1
METHOD AND APPARATUS FOR
PHOTOTHERMAL TREATMENT OF TISSUE
AT DEPTH
CROSS-REFERENCE TO RELATED 5
APPLICATION
This invention claims the benefit of now abandoned U.S. Provisional Patent Application Serial No. 60/389,871, filed Jun. 19, 2002, entitled "Method and Apparatus for Subder- 10 mal Heating," by G. Altshuler, et al., incorporated herein by reference in its entirety.
BACKGROUND
15
1. Field of the Invention
This invention relates to methods and apparatus for the photothermal treatment of tissue and, more particularly, to methods and apparatus for photothermal treatment of at least a selected region of tissue located starting at a depth at about 20 the boundary zone of dermal and subdermal tissue and extending therebelow.
2. Description of the Related Art
The benefits of being able to raise and/or lower the temperature in a selected region of tissue for various thera- 25 peutic and cosmetic purposes has been known for some time. For instance, heated pads or plates or various forms of electromagnetic radiation, including microwave radiation, electricity, infrared radiation and ultrasound have previously been used for heating subdermal muscles, ligaments, bones 30 and the like to, for example, increase blood flow, to otherwise promote the healing of various injuries and other damage, and for various therapeutic purposes, such as frostbite or hyperthermia treatment, treatment of poor blood circulation, physical therapy, stimulation of collagen, cellu- 35 lite treatment, adrenergic stimulation, wound healing, psoriasis treatment, body reshaping, non-invasive wrinkle removal, etc. The heating of tissues has also been utilized as a potential treatment for removing cancers or other undesired growths, infections and the like. Heating may be applied 40 over a small localized area, over a larger area, for example to the hands or feet, or over larger regions of tissue, including the entire body.
Since most of the techniques described above involve applying energy to tissue at depth through the patient's skin 45 surface, peak temperature generally occurs at or near the patient's skin surface and decrease, sometimes significantly, with depth. Further, while microwaves or ultrasonic and other acoustic radiation have been used in the past for certain heating treatments at depth, as disclosed in, for example, 50 U.S. Pat. No. 5,871,524 to Knowlton, U.S. Pat. No. 5,769, 879 to Richards, et al., U.S. Pat. No. 5,507,790 to Weiss, or U.S. Pat. No. 5,143,063 to Feliner, since such radiation, particularly microwaves, are potentially mutagenic and can otherwise result in cell or systemic damage and, particularly 55 for acoustic sources, are relatively expensive, and may not be practical for large-area treatment, these techniques have had limited use for the heating of tissues.
While optical and near infrared (NIR) radiation (collectively referred to hereinafter as "optical radiation" is gen- 60 erally both less expensive and, being non-mutagenic, safer than microwaves radiation, the use of optical radiation has heretofore not been considered suitable for most applications involving heating of tissue at depth, the term "tissue at depth" as used herein meaning tissue at the border zone of 65 the dermis and hypodermis, some of which tissue may be in the lower dermis, mostly at a depth deeper than 1 mm, and
2
tissue below this border zone to a depth of up to about 50 mm The reason why this radiation has not been considered suitable is because such radiation is both highly scattered and highly absorbed in surface layers of tissue, precluding significant portions of such radiation from reaching the tissue regions at depth to cause heating thereof. In view of the energy losses due to scattering and absorption, substantial optical (including NIR) energy must be applied in order for enough such energy to reach a region of tissues at depth to have a desired effect. However, such high energy can cause damage to the surface layers of tissue, making it difficult to achieve desired photothermal treatments in tissue regions at depth. For these reasons, optical radiation has heretofore had at most limited value for therapeutic and cosmetic treatments on tissue at depth.
Further, while heating of tissue at depth alone is useful for many treatments, there are treatments, for example to relieve pain and stiffness in muscles or joints, where heating in conjunction with massage or other mechanical stimulation, ultrasound or other acoustic stimulation or electrical stimulation of the tissue may also be useful.
Thus, a need exists for improved method and apparatus for photothermal treatment of tissue regions at depth, and in particular for treatment of subdermal regions of tissue, and for method and apparatus for combining heating with stimulation in such regions for various treatments.
SUMMARY OF THE INVENTION
The present invention generally relates to methods and apparatus for photothermal treatment, both therapeutic and cosmetic, of tissue located at depth in a patient's body, as this tern has previously been defined. Optical radiation utilized in practicing the invention is at a wavelength or wavelength band which is neither highly scattered in the patient's skin nor highly absorbed by water in tissue so that the maximum quantity of such radiation can reach the treatment region at depth. The wavelength utilized typically is between about 600 nm and about 1850 nm, more preferably between about 800 nm and about 1350 nm, and most preferably between about 1050 nm and about 1250 nm. Other potential ranges for certain depths of tissue are set forth in Table 1. The longer the wavelength, the lower the scattering; however, outside of the indicated bands, water absorption is so high that little radiation can reach tissue at depth. While the tissue to be treated may be a chromophore at the wavelength(s) utilized within the above bands, this is not a limitation on the invention, and absorption by water, and to a lesser extent fat or lipid, in the region is generally sufficient to achieve the desired heating. In some applications, absorption at certain wavelengths can be increased by delivering a suitable chromophore to the treatment region. The optical radiation source utilized may be a monochromatic source, such as a laser or light emitting diode (LED), or may be a wide spectrum source such as a halogen lamp or arc lamp. Where a wide spectrum source is used, filtering or shifting of wavelengths outside the above bands may be performed. The source may also be a pulsed source or a continuous wave (CW) source. Natural light sources such the sun can also be used to practice this invention. Where the source is a pulsed source, the source typically remains over a treatment region for the duration of each pulse, or a train of pulses may be applied. Where the source is a (CW) source, it is typically moved over the surface of the patients skin at a selected rate, the rate of movement determining the dwell time over a given treatment region.
3
The invention also requires that cooling be applied to the patient's skin surface concurrently with the application of optical radiation thereto. While the radiation reaches the tissue at depth to be treated quickly to begin the heating thereof, cooling propagates as a cold wave protecting tissue 5 above the treatment region and moving the depth of maximum heating further into the skin. Ideally the cooling wave propagates to a depth just above the treatment region, but does not extend to the treatment region at least until sufficient energy has been delivered to the treatment region to 10 effect the desired treatment Cooling may also be applied to the patient's skin prior to the application of radiation thereto to more effectively protect tissue above the treatment region and to more rapidly result in maximum heat being at or near the desired depth. This may also permit higher energy and 15 shorter duration for the radiation source. The head used to apply the radiation may also be used to apply cooling.
Another feature of the invention is that the radiation is applied at low power for an extended time, the time varying with the depth of treatment and with the treatment being 20 performed. For example, the time may vary from approximately 2 seconds to approximately 2 hours for depths of approximately 1 mm to 50 mm respectively. Depending on depth, the treatment being performed and other factors, the power density may vary from approximately 0.2 to 50 25 W/cm2, more preferably from approximately 0.5 to 20 W/cm2, and most preferably from 0.5 to 10 W/cm2 or 0.5 to 5 W/cm2.
Other advantages, novel features, and objects of the invention will become apparent from the following detailed 30 description of the invention when considered in conjunction with the accompanying drawings, which are schematic and which are not intended to be drawn to scale. In the figures, each identical, or substantially similar component that is illustrated in various figures is represented by a single 35 numeral or notation. For purposes of clarity, not every component is labeled in every figure, nor is every component of each embodiment of the invention shown where illustration is not necessary to allow those of ordinary skill in the art to understand the invention. 40
BRIEF DESCRIPTION OF THE DRAWINGS
Non-limiting embodiments of the present invention will 45 be described by way of example with reference to the accompanying drawings in which:
FIG. 1 is a schematic diagram of one embodiment of the invention, as applied to a tissue sample;
FIG. 2 is a schematic diagram of another embodiment of 50 the invention, showing an internal design configuration;
FIG. 3 is a schematic diagram of another embodiment of the invention, showing another internal design configuration;
FIG. 4 is a schematic diagram of another embodiment of 55 the invention, showing another internal design configuration;
FIG. 5 is a schematic diagram of another embodiment of the invention, showing another; internal design configura- g0 tion
FIG. 6 is a schematic diagram of another embodiment of the invention, showing another internal design configuration;
FIG. 7 is a schematic diagram illustrating a plurality of 65 devices of the invention being used in conjunction with each other;
4
FIG. 8 is a schematic diagram of another embodiment of the invention, showing yet another internal design configuration;
FIG. 9 is a schematic diagram of another embodiment of the invention having a different configuration;
FIG. 10 is a schematic drawing of a model of tissue, used in certain calculations;
FIG. 11 is a plot of the temperature produced by an embodiment of the invention in a tissue sample versus tissue depth;
FIG. 12 is a plot of a temperature relaxation profile produced by an embodiment of the invention in a tissue; and
FIG. 13 is a plot of depth of heating vs. treatment time as determined using Equation 12.
DETAILED DESCRIPTION
Applications in which the invention may be useful include the treatment of various diseases, particularly, cellulite and subcutaneous fat treatment, physical therapy, muscle and skeletal treatments, including relief of pain and stiffness for muscles and joints, and treatment of spinal cord problems, and treatment of cumulative trauma disorders (CTD's) such as carpel tunnel syndrome (CTS), tendonitis and bursitis, fibromyalgia, lymphedema and cancer therapy.
More specifically with respect to cancer therapy, hyperthermia resulting from utilizing the teachings of this invention may be utilized to treat various skin cancers including, but not limited to, basel cell carcinoma, squamous cell carcinoma, lymphoma and possibly treatment (palliative) of melanoma. Hyperthermia may also enhance the efficacy of radiation, for example x-ray, therapy, chemotherapy, therapy with immunmodulators such as ALDARA or PDT therapy. Such combination therapy may for example reduce required treatment time.
The tissue to be treated may be a collagen-rich tissue. Collagen-rich tissues that may be treated include superficial cortical bone, synovium joint capsules, tendon sheaths, menisci, myofascial interfaces, periosteum, fibrotic muscle, or major nerve trunks. The device may also be used for reshaping procedures such as non-invasive wrinkle removal through stimulation of collagen production in a subsurface region of tissue. Heating of the subsurface region of tissue to a temperature of between 37.5 and 45° C. may stimulate generation of new collagen and/or elastin. For example, expression of HSP70 ("Heat Shock Protein") may be stimulated when the tissue is heated to between 41 and 42° C. for between 20 and 30 minutes. Other proteins, cytokins and/or growth factors may also be stimulated or released in response to heating. Significant new collagen deposition, formation or rearrangement may be possible, which may improve skin appearance or texture, allowing wrinkles, fine lines, scars, stretch marks or other indicators to be removed. In general, there exists a relation between the temperature reached and the time of application that is necessary to stimulate new collagen deposition and prevent irreversible damage. Additionally, multiple treatments may be used in some treatment modalities.
Hypothermia resulting from utilizing the teachings of this invention may also be utilized for hair growth management, and for treatment of psoriasis, scars, rosacea and various conditions of toe and finger nails. For hair growth management, which includes temporary and permanent hair removal and control of hair growth, a dermal or subdermal temperature rise of a few degrees, for example to 42-45° C. can produce an anagen effluvium. This could be particularly useful for hair grow management on hairs containing little or
5
no melanin, for example gray, white or blond hairs. The efficacy of such treatment may be enhanced by using wavelengths absorbed by melanin or by performing the treatment in conjunction with other hair removal techniques. Hypothermia may also be used to treat psoriasis, including psoriasis 5 plaques and nail psoriasis. The teachings of this invention may thus be used to treat psoriasis, either alone or conjunction drug treatment, light treatment, for example with an excimer laser, flashlamp, uv or pulse dye laser, or other existing treatment. Scars, having different crosslinking and 10 different denaturation thresholds then normal tissue, may be treated by hypothermia to, for example, reduce turnover, turnover being significantly enhanced for scar tissue. A special handpiece with an aperture adjustable to the shape of the scar may be desirable for treating scars. Hypothermia 15 induced in accordance with the teachings of the invention may also be used to kill demodex mites resident in follicles which cause rosacea. Finally, hypothermia induced by this invention may be used to enhance or control growth rate of toe or finger nails or to otherwise treat conditions of these 20 nails, for example nail fungus and dystrophic nails. The nail (matrix) is relatively accessible to light treatment. The nails can be cooled by emergence in a water bath and exposed to the light. The mechanism for enhanced nail growth may be enhanced metabolism, blood supply (vasodialation by heat 25 and light) or biostimulation.
The application of thermal energy to tissue may also be used, for example, in physical therapy treatments, such as to enhance or accelerate wound healing or relieve pain. Beneficial effects may include a decrease in joint stiffness, an 30 increase in joint extensibility of collagenous structures such as tendons and scar tissue, pain relief, blood-flow changes, or a decrease in muscle spasm and increase in muscle tone. As another example, large protein molecules may have high absorption coefficients, and the heating of protein-rich col- 35 lagenous tissues may contribute to healing. A wide variety of conditions may be treated using this invention, for example, but not limited to, strained tendons, tenosynovitis, torn ligaments, tendonitis, bursitis, torn joint capsules, or torn muscles. As yet another example, other processes may be 40 activated or deactivated within the tissue during heating. For example, heating of the tissue may be used to enhance or modify the activity of a pharmaceutical or another bioactive substance or to facilitate the delivery thereof through the skin. Mechanical or electrical stimulation, such as massage, 45 may be used in conjunction with heating to achieve benefits greater then can be achieved by either alone. Pressure may also be applied to the skin surface above the treatment region to facilitate the treatment.
In another example, when tissue is heated to greater then 50 the damage temperature of the tissue, irreversible changes to the tissue may occur, up to and including cell death, apoptosis or the like. The damage temperature is the temperature by which cells, collagen, or other tissue components may be irreversibly damaged. The damage temperature may be 55 useful in certain therapeutic situations, for example, to damage unwanted cells or other structures, such as collagen, malignant or benign tumors, hair bulb, deep pigmented lesions or fat. Further, by heating tissue to a temperature above the body temperature (typically 37° C), but below the 60 damage temperature, it may be possible to change the dynamics of various biological processes, such as metabolism.
Where the tissue is a tumor, it may be desired to use heat in accordance with the teachings of this invention to kill the 65 tumor, or at least a portion thereof, such as a necrotic center. Where the tissue is an artificially created tissue, such as a
6
tissue-engineered scaffold, preferential heating of the center of the artificial tissue may be used, for example, to stimulate cell division within the tissue, to promote cell division or cell growth within the artificial tissue structure.
In certain embodiments, the present invention may be used for non-invasive or non-destructive reduction of localized fat deposits. For example, the invention may be used to heat fat or adipose cells past their damage temperature, causing cell damage and/or necrosis. Alternatively, the treated cells may undergo apoptosis, resulting in cell death. The dead cells may then be removed or resorbed into the body, for example, by the body's phagocytic or lymphatic systems. Fat reduction may also be achieved by heating fat or adipose cells to an elevated temperature, but below the damage temperature. For example, the fat cells may be heated to a temperature of between about 41° C. and about 45° C. Under these conditions, applying heat to subcutaneous fat may activate lipases or metabolize lipids contained within the adipose tissue found within the subcutaneous fat layer, or blood flow may increase to the heated area. Additionally, "lipolysis," or the process of breaking down fat in the body, may be regulated by enzymes sensitive to temperature, such as HSL ("hormone-sensitive lipase"). Thus, elevating the temperature of the adipose cells may increase the lipolysis rate, and thus contribute to a reduction in subdermal fat in the area being treated. This temperature can be below the temperature for vascular/lymph damage so damaged fatty cells and fatty acids can be easily removed from the treatment region. Additionally, application of the present invention may be used in combination with other fat-reduction techniques, such as medication, exercise, or adrenergic stimulation Heating of subcutaneous fat may also result in increased dermal thickness. Thus, fatty tissue may be replaced by fibrous and dermal tissue, this resulting in improved skin appearance. Thermal activation of lymph systems in subcutaneous fat can also be used to treat cellulite by removing proteins from extra cell spaces.
Stated another way, fat and/or cellulite reduction may be achieved utilizing the teachings of this invention by providing an elevated (but below damage threshold -43-48° C.) temperature in the targeted region at depth. The mild hyperthermia initiates biological response through one or several of the following pathways:
1. Increase of activity of enzymes regulating the process of lipolysis, in particular, hormone sensitive lipase (HSL). As a result, decrease of fat stores in hypodermis.
2. Stimulation of blood and lymph flow in the targeted area with multiple positive consequences, including (but not limited to) further decrease in the fat stores and accelerated regeneration of connective tissue.
3. Induction of apoptosis in adipocytes, with subsequent removal of residual cell material by the body's scavenging system.
4. Decrease of lipid's viscosity, resulting in increasing mobility of fat globules and permeability of adipocytes' membranes.
5. Stimulation and or reorganization of the connective tissue surrounding subdermal fat depots with or without concurrent changes of the dermal collagen.
The net result is a shift of balance between fat and connective tissue in hypodermis toward the latter and improved appearance of skin.
FIG. 1 shows an apparatus 100 for one embodiment of the invention. For this apparatus, optical energy 30 from a suitable energy source 1 passes through optical (for example, focusing) device 2, filter 3, cooling mechanism 4 and contact plate 8, before reaching tissue 31. A suitable
7
optical impedance matching lotion or other suitable substance would typically be applied between plate 8 and tissue 31 to provide enhanced optical and thermal contact. Tissue 31, as shown in FIG. 1, is divided into an upper region 5, which, for applications where radiation is applied to the skin 5 surface, would be the epidermis and dermis, and a lower region 6 which would be a subdermal region in the previous example. Energy 30, possibly in conjunction with one or a combination of focusing from optical device 2, and wavelength selection from filter 3, and with cooling from mecha- 10 nism 4, results in maximum heating occurring at a selected depth in tissue 31, which depth is, as previously indicated, at or near the junction of regions 5 and 6 or in lower region 6 for this invention. In some embodiments of the invention, certain of these components, such as, for example, filter 3 15 where a monochromatic source is utilized or optics 2, may not necessarily be present.
In some embodiments of the invention, energy source 1, optical device 2 and/or filter 3 may also require a cooling mechanism. This cooling mechanism may or may not be the 20 same as or connected to cooling mechanism 4 that cools tissue 31 through contact plate 8, as indicated by arrows 32 in FIG. 1. For example, in the embodiment shown in FIG. 1, cooling mechanism 7, shown separately from cooling mechanism 4, is used to cool filter 3. Energy source 1 may 25 be any suitable optical energy source able to produce optical energy 30 at a wavelength that produces heating within tissue 31 at the depth of a desired treatment region. The exact energy source, and the exact energy chosen, may be a function of the tissue 31 to be heated, the depth within the 30 tissue at which treatment is desired and of the absorption of that energy in the desired area to be treated. For example, energy source 1 may be a radiant lamp, a halogen lamp, an incandescent lamp, a arc lamp, a fluorescent lamp, a light emitting diode, a laser (including diode and fiber lasers), the 35 sun or other suitable optical energy source.
Energy source 1 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 40 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 45 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.
As previously indicated, in order to minimize both scattering and absorption of the applied optical radiation, the 50 optical radiation produced by energy source 1 should be radiation with a wavelength which is minimally scattered and absorbed, the available wavelengths decreasing with increasing depth as generally indicated in Table 1.
Certain wavelengths may be preferentially absorbed by 55 the tissue to be treated. As one example, if the tissue to be treated includes subcutaneous fat, certain wavelengths may be absorbed more effectively by the fat or adipose cells than by the surrounding tissues. For example, optical radiation having wavelengths around 925 nm, 1206 nm, 1730 nm and 60 2300 nm may be desirable (see for example copending application Ser. No. 09/277307, which is incorporated herein by reference, for suitable ranges); however, only the lower three of these ranges would typically provide sufficient penetration for use in practicing this invention. Using 65 electromagnetic radiation of these wavelengths, the coefficient of absorption by this radiation in the lipids, and in
8
particular the triglycerides located within the adipose tissue may be greater than that of the absorption coefficient of these wavelengths in water. Thus, these wavelengths when applied to a tissue sample, will preferentially be absorbed by the fat tissue, thus resulting in the preferential heating of this tissue. The selective heating of the fatty tissue can be enhanced by the lower heat capacity of fatty tissue vs. aqueous tissue. Also, the decreased blood perfusion of the subcutaneous fat vs. the dermis can be used to enhance selective heating of the fatty tissue. Compression sufficient to reduce blood flow within the target area can minimize unwanted heat convection, and therefore heat leakage, from the target area. The compression to the subdermal target area can be made selective by forming a skin fold and applying skin pressure sidewise. This results in compression of the subcutaneous fat and of skin outside the field of optical exposure. The skin on top of the skin fold, which skin is exposed to the optical radiation, is not compressed, and therefore the blood flow therein is not appreciably reduced so long as the length of the skin fold does not exceed a critical length. Blood flow within the part of the dermis exposed to optical radiation can help to remove unwanted excessive heat in this skin component.
Where optical device 2 is a focusing device, it may be any suitable device able to focus at least a portion of energy 30 arriving from energy source 1 at tissue 31, and in particular at a selected depth in tissue 31. For example, device 2 may include mirrors, prisms, reflectors, lenses such as Fresnel lenses, collimating lenses or focusing lenses, diffraction gratings, or other optical device.
Filter 3 may be any suitable filter able to select, or at least partially select, certain wavelengths or wavelength bands from energy source 1. In certain types of filters, a specific set of wavelengths may be blocked by the filter. It is also possible that undesired wavelengths in the energy from source 1 may be wavelength shifted in ways known in the art so as to enhance the energy available in the desired wavelength bands indicated above and in Table 1. Thus, filter 3 may include elements designed to absorb, reflect or alter certain wavelengths of electromagnetic radiation. For example, filter 3 may be used to remove certain types of wavelengths that are absorbed by surrounding tissues. For instance, dermis and epidermis tissues are primarily composed of water, as is much of the rest of the human body. By using a filter that selectively removes wavelengths that excite water molecules, the absorption of these wavelengths by the body may be greatly reduced, which may contribute to a reduction in the amount of heat generated by light absorption in these molecules. Thus, by passing radiation through a water-based filter, those frequencies of radiation which may excite water molecules will be absorbed in the water filter, and will not be transmitted into tissue 31. Thus, a water-based filter may be used to decrease the amount of radiation absorbed in tissue above the treatment region and converted into heat.
In other embodiments, filter 3 may be combined with other elements of the device, for example, cooling system 4 or cooling mechanism 7. Thus, water may both attenuate energy 30 arising from energy source 1, as well as cool the contact plate, and tissue in contact with the contact plate, or various other components of the device. More than one filter or filter type may also be present.
FIG. 1 shows a cooling mechanism 4 adjacent to the surface of tissue 31. Cooling mechanism 4 may be any suitable cooling mechanism able to reduce the temperature of tissue 31. Heat energy 32 may be drawn from tissue 31 across contact plate 8 into cooling mechanism 4. For
|
