Therapeutic laser system for activating tissue stem cell niches for the treatment of medical conditions

Abstract

A system for treating various medical conditions in humans includes a medical or therapeutic laser operating in the near-infrared wavelength range between 1250 nm and 1267 nm, with a target wavelength of 1260 nm, at a power level between 2 watts and 60 watts, for a duration not exceeding 60 seconds per dose. The emitted laser light directly and indirectly energizes the irradiated human tissue by activating cell signaling mediators, including but not limited to heat shock proteins, in the stem cell niche or mitochondria, thereby stimulating cellular activity to promote healing and reduce pain. In this particular wavelength range, water absorption of the laser light energy reaches a plateau, effectively acting as a conduit for delivering the laser light energy deeper into the tissue without causing thermal damage to the skin and tissue.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 412,726, filed October 3, 2022, the contents of which are incorporated herein by reference.

[0002] The subject matter disclosed herein relates generally to therapeutic lasers, and more particularly to therapeutic laser systems used to treat a wide range of medical conditions, comprising a laser that emits light of a specific wavelength, the laser light being delivered at specific energy parameters within the near-infrared (IR) spectrum (generally defined as wavelengths between 700 nanometers (nm) and 2500 nm) to optimize the penetration depth of the laser light into human tissue and minimize non-targeted absorption (scattering) of the laser light within the body. [Background technology]

[0003] Known laser-based systems and devices in the prior art for the treatment of various medical conditions typically include a therapeutic or medical laser and a means for controlling various parameters associated with the application of laser light to specific areas of the body. These parameters include the wavelength of the laser light and the power level and duration of the application of the laser light, i.e., the dose or joules (irradiance) of energy delivered by the applied laser light. The laser light energy is said to interact with cells and tissues of the body to stimulate cell and tissue regeneration and healing and reduce the amount of pain. This interaction of light energy with tissue is commonly referred to as photobiomodulation (PBM).

[0004] Generally, the wavelength of laser light determines the thermal effect as the light passes through the layers of skin and into the underlying tissue. Thermal effects ultimately limit the ability of lasers used to deliver higher doses of energy, access deeper levels of tissue, or deliver targeted energy without scattering to peripheral, non-target tissue. Therapeutic or medical lasers with wavelengths in the IR or near-infrared regions of the overall light spectrum are known to be used. Laser light with IR wavelengths has longer wavelengths than light in the visible spectrum. In some situations, these IR wavelengths may penetrate deeper into tissue than light with shorter wavelengths. Longer wavelengths are generally associated with tissue heating. Lasers in the IR spectrum (e.g., 1300 nm) are typically used in medical procedures for their thermal effect on tissue, such as for tissue ablation.

[0005] As the wavelength of a laser increases, so does the likelihood that the laser light will cause skin burns. Therefore, prior art laser systems and devices often incorporate cooling heads in an attempt to mitigate skin burns. For example, 1064 nm lasers are widely known and are typically used in conjunction with skin cooling modalities. However, the use of cooling heads increases the complexity and cost of the overall system. A type of laser known as a cold laser emits light energy that is absorbed by the body without heating it. Many of these cold lasers typically operate at wavelengths below 1200 nm and relatively low power levels in the microwatt or milliwatt range. For example, a cold laser emitting milliwatts of energy at a wavelength of 650 nm, with an aimed beam, has zero therapeutic utility.

[0006] For therapeutic or medical purposes, depending on the tissue type being treated, it may be beneficial to utilize lasers with longer wavelengths in the 1250 nm to 1267 nm range, with 1260 nm as the target wavelength, operated at higher power levels between 2 Watts and 60 Watts. This allows for relatively deep penetration of the laser light through the skin and / or bone into soft tissue without causing thermal damage to the tissue type through which the laser light passes.

[0007] Therefore, there is a need for a system incorporating a laser and a method for operating the laser at a specific combination of wavelength, power level, and duration to safely, consistently, and effectively treat a wide range of medical conditions, including both physical injury and disease, in humans. Summary of the Invention

[0008] It is an object of embodiments of the present invention to provide a laser-based system and method of use that treats and repairs damaged tissue in the body quickly, non-invasively, and in a reliable and consistent manner, thereby speeding healing of the injury while immediately reducing inflammation and pain, allowing individuals to recover faster and better.

[0009] Another object of embodiments of the present invention is to provide a non-invasive, drug-free, laser-based system and method of use that accelerates the healing process, thereby quickly restoring physical function and / or movement, and thus self-confidence and quality of life.

[0010] It is yet another object of embodiments of the present invention to provide a laser-based system and method of use that reduces inflammation within the body, relieves both acute and chronic pain, and stimulates the body's healing processes, thereby allowing a person to regain range of motion and mobility and return to normal function in a shorter period of time.

[0011] It is yet another object of embodiments of the present invention to provide a laser-based system and method of use that can be utilized by a wide range of medical professionals, such as orthopedic surgeons, pain specialists, chiropractors, and general practitioners, to treat their patients.

[0012] Another object of embodiments of the present invention is to provide a laser-based system and method of use that can be utilized by a wide range of people experiencing a variety of injuries and ailments, including professional athletes, professional and collegiate sports teams, as well as weekend sportsmen and the general public.

[0013] It is yet another object of embodiments of the present invention to eliminate the use of a cooling head or any other type of cooling device in connection with the operation of a laser device that is part of a laser-based system for the treatment of various medical conditions, such as, for example, sports injuries, sports conditioning, wound healing, diabetic, fibrotic, shingles, peripheral paresthesia including neuralgia, and the like.

[0014] It is yet another object of embodiments of the present invention to provide a laser-based system and method of use in which a selected wavelength and power combination for operating the laser results in a particular profile of chromophore activation that does not heat the skin and other non-target tissue to the same extent as other wavelength and power combinations.

[0015] It is yet another object of embodiments of the present invention to provide a laser-based system and method of use that utilizes a therapeutic laser to deliver higher levels or doses of energy to the stem cell niche (SCN) with significantly less scattering, absorption, and heating of non-target tissue in the body, without causing excessive heating or thermal damage to the non-target tissue (e.g., skin).

[0016] Another object of embodiments of the present invention is to provide laser-based systems with specific methods of use or protocols for the treatment of various medical conditions, the protocols differing primarily in the power level (i.e., irradiance) of the emitted laser light.

[0017] According to an exemplary embodiment of the present invention, a system for treating various medical conditions in humans includes a medical or therapeutic laser operating in the near-infrared wavelength range between 1250 nm and 1267 nm, with a target wavelength of 1260 nm, at a power level between 2 watts and 60 watts, for a duration not exceeding 60 seconds per dose. Laser light emitted at this combination of wavelength, power level, and duration directly and indirectly energizes stem cell niches or mitochondria in irradiated human tissue, for example, by activating cell signaling mediators, including but not limited to heat shock proteins, thereby stimulating cellular activity to promote healing and reduce pain. In this particular wavelength range, water absorption of laser light energy reaches a plateau, effectively acting as a conduit for delivering laser light energy deeper into tissue without causing thermal damage to the skin and tissue.

[0018] The above and other features and advantages of the present invention will become more apparent from the following detailed description taken in conjunction with the accompanying drawings. [Brief explanation of the drawings]

[0019] [Figure 1] 1 is a perspective view of a laser-based system for treating various medical conditions, in accordance with an exemplary embodiment of the present invention; [Figure 2] 2 is a perspective view of a fiber exit port that is part of the laser-based system of FIG. 1 in accordance with an exemplary embodiment of the present invention. [Figure 3] 2 is a first block diagram of the laser-based system of FIG. 1 showing various components located primarily in the housing portion of the laser-based system in accordance with an exemplary embodiment of the present invention. [Figure 4] FIG. 2 is a second block diagram of the laser-based system of FIG. 1 showing various components located primarily in the handpiece portion of the laser-based system, in accordance with an exemplary embodiment of the present invention. [Figure 5] 2 is a perspective view of a handpiece of the laser-based system of FIG. 1 in accordance with an exemplary embodiment of the present invention. [Figure 6] FIG. 6 is a top view of the handpiece of FIG. 5 in accordance with an exemplary embodiment of the present invention. [Figure 7] FIG. 6 is a front view of the handpiece of FIG. 5 in accordance with an exemplary embodiment of the present invention. [Figure 8] 6 is a cross-sectional and cutaway view of the handpiece of FIG. 5 in accordance with an exemplary embodiment of the present invention. [Figure 9] 6 is a detailed view of several component modules within the handpiece of FIG. 5, including a fiber cell, a skin temperature sensor, and an aiming laser module, according to an exemplary embodiment of the present invention. [Figure 10] 2A-2C are two different front views of the touchscreen display and input panel of the laser-based system of FIG. 1 illustrating two different examples of information and data visually displayed to a user of the system in accordance with an exemplary embodiment of the present invention. [Figure 11] 2A-2C are two different front views of the touchscreen display and input panel of the laser-based system of FIG. 1 illustrating two different examples of information and data visually displayed to a user of the system in accordance with an exemplary embodiment of the present invention. [Figure 12] 2 illustrates the back of a human body along with a four-point pattern including markers to assist a user in locating a laser beam that is part of the laser-based system of FIG. 1 during treatment of various medical conditions associated with the back of the human body according to an exemplary embodiment of the present invention. [Figure 13] 2 illustrates the back of a human body along with a four-point pattern including markers to assist a user in locating a laser beam that is part of the laser-based system of FIG. 1 during treatment of various medical conditions associated with the back of the human body according to an exemplary embodiment of the present invention. [Figure 14] 2 illustrates the posterior shoulder of a human body with a four-point pattern including markers to assist a user in locating a laser beam that is part of the laser-based system of FIG. 1 during treatment of various shoulder-related medical conditions according to an exemplary embodiment of the present invention. [Figure 15] 2 illustrates the posterior portion of a human knee with various locations including markers to assist a user in locating a laser beam that is part of the laser-based system of FIG. 1 during treatment of various knee-related medical conditions according to an exemplary embodiment of the present invention. [Figure 16] 2 illustrates a human face with various locations including markers to assist a user in locating a laser beam that is part of the laser-based system of FIG. 1 during treatment of various face-related medical conditions according to an exemplary embodiment of the present invention. [Figure 17] 2 illustrates a human face with various locations including markers to assist a user in locating a laser beam that is part of the laser-based system of FIG. 1 during treatment of various face-related medical conditions according to an exemplary embodiment of the present invention. [Figure 18] 2 illustrates the inside of a human forearm with various locations including markers to assist a user in locating a laser beam that is part of the laser-based system of FIG. 1 during treatment of various medical conditions related to the forearm (e.g., carpal tunnel syndrome) in accordance with an exemplary embodiment of the present invention. [Figure 19] 2 is a table illustrating the resulting power density of the laser of the laser-based system of FIG. 1 as other system parameters are varied in accordance with an exemplary embodiment of the present invention. [Figure 20] 2 illustrates a human hand having the medical condition of Dupuytren's contracture, with various locations on the hand including markers to assist a user in locating a laser beam that is part of the laser-based system of FIG. 1 during treatment of Dupuytren's contracture, according to an exemplary embodiment of the present invention. [Figure 21]2 illustrates a human hand having the medical condition of Dupuytren's contracture, with various locations on the palm including markers to assist a user in locating a laser beam that is part of the laser-based system of FIG. 1 during treatment of Dupuytren's contracture, according to an exemplary embodiment of the present invention. [Figure 22] 2 is a flowchart of steps in a general method for treating various medical conditions in a human or animal using the laser-based system of FIG. 1, in accordance with an exemplary embodiment of the present invention. [Figure 23] FIG. 2 is a perspective view of an alternative embodiment of a handpiece of the laser-based system of FIG. 1. [Figure 24] 24 is a side view of the handpiece of FIG. 23 showing the handle of the handpiece moved to a predetermined angular position relative to the bulb of the handpiece in accordance with an exemplary embodiment of the present invention. [Figure 25] 24 is a top perspective view of the handpiece of FIG. 23 showing the handle portion of the handpiece without an overmold, according to an exemplary embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0020] Various exemplary embodiments of the present invention of a laser-based system 100 (FIG. 1) and associated methods of use for the treatment of various medical conditions in humans are described and illustrated in detail herein. These embodiments include and utilize therapeutic or medical lasers operating at specific combinations of (1) wavelengths in the near-infrared region of the spectrum (e.g., within the wavelength range of 1250 nm to 1267 nm, and at the specific wavelength of 1260 nm), (2) power levels (e.g., 2 watts to 60 watts), and (3) durations (e.g., 60 seconds or less). The power level or irradiance and duration of the delivered laser light are combined to control the laser dose (i.e., the number of joules of energy delivered) to safely and effectively treat a wide range of medical conditions, including both physical injury and disease.

[0021] The inventors have discovered that there is a plateau in the absorption of laser light by water at wavelengths in the near-infrared range of approximately 1250 nm to 1267 nm. At wavelengths below 1250 nm, the emitted laser light lacks sufficient energy to provide consistent, if any, tissue treatment effects. That is, below 1250 nm, the laser light energy is absorbed and scattered by non-target peripheral tissue, causing significant non-target tissue heating and potential thermal injury. This limits the laser's ability to reach its target and the amount of energy that can be delivered.

[0022] On the other hand, at wavelengths above 1300 nm, the laser light irradiated contains excessive energy, which can result in skin burns. Therefore, there is a laser wavelength plateau with a bandwidth of approximately 50 nm, where the laser light can be effectively directed into the body's tissues to restore the tissue. In other words, the water absorption plateau can be utilized to overcome the energy threshold without skin burns. This applies to all Fitzpatrick skin types.

[0023] More specifically, for laser wavelengths ranging from 1250 nm to 1267 nm (plus or minus 20 nm, which is the current approximate tolerance band for diode lasers), the combined absorption of laser light energy by melanin and heme has been found to be low enough that energies applied in the range of 2 Watts to 60 Watts for up to 60 seconds (i.e., spot treatment) pass through the skin without burns. The specific wavelength of 1260 nm has been found to be most effective. The laser power setting can be adjusted within the range of 2 Watts to 60 Watts, depending on both the penetration depth and power density of the laser light required to reach or activate the stem cell niche (SCN), intracellular and extracellular matrix, and phospholipid layer of the target tissue.

[0024] Depending on how close the laser diode is to the skin, the same power density can be achieved with a range of 2 watts to 60 watts. However, the same field size cannot be achieved. In areas such as the sinuses, a relatively small or narrow field size is preferred, so the power is reduced and the laser is placed relatively close to the skin. In larger areas, such as the lower back, it is beneficial to apply the laser light for a shorter time with a wider field size at a higher power level.

[0025] At the same specific wavelength range of 1250 nm to 1267 nm (more specifically, 1260 nm), water absorption reaches a plateau, effectively acting as a conduit for delivering laser light energy deeper into tissue without heating it to the point of thermal injury. This allows the energy to overcome a threshold level and induce a threshold effect within the SCN of the target tissue, promoting signal transduction to facilitate tissue remodeling. This is the thermal effect in non-inflamed tissue. The energy promotes a more dynamic phospholipid environment, allowing energy penetration into the tissue without heating it, while simultaneously altering phospholipids and intra- and extracellular signaling to cause tissue remodeling and modification. The same effect can be achieved using continuous wave or pulsed wave lasers at these wavelengths and power settings.

[0026] In stable scars, stable fibrous tissue, and wounds, particularly but not exclusively in the central nervous system (CNS), lasers stimulate both interstitial collagenase and Yamanaka factor (YF) activity, leading to stem cell maturation and tissue remodeling. The SCN is a region of tissue that provides a specific microenvironment in which stem cells exist in an undifferentiated, self-renewing state. Cells of the SCN interact with stem cells to maintain them or promote their differentiation. The water absorption plateau allows more energy to be applied (i.e., a threshold level of energy that must be overcome), and once that threshold is overcome, the combination of collagenase destruction of scar tissue and stem cell maturation leads to remodeling into the correct tissue type.

[0027] In brain tissue, energy delivery is preferentially absorbed by the chromophores elastin and fibrin, leading to the remodeling of glial and other scar tissue through normal tissue healing mechanisms such as angiogenesis, macrophage migration, and IFN. This scar tissue remodeling is uniquely possible due to deeper tissue penetration and hydroconductive effects, which facilitate the remodeling of CNS lesions typical of TBI, Parkinson's disease, Alzheimer's disease, and mixed dementia. This is a thermal effect in non-inflamed tissue. The same effect can be achieved using continuous wave or pulsed wave lasers at these wavelengths. The key parameter is the deep thermal effect, where "thermal" refers to the delivery of energy photons to mitochondria and the creation of deep energy gradients.

[0028] The methods described and illustrated in detail herein include methods for treating pathological fibrous tissue deposition and / or injured tissue undergoing healing. This treatment is performed to rapidly remodel the tissue, whereby the tissue remodeling treatment is delivered by a laser. Lasers operating at 1260 nm within an applied power range of 2 Watts to 60 Watts are uniquely capable of penetrating tissue and inducing in vivo mechanical changes that induce repair in stable (non-inflamed), injured, and / or dysfunctional mammalian tissue (e.g., frozen shoulder, Dupuytren's contracture, plantar fasciitis, etc.) without causing thermal injury. Using this method, mechanisms of repair may include, for example, activation of the SCN, which provides more robust, reliable, and consistent results than previously described prior art methodologies.

[0029] The therapeutic method disclosed herein is unique in that it utilizes a wavelength range specifically selected for its optimal and unique combination of minimal absorption of light energy by heme and oxyhemoglobin, minimal absorption of light energy by melanin, and nonlinear absorption of light by water. That is, in certain regions of the wavelength range from 1250 nm to 1267 nm, there is lower water absorption than would be expected if a perfectly linear relationship existed. This method also utilizes power settings that allow laser energy to be directed from 1 cm up to 30 cm into the body, depending on the target area being activated. This unique combination of factors allows for higher levels of light energy (i.e., higher doses) to be delivered to target (injured) tissue, particularly the SCN of the target tissue, without thermal damage to the tissue, than can be achieved with other wavelength / power combination approaches. The doses of energy contemplated herein are delivered with significantly less scattering and heating of non-target tissue, which allows for higher levels or doses of energy to be delivered to the SCN without causing excessive heating or thermal damage to non-target tissue (e.g., skin).

[0030] Thus, embodiments of the present invention are uniquely capable of providing sufficient energy to generate an energy gradient in the SCN without burning and without the need for skin cooling, resulting in energetic activation of the SCN. This energetic activation manifests as the activation of dormant stem cell precursors and the differentiation of progenitor stem cells into effector cell types, accompanied by the release of cytokines associated with tissue repair, the inhibition of cytokines associated with promoting dysfunctional healing (e.g., scar formation), and the upregulation of genes associated with hypermetabolism and successful healing. Because of minimal absorption by melanin, the envisioned laser treatment is further suitable for use on all skin types, including sunburned skin, and is suitable for use on companion animals (cats and dogs), horses, and camels, for example, without the need for shaving.

[0031] While the SCN itself is a historically elusive tissue region and varies within each tissue type, a secondary marker for SCN activation is an increase in skin temperature in the area of ​​skin irradiated with the laser. This increase in skin temperature is a surrogate marker for changes in internal energy levels within the SCN. For the treatments contemplated herein to be effective, skin temperature must increase during the treatment session but not exceed 10 degrees Celsius (°C), and this delta should be maintained at +10°C for at least 45 seconds. This increase in skin temperature is a surrogate marker for changes in internal energy. If a sufficient energy dose is not delivered, SCN activation will not occur. Therefore, we hypothesize that there is a threshold energy level that must be overcome for the SCN to be activated, and that this threshold is uniquely overcome by the combination of wavelength, power setting, and duration contemplated herein.

[0032] Furthermore, there are multiple SCNs to consider, namely, skin, muscle, and brain. Therefore, to achieve proper healing at the appropriate tissue level, the laser power setting must be adjusted to access, for example, the relatively superficial cutaneous SCN or the somewhat deeper muscular SCN. The ability to penetrate bone also allows for the recruitment of neurally derived soft tissues, such as stem cell-mediated remodeling in the brain. Therefore, the specific combination of wavelength and power of the utilized laser light is important. Increasing the power but using wavelengths other than 1260 nm (e.g., 1230 nm or 1280 nm) will result in heating and thermal damage to peripheral tissues. Thermal damage occurs before the SCN is activated, and this thermal damage will limit energy penetration. Furthermore, power levels above 60 watts at 1260 nm have been shown to cause thermal damage. Furthermore, power levels below 2 watts do not provide enough energy to activate the SCN (except for the basilar membrane SCN), and the cytokine and gene expression changes associated with SCN activation are not observed. The use of lasers, when used in conjunction with modalities for detecting tissue density, such as ultrasound or MRI, can be further fine-tuned to provide a more accurate determination of power delivery at the target site. Greater precision may be desirable. For example, a person with a lot of skin and fat tissue on their skull will have a different power setting than someone with a relatively bony, thin head. When precision is required, it is preferable to use a paired diagnostic approach so that the level of fat being penetrated can be determined and the power setting changed accordingly.

[0033] Thus, the combination of both wavelength and power allows greater energy accessibility and generation to the target tissue, the SCN, than is achieved with other wavelength and power combinations. This higher level of energy delivery to the SCN results in the development of an energy gradient in the SCN, which enables Yamanaka factor activation and leads to the stimulation of tissue repair, and such repair is SCN tissue type-specific. Other wavelength and power combinations are unable to deliver significant energy directly to the SCN, primarily due to their different absorption profiles of melanin, heme, oxyheme, protein, fat, and water. These profiles cause tissue heating and energy scattering, which in combination reduces energy delivery to the SCN and prevents SCN activation. Furthermore, other lasers with different wavelength and power combinations, due to their absorption spectra, cause excessive peripheral heating and therefore thermal damage before reaching the SCN, and therefore are unable to deliver sufficient energy to activate the SCN. The relatively small degree of peripheral tissue heating and activation that occurs with embodiments of the laser treatment method of the present invention results in significant vasodilation in the region of the SCN without causing thermal damage. This vasodilation effectively functions as an enhanced conduit for SCN activation and messenger protein expression and transport. Therefore, the combination of wavelength and power allows for activation of the SCN to bring about healing.

[0034] Generally, when the wavelength of light is close to the size of the particles (i.e., biological components, e.g., collagen) through which the light passes, the light is drawn forward and is not deflected or scattered by the particles. This is known as the Mie effect. When near-infrared light in the wavelength range of 1250 nm to 1267 nm is irradiated onto the skin and penetrates the skin (i.e., the dermis and epidermis), the size of the particles (e.g., collagen fibers, keratin molecules, etc.) within the skin is approximately the same as the size of the photons. Therefore, within this specific wavelength range, the photons are hardly scattered or deflected and continue in their direction of travel. The media through which light passes (e.g., melanin, hemoglobin, oxyhemoglobin, proteins, and fats) have a relatively low ability to absorb light and absorb its energy. Water is the most active chromophore and the molecule with the highest absorption capacity. Therefore, due to the Mie effect, the light energy is drawn into the tissue with little scattering or absorption, reaching the SCN, a region with a relatively high water content. Therefore, when lasers of embodiments of the present invention operate within the 1250 nm to 1267 nm wavelength range and at various power levels from 2 Watts to 60 Watts, there is very little or minimal unwanted laser light scattering to non-target tissue, and therefore little or no off-target heating of tissue. That is, the majority of the laser light energy is focused on the target tissue for optimal therapeutic healing. Therefore, the 1250 nm to 1267 nm wavelength range is uniquely subject to Mie forward scattering, meaning that the tissue effectively draws energy forward into the tissue until it strikes a chromophore (most commonly water present in the SCN).

[0035] In the wavelength range of 1250 nm to 1267 nm, energy deflection and absorption by water, proteins, hemoglobin, oxyhemoglobin, and melanin is minimal but not zero. Minimal deflection and absorption allows for greater amounts of energy to be delivered without tissue heating. Above 1300 nm, energy absorption by water increases almost exponentially, resulting in tissue heating to levels that are not therapeutically useful.

[0036] The first high-water tissue or region of high-water content tissue below the dermis is the SCN within the basement membrane. This SCN is a region of relatively high water content due to its specialized extracellular matrix composition. Specifically, its water content allows this region to function as a chromophore that absorbs energy. The absorbed energy stimulates cellular activity, effectively creating an energy gradient, resulting in a highly energized and activated SCN. As energy passes through the tissue, a small amount of energy is absorbed by water, proteins, hemoglobin, oxyhemoglobin, and melanin, causing vasodilation and forming a positive feedback loop that enables SCN activation.

[0037] To achieve a consistent effect, the applied energy must be high enough to activate the SCN, but not so high as to burn the skin. Human skin is highly heterogeneous, and even more so when comparing human and animal skin. Different depths have different levels of melanin, as well as different fat and protein (muscle) contents, and varying degrees of oxygenated and deoxygenated hemoglobin as a result of circulatory insufficiency, such as Raynaud's syndrome and diabetes.

[0038] The inventors have discovered that by utilizing skin temperature as a secondary marker and applying near-infrared light energy using a handpiece with Gaussian light distribution in a pattern capable of delivering maximum power density for a specific length of time, it is possible to achieve a power density that consistently stimulates healing without causing burns in mammals, including humans, of all skin types and conditions, regardless of other phenotypic factors. Specifically, to achieve a consistent therapeutic effect, the skin must undergo an elevated temperature that must be maintained for 45 seconds or more, thereby repairing damaged soft tissue, including, but not limited to, healing non-inflammatory soft tissue, and remodeling.

[0039] Energy is delivered by a laser using a handpiece 108 that emits laser energy in a Gaussian pattern (although patterns with flat-top and other distributions are also available). The laser emission is visually indicated by a colored LED marker guide light that substantially or extensively overlaps the distribution of laser energy on the skin. At the center of this pattern, the laser energy is highest, and this region of highest irradiance provides light energy at a power density high enough to penetrate the SCN of different tissues (e.g., skin, muscle, brain, etc.). Energy is delivered transcutaneously, and the method of treatment (i.e., the protocol by which energy is delivered) is precise to access the therapeutic effect, as opposed to generalized tissue heating.

[0040] The maximum power density occurs at the center of the laser beam. Due to the specific heat capacity of the tissue, the temperature of the surrounding tissue increases. This thermal effect is useful for dilating and relaxing the patient's blood vessels during treatment. However, generalized heating of the skin is not necessary. Peripheral tissue heating is heterogeneous, with muscle and adipose tissues differing in specific heat capacity, with muscle tissue typically having a significantly higher specific heat capacity than adipose tissue. The intent of the methods described herein is to deliver energy to the SCN. Therefore, generalized warming of the skin may limit the ability to achieve the required temperature change and deliver sufficient energy to the SCN for consistent effects.

[0041] If the required power density were applied with a larger beam size, the skin would likely be burned. Therefore, considering the different specific heat capacities, different SCN depths in different tissue types, and the need to obtain a 10°C temperature rise for at least 30 seconds in all these situations, a series of protocols have been developed for optimal treatment of different tissue types and body regions.

[0042] Additionally, when the methods of the embodiments described herein are successfully practiced, a sensation of heat may be felt during laser irradiation, which may persist for 1-2 seconds after laser irradiation has ceased. This may be explained as heat arising from within the tissue, as opposed to superficial heating of the skin surface.

[0043] Generally, the wavelength used in the methods described herein is constant, the dose or joules of energy delivered by the laser is constant (per indication or body area), the essential treatment window is preferably 45 seconds, which is the time the skin must maintain a 10°C temperature rise, and the irradiance and fluence are not constant but are determined by the tissue and condition being treated.

[0044] With this informational background in mind, exemplary embodiments of laser-based systems 100, as well as exemplary embodiments of methods of using such systems 100 to treat various medical conditions associated with humans, are now described and illustrated in more detail. Referring to FIG. 1 , a perspective view of a laser-based system 100 in accordance with an exemplary embodiment of the present invention is shown. System 100 may have a main housing or console 104 and a separate, ergonomic handpiece 108 connected to housing 104 by cable 112. Housing or console 104 contains most of the components of system 100, which are described and illustrated in more detail below. Housing 104 and handpiece 108 (i.e., their outer housings) may each comprise plastic, metal, composite, or other suitable materials.

[0045] System 100 incorporates a therapeutic or medical laser (e.g., main laser module 116 and associated components, FIGS. 3 and 4 ) that provides laser light for use in treating various medical conditions in the human or other mammalian body according to various innovative treatment protocols or methods, some of which are described in more detail below. In an exemplary embodiment, main laser module 116 includes a laser diode. A user of system 100 holds handpiece 108 to apply the therapeutic laser to specific locations on a patient's body.

[0046] The cable 112 may include a fiber optic cable and multiple electrical signal wires. The fiber optic cable and wires may be coated, for example, with a silicone rubber sheath or other suitable material. Note that the terms "cable" and "fiber optic cable" are used interchangeably herein and both are referred to herein with the reference numeral 112. The fiber optic cable 112 may transmit laser light from a laser light source 116 disposed within the housing 104 to the hand piece 108, where it is emitted onto a patient's skin for the treatment of various medical conditions, as described and illustrated in more detail below. Electrical signal wires may transmit power from the housing 104 to the hand piece 108, as well as data signals (e.g., laser on / off signals) between the housing 104 and the hand piece 108. However, it should be understood that the broadest scope of the laser-based system 100 of the present invention is not limited to having a housing 104 separate from the hand piece 108. Alternatively, system 100 may have other exemplary embodiments including a single housing 104 for all components, including those in handpiece 108, or multiple housings 104 and one or more handpieces 108, including handpieces 108 that are robotically controlled and move autonomously based on predefined algorithms. These alternative embodiments will be apparent to those skilled in the art in light of the teachings herein.

[0047] In the exemplary embodiment, the top surface 120 of the housing 104 is provided with a mounting device 124 for the handpiece 108 so that the handpiece 108 can be conveniently stored or positioned there when not in use. The top surface 120 of the housing 104 also is provided with an oval-shaped device (not shown) around which the user can wrap the cable 112 when the handpiece 108 and cable 112 are not in use. In the exemplary embodiment, the fiber optic cable 112 may be approximately 10 feet long. However, in light of the teachings herein, the cable 112 may be of any desired length. Thus, one end of the cable 112 is connected to the handpiece 108, and the other end of the cable 112 is connected to a laser diode 116, or other laser light source, located inside the housing 104. The laser diode 116 provides laser light at a particular wavelength (e.g., 1260 nm), which travels through the fiber optic cable 112, out of the handpiece 108, and onto the human body, as will be described and illustrated in more detail below.

[0048] In the exemplary embodiment, the top surface 120 of the housing 104 also includes a fiber exit port 128 ( FIG. 2 ). The fiber exit port 128 provides a stable and secure means for the entire cable 112 (i.e., the fiber optic cable and electrical signal wires) to pass through the top surface 120 of the housing 104 and into the handpiece 108. The fiber optic cable 112 itself is generally relatively weak and prone to failure, primarily due to repeated movement of the cable 112 during normal use of the handpiece 108. To be suitable for medical applications, the housing 104 must function as a Faraday cage to shield against electromagnetic fields. In the prior art, it is known to screw and unscrew the fiber optic cable into a port located on the outside of the housing. However, when the fiber optic cable is removed from the housing in this manner, static electricity is generated, and dust can adhere to both the port and the fiber end. If the dust is not adequately cleaned, it can act as an energy focus, potentially causing the fiber optic cable or port to ignite. It is known to use a fiberscope (essentially a handheld microscope) which allows a person to view the end of the fiber optic cable and clean any dust particles using an alcohol swab, however, practice has shown that using a fiberscope is no way to properly clean the port.

[0049] Embodiments of the present invention alleviate this problem by running the fiber optic cable 112 (which is part of the overall cable 112) directly from the connection to the diode, through the housing 104 at the fiber exit port 128, and finally to the handpiece 108. This eliminates the need for a fiberscope and the relatively high failure rate inherent in screw-in / unscrew-type external port requirements. Nevertheless, the fiber optic cable 112 must exit the housing 104 without compromising the Faraday cage.

[0050] Referring also to FIG. 2 , a portion of the dedicated fiber exit port 128 of the cable 112 is illustrated in greater detail. Certain components of the fiber exit port 128 may be made of Delrin® or other suitable materials. A base 132 of the fiber exit port 128 is disposed within a hole (not shown) formed in the top surface 120 of the housing 104, thereby allowing access to the interior of the housing 104. The base 132 may have external threads formed thereon, which may be secured by a corresponding nut and washer disposed within the housing 104. The fiber exit port 128 may also pivot an exemplary total circular angular amount of 270 degrees, thereby allowing the cable 112 to move with a user of the system 100 as the user operates the handpiece 108 for the treatment of a person.

[0051] The interior of the fiber exit port 128 may be coated with a conductive material to allow a relatively low and safe amount of radio frequency radiation from the housing 104 when the system 100 is used in a medical environment. The interior structure of the fiber exit port 128 comprises an empty channel or void wide enough to allow the cable 112 to pass through, but not wide enough to allow radiation to pass through. Additionally, a relatively small amount of copper mesh may be included around the cable 112 at the base 132 of the fiber exit port 128 located inside the housing 104. This is done to ensure that any EMC / EMI radiation is controlled to a minimum and below the threshold requirements of the FDA and any other regulatory agencies that control and regulate medical devices. The cable 112 may be attached to the fiber exit port 128 outside the housing 104 to provide strain relief for the cable 112. The fiber exit port 128 provides a secure and durable connection for the cable 112 within the housing 104 and through holes in the housing 104 as the cable 112 moves around during use of the handpiece 108.

[0052] The housing 104 has been described above as having a top surface 120 including a fiber exit port 128, a mounting device 124 for holding the handpiece 108, and a device for winding the fiber optic cable 112 for holding or storing it. However, one skilled in the art should understand that the fiber exit port 128, and / or the mounting device 124 for holding the handpiece 108, and / or the device for winding the fiber optic cable 112 for holding or storing it, may be located on one or more other surfaces of the housing 104 (e.g., the back of the housing or any side of the housing). Furthermore, the fiber exit port 128, the mounting device 124 for holding the handpiece 108, and the device for winding the fiber optic cable 112 need not all be located on the same surface of the housing 104. For example, if none of these devices are located on the top surface 120 of the housing 104, the housing 104 will require less height when placed on a shelf or storage area.

[0053] 3 and 4, block diagrams of various components that make up the laser-based system 100 of FIG. 1 are shown, in accordance with exemplary embodiments of the present invention. FIG. 3 shows various components that are primarily located within the housing 104, while FIG. 4 shows various components that are primarily located within the handpiece 108.

[0054] The therapeutic laser may comprise a commercially available diode laser and its associated components located within or as part of a main laser module 116 (i.e., a fiber-coupled laser module). According to an exemplary embodiment of the present invention, the therapeutic laser 116 preferably operates at a wavelength of 1260 nm, which is in the near-infrared range, in order to take advantage of the various medical benefits from a laser 116 operating at 1260 nm, as described in detail above. The laser 116 may have an approximate wavelength bandwidth of plus or minus 15 nm, typical of modern diode lasers.

[0055] The housing 104 may contain various other components associated with the operation of the laser-based system 100. These components may include, for example, a main computer 136 and a system controller 140. The system controller 140 may include an integrated microprocessor signal processor or similar device that controls and reads data from various peripheral devices associated with the laser-based system 100, as described and illustrated in more detail below (e.g., USB memory, switches, drivers, sensors, etc.). The main computer 136 may be part of a commercially available medical authentication tablet computing device. As such, the medical tablet device also includes a combination touchscreen display and input panel 144 that allows a user to provide various inputs to the system 100 by touching the input panel 144 with a finger or a stylus. The touchscreen display 144 conveys visual information to the user regarding various operating parameters and modes of the laser-based system 100. Auditory information may also be provided to the user.

[0056] A push button switch 152 is located on the front panel 148 of the housing, allowing a user to turn the system 100 on and off for normal operation. The front panel 148 may also include a push button emergency power shut off switch 156, allowing a user to quickly stop all operation of the therapeutic laser system 100 in the event of an emergency occurring during operation of the device 100. The top, back, or side panels of the housing 104 may have holes that function as part of the fiber exit port 128 for connecting the cable 112 to the interior of the housing 104, as described and illustrated in more detail above with respect to Figures 1 and 2.

[0057] Disposed within the housing 104 are a main computer 136 and a system controller 140, along with their associated components. The main computer 136 executes the system 100's primary software program, which is stored in memory that is part of the main computer 136. In the exemplary embodiment, because the main computer 136 is part of a medical tablet device, the main computer 136 also executes a user interface software application program associated with the operation of the touchscreen display and input panel 144. That is, the main computer 136 processes user input signals from the touchscreen display and input panel 144 and provides signals to the touchscreen display and input panel 144 for visually displaying various system operating parameters (i.e., a graphical user interface or "GUI") to the user. The user input signals relate, for example, to the user's control of the laser 116 for treatment. The main computer 136 also sends and receives signals representing data and instructions to and from the system controller 140. The data and command signals relate to the settings and control of the laser 116, such as the "ready" and "standby" states of the laser 116 (which may be set by the main computer 136), the amount of power applied by the laser 116 during treatment (e.g., between 2 watts and 60 watts), and the operating mode of the laser 116 (e.g., continuous, intermittent / pulsed, or custom, and, if in custom mode, the number of repetition cycles).

[0058] The system controller 140 communicates with the main computer 136, the handpiece 108, the laser 116, and other components within the housing 104 using electrical signals. For example, the system controller 140 responds to signals from a photosensor (e.g., a photodiode detector) located within the laser module 116. The photosensor detects the amount of light scattered from the laser beam output from the laser module 116. Thus, this signal from the photosensor indicates the amount of power being output from the laser 116 at any given time. As a result, this signal can be used by the system controller 140 to calibrate the amount of power being output from the laser light module 116. This signal can also be provided by the system controller 140 to the main computer 136 to indicate that the amount of power provided by the laser 116 is out of an acceptable range. Another signal can be provided by the system controller 140 to the main computer 136 to indicate that the temperature of the laser module 116 is out of an acceptable range.

[0059] The system controller 140 controls the operation of a commercially available laser diode driver 160, which supplies power to the laser 116 for its operation. For example, the system controller 140 may receive an "on / off" signal from the handpiece 108 indicating the user's intent to start or stop operation of the laser 116 for treatment. This signal may be initiated by the user using a pushbutton switch 164 (FIGS. 5-8) located on the handpiece 108. The system controller 140 then controls the operation of the laser diode driver 160 and the laser 116 accordingly. For example, the operating mode of the laser 116 may be controlled between continuous, intermittent / pulsed, or custom modes. Output pulsing may also be possible. Diode lasers can typically be operated in a superpulse mode, also known as quasi-CW operation. This allows for more diode drive current to be applied in short pulses or pulse trains. Higher-power pulses provide more heating power at greater depths in tissue.

[0060] The enclosure 104 may also include one or more cooling fans 168 for cooling the temperature within the enclosure 104. The speed of these case cooling fans 168 may also be controlled by the system controller 140 to regulate the temperature within the enclosure 104 and to provide fault feedback related to fan operation. The system controller 140 may provide a signal to the main computer 136 indicating that a fan fault condition exists.

[0061] The system controller 140 also controls a thermoelectric (TE) cooler 172 within the housing 104 to control the temperature of the laser 116 within an exemplary temperature range of 18°C ​​to 32°C (approximately 64°F to 90°F). The thermoelectric cooler 172 may include commercially available devices that operate on convection cooling principles. The system controller 140 may continuously monitor the temperature of the laser 116 as a signal provided by the diode laser module 116. The thermoelectric cooler 172 may be physically located directly below the laser module 116 within the housing 104. If the temperature of the laser 116 exceeds an upper limit, the laser 116 is turned off by the system controller 140. The system controller 140 may provide a signal to the main computer 136 indicating that the temperature of the thermoelectric cooler 172 is outside or exceeds an acceptable range.

[0062] A power supply 176 within the housing 104 provides power to the thermoelectric cooler 172. The power supply 176 may include a commercially available unit that provides 450 watts of power. The system controller 140 may control the operation of the power supply 176 such that the power supply 176 is turned on and off as needed to power the thermoelectric cooler 172.

[0063] 5-9, various views of the handpiece 108 of the laser-based system 100 of FIG. 1 are shown. In an exemplary embodiment of the laser-based system 100 of the present invention, the handpiece 108 is lightweight and ergonomically designed with various contours formed on the exterior of the housing 180 of the handpiece 108. The various contours allow the handpiece 108 to be grasped and held in various orientations with maximum comfort and control by the user's hand. This design allows the handpiece 108 to fit comfortably in the user's hand, making use of the treatment laser 116 (i.e., "lasing") over extended periods of time comfortable and tolerable for the user. The housing 180 may include two separate sections or pieces made of plastic or other suitable material that fit together and are held together with threads.

[0064] At the "entrance" end 184 of the handpiece 108, the cable 112 enters the housing 180. The fiber optic portion of the cable 112 is secured within the handpiece 108 by an SMA connector connected to a corresponding SMA connector housing secured within the housing 180. The cable 112 is also secured to the handpiece 108 at the entrance end 184 of the housing 180 by a strain relief 188 or similar device. The strain relief 188 can be snapped onto the housing 180. In an exemplary embodiment, the cable 112 may be approximately 10 feet long, and the fiber optic portion of the cable 112 may be transparent to laser light at a selected wavelength of 1260 nm. The electrical signal wires within the cable 112 may be connected to the interior of the housing 180 at an appropriate physical location using appropriate connections. When the laser-based system 100 is not in use, the 10-foot cable 112 may be stored, for example, by wrapping the cable 112 around an oval-shaped device, as shown in FIG. 1.

[0065] The opposite end of the handpiece 108 may have a relatively flat surface 192 that faces the patient's skin during operation of the laser-based system 100 of an embodiment of the present invention. The flat opposing surface 192 may have several holes formed therein (see FIG. 7 ). A centrally located circular aperture or hole 196 may include a lens or lens system for directing the therapeutic laser beam from the handpiece housing 180 in the appropriate emission cone 200 ( FIG. 8 ) when using the laser 116 for treatment (i.e., when directed at the area of ​​the patient's skin to be treated). Alternatively, the centrally located circular aperture or hole 196 may not utilize a lens. The cable 112 may be positioned within the handpiece housing 180 such that the end of the cable 112 abuts the inner surface of the flat opposing surface 192 where the laser beam exits the handpiece housing 180. In this manner, the possibility of the laser beam undesirably heating the interior of the handpiece housing 180 is minimized.

[0066] As mentioned above, the laser light energy can be delivered by the laser 116 in a Gaussian pattern, or in a pattern with a flat top or other distribution. The laser-based system 100 can include the option to switch between a peaked Gaussian energy profile and a uniform energy distribution over the treatment area. This can be achieved by incorporating a rotating optical holder containing a lens for a Gaussian or a diffractive optical element for a uniform beam profile. The use of a diffractive optical element allows the treatment shape to be switched between a circular, square, or rectangular shape.

[0067] Additionally, the therapeutic laser beam diverges from the main or central aperture 196 of the handpiece 108 and expands to a diameter of approximately 3 inches at the treatment site. The beam continues to diverge as the light passes through the patient's skin. Thus, the energy density per unit area decreases significantly depending on the depth through the tissue to the site of inflammation or injury. Also, the energy can be concentrated or focused to deliver more energy directly to the injured tissue, which may be far below the skin surface, while keeping the energy density at the skin surface low enough to prevent patient discomfort.

[0068] Three smaller diameter circular apertures or holes 204 are positioned approximately equidistantly or equiangularly spaced (i.e., 120 degrees) in and around the flat opposing surface 192 of the handpiece 108 (see FIG. 7). According to an exemplary embodiment of the present invention, each of these three apertures 204 allows a distance-measuring laser beam to exit the handpiece housing 180 and be directed toward the skin of a patient being treated by the laser-based system 100 of the present invention, as will be described and illustrated in more detail below. The three aiming laser beams may be red and may be provided by suitable laser diode pointer modules 208 located within the handpiece housing 180. Each module 208 may operate similarly to a time-of-flight (TOF) module.

[0069] The three, or triangulated, laser beams are positioned to converge into a single "dot" or "spot" a predetermined distance (e.g., 10 inches) from the flat, opposing surface 192 of the handpiece housing 180. This distance is the desired and appropriate distance for the user to hold the handpiece 108 away from the patient's skin for proper operation of the laser-based system 100 of the present invention. This single laser beam spot or dot thus provides the user of the handpiece 108 with a visual indicator for its proper distance orientation and its proper spatial orientation (i.e., aiming of the therapeutic laser beam).

[0070] Another aperture or hole 212 is formed in the flat opposing surface 192 of the handpiece housing 180. This aperture 212 may house a skin temperature thermal sensor 216 (FIG. 4) that is used to measure the patient's skin temperature using reflected light while the treatment laser 116 is operating. The skin temperature sensor 216 may operate in real time. As such, a shutoff feature may be included within the laser-based system 100 of embodiments of the present invention, whereby if the patient's skin temperature exceeds a certain amount or threshold (e.g., 45°C or 113°F), the treatment laser 116 will cease operation to prevent any damage to the patient's skin or underlying tissue. Additionally, this skin temperature sensor 216 may be used to warn the operator before a "high temperature" or "overheat" condition is reached.

[0071] The incorporation of a skin temperature sensor 216 into the handpiece 108 offers many advantages over the prior art. For example, the sensor 216 allows the laser 116 to irradiate the tattooed skin area without burning the skin. The temperature sensor 216 shuts off or stops irradiating the laser light when the reflected skin temperature measured by the sensor 216 approaches a threshold for potential skin burns. Different dyes are commonly used in tattoos, and there is no reliable way to know the pigments used in those dyes. However, these dyes are known to absorb energy differently. In the prior art, the only way to irradiate the laser over a tattoo is to reduce the laser energy level, otherwise heat absorption would occur and skin damage would occur. This means that prior art laser-based medical devices cannot reach a therapeutic dose of energy. The best that such prior art devices can achieve is to heat the top 5 mm of the skin to the point of discomfort for the patient. In contrast, the peak of the laser beam in embodiments of the present invention is narrow enough that the user can navigate around the edges of a tattoo or mole if desired. Therefore, the skin temperature sensor 216 keeps the laser beam safe around tattoos and moles. The skin temperature sensor 216 also allows for laser irradiation on people with sensory impairments.

[0072] Although not shown, the front face 192 of the handpiece 108 may have an additional aperture or hole formed therein to accommodate a thermal camera disposed within the handpiece 108. The thermal camera can provide a real-time image of the treatment site along with a corresponding temperature profile on the skin surface. This would then provide visual feedback to the user as to any hot spots or low energy density zones being created by the laser. Miniature thermal cameras are commercially available that are physically small and low cost.

[0073] Additionally, active skin cooling may be possible, but would likely result in increased complexity of the laser-based system 100. Thus, higher energy densities can be employed for the therapeutic laser 116 while still maintaining the skin at a comfortable temperature.

[0074] Located generally above or on the top surface 220 of the handpiece housing 180 is a pushbutton switch 164 used to turn on the treatment laser 116 for application of the laser 116 to the patient's skin. This switch 164 allows the laser 116 to be turned on and off from the handpiece 108. In an exemplary embodiment, a user must press or “tap” the pushbutton switch 164 to turn on the treatment laser 116. Thus, when the pushbutton switch 164 is not pressed or engaged, the treatment laser 116 remains on. Pressing or “tapping” the pushbutton switch 164 once turns the laser off. Thus, the pushbutton switch 164 operates as a toggle switch. The pushbutton switch 164 may also have a cover to prevent inadvertent operation of the switch 164.

[0075] Also located above or on top surface 220 of handpiece housing 180, for example near push button on / off switch 164, is an LED 224 (FIG. 6) or similar visual illumination device. LED 224 is illuminated when treatment laser 116 is actively "on" and is not illuminated when treatment laser 116 is "off." Thus, LED 224 provides a visual indicator to a user of handpiece 108 that treatment laser 116 is emitting laser light.

[0076] Also located above or on the top surface 220 of the handpiece housing 180 adjacent to the LED 224 is a two- or three-digit numeric indicator 228 that provides a visual indication of the patient's current skin temperature as measured or sensed by the skin temperature thermal sensor 216 on the front surface 192 of the handpiece 108. The skin temperature is displayed on the indicator 228 in either Celsius or Fahrenheit and can be toggled between the two.

[0077] In an exemplary embodiment of the invention, during operation, handpiece 108 enables the therapeutic laser beam to be directed to different locations on the body in a unique sequence. To this end, handpiece 108 receives "ready" and "standby" signals from main computer 136 via system controller 140. When laser-based system 100 is in the "ready" state, the three, or triangulated, distance lasers 208 and the resulting aiming beams are on. This allows a user to activate therapeutic laser 116 by pressing pushbutton switch 164 on top surface 220 of handpiece 108. In contrast, when laser-based system 100 is in the "standby" state, the three, or triangulated distance lasers 208 and the resulting aiming beams are off, and the user is unable to fire therapeutic laser 116.

[0078] The various components disposed within the handpiece housing 180 may be mounted on one or more circuit boards and / or internal to the housing 180 and connected using ribbon cable electrical connectors and / or electrical wires.

[0079] 10 and 11, there are shown two different front views of the touchscreen display and input panel 144 illustrating two different examples of illustrative information and data that are visually displayed to and prompted for input by a user during operation of the laser-based system 100 of FIG. 1. The information and data relate to various operating modes and parameters of the system 100.

[0080] In operation of the laser-based system 100 of the exemplary embodiment of the present invention described in detail above and illustrated in FIGS. 1-9 , a user powers up the system 100 for operation by activating the power pushbutton switch 152 on the front panel 148 of the housing 104. The system 100 may then perform several initial checks of the various system components and software to verify their proper operation and communication with each other. Once the initial checks are complete, the user may be prompted to enter a pre-programmed multi-digit code (e.g., four digits) to access and operate the system 100. This ensures that only predetermined, authorized users can operate the system 100. The user may then operate the treatment laser 116 to treat a patient. This is done by the user selecting an operating mode for the system 100, which determines the type of laser light to be applied to the patient (e.g., continuous, intermittent / pulsed, or custom), the power level in watts of the applied laser light, and the duration for which the laser is applied to the patient.

[0081] During operation of the laser-based system 100, an activity log is maintained and updated and stored in memory, whereby all the various different operations performed by the system 100 are saved for future reference. If a malfunction occurs at any time during operation of the system 100 (e.g., if the temperature of the laser 116 exceeds an upper threshold), system operation will cease and an appropriate error message will be displayed to the user on the touchscreen display and input panel 144 so that the user can take corrective action.

[0082] 10 is a diagram of the touchscreen display and input panel 144, in which a numeric keypad 232 is visually displayed to a user, allowing the user to use a finger, stylus, or other device to enter a pre-programmed four-digit numeric code or passcode unique to that user, thereby enabling the user to access and operate the system 100. If the user enters an incorrect passcode, an error message is displayed on the touchscreen display 144. This type of numeric keypad input screen may be used to allow the user to enter numerical information during various other operational events during operation of the system 100.

[0083] Once the user enters the correct passcode, the touchscreen display and input panel 144 may transition to a treatment mode setting screen, where the user is prompted to enter the desired operating mode of the laser-based system 100 along with various parameters for the selected operating mode. In an exemplary embodiment of the laser-based system 100 of the present invention, the operating modes of the therapeutic laser may include continuous, intermittent / pulse, or custom. Generally, in continuous mode, the laser 116 may operate at a selected power level for a predetermined total duration. In intermittent / pulse mode, the laser 116 may operate for a predetermined total duration, with predetermined alternating periods of on and off times. In custom mode, the laser 116 may operate for a user-selected total duration, with user-selected alternating periods of on and off times. In any of these operating modes of the therapeutic laser 116, the user may select the power level of the laser 116 to be within an available range, for example, from 2 watts to 60 watts.

[0084] Once the user selects the laser 116 operating mode and its associated parameters, the laser-based system 100 may transition to a ready operating state that allows the user to irradiate the patient's skin with the therapeutic laser 116. FIG. 11 is a diagram of the touchscreen display and input panel 144 showing various information items and data visually displayed to the user. This information includes the selected operating mode (e.g., continuous) and power (e.g., 20 watts), and a timer that is set to zero in anticipation of the timer counting down once laser treatment begins. Additionally, the "READY" visual indicator may be solid red and not flashing, and a red "LASING READY" bar may be displayed at the bottom of the screen, indicating to the user that the therapeutic laser 116 is ready for use on the patient. The user may press the "END TREATMENT" indicator bar to stop laser 116 treatment.

[0085] 10 and 11 are exemplary displays of information and data provided to a user of laser-based system 100 on the touchscreen display and input panel. As previously mentioned, some of these displays require user input on the touchscreen display and input panel. Displays of information and data regarding other modes of operation (i.e., intermittent / pulse and custom) and their associated parameters will be apparent to those skilled in the art in light of the teachings herein.

[0086] Those skilled in the art should understand that the embodiments of the laser-based system 100 of the present invention described above and illustrated in Figures 1-9 are purely exemplary and do not necessarily define the broadest scope of the invention. Accordingly, consistent with the broadest scope of the invention, there are many other alternative ways to embody the housing 104 and handpiece 108 (including their respective components and functionality), which will be readily apparent to those skilled in the art in light of the teachings herein.

[0087] With reference to FIGS. 12-18, a general approach for achieving consistent, successful results for treating soft tissue injuries will now be described and illustrated. The laser-based system 100 described and illustrated herein can be used to treat relatively large areas of the human body, such as the back, shoulders, hamstrings, and quadriceps. The laser-based system 100 can also be used to treat smaller, more localized areas of the human body, such as the sinuses, hands, and feet. However, the general principles for treating all of these areas remain the same: the dose of laser light energy delivered to the tissue must be high enough to overcome the energy threshold and activate healing without causing thermal damage. This requires systematic management of the power density of the laser light to enable delivery of the appropriate dose of laser light energy to the affected area of ​​the body without causing thermal damage to the skin and tissue. FIG. 19 is a table illustrating the resulting power density of the laser 116 of the laser-based system 100 of FIG. 1 as other system parameters are varied, according to an exemplary embodiment of the present invention.

[0088] A common approach is to treat a specific area of ​​damaged tissue along with an approximately 20% margin outside that specific area. This is done by administering laser light energy in a non-overlapping pattern relative to the center of the applied laser beam. In an exemplary embodiment, the front surface 192 of the handpiece 108 is positioned approximately 10 inches from the target area of ​​skin. The table in FIG. 19 shows the resulting laser beam size and laser power density. The laser light delivers its energy in a Gaussian manner, with the center of the beam circle being the peak or highest amount of energy and the periphery of the beam circle being the lowest amount of energy. The power setting of the laser 116 determines the power density, and the patient's size is taken into account.

[0089] In this general approach, there are four basic, non-overlapping patterns of laser irradiation according to an exemplary embodiment of the present invention. Each of the four basic patterns uses a four-point pattern (i.e., four dots outlining a centrally located dot). As a result, treatments using the laser-based system 100 of FIG. 1 are relatively quick, i.e., most treatments are 10-15 minutes in duration.

[0090] Figure 12 illustrates the application of laser light energy in four separate four-point patterns to a relatively large area of ​​the human body, such as the back, thigh, or large arm, as shown in Figure 12. This is the first and simplest of the four patterns. Here, the centers of the four applied laser beams do not overlap. However, there is some overlap at the perimeter of each pattern.

[0091] In FIG. 12, the laser 116 is sequentially applied to the skin. The laser is first applied to the area marked 1. After a predetermined time, when the laser is held 10 inches from the skin, the laser is moved to position 2, which is approximately 5 inches from position 1. After a predetermined treatment time at position 2, the laser is moved to position 3 and then position 4. In FIG. 12, each circle marked 1, 2, 3, and 4 is the center of a laser beam approximately 0.5 inches in diameter. It is this beam center that has the highest power density. Conversely, the outer circles marked A, B, C, and D represent wider fields with a diameter of approximately 3.0 inches to the perimeter. By applying the laser in this manner, the beam centers with the highest energy density (1, 2, 3, and 4) do not overlap, but the wider fields (A, B, C, and D) do overlap to some extent.

[0092] The grid can be marked on the skin using a white body marker before starting the laser irradiation of the skin. A flexible disposable grid can be provided to the user as a guide for placing the markers on the patient's skin when the laser is held 10 inches from the skin. This four-point pattern delivers the required energy to the area in the most efficient manner. The four-point pattern can also be repeated multiple times (e.g., at positions 1, 2, 3, and 4) to treat larger areas, as seen in Figure 13.

[0093] Figure 14 shows the same first four-point pattern repeatedly applied to shoulder locations 1, 2, 3, and 4. Repeated application of the pattern without overlapping beam centers covers the entire injured area of ​​the shoulder, e.g., the rotator cuff.

[0094] Figure 15 shows a swollen knee due to injury and the resulting pattern of applied laser light. This is another example of the first four-point pattern. The numbered dots represent the corresponding centers of each four-point pattern. Again, there is no overlap of pattern centers.

[0095] Although not shown in Figure 15, different patterns of laser light energy can be applied to the knee. The same basic four-point pattern, albeit a somewhat odd shape, can be applied with wider spacing or distribution between beam centers. The pattern can also be modified or adapted to avoid laser irradiation of the center and kneecap, allowing laser irradiation only of the soft tissue surrounding the kneecap. Furthermore, if there is a lot of swelling around the knee, the user can continue to utilize the four-point pattern by widening the grid size or adding different grids. The methodology can also be varied depending on the patient's physiology; for example, a wider grid may be used for an older, smaller person, while multiple grids may be applied to the knee of a larger, athletic person.

[0096] 16 and 17 show an exemplary pattern of laser light applied to the sinuses. This may be a four-point pattern, the second of four basic patterns, specifically for treating the sinuses. As previously mentioned, the sinuses represent smaller, more discrete areas for treatment compared to larger areas such as the back. FIG. 16 illustrates different areas of the sinuses, while FIG. 17 illustrates various points that each correspond to the center of the applied laser beam. In FIG. 16, these sinus areas are the frontal sinus area 236, the ethmoid sinus area 240, the Mallory sinus area 244, and the sphenoid sinus area 248. This pattern can be marked on the patient's face using a laser safety marker before initiating treatment with the laser 116 to assist the user in properly positioning the laser beam. This pattern optimizes effectiveness without causing thermal damage.

[0097] FIG. 18 shows an exemplary pattern of laser light linearly applied to the inner portion of the forearm, for example, for the treatment of carpal tunnel. This can be a four-point pattern, the third of four basic patterns. This pattern is specific to the linear treatment of injuries such as carpal tunnel. For linear treatment areas, the pattern of laser application to the skin is tailored to the shape of the treatment area. The general principle is to laser the area to be treated and not overlap the beam center as the laser 1126 moves over the tissue.

[0098] 20 and 21, a fourth of the four basic patterns will now be described and illustrated. Specifically, a method or protocol for treating a specific medical condition known as Dupuytren's contracture (DC) using the laser-based system 100 of an exemplary embodiment of the present invention will be described and illustrated. A treatment method for alleviating the symptoms of DC is one example of a method used by the laser-based system 100 to reduce fibrosis. DC is a disease of connective tissue and therefore may be classified as a rheumatic disease. However, because there is no effective pharmacological intervention and treatment is usually surgical and invasive, DC is typically treated as a surgical disease. Peyronie's disease, frozen shoulder, and Lederhose disease are conditions grouped together with DC that have similar etiologies and typically provide similar symptomatic relief through the treatment methods described herein.

[0099] DC is typically graded as grades or stages 1 to 4 (or A to D). Stages A to C are shown in FIG. 21. The treatment method for DC with the laser-based system 100 of FIG. 1 is similar and progressive for all grades and stages. According to an exemplary embodiment of the present invention, the treatment laser 116 is set to an appropriate power setting ranging from 30 watts to 44 watts, depending on the skin depth of the patient's hand and the patient's thermal tolerance threshold. The laser (i.e., the front surface 192 of the handpiece 108) is held approximately 6 inches from the patient's hand so that the laser guide light illuminates a circle approximately 2 inches in circumference on the patient's hand. The laser is then held in place for 30 to 60 seconds, depending on the patient's thermal tolerance. Skin temperature in the area irradiated by the laser is a surrogate marker of the energy dose delivered to the extracellular matrix of the basement membrane. Skin temperature should increase by at least 10 degrees Celsius. Also, skin temperature should not increase above 118 degrees Fahrenheit (approximately 48 degrees Celsius). This delta in skin temperature in the lasered area or spot should be maintained for at least 30 seconds, and the laser should not remain in place for more than 60 seconds.

[0100] The treatment method begins with laser irradiation of the volar side of the hand and forearm according to the numbered sequence shown in Figure 20. In the palm, the focus of treatment is the tuberosity and / or cords. In the forearm, the focus of treatment is the flexor carpi ulnaris, a motor point located one-third of the distance between the medial epicondyle of the humerus and a point on the wrist crease just radial to the flexor carpi ulnaris tendon; the palmaris longus, a motor point located one-third of the distance between the medial epicondyle of the humerus and the wrist crease between the flexor carpi radialis tendon and the palmaris longus tendon; and the flexor carpi radialis, a motor point four inches distal to the center of the cubital crease.

[0101] After lasering point 1 on the hand, the laser is moved to point 2, and so on, with the process repeated at each numbered point or location on the hand. This method or protocol defines a non-overlapping treatment pattern that optimizes laser energy input while minimizing the risk of thermal injury. After the palm and forearm are completely treated, the dorsum of the hand is lasered for 2 minutes using a continuous, forward-backward zigzag pattern of laser movement.

[0102] Typically, the treatment described in the above method or protocol is repeated once a week at intervals of 5–7 days. There is an initial induction phase in which the patient receives treatment every morning for 1–2 weeks. This same induction phase can be used for any challenging condition, and morning induction is recommended because mitochondria have a circadian rhythm and are much higher energy producers in the morning. Furthermore, in the early stages of DC, the condition usually achieves remission within 3–5 treatments. To prevent relapse, periodic maintenance treatments may be recommended at 2–3-month intervals. DC grade 3 or higher generally requires completion of 5 or more treatments. Disease classification in DC is evolving, making it more difficult to provide an accurate correlation between disease stage and the duration / number of treatments required to achieve remission. For the purposes of this protocol and explanation, the most currently established grading system may be used. Ultimately, the grading and number of treatment cycles are left to the discretion of the treating clinician and the patient.

[0103] In patients with recurrence of grade 4 DC 12 to 18 months after surgical intervention, laser treatment according to the method or protocol described and illustrated herein immediately resolves pain in most patients. Using this protocol, release of the middle finger can be achieved relatively easily. However, release of the ring finger and little finger with laser treatment is less reliable. This may be due to the fact that there is a relatively large amount of internal residual damage and scar tissue present after DC surgery, which may limit laser treatment to some extent. The protocol provided herein is a method by which stabilization is achieved, i.e., there is no further progression of the condition after surgery.

[0104] It is recommended that treatment protocols and methods be performed in the morning rather than in the afternoon or evening. Research in the field of circadian rhythms suggests that mitochondria have a circadian rhythm and tend to (pre-configure) for increased ATP production in the morning. Observational studies of laser treatment using the methodology described herein also show that better results are achieved when treatment is performed in the morning in terms of McGill Pain Score, range of motion, and other symptoms.

[0105] The protocol and treatment method described and illustrated herein for Dupuytren's contracture forms a basic template for the treatment of fibrosis in general. For example, a treatment pattern for frozen shoulder involves setting the laser power at 44 watts at a distance of 10 inches, a skin temperature delta of 10°C, and a treatment duration of 60 seconds per laser point. Regardless of the body region or disease indication, to ensure reliable effectiveness of treatment with the laser-based system 100, the body temperature must rise by at least 10°C for at least 45 seconds.

[0106] Thus, as seen in the example pattern above, the laser light can be applied in a four-point pattern with non-overlapping beam centers while allowing for a larger overlap of the laser light areas. This is done to essentially deliver as much energy as possible to the desired treatment area without causing thermal damage.

[0107] Other methods or protocols for the treatment of various other medical conditions using the laser-based system 100 of Figure 1 are described and illustrated herein, and differ primarily in the power level or irradiance of the applied laser light, as described in more detail below.

[0108] 22, there is shown a flowchart of the steps of a method 252 for treating various medical conditions in mammals, such as humans and animals, using a laser 116. The method 252 of the flowchart in FIG. 22 is described and illustrated herein as a general method for treating various medical conditions in humans and animals. More specific steps of the method 252, including any variations involving the operation of the laser 116 in those steps, are described in more detail herein, along with various specific embodiments relating to the treatment of particular medical conditions (e.g., cancer).

[0109] After the entry step 256 in method 252, step 260 is performed in which a person (e.g., a nurse or other person appropriately trained in the use of the laser-based system 100 of the present invention) uses handpiece 108 to direct laser 116 at a specific location on the patient's skin. In an exemplary embodiment, the laser beam emitted from laser 116 is directed at the specific location at a distance of up to 10 inches from the skin. However, this distance may vary depending on the particular treatment method described herein.

[0110] Also in accordance with the present invention, the emitted laser light has a wavelength of 1260 nanometers (nm) and a power setting between 2 and 60 watts, although this power setting may vary depending on the particular treatment method, as described herein.

[0111] Next, in step 264, the applied laser beam is maintained at the site on the skin until the temperature at the particular site on the skin increases by 10 degrees Celsius (° C.), however, this particular temperature increase may vary depending on the particular treatment method, as described herein.

[0112] Following this, in step 268, a 10 degree Celsius temperature increase is maintained at the particular location on the skin for at least 45 seconds and no more than 60 seconds. However, the amount of time the temperature increase is maintained may vary depending on the particular treatment method, as described herein. Nevertheless, by maintaining the temperature increase in this manner, the irradiance and power density of the applied laser light is maintained at the particular location on the skin at 1 Watt per centimeter (W / cm) for a period of 45 to 60 seconds. 2 ) and 2.25W / cm 2 However, it should be noted that the irradiance and power density, as well as the duration, may all vary depending on the particular treatment method, as described herein.

[0113] In an exemplary embodiment, steps 260-268 may be repeated each time the handpiece 108 is moved to another location on the patient's skin. That is, once a determination is made as to which particular area on the human or animal body to be treated by the laser-based system 100 of an embodiment of the present invention is made, the first location is treated for a predetermined time as in steps 260-268. The handpiece 108 is then moved to another location within the overall area to be treated with the laser 116, and steps 260-268 are repeated. This process is similar to the locations shown in FIGS. 12-18 and 20-21. Once the entire area has been treated, the method 252 ends at step 272.

[0114] The methods and protocols described and illustrated herein can be used to alleviate conditions associated with increased or longevity lifespan, including peripheral nerve pain associated with diabetes, diabetic peripheral paresthesia and wounds, wound healing due to pressure ulcers, fibrosis, shingles, osteoarthritis, bursitis, tendonitis, joint pain, oral mucositis, acne, psoriasis, dermatitis, burns, and edema. Pressure ulcers are common and often impose high medical costs and significant liability risks on hospitals and other healthcare facilities, such as nursing homes and assisted living facilities.

[0115] The methods and protocols may also be used in critical care settings such as cystic fibrosis, liver cirrhosis, kidney disease, dementia and other acute, chronic, and progressive brain disorders, post-operative wound healing, and traumatic brain injury, to name a few. Additionally, these methods may be used to improve the performance of professional athletes and other people engaged in sports activities, allowing them to train harder, longer, and better. In this performance area, these methods may be used to reduce pain and inflammation caused by muscle strains and sprains resulting from sports and other activity injuries, and for sports conditioning, allowing for faster recovery and a more rapid return to exercise or competition.

[0116] The embodiments of the present invention described and illustrated herein provide many advantages over the prior art. These advantageous embodiments include:

[0117] 1. A method for treating a condition in a mammal, such as a human or animal, using a laser, comprising the steps of: irradiating a laser beam emitted from the laser at a specific location on the skin of the mammal at a distance of up to 10 inches from the skin at the specific location, the irradiated laser beam having a wavelength of 1260 nanometers (nm) and a power setting of between 2 and 60 watts; maintaining the irradiated laser beam at the specific location on the skin until a temperature increase at the specific location on the skin occurs by up to 10 degrees Fahrenheit (°F); and maintaining the temperature increase at the specific location on the skin for a period of at least 45 seconds but not more than 60 seconds, such that an irradiance and power density of the irradiated laser beam at the specific location on the skin is 1.0 Watts per square centimeter (W / cm) for a period of 45 to 60 seconds. 2 ) and 2.25W / cm 2 and

[0118] The method includes the steps of: irradiating a specific site on the skin with a laser beam at the specific site on the skin that shows any obvious signs of damage or is reasonably believed to show any degree of damage to underlying body tissue or bone; and irradiating a laser beam at a plurality of different spaced locations on the skin near the specific site, thereby enabling the irradiated laser beam to reach the stem cell niche closest to the area of ​​the specific site, thereby resulting in energetic activation of the stem cell niche and its contents.

[0119] The method, wherein the stem cell niche comprises a water-rich hydrophobic environment, energy from the irradiated laser beam is absorbed by the water-rich hydrophobic environment within the stem cell niche, and the absorption of the irradiated laser beam creates an energy gradient, which stimulates mitochondria from cells directly receiving the laser energy and / or neighboring cells to release cytokines, activating the stem cell niche and causing the delivery of mitochondrial signals from healthy tissue to unhealthy tissue.

[0120] The method, wherein the specific location on the skin is near a joint of the mammal, and the step of irradiating the specific location on the skin of the mammal with a laser beam emitted from the laser includes irradiating the laser beam at the specific location with a power setting of between 30 watts and 40 watts.

[0121] The method, wherein the joint includes a knee of the mammal, and the step of irradiating a laser beam emitted from the laser onto a specific site on the skin of the mammal includes irradiating the laser beam onto the front of the knee and the back of the knee.

[0122] A method for treating cancer in a human or animal using a laser, wherein the human or animal has been administered a checkpoint inhibitor or other immunotherapy modality that can be combined with cytotoxic chemotherapy, and the cancer manifests as a solid tumor, the method comprising: directing a laser beam emitted from the laser to a specific site on the skin of the human or animal at a distance of about 10 inches from the skin at the specific site, the specific site on the skin being directly above or near the tumor and tumor microenvironment area, and the specific site on the skin being a localized collection of immune cells, lymph nodes, and areas that provide nutrients to the tumor. and a power setting of between 30 and 60 watts; and maintaining the irradiated laser beam at the specific location on the skin until the temperature of the specific location on the skin increases by a maximum of 10 degrees Fahrenheit (°F); and maintaining the maximum 10°F temperature increase at the specific location on the skin for a period of at least 45 seconds and not more than 60 seconds, so that the irradiance and power density of the irradiated laser beam at the specific location on the skin is 1.0 watts per square centimeter (W / cm) for a period of 45 to 60 seconds. 2 ) and 2.25W / cm 2 and

[0123] The method, wherein the step of applying a laser beam comprises applying a laser beam to the specific site at least one day prior to administration of the checkpoint inhibitor or other immunotherapy modality to activate stem cell niches in the tumor and its adjacent microenvironment.

[0124] the method further comprising the step of irradiating said specific site with a laser beam at least one day prior to administration of said checkpoint inhibitor or other immunotherapeutic modality, followed by the step of irradiating said specific site with a laser beam on each day of said immunotherapy or other chemotherapy treatment, immediately prior to or during administration of said therapy.

[0125] The method, wherein the step of irradiating the specific site with a laser beam includes irradiating the laser beam with multiple sites on the skin near the tumor to cover the area of ​​the tumor and its adjacent microenvironment.

[0126] The method further includes methods of stimulating microsatellite instability ("MSI"), or other mechanisms, which may increase the immunogenicity of tumors to the endogenous immune system as a result of the production of tumor-associated neoantigens, thereby increasing the tumor's susceptibility to tumor-directed immunotherapy and correlating with susceptibility to other immunotherapeutic modalities targeting both tumor cells and their microenvironment.

[0127] The method further includes stimulating the cGAS / STING innate immune pathway by inducing intracellular production of small endogenous nucleic acids, wherein the STING activation stimulates cytokine / chemokine production and stimulates infiltration of therapeutic immune effector cells.

[0128] The methods include stimulating the function of exhausted T cell tumor infiltrates that are no longer functional and cannot be reactivated by various stimuli.

[0129] The method further includes altering the production, function, loading and release of tumor microvesicles ("MVs") from the tumor, thereby altering the diffusion of soluble molecules that have been shown to prepare distant metastatic niches for the dissemination of metastatic tumor cells.

[0130] 1. A method for treating the ear of a human or animal using a laser, comprising the steps of: irradiating a laser beam emitted from the laser at a specific location on the skin of the human or animal, the specific location being the ear of the human or animal or an area of ​​the skull proximate the ear of the human or animal, the laser beam being emitted from the laser at a distance of approximately 2 to 3 inches from the skin at the specific location, the wavelength of the irradiated laser beam being 1260 nanometers (nm) and a power setting between 2 and 10 watts; maintaining the irradiated laser beam at the specific location on the skin until a temperature rise of at least 5 degrees Fahrenheit (°F) is achieved at the specific location on the skin; and maintaining the temperature rise of at least 5°F at the specific location on the skin for at least 20 seconds, such that the irradiance and power density of the irradiated laser beam at the specific location on the skin is 1.0 watts per square centimeter (W / cm) for a period of 45 to 60 seconds. 2 2. A method for treating the ear of a human or animal with a laser, comprising the steps of:

[0131] The method, wherein the step of irradiating a laser beam at a specific location on the skin further includes irradiating a laser beam at up to three different, spaced apart locations on the skin from near the ear canal of the ear to the base of the earlobe.

[0132] 1. A method for treating a condition in a mammal, such as a human or animal, using a laser, comprising the steps of: irradiating a laser beam emitted from the laser at a specific location on the skin of the mammal, the specific location being the scalp or forehead of the human or animal, the laser beam being applied at a distance of up to 3 inches from the specific location of the skin, the wavelength of the irradiated laser beam being 1260 nanometers (nm) and a power setting of between 10 and 20 watts; maintaining the irradiated laser beam at the specific location on the skin until a temperature increase of 5 degrees Fahrenheit (°F) occurs at the specific location on the skin; and maintaining the 5°F temperature increase at the specific location on the skin for a period of at least 20 seconds but not more than 40 seconds, such that an irradiance and power density of the irradiated laser beam at the specific location on the skin is 1.0 watts per square centimeter (W / cm) for a period of 20 to 40 seconds. 2 ) and allowing energy from the irradiated laser beam to pass to tissue of the human or animal's brain, or central nervous system, or peripheral nervous system, resulting in increased vascular permeability and allowing energy from the irradiated laser beam to reach one or more stem cell niches in the superficial portions of the brain, central nervous system, and peripheral nervous system, creating a positive energy gradient therein.

[0133] Furthermore, a method for activating stem cell niches provides a sustained initiation of a cascade of intracellular activities focused on stem cell activation and the reduction of inflammatory responses, resulting in the restoration of normal cellular function. This regulated inflammatory response can be reduced, for example, in the case of an inappropriate pro-inflammatory response resulting in edema, slow-healing wounds, and / or fibrosis. Alternatively, it can be an inappropriate anti-inflammatory response resulting in an inappropriate response from the immune system, such as infection, or an inflammatory response resulting in prolonged activation of pain receptors, in which case the intracellular cascade affects afferent neurons.

[0134] A method of activating a stem cell niche, providing stem cell activation and sustained initiation of a cascade of intracellular activities that result in stimulation of T cell subsets necessary or useful for the reduction and / or elimination of neoplasia and neoplastic disease.

[0135] A method for activating a stem cell niche, providing sustained initiation of a cascade of intracellular activities focused on stem cell activation and reduction of negative inflammatory responses, thereby resulting in stimulation of T cell subsets to break tolerance associated with neoplastic and neoplastic diseases.

[0136] A method of activating the stem cell niche, providing sustained initiation of a cascade of intracellular activities that results in stem cell activation and restoration of normal cellular function with a focus on reducing the inflammatory response, thereby slowing inflammatory joint degeneration and enhancing the effectiveness of pre-surgical interventions, including but not limited to corticosteroid injections.

[0137] A method for non-invasively reaching and regulating meridians and acupoints used in traditional Chinese medicine.

[0138] A method of increasing blood flow to the central nervous system, including the brain, and associated stem cell niches maintained therein, which initiates and sustains a cascade of intracellular activities, the effects of which restore normal function of immune system components, including the glymphatic system, thereby producing effects including, but not limited to, removal of scar tissue components, including amyloid, from the CNS (including the brain), leading to improved cognitive function and alleviation of symptoms associated with various neurodegenerative diseases, including, but not limited to, Alzheimer's disease, Parkinson's disease, and dementia with Lewy bodies.

[0139] A method of activating stem cell niches in the central nervous system, including the brain, and associated stem cell niches maintained therein, initiating and sustaining a cascade of intracellular activities, the effects of which include restoring normal function of immune system components, including activation and stimulation of the glymphatic system, thereby producing effects including, but not limited to, removal of scar tissue components, including amyloid, from the CNS (including the brain), leading to improved cognitive function and a reduction in symptoms associated with various neurological and neurodegenerative diseases, including, but not limited to, CTE (chronic traumatic encephalopathy) and TBI (traumatic brain injury), Alzheimer's disease, Parkinson's disease, and dementia with Lewy bodies.

[0140] A method for increasing blood flow circulation to the central nervous system, including the brain, and associated stem cell niches maintained therein, which initiates and sustains a cascade of intracellular activity, the effects of which restore normal function of immune system components, including but not limited to the glymphatic system, thereby producing effects including but not limited to removal of scar tissue components, including amyloid, from the CNS (including the brain), leading to improved cognitive function and a reduction in symptoms associated with traumatic brain injury.

[0141] A method of activating stem cell niches in the central nervous system, including the brain, and associated stem cell niches maintained therein, initiating and sustaining a cascade of intracellular activities, the effect of which is to restore normal function of immune system components, including but not limited to the glymphatic system, thereby leading to restoration of normal function of immune system components, including but not limited to removal of scar tissue components, e.g., including amyloid, from the CNS (including the brain), improved cognitive function, and reduced symptoms associated with traumatic brain injury.

[0142] A method to turn a "cold" tumor into a "hot" one, thereby allowing cell-based or checkpoint-based immunotherapies to act / synergize with laser Rx, specifically by stimulating the release of pro-inflammatory chemokines and cytokines within the tumor, which in turn stimulates the migration and infiltration of effector T cells and other effector cells into the tumor for Rx effects.

[0143] A method for altering the structure and function of the tumor microenvironment (TME) by increasing its permeability to effector Rx cells and cancer therapeutics, specifically by altering neovascularization, angiogenesis and tumor lymphatic function, and other aspects of tumor biology.

[0144] A method for altering the structural-functional density of tumor extracellular matrix (ECM) so that tumor Rx is stimulated by either therapeutic cells or drugs.

[0145] A method for increasing neoantigen load in a tumor that correlates with response to immunotherapy. The neoantigens can be nucleic acid-based, protein-based, or lipid-based.

[0146] Methods to stimulate intratumoral DNA repair and microsatellite instability (MSI), which correlate with Rx sensitivity in many solid tumors.

[0147] A method for stimulating the cGAS / STING innate immune pathway by inducing the production of small endogenous nucleic acids in cells. STING activation stimulates cytokine / chemokine production, thereby helping to stimulate the infiltration of therapeutic immune effector cells.

[0148] A method for stimulating the function of exhausted T cell tumor infiltrates that are no longer functional and are no longer susceptible to reactivation by various stimuli.

[0149] Methods for altering the function, recruitment, and intratumoral dynamics of cancer stem cells, as well as their ability to be "seen" by both tumor-specific immune effector cells and therapeutics designed to target cancer stem cells.

[0150] A method to alter the production, function, loading and release of tumor microvesicles (MVs) from tumors, thereby modifying the diffusion of soluble molecules, which have been shown to prepare distant metastatic niches for dissemination by metastatic tumor cells.

[0151] Methods for modifying cell-cell and cell-ECM interactions that stimulate cell migration from tumors and all subsequent steps in micrometastasis formation: intravasation, systemic delivery, and extravasation in distant organs.

[0152] 23-25, various views of an alternative embodiment of a handpiece 300 that is part of the laser-based system 100 of FIG. 1 are shown. The handpiece 300 is similar in many respects to the handpiece 108 of the exemplary embodiment of the laser-based system 100 of FIGS. 1-9, described in detail above in this specification. Specifically, FIG. 23 is a perspective view of the handpiece 300. FIG. 24 is a side view of the handpiece 300, showing the handle portion 304 of the handpiece 300 moved to a predetermined angular position (e.g., 30 degrees) relative to the spherical portion 308 of the handpiece 300. FIG. 25 is a top perspective view of the handpiece 300, showing the handle 304 without the outer cover 312.

[0153] The sphere 308 forms the main body of the handpiece 300 and houses most of the handpiece components described and illustrated herein. The handle 304 allows the cable 112 to be positioned within and along the length of the handle 304. One end of the cable 112 is connected within the sphere 308, and the other end of the cable 112 is connected within the housing 104 ( FIG. 1 ). In this alternative embodiment of the handpiece 300, the handle 304 is rotatably attached to the sphere 308 using two diametrically opposed protrusions 316 located on the spherical end of the handle 304. The rotatable connection of the protrusions 316 to the sphere 308 allows the handle 304 to pivot or rotate relative to the sphere 308, specifically, about an axis that passes through the sphere 308 and is perpendicular to the flat front surface 192 of the sphere 308. This rotational adjustment feature of the handle 300 allows the user to rotate the handpiece 300 to a desired angle relative to the sphere. This makes the handpiece 300 relatively easy to use and less tiring over the typical period that the laser-based system 100 is used to treat a human or animal.

[0154] In an exemplary embodiment, the handle 304 can be rotated by a user of the handpiece 300 in 30 degree increments, i.e., 30, 60, and 90 degree angles relative to the sphere 308. However, it should be understood that these rotation angles are purely exemplary. Any amount of rotation can be utilized by one skilled in the art in light of the teachings herein.

[0155] In an exemplary embodiment, both the handle 304 and the bulb 308 may be constructed of a sturdy plastic material. The handle outer cover 312 may be constructed of rubber or other material that promotes a non-slip grip by the user of the handpiece 300. The outer cover 312 may have a honeycomb or other pattern formed therein to promote such a non-slip grip.

[0156] As best seen in FIG. 25 , with the outer cover 312 removed, the plastic portion 320 beneath the handle 304 has a slot or groove 324 formed therein. The slot 324 is wide enough to allow the cable 112 to pass through and exit the handle 304 when a user wishes to tilt the handle 304 relative to the sphere 308. Specifically, the outer cover 312 is not continuous, but instead has a seam 328 positioned above the slot 324. Then, when the handle 304 is rotated to a certain angle, the cable 112 passes through the slot 324 and the seam 328. The seam 328 is designed to ensure that a user holding the handle 304 experiences a seamless surface of the outer cover 312 without any noticeable cutouts. As the user adjusts the angle of the handle 304, the cable 112 moves through the slot 324 and out of the handle 304 ( FIG. 24 ), thereby allowing the sphere 308 to rotate freely while the user maintains a firm grip on the handle 304.

[0157] The terminology used herein is for the purpose of describing particular embodiments of the invention only and is not intended to be limiting of the invention. As used herein, the singular forms "a," "an," and "the" are intended to include the plural forms unless the context clearly dictates otherwise. It should be further understood that as used herein, the terms "comprises" and / or "comprising" specify the presence of stated features, integers, steps, operations, elements, and / or components, but do not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof.

[0158] While the present invention has been provided in detail in connection with only a limited number of embodiments, it should be readily understood that the invention is not limited to such disclosed embodiments. Rather, the present invention can be modified to incorporate any number of variations, alterations, substitutions, or equivalent arrangements not heretofore described, but which are commensurate with the spirit and scope of the invention. Furthermore, while various embodiments of the present invention have been described, it should be understood that example embodiments may include only some of the exemplary aspects that have been described. Accordingly, the present invention should not be deemed limited by the foregoing description, but is limited only by the scope of the appended claims.

Claims

1. 1. A method for treating a condition in a mammal, such as a human or animal, using a laser, said method comprising: directing a laser beam emitted from the laser at a specific location on the mammal's skin at a distance of up to 10 inches from the specific location of the skin, the directed laser beam having a wavelength of 1260 nanometers (nm) and a power setting between 2 watts and 60 watts; maintaining the applied laser beam at the specific location on the skin until the temperature at the specific location on the skin increases by up to 10 degrees Fahrenheit (°F); Maintaining a temperature rise of up to 10° F. at the specific location on the skin for a period of at least 45 seconds and not more than 60 seconds increases the irradiance and power density of the applied laser beam at the specific location on the skin to 1.0 watts per square centimeter (W / cm ) for a period of 45 to 60 seconds. ２ ) and 2.25 W / cm ２ and causing the laser to be less than 100 times the wavelength of radiation emitted by the laser.

2. The step of irradiating a specific site on the skin with a laser beam includes: applying a laser beam to the specific areas on the skin that show any visible signs of damage or are reasonably believed to show any degree of damage to underlying body tissue or bone; 2. The method of claim 1, further comprising the step of irradiating a laser beam at a plurality of different spaced locations on the skin near the specific site, thereby enabling the irradiated laser beam to reach the stem cell niche closest to the area of ​​the specific site, thereby resulting in energetic activation of the stem cell niche and its contents.

3. 3. The method of claim 2, wherein the stem cell niche comprises a water-rich hydrophobic environment, and wherein energy from the irradiated laser beam is absorbed by the water-rich hydrophobic environment within the stem cell niche, and wherein absorption of the irradiated laser beam creates an energy gradient, which stimulates mitochondria from cells directly receiving the laser energy and / or neighboring cells to release cytokines, activating the stem cell niche and causing delivery of mitochondrial signals from healthy tissue to unhealthy tissue.

4. 3. The method of claim 2, wherein the specific location on the skin is near a joint of the mammal, and the step of irradiating the specific location on the skin of the mammal with a laser beam emitted from the laser comprises irradiating the specific location with the laser beam at a power setting of between 30 watts and 40 watts.

5. 5. The method of claim 4, wherein the joint includes a knee of the mammal, and wherein the step of irradiating the specific site on the skin of the mammal with a laser beam emitted from the laser includes irradiating the laser beam on a front portion of the knee and a rear portion of the knee.

6. 1. A method for treating cancer in a human or animal using a laser, wherein the human or animal has been administered a checkpoint inhibitor or other immunotherapy modality that can be combined with cytotoxic chemotherapy, and the cancer manifests as a solid tumor, the method comprising: irradiating a laser beam emitted from the laser onto a specific site on the skin of the human or animal at a distance of approximately 10 inches from the skin at the specific site, the specific site on the skin being directly on or near a tumor and a tumor microenvironment area, and the specific site on the skin being also near localized accumulations of immune cells, lymph nodes and lymphatic or blood vessels that supply nutrients to the tumor, and bone marrow, the wavelength of the irradiated laser beam being 1260 nanometers (nm) and a power setting of between 30 and 60 watts; maintaining the applied laser beam at the specific location on the skin until the temperature of the specific location on the skin increases by up to 10 degrees Fahrenheit (°F); A temperature increase of up to 10° F. at the specific location on the skin is maintained for a period of at least 45 seconds and not more than 60 seconds, thereby increasing the irradiance and power density of the applied laser beam at the specific location on the skin to 1.0 watts per square centimeter (W / cm ) for a period of 45 to 60 seconds. ２ ) and 2.25 W / cm ２ and causing the laser to emit less than 100 wt.

7. 7. The method of claim 6, wherein the step of applying a laser beam comprises applying a laser beam to the specific site at least one day prior to administration of the checkpoint inhibitor or other immunotherapy modality to activate stem cell niches in the tumor and its immediate microenvironment.

8. 10. The method of claim 7, further comprising the step of irradiating said specific site with a laser beam at least one day prior to administration of said checkpoint inhibitor or other immunotherapy modality, followed by the step of irradiating said specific site with a laser beam on each day of said immunotherapy or other chemotherapy treatment, either immediately prior to or during administration of said therapy.

9. 7. The method of claim 6, wherein the step of directing the laser beam at the specific site comprises directing the laser beam at multiple sites on the skin near the tumor to cover the area of ​​the tumor and its immediate microenvironment.

10. 10. The method of claim 6, further comprising stimulating microsatellite instability ("MSI"), or other mechanisms, which may increase the immunogenicity of tumors to the endogenous immune system as a result of the production of tumor-associated neoantigens, thereby increasing the tumor's susceptibility to tumor-directed immunotherapy and correlating with susceptibility to other immunotherapeutic modalities targeting both tumor cells and their microenvironment.

11. The method of claim 6, further comprising stimulating the cGAS / STING innate immune pathway by inducing intracellular production of small endogenous nucleic acids, wherein the STING activation stimulates cytokine / chemokine production and stimulates infiltration of therapeutic immune effector cells.

12. 7. The method of claim 6, further comprising stimulating the function of exhausted T cell tumor infiltrates that are no longer functional and cannot be reactivated by various stimuli.

13. 7. The method of claim 6, further comprising altering the production, function, loading and release of tumor microvesicles ("MVs") from the tumor, thereby altering the diffusion of soluble molecules that have been shown to prepare distant metastatic niches for the dissemination of metastatic tumor cells.

14. 1. A method for treating the ear of a human or animal using a laser, the method comprising: irradiating a laser beam emitted from the laser onto a specific site on the skin of the human or animal, the specific site being the ear of the human or animal or an area of ​​the skull adjacent to the ear of the human or animal, the laser beam being irradiated at a distance of about 2 to 3 inches from the skin of the specific site, the wavelength of the irradiated laser beam being 1260 nanometers (nm), and the power setting being between 2 and 10 watts; maintaining the applied laser beam at the specific location on the skin until a temperature increase of at least 5 degrees Fahrenheit (°F) is achieved at the specific location on the skin; A temperature rise of at least 5° F. at the specific location on the skin is maintained for at least 20 seconds, thereby increasing the irradiance and power density of the applied laser beam at the specific location on the skin to 1.0 Watts per square centimeter (W / cm ) for a period of 45 to 60 seconds. ２ 2. A method for treating the ear of a human or animal with a laser, comprising the steps of:

15. The step of irradiating the specific site on the skin with a laser beam further comprises:

15. The method of claim 14, comprising applying laser light to up to three different spaced locations on the skin from near the ear canal to the base of the ear lobe.

16. 1. A method for treating a condition in a mammal, such as a human or animal, using a laser, said method comprising: irradiating a laser beam emitted from the laser onto a specific location on the skin of the mammal, the specific location being the scalp or forehead of the human or animal, the laser beam being irradiated at a distance of up to 3 inches from the skin of the specific location, the wavelength of the irradiated laser beam being 1260 nanometers (nm), and the power setting being between 10 watts and 20 watts; maintaining the applied laser beam at the specific location on the skin until the temperature at the specific location on the skin increases by 5 degrees Fahrenheit (°F); Maintaining a temperature rise of 5°F at the specific location on the skin for a period of at least 20 seconds and not more than 40 seconds results in an irradiance and power density of the applied laser beam at the specific location on the skin of 1.0 watts per square centimeter (W / cm) for a period of 20 to 40 seconds. ２ ) and allowing energy from the irradiated laser beam to pass to tissue of the brain, or central nervous system, or peripheral nervous system of the human or animal, resulting in increased vascular permeability and allowing energy from the irradiated laser beam to reach one or more stem cell niches in the superficial portions of the brain, central nervous system, and peripheral nervous system, creating a positive energy gradient therein.

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