WO2014149021A2

WO2014149021A2 - Non-invasive fat reduction by hyperthermic treatment

Info

Publication number: WO2014149021A2
Application number: PCT/US2013/032079
Authority: WO
Inventors: Bo Chen; Mirko Georgiev Mirkov
Original assignee: Cynosure, Inc.
Priority date: 2013-03-15
Filing date: 2013-03-15
Publication date: 2014-09-25

Description

NON-INVASIVE FAT REDUCTION

BY HYPERTHERMIC TREATMENT

Cross Reference to Related Applications

[0001] This application is a continuation-in-part of International Patent Application No. PCT/US2011/063113 entitled "Non-Invasive Fat Reduction by Hyperthermic Treatment," which was filed on December 2, 2011, which claims priority to U.S. Provisional Patent Application Serial No. 61/419,440 entitled "Non-Invasive Fat Reduction by Hyperthermic Treatment," which was filed on December 3, 2010. The entirety of the aforementioned applications is herein incorporated by reference.

Field of the Invention

[0001] The present disclosure relates to the field of aesthetic medical procedures.

Specifically, the disclosure provides for systems and methods of tissue remodeling by ameliorating fat deposits.

Background

[0002] Eliminating unwanted body fat has become important from both health and aesthetic standpoints. Reducing these unwanted fat deposits (e.g., "love handles") in various anatomic locations such as the flanks, abdomen, and thighs has been shown to improve overall health, with positive effects on one's self image. Routines such as dieting and exercise can reduce body fat, but certain areas of the body may not be responsive to such measures, and reductions in fat accumulation can be difficult to achieve without surgical intervention and physical removal. Liposuction is a reasonable therapeutic option for this condition.

Although dramatic clinical improvement can be achieved with this surgical procedure, there is considerable associated postoperative recovery and monetary expense. As such, noninvasive or minimally invasive procedures with quick postoperative recovery and a low side-effect profile are in considerable demand. Various methods for localized fat destruction are emerging as alternatives to traditional liposuction. Non-invasively achieved fat reduction has been developed using lasers, focused ultrasound, radiofrequency devices, and selective cryo lysis. Removal of bodyfat from irradiation of adipocytes with a 635nm wavelength laser has been claimed, but further evidence including histological studies is still needed to further establish this approach. Focused ultrasound and radiofrequency devices rely on acute heating and therefore thermally damaging deep fat in a localized area, but deep nodules and prolonged pain are often reported as side effects.

Summary of the Invention

[0003] The invention disclosed herein relates to devices and methods for low-temperature treatments that disrupt subcutaneous adipose tissues. These treatments are suitable for tissue remodeling and cosmetic applications. The invention contemplates achieving a balance between heat deposition and cooling, such that an optimal temperature range in the treatment site is maintained. Specifically, the invention provides for a tissue treatment method including delivering to a treatment site within a tissue of a patient sufficient energy to heat the tissue to a mean temperature above 40°C; and maintaining a temperature below 47°C within and proximal to the treatment site, thereby damaging adipocytes within the treatment site without substantial damage to epithelial or vascular tissues proximal to the treatment site. Heating of tissues within the treatment site is accomplished with laser radiation having a wavelength capable of deep tissue penetrance, such as in the near infrared spectra, e.g., ranging from about 800nm to about 1200nm, for example but not limited to a 1064nm laser. Treatment times range from about 2 to about 60 minutes, and depend on the particular fluence value. Accordingly, a useful power density range for such treatments includes an average power density of about l-10W/cm2, and preferably an average power density of about 4-6W/cm2.

[0004] Thermal control of the treatment site is achieved with a number of approaches, that can be employed individually and in combination. In one embodiment, energy is delivered to the treatment site in the form of periodic pulsed radiation. In another embodiment, energy delivery is modulated based on real-time temperature monitoring of the treatment site, which can be done through a variety of temperature sensing means, such as through thermal imaging sensors. Some useful ways of controlling temperature occur through such approaches as application of an external cooling means, such as a contact chiller, or through convection cooling based on exposing the treatment site to one or more streams of relatively cool air. Cooling may occur simultaneously with treatment, and can extend beyond the end of treatment for an appropriate time, to reduce post-operative inflammation and pain.

Cooling can be intermittent during energy delivery as well, for example the cooling systems may be activated during treatment based on temperature information obtained through thermal sensors. Cooling can also be effectuated by manipulating the treatment site to increase surface area of tissues proximal to the treatment site, thereby increasing the rate of cooling of the tissues proximal to the treatment site.

[0005] In another aspect, a tissue treatment method includes delivering to a treatment site within a target tissue of a patient one or more exogenous chomophores, the exogenous chromophores having energy absorption coefficients at least two times greater than endogenous chromophores in the treatment site; and applying energy to the treatment site thereby differentially heating the target tissues containing the exogenous chromophores relative to proximal tissues not having the chromophores, wherein heat is conducted from the exogenous chromophores into the target tissues of the treatment site and the tissues are thereby remodeled. In one embodiment, the exogenous chromphores selectively absorb energy at or near the wavelength of the laser. In certain embodiments, the exogenous chromophore is a cyanine dye, such as indocyanine green, which is useful where the laser wavelength provided is in the near infrared spectra. The exogenous chomophores are delivered transdermally into the target tissues prior to application of laser energy. Heat is conducted from the exogenous chromophores to the tissues of the treatment site raising the mean temperature in the target tissues to above 40°C. Tissues proximal to the target tissues are cooled during energy delivery to a mean temperature below 47°C.

Brief Description of the Figures

[0006] FIG. 1 illustrates the absorption coefficients of skin chromophores and ICG solutions at concentrations of 65 and 650 micromolar.

[0007] FIG. 2 shows the temperature profile within the fat layer, using pulsed radiation to maintain a hyperthermic temperature range of the fat layer between about 42 and about 46 degrees C.

[0008] FIG. 3 illustrates a tissue fold, with radiation applied from two opposing sides of the fold. By manipulating the treatment site, the surface area of the dermal tissue is increased, while the target tissue is relatively contained by comparison. This permits greater cooling of the dermal tissue while permitting greater energy deposition in the target tissue. [0009] FIG. 4 shows typical time/temperature profiles within abdominal adipose tissue using various power densities.

[0010] FIG. 5 shows human adipose tissue at 1 -month post treatment. FIG. 5a provides a histological cross section of treated tissue showing a deep layer of necrotic adipose tissue. FIG. 5b illustrates a fat specimen from treated tissue.

[0011] FIG. 6: illustrates a LZP series LED emitter from LED Engin, Inc., San Jose, CA. Left side: a sample picture of a 24-die LED emitter. Dimension 12 * 12 mm2. Right side: the electrical layout of tile emitter. The assembly contains total of 24 dies and one optional die or detector.

[0012] FIG. 7. shows one embodiment of treatment module.

Detailed Description

[0013] At the sub-cellular level, many studies have shown that the plasma membrane (containing both protein and lipid) is sensitive to external heat, and as such has been the primary target of heat-based cellular disruptive treatments. Besides the cell's plasma membrane, some other systems/organelles having similar lipid bilayer morphologies

(including constitutive systems, mitochondria, ribosomes, the Golgi apparatus, lysosome, centrosome, and the endoplasmic reticulum) as well as the cytoskeleton and structural proteins are possible targets to cause cell injury and disruption. Usually, supraphysiological thermal insult is a complex matter with thermal morphological and functional alterations of multiple organelles, and always has a pleotropic (i.e., multi-target) effect on cells.

[0014] Because the lipid bilayer components of the adipocyte cell membranes are held together only by forces of hydratation, the lipid bilayer is the most vulnerable to heat damage. Even at temperatures of only 6°C above physiological normal (i.e. about 43°C), the structural integrity of the lipid bilayer is lost (see, Moussa N, Tell E, Cravalho E. "Time progression of hemolysis or erythrocyte populations exposed to supraphysiologic temperatures" J Biomech Eng 1979,101 :213-217). In 1989, Gaylor and Rocchio measured the stability of mammalian skeletal muscle cell membranes in isolated cell culture to supraphysiologic temperature by determining the kinetics of onset of altered membrane permeability to intracellular carboxyfluorescein dye and proposed a set of coefficients for cell membrane rupture. They found that the supraphysiologic temperatures damaged membranes at a rate which was temperature-dependent and that cell membrane lysis was probably the initial destructive event of tissue damage. The cell membranes showed evidence of damage when heated and maintained at 45°C for more than 5 minutes (see, Gaylor, D. C. "Physical mechanism of celluar injury in electrical trauma" Massachusetts Institute of Technology. Ph. D.

Dissertation. (1989).

[0015] After injury, some tissues such as the epidermis of skin can totally regenerate.

Tissue regeneration is initiated by production of various growth factors described in the scientific literature. Vascular and fibroblast growth factors stimulate new blood vessel growth, which stimulate fibroblast proliferation and collagen formation, and feed and support the functioning regenerated tissue. On the other hand, tissues such as adipose tissues only partially regenerate, and do so over a much longer period of time (over years).

[0016] In a typical tissue remodeling treatment, it is primarily the adipocytes underneath the skin surface, that are targeted. For a given trans-dermal laser treatment, the light has to traverse the dermis, which contains various chromophores. This reduces the energy that can be selectively deposited into adipocytes found in deeper tissues, and it causes heating and undesirable thermal effects at the skin surface and through the dermis.

[0017] To overcome the problem of unwanted thermal effects on non-target tissues, we disclose several approaches. One possible approach involves selective energy deposition at a treatment site, for example by application of an exogenous chromophore to a subdermal treatment site prior to delivery of transdermal radiation to the treatment site. The

chromophore, when injected into target tissues thus enhances the selective energy absorption within the target tissues due to energy absorbance by the chromophore, i.e., within adipocytes located relatively deep in the tissues, such as the deep dermis and subdermal layers, hypodermis and superficial fascia. Another approach involves various treatment methods that all seek to control the temperature at the treatment site, and include such techniques as pulsed radiation, tissue manipulation, external cooling or real-time temperature monitoring, as well as combinations of these with or without using exogenous chromophores. Exogenous Chromophores

[0018] In one exemplary method, an exogenous chromophore is introduced to a treatment site prior to treatment. The chromophore is delivered through various techniques known in the art including injection, e.g., a needle syringe, a tattoo gun, or a needle-free hypodermal injection device which creates an ultra- fine stream of high-pressure fluid that penetrates the skin and delivers the chromophore into the target site.

[0019] A useful exogenous chromophore is exemplified by one of any of the available medical or food-grade dyes having a higher energy absorption at a defined wavelength (of the chosen therapeutic light source) as compared to any endogenous chromophores found within human tissues at the treatment site (such as water, hemoglobin, melanin etc.). When selecting possible exogenous chromophores, a higher energy absorbance differential relative to endogenous chromophores is preferred. The particular selection will depend on several variables such as but not limited to the subject to be treated, their natural pigmentation at the treatment site, the physiology and morphology of the treatment site, and the desired outcome of the treatment, e.g., aggressive remodeling of tissues or minor smoothing of the site. Other considerations include the susceptibility of the exogenous chromophore to photodamage and the ability of the body to clear excess chromophore from the treatment site. Persistence of visible quantities of exogenous chromophore at the treatment site following treatment is undesirable.

[0020] The light energy source is selected from one of any of a number of currently available sources, such as laser light or LED light. Using laser light as an exemplary source, an appropriate laser is one having energy and wavelength profiles providing penetration depth that is comparable to or longer than the depth of the subject's dermal tissues at the thickest point within the treatment area. The wavelength of operation for lasers meeting this requirement is variable, but currently preferred systems employ wavelengths in the visible or near infrared regions of the electromagnetic spectrum, and more preferably in the near infrared spectrum. One example of preferable wavelength is 800nm. This wavelength has deeper penetration depth than human skin thickness, and has minimum absorption in blood and water which are major endogenous chromophores in human skin. By way of further nonlimiting example, in the case where an 800nm wavelength laser source is chosen as the energy source and an exogenous chromophore is to be employed, any chromophore having high energy absorption near 800nm is suitable. Indocyanine Green (ICG) is one possible choice for an exogenous chromophore. It is a cyanine dye and has a peak spectral absorption at about 800nm. ICG is commercially available, and has a proven record of safety for human use. It has been used widely in medical diagnostics for determining cardiac output, hepatic function, and liver blood flow, and for ophthalmic angiography.

[0021] An embodiment that allows the procedure above includes a trans-dermal injection system which could deliver the chosen chromophore into the target tissue within the fat layer to enhance the light absorption of by adipocytes, optionally a surface cooling system such as a chiller, and possibly thermal sensors in the device or imaging systems in the surgical theater, to monitor the treatment parameters, such as tissue temperature in deep tissue and on skin surface, etc.

[0022] FIG. 1 compares the absorption coefficients of 65 micromolar and 650 micromolar ICG solutions, to absorption coefficients of some major endogenous chromophores found naturally in human dermis. At 800nm, a 650 micromolar ICG solution has 14 times higher energy absorption than blood (for both hemoglobin and deoxyhemoglobin), and its energy absorption is more than 7700 times higher than water. Although human melanin has comparable absorption coefficient, it primarily locates in skin epidermis within the first 100 micrometers of dermal tissue. This endogenous chromophore does cause some heating of the dermis in the treatment beam path with consequent potential for thermal damage to tissues within or proximal to that path, but this effect could be protected against by sufficient external surface cooling of the skin if necessary. Furthermore, it is less of a concern for lighter pigmented skin due to its lower volume density in lighter skin types. The volume fraction (fv) of melanosomes in epidermis varies with skin color: for light skinned

Caucasians, fv = 1-3%; for well-tanned Caucasians and those of Mediterranean lineage, fv = 11-16%; and for persons of African decent the variability is much higher, where fv = 18- 43%.

Thermal Control

[0023] Adaptations to limit thermal damage to non-target tissues can be used with the above exogenous chromophores or can be used themselves. Equipment such as thermal sensors, imaging systems and laser control systems that monitor the treatment parameters, e.g., position of the laser, contact of cooling plate with treatment surface, duration and dosage of laser energy at the treatment site, temperature of the target site within deep tissues and on the skin surface are described in our U.S. patent application 12/135,967 incorporated herein by reference. Contact cooling systems for surgical application are similarly known in the art, and are useful in combination with the approaches described herein. These all provide methods for controlling the deposition of thermal energy in both the target tissues and the non-target tissues within the treatment zone. For example, periodic pulsing of the laser provides another means of modulating heat deposition in the treatment site, as described in our application PCT US2010/026211 incorporated herein by reference.

[0024] We have observed that hyperthermic treatment of fatty tissue, which at a treatment site raises the mean tissue temperature above about 40°C, and more preferably about 42-46°C will induce thermal injury to adipocytes in the treatment area. Notably, 46°C is not the upper limit of treatment, as higher temperatures (47-50°C or more e.g. 60°C, 70°C, 80°C, etc) will denature cells and even ablate tissues, but these also raise the mean heat level in the non- target tissues causing collateral damage. The injury will trigger the adipocytes to undergo apoptosis or lipolysis, and the residual cellular debris is gradually removed by the body through inflammation and the resultant immune system clearing process, which takes weeks to months depending on the extent of injury at the site. Since the regeneration process of adipose tissue is very slow (over years), the total volume of fat within the treatment area will decrease due to loss of adipocytes that would otherwise act as storage units for such fat.

[0025] To accomplish this, laser irradiation of the treatment site is conducted in order to achieve a supraphysiological temperature (greater than 37°C) in the treatment site over a period of time— for example, a few minutes to hours or so depending on the particular temperature applied. Various preferred embodiments endeavor to confine substantially, the hyperthermic region to fat layers in the target tissue, while keeping dermal temperatures in the treatment are below injury threshold (i.e., lower than about 46-47°C). By choosing the laser parameters (such as radiation pattern, fluence and exposure time, etc) and factoring the cooling rate on the skin surface, an optimized temperature profile/gradient in the target tissue is achieved.

[0026] One technique, Selective Photothermolysis (SPTL) has been widely used for many photothermal therapies, such as hair removal and superficial vascular treatment. The objective behind SPTL is to choose an energy source, e.g., laser light, having a specific wavelength that is selectively or preferentially absorbed by the targeted tissue (such as adipocytes and lipid bilayer structures), with less absorption and therefore less thermal effect on the surrounding tissues (such as epidermis). Optimal SPTL is achieved when the targeted tissue has a much higher energy absorption compared to other surrounding tissues.

Frequently, this effect is controlled by selecting lasers having particular wavelengths for specific cosmetic purposes. But in certain procedures, selection of wavelength alone is not itself sufficient to create a large enough energy absorption differential between target and non-target tissues to achieve optimal therapeutic effects without some degree of damage to surrounding non-target tissues. We have developed several approaches which increase the energy absorption differential and control heating at the treatment site, in order to minimize collateral damage of non-target tissues. Each will be discussed in turn.

[0027] One method of controlling temperature at the treatment site involves modulating the radiation exposure through pulsed applications of laser light. As shown in FIG. 2, a near infrared laser having a wavelength of 1064nm is selected based on its tissue penetrance and relatively low absorption by melanin and water, the major chromophores in the skin.

Exemplary power densities are l-10W/cm2, and a particularly useful range is about 4- 6W/cm2. To maintain an appropriate hyperthermic temperature range in the target tissue (about 40-45°C in the fat layer) while avoiding pain and other unwanted side effects related to overheating, the laser is pulsed, generating an on/off pattern, which causes the temperature to cycle within the appropriate hyperthermic temperature range. With the laser on, the temperature rises to the upper limits of the desired range. A periodic pause permits temperatures in the target site to drop, and optionally the cooling can be further enhanced by using external devices. Laser radiation will resume before tissue temperature drops below the appropriate hyperthermic temperature range. The pulses are repeated for the duration of the treatment (e.g., about 16 minutes as illustrated).

[0028] FIG. 3 illustrates one embodiment, where the target tissue is physically manipulated to create a tissue "fold" having an internal central region of subcutaneous adipose tissue. The fold is irradiated (and also cooled) from opposing external sides. The convergence/overlap of radiation along the light paths increases the heat flux into the tissue fold, but the dermal cooling occurring at each side of the fold behaves similar to single beam approaches. This enhances the efficacy of adipose tissue heating leading to better fat reduction, while decreasing undesired treatment site tissue damage.

[0029] FIG. 4 shows the time/temperature profiles in vivo, for human abdominal fat treated using a 1064nm wavelength laser with an 18mm spot size, using the double sided treatment configuration shown in FIG. 3 above. Two power densities were tested, 4.7 and 5.9W/cm2. External air cooling of the site was employed to maintain a skin surface temperature of below 30°C, as monitored by an external thermal camera. Temperature in the subcutaneous fat layer was monitored by a thermal probe inserted about 1 cm below the skin, the position reflecting the position at which Tmax is observed. Temperatures exceeded 40°C after 133 seconds (at 5.9W/cm2) or 250 seconds (at 4.7W/cm2) respectively.

[0030] FIG. 5 illustrates the effect on human abdominal tissue at 1 month post-treatment. A 1064nm laser having an 18mm spot size and employing a power density of 5.1W/cm2 was used for the 30 minute treatment, pulsed such that the laser was "on" for about 66% of the treatment time. FIG5a shows a tissue biopsy stained with H&E, that reveals a necrotic region deep in the adipose tissue below the dermal layer. FIG5b illustrates the gross morphology of the fat specimen in cross section. A necrotic zone is seen in the middle portion of the tissue, shown within the superimposed oval. In both tissue samples, the dermal tissues were not damaged.

[0031] Other embodiments utilize non-laser light sources to achieve tissue remodeling. For example, a light-emitting diode (LED) provides an efficient semiconductor light source. LEDs have the advantages of long lifespan, providing 35,000 to 50,000 hours of useful life. Another advantage of LEDs is their compact sizes. A single LED chip can be smaller than 2 mm and can be easily attached to printed circuit boards (PCB). With the continuous development of semiconductor technology, the performance of LEDs in luminous intensity and availability of various wavelengths has been greatly improved. A single high-power LED (HPLED) can now be driven at currents from hundreds of mA to more than an ampere with output optical power over 1 Watt. The peak wavelength of LEDs are increasingly stable, with narrower spectral bandwidths available in various wavelengths across the ultraviolet, visible and infrared spectrum. These features create huge potentials for LEDs to be used in medicine, photobiology, photochemistry and optical communication. Besides monochromatic LEDs which can be driven and controlled easily with a long life and low cost, multiple LED dies can nowadays be arranged and attached to a PCB to radiate a much larger area with a high optical power density. A commercially available assembly of such a LED array is illustrated in FIG.6, using the LZP series LED emitter from LED Engin, Inc., San Jose, CA. This specific example is a 24-die assembly with a dimension 12 · 12 mm2 and peak wavelength at 940nm. Its output optical power can reach 13.2 Watt when driven at current 1 A for each die. The average optical power density is 9.2W/cm2 on the emitter surface.

[0032] A methodology to non-invasively eliminate subcutaneous fat by hyperthermic treatment includes exposing tissue to radiation from LEDs, to deliver sufficient energy through the skin into the fat layer to heat up fatty tissue to hyperthermic treatment temperatures, preferably above 40°C, and more preferably about 45°C, and to maintain this treatment temperature in the fat layer for a period of time, preferably 5-60 minutes, and more preferably 15-30 minutes. It may be advantageous to simultaneously cool and maintain the skin temperature below hyperthermic treatment temperatures, preferably below 45°C and more preferably below 40°C during the treatment to prevent any thermal injury to the skin.

[0033] An embodiment that allows the above procedure would consist of a number of components that can include 1) one or multiple LED arrays, 2) a surface cooling system, such as a contact cooling system or an air cooling system, and 3) possibly sensors or imaging systems to monitor the treatment status, such as temperature sensors for monitoring temperature in the target tissues or on the skin surface, or contact sensors for checking the contact of skin with the cooling plates in case a contact cooling method is applied. A LED array is preferred, and such array can employ wavelengths whose light penetration depths are deeper than the thickness of the skin at the treatment site. Wavelengths in the visible or near infrared regions of the electromagnetic spectrum, more preferable in the near infrared regions, are currently preferred. One useful wavelength is 940mn. At this wavelength, light has deeper penetration depth than the thickness of human skin and a relatively low absorption in melanin and water. A light source with power density in the range of l-10W/cm2 is preferable, more preferable about 1-4 W/cm2.

[0034] To maintain hyperthermic temperature in the fat layer and avoid pain or other side effects related to the overheating of target tissues, power modulation of the treatment light can be applied during the treatment period. As the tissue temperature enters the hyperthermic temperature range, treatment is maintained until the desired effect is achieved. However, if the temperature approaches an upper treatment temperature limit Ύτηαχ, the light is paused or attenuated for a period of time (and surface cooling could be either continued or paused). Irradiation resumes before target tissue temperatures drop below the hyperthermic temperature range. Such power modulation will be repeated till the end of the treatment. [0035] In an array configuration, multiple LEDs may be arranged to irrradiate a broader treatment area, or various wavelengths can utilized in order to permit differential heating of target tissues, e.g., different depths within the tissue. The power and wavelength can be modulated individually or at the same time to achieve the designed temporal and spatial temperature profiles. FIG. 7 illustrates one embodiment of treatment module, where a LED array is physically secured onto the target area by a belt mechanism. A few of such LED assemblies may be hinged together to accommodate the need for different treatment sizes. The whole treatment system can include multiple hand-pieces (each hand-piece includes a LED array, a optical coupler, associated cooling assembly and an adapter for connecting multiple hand-pieces), a controller, a mounting assembly to secure multiple hand-pieces onto the skin, and optionally, a temperature or contact sensing device. In other embodiments, a different form and number of light sources can be used together.

Equivalents

[0036] Other variations on the invention are possible, and deemed equivalent to and within the scope of the invention described. For example, while uniform beam laser systems have been described above, a non-uniform beam can be employed. Such non-uniform output beams are described in our U.S. patent 7,856,985 and application PCT/US 10/26432, both incorporated herein by reference. Another equivalent source of deep energy delivery is a focused ultrasound device having a focal depth longer than the skin thickness at the treatment location. In another embodiment, a focused ultrasound device having a scanning system is employed, which can overlay the focused ultrasound energy uniformly over the whole treatment area. In still other embodiments, RF energy is used to generate the hyperthermic condition in the target tissue. Other modifications to the present system and methods will become apparent to those having skill in the relevant medical arts in view of the teachings contained herein.

Claims

We claim:

1) A tissue treatment method comprising: delivering to a treatment site within a tissue of a patient sufficient energy to heat the tissue to a mean temperature above 40°C; and maintaining a temperature below 47°C within and proximal to the treatment site, thereby damaging adipocytes within the treatment site without substantial damage to epithelial or vascular tissues proximal to the treatment site.

2) The method of claim 1 , wherein the delivery of energy to tissues within the treatment site is accomplished by irradiation of the tissues by one or more LEDs having a wavelength in the range of 600nm to 1200nm.

3) The method of claim 2, wherein the wavelength is 930nm to 950nm.

4) The method of claim 1 , wherein the delivery of energy to tissues within the treatment site is accomplished by irradiation of the tissues by one or more LEDs, the total average power density of the one or more LEDs being about l-10W/cm2.

5) The method of claim 4, wherein the total average power density of the one or more LEDs being about l-4W/cm2.

6) The method of claim 1 , wherein energy is delivered to the treatment site in the form of periodic pulsed radiation.

7) The method of claim 1 further comprising modulating energy delivery based on real-time temperature monitoring of the treatment site.

8) The method of claim 7, wherein temperature monitoring occurs through thermal imaging sensors.

9) The method of claim 1 , wherein the heating of tissues within the treatment site occurs for about 2 to about 60 minutes. 10) The method of claim 9, wherein the heating of tissues in the treatment site further comprises simultaneous cooling of tissues proximal to the treatment site.

11) The method of claim 10, wherein cooling is intermittent during energy delivery.

12) The method of claim 10, further comprising manipulating the treatment site to increase surface area of tissues proximal to the treatment site, thereby increasing the rate of cooling of the tissues proximal to the treatment site.

13) A tissue treatment method comprising: delivering to a treatment site within a target tissue of a patient one or more exogenous chomophores, the exogenous chromophores having energy absorption coefficients at least two times greater than endogenous chromophores in the treatment site; and applying energy to the treatment site thereby differentially heating the target tissues containing the exogenous chromophores relative to proximal tissues not having the chromophores, wherein heat is conducted from the exogenous chromophores into the target tissues of the treatment site and the tissues are thereby remodeled.

14) The method of claim 13, wherein the energy is provided using one or more LEDs.

15) The method of claim 14, wherein the exogenous chromphores selectively absorb energy at or near the wavelength of the LED.

16) The method of claim 15, where one of the exogenous chromophores is a cyanine dye.

17) The method of claim 16, wherein one of the exogenous chromophores is indocyanine green and the wavelength provided by the LED is in the near infrared spectra.

18) The method of claim 13, wherein the one or more exogenous chomophores are delivered transdermally into the target tissues prior to application of energy.

19) The method of claim 13, wherein heat is conducted from the exogenous chromophores into the target tissues of the treatment site raising the mean temperature in the target tissues to above 40°C. 20) The method of claim 13, wherein tissues proximal to the target tissues are cooled during energy delivery.