel, tendon, or facia) whereas in other embodiments it is desirable to cause little or no damage while administering an effective amount of EMR at a specified wavelength (e g , photodynamic therapy) As noted above with respect to damage islets, however, the healing of damaged tissues is more effective with smaller damage islets, for which the ratio of the wound margin to volume is greater
  • the size of the EMR-treated islets can range from 1 ⁇ m to maximum length of targeted tissue in any particular dimension
  • a lattice of substantially linear islets can consist of parallel islets having a length of approximately 300 mm and a width of approximately 10 ⁇ m to 3 mm to treat the length of a blood vessel
  • the depth can be approximately 10 ⁇ m to 4 mm and the diameter can be approximately 10 ⁇ m to 1 mm
  • the diameter or major axis can be, for example, and without limitation, approximately 10 ⁇ m to 1 mm
  • the islets can be used to treat a specific portion of the target tissue surrounding a region of injury or in other embodiments treat the entire target tissue so as to induce a generalized tissue response throughout the target
  • optical and photochemical islets typically may not have clear boundaries between treated and untreated volumes
  • thermal islets typically will exhibit a temperature gradient from the center of the islet to its boundaries
  • untreated tissue surrounding the islet also will exhibit a temperature gradient due to conduction of heat
  • damage islets can have irregular or indistinct boundaries due to partially damaged cells or structures or partially coagulated proteins As used herein, therefore, the size of an islet within a lattice of is
  • the minimum size of an EMR-treated islet increases with the targeted depth in the tissue
  • the practical minimum diameter or width of a non-ablative islet is estimated to be approximately 100 ⁇ m, although much larger islets (e g , 1-10 mm) are possible (However, islets smaller than 100 ⁇ m are theoretically possible, especially in the context of ablation where scattering effects may be reduced, and such islets are not outside the scope of the embodiments and claims )
  • the size of a damage islet can be either smaller or larger than the size of the corresponding optical islet, but is generally larger as greater amounts of EMR energy are applied to the optical islet due to heat diffusion
  • the wavelength, beam size, convergence, energy and pulse width have to be optimized
  • the EMR-treated islets can be located at varying points within a tissue, including surface and subsurface locations, locations at relatively limited depths, and locations spanning substantial depths
  • the desired depth of the islets depends upon the intended cosmetic or medical application, including the location of the targeted molecules, cells, tissues or intercellular structures
  • optical islets can be induced at varying depths m a tissue or organ, depending upon the depth of penetration of the EMR energy, which depends in part upon the wavelength(s) and beam size
  • the islets can be shallow islets that penetrate only surface layers of a tissue (e g , 0-50 ⁇ m), deeper islets that span several layers of a tissue (e g , 50-500 ⁇ m), or very deep, subsurface islets ((e g , 500 ⁇ m - 5 mm or more)
  • depths of up to 25 mm can be achieved
  • microwave and radio frequency EMR depths of several centimeters can be achieved
  • subsurface islets can be produced by targeting chromophores present only at the desired depth(s), or by cooling upper layers of a tissue while delivering EMR
  • long pulse widths coupled with surface cooling can be particularly effective
  • the percentage of tissue volume which is EMR-treated is referred to as the "fill factor" or/ and can affect whether optical islets become thermal islets, damage islets or photochemical islets
  • the fill factor is defined by the volume of the islets with respect to a reference volume that contains all of the islets
  • the fill factor may be uniform for a periodic lattice of uniformly sized EMR- treated islets, or it may vary over the treatment area
  • Non-uniform fill factors can be created in situations including, but not limited to, the creation of thermal islets using topical application of EMR-absorbing particles in a lotion or suspension (see below)
  • an average fill factor (£ vg ) can be calculated by dividing the volume of all EMR-treated islets V,' slet by the volume of all tissue V," ssue in the treatment area,
  • the fill factor can be decreased by increasing the center-to -center distance(s) of islets of fixed volume(s), and/or decreasing the volume(s) of islets of fixed center-to-center distance(s)
  • the calculation of the fill factor will depend on volume of an EMR-treated islet as well as on the spacing between the islets
  • the fill factor will depend on the ratio of the size of the islet to the spacing between the nearest islets d
  • the fill factor will be
  • the fill factor will be the ratio of the volume of the spherical islet to the volume of the cube defined by the neighboring centers of the islets
  • d is the shortest distance between the centers of the nearest islets and r is the radius of a spherical EMR-treated islet
  • Similar formulas can be obtained to calculate fill factors of lattices of islets of different shapes, such as lines, disks, ellipsoids, rectanguloids, or other shapes (In the art, the fill factor is sometimes determined two dimensionally for convenience, e g , based on the percentage of the area of EMR-islets formed at the surface of a tissue to the total surface area )
  • untreated tissue volumes act as a thermal sink, these volumes can absorb energy from treated volumes without themselves becoming thermal or damage islets Thus, a relatively low fill factor can allow for the delivery of high fluence energy to some volumes while preventing the development of bulk tissue damage
  • the untreated tissue volumes act as a thermal sink, as the fill factor decreases, the likelihood of optical islets reaching critical temperatures to produce thermal islets or damage islets also decreases (even if the EMR power density and total exposure remain constant for the islet areas)
  • the center-to-center spacing of islets is determined by a number of factors, including the size of the islets and the treatment being performed Generally, it is desired that the spacing between adjacent islets be sufficient to protect the tissues and facihtate the healing of any damage thereto, while still permitting the desired therapeutic effect to be achieved
  • the fill factor can vary in the range of 0 1-90%, with ranges of 0 1-1%, 1-10%, 10-30% and 30-50% for different applications
  • the interaction between the fill factor and the thermal relaxation time of a lattice of EMR- treated islets is discussed in detail below In the case of lattices of thermal islets, it can be important that the fill factor be sufficiently low to prevent excessive heating and damage to islets, whereas with damage islets it can be important that the fill factor be sufficiently low to ensure that there is undamaged tissue around each of the damage islets sufficient to prevent bulk tissue damage and to permit the damaged volumes to heal
  • EMR-treated islets can be used in a variety of applications m a variety of different organs and tissues
  • EMR treatments can be applied to tissues including, but not limited to, tissue mucosal tissues (e g , oral mucosa, gastrointestinal mucosa), ophthalmic tissues (e g , retinal tissues), tissues of the ear, vaginal tissue, glandular tissues (e g , prostate tissue), internal organs, muscle tissues, blood vessels, tendons and ligaments
  • the methods can be used to treat conditions including, but not limited to, lesions (e g , sores, ulcers), undesired blood vessels, hyperplastic growths (e g , tumors, polyps, benign prostatic hyperplasia), hypertrophic growths (e g , benign prostatic hypertrophy), neovascularization (e g , tumor-associated angiogenesis), arterial or venous malformations (e g , hemangiomas, nevus flammeus),
  • the embodiments described herein are particularly suited to treating internal tissues of the body, for example, in surgical and medical applications
  • forming EMR-islets during a surgical procedure in which a ligament or tendon is being repaired by irradiating a portion of the ligament or tendon with light to form a set of islets on the portion of the ligament or tendon that has been irradiated
  • the treatment will promote faster healing of the ligament, tendon or other tissue
  • the EMR therapy can be conducted directly on the ligament or tendon (or other internal tissue) without requiring an additional invasive action or procedure such as making an incision solely for the purposes of the EMR therapy (Of course, while this advantage is desirable for many embodiments, one skilled in the art will readily appreciate that the advantage is not necessary to all embodiments, and that embodiments withm the scope of the claims may include invasive aspects, for example, making an incision, solely
  • EMR-treated islets in surgical and other internal applications are small selective microzones of coagulated tissue, which, for example, may have widths of approximately 100 ⁇ m, depths of approximately 400 ⁇ m and a center-to-center spacing of approximately 500 ⁇ m (although many other dimensions are possible)
  • Selective microzones of coagulated tissue can be used for many purposes, for example, to stimulate repair of ligaments, vessels, tendons, etc as part of surgical or post-surgical treatments to aid in the repair and reconstruction of damaged tissues
  • the application of microzones of thermal injury to the reattachment zone of a grafted ligament, or to fracture zone of bone, or to a vessel stimulates responses of the hard and soft tissue to heal and repair more quickly In other cases in which multiple surgeries are required to treat conditions these are often due to incomplete and inadequate healing following initial treatments
  • Application of fractional thermolysis, in the form of lattices of EMR treatment islets, to the treated tissue stimulates further healing without the complications of more invasive surgical procedures This may have significant advantage by reducing the impact
  • Such methods and apparatus are provided for performing a therapeutic treatment on a patient's tissue by concentrating applied radiation of at least one selected wavelength at a plurality of selected, three-dimensionally located, treatment portions, which treatment portions are within non-treatment portions
  • the ratio of treatment portions to the total volume may vary from 0 1% to 90%, but is preferably less than 50%
  • Various techniques, including wavelength, may be utilized to control the depth to which radiation is concentrated and suitable optical systems may be provided to concentrate applied radiation in parallel or in series for selected combinations of one or more treatment portions
  • EMR lattices of islets of tissue injury has the advantage of extending and recruiting the healing needed to more fully and completely restore function to the entire affected tissue
  • the EMR lattices preferably will be of sufficient density, depth and volume to stimulate cellular reactions throughout the adjacent and affected surrounding tissue, although treatments of less than the entire affected tissue or of lower potency are possible according to certain embodiments
  • Treatment of the surrounding affected target tissue as well as the affected tissue damaged m the process of access to the target tissue speeds recovery and function
  • the EMR treatment islets may be microscopic in size Additionally, in some applications, the EMR treatment islets may be formed at temperatures below those that produce coagulation or destruction In still other cases, EMR treatment islets may be formed by ablating or desiccating tissue In such cases, the EMR treatment islets will still promote healing, believed to be associated with the mechanisms of photobiostimulation and photobio modulation (However, regardless of the actual healing mechanism, the application of such EMR treatment islets at such temperatures promote healing )
  • Embodiments described herein are capable performing a therapeutic treatment on internal tissue by concentrating applied radiation of at least one selected wavelength at a plurality of selected, three-dimensionally located, treatment portions, which treatment portions are within non-treatment portions
  • a device 410 similar to Palomar Medical Technologies, Inc 's Luxl540 handpiece may be used Such a device would have an EMR transmission area 412 of approximately 10 mm
  • the device 10 emits EMR having a wavelength of 1540 nm with 100 EMR beams per cm 2 , at a fluence of up to 100 mJ per EMR beam, a pulse width of 5 - 30 ms and a repetition rate of up to 2 5 pulses per second
  • Many other specifications are possible and other embodiments will have specifications optimized for a particular application
  • device 414 has a much smaller area 416 for transmitting EMR located at the end of an extended, and also has a curved neck 418 is shown
  • the electromagnetic radiation is transmitted along curved neck 418 by a waveguide contained within neck 418
  • Additional optical elements may be required in device 414 to produce a homogenous output at area 416 due to the curved neck 418
  • a device having a straight neck may be preferable to simply the optical system
  • the device 414 otherwise operates in a manner similar to the device 410
  • device 410, or a device of similar size may be used to treat relatively larger areas of tissue, such as repaired muscle and tendons, or a relatively large section of bone
  • Device 414, or a device of similar size may be used to perform treatments in a more precise fashion, for example, treating damaged vessels, or nerves of a wound zone in a spinal cord
  • Extremely small EMR transmission areas may be used for even finer applications, and may be small enough to produce only several small microscopic or nearly microscopic EMR-treatment islets
  • a device having an optical fiber coupled to a micro-lens array may be used
  • the micro-lens array may be manufactured as discussed herein, but using nano or nano-like technologies to create a lens array of very small size
  • fine and delicate treatments can be performed on very small tissue volumes and structures
  • such devices may be used for treating and/or stimulating a nerve bundle or an individual nerve cell or group of nerve cells or increasing the permeability of a membrane or thin sheath or other similar tissue structure or treating or performing a procedure on small structures in the body such as auditory bones of the ear or valves and other structures in the heart
  • Many other embodiments are possible
  • Size and shape of the handpiece may also be designed to reach and limit properly the zone of tissue to which the EMR is applied
  • EMR-treated islets can be created to promote the overall healing of all or a substantial portion of the affected length of the blood vessel Following the repair, the vessel may be stressed due to the trauma as well as from the fact that the vessel was stretched to allow the vessel to be repaired In such a case, EMR-treated islets can be used to speed the vessel's recovery even along portions that are remote from the site of the injury
  • a catheter or similar device can be inserted into the vessel and drawn along the affected length of the vessel while emitting EMR to create the islets or the vessel could be treated along an extensive proximal and distal length at the time of resection
  • lattices of damage islets can be used to treat hypertrophic scars by inducing shrinkage and tightening of the scar tissue, and replacement of abnormal connective tissue with normal connective tissue Tissue may be treated according to different regimes to alleviate, reduce and/or prevent scarring
  • an area of tissue such as skin or a vessel, requiring a surgical incision or procedure can be treated prior to the surgery, in some cases just prior to the surgery and in other cases well in advance of the surgery such as several weeks prior
  • Such prior treatments will stimulate a healing response in the tissue where the incision is to be formed, which will improve post-surgical healing of the incision and reduce the amount of scarring
  • Tissue may also be treated contemporaneously at the time of surgery, for example, while an incision is open Similarly, a tendon, muscle, blood vessel or other tissue can be treated at a location where the tendon, muscle, blood vessel or other tissue is joined or otherwise repaired to reduce or eliminate the amount of scarring at the site of the repair
  • scar tissue may be treated after it is formed in subsequent procedures or during rehabilitation or therapy to reduce or eliminate the scar tissue or prevent the further formation of scar tissue D Ablation or Welding of Internal Tissue
  • the creation of lattices of damage islets can be used in order to damage or destroy or induce healing responses of internal tissue to treat various conditions
  • the methods and devices can also be used to weld tissues together by creating islets to form the welded areas in the tissue surrounded by healthy tissues
  • the methods and devices can also be used to ablate a surface of the tissue (The surface of the tissue can be the naturally occurring surface, and can also be a surface that is created, for example, by cutting or otherwise altering the tissue during a treatment or procedure
  • FIG 4 shows a broad overview schematic of an apparatus 100 that can be used in one embodiment to produce islets of treatment in the tissue
  • optical energy 232 from a suitable energy source 234 passes through optical device 236, filter 238, cooling mechanisms 240, 242, and cooling or heating plate 244, before reaching tissue 246 (/ e , the subject's tissue)
  • the EMR from the energy source 234 is focused by the optical device 236 and shaped by masks, optics, or other elements in order to create islets of treatment
  • certain of these components such as, for example, filter 328 where a monochromatic energy source is utilized or optics 236, may not necessarily be present
  • the apparatus may not contact the tissue
  • there is no cooling mechanism such that there is only passive cooling between the contact plate and the tissue
  • a suitable optical impedance matching lotion or other suitable substance may be applied between plate 244 and tissue 246 to provide enhanced optical and thermal coupling, although this may not be required
  • many of these components such as, for example, filter 328 where a monochromatic energy source is utilized or optic
  • FIGs 1A-1C show another schematic representation of a system 208 for creating islets of treatment
  • Figures IA- 1C show a system for delivering optical radiation to a treatment volume V located at a depth d m the tissue and having an area
  • Figures IA- IC also show treatment or target portions 214 (/ e , islets of treatment) in the tissue 200
  • a portion of a skeletal muscle tissue 200 is shown, which includes an epimysium 206 overlying a portion of a rezicle 204
  • the treatment volume V may be below the tissue surface 202 in one or more tissue layers or the treatment volume may extend from the tissue surface through one or more tissue layers
  • the system 208 of Figures 1 A-IC can be incorporated within a hand held device
  • System 208 includes an energy source 210 to produce electromagnetic radiation (EMR)
  • EMR electromagnetic radiation
  • the output from energy source 210 is applied to an optical system 212, which is preferably in the form of a delivery head in contact with the surface of the tissue, as shown in Fig 1C
  • the delivery head can include, for example, a contact plate or cooling element 216 that contacts the tissue
  • the system 208 can also include detectors 216 and controllers 218
  • the detectors 216 can, for instance, detect contact with the tissue and/or the speed of movement of the device over the tissue and can, for example, image the tissue
  • the controller 218 can be used, for example, to control the pulsing of an EMR source in relation to contact with the tissue and/or the speed of movement of the hand piece (Note that throughout this specification, the terms "head”, "hand piece” and “hand held device” may be used interchangeably Each of these components is discussed in greater detail below
  • the EMR-treatment mechanism 306 can be gradually moved forward or withdrawn as the pulsations are emitted resulting m an array of islets in the internal wall of the surface spaced according to the repetition rate and velocity of the motion of the device In this way treatment may be applied to internal structures through an endoscope (or, in alternate embodiments, a catheter or other device) such that more extensive surgical access is not required
  • an endoscope or, in alternate embodiments, a catheter or other device
  • the devices, methods and parameters used will vary with, for example, the treatment being performed, the type of tissue being treated, and the location of the tissue Examples of other possible treatments include, without limitation, arthroscopic knee surgery, esophageal treatments, stomach and intestinal treatments, muscle and fasciae treatments, carpal tunnel, etc
  • the technique can also be applied to conventional light-based liposuction treatments
  • a small cannula, or tube, containing a laser fiber may be inserted into the skin and passed throughout the treatment area The laser's energy may be applied directly to the fat
  • the energy source 210 may be any suitable optical energy source, including coherent and non-coherent sources, able to produce optical energy at a desired wavelength or a desired wavelength band or in multiple wavelength bands
  • the exact energy source 210, and the exact energy chosen, may be a function of the type of treatment to be performed, the tissue to be heated, the depth within the tissue at which treatment is desired, and of the absorption of that energy in the desired area to be treated
  • energy source 210 may be a radiant lamp, a halogen lamp, an incandescent lamp, an arc lamp, a fluorescent lamp, a light emitting diode, a laser (including diode and fiber lasers), the sun, or other suitable optical energy source
  • multiple energy sources may be used which are identical or different
  • multiple laser sources may be used and they may generate optical energy having the same wavelength or different wavelengths
  • multiple lamp sources may be used and they may be filtered to provide the same or different wavelength band or bands
  • different types of sources may be included in the same device, for example, mixing
  • Energy source 210 may produce electromagnetic radiation, such as near infrared or visible light radiation over a broad spectrum, over a limited spectrum, or at a single wavelength, such as would be produced by a light emitting diode or a laser
  • electromagnetic radiation such as near infrared or visible light radiation over a broad spectrum, over a limited spectrum, or at a single wavelength, such as would be produced by a light emitting diode or a laser
  • a narrow spectral source may be preferable, as the wavelength(s) produced by the energy source may be targeted towards a specific tissue type or may be adapted for reaching a selected depth
  • a wide spectral source may be preferable, for example, in systems where the wavelength(s) to be applied to the tissue may change, for example, by applying different filters, depending on the application
  • many types of electromagnetic radiation, and other forms of energy in some cases may be used
  • UV, violet, blue, green, yellow light or infrared radiation e g , about 290-600 nm, 1400
  • the energy source 210 can be any variety of a coherent light source, such as a solid-state laser, dye laser, diode laser, fiber laser, or other coherent light source
  • the energy source 210 can be a neodymium (Nd) laser, such as a Nd YAG laser
  • the energy source 210 includes a neodymium (Nd) laser generating radiation having a wavelength around 1064 nm
  • a laser includes a lasing medium, e g , in this embodiment a neodymium YAG laser rod (a YAG host crystal doped with Nd +3 ions), and associated optics (e g , mirrors) that are coupled to the laser rod to form an optical cavity for generating lasing radiation
  • other laser sources such as chromium (Cr), Ytterbium (Yt) or diode lasers, or broadband sources, e g , lamps, can be employed for generating the treatment radiation Lasers
  • Laser emission may be delivered to the treatment site by an optical waveguide, or, in other embodiments, a plurality of waveguides or laser media may be pumped by a plurality of laser sources (lamps) next to the treatment site
  • Such dye lasers can result in energy exposure up to several hundreds of J/cm 2 , pulse duration from picoseconds to tens of seconds, and a fill factor from about 0 1% to 90 %
  • a coherent source is a fiber laser
  • Fiber lasers are active waveguides a doped core or undoped core (Raman laser), with coherent or non-coherent pumping Rare earth metal ions can be used as the doping material
  • the core and cladding materials can be quartz, glass or ceramic
  • the core diameter may be from microns to hundreds of microns Pumping light may be launched into the core through the core facet or through cladding
  • the light conversion efficiency of such a fiber laser may be up to about 80% and the wavelength range can be from about 1,100 to 3,000 nm
  • a combination of different rare-earth ions, with or without additional Raman conversion, can provide simultaneous generation of different wavelengths, which may benefit treatment results
  • the range can be extended with the help of second harmonic generation (SHG) or optical parametric oscillator (OPO) optically connected to the fiber laser output
  • Fiber lasers can be combined into the bundle or can be used as a single fiber laser
  • the optical output can be directed to the target with the help of
  • non-coherent sources of electromagnetic radiation e g , arc lamps, incandescence lamps, halogen lamps, light bulbs
  • HCL hollow cathode lamps
  • EDL electrodeless discharge lamps
  • HCL and EDL may generate emission lines from chemical elements
  • the output emission may be concentrated on the target with reflectors and concentrators Energy exposures up to about several tens of J/cm 2 , pulse durations from about picoseconds to tens of seconds, and fill factors of about 1% to 90 % can be achieved
  • Linear arc lamps use a plasma of noble gases overheated by pulsed electrical discharge as a light source Commonly used gases are xenon, krypton and their mixtures, in different proportions
  • the filling pressure can be from about several torr to thousands of torr
  • the lamp envelope for the linear flash lamp can be made from fused silica, doped silica or glass, or sapphire
  • the emission bandwidth is about 180-2,500 nm for clear envelope, and may be modified with a proper choice of dopant ions inside the lamp envelope, dielectric coatings on the lamp envelope, absorptive filters, fluorescent converters, or a suitable combination of these approaches
  • a Xenon-filled linear flash lamp with a trapezoidal concentrator made from BK7 glass can be used as set forth in some embodiments below, the distal end of the optical train can, for example, be an array of microp ⁇ sms attached to the output face of the concentrator
  • the spectral range of EMR generated by such a lamp can be about 300 - 2000 nm, energy exposure can be up to about 1,000 J/cm2, and the pulse duration can be from about 0 lms to 10s
  • Incandescent lamps are one of the most common light sources and have an emission band from 300 to 4,000 nm at a filament temperature of about 2,500 C
  • the output emission can be concentrated on the target with reflectors and/or concentrators
  • Incandescent lamps can achieve energy exposures of up to about several hundreds of J/cm 2 and pulse durations from about seconds to tens of seconds
  • Halogen tungsten lamps utilize the halogen cycle to extend the lifetime of the lamp and permit it to operate at an elevated filament temperature (up to about 3,500 C), which greatly improves optical output
  • the emission band of such a lamp is in the range of about 300 to 3,000 nm
  • the output emission can be concentrated on the target with reflectors and/or concentrators
  • Such lamps can achieve energy exposures of up to thousand of J/cm 2 and pulse durations from about 0 2 seconds to continuous emission
  • LEDs Light-emitting diodes
  • the energy source 210 or the optical system 212 can include any suitable filter able to select, or at least partially select, certain wavelengths or wavelength bands from energy source 210
  • the filter may block a specific set of wavelengths
  • undesired wavelengths in the energy from energy source 210 may be wavelength shifted in ways known in the art so as to enhance the energy available in the desired wavelength bands
  • filter may include elements designed to absorb, reflect or alter certain wavelengths of electromagnetic radiation
  • filter may be used to remove certain types of wavelengths that are absorbed by surrounding tissues or hemoglobin
  • many internal tissues are primarily composed of water, such as most organs and much of the rest of the human body
  • optical system 212 of Figures IA- 1C functions to receive radiation from the source 210 and to focus or concentrate such radiation to one or more beams
  • optical system 212 may focus / concentrate the energy from each source into one or more beams and each such beam may include only the energy from one source or a combination of energy from multiple sources
  • portions 214 may have various shapes and depths as described above
  • the optical system 212 as shown in Figs 1 A-IC may focus energy on portions 214 or a selected subset of portions 214 simultaneously Alternatively, the optical system 212 may contain an optical or mechanical-optical scanner for moving radiation focused to depth d to successive portions 214 In another alternative embodiment, the optical system 212 may generate an output focused to depth d and may be physically moved on the tissue surface over volume V, either manually or by a suitable two- dimensional or three-dimensional (including depth) positioning mechanism, to direct radiation to desired successive portions 214 For the two later embodiments, the movement may be directly from portion to portion to be focused on or the movement may be in a standard predetermined pattern, for example a grid, spiral or other pattern, with the EMR source being fired only when over a desired portion 214 Where an acoustic, RF or other non-optical EMR source is used as energy source 210, the optical system 212 can be a suitable system for concentrating or focusing such EMR, for example a phased array, and the term "optical system" should be
  • the system 208 can also include a cooling element 215 to cool the surface of the tissue 200 over treatment volume V
  • a cooling element 215 can act on the optical system 212 to cool the portion of this system in contact with the tissue, and thus the portion of the tissue in contact with such element
  • the cooling element 215 might not be used or, alternatively, might not be cooled during treatment (e g , cooling only applied before and/or after treatment)
  • cooling can be applied fractionally on a portion of the tissue surface (cooling islets), for example, between optical islets
  • cooling of the tissue is not required and a cooling element might not be present on the hand piece
  • cooling may be applied only to the portions of tissue between the treatment islets in order to increase contrast
  • cooling may be used to control the depth of effective treatment by preventing the internal surfaces from reaching temperatures that are damaging
  • one way to protect the inner vessel wall surface would be to perfuse or prefill the vessel with cooled fluid such as salme, lactated ringers, or blood plasma during application of radiation to the external wall surface as part of treatment
  • materials may be externally appied to facilitate treatment
  • heat, radiation absorptive material, and/or reflective material may be used to guide, direct, restrict and focus energy to a target tissue or prevent exposure to another adjacent tissue
  • a heated radiation absorptive or reflective surface may be used to enhance depth of penetration or extent of tissue action
  • the tissue may be preheated or precooled to a set point temperature to enable treatment at a specific and/or predetermined target depth
  • EMR can be applied from two or more different locations during the treatment, such as from two sides of a muscle, blood vessel or other tissue or from within and without an organ or blood vessel or from locations internal and external to a body
  • Such treatments may serve various functions
  • EMR can be applied to two sides of (or from two locations within) a muscle, organ wall or other tissue using parameters that are selected such that EMR from each individual location does not cause the formation of EMR-treated islets standing alone, but that does create EMR-treated islets withm the muscle, organ wall or other tissue throughout a volume of tissue where the EMR from the two locations converges and/or overlaps at a sufficient intensity to cause the formation of EMR-treated islets
  • the parameters may be chosen to not cause the formation of EMR-treated islets at the surface of the tissue Alternatively, the parameters could be chosen to treat the entire volume between the locations where EMR is applied, including at any surface of the tissue The later case may be used, for example, if the treatment would benefit from irradiating the tissue from
  • the cooling (or blocking, reflecting or heating) element 215 can include a system for cooling (blocking, reflecting or heating) the optical system (and hence the portion in contact with the tissue) as well as a contact plate that touches the tissue when in use
  • the contact plate can be, for example, a flat plate, a series of conducting pipes, a sheathing blanket, or a series of channels for the passage of air, water, oil or other fluids or gases Mixtures of these substances may also be used
  • the cooling system can be a water-cooled contact plate or ring
  • the cooling mechanism may be a plate and may also include a series of channels carrying a coolant fluid or a refrigerant fluid (for example, a cryogen), which channels are in contact with a plate that is in contact with the tissue
  • the cooling system may comprise a water or refrigerant fluid (for example Rl 34A) spray, a cool air spray or air flow across the surface of the tissue
  • cooling may be accomplished through chemical reactions (for example, endothermic reactions), or through electronic cooling, such as Peltier cooling
  • cooling mechanism may be used to maintain the surface temperature of the tissue at its normal temperature, which may be, for example, 37 0 C, but will vary depending on the type of tissue being heated
  • a contact plate of the cooling element may be made out of a suitable heat transfer material, and also, where the plate contacts the tissue, of a material having a good optical match with the tissue Sapphire is an example of a suitable material for the contact plate Where the contact plate has a high degree of thermal conductivity, it may allow cooling of the surface of the tissue by the cooling mechanism In other embodiments, contact plate may be an integral part of cooling mechanism, or may be absent In some embodiments, such as shown in Figs IA- 1C, energy from energy source 210 may pass through contact plate In these configurations, contact plate may be constructed out of materials able to transmit at least a portion of energy, for example, glass, sapphire, or a clear plastic In addition, the contact plate may be constructed in such a way as to allow only a portion of energy to pass through contact plate, for example, via a series of holes, passages, apertures in a mask, lenses, etc within the contact plate In other embodiments, energy may not be directed through the cooling mechanism 215
  • D Devices for Producing a Multiplicity of Treated Islets A number of different devices and structures can be used to spatially modulate and/or concentrate EMR in order to generate islets of treatment m the tissue
  • the devices can use reflection, refraction, interference, diffraction, and deflection of incident light to create treatment islets
  • a number of these devices are b ⁇ efly summarized below, with a more detailed explanation of the devices in the remainder of the specification, and in particular m connection with the section entitled Devices and Systems for Producing Islets of Treatment.
  • Example 4 Methods for generating islets of treatment, and numerous other devices and methods for creating islets of treatment are set forth throughout this specification
  • some devices and methods for generating islets of treatment are briefly set forth below, the invention is not limited to these particular methods and devices
  • a mask can be used to block portions of the EMR generated by the EMR source from reaching the tissue
  • the mask can contain a number of holes, lines, or slits, which function to spatially modulate the EMR to create islets of treatment
  • Figures 39 and 40 illustrate two embodiments in which the islets of treatment are formed generally through the use of a mirror containing holes or other transmissive portions Light passes through the holes in the mirror and strikes the tissue, creating islets of treatment Light reflected by the mirror stays in the optical system through a system of reflectors and may be redirected through the holes to improve efficiency
  • One effective mask is a contact cooling mask ( ⁇ e , it contacts the tissue during treatment) with a high reflection and minimum absorption for masking light
  • spatial modulation and concentration of the EMR can be achieved by shaping an end portion of a light guide with prisms, pyramids, cones, grooves, hemispheres, or the like in order to create output light spatial modulation and concentration, and therefore to form islets of treatment in a tissue
  • Figures 9 A through 1OA depict such embodiments Numerous exemplary types of imaging optics and/or diffractive optics can also be used m this embodiment
  • the end of the light guide can be shaped in order to introduce light total internal reflection (TIR) when the distal end of the device is in contact with air, while allowing EMR to pass through when the distal end is m contact with a lotion or tissue surface
  • TIR light total internal reflection
  • some embodiments can use spatially modulated phase arrays to introduce phase shifts between different portions of the incident beam As a result of interference between the said portions, amplitude modulation is introduced in the output beam
  • the embodiment of Figure 11 uses a line or array of non-coherent EMR sources to create islets of treatment
  • Other embodiments such as that shown in Figure 12C, use an array of diode laser bars in order to form islets of treatment
  • Figures 12E, 13B-D, and 14A are exemplary embodiments that use a bundle of optical fibers
  • Some embodiments can include a sensor for determining the speed of movement of the hand piece across the target area of the tissue
  • the hand piece can further include circuitry in communication with the sensor for controlling the optical energy in order to create islets of treatment
  • the circuitry can control, for example, pulsing of the optical energy source based on the speed of movement of the head portion across the tissue in order to create islets of treatment
  • the circuitry can control movement of the energy source, a scanner or other mechanism within the apparatus based on the speed of movement of the head portion across the tissue in order to expose only certain areas of the tissue to the EMR energy as the head is moved over the tissue in order to create islets of treatment
  • Figures 15 and 16 are exemplary embodiments according to this aspect
  • spatially selective islets of treatment can be created by applying to the tissue surface a desired pattern of a topical composition containing a preferentially absorbing exogenous chromophore
  • the chromophore can also be introduced into the tissue with a needle, for example, a micro needle as used for tattoos
  • the EMR energy may illuminate the entire tissue surface where such pattern of topical composition has been applied
  • the chromophores can heat up, thus creating islets of treatment in the tissue
  • the EMR energy may be focused on the pattern of topical composition
  • a variety of substances can be used as chromophores including, but not limited to, carbon, metals (Au, Ag, Fe, etc ), organic dyes (Methylene Blue, Toluidine Blue, etc ), non-organic pigments, nanoparticles (such as fullerenes), nanoparticles with a shell, carbon fibers, etc
  • the desired pattern can be random and need not be regular or pre-determined It can vary as a
  • Some embodiments can produce thermal (and damage) lattices (or treatment islets) by employing uniform EMR beams and spatially modulated cooling devices The resulting thermal lattice in such cases will be inverted with respect to the original cooling matrix 7 Creating, blocking or facilitating patterned treatment through perfusion of tissue with chromophore or other radiation manipulative chemical material
  • E Controllers and Feedback Systems Some embodiments can also include speed sensors, contact sensors, imaging arrays, and controllers to aid in various functions of applying EMR to the tissue System 208 of Fig 1 A-IB includes an optional detector 216, which may be, for example, a capacitive imaging array, a CCD camera, a photodetector, or other suitable detector for a selected characteristic of the tissue
  • the output from detector 216 can be applied to a controller 218, which is typically a suitably programmed microprocessor or other such circuitry, but may be special purpose hardware or a hybrid of hardware and software
  • Control 218 can, for example, control the turning on and turning off of the light source 210 or other mechanism for exposing the light to the tissue (e g , shutter), and control 218 may also control the power profile of the radiation Controller 218 can also be used, for example, to control the focus depth for the optical system 212 and to control the portion or portions 214 to which radiation is focused/concentrated at any given time
  • controller 218 can be used to control the
  • the lattices can also be produced using non-optical sources
  • microwave, radio frequency and low frequency or DC EMR sources can be used as energy sources to create lattices of EMR-treated islets
  • the tissue surface can be directly contacted with heating elements in the pattern of the desired lattice
  • TRT thermal relaxation time
  • the LTRT is dependent on the lattice fill factor,/ which can be illustrated by first considering the particular case of the two-dimensional lattice Disregarding the effect of the precise voxel and islet shapes, it can be assumed that the islet and the voxel are infinite cylinders of radii r 0 andi?
  • LTI lattice Temperature Relaxation Time
  • LOI lattice of optical islets
  • the pulse width may be specified in the context of the theory of selective photothermo lysis (Anderson et al (1983), Science 220 524-26, Altshuler et al (2001), Lasers in Surgery and Medicine 29 416-32) In its original formulation this theory deals with isolated targets inside tissue It points out that the selective heating of a target is possible if the pulse width is smaller than some time interval characteristic for the target and referred to as the temperature relaxation time (TRT)
  • TRT is the cooling time of the target, which is the time required by an instantly heated target to cool to 1/e of its initial temperature
  • the lattice temperature dynamics depends on the relation between the islet and voxel areas rather than by the precise islet and voxel shapes This should be valid if the voxels are not very anisotropic, i e , long in one direction and short in the others
  • the anisotropic lattices may be considered as the lattices of smaller dimensionality
  • the lattice dimensionality is reduced from 2 to 1 if the voxels are very long and narrow rectangles it is possible to switch from such rectangles to the infinitely long stripes of the same width making up a one-dimensional lattice
  • Thermal dynamics of LTI depends on the method of the LOI introduction into the tissue First method is a “sequential method” or “sequential LOI” In this case in every time instant just one (or several distant) optical islet is being created in the tissue Laser beam scanners can be used to create sequential LOI Second method is “parallel method” or “parallel LOI” In this case, a multitude of optical islets are created in the tissue simultaneously during the optical pulse Thermal interaction between islets in the sequential LOI is minimal For parallel LOI, thermal interaction between different islets can be very significant To evaluate the lattice thermal relaxation time (LTRT), for parallel LOI, the same reasoning used to find the TRT of an individual islet is followed The islets are heated instantly to temperature T 0 keeping the space outside them at the constant background temperature 7b ⁇ T 0 By letting the islets cool through the conduction of heat to the surrounding tissue, the lattice will approach thermal equilibrium at the stationary temperature
  • LTRT lattice thermal relaxation time
  • the LTRT may be defined as the characteristic cooling time when the islet temperature (more precisely, the maximum temperature within the islet) reaches the intermediate value between the initial and stationary temperatures
  • the LTRT of a very sparse lattice equals the TRT of an individual islet For such a lattice each islet cools independently on the others For denser lattices, however, the temperature profiles from different islets overlap causing the LTRT to decrease
  • This cooperative effect was studied by evaluating the LTRT to TRT ratio as a function of the fill factor for the particular case of the lattice of the cylindrical islets, as described herein
  • the LTRT decreases monotonically with the growth of the fill factor Therefore, the denser is the islet lattice the smaller is the time while the lattice relaxes by coming down to the thermal equilibrium with the surrounding tissue When the fill factor approaches unity, the LTRT approaches some limit close but somewhat larger than the TRT
  • the distinction is due to some disagreement between the definition of LTRT used here and the conventional definition of TRT
  • the real temperature decay is not exponential due to the heating of the surrounding tissues Therefore, the time necessary for the target to decrease its temperature to 1/e of its
  • the islets may not appear even if the left-hand-side inequality holds F mm can be found as a fluence needed to heat up tissue in a islet to the threshold temperature for the tissue coagulation, T i ⁇ If the pulse width is short enough to neglect the heat conduction, the threshold fluence for the protein coagulation is given by
  • the threshold of the bulk damage F max is the fiuence needed to heat up tissue, both within the islets and between the islets (bulk tissue), to the threshold temperature Because the volume of this tissue is 1// times larger than the volume occupied by islets
  • the second criterion is more restrictive
  • the second criterion yields the safety margin
  • F m ⁇ X /F mn 2 1
  • Isolated islets are considered before the islet lattices
  • a typical method of creating a 3-dimensional (three-dimensional) optical islet is focusing light inside the tissue The optical islet of a high contrast may be obtained if the numerical aperture (NA) of the input beam is sufficiently large However, if the NA is too large one may expect trapping and waveguide propagation of light in superficial layers of the tissue, which may have a higher or different index of refraction than the underlying tissue H
  • the plane or cylindrical optical islets perpendicular to the tissue surface may be obtained by using a narrow collimated light beam in the tissue
  • a beam is considered collimated m the tissue if it neither converges nor diverges in a non-scattering space with the refractive index matching that of tissue at the depth of treatment z 0
  • Minimal diameter of collimated beam can be found from the formula (Yariv (1989) Quantum Electronics (NY John Wiley and Sons))
  • the spot profile may be a line (st ⁇ pe) for the one-dimensional islet and some limited shape like circle or square for the two-dimensional islet
  • a circular optical beam (wavelength 1200 nm) of diameter 100 ⁇ m striking the tissue through sapphire
  • the transverse intensity profile of the beam is flat at small depths and transfers to a Gaussian when moving deeper into the tissue Therefore, the optical islet is a cylinder very sharp at the top and somewhat blurred at the bottom
  • the penetration depth is defined as the depth into the tissue where the irradiance is 1/e of the fluence incident onto the tissue surface
  • This effect is well studied for beams wider than, typically, 1 mm (Klavuhn (2000) Illumination geometry the importance of laser beam spatial characteristics Laser hair removal technical note No 2 (Published by Lumenis Inc))
  • the beam is only several tens of micrometers in diameter, which is much smaller than the diffuse length of light in the tissue, the propagation dynamics may be very different from that of wider beams
  • the irradiance decreases monotonically when moving deeper into the tissue along the beam axis whereas for the wider beams a subsurface irradiance maximum may occur
  • the total bulk irradiance in tissue is the sum of the direct and scattered components and the subsurface maximum is due to the scattered component only When the beam diameter decreases the on
  • the LOI approach is thought to provide a significantly higher safety margin over the traditional approach between the threshold of therapeutic effect and the threshold of unwanted side effects
  • the safety margin is defined as F max /F mn , where F m ⁇ n is the threshold of the desired therapeutic effect and F max is the threshold of the continuous bulk damage
  • the theoretical upper limit for the safety margin is l/f, where/ is the fill factor of the lattice
  • the safety margin is determined by the expression F max -T 1 ), where T max is the temperature of water vaporization, T tr is the minimal temperature, which still provides the therapeutic effect
  • This margin can be up to 2 times higher than in case of traditional photothermal treatment It should also be emphasized that the periodicity of the lattice is important for keeping the safety margin stable and for maintaining reproducibility of results
  • the efficacy of the lattice treatment can be increased by minimizing the size of the islets and maximizing the fill factor of the lattice
  • Small-size spherical or elliptical islets can be produced by using wavelengths in the 900 to 1800 nm range and focusing technique with a high numerical aperture for depth in the tissue up to 0 7 mm with minimal irradiation of surface layers of the tissue
  • the positions of the optical islets correspond to the locations of ballistic foci For deeper focusing, the ballistic focus disappears and the maximal irradiance stabilizes at ⁇ 0 5 mm depth (the diffuse focus)
  • the depth of the resulting column can be controlled by the fluence
  • the minimal threshold fluence can be achieved in the 1400 -1420 nm wavelength range and the absolute value of this fluence is between 12 and 80 J/cm 2
  • the minimal threshold fluences are found at 1405 nm (400 J/cm 2 ) and 1530 nm (570 J/cm 2 )
  • a LOI can be created at a depth up to several millimeters in tissue, but in this case the size of the islets will also grow to several millimeters
  • the extent of the optical damage is determined by the size of the optical islets and the fluence A damage islet is collocated with the original optical islet if the pulse width is shorter than the thermal relaxation time of the optical islet and the fluence is close to the minimal effective fluence
  • the damage islets can grow in size even after termination of the optical pulse and, as a result, the fill factors of LTI an LDI can be higher than the fill factor of the original LOI Islets of a lattice can be created in tissue sequentially using scanner or concurrently using lattice of optical beams
  • Figs 19A-25C illustrate various systems for delivering radiation in parallel to a plurality of target portions 214
  • the arrays of these figures are typically fixed focus arrays for a particular depth d This depth may be changed either by using a different array having a different focus depth, by selectively changing the position of the array relative to the surface of the tissue or to target volume V or by controlling the amplitude- phase distribution of the incident radiation
  • Figs 26-29 show various optical lens arrays which may be used m conjunction with the scanning or deflector systems of Figs 30 A- 35 to move to successive one or more focused portions 214 within target volume V
  • Figs 36 and 37 show two different variable focus optical systems which may, for example, be moved mechanically or manually over the tissue to illuminate successive portions 214 thereon
  • Figs 19A-C show a focusing element 1 on a substrate 3, the focusing element having a border which is in a hexagonal pattern (Fig 19A), a square pattern (Fig 19B), and a circular or elliptical pattern (Fig 19C) Standard optical materials can be used for these elements While the hexagonal and square patterns of Figs 19A and 19B can completely fill the working area of the focusing element plate 4, this is not true for the element pattern of Fig 19C Radiation from source 210 would typically be applied simultaneously to all of the focusing elements 1, however, the radiation may also be applied sequentially to these elements by use of a suitable scanning mechanism, or may be scanned in one direction, illuminating/irradiating for example four of the elements at a time
  • Figs 2OA and 2OB are cross-sectional views of a micro-lens system fused in a refracting material 8, for example, porous glass
  • the refractive index for the material of lenses 5 must be greater than the refractive index of refracting material 8
  • beam 11 initially passes through planar surface 10 of refracting material 8 and is then refracted both by primary surface 6 and by secondary surface 7 of each micro-lens 5, resulting in the beam being focused to a focal point 12
  • the process is reversed in Fig B20A, but the result is the same
  • the incident beam 11 is refracted by a primary lens surface 6 formed of the refracting material 8
  • Surfaces 6 and 7 for the various arrays can be either spherical or asphe ⁇ cal
  • the lens pieces 15 are mounted to a substrate and are in an immersion material 16
  • the refraction index of lens pieces 15 are greater than the refraction index of immersion material 16
  • Immersion material 16 can be in a gas (air), liquid (water, cryogen spray) or a suitable solid gas and liquid can be used for cooling of the tissue
  • the immersion material is generally at the primary and secondary plane surfaces, 13 and 14, respectively
  • the focusing depth can be adjusted by changing the refractive index of immersion material
  • the primary surface 6 and secondary surface 7 of each lens piece 15 allows higher quality focusing to be achieved
  • the lens pieces 15 are fixed on a surface of a refracting material
  • Fresnel lenses Figs 22 A-D show Fresnel lens surfaces 17 and 18 formed on a refracting material 8 Changing the profile of Fresnel lens surface 17 and 18, the relationship between the radius of center 17 and ring 18 of the Fresnel surface, makes it possible to achieve a desired quality of focusing
  • the arrays of Figs 22C and 22D permit a higher quality focusing to be achieved and are other preferred arrays
  • Surfaces 17 and 18 can be either spherical or aspherical
  • a holographic lens 19 on a surface of refracting material 8
  • Holographic lenses 19 may be formed on either of the surfaces of refracting material 8 as shown in Figs
  • Fig 23C shows that the holographic material 20 substituted for the refracting material 8 of Figs 23 A and 23B
  • the holographic lens is formed in the volume of material 20 Techniques other than holography can be used to induce phase variations into different portions of the incident beam and, thus, provide amplitude modulation of the output beams
  • the focusing elements are formed by gradient lenses 22 having primary plane surfaces 23 and secondary plane surfaces 24 As shown in Fig 24B, such gradient lenses may be sandwiched between a pair of refracting material plates 8 which provide support, protection and possibly cooling for the lenses
  • Figs 7A-7C illustrate various matrix arrays of cylindrical lenses 25
  • the relation of the lengths 26 and diameters 27 of the cylindrical lenses 25 can vary as shown in the figures
  • the cylindrical lens 25 of Figs 7B and 7C provide a line focus rather than a spot or circle focus as for the arrays previously shown
  • Figs 8A-8D are cross-sectional views of one layer of a matrix cylindrical lens system
  • the incident beam 11 is refracted by cylindrical lenses 25 (Figs 8A and 8B) or half cylinder lenses 29 (Figs 8C and 8D) and focus to a line focus 28
  • the cylindrical lenses 29 are in the immersion material 16
  • the line focuses for adjacent lenses may be oriented in different directions, the orientations being at right angles to each other for certain of the lenses in these figures
  • a matrix of focal spots is achieved by passing incident beam 11 through two layers of cylindrical lenses 32 and 35
  • Figs 25B and 25C are cross-sections looking in two orthogonal directions at the array shown in Fig 25A
  • Fig 26 shows a one-lens objective 43 with a beam splitter 38
  • the beam 11 incident on angle beam splitter (phase mask) 38 divides and then passes through the refracting surfaces 41 and 42 of lens 43 to focus at central point 39 and off-center point
  • 40 Surfaces 41 and 42 can be spherical and/or aspherical Plate 54 having optical planar surfaces 53 and 55 permits a fixed distance to be achieved between optical surface 55 and focusing points 39, 40 Angle beam splitter 38 can act as an optical grating that can split beam 11 into several beams and provide several focuses In Fig 27, a two lens 43,46 objective provides higher quality focusing and numerical aperture as a result of optimal positioning of optical surfaces 41, 42 and 44 All of these surfaces can be spherical or aspherical Optical surface 45 of lens 46 can be planar to increase numerical aperture and can be in contact with plate 54 Plate 54 can also be a cooling element as previously discussed Fig 28 differs from the previous figures in providing a three-lens objective, lenses 43, 46 and 49 Fig 29 shows a four lens objective system, the optical surfaces 50 and 51 of lens 52 allowing an increased radius of treatment area ( ⁇ e , the distance between points 39 and 40)
  • Figs 30A, 30B and 30C illustrate three optical systems, which may be utilized as scanning front ends to the various objectives shown in Figs 26-29
  • the colhmated initial beam 11 impinges on a scanning mirror 62 and is reflected by this mirror to surface 41 of the first lens 43 of the objective optics Scanning mirror 62 is designed to move optical axis 63 over an angle f Rotational displacement of a normal
  • a lens 58 may be inserted before scanning mirror 62 as shown in Fig 3OB
  • Optical surfaces 56 and 57 of lens 58 can be spherical or asphe ⁇ cal
  • a lens 61 may be inserted between lens 58 and mirror 62, the lens 61 having optical surfaces 59 and 60
  • Figs 31A, 31B and 31C are similar to Figs 30A, 30B and 30C except that the light source is a point source or optical fiber 65 rather than collimated beam 11 Beam 66 from point source 65, for example the end of a fiber, is incident on scanning mirror 62 (Fig 3 IA) or on surface 57 of lens 58 (Figs 31B and 31C)
  • the light source is a point source or optical fiber 65 rather than collimated beam 11 Beam 66 from point source 65, for example the end of a fiber, is incident on scanning mirror 62 (Fig 3 IA) or on surface 57 of lens 58 (Figs 31B and 31C)
  • Figs 32A and 32B show a two mirror scanning system
  • scanning mirror 67 rotates over an angle f2
  • scanning mirror 62 rotates over an angle fl
  • Beam 63 is initially incident on mirror 67 and is reflected by mirror 67 to mirror 62, from which it is reflected to surface 41 of optical lens 43
  • an objective lens 106 is inserted between the mirrors While a simple one-lens objective 106 is shown m this figure, more complex objectives may be employed
  • Objective lens 106 refracts the beam from the center of scanning mirror 67 to the center of scanning mirror 62
  • scanning is performed by scanning lens 70, which is movable in direction s
  • optical surface 68 refracts a ray of light along optical axis 71 to direction 72
  • scanning is performed by rotating lens 76 to, for example, position 77
  • Surface 74 is planar and surface 75 is selected so that it does not influence the direction of refracted optical axis 72 In Fig 35, scanning is performed by the moving of point source or optical fiber 65 in directions
  • Figs 36 and 37 show zoom lens objectives to move the damage islets to different depths
  • a first component is made up of a single lens 81 movable along the optical axis relative to a second component, which is unmovable and consists of two lenses 84 and 87
  • Lens 84 is used to increase numerical aperture
  • optical surfaces 79, 80, 82, 83 and 85 can be aspherical
  • the relative position of the first and second components determines the depth of focal spot 12
  • Fig 37 shows zoom lens objectives with spherical optical surfaces
  • the first component is made up of a single lens 90 movable with respect to the second component along the optical axis
  • the second component which is immovable, consists of five lenses 93, 96, 99, 102, and 105
  • the radius of curvature of surfaces 88 and 89 are selected so as to compensate for aberrations of the immovable second component
  • the depth of focus may be controlled by controlling the distance between the first and second components
  • Either of the lens systems shown in Figs 36 and 37 may be mounted so as to be movable either manually or under control of control 218 to selectively focus on desired portions 214 of target volume V or to non-selectively focus on portions of the target volume
  • depth d for volume V and the focal depth of an optical system are substantially the same when focusing to shallow depths, it is generally necessary m a scattering medium such as tissue to focus to a greater depth, sometimes a substantially greater depth, in order to achieve a focus at a deeper depth d
  • a scattering medium such as tissue
  • the reason for this is that scattering prevents a tight focus from being achieved and results in the minimum spot size, and thus maximum energy concentration, for the focused beam being at a depth substantially above that at which the beam is focused
  • the focus depth can be selected to achieve a minimum spot size at the desired depth d based on the known characteristics of the tissue
  • the pulse width of the applied radiation should be less than the thermal relaxation time (TRT) of each of the targeted portions or optical islets, since a longer duration may result in heat migrating beyond the boundaries of these portions
  • TRT thermal relaxation time
  • the pulse-widths can be longer than the thermal relaxation time if density of the targets is not too high, so that the combined heat from the target areas at any point outside these areas is well below the damage threshold for tissue at such point
  • thermal diffusion theory indicates that pulse width ⁇ for a spherical islet should be ⁇ 500 D 2 /24 and the pulse width for a cylindrical islet with a diameter D is ⁇ 50 D 2 /16, where D is the characteristic size of the target
  • the pulse-widths can sometimes be longer than the thermal relaxation time if density of the targets is not too high, so that the combined heat from the target areas at any point outside these areas is well below the damage threshold for tissue at
  • the required power from the radiation source depends on the desired therapeutic effect, increasing with increasing depth and cooling and with decreasing absorption due to wavelength The power also decreases with increasing pulse width
  • Numerical aperture is a function of the angle of a focused radiation beam from an optical device (Not all embodiments require focusing, however ) It is preferable, but not essential, that this number, and thus the angle of the beam, be as large as possible so that the energy at portions in a tissue volume where radiation is concentrated is substantially greater than that at other points m the tissue volume V, thereby minimizing damage to the tissue in region being treated, and in portions of tissue volume V other than the EMR treated islets, while still achieving the desired therapeutic effect
  • Higher numerical aperture of the beam risk of damage to the integrity of the tissue and its function , but it is limited by scattering and absorption of higher incidence angle optical rays As can be seen from Table Bl, the preferable numerical aperture decreases as the focus depth increases
  • EMR treated islets Each device would be sized according to its intended purposes, and may be relatively large or, m some cases, small for performing treatments in certain parts of the body A number of different devices and structures can be used to generate islets of treatment in the tissue
  • figure 38 illustrates one system for producing the islets of treatment on tissue 280
  • An applicator 282 is provided with a handle so that its head 284 can be near or m contact with the tissue 280 and scanned in a direction 286 over the tissue 280
  • the applicator 282 can include an islet pattern generator 288 that produces a pattern of areas of enhanced permeability of the tissue or arrangement 290 of islets particles 292 on the surface of the tissue 280, which when treated with EMR from applicator 210 produces a pattern of enhanced permeability
  • the generator 288 produces thermal, damage or photochemical islets into the surface or deeper layers or portions of the tissue
  • the applicator 282 includes a motion detector 294 that detects the scanning of the head 284 relative to the tissue surface 296 This generated information is used by the islet pattern generator 288 to ensure that the desired fill factor or islet density and power is produced on the tissue surface 296 For example, if the head 284 is scanned more quickly, the pattern generator responds by imprinting islets more quickly.
  • EMR sources that can be used with the applicator 282 and on the methods and structures that can be used to generate the islets of treatment
  • the hand piece 310 includes a housing 313, a diode laser bar 315, and a cooling or heating plate 317
  • the housing 313 supports the diode laser bar 315 and the cooling or heating plate 317, and the housing 313 can also support control features (not shown), such as a button to fire the diode laser bar
  • the divergence of the beam emanating from the emitters 702 is between 6 and 12 degrees along one axis (the slow axis) and between 60 and 90 degrees along the fast axis
  • the plate 704 may serve as either a cooling or a heating surface and also serves to locate the emitters 702 in close and fixed proximity to the surface of the tissue to be treated
  • the distance between the emitters 702 and the plate 704 can be between about 50 and 1000 micrometers, and more particularly between about 100 and 1000 micrometers in some embodiments, in order to minimize or prevent distortion effects on the laser beam without using any optics for low cost and simplicity of manufacture
  • the distance between the emitters 702 and the tissue can be between about 50 and 1000 micrometers, and more particularly 100 and 1000 micrometers in some embodiments
  • imaging optics are not needed, but other embodiments may include additional optics to image the emitter surfaces 702 directly onto the tissue surface In other embodiments, greater than or less than twenty-five emitters can be located on the diode laser
  • Figure 12B shows a perspective view of one embodiment of a diode laser bar 330 that can be used for the diode laser bar 315 in Figure 12A
  • the diode laser bar 330 has length L of around 1 cm, a width W of around 1 mm, and a thickness T of around 0 0015 mm
  • the depiction of Figure 12B shows 12 emitters 332, each of which emits radiation 334 as shown in Figure 12B
  • the diode laser bar 330 can be placed within the device 310 of Figure 12A so that the side S of the diode laser bar 315 is oriented as shown in Figure 12A The emitters, therefore, emit radiation downward toward the tissue 319 m the embodiment of Figure 12A
  • the plate 317 can be of any type, such as those set forth above, in which light from an EMR source can pass through the plate 317
  • the plate 317 can be a thin sapphire plate
  • other optical materials with good optical transparency and high thermal conductivity /diffusivity such as, for example, diamond
  • the plate 317 can be used to separate the diode laser bar 315 from the tissue 319 during use
  • the plate 317 can provide cooling or heating to the tissue, if desired
  • the area in which the plate 317 touches the tissue can be referred to as the treatment window
  • the diode laser bar 315 can be disposed within the housing 313 such that the emitters are m close proximity to the plate 317, and therefore in close proximity to the tissue when in use
  • one way to create islets of treatment is to place the housing 313, including the diode laser bar 315, in close proximity to the tissue, and then fire the laser Wavelengths near 1750 - 2000 nm and in the 1400-1600 nm range can be used for creating subsurface islets of treatment with minimal effect on the epidermis due to high water absorption Wavelengths m the 290-10,000 can be used in some embodiments, while in other wavelengths in the 900-10,000 nm range can be used for creating surface and subsurface islets on the tissue Without moving the hand piece across the tissue, a series of treatment islets along a line can be formed in the tissue Figure 38 shows one possible arrangement 290 of islets on the surface of the tissue 280 from the use of such a diode laser bar, where the diode laser bar 315 is pulsed as it moves over the tissue in direction A of Figure 12A
  • the user can simply place the hand piece in contact with the target tissue area and move the hand piece over the tissue while the diode laser is continuously fired to create a series of lines of treatment
  • the diode laser bar 330 of Figure 12B 12 lines of treatment would appear on the tissue (one line for each emitter)
  • an optical fiber can couple to the output of each emitter of the diode laser bar
  • the diode laser bar need not be as close to the tissue during use
  • the optical fibers can, instead, couple the light from the emitters to the plate that will be in close proximity to the tissue when in use
  • Figure 12C shows another embodiment, which uses multiple diode laser bars to create a matrix of islets of treatment
  • multiple diode laser bars can be arranged to form a stack of bars 325
  • the stack of bars 325 includes five diode laser bars
  • the stack of bars 325 can be mounted in the housing 313 of a hand piece HlOl with the emitters very close to a cooling plate 317
  • the hand piece 310 of Figure 12C can be brought close to the tissue surface 319, such that the cooling plate 317 is in contact with the tissue
  • the user can simply move the hand piece over the tissue as the diode lasers are pulsed to create a matrix of islets of treatment in the tissue
  • the emission wavelengths of the stacked bars need not be identical In some embodiments, it may be advantageous to mix different wavelength bars in the same stack to achieve the desired treatment results
  • the depth of penetration can be varied, and therefore the islets of treatment spot depth can also be varied
  • the lines or spots of islets of treatment created by the individual bars can be located at different depths
  • the user of the hand piece 310 of Figure 12A or 12C can place the treatment window of the hand piece in contact with a first location on the tissue, fire the diode lasers in the first location, and then place the hand piece m contact with a second location on the tissue and repeat firing
  • a variety of optical systems can be used to couple light from the diode laser bar to the tissue
  • imaging optics can be used to re-image the emitters onto the tissue surface, which allows space to be incorporated between the diode laser bar 315 (or the stack of bars 325) and the cooling plate 317
  • a diffractive optic can be located between the diode laser bar 315 and the output window (i e , the cooling plate 317) to create an arbitrary matrix of treatment spots
  • Numerous exemplary types of imaging optics and/or diffractive optics can also be used to create an arbitrary matrix of treatment spots.
  • the housing 313 of the hand piece 310 includes a stack 325 of diode laser bars and a plate 317 as in previous embodiments
  • This embodiment also includes four diffractive optical elements 330 disposed between the stack 250 and the plate 317
  • more or fewer than four diffractive optical elements 330 can be included
  • the diffractive optical elements 330 can diffract and/or focus the energy from the stack 325 to form a pattern of islets of treatment in the tissue 319
  • one or more motors 334 is included in the hand piece 310 m order to move the diffractive optical elements 330
  • the motor 334 can be any suitable motor, including, for example, a linear motor or a piezoelectric motor
  • the motor 334 can move one or more of the diffractive optical elements 330 in a horizontal direction so that those elements 330 are no longer in the optical path, leaving only one (or perhaps more) of the diffractive optical elements 334 in the optical path
  • another suitable motor including, for example, a linear motor or a piez
  • the diffractive optics 330 can be moved in position between the stack 325 and the cooling plate 317 m order to focus the energy into different patterns
  • the user is able to choose from a number of different islets of treatment patterns m the tissue through the use of the same hand piece 310
  • the user can manually place the hand piece 310 on the target area of the tissue prior to firing, similar to the embodiments described earlier
  • the hand piece aperture need not tough the tissue
  • the hand piece may include a stand off mechanism (not shown) for establishing a predetermined distance between the hand piece aperture and the tissue surface
  • Figure 12E shows another embodiment
  • optical fibers 340 are used to couple light to the output/aperture of the hand piece 310 Therefore, the diode laser bar (or diode laser bar stacks or other light source) can be located in a base unit or in the hand piece 310 itself In either case, the optical fibers couple the light to the output/aperture of the hand piece 310
  • the optical fibers 340 may be bonded to the treatment window or cooling plate 317 in a matrix arrangement with arbitrary or regular spacing between each of the optical fibers 340
  • Figure 12E depicts five such optical fibers 340, although fewer or, more likely, more optical fibers 340 can be used in other embodiments
  • a matrix arrangement of 30 by 10 optical fibers may be used in one exemplary embodiment
  • the diode laser bar (or diode laser bar stacks) is located in the base unit (which is not shown)
  • the diode laser bar (or diode laser bar stacks) can also be kept in the hand piece
  • the use of optical fibers 340 allow the bar(s) to be located at an arbitrary position within the hand piece 310 or, alternatively, outside the hand piece 310
  • a diode laser bar assembly As an example of an application of a diode laser bar to create thermal damage zones in the epidermis of human tissue, a diode laser bar assembly, as depicted in
  • the diode bar assembly had a sapphire window, which was placed m contact with the tissue and the laser was pulsed for about 10 ms
  • the treated tissue was then sliced through the center of the laser- treated zones to reveal a cross-section of the stratum corneum, epidermis and dermis
  • the resulting thermal damage channels were approximately 100 ⁇ m in diameter and 125-150 ⁇ m in depth for the 10 mJ per channel treatments
  • the spectral range of the EMR is 300 - 3000 nm
  • the energy exposure up to 1000 J/cm 2 is from about 0 lms to 10s
  • the fill factor is about 1% to 90 %
  • Another embodiment involves the use of imaging optics to image the tissue and use that information to determine medication application rates, application of EMR, or the like in order to optimize performance For instance, some medical treatments require that the medication application rate be accurately measured and its effect be analyzed in real time
  • the tissue surface imaging system can detect the size of reversible or irreversible holes created with techniques proposed in this specification for creating treatment islets in the stratum corneum
  • a capacitive imaging array can be used in combination with an image enhancing lotion and a specially optimized navigation / image processing algorithm to measure and control the application rate
  • capacitive imaging array is set forth above in connection with Figure 15 Such capacitive image arrays can be used, for example, within the applicator
  • the capacitive imaging arrays 350, 352 can also image the tissue Acquired images can be viewed in real time during treatment via a display window of the device
  • a suitable capacitive sensor for this embodiment is a sensor having an array of 8 image-sensing rows by 212 image-sensing columns
  • a typical capacitive array sensor is capable of processing about 2000 images per second
  • an orientation of the sensor can be selected to aid in functionality In one embodiment, for instance, the images are acquired and processed along the columns
  • Figures 39 and 40 illustrate still other exemplary embodiments in which the islets of treatment are formed generally through the use of a mirror containing holes or other transmissive portions Light passes through the holes in the mirror and strikes the tissue, creating islets of treatment Light reflected by the mirror stays in the optical system and through a system of reflectors is re-reflected back toward the mirror which again allows light to pass through the holes
  • the use of a mirror containing holes can be more efficient than the use of a mask with holes, where the mask absorbs rather than reflects light
  • the patterned optical radiation to form the islets of treatment is generated by a specially designed laser system 420 and an output mirror
  • the laser system 420 and output mirror 422 can be contained in, for instance, a hand piece
  • the laser system 420 can be contained in a base unit and the light passing through the holes in the mirror can be transported to the hand piece aperture through a coherent fiber optic cable
  • the laser can be mounted m the hand piece and microbeams from the laser can be directed to the tissue with an optical system
  • the laser system 420 comprises a pump source 426, which optically or electrically pumps the gain medium 428 or active laser medium
  • the gam medium 428 is in a laser cavity defined by rear mirror 430 and output mirror 422
  • Any type of EMR source, including coherent and non-coherent sources, can be used in this embodiment instead of the particular laser system 420 shown in Figure 39
  • the output mirror 422 includes highly reflective portions 432 that provide feedback (or reflection) into the laser cavity
  • the output mirror 422 also includes highly transmissive portions 434, which function to produce multiple beams of light that irradiate the surface 438 of
  • one or more optical elements can be added to the mirror 422 in order to image a sieve pattern of the output mirror 422 onto the surface of the tissue 440
  • the output mirror 422 is usually held away from the tissue surface 438 by a distance dictated by the imaging optical elements Proper choice of the laser cavity length L, operational wavelength ⁇ of the source
  • the gain g of the laser media 428, dimensions or diameter D of the transmissive portions 434 ( ⁇ e , if circular) in the output mirror 422, and the output coupler (if used) can help to produce output beams 436 with optimal properties for creating islets of treatment
  • D2/4 ⁇ L ⁇ 1 effective output beam diameter is made considerably smaller than D, achieving a size close to the system's wavelength ⁇ of operation
  • This regime can be used to produce any type of treatment islets
  • the operational wavelength ranges from about 0 29 ⁇ m to 100 ⁇ m and the incident fluence is in the range from 1 mJ/cm 2 to 100 J/cm 2
  • the effective heating pulse width can be m the range of less than 100 times the thermal relaxation time of a patterned compound (e g , from 100 fsec to lsec)
  • the chromophore layer is not used Instead the wavelength of light is selected to directly create the pathways
  • the spectrum of the light is in the range of or around the absorption peaks for water These include, for example, 970 nm, 1200 nm, 1470 nm, 1900 nm, 2940 nm, and/or any wavelength > 1800 nm
  • the spectrum is tuned close to the absorption peaks for lipids, such as 0 92 ⁇ m, 1 2 ⁇ m, 1 7 ⁇ m, and/or 2 3 ⁇ m, and wavelengths like 3 4 ⁇ m, and longer or absorption peaks for proteins, such as keratin, or other endogenous tissue chromophores contained in the tissue
  • the wavelength can also be selected from the range in which this absorption coefficient is higher than 1 cm “1 , such as higher than about 10 cm "1 Typically, the wavelength ranges from about 0 29 ⁇ m to 100 ⁇ m and the incident fluence is in the range from 1 mJ/cm 2 to 1000 J/cm 2
  • the effective heating pulse width is preferably less than 100 x thermal relaxation time of the targeted chromophores (e g , from 100 fsec to 1 sec)
  • Figures 10A- 1OC show another embodiment in which the output EMR from the hand piece is totally internally reflected when the hand piece is not in contact with a tissue When the hand piece is in contact with a tissue, the output EMR is spatially modulated in order to create islets of treatment in the tissue
  • the embodiment of Figures 10A- 1OC can include an EMR source 542, an optical reflector 546, one or more optical filters 548, a light duct 550 (or concentrator), and a cooling plate (not pictured)
  • the total internal reflection in the embodiment of Figures lOA-lOC is caused by the shape of the distal end 544 of the light duct 550
  • the distal end 550 can be an array of prisms, pyramids, hemispheres, cones, etc , such as set forth in Figures 1OB and 1OC
  • the array of elements have dimensions and shapes that introduce light total internal reflection (TIR) when the distal end 544 is in a contact with air, as shown in Figure 1OB
  • the distal end 544 does not cause TIR (it frustrates TIR) when the distal end 544 is in a contact with a lotion or tissue surface, as shown in Figure 1OC
  • the spectral range of electromagnetic radiation is about 300 - 3000 nm
  • the energy exposure is up to about 1000 J/cm 2
  • the laser pulse duration is from about 0 lms to 10 seconds
  • the fill factor is from about 1% to 90%
  • FIG. 1OA, 1OB, and 1OC depict the use of a non-coherent light source m a hand piece
  • a mechanism can also be used to cause TIR in an embodiment using a coherent light source, such as, for example, a solid state laser or a diode laser bar
  • a coherent light source such as, for example, a solid state laser or a diode laser bar
  • the light from the diode laser bar 315 can also be coupled to the tissue via a total internal reflection (TIR) prism
  • TIR total internal reflection
  • a distal end with prisms or the like can be used to re- image the emitters onto the tissue
  • a TIR prism can be used When the TIR prism is not in contact with tissue, light from the diode laser bar would be internally reflected and no light would be emitted from the hand piece However, when the tissue is coated with TIR prism
  • Figures 14A, 14B, and 14C show additional embodiments
  • Figure 14 A shows an embodiment in which the apparatus includes a laser source 620, focusing optics (e g , a lens) 622, and a fiber bundle 624
  • the laser source 620 can be any suitable source for this application, for example, a solid state laser, a fiber laser, a diode laser, or a dye laser
  • the laser source 620 can be an active rod made from garnet doped with rare earth ions
  • the laser source 620 can be housed in a hand piece or in a separate base unit
  • the laser source 620 is surrounded by a reflector 626 (which can be a high reflector HR) and an output coupler 628 (OC)
  • the reflector 626 and the coupler 628 are not used
  • Various types and geometries of reflectors can be used for reflector 626
  • the fiber bundle 624 is located optically downstream from the lens 622, so that the optical lens 622 directs and
  • an optical element 630 such as a lens array, can be used to direct and output the EMR from the fiber bundle 624 in order to focus the EMR onto the tissue 632
  • the optical element 630 can be any suitable element or an array of elements
  • the optical element 630 is a micro lens array In other embodiments, an optical element 630 might not be used In such an embodiment, the outputs of the fibers in the fiber bundle 624 can be connected to one side of a treatment window (such as a cooling plate of the apparatus), where the other side of the treatment window is in contact with the tissue 632
  • the laser source 620 In operation, the laser source 620 generates EMR and the reflector 626 reflects some of it back toward the output coupler 628 The EMR then passes through the output coupler 628 to the optical lens 622, which directs and focuses the EMR into the fiber bundle 624 The micro lens array 630 at the end of the fiber bundle 624 focuses the
  • the apparatus includes a laser source 620 and a phase mask 640
  • the laser source 620 can be any type of laser source and can be housed in a hand piece or in a separate base unit, such as in the embodiment of Figure 14A
  • the laser source 620 can be an active rod made from garnet doped with rare earth ions
  • the laser source 620 can be surrounded by a reflector 626 (which can be a high reflector HR) and can output EMR into an output coupler 628 (OC)
  • the embodiment of Figure 14B includes a phase mask 640 that is located between the output coupler 628 and an optical element 642
  • the phase mask 640 can include a set of apertures that spatially modulate the EMR
  • Various types of phase masks can be used in order to spatially modulate the EMR in order to form islets of treatment on the tissue 632
  • the optical element 642 can be any suitable element or an array of elements (such as lenses or micro lenses) that focuses the EMR radiation onto the tissue 632
  • the optical element 642 is a lens
  • the laser source 620 In operation, the laser source 620 generates EMR and the reflector 626 reflects some of it back toward the output coupler 628 The EMR then passes through the output coupler 628 to the phase mask 640, which spatially modulates the radiation
  • the optical element 642 which is optically downstream from the phase mask 640 so that it receives output EMR from the phase mask 640, generates an image of the apertures on the tissue
  • Figure 14C shows another embodiment
  • the apparatus includes multiple laser sources 650 and optics to focus the EMR onto the tissue 632
  • the multiple laser sources 650 can be any suitable sources for this application, for example, diode lasers or fiber lasers
  • the laser sources 650 can be a bundle of active rods made from garnet doped with rare earth ions
  • the laser sources 650 can optionally be surrounded by a reflector and/or an output coupler, similar to the embodiments of Figures 14A and 14B
  • an optical element 642 can be used for focusing the EMR onto the tissue 632
  • Any suitable element or an array of elements can be used for the optical element 642
  • the optical element for example, can be a lens 642
  • the bundle of lasers 650 generate EMR
  • the EMR is spatially modulated by spacing apart the laser sources 650 as shown in Figure 14C
  • the EMR that is output from the laser sources 650 therefore, is spatially modulated
  • This EMR passes through the output coupler 628 to the optical element 642, which focuses the EMR onto the tissue 632 to form islets of treatment
  • the spectral range of electromagnetic radiation is about 400 - 3000 nm
  • the energy exposure is up to about 1000 J/cm 2
  • the laser pulse duration is from about lOps to 10s
  • the fill factor is from about 1% to 90%
  • numerical Ranges As used herein, the recitation of a numerical range for a variable is intended to convey that the embodiments may be practiced using any of the values within that range, including the bounds of the range
  • the variable can be equal to any integer value within the numerical range, including the end-points of the range
  • the variable can be equal to any real value within the numerical range, including the end-points of the range
  • a va ⁇ able which is described as having values between 0 and 2 can take the values 0, 1 or 2 if the variable is inherently discrete, and can take the values 0 0, 0 1, 0 01, 0 001, or any other real values > 0 and ⁇ 2 if the variable is inherently continuous
  • the variable can take multiple values in the range, including any sub-range of values within the cited range
  • EMR includes the range of wavelengths approximately between 200 nm and 10 mm
  • Optical radiation, i e EMR in the spectrum having wavelengths in the range between approximately 200 nm and 100 ⁇ m
  • the term “narrow-band” refers to the electromagnetic radiation spectrum, having a single peak or multiple peaks with FWHM (full width at half maximum) of each peak typically not exceeding 10% of the central wavelength of the respective peak
  • the actual spectrum may also include broad-band components, either providing additional treatment benefits or having no effect on treatment
  • the term optical when used in a term other than term “optical radiation" applies to the entire EMR spectrum
  • the term “optical path” is a path suitable for EMR radiation other than "optical radiation " It should be noted, however, that other energy may be used to for treatment islets in similar fashion
  • non EMR sources such as ultrasound, photo-a

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Abstract

L'invention concerne des procédés destinés à traiter des tissus au moyen de rayonnement électromagnétique (REM) afin de produire des réseaux d'îlots traités par REM dans le tissu. De manière spécifique, l'invention concerne des procédés destinés à traiter des tissus osseux et des tissus mous internes tels que, mais sans que ceci soit limitatif, des organes, des os, des muscles, des tendons, des ligaments, des vaisseaux et des nerfs présentant de tels îlots traités par REM. L'invention concerne également des dispositifs et des systèmes destinés à produire des réseaux d'îlots traités par REM dans un tissu, et les applications cosmétiques et médicales de ces dispositifs et systèmes.
PCT/US2007/086827 2006-12-07 2007-12-07 Utilisation de la technologie rem sur des incisions et des tissus internes WO2008070851A2 (fr)

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ITFI20100015A1 (it) * 2010-02-04 2011-08-05 El En Spa "dispositivo per il trattamento del canale vaginale e relativo apparecchio"
WO2011103005A1 (fr) * 2010-02-16 2011-08-25 Checkpoint Surgical, Llc Systèmes et procédés pour stimulation neurale régionale
KR20160042069A (ko) * 2013-08-09 2016-04-18 더 제너럴 하스피탈 코포레이션 진피 기미의 치료를 위한 방법 및 장치
US9457431B2 (en) 2012-05-22 2016-10-04 Koninklijke Philips N.V. Cutting head for a device for cutting hair
CN106686643A (zh) * 2015-11-06 2017-05-17 三星电子株式会社 用于调节来自无线设备的电磁辐射的方法和***
US11529230B2 (en) 2019-04-05 2022-12-20 Amo Groningen B.V. Systems and methods for correcting power of an intraocular lens using refractive index writing
US11564839B2 (en) 2019-04-05 2023-01-31 Amo Groningen B.V. Systems and methods for vergence matching of an intraocular lens with refractive index writing
US11583389B2 (en) 2019-04-05 2023-02-21 Amo Groningen B.V. Systems and methods for correcting photic phenomenon from an intraocular lens and using refractive index writing
US11583388B2 (en) 2019-04-05 2023-02-21 Amo Groningen B.V. Systems and methods for spectacle independence using refractive index writing with an intraocular lens
US11678975B2 (en) 2019-04-05 2023-06-20 Amo Groningen B.V. Systems and methods for treating ocular disease with an intraocular lens and refractive index writing
US11944574B2 (en) 2019-04-05 2024-04-02 Amo Groningen B.V. Systems and methods for multiple layer intraocular lens and using refractive index writing

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITFI20100015A1 (it) * 2010-02-04 2011-08-05 El En Spa "dispositivo per il trattamento del canale vaginale e relativo apparecchio"
WO2011096006A1 (fr) * 2010-02-04 2011-08-11 El.En. S.P.A. Dispositif pour le traitement du canal vaginal et équipement associé
WO2011103005A1 (fr) * 2010-02-16 2011-08-25 Checkpoint Surgical, Llc Systèmes et procédés pour stimulation neurale régionale
US9457431B2 (en) 2012-05-22 2016-10-04 Koninklijke Philips N.V. Cutting head for a device for cutting hair
KR20160042069A (ko) * 2013-08-09 2016-04-18 더 제너럴 하스피탈 코포레이션 진피 기미의 치료를 위한 방법 및 장치
CN106686643A (zh) * 2015-11-06 2017-05-17 三星电子株式会社 用于调节来自无线设备的电磁辐射的方法和***
US11529230B2 (en) 2019-04-05 2022-12-20 Amo Groningen B.V. Systems and methods for correcting power of an intraocular lens using refractive index writing
US11564839B2 (en) 2019-04-05 2023-01-31 Amo Groningen B.V. Systems and methods for vergence matching of an intraocular lens with refractive index writing
US11583389B2 (en) 2019-04-05 2023-02-21 Amo Groningen B.V. Systems and methods for correcting photic phenomenon from an intraocular lens and using refractive index writing
US11583388B2 (en) 2019-04-05 2023-02-21 Amo Groningen B.V. Systems and methods for spectacle independence using refractive index writing with an intraocular lens
US11678975B2 (en) 2019-04-05 2023-06-20 Amo Groningen B.V. Systems and methods for treating ocular disease with an intraocular lens and refractive index writing
US11931296B2 (en) 2019-04-05 2024-03-19 Amo Groningen B.V. Systems and methods for vergence matching of an intraocular lens with refractive index writing
US11944574B2 (en) 2019-04-05 2024-04-02 Amo Groningen B.V. Systems and methods for multiple layer intraocular lens and using refractive index writing

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