Patent Application
20170112574
Field of the Invention
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. 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.
Description of the Related Art
Electromagnetic radiation, particularly in the form of laser light, has been used in a variety of cosmetic and medical applications, including uses in dermatology, dentistry, ophthalmology, gynecology, otorhinolaryngology and internal medicine. For most dermatological applications, the EMR treatment can be performed with a device that delivers the EMR to the surface of the targeted tissues. For applications in internal medicine, 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. As a general matter, the EMR treatment is typically designed to (a) deliver one or more particular wavelengths (or a particular continuous range of wavelengths) of EMR to a tissue to induce a particular chemical reaction, (b) deliver EMR energy to a tissue to cause an increase in temperature, (c) deliver EMR energy to a tissue to damage or destroy cellular or extracellular structures, or (d) deliver EMR energy to a tissue to activate an exogenous substance that has been injected (as in the case of some cancer treatments) or topically applied (as in the case of some acne treatments).
EMR treatments of various tissues, including internal tissues and tissues involved in surgical, medical, therapeutic, post-operative, and other procedures, 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. For example, the wavelengths typically utilized for selective photothermolysis 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. Thus, larger and more powerful EMR sources may be required in order to achieve a desired therapeutic result. However, increasing power may cause undesired and potentially dangerous heating of tissue.
In some cases when treating internal tissues, such as nerves or small structures involved in certain surgical procedures, bulk heating of the entire tissue may be detrimental. Similarly, certain tissues may have already been damaged by trauma or during the course of surgical or other procedures, and may thus be more susceptible than healthy tissue to unwanted damage from the application of too much EMR. Additionally, internal tissues may benefit from the application of EMR using techniques that promote the repair of tissue, accelerate the healing process, and/or accentuate the healing process. The use of new devices and techniques may promote healing and/or prevent damage to such tissue.
In the cosmetic field for the treatment of various skin conditions, methods and devices have been developed that irradiate or cause damage in a portion of the tissue area and/or volume being treated. These methods and devices have become known as fractional technology. Fractional technology is thought to be a safer method of treatment of skin for cosmetic purposes, because the damage occurs within smaller sub-volumes or islets within the larger volume being treated. The tissue surrounding the islets is spared from the damage. Because the resulting islets are surrounded by neighboring healthy tissue the healing process is thorough and fast.
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.
Preferred embodiments of this aspect of the invention may include one or more of the following. 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 of damaged tissue corresponding to the irradiated portions of the internal tissue, wherein the subvolumes are separated by undamaged tissue.
Preferred embodiments of this aspect of the invention may include one or more of the following. The treatment device may include a cannula or a catheter. The internal tissue to be treated is a blood vessel, and the treatment device is inserted into a lumen of the blood vessel. The ratio of the subvolumes of treated tissue to the volume of internal tissue being treated is between about 0.1% and about 90%, or more specifically may be about 10% to about 50%, or even more specifically may be about 10% to about 30%.
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; precooling 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 radiation from said source is applied. The optical system may provide a plurality of foci for concentrating said treatment radiation to at least one depth in said volume of internal tissue and to selected areas of said volume, with the at least one depth and the areas defining three dimensional treatment portions at the foci in the volume within untreated portions of the volume. The device further may include a controller for selectively activating the source so as to successively irradiate the plurality of foci.
Preferred embodiments of this aspect of the invention may include one or more of the following. The device may include a cooling system configured to cool the volume of internal tissue. The cooling system may be configured to cool the volume of internal tissue during operation to a selected temperature and to a selected depth. The device may include cannula or a catheter each configured to emit radiation from a portion thereof.
In various embodiments, 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. Such 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 non-surgical and non-medical procedures, for example, as during therapy or the treatment of post-operative and other wounds.
The following drawings are illustrative of embodiments and are not meant to limit the scope of the invention as encompassed by the claims.
When using electromagnetic radiation (EMR) to treat tissues, there are many advantages to producing lattices of EMR-treated islets in the tissue rather than large, continuous regions of EMR-treated tissue. 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.” When the absorption of EMR energy results in significant temperature elevation in the EMR-treated islets, the lattice is referred to herein as a lattice of “thermal islets.” When 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.” When an amount of energy (usually at a particular wavelength) sufficient to initiate a certain photochemical reaction is delivered, the lattice is referred to herein as a lattice of “photochemical islets.” By producing EMR-treated islets rather than continuous and/or uniform regions of EMR-treatment, more EMR energy can be delivered to an islet without producing a thermal islet or damage islet, and/or the risk of bulk tissue damage can be lowered.
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. One skilled in the art will recognize that many combinations of parameters are possible that will result in such local maxima of EMR-treatment within the tissue.
When using electromagnetic radiation (EMR) to treat tissues, whether for purposes of photodynamic therapy, photobiomodulation, photobiostimulation, photobiosuspension, thermal stimulation, thermal coagulation, thermal ablation or other applications, there are substantial advantages to producing lattices of EMR-treated islets in the tissue rather than large, continuous regions of EMR-treated tissue. The 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.” When the absorption of EMR energy results in significant temperature elevation in the EMR-treated islets, the lattice is referred to herein as a lattice of “thermal islets.” When 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.” When an amount of energy (usually at a particular wavelength) sufficient to initiate a certain photochemical reaction is delivered, the lattice is referred to herein as a lattice of “photochemical islets.”
By producing EMR-treated islets rather than continuous regions of EMR-treatment, 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. Moreover, with respect to damage islets, it should be noted that the regenerative and repair responses of the body occur at wound margins (i.e., the boundary surfaces between damaged and intact areas) and, therefore, healing of damaged tissues is more effective with smaller damage islets, for which the ratio of the wound margin to volume is greater.
As described more fully below, the percentage of tissue volume which is EMR-treated versus untreated (or differently- or less-treated) can determine whether optical islets become thermal islets, damage islets or photochemical islets. This percentage is referred to as the “fill factor”, and 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).
Because 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. Finally, because 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, otorhinolaryngology 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. Although 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. Depending upon the nature of the treatment, in particular the amount of energy transfer to the islets, the degree of heating of the tissue, or the wavelength(s) of the energy, 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). These different categories of EMR-treated islets, devices and systems for producing such EMR-treated islets, and cosmetic and medical applications for such devices and systems are separately discussed in detail below. As used herein, the terms “treatment islet,” “islets of treatment,” and “EMR-treated islets” are used interchangeably to mean any of the categories of islets described below.
A. Optical Islets
EMR-treatment of completely or partially isolated volumes or islets of tissue produces a lattice of EMR-treated islets surrounded by untreated volumes. Although 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 infra-red spectrum. Other forms of EMR may be useful, including, without limitation, microwave, radio frequency, low frequency and EMR induced by direct current.
As noted above, when the total energy transfer per unit cross-sectional area (i.e., fluence) or the rate of energy transfer per unit cross-sectional area (i.e., flux) becomes sufficiently high, 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. Thus, although all thermal islets and damage islets are also optical islets, not all optical islets are thermal islets or damage islets. In some embodiments, as described below, it can be desirable to produce optical islets without producing thermal or damage islets. In such embodiments, the fill factor can be decreased in order to provide a greater volume of untreated tissue to act as a thermal sink.
B. Thermal Islets
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. By using a sufficiently short pulse width relative to the temperature relaxation time of the target, it is possible to avoid merging or overlapping of thermal islets in a lattice.
C. Damage Islets
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, photoablation, or water vaporization. Depending upon the intended use, damage islets with lesser degrees of damage (e.g., protein coagulation, thermal injury) or greater degrees of damage (e.g., photodisruption, photoablation, or water vaporization) may be appropriate. As before, damage 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) tissue (e.g., melanin, hemoglobin), by exogenous chromophores within the tissue (e.g., tattoo ink, ALA) or, as described below, by exogenous chromophores applied to the surface of the tissue.
In some embodiments, 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, Welch et al., eds. (Plenum Press, New York), pp. 561-606). 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, Welch et al., eds. (Plenum Press, New York), pp. 561-606; Henriques (1947), Arch. Pathol. 43:480-502) is employed. Other mechanisms and models of damage islet formation can apply to embodiments with relatively short and intense pulses, particularly in connection with photodisruption, photoablation, and water vaporization.
D. Photochemical Islets
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 biomolecules or exogenous molecules. For example, 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. Alternatively, for example, 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.
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:
A. The Shape of EMR-Treated Islets.
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. Thus, depending upon the wavelength(s), temporal characteristics (e.g., continuous versus pulsed delivery), and fluence of the EMR; the geometry, incidence and focusing of the EMR beam; and the index of refraction, absorption coefficient, scattering coefficient, anisotropy factor (the mean cosine of the scattering angle), and the configuration of the tissue layers; and the presence or absence of exogenous chromophores and other substances, 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 beams can be convergent, defining volumes of decreasing cross-sectional area in the plane orthogonal to the central axis of the beams (e.g., cones, pyramids). The cross-sectional areas can be regular in shape (e.g., ellipses, polygons) or can be arbitrary in shape. In addition, depending upon the wavelength(s) and fluence of an EMR beam, and the absorption and scattering characteristics of a tissue for the wavelength(s), an EMR beam may penetrate to certain depths before being initially or completely absorbed or dissipated and, therefore, an EMR-treated islet may not extend through the entire depth of the tissue but, rather, may extend between the surface and a particular depth, or between two depths below the surface.
Generally, though not necessarily, the lattice is a periodic structure of islets, and can be arranged in one, two, or three dimensions. For instance, a two-dimensional (2D) lattice is periodic in two dimensions and translation invariant or non-periodic in the third. For example, and without limitation, there can be layer, square, hexagonal or rectangle lattices. The lattice dimensionality can be different from that of an individual islet. A single row of equally spaced cylinders is an example of a 1D lattice of 3D islets. For certain applications, 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.
Referring to
The parameters for obtaining a particular islet shape can be determined empirically with only routine experimentation. For example, 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. Alternatively, a 1200 nm laser operating with a highly converting beam at approximately 0.5-10 J and a pulse width of 0.5-3 sec, can produce a generally ellipsoid-shaped islet.
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 in 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. The 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.
As a general matter, the size of the EMR-treated islets can range from 1 μm to maximum length of targeted tissue in any particular dimension. For example, and without limitation, a lattice of substantially linear islets can consist of parallel islets having a length of approximately 300 mm and a width of approximately 10 μm to 3 mm to treat the length of a blood vessel. As another example, and without limitation, for substantially cylindrical islets in which the axis of the cylinder is orthogonal to the tissue surface, the depth can be approximately 10 μm to 4 mm and the diameter can be approximately 10 μm to 1 mm. For substantially spherical or ellipsoidal islets, the diameter or major axis can be, for example, and without limitation, approximately 10 μm to 1 mm. Thus, in some embodiments, 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.
When considering the size of the optical, thermal, damage or photochemical islets, it is important to note that the boundaries of the islets may not be clearly demarcated but, rather, may vary continuously or blend into the untreated tissue (or differently- or less-treated tissue). For example, EMR beams are subject to scattering in various tissues and, therefore, even beams of coherent light will become diffuse as they penetrate through multiple layers of cells or tissues. As a result, optical and photochemical islets typically may not have clear boundaries between treated and untreated volumes. For some parameters, the transition from treated to untreated tissue will be quick and the boundaries of the islet will be well defined. For other parameters, the transition will be more gradual and less well defined. Similarly, thermal islets typically will exhibit a temperature gradient from the center of the islet to its boundaries, and untreated tissue surrounding the islet also will exhibit a temperature gradient due to conduction of heat. Finally, 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 islets, refers to the size of the islet as defined by the intended minimum or threshold amount of EMR energy delivered. This amount is expressed as the minimum fluence, Fmin, and is determined by the nature of the cosmetic or medical application. For example, for photodynamic therapy, Fmin can be determined by the minimum fluence necessary to cause the desired photochemical reaction. Similarly, for increasing the permeability of the tissue, Fmin can be determined by the minimum fluence necessary to achieve the desired tissue temperature, and for destroying tissue, Fmin can be determined by the minimum fluence necessary to ablate the tissue or vaporize water. In each case, the size of the EMR-treated islet is defined by the size of the tissue volume receiving the desired minimum fluence.
Because of the scattering effects of tissue, the minimum size of an EMR-treated islet increases with the targeted depth in the tissue. For a depth of approximately 1 mm into a subject's tissue, the practical minimum diameter or width of a non-ablative islet is estimated to be approximately 100 μm, although much larger islets (e.g., 1-10 mm) are possible. (However, islets smaller than 100 μm 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. For a minimum size islet at any particular depth in the tissue, the wavelength, beam size, convergence, energy and pulse width have to be optimized.
C. The Depth of EMR-Treated Islets.
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.
For example, optical islets can be induced at varying depths in 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. Thus, the islets can be shallow islets that penetrate only surface layers of a tissue (e.g., 0-50 μm), deeper islets that span several layers of a tissue (e.g., 50-500 μm), or very deep, subsurface islets ((e.g., 500 μm-5 mm or more). Using optical energy, depths of up to 25 mm can be achieved. Using microwave and radio frequency EMR, depths of several centimeters can be achieved.
For thermal islets or damage islets, 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. For creating deep thermal or damage islets, long pulse widths coupled with surface cooling can be particularly effective.
D. Fill Factor of EMR-Treated Lattices
In a given lattice of EMR-treated islets, the percentage of tissue volume which is EMR-treated is referred to as the “fill factor” or f, 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). For such situations, an average fill factor (favg) can be calculated by dividing the volume of all EMR-treated islets Viislet by the volume of all tissue Vitissue in the treatment area,
Generally, 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). Thus, the calculation of the fill factor will depend on volume of an EMR-treated islet as well as on the spacing between the islets. In a periodic lattice, where the centers of the nearest islets are separated by a distance d, the fill factor will depend on the ratio of the size of the islet to the spacing between the nearest islets d. For example, in a lattice of parallel cylindrical islets, the fill factor will be:
where d is the shortest distance between the centers of the nearest islets and r is the radius of a cylindrical EMR-treated islet. In a lattice of spherical islets, 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:
where 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.)
Because 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. Finally, because 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 facilitate the healing of any damage thereto, while still permitting the desired therapeutic effect to be achieved. In general, 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 in a variety of different organs and tissues. For example, 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. As a general matter, 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), and undesired pigmentation (e.g., pigmented birthmarks, tattoos). The time for recovery or healing of such damage islets can be controlled by changing the size of the damage islets and the fill factor of the lattice.
For example, the embodiments described herein are particularly suited to treating internal tissues of the body, for example, in surgical and medical applications. As an example, 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. Further, because the ligament or tendon is already being accessed for purposes of the surgical repair, for example, through an incision or using an endoscope, 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 within the scope of the claims may include invasive aspects, for example, making an incision, solely for the purpose of accessing and treating internal tissues, such as ligaments, bones, tendons, muscles, organs, blood vessels, bones, nerves, etc.) with EMR for the purposes of forming lattices of damage islets.) Although many other applications are possible, several specific applications are discussed below as exemplary embodiments.
A. Surgical and Other Applications Pertaining to Internal Tissues within a Body:
One particularly useful embodiment 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 depths of approximately 400 μm and a center-to-center spacing of approximately 500 μm (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 and need for further surgical procedures and reduce post-surgical complications. Retreatment of the injured tissue using arthroscopic methods can be used in the course of a series of treatments as part of the overall physical medicine therapy leading to a faster, more complete recovery with fewer complications.
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.
When the density and distribution of these is sufficient within the targeted region a generalized recruitment of healing throughout the region appears to be elicited. This has the advantage that repair is elicited without initial loss of function.
Application of EMR to form 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 in the process of access to the target tissue speeds recovery and function. In some embodiments, 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 photobiomodulation. (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. For example, referring to
As an example of another embodiment, referring to
In operation, 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. For example, in one embodiment, 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. Using such small and even microscopic or nearly microscopic devices to create EMR-islets, fine and delicate treatments can be performed on very small tissue volumes and structures. For, for example, 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.
The specific wavelength, focal depth and intensity will be based upon the intended use. The differences in tissue properties, size, thickness and constituent properties will need to be considered. 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.
B. Improving Healing of Incisions, Points of Reattachment, and Other Wounds:
The creation of lattices of damage islets can be used to decrease the time needed for the healing of wounds by recruitment of tissue surrounding the wound margin to participate more fully in the repair and healing process with minimal to no negative impact on the structure and function of the surrounding tissue's capability to perform its normal function. In surgical procedures, tissue is often removed and dissected prior to reattachment and repair. Also in order to gain access to the intended surgical site other structure needs to be opened and cut. These tissues may also need to be reattached.
Using convention surgical techniques and procedures, the recovery site and wound zone is limited to the tissue at the opposing sides of the incision. Much of the ability to restore function, however, depends upon surrounding tissue response and repair. Examples include cases in which a section of vein is removed for grafting to another body site or reattachment of ligaments following a significant tear. The ability to recruit repair mechanisms in adjacent tissue and all along the affected length of the vessel, connective tissue or organ is limited by the vast distances from the incision and attachment site. The natural chemical signals that mediate the natural healing and repair responses of the tissue leading to upregulation and regrowth are at best weak if at all present due to the extensive distance involved to reach the adjacent tissue. In some cases, scar tissue may form and has potential to inhibit and limit repair and restoration of tissue strength and function.
Application of EMR to form lattices of treatment islets, however, promotes recovery by extending and recruiting the healing needed to more fully and completely restore function to throughout the length, breadth and extent of the entire affected tissue.
As one example, in a case where a blood vessel is damaged and a section of the blood vessel is remove prior to rejoining the ends of the blood vessel, 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. To provide the treatment, 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.
C. Treating Subcutaneous Tissue Scars:
The creation of 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. For example, 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.
Similarly, 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.
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. Furthermore, many internal tissue will have sufficient moisture to provide optical coupling with the device, and the parameters of the device may be optimized to provide impedance matching in those cases, if required or desired. For surgical procedures, any such lotion or substance must be suitable for use within a body. Tissue 246, as shown in
The system 208 of
In other embodiments, fiber delivery of laser light using endoscopic methods or arthroscopic scope enable treatments of certain tissues without more extensive surgical procedures. For example, referring to
In operation, tube 304 is inserted into a blood vessel 312 (or other lumen or other tissue, such as fat tissue, or organs such as the heart, stomach or other organs of the digestive tract). Once inserted and positioned, the EMR-transmission mechanism 306 is pulled back through and along the length of the vessel to be treated. The motion sensor 310 measures the speed of motion of the EMR-transmission mechanism relative to the internal wall of the blood vessel 312. A controller (not shown) causes EMR to be irradiated from the EMR-transmission mechanism 306 in pulses at a predetermined rate based on the speed that EMR-transmission mechanism 306 travels within the vessel 312. This causes the light beams 314 to be irradiated intermittently along the blood vessel 312 and create a pattern of EMR-treated islets 316 along the blood vessel 312.
In an alternate embodiment shown in
The EMR-treatment mechanism 306 can be gradually moved forward or withdrawn as the pulsations are emitted resulting in 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. Many alternate embodiments are possible and 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.
Similarly, the technique can also be applied to conventional light-based liposuction treatments. For example, 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 cells such that EMR-islets are created within the tissue, causing the fat cells to rupture and drain away. Additionally, EMR-islets can be formed, simultaneously or in a separate step or procedure, in surrounding tissue to cause a healing response in the tissue surrounding the fat cells that, for example, will allow the tissue to reform as firm tissue and reduce sagging and other effects from the loss of significant amounts fat cells.
A. Electromagnetic Radiation Sources
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. For example, 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. In addition, multiple energy sources may be used which are identical or different. For example, multiple laser sources may be used and they may generate optical energy having the same wavelength or different wavelengths. As another example, multiple lamp sources may be used and they may be filtered to provide the same or different wavelength band or bands. In addition, different types of sources may be included in the same device, for example, mixing both lasers and lamps.
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. In certain cases, 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. In other embodiments, 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.
Depending on the application, many types of electromagnetic radiation, and other forms of energy in some cases, may be used. For example, UV, violet, blue, green, yellow light or infrared radiation (e.g., about 290-600 nm, 1400-3000 nm) can be used for treatment of superficial targets, such as vascular and fascia. Blue, green, yellow, red and near IR light in a range of about 450 to about 1300 nm can be used for treatment of a target at depths up to about 1 millimeter below the tissue surface. Near infrared light in a range of about 800 to about 1400 nm, about 1500 to about 1800 nm or in a range of about 2050 nm to about 2350 nm can be used for treatment of deeper targets (e.g., up to about 3 millimeters beneath the surface)—(See Table 1B). Additionally, acoustic, RF or other EMF sources may also be employed in suitable applications.
1. Coherent Light Sources.
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. For example, the energy source 210 can be a neodymium (Nd) laser, such as a Nd:YAG laser. In this exemplary embodiment, the energy source 210 includes a neodymium (Nd) laser generating radiation having a wavelength around 1064 nm. Such 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. In other embodiments, 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 and other coherent light sources can be used to cover wavelengths within the 100 to 100,000 nm range. Examples of coherent energy sources are solid state, dye, fiber, and other types of lasers. For example, a solid state laser with lamp or diode pumping can be used. The wavelength generated by such a laser can be in the range of 400-3,500 nm. This range can be extended to 100-20,000 nm by using non-linear frequency converting. Solid state lasers can provide maximum flexibility with pulse width range from femtoseconds to a continuous wave.
Another example of a coherent source is a dye laser with non-coherent or coherent pumping, which provide wavelength-tunable light emission. Dye lasers can utilize a dye dissolved either in liquid or solid matrices. Typical tunable wavelength bands cover 400-1,200 nm and a laser bandwidth of about 0.1-10 nm. Mixtures of different dyes can provide multi wavelength emission. Dye laser conversion efficiency is about 0.1-1% for non-coherent pumping and up to about 80% with coherent pumping. 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/cm2, pulse duration from picoseconds to tens of seconds, and a fill factor from about 0.1% to 90%.
Another example of 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 a variety of optical elements described below, or can be directly placed in contact with the tissue with or without a protective/cooling interface window. Such fiber lasers can result in energy exposures of up to about several hundreds of J/cm2 and pulse durations from about picoseconds to tens of seconds.
Diode lasers can be used for, e.g., the 400-100,000 nm range. Since many photodermatology applications require a high-power light source, the configurations described below using diode laser bars can be based upon about 10-100 W, 1-cm-long, cw diode laser bar. Note that other sources (e.g., LEDs and microlasers) or embodiments can be designed using lower power (mW to 10W) sources can be substituted in the configurations described for use with diode laser bars with suitable modifications to the optical and mechanical sub-systems.
Other types of lasers (e.g., gas, excimer, etc.) can also be used.
2. Non-Coherent Light Sources
A variety of non-coherent sources of electromagnetic radiation (e.g., arc lamps, incandescence lamps, halogen lamps, light bulbs) can be used as an energy source. There are several monochromatic lamps available such as, for example, hollow cathode lamps (HCL) and electrodeless discharge lamps (EDL). HCL and EDL may generate emission lines from chemical elements. For example, sodium emits bright yellow light at 550 nm. The output emission may be concentrated on the target with reflectors and concentrators. Energy exposures up to about several tens of J/cm2, 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.
In some embodiments, 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 microprisms 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 0.1 ms to 10 s.
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/cm2 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/cm2 and pulse durations from about 0.2 seconds to continuous emission.
Light-emitting diodes (LEDs) that emit light in the 290-2,000 nm range can be used to cover wavelengths not directly accessible by diode lasers.
Referring again to
B. Optical System
Generally, optical system 212 of
If an optical system 212 is used, the energy of the applied light can be concentrated to deliver more energy to target portions 214. Depending on system parameters, portions 214 may have various shapes and depths as described above.
The optical system 212 as shown in
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 interpreted, where appropriate, to include such a system.
C. Accessory Elements for Cooling, Heating, Reflecting, Absorbing, Blocking as Ancillary Process to Guide, Restrict or Modify Effects of Radiation on Tissue.
As discussed above, the system 208 can also include a cooling element 215 to cool the surface of the tissue 200 over treatment volume V. As shown in
Treatment of internal tissues of the body during may be manipulated so that the cooling element is applied to the internal side of the tissue or through liquid perfused through the tissue. In these embodiments, cooling may be used to control the depth of effective treatment by preventing the internal surfaces from reaching temperatures that are damaging. When treating a vessel, for instance, one way to protect the inner vessel wall surface would be to perfuse or prefill the vessel with cooled fluid such as saline, lactated ringers, or blood plasma during application of radiation to the external wall surface as part of treatment.
In alternate embodiments, materials may be externally applied to facilitate treatment. For example, 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. In some applications, the tissue may be preheated or precooled to a set point temperature to enable treatment at a specific and/or predetermined target depth.
Similarly, 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. For example, in one embodiment, 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 within 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 one or more sides or locations to create a more uniform intensity and/or dispersion of EMR throughout the tissue volume. One skilled in the art will further appreciate that such a technique could also be applied without forming EMR-treated islets and instead treating a relatively larger contiguous volume of tissue or treating only a single relatively small tissue volume.
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. For example, in one embodiment, 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. In yet another embodiment, the cooling system may comprise a water or refrigerant fluid (for example R134A) spray, a cool air spray or air flow across the surface of the tissue. In other embodiments, cooling may be accomplished through chemical reactions (for example, endothermic reactions), or through electronic cooling, such as Peltier cooling.
In certain cases, cooling mechanism may be used to maintain the surface temperature of the tissue at its normal temperature, which may be, for example, 37° C., but will vary depending on the type of tissue being heated. In other embodiments, cooling mechanism may be used to decrease the temperature of the surface of the tissue to a temperature below the normal temperature of that type of tissue. For example, the cooling mechanism may be able to decrease the surface temperature of tissue to, for example, a range between 25° C. and −5° C. In other embodiments, a plate can function as a heating plate in order to heat the tissue. Some embodiments can include a plate that can be used for cooling and heating.
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
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 in the tissue. For example, the devices can use reflection, refraction, interference, diffraction, and deflection of incident light to create treatment islets. A number of these devices are briefly summarized below, with a more detailed explanation of the devices in the remainder of the specification, and in particular in 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. In addition, although 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.
Splitting of EMR by reflection of the light can be obtained using specular or diffuse reflection of the light from surfaces with refractive indices higher than 1. Splitting of EMR by refraction can be obtained using refraction on angular or curved surfaces. Diffraction splitting is based on the fact that light can bend around edges. Deflection splitting can be achieved when light propagates inside a media with a non-even distribution of refractive indices.
1. Blocking Portions of the EMR Beam
In some embodiments, 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.
2. Focusing, Directing, or Concentrating the EMR Beam
In some embodiments, 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. For example,
In addition, in some embodiments, such as that of
Alternatively, 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.
3. Arrays of EMR Sources
Instead of splitting the EMR into multiple beams, one can use a plurality of light sources or a single light source with a serial or parallel optical multiplexer to form islets of treatment in the tissue. For example, the embodiment of
4. Pulsing the EMR Source
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. In another embodiment, 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.
5. Lattices of Exogenous Chromophores
In other embodiments, 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. In this case, the EMR energy may illuminate the entire tissue surface where such pattern of topical composition has been applied. Upon application of appropriate EMR, the chromophores can heat up, thus creating islets of treatment in the tissue. Alternatively, 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 function of the tissue condition at the desired treatment area and be generated ad hoc.
Some embodiments provide a film or substrate material with a lattice of dots, lines or other shapes, either on the surface of the film or embedded within the film, in which the dots, lines or other shapes include a chromophore appropriate to the EMR source. The dots, lines or other shapes may be the same or different sizes and different shapes may be included on the film.
6. Creating Thermal Lattices Using Patterned Cooling
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.
Some embodiments for treatment internal tissue may use associative agents to target light to specific cells or aspects of the tissue by pretreating tissue or applications to the tissue during treatment. Dyes or other such agents can be used to absorb or protect vessels within a target tissue.
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
In other embodiments, real time acquired images can be used for statistical analysis of, for example, a marker concentration in an exogenous substance or for other purposes associated with the procedure. Images can also be used to visualize tissue that it out of the line of sight of a surgeon during a procedure. The imaging system can also function as a contact sensor. This allows for real time determination of immediate contact of a hand piece with the tissue. The combination of hardware and software allows this determination within one image frame. The algorithm measures in real time a tissue contact and navigation parameters (position, velocity and acceleration) along the x-axis and y-axis. A capacitive sensor along with image processing and special lotion can be used for detecting tissue imperfections and measuring the size of the imperfection in real time. The resolution of the sensor will depend on pixel size, image processing and the sub pixel sampling.
The capacitive sensor and image processing also allow for determination of whether the device is operating on biological tissue or some form of other surface. It is possible under proper sampling conditions to extract the type of tissue the device is moving across.
F. Creation of Lattices Using Non-Optical EMR Sources
The lattices can also be produced using non-optical sources. For example, as noted above, microwave, radio frequency and low frequency or DC EMR sources can be used as energy sources to create lattices of EMR-treated islets. In addition, for treating tissue surfaces, the tissue surface can be directly contacted with heating elements in the pattern of the desired lattice.
The following examples illustrate some preferred modes of practicing some of the embodiments, but are not intended to limit the scope of the claimed invention. Alternative parameters, materials, methods and devices may be utilized to obtain similar, additional or other results.
B. Theoretical Model of Islet Lattice Relaxation.
The theory of selective photothermolysis considers the thermal relaxation time (TRT) of an individual target as the characteristic time required for an overheated target to come to the thermal equilibrium with its environment. It is suggested that the TRT is d2/(8α), d2/(16α), and d2/(24α) for the planar (one-dimensional), cylindrical (two-dimensional), and spherical (three-dimensional) targets, with d being the target width (one-dimensional) or diameter (two or three-dimensional).
This definition can be extended to an islet lattice. Significantly, if the lattice is very sparse, i.e., the fill factor is much smaller than 1, the LTRT can be almost equal to the TRT of an individual islet. It can be expected, however, that dense lattices will come to an equilibrium faster than the sparse ones, as well as that the LTRT will be determined predominantly by the dimensionality of the lattice, its fill factor, and the islet TRT.
A precise definition of LTRT was formulated as follows: let the islets be heated to temperature T0 at time zero with the tissue temperature in between them being Tb<T0. If no external action occurs, the temperature gradients in the lattice will decay in time and the lattice will approach the thermal equilibrium at stationary temperature Tst=Tb+(T0−Tb)·f. Since the stationary temperature cannot be reached for a finite time, the LTRT can be defined as the time needed for the islets to cool down to the intermediate temperature
with e being the natural logarithm base.
The LTRT is dependent on the lattice fill factor, f 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 r0 and R=r0/√{square root over (f)}, respectively. Apparently, the cylindrical pattern cannot be translated in space to form a lattice. However, it is unlikely that the transformation of the actual voxel into the cylinder of the same cross-sectional area can change the LTRT appreciably. The significance of this transformation is that it decreases the dimensionality of the problem to 1. The time-dependent heat equation within the cylindrical voxel was solved mathematically by applying a periodic (symmetry) boundary conditions on its outer surface.
Therefore, the heat equation, the initial condition, and the boundary conditions in the cylindrical frame can be written as follows:
where ρ, c, and κ are the density, the specific heat, and the thermal conductivity of the tissue. It is suggested that Tb=0, which does not limit the generality of the analysis. Introducing the dimensionless time τ=t/TRT and the dimensionless coordinate ξ=r/r0 (where TRT=d02/(16α)=r02/(4α) is the TRT of the cylindrical islet and α=κ/(ρc) is the thermal diffusivity) the following equations were obtained:
Equations (A15)-(A17) can be solved numerically to evaluate the LTRT, that is the time when the temperature at the voxel center reduces to
It is worth noting that set (A15)-(A17) is linear with respect to temperature and the LTRT does not depend on the initial temperature thereof. Consequently, the ratio of the LTRT to the islet TRT depends on the lattice fill factor only. Apparently, this simplification comes from the assumptions made for reducing the dimensionality of the problem.
C. Lattice Temperature Relaxation Time
To obtain the lattices of the thermal islets (LTI), a corresponding lattice of optical islets (LOI) has to be created first. The next step is to make the pulse width short enough to avoid overlapping of the adjacent thermal islets. It should be emphasized that LTI is a time-dependent structure and the latter requirement implies that the islets should not overlap at the time instant when the temperature reaches its maximum.
The limitation on the pulse width may be specified in the context of the theory of selective photothermolysis (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). The TRT, in essence, is the cooling time of the target, which is the time required by an instantly heated target to cool to lie of its initial temperature. This concept is applicable easily to the individual islets. It may be pointed out that the TRT of the planar islet (layer of the tissue, one-dimensional) is d2/(8α) with d and α being the target width and the thermal diffusivity of the tissue, respectively. For the cylindrical (two-dimensional) and spherical (three-dimensional) targets the corresponding relations read: d2/(16α) and d2/(24α) with d being the islet diameter (Altshuler et al. (2001), Lasers in Surgery and Medicine 29: 416-32). This concept was generalized to periodic lattices of the optical islets as discussed below.
It is postulated that 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, in turn, may be considered as the lattices of smaller dimensionality. In particular, 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 T0 keeping the space outside them at the constant background temperature Tb<T0. By letting the islets cool through the conduction of heat to the surrounding tissue, the lattice will approach thermal equilibrium at the stationary temperature
T
st
=T
b(T0−Tb)·f, (A22)
which depends on the fill factor. 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:
Using this definition 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 initial value is always larger than TRT and this time is the actual upper limit of LTRT (the LTRT approaches this limit when the fill factor is zero).
As a rough estimate of the dependence of the LTRT to TRT ratio on the fill factor, a simple relation may be used:
providing a good fit of the numeric data for f>0.1. Actually, equation (A24) means that the LTRT is proportional to the time interval, Δ2/(2·α), while the heat front covers the distance between the islets Δ=d/√{square root over (f)}. If the voxel size is very large compared to the islet diameter, the contrast of the thermal lattice may become small before the heat front covers distance Δ. Therefore, equation (A24) overestimates the LTRT appreciably if f<0.1.
D. Light Fluence Parameters for Islet Formation in a Tissue.
In order to get isolated islets, the incident fluence has to be bounded from both above and below: Fmin<F<Fmax. The meaning of the latter expression is that the fluence has to be large enough to provide the desired effect within the islets but should be insufficient to cause the same effect in the whole bulk of the tissue. Practically, the right-hand-side inequality is sufficient to avoid the bulk effect in all cases while the left-hand-side warrants the formation of the islets only if the pulse width is rather short so that the relation between the delivered light energy and the attained effect is local. This means that the effect depends on the total irradiance at the same point of the tissue rather than on the average irradiance over some area. For the longer pulses, however, the dependence may become non-local due to the heat and mass transfer within the tissue (Sekins et al. (1990) In Therapeutic Heat and Cold, 4-th edition Ed. Lehmann (Baltimore: Williams & Wilkins) pp. 62-112). Therefore, the islets may not appear even if the left-hand-side inequality holds. Fmin can be found as a fluence needed to heat up tissue in a islet to the threshold temperature for the tissue coagulation, Ttr. If the pulse width is short enough to neglect the heat conduction, the threshold fluence for the protein coagulation is given by:
F
min
=ρc(Ttr−Ti)/μa, (A18)
where ρ is the tissue density, c is its specific heat, μa is the tissue absorption coefficient, and Ti is the initial temperature. The threshold of the bulk damage Fmax is the fluence 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/f times larger than the volume occupied by islets:
F
max
=F
min
/f. (A19)
This formula is based on the assumption that the treatment is safe provided that enough intact tissue is left between the islets for assured recovery. A more conservative assumption is that, in addition to the first criterion, the treatment is safe until the temperature in the islets reaches the threshold of thermomechanical effects, Tmax. In this case
F
max
=F
min·(Tmax−Ti)/(Ttr−Ti) (A20)
The first criterion predicts a significant safety gap. For example, for f=0.25, the islets and spaces between them have equal safety margins, Fmax/Fmin=4. The second criterion is more restrictive. For tissue, Tmax can be determined as the temperature of vaporization of water Tmax=100° C. Protein coagulation temperature for ms range pulse width is Ttr=67° C. and the second criterion yields the safety margin Fmax/Fmin=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. Monte-Carlo Simulations of Light Transport.
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 in 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 zo. Minimal diameter of collimated beam can be found from the formula (Yariv (1989) Quantum Electronics (NY: John Wiley and Sons)):
d
min=5(z0λ/π)1/2 (A21)
where λ is the wavelength. For typical depth z0=1 mm and λ=1500 nm, dmin=0.1 mm. The spot profile may be a line (stripe) for the one-dimensional islet and some limited shape like circle or square for the two-dimensional islet. For a circular optical beam (wavelength 1200 nm) of diameter 100 μm 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. It will be demonstrated below that the weak irradiance outside the original cylinder may not contribute to the tissue damage provided the pulse is short enough. This opens the opportunity of creating the damage islets of a very precise cylindrical shape.
I. Effects of Beam Diameter and Wavelength on Penetration Depth.
To evaluate the shape of an islet it is important to account for an effect of beam diameter on the penetration depth of light into the tissue. 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)). However, if 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. In particular, for such narrow 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. It should be noted herewith that 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-axis irradiance becomes predominantly due to the direct component and the subsurface maximum disappears.
The dependence of wavelength to penetration depth appears to be rather flat in contrast to the case of the wide beam (Jacques et al. (1995) In Optical-thermal response of laser-irradiated tissue eds. Welch et al. (NY and London: Plenum Press) pp. 561-606; Jacques (1996) In Advances in Optical Imaging and Photon Migration eds. Alfano et al. 2: 364-71; Anderson et al. (1994), Proc. SPIE MS-102: 29-35). The maximum variation of the penetration depth in the specified range is 30-35% only. The penetration depth is limited by the water absorption and the tissue scattering. Apparently, the effect of scattering is stronger for the narrow beams than for the wide ones. The tissue scattering becomes smaller with the wavelength rise while the water absorption increases. These two effects partially compensate each other and the net variations of the penetration depth are rather small.
J. Dynamics of Damage Development.
The lattices of the damage islets develop from those of the thermal islets. The dynamics of the damage development is thought to be governed by the Arrhenius formula. The relationship between the temperature and damage islets is not straightforward. Various tissue sites may show the same peak temperature but a different damage degree, depending on the time the temperature is maintained above the activation threshold of the coagulation or other desired reaction. Moreover, if the pulse width is small the temperature islets can become very sharp at the end of the pulse. If this is the case, the steep temperature gradients may cause the islets to extend and damage the surrounding tissue after the light is off. The effect of such extension leads to onset of bulk damage when the fill factor increases beyond the safe limit.
The LOI technique has several fundamental differences and potential advantages vs. traditional treatment, which employs uniform optical beams for bulk tissue heating and damage. The following conclusions were reached from the computational and theoretical models of islets and islet formation:
(1) In addition to traditional parameters characterizing light treatment, such as the wavelength, the fluence, the pulse width and the spot size, two new important factors are introduced: the fill factor (fractional volume) and the size of islets. Furthermore, the resulting therapeutic effect can be influenced by the geometry (shape, symmetry) and dimensionality of the lattice and islets. LOI can be introduced at different depths at the tissue. For example, in the tissue LOI can be localized in targeted or selective layers of the tissue and surrounding area. For deep LOI, a focusing technique and selective superficial cooling may be preferable used, but other embodiments are possible. A suitable range of wavelengths for the LOI treatment is the near-infrared range (900-3000 nm), with water serving as the main target chromophore.
(2) 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 Fmax/Fmin, where Fmin is the threshold of the desired therapeutic effect and Fmax is the threshold of the continuous bulk damage. The theoretical upper limit for the safety margin is 1/f, where f is the fill factor of the lattice. Practically, the safety margin is determined by the expression Fmax=Fmin·(Tmax−Ti)/(Ttr−Ti), where Tmax is the temperature of water vaporization, Ttr 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.
(3) 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).
(4) Small size column-like islets can be created in the tissue using collimated micro beams. The confocal parameter of such a beam must be longer than the depth of column in the tissue. For depths exceeding 0.5 mm, the diameter of the micro beam is generally larger than 0.1 mm. In contrast with broad beams, the depth of penetration of the micro beams is relatively insensitive to the wavelength in the range 800-1800 nm. However, the threshold fluence for tissue damage depends strongly on the wavelength. The minimal threshold fluences can be found in the range between 1380 and 1570 nm. The depth of the resulting column can be controlled by the fluence. For a superficial column with 0.25 to 0.5 mm depth, 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/cm2. For a deeper-penetrating column of a 0.75 mm depth, the minimal threshold fluences are found at 1405 nm (400 J/cm2) and 1530 nm (570 J/cm2). In principle, 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.
(5) 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. For higher fluences, 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. In the latter case, the optimal pulse width is shorter than the thermal relaxation time of the lattice, approximately given by LTRT=TRT/3f, where LTRT and TRT are the thermal relaxation times of the LOI and a single islet, respectively.
The concept of the lattices of optical islets can be used as a safe yet effective treatment modality in applications where the target of treatment is within the body and/or the location of irradiation of EMR is within the body. The same concept can be applied for other sources of energy such as microwave, radiofrequency, ultrasound, and others. Although the present embodiments are generally described with respect to electromagnetic radiation, it will be understood that embodiments using other forms of energy instead of or in addition to electromagnetic radiation are possible and are within the scope of the present invention.
A. Focusing Elements
B. Micro Lens Systems
C. Lenses and Lens Arrays in Immersion Materials
In
D. Fresnel Lenses
E. Holographic Lenses and Spatially Modulated Phase Arrays
In
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.
F. Gradient Lenses
In
G. Cylindrical Lenses
In
Described above optical system can be used with a pulse laser (0.1-100 ms) to introduce simultaneously into the tissue a lattice of optical islets. For example it can be an Er:glass laser (1.56 microns wavelength) or a Nd:YAG laser (1.44 microns) with fiber delivery and imaging optics to formed uniform beam before focusing elements.
H. One, Two, and Three-Lens Objectives
In
I. Mirror-Containing Optical Systems
J. Scanning Systems
In
In
K. Zoom Lens Objectives
L. Focus Depth.
While as may be seen from Table B1, 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 in 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. 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.
M. Wavelength.
Both scattering and absorption are wavelength dependent. Therefore, while for shallow depths a fairly wide band of wavelengths can be utilized while still achieving a focused beam, the deeper the focus depth, the more scattering and absorption become factors, and the narrower the band of wavelengths available at which a reasonable focus can be achieved. Table B1 indicates preferred wavelength bands for various depths, although acceptable, but less than optimal, results may be possible outside these bands.
N. Pulse Width.
Normally 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. When relatively small islets are desired, pulse durations will also be relatively short. However, as depth increases, and the spot sizes thus also increase, maximum pulse width or duration also increase. 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. Generally, thermal diffusion theory indicates that pulse width τ for a spherical islet should be τ<500 D2/24 and the pulse width for a cylindrical islet with a diameter D is τ<50 D2/16, where D is the characteristic size of the target. Further, 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 such point. Also, as will be discussed later, with a suitable cooling regimen, the above limitation may not apply, and pulse durations in excess of the thermal relaxation time, sometimes substantially in excess of TRT, may be utilized.
O. Power.
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.
P. Numerical Aperture.
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 in 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 B1, the preferable numerical aperture decreases as the focus depth increases.
In addition to the exemplary embodiments discussed earlier, many other embodiments are possible for internal treatments using EMR treated islets. Each device would be sized according to its intended purposes, and may be relatively large or, in 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.
For example,
In one embodiment, 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. The following description describes this embodiment, as well as other embodiments, in greater detail. Further, the following sections elaborate on the types of 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.
Other embodiments may use one or more diode laser bars as the EMR source. Because many applications require a high-power light source, a standard 40-W, 1-cm-long, cw diode laser bar can be used in some embodiments. Any suitable diode laser bar can be used including, for example, 10-100 W diode laser bars. A number of types of diode lasers, such as those set forth above, can be used within the scope. Other sources (e.g., LEDs and diode lasers with SHG) can be substituted for the diode laser bar with suitable modifications to the optical and mechanical sub-systems.
The diode laser bar 315 can be, in one embodiment, ten to fifty emitters (having widths of 50-to-150 μm in some embodiments or 100-to-150 μm in others) that are located along a 1-cm long diode bar with spacing of 50 to 900 μm. In other embodiments, greater than or less than fifty emitters can be located on the diode laser bar 315, the emitter spacing, and the length of the diode laser bar 315 can also vary. In addition, the width of the emitters can vary. The emitter spacing and the number of emitters can be customized during the manufacturing process.
The diode laser bar 315 can be, in one embodiment, twenty-five 100-to-150 μm or 50-to-150 μm wide emitters that are located along a 1 cm long diode bar, each separated by around 50 to 900 microns in some embodiments, and approximately 500 microns in others.
In the embodiment of
Referring again to
In operation, 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 in 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.
In another embodiment, 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. For example, using the diode laser bar 330 of
In another embodiment, an optical fiber can couple to the output of each emitter of the diode laser bar. In such an embodiment, 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.
In operation, the hand piece 310 of
During operation, the user of the hand piece 310 of
In addition to the embodiments set forth above in which the diode laser bar(s) is located close to the tissue surface to create islets of treatment, a variety of optical systems can be used to couple light from the diode laser bar to the tissue. For example, with reference to
Another embodiment is depicted in
In operation, by incorporating more than one diffractive optics 330 in the hand piece 310 along with a motor 334 for moving the different diffractive optics 330 between the stack 325 of diode laser bars and the plate 317, the diffractive optics 330 can be moved in position between the stack 325 and the cooling plate 317 in order to focus the energy into different patterns. Thus, in such an embodiment, the user is able to choose from a number of different islets of treatment patterns in the tissue through the use of the same hand piece 310. In order to use this embodiment, 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. In other embodiments, the hand piece aperture need not tough the tissue. In such an embodiment, 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.
In the embodiment of
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
In some embodiments using a Xe-filled linear flash lamp, the spectral range of the EMR is 300-3000 nm, the energy exposure up to 1000 J/cm2, the pulse duration is from about 0.1 ms to 10 s, and 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. For this purpose, 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.
The use of a capacitive imaging array is set forth above in connection with
One example of 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. To allow for processing images in real time, 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.
In the embodiment of
According to one aspect, 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 the tissue 440.
In one implementation, the output mirror 422 functions as a diffractive multi-spot sieve mirror. Such an output mirror 422 can also serve as a terminal or contact component of the optical system 420 to the surface 438 of the tissue 440. In other embodiments, the output mirror 422 can be made from any reflective material.
Because of the higher refractive index of the illuminated tissue of the tissue 440, divergence of the beams is reduced when it is coupled into the tissue 440. In other embodiments, one or more optical elements (not shown) 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. In this latter example, 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 λ of the source 426, the gain g of the laser media 428, dimensions or diameter D of the transmissive portions 434 (i.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. For example, when D2/4λL<1, effective output beam diameter is made considerably smaller than D, achieving a size close to the system's wavelength λ of operation. This regime can be used to produce any type of treatment islets.
Typically, the operational wavelength ranges from about 0.29 μm to 100 μm and the incident fluence is in the range from 1 mJ/cm2 to 100 J/cm2. The effective heating pulse width can be in the range of less than 100 times the thermal relaxation time of a patterned compound (e.g., from 100 fsec to 1 sec).
In other embodiments, the chromophore layer is not used. Instead the wavelength of light is selected to directly create the pathways.
In one example, 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. In other examples, the spectrum is tuned close to the absorption peaks for lipids, such as 0.92 μm, 1.2 μm, 1.7 μm, and/or 2.3 μm, and wavelengths like 3.4 μm, 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 μm to 100 μm and the incident fluence is in the range from 1 mJ/cm2 to 1000 J/cm2. The effective heating pulse width is preferably less than 100× thermal relaxation time of the targeted chromophores (e.g., from 100 fsec to 1 sec).
The embodiment of
In the exemplary embodiment of
The embodiments of
G. Solid State Laser Embodiments
In the exemplary embodiment as in
In one embodiment, 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 (such as lenses or micro lenses) for focusing EMR. In the embodiment of
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 EMR onto the tissue 632.
The embodiment of
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.
In the embodiment of
In operation, the bundle of lasers 650 generate EMR. The EMR is spatially modulated by spacing apart the laser sources 650 as shown in
In the exemplary embodiment of
Several sets of exemplary parameters for treatment according to some embodiments of the invention are provided in Table D1.
In some embodiments using a flash lamp, the technical specifications can be as summarized in Table E1 below. These embodiments can be used for a number of applications.
While only certain embodiments have been described, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope as defined by the appended claims. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments described specifically herein. Such equivalents are intended to be encompassed in the scope of the appended claims.
The patent, scientific and medical publications referred to herein establish knowledge that was available to those of ordinary skill in the art at the time the invention was made. The entire disclosures of the issued U.S. patents, published and pending patent applications, and other references cited herein are hereby incorporated by reference in their entirety.
All technical and scientific terms used herein, unless otherwise defined below, are intended to have the same meaning as commonly understood by one of ordinary skill in the art. References to techniques employed herein are intended to refer to the techniques as commonly understood in the art, including variations on those techniques or substitutions of equivalent or later-developed techniques which would be apparent to one of skill in the art. In addition, in order to more clearly and concisely describe the claimed subject matter, the following definitions are provided for certain terms which are used in the specification and appended claims.
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. Thus, for a variable which is inherently discrete, the variable can be equal to any integer value within the numerical range, including the end-points of the range. Similarly, for a variable which is inherently continuous, the variable can be equal to any real value within the numerical range, including the end-points of the range. As an example, and without limitation, a variable 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. Finally, the variable can take multiple values in the range, including any sub-range of values within the cited range.
Or.
As used herein, unless specifically indicated otherwise, the word “or” is used in the inclusive sense of “and/or” and not the exclusive sense of “either/or.”
As used herein, 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 μm, is preferably employed in the embodiments described above, but, also as discussed above, many other wavelengths of energy can be used alone or in combination. 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. Additionally, the term optical (when used in a term other than term “optical radiation”) applies to the entire EMR spectrum. For example, as used herein, 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. For example, non EMR sources such as ultrasound, photo-acoustic and other sources of energy may also be used to form treatment islets. Thus, although the embodiments described herein are described with regard to the use of EMR to form the islets, other forms of energy to form the islets are within the scope of the invention and the claims.
This application claims priority as a continuation application to U.S. application Ser. No. 11/952,745, which was filed on Dec. 7, 2007 and entitled “Use of Fraction EMR Technology on Incisions and Internal Tissues”, which claims the benefit of U.S. Provisional Application No. 60/868,982, filed Dec. 7, 2006, which is incorporated herein by reference. This application claims priority as a continuation application to U.S. application Ser. No. 11/952,745, filed on Dec. 7, 2007, which is a continuation-in-part application of U.S. application Ser. Nos. 11/097,841, 11/098,000, 11/098,036, and 11/098,015, each of which was filed Apr. 1, 2005 and entitled “Methods and products for producing lattices of EMR-treated islets in tissues, and uses therefore” and each of which claims priority to U.S. Provisional Application No. 60/561,052, filed Apr. 9, 2004, U.S. Provisional Application No. 60/614,382, filed Sep. 29, 2004, U.S. Provisional Application No. 60/641,616, filed Jan. 5, 2005, and U.S. Provisional Application No. 60/620,734, filed Oct. 21, 2004. Each of these applications and provisional applications are incorporated herein by reference in their entirety.
| Number | Date | Country | |
|---|---|---|---|
| 60868982 | Dec 2006 | US | |
| 60561052 | Apr 2004 | US | |
| 60614382 | Sep 2004 | US | |
| 60641616 | Jan 2005 | US | |
| 60620734 | Oct 2004 | US | |
| 60561052 | Apr 2004 | US | |
| 60614382 | Sep 2004 | US | |
| 60641616 | Jan 2005 | US | |
| 60620734 | Oct 2004 | US | |
| 60651052 | Feb 2005 | US | |
| 60614382 | Sep 2004 | US | |
| 60641616 | Jan 2005 | US | |
| 60620734 | Oct 2004 | US | |
| 60561052 | Apr 2004 | US | |
| 60614382 | Sep 2004 | US | |
| 60641616 | Jan 2005 | US | |
| 60620734 | Oct 2004 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 11952745 | Dec 2007 | US |
| Child | 15401910 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 11097841 | Apr 2005 | US |
| Child | 11952745 | US | |
| Parent | 11098000 | Apr 2005 | US |
| Child | 11952745 | US | |
| Parent | 11098036 | Apr 2005 | US |
| Child | 11952745 | US | |
| Parent | 11098015 | Apr 2005 | US |
| Child | 11952745 | US |
