US20060253177A1 - Device and method for providing phototherapy to the brain - Google Patents

Device and method for providing phototherapy to the brain Download PDF

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Publication number
US20060253177A1
US20060253177A1 US11/482,220 US48222006A US2006253177A1 US 20060253177 A1 US20060253177 A1 US 20060253177A1 US 48222006 A US48222006 A US 48222006A US 2006253177 A1 US2006253177 A1 US 2006253177A1
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United States
Prior art keywords
scalp
light
therapy apparatus
light source
brain
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Abandoned
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US11/482,220
Inventor
Luis Taboada
Jackson Streeter
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De Taboada Luis H
PHOTOTHERA IP HOLDINGS Inc
Pthera LLC
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Individual
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Priority claimed from US10/287,432 external-priority patent/US20030109906A1/en
Priority to US11/482,220 priority Critical patent/US20060253177A1/en
Application filed by Individual filed Critical Individual
Publication of US20060253177A1 publication Critical patent/US20060253177A1/en
Assigned to LIGHTHOUSE CAPITAL PARTNERS VI, L.P. reassignment LIGHTHOUSE CAPITAL PARTNERS VI, L.P. SECURITY AGREEMENT Assignors: PHOTOTHERA, INC.
Assigned to WARBURG PINCUS PRIVATE EQUITY IX, L.P. reassignment WARBURG PINCUS PRIVATE EQUITY IX, L.P. SECURITY AGREEMENT Assignors: PHOTOTHERA, INC.
Assigned to PHOTOTHERA, INC. reassignment PHOTOTHERA, INC. RELEASE BY SECURED PARTY (SEE DOCUMENT FOR DETAILS). Assignors: LIGHTHOUSE CAPITAL PARTNERS VI, L.P.
Assigned to PHOTOTHERA, INC. reassignment PHOTOTHERA, INC. TERMINATION OF PATENT SECURITY AGREEMENT Assignors: WARBURG PINCUS PRIVATE EQUITY IX, L.P.
Priority to US12/617,658 priority patent/US20100094384A1/en
Priority to US12/650,423 priority patent/US10758743B2/en
Priority to US12/817,090 priority patent/US9993659B2/en
Priority to US12/846,560 priority patent/US10683494B2/en
Assigned to OXFORD FINANCE CORPORATION, COMERICA BANK reassignment OXFORD FINANCE CORPORATION SECURITY AGREEMENT Assignors: PHOTOTHERA, INC.
Priority to US13/111,840 priority patent/US10315042B2/en
Assigned to PHOTOTHERA IP HOLDINGS, INC. reassignment PHOTOTHERA IP HOLDINGS, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: PHOTOTHERA, INC.
Assigned to DE TABOADA, LUIS H. reassignment DE TABOADA, LUIS H. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ADVANCED PHOTONICS SOLUTIONS, INC.
Assigned to PTHERA, LLC reassignment PTHERA, LLC ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: DE TABOADA, LUIS H.
Priority to US16/190,229 priority patent/US10913943B2/en
Assigned to PHOTOTHERA, INC. reassignment PHOTOTHERA, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: DE TABOADA, LUIS, STREETER, JACKSON
Abandoned legal-status Critical Current

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/06Radiation therapy using light
    • A61N5/0613Apparatus adapted for a specific treatment
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/06Radiation therapy using light
    • A61N5/0613Apparatus adapted for a specific treatment
    • A61N5/0622Optical stimulation for exciting neural tissue
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/06Radiation therapy using light
    • A61N5/067Radiation therapy using light using laser light
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/40Applying electric fields by inductive or capacitive coupling ; Applying radio-frequency signals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N2005/002Cooling systems
    • A61N2005/007Cooling systems for cooling the patient
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/06Radiation therapy using light
    • A61N2005/0635Radiation therapy using light characterised by the body area to be irradiated
    • A61N2005/0643Applicators, probes irradiating specific body areas in close proximity
    • A61N2005/0645Applicators worn by the patient
    • A61N2005/0647Applicators worn by the patient the applicator adapted to be worn on the head
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/06Radiation therapy using light
    • A61N2005/065Light sources therefor
    • A61N2005/0651Diodes
    • A61N2005/0652Arrays of diodes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/06Radiation therapy using light
    • A61N2005/0658Radiation therapy using light characterised by the wavelength of light used
    • A61N2005/0659Radiation therapy using light characterised by the wavelength of light used infrared
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/06Radiation therapy using light
    • A61N5/0613Apparatus adapted for a specific treatment
    • A61N5/0616Skin treatment other than tanning
    • A61N5/0617Hair treatment
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00Ultrasound therapy

Definitions

  • Stroke also called cerebrovascular accident (CVA)
  • CVA cerebrovascular accident
  • a stroke is a sudden disruption of blood flow to a discrete area of the brain that is brought on by a clot lodging in an artery supplying that area of that brain, or by a cerebral hemorrhage due to a ruptured aneurysm or a burst artery.
  • the consequence of stroke is a loss of function in the affected brain region and concomitant loss of bodily function in areas of the body controlled by the affected brain region.
  • loss of function varies greatly from mild or severe, and may be temporary or permanent. Lifestyle factors such as smoking, diet, level of physical activity and high cholesterol increase the risk of stroke, and thus stroke is a major cause of human suffering in developed nations. Stroke is the third leading cause of death in most developed nations, including the United States.
  • Thrombolytic therapy includes aspirin or intravenous heparin to prevent further clot formation and to maintain blood flow after an ischemic stroke.
  • Thrombolytic drugs include tissue plasminogen activator (TPA) and genetically engineered versions thereof, and streptokinase.
  • TPA tissue plasminogen activator
  • streptokinase does not appear to improve the patient's outlook unless administered early (within three hours of stroke).
  • streptokinase does not appear to improve the patient's outlook unless administered early (within three hours of stroke).
  • TPA when administered early appears to substantially improve prognosis, but slightly increases the risk of death from hemorrhage.
  • a CT scan must first confirm that the stroke is not hemorrhagic, which delays administration of the drug.
  • patients taking aspirin or other blood thinners and patients with clotting abnormalities should not be given TPA.
  • Neuroprotective drugs target surviving but endangered neurons in a zone of risk surrounding the area of primary infarct. Such drugs are aimed at slowing down or preventing the death of such neurons, to reduce the extent of brain damage.
  • Certain neuroprotective drugs are anti-excitotoxic, i.e., work to block the excitotoxic effects of excitatory amino acids such as glutamate that cause cell membrane damage under certain conditions.
  • Other drugs such as citicoline work by repairing damaged cell membranes.
  • Lazaroids such as Tirilazed (Freedox) counteract oxidative stress produced by oxygen-free radicals produced during stroke.
  • drugs for stroke treatment include agents that block the enzyme known as PARP, and calcium-channel blockers such as nimodipine (Nimotop) that relax the blood vessels to prevent vascular spasms that further limit blood supply.
  • nimodipine Namotop
  • drug therapy includes the risk of adverse side effects and immune responses.
  • Surgical treatment for stroke includes carotid endarterectomy, which appears to be especially effective for reducing the risk of stroke recurrence for patients exhibiting arterial narrowing of more than 70%.
  • endarterectomy is highly invasive, and risk of stroke recurrence increases temporarily after surgery.
  • Experimental stroke therapies include an angiography-type or angioplasty-type procedure using a thin catheter to remove or reduce the blockage from a clot.
  • Such procedures have extremely limited availability and increase the risk of embolic stroke.
  • Other surgical interventions, such as those to repair an aneurysm before rupture remain controversial because of disagreement over the relative risks of surgery versus leaving the aneurysm untreated.
  • the therapy apparatus comprises a light source having an output emission area positioned to irradiate a portion of the brain with an efficacious power density and wavelength of light.
  • the therapy apparatus further comprises an element interposed between the light source and the patient's scalp. The element is adapted to inhibit temperature increases at the scalp caused by the light.
  • the therapy apparatus comprises a light source positioned to irradiate at least a portion of a patient's head with light.
  • the light has a wavelength and power density which penetrates the cranium to deliver an efficacious amount of light to brain tissue.
  • the therapy apparatus further comprises a material which inhibits temperature increases of the head.
  • the therapy apparatus comprises a light source adapted to irradiate at least a portion of the brain with an efficacious power density and wavelength of light.
  • the therapy apparatus further comprises an element adapted to inhibit temperature increases at the scalp. At least a portion of the element is in an optical path of the light from the light source to the scalp.
  • the therapy apparatus comprises a light source adapted to irradiate at least a portion of the brain with an efficacious power density and wavelength of light.
  • the therapy apparatus further comprises a controller for energizing said light source so as to selectively produce a plurality of different irradiation patterns on the patient's scalp.
  • Each of said irradiation patterns is comprised of at least one illumination area that is small compared to the patient's scalp, and at least one non-illuminated area.
  • Another aspect of the present invention provides a method comprising interposing a head element between a light source and the patient's scalp.
  • the element is comprised of a material which, for an efficacious power density at the brain, inhibits temperature increases at the scalp.
  • the therapy apparatus comprises a light source adapted to irradiate at least a portion of the brain with an efficacious power density and wavelength of light.
  • the therapy apparatus further comprises a biomedical sensor configured to provide real-time feedback information.
  • the therapy apparatus further comprises a controller coupled to the light source and the biomedical sensor. The controller is configured to adjust said light source in response to the real-time feedback information.
  • Another aspect of the present invention provides a method of treating brain tissue.
  • the method comprises introducing light of an efficacious power density onto brain tissue by directing light through the scalp of a patient. Directing the light comprises providing a sufficiently large spot size on said scalp to reduce the power density at the scalp below the damage threshold of scalp tissue, while producing sufficient optical power at said scalp to achieve said efficacious power density at said brain tissue.
  • Another aspect of the present invention provides a method of treating a patient's brain.
  • the method comprises covering at least a significant portion of the patient's scalp with a light-emitting blanket.
  • Another aspect of the present invention provides a method of treating a patient's brain following a stroke.
  • the method comprises applying low-level light therapy to the brain no earlier than several hours following said stroke.
  • Another aspect of the present invention provides a method for treating a patient's brain.
  • the method comprises introducing light of an efficacious power density onto a target area of the brain by directing light through the scalp of the patient.
  • the light has a plurality of wavelengths and the efficacious power density is at least 0.01 mW/cm 2 at the target area.
  • Another aspect of the present invention provides a method for treating a patient's brain.
  • the method comprises directing an efficacious power density of light through the scalp of the patient to a target area of the brain concurrently with applying an efficacious amount of ultrasonic energy to the brain.
  • Anther aspect of the present invention provides a method of providing a neuroprotective effect in a patient that had an ischemic event in the brain.
  • the method comprises identifying a patient who has experienced an ischemic event in the brain.
  • the method further comprises estimating the time of the ischemic event.
  • the method further comprising commencing administration of a neuroprotective effective amount of light energy to the brain no less than about two hours following the time of the ischemic event.
  • FIG. 1 schematically illustrates a therapy apparatus comprising a cap which fits securely over the patient's head.
  • FIG. 2 schematically illustrates a fragmentary cross-sectional view taken along the lines 2 - 2 of FIG. 1 , showing one embodiment of a portion of a therapy apparatus comprising an element and its relationship to the scalp and brain.
  • FIG. 3 schematically illustrates an embodiment with an element comprising a container coupled to an inlet conduit and an outlet conduit for the transport of a flowing material through the element.
  • FIG. 4A schematically illustrates a fragmentary cross-sectional view taken along the lines 2 - 2 of FIG. 1 , showing another embodiment of a portion of a therapy apparatus comprising an element with a portion contacting the scalp and a portion spaced away from the scalp.
  • FIG. 4B schematically illustrates a fragmentary cross-sectional view taken along the lines 2 - 2 of FIG. 1 , showing an embodiment of a portion of a therapy apparatus comprising a plurality of light sources and an element with portions contacting the scalp and portions spaced away from the scalp.
  • FIGS. 5A and 5B schematically illustrate cross-sectional views of two embodiments of the element in accordance with FIG. 4B taken along the line 4 - 4 .
  • FIGS. 6A-6C schematically illustrate an embodiment in which the light sources are spaced away from the scalp.
  • FIGS. 7A and 7B schematically illustrate the diffusive effect on the light by the element.
  • FIGS. 8A and 8B schematically illustrate two light beams having different cross-sections impinging a patient's scalp and propagating through the patient's head to irradiate a portion of the patient's brain tissue.
  • FIG. 9A schematically illustrates a therapy apparatus comprising a cap and a light source comprising a light blanket.
  • FIGS. 9B and 9C schematically illustrate two embodiments of the light blanket.
  • FIG. 10 schematically illustrates a therapy apparatus comprising a flexible strap and a housing.
  • FIG. 11 schematically illustrates a therapy apparatus comprising a handheld probe.
  • FIG. 12 is a block diagram of a control circuit comprising a programmable controller.
  • FIG. 13 schematically illustrates a therapy apparatus comprising a light source and a controller.
  • FIG. 14 schematically illustrates a light source comprising a laser diode and a galvometer with a mirror and a plurality of motors.
  • FIGS. 15A and 15B schematically illustrate two irradiation patterns that are spatially shifted relative to each other.
  • Low level light therapy or phototherapy involves therapeutic administration of light energy to a patient at lower power outputs than those used for cutting, cauterizing, or ablating biological tissue, resulting in desirable biostimulatory effects while leaving tissue undamaged.
  • LLLT Low level light therapy
  • light sources positioned outside the body.
  • absorption of the light energy by intervening tissue can limit the amount of light energy delivered to the target tissue site, while heating the intervening tissue.
  • scattering of the light energy by intervening tissue can limit the power density or energy density delivered to the target tissue site.
  • Brute force attempts to circumvent these effects by increasing the power and/or power density applied to the outside surface of the body can result in damage (e.g., burning) of the intervening tissue.
  • Non-invasive phototherapy methods are circumscribed by setting selected treatment parameters within specified limits so as to preferably avoid damaging the intervening tissue.
  • a review of the existing scientific literature in this field would cast doubt on whether a set of undamaging, yet efficacious, parameters could be found.
  • certain embodiments, as described herein, provide devices and methods which can achieve this goal.
  • Such embodiments may include selecting a wavelength of light at which the absorption by intervening tissue is below a damaging level. Such embodiments may also include setting the power output of the light source at very low, yet efficacious, power densities (e.g., between approximately 100 ⁇ W/cm 2 to approximately 10 W/cm 2 ) at the target tissue site, and time periods of application of the light energy at a few seconds to minutes to achieve an efficacious energy density at the target tissue site being treated. Other parameters can also be varied in the use of phototherapy. These other parameters contribute to the light energy that is actually delivered to the treated tissue and may play key roles in the efficacy of phototherapy.
  • the irradiated portion of the brain can comprise the entire brain.
  • FIGS. 1 and 2 schematically illustrate an embodiment of a therapy apparatus 10 for treating a patient's brain 20 .
  • the therapy apparatus 10 comprises a light source 40 having an output emission area 41 positioned to irradiate a portion of the brain 20 with an efficacious power density and wavelength of light.
  • the therapy apparatus 10 further comprises an element 50 interposed between the light source 40 and the patient's scalp 30 .
  • the element 50 is adapted to inhibit temperature increases at the scalp 30 caused by the light.
  • the term “element” is used in its broadest sense, including, but not limited to, as a reference to a constituent or distinct part of a composite device.
  • the element 50 is adapted to contact at least a portion of the patient's scalp 30 , as schematically illustrated in FIGS. 1-4 .
  • the element 50 is in thermal communication with and covers at least a portion of the scalp 30 .
  • the element 50 is spaced away from the scalp 30 and does not contact the scalp 30 .
  • the light passes through the element 50 prior to reaching the scalp 30 such that the element 50 is in the optical path of light propagating from the light source 40 , through the scalp 30 , through the bones, tissues, and fluids of the head (schematically illustrated in FIG. 1 by the region 22 ), to the brain 20 .
  • the light passes through a transmissive medium of the element 50 , while in other embodiments, the light passes through an aperture of the element 50 .
  • the element 50 may be utilized with various embodiments of the therapy apparatus 10 .
  • the light source 40 is disposed on the interior surface of a cap 60 which fits securely over the patient's head.
  • the cap 60 provides structural integrity for the therapy apparatus 10 and holds the light source 40 and element 50 in place.
  • Exemplary materials for the cap 60 include, but are not limited to, metal, plastic, or other materials with appropriate structural integrity.
  • the cap 60 may include an inner lining 62 comprising a stretchable fabric or mesh material, such as Lycra or nylon.
  • the light source 40 is adapted to be removably attached to the cap 60 in a plurality of positions so that the output emission area 41 of the light source 40 can be advantageously placed in a selected position for treatment of a stroke or CVA in any portion of the brain 20 .
  • the light source 40 can be an integral portion of the cap 60 .
  • the light source 40 illustrated by FIGS. 1 and 2 comprises at least one power conduit 64 coupled to a power source (not shown).
  • the power conduit 64 comprises an electrical conduit which is adapted to transmit electrical signals and power to an emitter (e.g., laser diode or light-emitting diode).
  • the power conduit 64 comprises an optical conduit (e.g., optical waveguide) which transmits optical signals and power to the output emission area 41 of the light source 40 .
  • the light source 40 comprises optical elements (e.g., lenses, diffusers, and/or waveguides) which transmit at least a portion of the optical power received via the optical conduit 64 .
  • the therapy apparatus 10 contains a power source (e.g., a battery) and the power conduit 64 is substantially internal to the therapy apparatus 10 .
  • the patient's scalp 30 comprises hair and skin which cover the patient's skull. In other embodiments, at least a portion of the hair is removed prior to the phototherapy treatment, so that the therapy apparatus 10 substantially contacts the skin of the scalp 30 .
  • the element 50 is adapted to contact the patient's scalp 30 , thereby providing an interface between the therapy apparatus 10 and the patient's scalp 30 .
  • the element 50 is coupled to the light source 40 and in other such embodiments, the element is also adapted to conform to the scalp 30 , as schematically illustrated in FIG. 1 . In this way, the element 50 positions the output emission area 41 of the light source 40 relative to the scalp 30 .
  • the element 50 is mechanically adjustable so as to adjust the position of the light source 40 relative to the scalp 30 . By fitting to the scalp 30 and holding the light source 40 in place, the element 50 inhibits temperature increases at the scalp 30 that would otherwise result from misplacement of the light source 40 relative to the scalp 30 .
  • the element 50 is mechanically adjustable so as to fit the therapy apparatus 10 to the patient's scalp 30 .
  • the element 50 provides a reusable interface between the therapy apparatus 10 and the patient's scalp 30 .
  • the element 50 can be cleaned or sterilized between uses of the therapy apparatus, particularly between uses by different patients.
  • the element 50 provides a disposable and replaceable interface between the therapy apparatus 10 and the patient's scalp 30 .
  • the element 50 comprises a container (e.g., a cavity or bag) containing a material (e.g., gel).
  • the container can be flexible and adapted to conform to the contours of the scalp 30 .
  • Other exemplary materials contained in the container of the element 50 include, but are not limited to, thermal exchange materials such as glycerol and water.
  • the element 50 of certain embodiments substantially covers the entire scalp 30 of the patient, as schematically illustrated in FIG. 2 . In other embodiments, the element 50 only covers a localized portion of the scalp 30 in proximity to the irradiated portion of the scalp 30 .
  • the element 50 is within an optical path of the light from the light source 40 to the scalp 30 .
  • the element 50 is substantially optically transmissive at a wavelength of the light emitted by the output emission area 41 of the light source 40 and is adapted to reduce back reflections of the light. By reducing back reflections, the element 50 increases the amount of light transmitted to the brain 20 and reduces the need to use a higher power light source 40 which may otherwise create temperature increases at the scalp 30 .
  • the element 50 comprises one or more optical coatings, films, layers, membranes, etc. in the optical path of the transmitted light which are adapted to reduce back reflections.
  • the element 50 reduces back reflections by fitting to the scalp 30 so as to substantially reduce air gaps between the scalp 30 and the element 50 in the optical path of the light.
  • the refractive-index mismatches between such an air gap and the element 50 and/or the scalp 30 would otherwise result in at least a portion of the light propagating from the light source 40 to the brain 20 to be reflected back towards the light source 40 .
  • certain embodiments of the element 50 comprise a material having, at a wavelength of light emitted by the light source 40 , a refractive index which substantially matches the refractive index of the scalp 30 (e.g., about 1.3), thereby reducing any index-mismatch-generated back reflections between the element 50 and the scalp 30 .
  • materials with refractive indices compatible with embodiments described herein include, but are not limited to, glycerol, water, and silica gels.
  • Exemplary index-matching gels include, but are not limited to, those available from Nye Lubricants, Inc. of Fairhaven, Mass.
  • the element 50 is adapted to cool the scalp 30 by removing heat from the scalp 30 so as to inhibit temperature increases at the scalp 30 .
  • the element 50 comprises a reservoir (e.g., a chamber or a conduit) adapted to contain a coolant.
  • the coolant flows through the reservoir near the scalp 30 .
  • the scalp 30 heats the coolant, which flows away from the scalp 30 , thereby removing heat from the scalp 30 by active cooling.
  • the coolant in certain embodiments circulates between the element 50 and a heat transfer device, such as a chiller, whereby the coolant is heated by the scalp 30 and is cooled by the heat transfer device.
  • Exemplary materials for the coolant include, but are not limited to, water or air.
  • the element 50 comprises a container 51 (e.g., a flexible bag) coupled to an inlet conduit 52 and an outlet conduit 53 , as schematically illustrated in FIG. 3 .
  • a flowing material e.g., water, air, or glycerol
  • the container 51 can be disposable and replacement containers 51 can be used for subsequent patients.
  • the element 50 comprises a container (e.g., a flexible bag) containing a material which does not flow out of the container but is thermally coupled to the scalp 30 so as to remove heat from the scalp 30 by passive cooling.
  • a container e.g., a flexible bag
  • exemplary materials include, but are not limited to, water, glycerol, and gel.
  • the non-flowing material can be pre-cooled (e.g., by placement in a refrigerator) prior to the phototherapy treatment to facilitate cooling of the scalp 30 .
  • the element 50 is adapted to apply pressure to at least a portion of the scalp 30 .
  • the element 50 can blanch the portion of the scalp 30 by forcing at least some blood out the optical path of the light energy.
  • the blood removal resulting from the pressure applied by the element 50 to the scalp 30 decreases the corresponding absorption of the light energy by blood in the scalp 30 .
  • temperature increases due to absorption of the light energy by blood at the scalp 30 are reduced.
  • the fraction of the light energy transmitted to the subdermal target tissue of the brain 20 is increased.
  • FIGS. 4A and 4B schematically illustrate embodiments of the element 50 adapted to facilitate the blanching of the scalp 30 .
  • certain element portions 72 contact the patient's scalp 30 and other element portions 74 are spaced away from the scalp 30 .
  • the element portions 72 contacting the scalp 30 provide an optical path for light to propagate from the light source 40 to the scalp 30 .
  • the element portions 72 contacting the scalp 30 also apply pressure to the scalp 30 , thereby forcing blood out from beneath the element portion 72 .
  • FIG. 4B schematically illustrates a similar view of an embodiment in which the light source 40 comprises a plurality of light sources 40 a , 40 b , 40 c.
  • FIG. 5A schematically illustrates one embodiment of the cross-section along the line 4 - 4 of FIG. 4B .
  • the element portions 72 contacting the scalp 30 comprise ridges extending along one direction, and the element portions 74 spaced away from the scalp 30 comprise troughs extending along the same direction. In certain embodiments, the ridges are substantially parallel to one another and the troughs are substantially parallel to one another.
  • FIG. 5B schematically illustrates another embodiment of the cross-section along the line 4 - 4 of FIG. 4B .
  • the element portions 72 contacting the scalp 30 comprise a plurality of projections in the form of a grid or array.
  • the portions 72 are rectangular and are separated by element portions 74 spaced away from the scalp 30 , which form troughs extending in two substantially perpendicular directions.
  • the portions 72 of the element 50 contacting the scalp 30 can be a substantial fraction of the total area of the element 50 or of the scalp 30 .
  • FIGS. 6A-6C schematically illustrate an embodiment in which the light sources 40 are spaced away from the scalp 30 .
  • the light emitted by the light sources 40 propagates from the light sources 40 through the scalp 30 to the brain 20 and disperses in a direction generally parallel to the scalp 30 , as shown in FIG. 6A .
  • the light sources 40 are preferably spaced sufficiently far apart from one another such that the light emitted from each light source 40 overlaps with the light emitted from the neighboring light sources 40 at the brain 20 .
  • FIG. 6B schematically illustrates this overlap as the overlap of circular spots 42 at a reference depth at or below the surface of the brain 20 .
  • FIG. 6C schematically illustrates this overlap as a graph of the power density at the reference depth of the brain 20 along the line L-L of FIGS. 6A and 6B .
  • Summing the power densities from the neighboring light sources 40 serves to provide a more uniform light distribution at the tissue to be treated.
  • the summed power density is preferably less than a damage threshold of the brain 20 and above an efficacy threshold.
  • the element 50 is adapted to diffuse the light prior to reaching the scalp 30 .
  • FIGS. 7A and 7B schematically illustrate the diffusive effect on the light by the element 50 .
  • An exemplary energy density profile of the light emitted by a light source 40 is peaked at a particular emission angle.
  • the energy density profile of the light does not have a substantial peak at any particular emission angle, but is substantially evenly distributed among a range of emission angles.
  • the element 50 distributes the light energy substantially evenly over the area to be illuminated, thereby inhibiting “hot spots” which would otherwise create temperature increases at the scalp 30 .
  • the element 50 can effectively increase the spot size of the light impinging the scalp 30 , thereby advantageously lowering the power density at the scalp 30 , as described more fully below.
  • the element 50 can diffuse the light to alter the total light output distribution to reduce inhomogeneities.
  • the element 50 provides sufficient diffusion of the light such that the power density of the light is less than a maximum tolerable level of the scalp 30 and brain 20 . In certain other embodiments, the element 50 provides sufficient diffusion of the light such that the power density of the light equals a therapeutic value at the target tissue.
  • the element 50 can comprise exemplary diffusers including, but are not limited to, holographic diffusers such as those available from Physical Optics Corp. of Torrance, Calif. and Display Optics P/N SN1333 from Reflexite Corp. of Avon, Conn.
  • Phototherapy for the treatment of stroke is based in part on the discovery that power density (i.e., power per unit area or number of photons per unit area per unit time) and energy density (i.e., energy per unit area or number of photons per unit area) of the light energy applied to tissue appear to be significant factors in determining the relative efficacy of low level phototherapy.
  • This discovery is particularly applicable with respect to treating and saving surviving but endangered neurons in a zone of danger surrounding the primary infarct after a stroke or cerebrovascular accident (CVA).
  • CVA cerebrovascular accident
  • biostimulative effect may include interactions with chromophores within the target tissue, which facilitate production of ATP thereby feeding energy to injured cells which have experienced decreased blood flow due to the stroke. Because strokes correspond to blockages or other interruptions of blood flow to portions of the brain, it is thought that any effects of increasing blood flow by phototherapy are of less importance in the efficacy of phototherapy for stroke victims. Further information regarding the role of power density and exposure time is described by Hans H. F. I. van Breugel and P. R.
  • FIGS. 8A and 8B show the effects of scattering by intervening tissue. Further information regarding the scattering of light by tissue is provided by V. Tuchin in “Tissue Optics: Light Scattering Methods and Instruments for Medical Diagnosis,” SPIE Press (2000), Bellingham, Wash., pp. 3-11, which is incorporated in its entirety by reference herein.
  • FIG. 8A schematically illustrates a light beam 80 impinging a portion 90 of a patient's scalp 30 and propagating through the patient's head to irradiate a portion 100 of the patient's brain tissue 20 .
  • the light beam 80 impinging the scalp 30 is collimated and has a circular cross-section with a radius of 2 cm and a cross-sectional area of approximately 12.5 cm 2 .
  • FIG. 8B schematically illustrates a light beam 82 having a significantly smaller cross-section impinging a smaller portion 92 of the scalp 30 to irradiate a portion 102 of the brain tissue 20 .
  • FIGS. 8A and 8B are collimated and has a circular cross-section with a radius of 1 cm and a cross-sectional area of approximately 3.1 cm 2 .
  • the collimations, cross-sections, and radii of the light beams 80 , 82 illustrated in FIGS. 8A and 8B are exemplary; other light beams with other parameters are also compatible with embodiments described herein. In particular, similar considerations apply to focussed beams or diverging beams, as they are similarly scattered by the intervening tissue.
  • the cross-sections of the light beams 80 , 82 become larger while propagating through the head due to scattering from interactions with tissue of the head.
  • the angle of dispersion is 15 degrees and the irradiated brain tissue 20 is 2.5 cm below the scalp 30
  • the resulting area of the portion 100 of brain tissue 20 irradiated by the light beam 80 in FIG. 8A is approximately 22.4 cm 2
  • the resulting area of the portion 102 of brain tissue 20 irradiated by the light beam 82 in FIG. 8B is approximately 8.8 cm 2 .
  • Irradiating the portion 100 of the brain tissue 20 with a power density of 10 mW/cm 2 corresponds to a total power within the portion 100 of approximately 224 mW (10 mW/cm 2 ⁇ 22.4 cm 2 ).
  • the incident light beam 80 at the scalp 30 will have a total power of approximately 4480 mW (224 mW/0.05) and a power density of approximately 358 mW/cm 2 (4480 mW/12.5 cm 2 ).
  • irradiating the portion 102 of the brain tissue 20 with a power density of 10 mW/cm 2 corresponds to a total power within the portion 102 of approximately 88 mW (10 mW/cm 2 ⁇ 8.8 cm 2 ), and with the same 5% transmittance, the incident light beam 82 at the scalp 30 will have a total power of approximately 1760 mW (88 mW/0.05) and a power density of approximately 568 mW/cm 2 (1760 mW/3.1 cm 2 ).
  • exemplary calculations illustrate that to obtain a desired power density at the brain 20 , higher total power at the scalp 30 can be used in conjunction with a larger spot size at the scalp 30 .
  • a desired power density at the brain 20 can be achieved with lower power densities at the scalp 30 which can reduce the possibility of overheating the scalp 30 .
  • the light can be directed through an aperture to define the illumination of the scalp 30 to a selected smaller area.
  • the light source 40 preferably generates light in the visible to near-infrared wavelength range.
  • the light source 40 comprises one or more laser diodes, which each provide coherent light.
  • the emitted light may produce “speckling” due to coherent interference of the light.
  • This speckling comprises intensity spikes which are created by constructive interference and can occur in proximity to the target tissue being treated.
  • the average power density may be approximately 10 mW/cm 2
  • the power density of one such intensity spike in proximity to the brain tissue to be treated may be approximately 300 mW/cm 2 .
  • this increased power density due to speckling can improve the efficacy of treatments using coherent light over those using incoherent light for illumination of deeper tissues.
  • the light source 40 provides incoherent light.
  • Exemplary light sources 40 of incoherent light include, but are not limited to, incandescent lamps or light-emitting diodes.
  • a heat sink can be used with the light source 40 (for either coherent or incoherent sources) to remove heat from the light source 40 and to inhibit temperature increases at the scalp 30 .
  • the light source 40 generates light which is substantially monochromatic (i.e., light having one wavelength, or light having a narrow band of wavelengths). So that the amount of light transmitted to the brain is maximized, the wavelength of the light is selected in certain embodiments to be at or near a transmission peak (or at or near an absorption minimum) for the intervening tissue. In certain such embodiments, the wavelength corresponds to a peak in the transmission spectrum of tissue at about 820 nanometers. In other embodiments, the wavelength of the light is preferably between about 630 nanometers and about 1064 nanometers, more preferably between about 780 nanometers and about 840, nanometers, and most preferably includes wavelengths of about 790, 800, 810, 820, or 830 nanometers. It has also been found that an intermediate wavelength of about 739 nanometers appears to be suitable for penetrating the skull, although other wavelengths are also suitable and may be used.
  • the light source 40 generates light having a plurality of wavelengths. In certain such embodiments, each wavelength is selected so as to work with one or more chromophores within the target tissue. Without being bound by theory, it is believed that irradiation of chromophores increases the production of ATP in the target tissue, thereby producing beneficial effects.
  • the light source 40 is adapted to generate light having a first wavelength concurrently with light having a second wavelength. In certain other embodiments, the light source 40 is adapted to generate light having a first wavelength sequentially with light having a second wavelength.
  • the light source 40 includes at least one continuously emitting GaAlAs laser diode having a wavelength of about 830 nanometers. In another embodiment, the light source 40 comprises a laser source having a wavelength of about 808 nanometers. In still other embodiments, the light source 40 includes at least one vertical cavity surface-emitting laser (VCSEL) diode.
  • VCSEL vertical cavity surface-emitting laser
  • Other light sources 40 compatible with embodiments described herein include, but are not limited to, light-emitting diodes (LEDs) and filtered lamps.
  • the light source 40 is capable of emitting light energy at a power sufficient to achieve a predetermined power density at the subdermal target tissue (e.g., at a depth of approximately 2 centimeters from the dura). It is presently believed that phototherapy of tissue is most effective when irradiating the target tissue with power densities of light of at least about 0.01 mW/cm 2 and up to about 1 W/cm 2 .
  • the subsurface power density is at least about 0.01, 0.05, 0.1, 0.5, 1, 5, 10, 15, 20, 30, 40, 50, 60, 70, 80, or 90 mW/cm 2 , respectively, depending on the desired clinical performance.
  • the subsurface power density is preferably about 0.01 mW/cm 2 to about 100 mW/cm 2 , more preferably about 0.01 mW/cm 2 to about 50 mW/cm 2 , and most preferably about 2 mW/cm 2 to about 20 mW/cm 2 . It is believed that these subsurface power densities are especially effective at producing the desired biostimulative effects on the tissue being treated.
  • surface power densities preferably between about 10 mW/cm 2 to about 10 W/cm 2 , or more preferably between about 100 mW/cm 2 to about 500 mW/cm 2 , will typically be used to attain the selected power densities at the subdermal target tissue.
  • the light source 40 is preferably capable of emitting light energy having a total power output of at least about 25 mW to about 100 W.
  • the total power output is limited to be no more than about 30, 50, 75, 100, 150, 200, 250, 300, 400, or 500 mW, respectively.
  • the light source 40 comprises a plurality of sources used in combination to provide the total power output.
  • the actual power output of the light source 40 is preferably controllably variable. In this way, the power of the light energy emitted can be adjusted in accordance with a selected power density at the subdermal tissue being treated.
  • a light source 40 that includes only a single laser diode that is capable of providing about 25 mW to about 100 W of total power output at the skin surface.
  • the laser diode can be optically coupled to the scalp 30 via an optical fiber or can be configured to provide a sufficiently large spot size to avoid power densities which would burn or otherwise damage the scalp 30 .
  • the light source 40 utilizes a plurality of sources (e.g., laser diodes) arranged in a grid or array that together are capable of providing at least about 25 mW to about 100 W of total power output at the skin surface.
  • the light source 40 of other embodiments may also comprise sources having power capacities outside of these limits.
  • FIG. 9A schematically illustrates another embodiment of the therapy apparatus 10 which comprises the cap 60 and a light source comprising a light-emitting blanket 110 .
  • FIG. 9B schematically illustrates an embodiment of the blanket 110 comprising a flexible substrate 111 (e.g., flexible circuit board), a power conduit interface 112 , and a sheet formed by optical fibers 114 positioned in a fan-like configuration.
  • FIG. 9 C schematically illustrates an embodiment of the blanket 110 comprising a flexible substrate 111 , a power conduit interface 112 , and a sheet formed by optical fibers 114 woven into a mesh.
  • the blanket 110 is preferably positioned within the cap 60 so as to cover an area of the scalp 30 corresponding to a portion of the brain 20 to be treated.
  • the power conduit interface 112 is adapted to be coupled to an optical fiber conduit 64 which provides optical power to the blanket 110 .
  • the optical power interface 112 of certain embodiments comprises a beam splitter or other optical device which distributes the incoming optical power among the various optical fibers 114 .
  • the power conduit interface 112 is adapted to be coupled to an electrical conduit which provides electrical power to the blanket 110 .
  • the power conduit interface 112 comprises one or more laser diodes, the output of which is distributed among the various optical fibers 114 of the blanket 110 .
  • the blanket 110 comprises an electroluminescent sheet which responds to electrical signals from the power conduit interface 112 by emitting light.
  • the power conduit interface 112 comprises circuitry adapted to distribute the electrical signals to appropriate portions of the electroluminescent sheet.
  • the side of the blanket 110 nearer the scalp 30 is preferably provided with a light scattering surface, such as a roughened surface to increase the amount of light scattered out of the blanket 110 towards the scalp 30 .
  • the side of the blanket 110 further from the scalp 30 is preferably covered by a reflective coating so that light emitted away from the scalp 30 is reflected back towards the scalp 30 .
  • This configuration is similar to configurations used for the “back illumination” of liquid-crystal displays (LCDs).
  • Other configurations of the blanket 110 are compatible with embodiments described herein.
  • the light source 40 generates light which cause eye damage if viewed by an individual.
  • the apparatus 50 can be configured to provide eye protection so as to avoid viewing of the light by individuals. For example, opaque materials can be appropriately placed to block the light from being viewed directly.
  • interlocks can be provided so that the light source 40 is not activated unless the apparatus 50 is in place, or other appropriate safety measures are taken.
  • the phototherapy methods for the treatment of stroke described herein may be practiced and described using, for example, a low level laser therapy apparatus such as that shown and described in U.S. Pat. No. 6,214,035, U.S. Pat. No. 6,267,780, U.S. Pat. No. 6,273,905 and U.S. Pat. No. 6,290,714, which are all incorporated in their entirety by reference herein, as are the references incorporated by reference therein.
  • the illustrated therapy apparatus 10 includes a light source 40 , an element 50 , and a flexible strap 120 adapted for securing the therapy apparatus 10 over an area of the patient's head.
  • the light source 40 can be disposed on the strap 120 itself, or in a housing 122 coupled to the strap 120 .
  • the light source 40 preferably comprises a plurality of diodes 40 a , 40 b , . . . capable of emitting light energy having a wavelength in the visible to near-infrared wavelength range.
  • the element 50 is adapted to be positioned between the light source 40 and the patient's scalp 30 .
  • the therapy apparatus 10 further includes a power supply (not shown) operatively coupled to the light source 40 , and a programmable controller 126 operatively coupled to the light source 40 and to the power supply.
  • the programmable controller 126 is configured to control the light source 40 so as to deliver a predetermined power density to the brain tissue 20 .
  • the light source 40 comprises the programmable controller 126 .
  • the programmable controller 126 is a separate component of the therapy apparatus 10 .
  • the strap 120 comprises a loop of elastomeric material sized appropriately to fit snugly onto the patient's scalp 30 .
  • the strap 120 comprises an elastomeric material to which is secured any suitable securing means 130 , such as mating Velcro strips, buckles, snaps, hooks, buttons, ties, or the like.
  • suitable securing means 130 such as mating Velcro strips, buckles, snaps, hooks, buttons, ties, or the like.
  • the precise configuration of the strap 120 is subject only to the limitation that the strap 120 is capable of maintaining the light source 40 in a selected position so that light energy emitted by the light source 40 is directed towards the targeted brain tissue 20 .
  • the housing 122 comprises a layer of flexible plastic or fabric that is secured to the strap 120 .
  • the housing 122 comprises a plate or an enlarged portion of the strap 120 .
  • Various strap configurations and spatial distributions of the light sources 40 are compatible with embodiments described herein so that the therapy apparatus 10 can treat selected portions of brain tissue.
  • the therapy apparatus 10 for delivering the light energy includes a handheld probe 140 , as schematically illustrated in FIG. 11 .
  • the probe 140 includes a light source 40 and an element 50 as described herein.
  • FIG. 12 is a block diagram of a control circuit 200 comprising a programmable controller 126 according to embodiments described herein.
  • the control circuit 200 is configured to adjust the power of the light energy emitted by the light source 40 to generate a predetermined surface power density at the scalp 30 corresponding to a predetermined energy delivery profile, such as a predetermined subsurface power density, to the target area of the brain 20 .
  • the programmable controller 126 comprises a logic circuit 210 , a clock 212 coupled to the logic circuit 210 , and an interface 214 coupled to the logic circuit 210 .
  • the clock 212 of certain embodiments provides a timing signal to the logic circuit 210 so that the logic circuit 210 can monitor and control timing intervals of the applied light. Examples of timing intervals include, but are not limited to, total treatment times, pulsewidth times for pulses of applied light, and time intervals between pulses of applied light.
  • the light sources 40 can be selectively turned on and off to reduce the thermal load on the scalp 30 and to deliver a selected power density to particular areas of the brain 20 .
  • the interface 214 of certain embodiments provides signals to the logic circuit 210 which the logic circuit 210 uses to control the applied light.
  • the interface 214 can comprise a user interface or an interface to a sensor monitoring at least one parameter of the treatment.
  • the programmable controller 126 is responsive to signals from the sensor to preferably adjust the treatment parameters to optimize the measured response.
  • the programmable controller 126 can thus provide closed-loop monitoring and adjustment of various treatment parameters to optimize the phototherapy.
  • the signals provided by the interface 214 from a user are indicative of parameters that may include, but are not limited to, patient characteristics (e.g., skin type, fat percentage), selected applied power densities, target time intervals, and power density/timing profiles for the applied light.
  • the logic circuit 210 is coupled to a light source driver 220 .
  • the light source driver 220 is coupled to a power supply 230 , which in certain embodiments comprises a battery and in other embodiments comprises an alternating current source.
  • the light source driver 220 is also coupled to the light source 40 .
  • the logic circuit 210 is responsive to the signal from the clock 212 and to user input from the user interface 214 to transmit a control signal to the light source driver 220 . In response to the control signal from the logic circuit 210 , the light source driver 220 adjust and controls the power applied to the light sources 40 .
  • Other control circuits besides the control circuit 200 of FIG. 12 are compatible with embodiments described herein.
  • the logic circuit 110 is responsive to signals from a sensor monitoring at least one parameter of the treatment to control the applied light.
  • a sensor monitoring at least one parameter of the treatment For example, certain embodiments comprise a temperature sensor thermally coupled to the scalp 30 to provide information regarding the temperature of the scalp 30 to the logic circuit 210 .
  • the logic circuit 210 is responsive to the information from the temperature sensor to transmit a control signal to the light source driver 220 so as to adjust the parameters of the applied light to maintain the scalp temperature below a predetermined level.
  • Other embodiments include exemplary biomedical sensors including, but not limited to, a blood flow sensor, a blood gas (e.g., oxygenation) sensor, an ATP production sensor, or a cellular activity sensor.
  • Such biomedical sensors can provide real-time feedback information to the logic circuit 210 .
  • the logic circuit 110 is responsive to signals from the sensors to preferably adjust the parameters of the applied light to optimize the measured response.
  • the logic circuit 110 can thus provide closed-loop monitoring and adjustment of various parameters of the applied light to optimize the phototherapy.
  • the therapy apparatus 310 comprises a light source 340 adapted to irradiate a portion of the patient's brain 20 with an efficacious power density and wavelength of light.
  • the therapy apparatus 310 further comprises a controller 360 for energizing said light source 340 , so as to selectively produce a plurality of different irradiation patterns on the patient's scalp 30 .
  • Each of the irradiation patterns is comprised of a least one illuminated area that is small compared to the patient's scalp 30 , and at least one non-illuminated area.
  • the light source 340 includes an apparatus for adjusting the emitted light to irradiate different portions of the scalp 30 .
  • the apparatus physically moves the light source 40 relative to the scalp 30 .
  • the apparatus does not move the light source 40 , but redirects the emitted light to different portions of the scalp 30 .
  • the light source 340 comprises a laser diode 342 and a galvometer 344 , both of which are electrically coupled to the controller 360 .
  • the galvometer 344 comprises a mirror 346 mounted onto an assembly 348 which is adjustable by a plurality of motors 350 .
  • the therapy apparatus 310 comprises an element 50 adapted to inhibit temperature increases at the scalp 30 as described herein.
  • FIG. 15A schematically illustrates an irradiation pattern 370 in accordance with embodiments described herein.
  • the irradiation pattern 370 comprises at least one illuminated area 372 and at least one non-illuminated area 374 .
  • the irradiation pattern 370 is generated by scanning the mirror 346 so that the light impinges the patient's scalp 30 in the illuminated area 372 but not in the non-illuminated area 374 .
  • Certain embodiments modify the illuminated area 372 and the non-illuminated area 374 as a function of time.
  • This selective irradiation can be used to reduce the thermal load on particular locations of the scalp 30 by moving the light from one illuminated area 372 to another.
  • the irradiation pattern 370 schematically illustrated in FIG. 15A
  • the illuminated areas 372 of the scalp 30 are heated by interaction with the light, and the non-illuminated areas 374 are not heated.
  • the complementary irradiation pattern 370 ′ schematically illustrated in FIG. 15B
  • the previously non-illuminated areas 374 are now illuminated areas 372 ′
  • the previously illuminated areas 372 are now non-illuminated areas 374 ′.
  • a comparison of the illuminated areas 372 of the irradiation pattern 370 of FIG. 15A with the illuminated area 372 ′ of the irradiation pattern 370 ′ of FIG. 15B shows that the illuminated areas 372 , 372 ′ do not significantly overlap one another. In this way, the thermal load at the scalp 30 due to the absorption of the light can be distributed across the scalp 30 , thereby avoiding unduly heating one or more portions of the scalp 30 .
  • Preferred methods of phototherapy are based at least in part on the finding described above that, for a selected wavelength, the power density (light intensity or power per unit area, in W/cm 2 ) or the energy density (energy per unit area, in J/cm 2 , or power density multiplied by the exposure time) of the light energy delivered to tissue is an important factor in determining the relative efficacy of the phototherapy, and efficacy is not as directly related to the total power or the total energy delivered to the tissue.
  • power density or energy density as delivered to a portion of the patient's brain 20 which can include the area of infarct after a stroke, appears to be important factors in using phototherapy to treat and save surviving but endangered neurons in a zone of danger surrounding the infarcted area. Certain embodiments apply optimal power densities or energy densities to the intended target tissue, within acceptable margins of error.
  • neurodegeneration refers to the process of cell destruction resulting from primary destructive events such as stroke or CVA, as well as from secondary, delayed and progressive destructive mechanisms that are invoked by cells due to the occurrence of the primary destructive event.
  • Primary destructive events include disease processes or physical injury or insult, including stroke, but also include other diseases and conditions such as multiple sclerosis, amylotrophic lateral sclerosis, epilepsy, Alzheimer's disease, dementia resulting from other causes such as AIDS, cerebral ischemia including focal cerebral ischemia, and physical trauma such as crush or compression injury in the CNS, including a crush or compression injury of the brain, spinal cord, nerves or retina, or any acute injury or insult producing neurodegeneration.
  • Secondary destructive mechanisms include any mechanism that leads to the generation and release of neurotoxic molecules, including apoptosis, depletion of cellular energy stores because of changes in mitochondrial membrane permeability, release or failure in the reuptake of excessive glutamate, reperfusion injury, and activity of cytokines and inflammation. Both primary and secondary mechanisms contribute to forming a “zone of danger” for neurons, wherein the neurons in the zone have at least temporarily survived the primary destructive event, but are at risk of dying due to processes having delayed effect.
  • neurodegeneration refers to a therapeutic strategy for slowing or preventing the otherwise irreversible loss of neurons due to neurodegeneration after a primary destructive event, whether the neurodegeneration loss is due to disease mechanisms associated with the primary destructive event or secondary destructive mechanisms.
  • neuroprotective-effective refers to a characteristic of an amount of light energy, wherein the amount is a power density of the light energy measured in mW/cm 2 .
  • a neuroprotective-effective amount of light energy achieves the goal of preventing, avoiding, reducing, or eliminating neurodegeneration.
  • a method for the treatment of stroke in a patient in need of such treatment involves delivering a neuroprotective-effective amount of light energy having a wavelength in the visible to near-infrared wavelength range to a target area of the patient's brain 20 .
  • the target area of the patient's brain 20 includes the area of infarct, i.e. to neurons within the “zone of danger.”
  • the target area includes portions of the brain 20 not within the zone of danger.
  • delivering the neuroprotective amount of light energy includes selecting a surface power density of the light energy at the scalp 30 corresponding to the predetermined power density at the target area of the brain 20 .
  • a surface power density of the light energy at the scalp 30 corresponding to the predetermined power density at the target area of the brain 20 .
  • light propagating through tissue is scattered and absorbed by the tissue.
  • Calculations of the power density to be applied to the scalp 30 so as to deliver a predetermined power density to the selected target area of the brain 20 preferably take into account the attenuation of the light energy as it propagates through the skin and other tissues, such as bone and brain tissue.
  • Factors known to affect the attenuation of light propagating to the brain 20 from the scalp 30 include, but are not limited to, skin pigmentation, the presence and color of hair over the area to be treated, amount of fat tissue, the presence of bruised tissue, skull thickness, and the location of the target area of the brain 20 , particularly the depth of the area relative to the surface of the scalp 30 .
  • phototherapy may utilize an applied power density of 500 mW/cm 2 .
  • treating a patient suffering from the effects of stroke comprises placing the therapy apparatus 10 in contact with the scalp 30 and adjacent the target area of the patient's brain 20 .
  • the target area of the patient's brain 20 can be previously identified such as by using standard medical imaging techniques.
  • treatment further includes calculating a surface power density at the scalp 30 which corresponds to a preselected power density at the target area of the patient's brain 20 .
  • the calculation of certain embodiments includes factors that affect the penetration of the light energy and thus the power density at the target area. These factors include, but are not limited to, the thickness of the patient's skull, type of hair and hair coloration, skin coloration and pigmentation, patient's age, patient's gender, and the distance to the target area within the brain 20 .
  • the power density and other parameters of the applied light are then adjusted according to the results of the calculation.
  • the power density selected to be applied to the target area of the patient's brain 20 depends on a number of factors, including, but not limited to, the wavelength of the applied light, the type of CVA (ischemic or hemorrhagic), and the patient's clinical condition, including the extent of the affected brain area.
  • the power density of light energy to be delivered to the target area of the patient's brain 20 may also be adjusted to be combined with any other therapeutic agent or agents, especially pharmaceutical neuroprotective agents, to achieve the desired biological effect.
  • the selected power density can also depend on the additional therapeutic agent or agents chosen.
  • the treatment proceeds continuously for a period of about 10 seconds to about 2 hours, more preferably for a period of about 1 to about 10 minutes, and most preferably for a period of about 1 to 5 minutes.
  • the light energy is preferably delivered for at least one treatment period of at least about five minutes, and more preferably for at least one treatment period of at least ten minutes.
  • the light energy can be pulsed during the treatment period or the light energy can be continuously applied during the treatment period.
  • the treatment may be terminated after one treatment period, while in other embodiments, the treatment may be repeated for at least two treatment periods.
  • the time between subsequent treatment periods is preferably at least about five minutes, more preferably at least about 1 to 2 days, and most preferably at least about one week.
  • the apparatus 10 is wearable over multiple concurrent days (e.g., embodiments of FIGS. 1, 3 , 9 A, 10 , and 13 ).
  • the length of treatment time and frequency of treatment periods can depend on several factors, including the functional recovery of the patient and the results of imaging analysis of the infarct.
  • one or more treatment parameters can be adjusted in response to a feedback signal from a device (e.g., magnetic resonance imaging) monitoring the patient.
  • the light energy may be continuously provided, or it may be pulsed. If the light is pulsed, the pulses are preferably at least about 10 nanosecond long and occur at a frequency of up to about 100 kHz. Continuous wave light may also be used.
  • thrombolytic therapies currently in use for treatment of stroke are typically begun within a few hours of the stroke. However, many hours often pass before a person who has suffered a stroke receives medical treatment, so the short time limit for initiating thrombolytic therapy excludes many patients from treatment.
  • phototherapy treatment of stroke appears to be more effective if treatment begins no earlier than several hours after the ischemic event has occurred. Consequently, the present methods of phototherapy may be used to treat a greater percentage of stroke patients.
  • a method provides a neuroprotective effect in a patient that had an ischemic event in the brain.
  • the method comprises identifying a patient who has experienced an ischemic event in the brain.
  • the method further comprises estimating the time of the ischemic event.
  • the method further comprises commencing administration of a neuroprotective effective amount of light energy to the brain.
  • the administration of the light energy is commenced no less than about two hours following the time of the ischemic event.
  • phototherapy treatment can be efficaciously performed preferably within 24 hours after the ischemic event occurs, and more preferably no earlier than two hours following the ischemic event, still more preferably no earlier than three hours following the ischemic event, and most preferably no earlier than five hours following the ischemic event.
  • one or more of the treatment parameters can be varied depending on the amount of time that has elapsed since the ischemic event.
  • the phototherapy for the treatment of stroke occurs preferably about 6 to 24 hours after the onset of stroke symptoms, more preferably about 12 to 24 hours after the onset of symptoms. It is believed, however, that if treatment begins after about 2 days, its effectiveness will be greatly reduced.
  • NHNP Normal Human Neural Progenitor
  • a Photo Dosing Assembly was used to provide precisely metered doses of laser light to the NHNP cells in the 96 well plates.
  • the PDA included a Nikon Diaphot inverted microscope (Nikon of Melville, N.Y.) with a LUDL motorized x,y,z stage (Ludl Electronic Products of Hawthorne, N.Y.).
  • An 808 nanometer laser was routed into the rear epi-fluorescent port on the microscope using a custom designed adapter and a fiber optic cable. Diffusing lenses were mounted in the path of the beam to create a “speckled” pattern, which was intended to mimic in vivo conditions after a laser beam passed through human skin.
  • the CellTiter-Glo reagent is added in an amount equal to the volume of media in the well and results in cell lysis followed by a sustained luminescent reaction that was measured using a Reporter luminometer (Turner Biosystems of Sunnyvale, Calif.). Amounts of ATP present in the NHNP cells were quantified in Relative Luminescent Units (RLUs) by the luminometer.
  • RLUs Relative Luminescent Units
  • the two metrics described above, (RLUs and % Reduction) were then used to compare NHNP culture wells that had been lased with 50 mW/cm 2 at a wavelength of 808 nanometers.
  • RLUs and % Reduction were then used to compare NHNP culture wells that had been lased with 50 mW/cm 2 at a wavelength of 808 nanometers.
  • 20 wells were lased for 1 second and compared to an unlased control group of 20 wells.
  • the CellTiter-Glo reagent was added 10 minutes after lasing completed and the plate was read after the cells had lysed and the luciferase reaction had stabilized.
  • the average RLUs measured for the control wells was 3808 ⁇ 3394 while the laser group showed a two-fold increase in ATP content to 7513 ⁇ 6109.
  • the alamarBlue assay was performed with a higher cell density and a lasing time of 5 seconds.
  • the plating density (calculated to be between 7,500-26,000 cells per well based on the certificate of analysis provided by the manufacturer) was difficult to determine since some of the cells had remained in the spheroids and had not completely differentiated. Wells from the same plate can still be compared though, since plating conditions were identical.
  • the phototherapy is combined with other types of treatments for an improved therapeutic effect.
  • Treatment can comprise directing light through the scalp of the patient to a target area of the brain concurrently with applying an electromagnetic field to the brain.
  • the light has an efficacious power density at the target area and the electromagnetic field has an efficacious field strength.
  • the apparatus 50 can also include systems for electromagnetic treatment, e.g., as described in U.S. Pat. No. 6,042,531 issued to Holcomb, which is incorporated in its entirety by reference herein.
  • the electromagnetic field comprises a magnetic field
  • the electromagnetic field comprises a radio-frequency (RF) field.
  • RF radio-frequency
  • treatment can comprise directing an efficacious power density of light through the scalp of the patient to a target area of the brain concurrently with applying an efficacious amount of ultrasonic energy to the brain.
  • a system can include systems for ultrasonic treatment, e.g., as described in U.S. Pat. No. 5,954,470 issued to Fry et al., which is incorporated in its entirety by reference herein.

Abstract

A therapy apparatus for treating a patient's brain is provided. The therapy apparatus includes a light source having an output emission area positioned to irradiate a portion of the brain with an efficacious power density and wavelength of light. The therapy apparatus further includes an element interposed between the light source and the patient's scalp. The element is adapted to inhibit temperature increases at the scalp caused by the light.

Description

    CLAIM OF PRIORITY
  • This application is a continuation of U.S. patent application Ser. No. 10/682,379, filed Oct. 9, 2003, and which claims benefit to U.S. Provisional Application No. 60/442,693, filed Jan. 24, 2003 and U.S. Provisional Application No. 60/487,979, filed Jul. 17, 2003, and which is a continuation-in-part of U.S. patent application Ser. No. 10/287,432, filed Nov. 1, 2002, which claims benefit to U.S. Provisional Application No. 60/336,436, filed Nov. 1, 2001 and U.S. Provisional Application No. 60/369,260, filed Apr. 2, 2002. U.S. patent application Ser. No. 10/682,379 and 10/287,432 and U.S. Provisional Application Nos. 60/442,693, 60/487,979, 60/336,436, and 60/369,260 are incorporated in their entireties by reference herein.
  • BACKGROUND OF THE INVENTION
  • 1. Field of the Invention
  • The present invention relates in general to phototherapy, and more particularly, to novel apparatuses and methods for phototherapy of brain tissue affected by stroke.
  • 2. Description of the Related Art
  • Stroke, also called cerebrovascular accident (CVA), is a sudden disruption of blood flow to a discrete area of the brain that is brought on by a clot lodging in an artery supplying that area of that brain, or by a cerebral hemorrhage due to a ruptured aneurysm or a burst artery. The consequence of stroke is a loss of function in the affected brain region and concomitant loss of bodily function in areas of the body controlled by the affected brain region. Depending upon the extent and location of the primary insult in the brain, loss of function varies greatly from mild or severe, and may be temporary or permanent. Lifestyle factors such as smoking, diet, level of physical activity and high cholesterol increase the risk of stroke, and thus stroke is a major cause of human suffering in developed nations. Stroke is the third leading cause of death in most developed nations, including the United States.
  • Until recently, stroke treatment was restricted to providing basic life support at the time of the stroke, followed by rehabilitation. Recently, new drug therapies have taken the approach of breaking up blood clots or protecting surviving at-risk neurons from further damage.
  • Thrombolytic therapy includes aspirin or intravenous heparin to prevent further clot formation and to maintain blood flow after an ischemic stroke. Thrombolytic drugs include tissue plasminogen activator (TPA) and genetically engineered versions thereof, and streptokinase. However, streptokinase does not appear to improve the patient's outlook unless administered early (within three hours of stroke). TPA when administered early appears to substantially improve prognosis, but slightly increases the risk of death from hemorrhage. In addition, over half of stroke patients arrive at the hospital more than three hours after a stroke, and even if they arrive quickly, a CT scan must first confirm that the stroke is not hemorrhagic, which delays administration of the drug. Also, patients taking aspirin or other blood thinners and patients with clotting abnormalities should not be given TPA.
  • Neuroprotective drugs target surviving but endangered neurons in a zone of risk surrounding the area of primary infarct. Such drugs are aimed at slowing down or preventing the death of such neurons, to reduce the extent of brain damage. Certain neuroprotective drugs are anti-excitotoxic, i.e., work to block the excitotoxic effects of excitatory amino acids such as glutamate that cause cell membrane damage under certain conditions. Other drugs such as citicoline work by repairing damaged cell membranes. Lazaroids such as Tirilazed (Freedox) counteract oxidative stress produced by oxygen-free radicals produced during stroke. Other drugs for stroke treatment include agents that block the enzyme known as PARP, and calcium-channel blockers such as nimodipine (Nimotop) that relax the blood vessels to prevent vascular spasms that further limit blood supply. However, the effect of nimodipine is reduced if administered beyond six hours after a stroke and it is not useful for ischemic stroke. In addition, drug therapy includes the risk of adverse side effects and immune responses.
  • Surgical treatment for stroke includes carotid endarterectomy, which appears to be especially effective for reducing the risk of stroke recurrence for patients exhibiting arterial narrowing of more than 70%. However, endarterectomy is highly invasive, and risk of stroke recurrence increases temporarily after surgery. Experimental stroke therapies include an angiography-type or angioplasty-type procedure using a thin catheter to remove or reduce the blockage from a clot. However, such procedures have extremely limited availability and increase the risk of embolic stroke. Other surgical interventions, such as those to repair an aneurysm before rupture remain controversial because of disagreement over the relative risks of surgery versus leaving the aneurysm untreated.
  • Against this background, a high level of interest remains in finding new and improved therapeutic apparatuses and methods for the treatment of stroke. In particular, a need remains for relatively inexpensive and non-invasive approaches to treating stroke that also avoid the limitations of drug therapy.
  • SUMMARY OF THE INVENTION
  • One aspect of the present invention provides a therapy apparatus for treating a patient's brain. The therapy apparatus comprises a light source having an output emission area positioned to irradiate a portion of the brain with an efficacious power density and wavelength of light. The therapy apparatus further comprises an element interposed between the light source and the patient's scalp. The element is adapted to inhibit temperature increases at the scalp caused by the light.
  • Another aspect of the present invention provides a therapy apparatus for treating brain tissue. The therapy apparatus comprises a light source positioned to irradiate at least a portion of a patient's head with light. The light has a wavelength and power density which penetrates the cranium to deliver an efficacious amount of light to brain tissue. The therapy apparatus further comprises a material which inhibits temperature increases of the head.
  • Another aspect of the present invention provides a therapy apparatus for treating a patient's brain. The therapy apparatus comprises a light source adapted to irradiate at least a portion of the brain with an efficacious power density and wavelength of light. The therapy apparatus further comprises an element adapted to inhibit temperature increases at the scalp. At least a portion of the element is in an optical path of the light from the light source to the scalp.
  • Another aspect of the present invention provides a therapy apparatus for treating a patient's brain. The therapy apparatus comprises a light source adapted to irradiate at least a portion of the brain with an efficacious power density and wavelength of light. The therapy apparatus further comprises a controller for energizing said light source so as to selectively produce a plurality of different irradiation patterns on the patient's scalp. Each of said irradiation patterns is comprised of at least one illumination area that is small compared to the patient's scalp, and at least one non-illuminated area.
  • Another aspect of the present invention provides a method comprising interposing a head element between a light source and the patient's scalp. The element is comprised of a material which, for an efficacious power density at the brain, inhibits temperature increases at the scalp.
  • Another aspect of the present invention provides a therapy apparatus for treating a patient's brain. The therapy apparatus comprises a light source adapted to irradiate at least a portion of the brain with an efficacious power density and wavelength of light. The therapy apparatus further comprises a biomedical sensor configured to provide real-time feedback information. The therapy apparatus further comprises a controller coupled to the light source and the biomedical sensor. The controller is configured to adjust said light source in response to the real-time feedback information.
  • Another aspect of the present invention provides a method of treating brain tissue. The method comprises introducing light of an efficacious power density onto brain tissue by directing light through the scalp of a patient. Directing the light comprises providing a sufficiently large spot size on said scalp to reduce the power density at the scalp below the damage threshold of scalp tissue, while producing sufficient optical power at said scalp to achieve said efficacious power density at said brain tissue.
  • Another aspect of the present invention provides a method of treating a patient's brain. The method comprises covering at least a significant portion of the patient's scalp with a light-emitting blanket.
  • Another aspect of the present invention provides a method of treating a patient's brain following a stroke. The method comprises applying low-level light therapy to the brain no earlier than several hours following said stroke.
  • Another aspect of the present invention provides a method for treating a patient's brain. The method comprises introducing light of an efficacious power density onto a target area of the brain by directing light through the scalp of the patient. The light has a plurality of wavelengths and the efficacious power density is at least 0.01 mW/cm2 at the target area.
  • Another aspect of the present invention provides a method for treating a patient's brain. The method comprises directing light through the scalp of the patient to a target area of the brain concurrently with applying an electromagnetic field to the brain. The light has an efficacious power density at the target area and the electromagnetic field has an efficacious field strength.
  • Another aspect of the present invention provides a method for treating a patient's brain. The method comprises directing an efficacious power density of light through the scalp of the patient to a target area of the brain concurrently with applying an efficacious amount of ultrasonic energy to the brain.
  • Anther aspect of the present invention provides a method of providing a neuroprotective effect in a patient that had an ischemic event in the brain. The method comprises identifying a patient who has experienced an ischemic event in the brain. The method further comprises estimating the time of the ischemic event. The method further comprising commencing administration of a neuroprotective effective amount of light energy to the brain no less than about two hours following the time of the ischemic event.
  • For purposes of summarizing the present invention, certain aspects, advantages, and novel features of the present invention have been described herein above. It is to be understood, however, that not necessarily all such advantages may be achieved in accordance with any particular embodiment of the present invention. Thus, the present invention may be embodied or carried out in a manner that achieves or optimizes one advantage or group of advantages as taught herein without necessarily achieving other advantages as may be taught or suggested herein.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • FIG. 1 schematically illustrates a therapy apparatus comprising a cap which fits securely over the patient's head.
  • FIG. 2 schematically illustrates a fragmentary cross-sectional view taken along the lines 2-2 of FIG. 1, showing one embodiment of a portion of a therapy apparatus comprising an element and its relationship to the scalp and brain.
  • FIG. 3 schematically illustrates an embodiment with an element comprising a container coupled to an inlet conduit and an outlet conduit for the transport of a flowing material through the element.
  • FIG. 4A schematically illustrates a fragmentary cross-sectional view taken along the lines 2-2 of FIG. 1, showing another embodiment of a portion of a therapy apparatus comprising an element with a portion contacting the scalp and a portion spaced away from the scalp.
  • FIG. 4B schematically illustrates a fragmentary cross-sectional view taken along the lines 2-2 of FIG. 1, showing an embodiment of a portion of a therapy apparatus comprising a plurality of light sources and an element with portions contacting the scalp and portions spaced away from the scalp.
  • FIGS. 5A and 5B schematically illustrate cross-sectional views of two embodiments of the element in accordance with FIG. 4B taken along the line 4-4.
  • FIGS. 6A-6C schematically illustrate an embodiment in which the light sources are spaced away from the scalp.
  • FIGS. 7A and 7B schematically illustrate the diffusive effect on the light by the element.
  • FIGS. 8A and 8B schematically illustrate two light beams having different cross-sections impinging a patient's scalp and propagating through the patient's head to irradiate a portion of the patient's brain tissue.
  • FIG. 9A schematically illustrates a therapy apparatus comprising a cap and a light source comprising a light blanket.
  • FIGS. 9B and 9C schematically illustrate two embodiments of the light blanket.
  • FIG. 10 schematically illustrates a therapy apparatus comprising a flexible strap and a housing.
  • FIG. 11 schematically illustrates a therapy apparatus comprising a handheld probe.
  • FIG. 12 is a block diagram of a control circuit comprising a programmable controller.
  • FIG. 13 schematically illustrates a therapy apparatus comprising a light source and a controller.
  • FIG. 14 schematically illustrates a light source comprising a laser diode and a galvometer with a mirror and a plurality of motors.
  • FIGS. 15A and 15B schematically illustrate two irradiation patterns that are spatially shifted relative to each other.
  • DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
  • Low level light therapy (“LLLT”) or phototherapy involves therapeutic administration of light energy to a patient at lower power outputs than those used for cutting, cauterizing, or ablating biological tissue, resulting in desirable biostimulatory effects while leaving tissue undamaged. In non-invasive phototherapy, it is desirable to apply an efficacious amount of light energy to the internal tissue to be treated using light sources positioned outside the body. (See, e.g., U.S. Pat. No. 6,537,304 to Oron and U.S. patent application Ser. No. 10/353,130, both of which are incorporated in their entireties by reference herein.) However, absorption of the light energy by intervening tissue can limit the amount of light energy delivered to the target tissue site, while heating the intervening tissue. In addition, scattering of the light energy by intervening tissue can limit the power density or energy density delivered to the target tissue site. Brute force attempts to circumvent these effects by increasing the power and/or power density applied to the outside surface of the body can result in damage (e.g., burning) of the intervening tissue.
  • Non-invasive phototherapy methods are circumscribed by setting selected treatment parameters within specified limits so as to preferably avoid damaging the intervening tissue. A review of the existing scientific literature in this field would cast doubt on whether a set of undamaging, yet efficacious, parameters could be found. However, certain embodiments, as described herein, provide devices and methods which can achieve this goal.
  • Such embodiments may include selecting a wavelength of light at which the absorption by intervening tissue is below a damaging level. Such embodiments may also include setting the power output of the light source at very low, yet efficacious, power densities (e.g., between approximately 100 μW/cm2 to approximately 10 W/cm2) at the target tissue site, and time periods of application of the light energy at a few seconds to minutes to achieve an efficacious energy density at the target tissue site being treated. Other parameters can also be varied in the use of phototherapy. These other parameters contribute to the light energy that is actually delivered to the treated tissue and may play key roles in the efficacy of phototherapy. In certain embodiments, the irradiated portion of the brain can comprise the entire brain.
  • Element to Inhibit Temperature Increases at the Scalp
  • FIGS. 1 and 2 schematically illustrate an embodiment of a therapy apparatus 10 for treating a patient's brain 20. The therapy apparatus 10 comprises a light source 40 having an output emission area 41 positioned to irradiate a portion of the brain 20 with an efficacious power density and wavelength of light. The therapy apparatus 10 further comprises an element 50 interposed between the light source 40 and the patient's scalp 30. The element 50 is adapted to inhibit temperature increases at the scalp 30 caused by the light.
  • As used herein, the term “element” is used in its broadest sense, including, but not limited to, as a reference to a constituent or distinct part of a composite device. In certain embodiments, the element 50 is adapted to contact at least a portion of the patient's scalp 30, as schematically illustrated in FIGS. 1-4. In certain such embodiments, the element 50 is in thermal communication with and covers at least a portion of the scalp 30. In other embodiment, the element 50 is spaced away from the scalp 30 and does not contact the scalp 30.
  • In certain embodiments, the light passes through the element 50 prior to reaching the scalp 30 such that the element 50 is in the optical path of light propagating from the light source 40, through the scalp 30, through the bones, tissues, and fluids of the head (schematically illustrated in FIG. 1 by the region 22), to the brain 20. In certain embodiments, the light passes through a transmissive medium of the element 50, while in other embodiments, the light passes through an aperture of the element 50. As described more fully below, the element 50 may be utilized with various embodiments of the therapy apparatus 10.
  • In certain embodiments, the light source 40 is disposed on the interior surface of a cap 60 which fits securely over the patient's head. The cap 60 provides structural integrity for the therapy apparatus 10 and holds the light source 40 and element 50 in place. Exemplary materials for the cap 60 include, but are not limited to, metal, plastic, or other materials with appropriate structural integrity. The cap 60 may include an inner lining 62 comprising a stretchable fabric or mesh material, such as Lycra or nylon. In certain embodiments, the light source 40 is adapted to be removably attached to the cap 60 in a plurality of positions so that the output emission area 41 of the light source 40 can be advantageously placed in a selected position for treatment of a stroke or CVA in any portion of the brain 20. In other embodiments, the light source 40 can be an integral portion of the cap 60.
  • The light source 40 illustrated by FIGS. 1 and 2 comprises at least one power conduit 64 coupled to a power source (not shown). In some embodiments, the power conduit 64 comprises an electrical conduit which is adapted to transmit electrical signals and power to an emitter (e.g., laser diode or light-emitting diode). In certain embodiments, the power conduit 64 comprises an optical conduit (e.g., optical waveguide) which transmits optical signals and power to the output emission area 41 of the light source 40. In certain such embodiments, the light source 40 comprises optical elements (e.g., lenses, diffusers, and/or waveguides) which transmit at least a portion of the optical power received via the optical conduit 64. In still other embodiments, the therapy apparatus 10 contains a power source (e.g., a battery) and the power conduit 64 is substantially internal to the therapy apparatus 10.
  • In certain embodiments, the patient's scalp 30 comprises hair and skin which cover the patient's skull. In other embodiments, at least a portion of the hair is removed prior to the phototherapy treatment, so that the therapy apparatus 10 substantially contacts the skin of the scalp 30.
  • In certain embodiments, the element 50 is adapted to contact the patient's scalp 30, thereby providing an interface between the therapy apparatus 10 and the patient's scalp 30. In certain such embodiments, the element 50 is coupled to the light source 40 and in other such embodiments, the element is also adapted to conform to the scalp 30, as schematically illustrated in FIG. 1. In this way, the element 50 positions the output emission area 41 of the light source 40 relative to the scalp 30. In certain such embodiments, the element 50 is mechanically adjustable so as to adjust the position of the light source 40 relative to the scalp 30. By fitting to the scalp 30 and holding the light source 40 in place, the element 50 inhibits temperature increases at the scalp 30 that would otherwise result from misplacement of the light source 40 relative to the scalp 30. In addition, in certain embodiments, the element 50 is mechanically adjustable so as to fit the therapy apparatus 10 to the patient's scalp 30.
  • In certain embodiments, the element 50 provides a reusable interface between the therapy apparatus 10 and the patient's scalp 30. In such embodiments, the element 50 can be cleaned or sterilized between uses of the therapy apparatus, particularly between uses by different patients. In other embodiments, the element 50 provides a disposable and replaceable interface between the therapy apparatus 10 and the patient's scalp 30. By using pre-sterilized and pre-packaged replaceable interfaces, certain embodiments can advantageously provide sterilized interfaces without undergoing cleaning or sterilization processing immediately before use.
  • In certain embodiments, the element 50 comprises a container (e.g., a cavity or bag) containing a material (e.g., gel). The container can be flexible and adapted to conform to the contours of the scalp 30. Other exemplary materials contained in the container of the element 50 include, but are not limited to, thermal exchange materials such as glycerol and water. The element 50 of certain embodiments substantially covers the entire scalp 30 of the patient, as schematically illustrated in FIG. 2. In other embodiments, the element 50 only covers a localized portion of the scalp 30 in proximity to the irradiated portion of the scalp 30.
  • In certain embodiments, at least a portion of the element 50 is within an optical path of the light from the light source 40 to the scalp 30. In such embodiments, the element 50 is substantially optically transmissive at a wavelength of the light emitted by the output emission area 41 of the light source 40 and is adapted to reduce back reflections of the light. By reducing back reflections, the element 50 increases the amount of light transmitted to the brain 20 and reduces the need to use a higher power light source 40 which may otherwise create temperature increases at the scalp 30. In certain such embodiments, the element 50 comprises one or more optical coatings, films, layers, membranes, etc. in the optical path of the transmitted light which are adapted to reduce back reflections.
  • In certain such embodiments, the element 50 reduces back reflections by fitting to the scalp 30 so as to substantially reduce air gaps between the scalp 30 and the element 50 in the optical path of the light. The refractive-index mismatches between such an air gap and the element 50 and/or the scalp 30 would otherwise result in at least a portion of the light propagating from the light source 40 to the brain 20 to be reflected back towards the light source 40.
  • In addition, certain embodiments of the element 50 comprise a material having, at a wavelength of light emitted by the light source 40, a refractive index which substantially matches the refractive index of the scalp 30 (e.g., about 1.3), thereby reducing any index-mismatch-generated back reflections between the element 50 and the scalp 30. Examples of materials with refractive indices compatible with embodiments described herein include, but are not limited to, glycerol, water, and silica gels. Exemplary index-matching gels include, but are not limited to, those available from Nye Lubricants, Inc. of Fairhaven, Mass.
  • In certain embodiments, the element 50 is adapted to cool the scalp 30 by removing heat from the scalp 30 so as to inhibit temperature increases at the scalp 30. In certain such embodiments, the element 50 comprises a reservoir (e.g., a chamber or a conduit) adapted to contain a coolant. The coolant flows through the reservoir near the scalp 30. The scalp 30 heats the coolant, which flows away from the scalp 30, thereby removing heat from the scalp 30 by active cooling. The coolant in certain embodiments circulates between the element 50 and a heat transfer device, such as a chiller, whereby the coolant is heated by the scalp 30 and is cooled by the heat transfer device. Exemplary materials for the coolant include, but are not limited to, water or air.
  • In certain embodiments, the element 50 comprises a container 51 (e.g., a flexible bag) coupled to an inlet conduit 52 and an outlet conduit 53, as schematically illustrated in FIG. 3. A flowing material (e.g., water, air, or glycerol) can flow into the container 51 from the inlet conduit 52, absorb heat from the scalp 30, and flow out of the container 51 through the outlet conduit 53. Certain such embodiments can provide a mechanical fit of the container 51 to the scalp 30 and sufficient thermal coupling to prevent excessive heating of the scalp 30 by the light. In certain embodiments, the container 51 can be disposable and replacement containers 51 can be used for subsequent patients.
  • In still other embodiments, the element 50 comprises a container (e.g., a flexible bag) containing a material which does not flow out of the container but is thermally coupled to the scalp 30 so as to remove heat from the scalp 30 by passive cooling. Exemplary materials include, but are not limited to, water, glycerol, and gel. In certain such embodiments, the non-flowing material can be pre-cooled (e.g., by placement in a refrigerator) prior to the phototherapy treatment to facilitate cooling of the scalp 30.
  • In certain embodiments, the element 50 is adapted to apply pressure to at least a portion of the scalp 30. By applying sufficient pressure, the element 50 can blanch the portion of the scalp 30 by forcing at least some blood out the optical path of the light energy. The blood removal resulting from the pressure applied by the element 50 to the scalp 30 decreases the corresponding absorption of the light energy by blood in the scalp 30. As a result, temperature increases due to absorption of the light energy by blood at the scalp 30 are reduced. As a further result, the fraction of the light energy transmitted to the subdermal target tissue of the brain 20 is increased.
  • FIGS. 4A and 4B schematically illustrate embodiments of the element 50 adapted to facilitate the blanching of the scalp 30. In the cross-sectional view of a portion of the therapy apparatus 10 schematically illustrated in FIG. 4A, certain element portions 72 contact the patient's scalp 30 and other element portions 74 are spaced away from the scalp 30. The element portions 72 contacting the scalp 30 provide an optical path for light to propagate from the light source 40 to the scalp 30. The element portions 72 contacting the scalp 30 also apply pressure to the scalp 30, thereby forcing blood out from beneath the element portion 72. FIG. 4B schematically illustrates a similar view of an embodiment in which the light source 40 comprises a plurality of light sources 40 a, 40 b, 40 c.
  • FIG. 5A schematically illustrates one embodiment of the cross-section along the line 4-4 of FIG. 4B. The element portions 72 contacting the scalp 30 comprise ridges extending along one direction, and the element portions 74 spaced away from the scalp 30 comprise troughs extending along the same direction. In certain embodiments, the ridges are substantially parallel to one another and the troughs are substantially parallel to one another. FIG. 5B schematically illustrates another embodiment of the cross-section along the line 4-4 of FIG. 4B. The element portions 72 contacting the scalp 30 comprise a plurality of projections in the form of a grid or array. More specifically, the portions 72 are rectangular and are separated by element portions 74 spaced away from the scalp 30, which form troughs extending in two substantially perpendicular directions. The portions 72 of the element 50 contacting the scalp 30 can be a substantial fraction of the total area of the element 50 or of the scalp 30.
  • FIGS. 6A-6C schematically illustrate an embodiment in which the light sources 40 are spaced away from the scalp 30. In certain such embodiments, the light emitted by the light sources 40 propagates from the light sources 40 through the scalp 30 to the brain 20 and disperses in a direction generally parallel to the scalp 30, as shown in FIG. 6A. The light sources 40 are preferably spaced sufficiently far apart from one another such that the light emitted from each light source 40 overlaps with the light emitted from the neighboring light sources 40 at the brain 20. FIG. 6B schematically illustrates this overlap as the overlap of circular spots 42 at a reference depth at or below the surface of the brain 20. FIG. 6C schematically illustrates this overlap as a graph of the power density at the reference depth of the brain 20 along the line L-L of FIGS. 6A and 6B. Summing the power densities from the neighboring light sources 40 (shown as a dashed line in FIG. 6C) serves to provide a more uniform light distribution at the tissue to be treated. In such embodiments, the summed power density is preferably less than a damage threshold of the brain 20 and above an efficacy threshold.
  • In certain embodiments, the element 50 is adapted to diffuse the light prior to reaching the scalp 30. FIGS. 7A and 7B schematically illustrate the diffusive effect on the light by the element 50. An exemplary energy density profile of the light emitted by a light source 40, as illustrated by FIG. 7A, is peaked at a particular emission angle. After being diffused by the element 50, as illustrated by FIG. 7B, the energy density profile of the light does not have a substantial peak at any particular emission angle, but is substantially evenly distributed among a range of emission angles. By diffusing the light emitted by the light source 40, the element 50 distributes the light energy substantially evenly over the area to be illuminated, thereby inhibiting “hot spots” which would otherwise create temperature increases at the scalp 30. In addition, by diffusing the light prior to its reaching the scalp 30, the element 50 can effectively increase the spot size of the light impinging the scalp 30, thereby advantageously lowering the power density at the scalp 30, as described more fully below. In addition, in embodiments with multiple light sources 40, the element 50 can diffuse the light to alter the total light output distribution to reduce inhomogeneities.
  • In certain embodiments, the element 50 provides sufficient diffusion of the light such that the power density of the light is less than a maximum tolerable level of the scalp 30 and brain 20. In certain other embodiments, the element 50 provides sufficient diffusion of the light such that the power density of the light equals a therapeutic value at the target tissue. The element 50 can comprise exemplary diffusers including, but are not limited to, holographic diffusers such as those available from Physical Optics Corp. of Torrance, Calif. and Display Optics P/N SN1333 from Reflexite Corp. of Avon, Conn.
  • Power Density
  • Phototherapy for the treatment of stroke is based in part on the discovery that power density (i.e., power per unit area or number of photons per unit area per unit time) and energy density (i.e., energy per unit area or number of photons per unit area) of the light energy applied to tissue appear to be significant factors in determining the relative efficacy of low level phototherapy. This discovery is particularly applicable with respect to treating and saving surviving but endangered neurons in a zone of danger surrounding the primary infarct after a stroke or cerebrovascular accident (CVA). Preferred methods described herein are based at least in part on the finding that, given a selected wavelength of light energy, it is the power density and/or the energy density of the light delivered to tissue (as opposed to the total power or total energy delivered to the tissue) that appears to be important factors in determining the relative efficacy of phototherapy.
  • Without being bound by theory, it is believed that light energy delivered within a certain range of power densities and energy densities provides the desired biostimulative effect on the intracellular environment, such that proper function is returned to previously nonfunctioning or poorly functioning mitochondria in at-risk neurons. The biostimulative effect may include interactions with chromophores within the target tissue, which facilitate production of ATP thereby feeding energy to injured cells which have experienced decreased blood flow due to the stroke. Because strokes correspond to blockages or other interruptions of blood flow to portions of the brain, it is thought that any effects of increasing blood flow by phototherapy are of less importance in the efficacy of phototherapy for stroke victims. Further information regarding the role of power density and exposure time is described by Hans H. F. I. van Breugel and P. R. Dop Bär in “Power Density and Exposure Time of He—Ne Laser Irradiation Are More Important Than Total Energy Dose in Photo-Biomodulation of Human Fibroblasts In Vitro,” Lasers in Surgery and Medicine, Volume 12, pp. 528-537 (1992), which is incorporated in its entirety by reference herein.
  • The significance of the power density used in phototherapy has ramifications with regard to the devices and methods used in phototherapy of brain tissue, as schematically illustrated by FIGS. 8A and 8B, which show the effects of scattering by intervening tissue. Further information regarding the scattering of light by tissue is provided by V. Tuchin in “Tissue Optics: Light Scattering Methods and Instruments for Medical Diagnosis,” SPIE Press (2000), Bellingham, Wash., pp. 3-11, which is incorporated in its entirety by reference herein.
  • FIG. 8A schematically illustrates a light beam 80 impinging a portion 90 of a patient's scalp 30 and propagating through the patient's head to irradiate a portion 100 of the patient's brain tissue 20. In the exemplary embodiment of FIG. 8A, the light beam 80 impinging the scalp 30 is collimated and has a circular cross-section with a radius of 2 cm and a cross-sectional area of approximately 12.5 cm2. For comparison purposes, FIG. 8B schematically illustrates a light beam 82 having a significantly smaller cross-section impinging a smaller portion 92 of the scalp 30 to irradiate a portion 102 of the brain tissue 20. The light beam 82 impinging the scalp 30 in FIG. 8B is collimated and has a circular cross-section with a radius of 1 cm and a cross-sectional area of approximately 3.1 cm2. The collimations, cross-sections, and radii of the light beams 80, 82 illustrated in FIGS. 8A and 8B are exemplary; other light beams with other parameters are also compatible with embodiments described herein. In particular, similar considerations apply to focussed beams or diverging beams, as they are similarly scattered by the intervening tissue.
  • As shown in FIGS. 8A and 8B, the cross-sections of the light beams 80, 82 become larger while propagating through the head due to scattering from interactions with tissue of the head. Assuming that the angle of dispersion is 15 degrees and the irradiated brain tissue 20 is 2.5 cm below the scalp 30, the resulting area of the portion 100 of brain tissue 20 irradiated by the light beam 80 in FIG. 8A is approximately 22.4 cm2. Similarly, the resulting area of the portion 102 of brain tissue 20 irradiated by the light beam 82 in FIG. 8B is approximately 8.8 cm2.
  • Irradiating the portion 100 of the brain tissue 20 with a power density of 10 mW/cm2 corresponds to a total power within the portion 100 of approximately 224 mW (10 mW/cm2×22.4 cm2). Assuming only approximately 5% of the light beam 80 is transmitted between the scalp 30 and the brain tissue 20, the incident light beam 80 at the scalp 30 will have a total power of approximately 4480 mW (224 mW/0.05) and a power density of approximately 358 mW/cm2 (4480 mW/12.5 cm2). Similarly, irradiating the portion 102 of the brain tissue 20 with a power density of 10 mW/cm2 corresponds to a total power within the portion 102 of approximately 88 mW (10 mW/cm2×8.8 cm2), and with the same 5% transmittance, the incident light beam 82 at the scalp 30 will have a total power of approximately 1760 mW (88 mW/0.05) and a power density of approximately 568 mW/cm2 (1760 mW/3.1 cm2). These calculations are summarized in Table 1.
    TABLE 1
    2 cm Spot Size 1 cm Spot Size
    (FIG. 8A) (FIG. 8B)
    Scalp:
    Area 12.5 cm2 3.1 cm2
    Total power 4480 mW 1760 mW
    Power density 358 mW/cm2 568 mW/cm2
    Brain:
    Area 22.4 cm2 8.8 cm2
    Total power 224 mW 88 mW
    Power density
    10 mW/cm 2 10 mW/cm2
  • These exemplary calculations illustrate that to obtain a desired power density at the brain 20, higher total power at the scalp 30 can be used in conjunction with a larger spot size at the scalp 30. Thus, by increasing the spot size at the scalp 30, a desired power density at the brain 20 can be achieved with lower power densities at the scalp 30 which can reduce the possibility of overheating the scalp 30. In certain embodiments, the light can be directed through an aperture to define the illumination of the scalp 30 to a selected smaller area.
  • Light Source
  • The light source 40 preferably generates light in the visible to near-infrared wavelength range. In certain embodiments, the light source 40 comprises one or more laser diodes, which each provide coherent light. In embodiments in which the light from the light source 40 is coherent, the emitted light may produce “speckling” due to coherent interference of the light. This speckling comprises intensity spikes which are created by constructive interference and can occur in proximity to the target tissue being treated. For example, while the average power density may be approximately 10 mW/cm2, the power density of one such intensity spike in proximity to the brain tissue to be treated may be approximately 300 mW/cm2. In certain embodiments, this increased power density due to speckling can improve the efficacy of treatments using coherent light over those using incoherent light for illumination of deeper tissues.
  • In other embodiments, the light source 40 provides incoherent light. Exemplary light sources 40 of incoherent light include, but are not limited to, incandescent lamps or light-emitting diodes. A heat sink can be used with the light source 40 (for either coherent or incoherent sources) to remove heat from the light source 40 and to inhibit temperature increases at the scalp 30.
  • In certain embodiments, the light source 40 generates light which is substantially monochromatic (i.e., light having one wavelength, or light having a narrow band of wavelengths). So that the amount of light transmitted to the brain is maximized, the wavelength of the light is selected in certain embodiments to be at or near a transmission peak (or at or near an absorption minimum) for the intervening tissue. In certain such embodiments, the wavelength corresponds to a peak in the transmission spectrum of tissue at about 820 nanometers. In other embodiments, the wavelength of the light is preferably between about 630 nanometers and about 1064 nanometers, more preferably between about 780 nanometers and about 840, nanometers, and most preferably includes wavelengths of about 790, 800, 810, 820, or 830 nanometers. It has also been found that an intermediate wavelength of about 739 nanometers appears to be suitable for penetrating the skull, although other wavelengths are also suitable and may be used.
  • In other embodiments, the light source 40 generates light having a plurality of wavelengths. In certain such embodiments, each wavelength is selected so as to work with one or more chromophores within the target tissue. Without being bound by theory, it is believed that irradiation of chromophores increases the production of ATP in the target tissue, thereby producing beneficial effects. In certain embodiments, the light source 40 is adapted to generate light having a first wavelength concurrently with light having a second wavelength. In certain other embodiments, the light source 40 is adapted to generate light having a first wavelength sequentially with light having a second wavelength.
  • In certain embodiments, the light source 40 includes at least one continuously emitting GaAlAs laser diode having a wavelength of about 830 nanometers. In another embodiment, the light source 40 comprises a laser source having a wavelength of about 808 nanometers. In still other embodiments, the light source 40 includes at least one vertical cavity surface-emitting laser (VCSEL) diode. Other light sources 40 compatible with embodiments described herein include, but are not limited to, light-emitting diodes (LEDs) and filtered lamps.
  • The light source 40 is capable of emitting light energy at a power sufficient to achieve a predetermined power density at the subdermal target tissue (e.g., at a depth of approximately 2 centimeters from the dura). It is presently believed that phototherapy of tissue is most effective when irradiating the target tissue with power densities of light of at least about 0.01 mW/cm2 and up to about 1 W/cm2. In various embodiments, the subsurface power density is at least about 0.01, 0.05, 0.1, 0.5, 1, 5, 10, 15, 20, 30, 40, 50, 60, 70, 80, or 90 mW/cm2, respectively, depending on the desired clinical performance. In certain embodiments, the subsurface power density is preferably about 0.01 mW/cm2 to about 100 mW/cm2, more preferably about 0.01 mW/cm2 to about 50 mW/cm2, and most preferably about 2 mW/cm2 to about 20 mW/cm2. It is believed that these subsurface power densities are especially effective at producing the desired biostimulative effects on the tissue being treated.
  • Taking into account the attenuation of energy as it propagates from the skin surface, through body tissue, bone, and fluids, to the subdermal target tissue, surface power densities preferably between about 10 mW/cm2 to about 10 W/cm2, or more preferably between about 100 mW/cm2 to about 500 mW/cm2, will typically be used to attain the selected power densities at the subdermal target tissue. To achieve such surface power densities, the light source 40 is preferably capable of emitting light energy having a total power output of at least about 25 mW to about 100 W. In various embodiments, the total power output is limited to be no more than about 30, 50, 75, 100, 150, 200, 250, 300, 400, or 500 mW, respectively. In certain embodiments, the light source 40 comprises a plurality of sources used in combination to provide the total power output. The actual power output of the light source 40 is preferably controllably variable. In this way, the power of the light energy emitted can be adjusted in accordance with a selected power density at the subdermal tissue being treated.
  • Certain embodiments utilize a light source 40 that includes only a single laser diode that is capable of providing about 25 mW to about 100 W of total power output at the skin surface. In certain such embodiments, the laser diode can be optically coupled to the scalp 30 via an optical fiber or can be configured to provide a sufficiently large spot size to avoid power densities which would burn or otherwise damage the scalp 30. In other embodiments, the light source 40 utilizes a plurality of sources (e.g., laser diodes) arranged in a grid or array that together are capable of providing at least about 25 mW to about 100 W of total power output at the skin surface. The light source 40 of other embodiments may also comprise sources having power capacities outside of these limits.
  • FIG. 9A schematically illustrates another embodiment of the therapy apparatus 10 which comprises the cap 60 and a light source comprising a light-emitting blanket 110. FIG. 9B schematically illustrates an embodiment of the blanket 110 comprising a flexible substrate 111 (e.g., flexible circuit board), a power conduit interface 112, and a sheet formed by optical fibers 114 positioned in a fan-like configuration. FIG. 9C schematically illustrates an embodiment of the blanket 110 comprising a flexible substrate 111, a power conduit interface 112, and a sheet formed by optical fibers 114 woven into a mesh. The blanket 110 is preferably positioned within the cap 60 so as to cover an area of the scalp 30 corresponding to a portion of the brain 20 to be treated.
  • In certain such embodiments, the power conduit interface 112 is adapted to be coupled to an optical fiber conduit 64 which provides optical power to the blanket 110. The optical power interface 112 of certain embodiments comprises a beam splitter or other optical device which distributes the incoming optical power among the various optical fibers 114. In other embodiments, the power conduit interface 112 is adapted to be coupled to an electrical conduit which provides electrical power to the blanket 110. In certain such embodiments, the power conduit interface 112 comprises one or more laser diodes, the output of which is distributed among the various optical fibers 114 of the blanket 110. In certain other embodiments, the blanket 110 comprises an electroluminescent sheet which responds to electrical signals from the power conduit interface 112 by emitting light. In such embodiments, the power conduit interface 112 comprises circuitry adapted to distribute the electrical signals to appropriate portions of the electroluminescent sheet.
  • The side of the blanket 110 nearer the scalp 30 is preferably provided with a light scattering surface, such as a roughened surface to increase the amount of light scattered out of the blanket 110 towards the scalp 30. The side of the blanket 110 further from the scalp 30 is preferably covered by a reflective coating so that light emitted away from the scalp 30 is reflected back towards the scalp 30. This configuration is similar to configurations used for the “back illumination” of liquid-crystal displays (LCDs). Other configurations of the blanket 110 are compatible with embodiments described herein.
  • In certain embodiments, the light source 40 generates light which cause eye damage if viewed by an individual. In such embodiments, the apparatus 50 can be configured to provide eye protection so as to avoid viewing of the light by individuals. For example, opaque materials can be appropriately placed to block the light from being viewed directly. In addition, interlocks can be provided so that the light source 40 is not activated unless the apparatus 50 is in place, or other appropriate safety measures are taken.
  • Light Delivery Apparatuses
  • The phototherapy methods for the treatment of stroke described herein may be practiced and described using, for example, a low level laser therapy apparatus such as that shown and described in U.S. Pat. No. 6,214,035, U.S. Pat. No. 6,267,780, U.S. Pat. No. 6,273,905 and U.S. Pat. No. 6,290,714, which are all incorporated in their entirety by reference herein, as are the references incorporated by reference therein.
  • Another suitable phototherapy apparatus in accordance with embodiments described here is illustrated in FIG. 10. The illustrated therapy apparatus 10 includes a light source 40, an element 50, and a flexible strap 120 adapted for securing the therapy apparatus 10 over an area of the patient's head. The light source 40 can be disposed on the strap 120 itself, or in a housing 122 coupled to the strap 120. The light source 40 preferably comprises a plurality of diodes 40 a, 40 b, . . . capable of emitting light energy having a wavelength in the visible to near-infrared wavelength range. The element 50 is adapted to be positioned between the light source 40 and the patient's scalp 30.
  • The therapy apparatus 10 further includes a power supply (not shown) operatively coupled to the light source 40, and a programmable controller 126 operatively coupled to the light source 40 and to the power supply. The programmable controller 126 is configured to control the light source 40 so as to deliver a predetermined power density to the brain tissue 20. In certain embodiments, as schematically illustrated in FIG. 10 the light source 40 comprises the programmable controller 126. In other embodiments the programmable controller 126 is a separate component of the therapy apparatus 10.
  • In certain embodiments, the strap 120 comprises a loop of elastomeric material sized appropriately to fit snugly onto the patient's scalp 30. In other embodiments, the strap 120 comprises an elastomeric material to which is secured any suitable securing means 130, such as mating Velcro strips, buckles, snaps, hooks, buttons, ties, or the like. The precise configuration of the strap 120 is subject only to the limitation that the strap 120 is capable of maintaining the light source 40 in a selected position so that light energy emitted by the light source 40 is directed towards the targeted brain tissue 20.
  • In the exemplary embodiment illustrated in FIG. 10, the housing 122 comprises a layer of flexible plastic or fabric that is secured to the strap 120. In other embodiments, the housing 122 comprises a plate or an enlarged portion of the strap 120. Various strap configurations and spatial distributions of the light sources 40 are compatible with embodiments described herein so that the therapy apparatus 10 can treat selected portions of brain tissue.
  • In still other embodiments, the therapy apparatus 10 for delivering the light energy includes a handheld probe 140, as schematically illustrated in FIG. 11. The probe 140 includes a light source 40 and an element 50 as described herein.
  • FIG. 12 is a block diagram of a control circuit 200 comprising a programmable controller 126 according to embodiments described herein. The control circuit 200 is configured to adjust the power of the light energy emitted by the light source 40 to generate a predetermined surface power density at the scalp 30 corresponding to a predetermined energy delivery profile, such as a predetermined subsurface power density, to the target area of the brain 20.
  • In certain embodiments, the programmable controller 126 comprises a logic circuit 210, a clock 212 coupled to the logic circuit 210, and an interface 214 coupled to the logic circuit 210. The clock 212 of certain embodiments provides a timing signal to the logic circuit 210 so that the logic circuit 210 can monitor and control timing intervals of the applied light. Examples of timing intervals include, but are not limited to, total treatment times, pulsewidth times for pulses of applied light, and time intervals between pulses of applied light. In certain embodiments, the light sources 40 can be selectively turned on and off to reduce the thermal load on the scalp 30 and to deliver a selected power density to particular areas of the brain 20.
  • The interface 214 of certain embodiments provides signals to the logic circuit 210 which the logic circuit 210 uses to control the applied light. The interface 214 can comprise a user interface or an interface to a sensor monitoring at least one parameter of the treatment. In certain such embodiments, the programmable controller 126 is responsive to signals from the sensor to preferably adjust the treatment parameters to optimize the measured response. The programmable controller 126 can thus provide closed-loop monitoring and adjustment of various treatment parameters to optimize the phototherapy. The signals provided by the interface 214 from a user are indicative of parameters that may include, but are not limited to, patient characteristics (e.g., skin type, fat percentage), selected applied power densities, target time intervals, and power density/timing profiles for the applied light.
  • In certain embodiments, the logic circuit 210 is coupled to a light source driver 220. The light source driver 220 is coupled to a power supply 230, which in certain embodiments comprises a battery and in other embodiments comprises an alternating current source. The light source driver 220 is also coupled to the light source 40. The logic circuit 210 is responsive to the signal from the clock 212 and to user input from the user interface 214 to transmit a control signal to the light source driver 220. In response to the control signal from the logic circuit 210, the light source driver 220 adjust and controls the power applied to the light sources 40. Other control circuits besides the control circuit 200 of FIG. 12 are compatible with embodiments described herein.
  • In certain embodiments, the logic circuit 110 is responsive to signals from a sensor monitoring at least one parameter of the treatment to control the applied light. For example, certain embodiments comprise a temperature sensor thermally coupled to the scalp 30 to provide information regarding the temperature of the scalp 30 to the logic circuit 210. In such embodiments, the logic circuit 210 is responsive to the information from the temperature sensor to transmit a control signal to the light source driver 220 so as to adjust the parameters of the applied light to maintain the scalp temperature below a predetermined level. Other embodiments include exemplary biomedical sensors including, but not limited to, a blood flow sensor, a blood gas (e.g., oxygenation) sensor, an ATP production sensor, or a cellular activity sensor. Such biomedical sensors can provide real-time feedback information to the logic circuit 210. In certain such embodiments, the logic circuit 110 is responsive to signals from the sensors to preferably adjust the parameters of the applied light to optimize the measured response. The logic circuit 110 can thus provide closed-loop monitoring and adjustment of various parameters of the applied light to optimize the phototherapy.
  • In certain embodiments, as schematically illustrated in FIG. 13, the therapy apparatus 310 comprises a light source 340 adapted to irradiate a portion of the patient's brain 20 with an efficacious power density and wavelength of light. The therapy apparatus 310 further comprises a controller 360 for energizing said light source 340, so as to selectively produce a plurality of different irradiation patterns on the patient's scalp 30. Each of the irradiation patterns is comprised of a least one illuminated area that is small compared to the patient's scalp 30, and at least one non-illuminated area.
  • In certain embodiments, the light source 340 includes an apparatus for adjusting the emitted light to irradiate different portions of the scalp 30. In certain such embodiments, the apparatus physically moves the light source 40 relative to the scalp 30. In other embodiments, the apparatus does not move the light source 40, but redirects the emitted light to different portions of the scalp 30. In an exemplary embodiment, as schematically illustrated in FIG. 14, the light source 340 comprises a laser diode 342 and a galvometer 344, both of which are electrically coupled to the controller 360. The galvometer 344 comprises a mirror 346 mounted onto an assembly 348 which is adjustable by a plurality of motors 350. Light emitted by the laser diode 342 is directed toward the mirror 346 and is reflected to selected portions of the patient's scalp 30 by selectively moving the mirror 346 and selectively activating the laser diode 342. In certain embodiments, the therapy apparatus 310 comprises an element 50 adapted to inhibit temperature increases at the scalp 30 as described herein.
  • FIG. 15A schematically illustrates an irradiation pattern 370 in accordance with embodiments described herein. The irradiation pattern 370 comprises at least one illuminated area 372 and at least one non-illuminated area 374. In certain embodiments, the irradiation pattern 370 is generated by scanning the mirror 346 so that the light impinges the patient's scalp 30 in the illuminated area 372 but not in the non-illuminated area 374. Certain embodiments modify the illuminated area 372 and the non-illuminated area 374 as a function of time.
  • This selective irradiation can be used to reduce the thermal load on particular locations of the scalp 30 by moving the light from one illuminated area 372 to another. For example, by irradiating the scalp 30 with the irradiation pattern 370 schematically illustrated in FIG. 15A, the illuminated areas 372 of the scalp 30 are heated by interaction with the light, and the non-illuminated areas 374 are not heated. By subsequently irradiating the scalp 30 with the complementary irradiation pattern 370 ′ schematically illustrated in FIG. 15B, the previously non-illuminated areas 374 are now illuminated areas 372′, and the previously illuminated areas 372 are now non-illuminated areas 374′. A comparison of the illuminated areas 372 of the irradiation pattern 370 of FIG. 15A with the illuminated area 372′ of the irradiation pattern 370′ of FIG. 15B shows that the illuminated areas 372, 372′ do not significantly overlap one another. In this way, the thermal load at the scalp 30 due to the absorption of the light can be distributed across the scalp 30, thereby avoiding unduly heating one or more portions of the scalp 30.
  • Methods of Light Delivery
  • Preferred methods of phototherapy are based at least in part on the finding described above that, for a selected wavelength, the power density (light intensity or power per unit area, in W/cm2) or the energy density (energy per unit area, in J/cm2, or power density multiplied by the exposure time) of the light energy delivered to tissue is an important factor in determining the relative efficacy of the phototherapy, and efficacy is not as directly related to the total power or the total energy delivered to the tissue. In the methods described herein, power density or energy density as delivered to a portion of the patient's brain 20, which can include the area of infarct after a stroke, appears to be important factors in using phototherapy to treat and save surviving but endangered neurons in a zone of danger surrounding the infarcted area. Certain embodiments apply optimal power densities or energy densities to the intended target tissue, within acceptable margins of error.
  • As used herein, the term “neurodegeneration” refers to the process of cell destruction resulting from primary destructive events such as stroke or CVA, as well as from secondary, delayed and progressive destructive mechanisms that are invoked by cells due to the occurrence of the primary destructive event. Primary destructive events include disease processes or physical injury or insult, including stroke, but also include other diseases and conditions such as multiple sclerosis, amylotrophic lateral sclerosis, epilepsy, Alzheimer's disease, dementia resulting from other causes such as AIDS, cerebral ischemia including focal cerebral ischemia, and physical trauma such as crush or compression injury in the CNS, including a crush or compression injury of the brain, spinal cord, nerves or retina, or any acute injury or insult producing neurodegeneration. Secondary destructive mechanisms include any mechanism that leads to the generation and release of neurotoxic molecules, including apoptosis, depletion of cellular energy stores because of changes in mitochondrial membrane permeability, release or failure in the reuptake of excessive glutamate, reperfusion injury, and activity of cytokines and inflammation. Both primary and secondary mechanisms contribute to forming a “zone of danger” for neurons, wherein the neurons in the zone have at least temporarily survived the primary destructive event, but are at risk of dying due to processes having delayed effect.
  • As used herein, the term “neuroprotection” refers to a therapeutic strategy for slowing or preventing the otherwise irreversible loss of neurons due to neurodegeneration after a primary destructive event, whether the neurodegeneration loss is due to disease mechanisms associated with the primary destructive event or secondary destructive mechanisms.
  • As used herein, the term “neuroprotective-effective” as used herein refers to a characteristic of an amount of light energy, wherein the amount is a power density of the light energy measured in mW/cm2. A neuroprotective-effective amount of light energy achieves the goal of preventing, avoiding, reducing, or eliminating neurodegeneration.
  • Thus, a method for the treatment of stroke in a patient in need of such treatment involves delivering a neuroprotective-effective amount of light energy having a wavelength in the visible to near-infrared wavelength range to a target area of the patient's brain 20. In certain embodiments, the target area of the patient's brain 20 includes the area of infarct, i.e. to neurons within the “zone of danger.” In other embodiments, the target area includes portions of the brain 20 not within the zone of danger. Without being bound by theory, it is believed that irradiation of healthy tissue in proximity to the zone of danger increases the production of ATP and copper ions in the healthy tissue and which then migrate to the injured cells within the region surrounding the infarct, thereby producing beneficial effects. Additional information regarding the biomedical mechanisms or reactions involved in phototherapy is provided by Tiina I. Karu in “Mechanisms of Low-Power Laser Light Action on Cellular Level”, Proceedings of SPIE Vol. 4159 (2000), Effects of Low-Power Light on Biological Systems V, Ed. Rachel Lubart, pp. 1-17, which is incorporated in its entirety by reference herein.
  • In certain embodiments, delivering the neuroprotective amount of light energy includes selecting a surface power density of the light energy at the scalp 30 corresponding to the predetermined power density at the target area of the brain 20. As described above, light propagating through tissue is scattered and absorbed by the tissue. Calculations of the power density to be applied to the scalp 30 so as to deliver a predetermined power density to the selected target area of the brain 20 preferably take into account the attenuation of the light energy as it propagates through the skin and other tissues, such as bone and brain tissue. Factors known to affect the attenuation of light propagating to the brain 20 from the scalp 30 include, but are not limited to, skin pigmentation, the presence and color of hair over the area to be treated, amount of fat tissue, the presence of bruised tissue, skull thickness, and the location of the target area of the brain 20, particularly the depth of the area relative to the surface of the scalp 30. For example, to obtain a desired power density of 50 mW/cm2 in the brain 20 at a depth of 3 cm below the surface of the scalp 30, phototherapy may utilize an applied power density of 500 mW/cm2. The higher the level of skin pigmentation, the higher the power density applied to the scalp 30 to deliver a predetermined power density of light energy to a subsurface site of the brain 20.
  • In certain embodiments, treating a patient suffering from the effects of stroke comprises placing the therapy apparatus 10 in contact with the scalp 30 and adjacent the target area of the patient's brain 20. The target area of the patient's brain 20 can be previously identified such as by using standard medical imaging techniques. In certain embodiments, treatment further includes calculating a surface power density at the scalp 30 which corresponds to a preselected power density at the target area of the patient's brain 20. The calculation of certain embodiments includes factors that affect the penetration of the light energy and thus the power density at the target area. These factors include, but are not limited to, the thickness of the patient's skull, type of hair and hair coloration, skin coloration and pigmentation, patient's age, patient's gender, and the distance to the target area within the brain 20. The power density and other parameters of the applied light are then adjusted according to the results of the calculation.
  • The power density selected to be applied to the target area of the patient's brain 20 depends on a number of factors, including, but not limited to, the wavelength of the applied light, the type of CVA (ischemic or hemorrhagic), and the patient's clinical condition, including the extent of the affected brain area. The power density of light energy to be delivered to the target area of the patient's brain 20 may also be adjusted to be combined with any other therapeutic agent or agents, especially pharmaceutical neuroprotective agents, to achieve the desired biological effect. In such embodiments, the selected power density can also depend on the additional therapeutic agent or agents chosen.
  • In preferred embodiments, the treatment proceeds continuously for a period of about 10 seconds to about 2 hours, more preferably for a period of about 1 to about 10 minutes, and most preferably for a period of about 1 to 5 minutes. In other embodiments, the light energy is preferably delivered for at least one treatment period of at least about five minutes, and more preferably for at least one treatment period of at least ten minutes. The light energy can be pulsed during the treatment period or the light energy can be continuously applied during the treatment period.
  • In certain embodiments, the treatment may be terminated after one treatment period, while in other embodiments, the treatment may be repeated for at least two treatment periods. The time between subsequent treatment periods is preferably at least about five minutes, more preferably at least about 1 to 2 days, and most preferably at least about one week. In certain embodiments in which treatment is performed over the course of multiple days, the apparatus 10 is wearable over multiple concurrent days (e.g., embodiments of FIGS. 1, 3, 9A, 10, and 13). The length of treatment time and frequency of treatment periods can depend on several factors, including the functional recovery of the patient and the results of imaging analysis of the infarct. In certain embodiments, one or more treatment parameters can be adjusted in response to a feedback signal from a device (e.g., magnetic resonance imaging) monitoring the patient.
  • During the treatment, the light energy may be continuously provided, or it may be pulsed. If the light is pulsed, the pulses are preferably at least about 10 nanosecond long and occur at a frequency of up to about 100 kHz. Continuous wave light may also be used.
  • The thrombolytic therapies currently in use for treatment of stroke are typically begun within a few hours of the stroke. However, many hours often pass before a person who has suffered a stroke receives medical treatment, so the short time limit for initiating thrombolytic therapy excludes many patients from treatment. In contrast, phototherapy treatment of stroke appears to be more effective if treatment begins no earlier than several hours after the ischemic event has occurred. Consequently, the present methods of phototherapy may be used to treat a greater percentage of stroke patients.
  • In certain embodiments, a method provides a neuroprotective effect in a patient that had an ischemic event in the brain. The method comprises identifying a patient who has experienced an ischemic event in the brain. The method further comprises estimating the time of the ischemic event. The method further comprises commencing administration of a neuroprotective effective amount of light energy to the brain. The administration of the light energy is commenced no less than about two hours following the time of the ischemic event. In certain embodiments, phototherapy treatment can be efficaciously performed preferably within 24 hours after the ischemic event occurs, and more preferably no earlier than two hours following the ischemic event, still more preferably no earlier than three hours following the ischemic event, and most preferably no earlier than five hours following the ischemic event. In certain embodiments, one or more of the treatment parameters can be varied depending on the amount of time that has elapsed since the ischemic event.
  • Without being bound by theory, it is believed that the benefit in delaying treatment occurs because of the time needed for induction of ATP production, and/or the possible induction of angiogenesis in the region surrounding the infarct. Thus, in accordance with one preferred embodiment, the phototherapy for the treatment of stroke occurs preferably about 6 to 24 hours after the onset of stroke symptoms, more preferably about 12 to 24 hours after the onset of symptoms. It is believed, however, that if treatment begins after about 2 days, its effectiveness will be greatly reduced.
  • EXAMPLE
  • An in vitro experiment was done to demonstrate one effect of phototherapy on neurons, namely the effect on ATP production. Normal Human Neural Progenitor (NHNP) cells were obtained cryopreserved through Clonetics of Baltimore, Md., catalog # CC-2599. The NHNP cells were thawed and cultured on polyethyleneimine (PEI) with reagents provided with the cells, following the manufacturers' instructions. The cells were plated into 96 well plates (black plastic with clear bottoms, Becton Dickinson of Franklin Lakes, N.J.) as spheroids and allowed to differentiate into mature neurons over a period of two weeks.
  • A Photo Dosing Assembly (PDA) was used to provide precisely metered doses of laser light to the NHNP cells in the 96 well plates. The PDA included a Nikon Diaphot inverted microscope (Nikon of Melville, N.Y.) with a LUDL motorized x,y,z stage (Ludl Electronic Products of Hawthorne, N.Y.). An 808 nanometer laser was routed into the rear epi-fluorescent port on the microscope using a custom designed adapter and a fiber optic cable. Diffusing lenses were mounted in the path of the beam to create a “speckled” pattern, which was intended to mimic in vivo conditions after a laser beam passed through human skin. The beam diverged to a 25 millimeter diameter circle when it reached the bottom of the 96 well plates. This dimension was chosen so that a cluster of four adjacent wells could be lased at the same time. Cells were plated in a pattern such that a total of 12 clusters could be lased per 96 well plate. Stage positioning was controlled by a Silicon Graphics workstation and laser timing was performed by hand using a digital timer. The measured power density passing through the plate for the NHNP cells was 50 mW/cm2.
  • Two independent assays were used to measure the effects of 808 nanometer laser light on the NHNP cells. The first was the CellTiter-Glo Luminescent Cell Viability Assay (Promega of Madison, Wis.). This assay generates a “glow-type” luminescent signal produced by a luciferase reaction with cellular ATP. The CellTiter-Glo reagent is added in an amount equal to the volume of media in the well and results in cell lysis followed by a sustained luminescent reaction that was measured using a Reporter luminometer (Turner Biosystems of Sunnyvale, Calif.). Amounts of ATP present in the NHNP cells were quantified in Relative Luminescent Units (RLUs) by the luminometer.
  • The second assay used was the alamarBlue assay (Biosource of Camarillo, Calif.). The internal environment of a proliferating cell is more reduced than that of a non-proliferating cell. Specifically, the ratios of NADPH/NADP, FADH/FAD, FMNH/FMN and NADH/NAD, increase during proliferation. Laser irradiation is also thought to have an effect on these ratios. Compounds such as alamarBlue are reduced by these metabolic intermediates and can be used to monitor cellular states. The oxidization of alamarBlue is accompanied by a measurable shift in color. In its unoxidized state, alamarBlue appears blue; when oxidized, the color changes to red. To quantify this shift, a 340PC microplate reading spectrophotometer (Molecular Devices of Sunnyvale, Calif.) was used to measure the absorbance of a well containing NHNP cells, media and alamarBlue diluted 10% v/v. The absorbance of each well was measured at 570 nanometers and 600 nanometers and the percent reduction of alamarBlue was calculated using an equation provided by the manufacturer.
  • The two metrics described above, (RLUs and % Reduction) were then used to compare NHNP culture wells that had been lased with 50 mW/cm2 at a wavelength of 808 nanometers. For the CellTiter-Glo assay, 20 wells were lased for 1 second and compared to an unlased control group of 20 wells. The CellTiter-Glo reagent was added 10 minutes after lasing completed and the plate was read after the cells had lysed and the luciferase reaction had stabilized. The average RLUs measured for the control wells was 3808±3394 while the laser group showed a two-fold increase in ATP content to 7513±6109. The standard deviations were somewhat high due to the relatively small number of NHNP cells in the wells (approximately 100 per well from visual observation), but a student's unpaired t-test was performed on the data with a resulting p-value of 0.02 indicating that the two-fold change is statistically significant.
  • The alamarBlue assay was performed with a higher cell density and a lasing time of 5 seconds. The plating density (calculated to be between 7,500-26,000 cells per well based on the certificate of analysis provided by the manufacturer) was difficult to determine since some of the cells had remained in the spheroids and had not completely differentiated. Wells from the same plate can still be compared though, since plating conditions were identical. The alamarBlue was added immediately after lasing and the absorbance was measured 9.5 hours later. The average measured values for percent reduction were 22% ±7.3% for the 8 lased wells and 12.4 %±5.9% for the 3 unlased control wells (p-value=0.076). These alamarBlue results support the earlier findings in that they show a similar positive effect of the laser treatment on the cells.
  • Increases in cellular ATP concentration and a more reduced state within the cell are both related to cellular metabolism and are considered to be indications that the cell is viable and healthy. These results are novel and significant in that they show the positive effects of laser irradiation on cellular metabolism in in-vitro neuronal cell cultures.
  • In certain embodiments, the phototherapy is combined with other types of treatments for an improved therapeutic effect. Treatment can comprise directing light through the scalp of the patient to a target area of the brain concurrently with applying an electromagnetic field to the brain. In such embodiments, the light has an efficacious power density at the target area and the electromagnetic field has an efficacious field strength. For example, the apparatus 50 can also include systems for electromagnetic treatment, e.g., as described in U.S. Pat. No. 6,042,531 issued to Holcomb, which is incorporated in its entirety by reference herein. In certain embodiments, the electromagnetic field comprises a magnetic field, while in other embodiments, the electromagnetic field comprises a radio-frequency (RF) field. As another example, treatment can comprise directing an efficacious power density of light through the scalp of the patient to a target area of the brain concurrently with applying an efficacious amount of ultrasonic energy to the brain. Such a system can include systems for ultrasonic treatment, e.g., as described in U.S. Pat. No. 5,954,470 issued to Fry et al., which is incorporated in its entirety by reference herein.
  • The explanations and illustrations presented herein are intended to acquaint others skilled in the art with the invention, its principles, and its practical application. Those skilled in the art may adapt and apply the invention in its numerous forms, as may be best suited to the requirements of a particular use. Accordingly, the specific embodiments of the present invention as set forth are not intended as being exhaustive or limiting of the invention.

Claims (16)

1. A therapy apparatus for treating a patient's brain, the therapy apparatus comprising:
a light source having an output emission area positioned to irradiate a target portion of the brain with light having a wavelength between about 630 nanometers and about 1064 nanometers, the light having an efficacious power density of at least about 1 mW/cm2 at the target portion; and
a material interposed between the light source and the patient's scalp, the material being substantially transmissive to the light and thermally conductive so as to absorb heat from the scalp.
2. The therapy apparatus of claim 1, wherein the light passes through the material prior to reaching the scalp.
3. The therapy apparatus of claim 1, wherein the material is adapted to contact the patient's scalp.
4. The therapy apparatus of claim 3, wherein the material is attached to the light source and is adapted to conform to the scalp so as to position the light source relative to the scalp.
5. The therapy apparatus of claim 4, wherein the material is mechanically adjustable so as to adjust a position of the light source relative to the scalp.
6. The therapy apparatus of claim 4, wherein the material is mechanically adjustable so as to fit the therapy apparatus to the scalp.
7. The therapy apparatus of claim 6, further comprising a bag containing the material, the bag and the material adapted to conform to contours of the scalp.
8. The therapy apparatus of claim 4, wherein at least a portion of the material is within an optical path of the light from the source to the scalp.
9. The therapy apparatus of claim 8, wherein the material is adapted to reduce back reflections of the light.
10. The therapy apparatus of claim 9, wherein the material is adapted to fit to the scalp so as to substantially reduce air gaps between the scalp and the material in the optical path of the light.
11. The therapy apparatus of claim 9, wherein the material has a refractive index which substantially matches a refractive index of the scalp.
12. The therapy apparatus of claim 1, wherein the material is pre-cooled prior to treatment of the brain.
13. The therapy apparatus of claim 1, wherein the material is adapted to apply pressure to at least a portion of the scalp, thereby blanching the portion of the scalp and decreasing absorption of the light by blood in the scalp.
14. The therapy apparatus of claim 1, wherein the material is adapted to diffuse the light prior to reaching the scalp.
15. A method of irradiating a portion of brain tissue of a patient, the method comprising:
positioning a light source at a first position and directing light from the light source through a first illuminated area of the patient's scalp to irradiate the portion with light having a power density of at least about 1 mW/cm2; and
moving the light source from the first position to a second position and directing light from the light source through a second illuminated area of the patient's scalp to irradiate the portion with light having a power density of at least about 1 mW/cm2, the second illuminated area separated from the first illuminated area by at least one non-illuminated area.
16. A method of treating a portion of brain tissue of a patient, the method comprising:
removing at least a portion of the hair from a patient's scalp from an area of the scalp; and
introducing light having an efficacious power density of at least about 1 mW/cm2 at the portion of brain tissue by directing light through the area of the scalp, wherein the light has a power density at the scalp below a damage threshold of scalp tissue and has sufficient optical power at the scalp to achieve the efficacious power density at the portion of brain tissue.
US11/482,220 2001-11-01 2006-07-07 Device and method for providing phototherapy to the brain Abandoned US20060253177A1 (en)

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US11/482,220 US20060253177A1 (en) 2001-11-01 2006-07-07 Device and method for providing phototherapy to the brain
US12/617,658 US20100094384A1 (en) 2001-11-01 2009-11-12 System and method for providing phototherapy to the brain
US12/650,423 US10758743B2 (en) 2001-11-01 2009-12-30 Method for providing phototherapy to the brain
US12/817,090 US9993659B2 (en) 2001-11-01 2010-06-16 Low level light therapy for enhancement of neurologic function by altering axonal transport rate
US12/846,560 US10683494B2 (en) 2001-11-01 2010-07-29 Enhanced stem cell therapy and stem cell production through the administration of low level light energy
US13/111,840 US10315042B2 (en) 2001-11-01 2011-05-19 Device and method for providing a synergistic combination of phototherapy and a non-light energy modality to the brain
US16/190,229 US10913943B2 (en) 2001-11-01 2018-11-14 Enhanced stem cell therapy and stem cell production through the administration of low level light energy

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US33643601P 2001-11-01 2001-11-01
US36926002P 2002-04-02 2002-04-02
US10/287,432 US20030109906A1 (en) 2001-11-01 2002-11-01 Low level light therapy for the treatment of stroke
US44269303P 2003-01-24 2003-01-24
US48797903P 2003-07-17 2003-07-17
US50214703P 2003-09-11 2003-09-11
US10/682,379 US7303578B2 (en) 2001-11-01 2003-10-09 Device and method for providing phototherapy to the brain
US11/482,220 US20060253177A1 (en) 2001-11-01 2006-07-07 Device and method for providing phototherapy to the brain

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US10/682,379 Continuation US7303578B2 (en) 2001-11-01 2003-10-09 Device and method for providing phototherapy to the brain
US10/682,379 Continuation-In-Part US7303578B2 (en) 2001-11-01 2003-10-09 Device and method for providing phototherapy to the brain
US12/846,560 Continuation-In-Part US10683494B2 (en) 2001-11-01 2010-07-29 Enhanced stem cell therapy and stem cell production through the administration of low level light energy

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US11/844,205 Continuation-In-Part US8308784B2 (en) 2001-11-01 2007-08-23 Low level light therapy for enhancement of neurologic function of a patient affected by Parkinson's disease
US12/617,658 Continuation US20100094384A1 (en) 2001-11-01 2009-11-12 System and method for providing phototherapy to the brain
US12/650,423 Continuation US10758743B2 (en) 2001-11-01 2009-12-30 Method for providing phototherapy to the brain
US12/846,560 Continuation-In-Part US10683494B2 (en) 2001-11-01 2010-07-29 Enhanced stem cell therapy and stem cell production through the administration of low level light energy

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US10/938,423 Abandoned US20050107851A1 (en) 2001-11-01 2004-09-10 Device and method for providing phototherapy to the brain
US11/038,770 Expired - Lifetime US7309348B2 (en) 2003-01-24 2005-01-19 Method for treatment of depression
US11/482,220 Abandoned US20060253177A1 (en) 2001-11-01 2006-07-07 Device and method for providing phototherapy to the brain
US11/766,037 Abandoned US20080004565A1 (en) 2003-01-24 2007-06-20 Method of treating or preventing depression
US12/561,231 Active 2029-04-23 US10653889B2 (en) 2001-11-01 2009-09-16 Method for providing phototherapy to the brain
US12/561,194 Active 2030-03-21 US10857376B2 (en) 2001-11-01 2009-09-16 Device for providing phototherapy to the brain
US12/617,658 Abandoned US20100094384A1 (en) 2001-11-01 2009-11-12 System and method for providing phototherapy to the brain
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US12/561,194 Active 2030-03-21 US10857376B2 (en) 2001-11-01 2009-09-16 Device for providing phototherapy to the brain
US12/617,658 Abandoned US20100094384A1 (en) 2001-11-01 2009-11-12 System and method for providing phototherapy to the brain
US12/650,423 Expired - Lifetime US10758743B2 (en) 2001-11-01 2009-12-30 Method for providing phototherapy to the brain

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Cited By (45)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070261127A1 (en) * 2005-07-22 2007-11-08 Boyden Edward S Light-activated cation channel and uses thereof
US20080085265A1 (en) * 2005-07-22 2008-04-10 Schneider M B System for optical stimulation of target cells
US20090099038A1 (en) * 2005-07-22 2009-04-16 Karl Deisseroth Cell line, system and method for optical-based screening of ion-channel modulators
US20090254154A1 (en) * 2008-03-18 2009-10-08 Luis De Taboada Method and apparatus for irradiating a surface with pulsed light
US20110040356A1 (en) * 2009-08-12 2011-02-17 Fredric Schiffer Methods for Treating Psychiatric Disorders Using Light Energy
US20110066213A1 (en) * 2009-05-01 2011-03-17 Maik Huttermann Light therapy treatment
US20110172653A1 (en) * 2008-06-17 2011-07-14 Schneider M Bret Methods, systems and devices for optical stimulation of target cells using an optical transmission element
US8025687B2 (en) 2003-01-24 2011-09-27 Photothera, Inc. Low level light therapy for enhancement of neurologic function
US20110313234A1 (en) * 2010-06-21 2011-12-22 Yen-Lung Lin Electromagnetic stimulation device and method thereof
US8149526B2 (en) 2008-09-18 2012-04-03 Photothera, Inc. Single use lens assembly
US20120127557A1 (en) * 2010-11-19 2012-05-24 Canon Kabushiki Kaisha Apparatus and method for irradiating a medium
US8308784B2 (en) 2006-08-24 2012-11-13 Jackson Streeter Low level light therapy for enhancement of neurologic function of a patient affected by Parkinson's disease
US8603790B2 (en) 2008-04-23 2013-12-10 The Board Of Trustees Of The Leland Stanford Junior University Systems, methods and compositions for optical stimulation of target cells
US8696722B2 (en) 2010-11-22 2014-04-15 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic magnetic resonance imaging
US8716447B2 (en) 2008-11-14 2014-05-06 The Board Of Trustees Of The Leland Stanford Junior University Optically-based stimulation of target cells and modifications thereto
US8729040B2 (en) 2008-05-29 2014-05-20 The Board Of Trustees Of The Leland Stanford Junior University Cell line, system and method for optical control of secondary messengers
US8845704B2 (en) 2007-05-11 2014-09-30 Clarimedix Inc. Visible light modulation of mitochondrial function in hypoxia and disease
US8864805B2 (en) 2007-01-10 2014-10-21 The Board Of Trustees Of The Leland Stanford Junior University System for optical stimulation of target cells
US8932562B2 (en) 2010-11-05 2015-01-13 The Board Of Trustees Of The Leland Stanford Junior University Optically controlled CNS dysfunction
US9079940B2 (en) 2010-03-17 2015-07-14 The Board Of Trustees Of The Leland Stanford Junior University Light-sensitive ion-passing molecules
US9101759B2 (en) 2008-07-08 2015-08-11 The Board Of Trustees Of The Leland Stanford Junior University Materials and approaches for optical stimulation of the peripheral nervous system
US9175095B2 (en) 2010-11-05 2015-11-03 The Board Of Trustees Of The Leland Stanford Junior University Light-activated chimeric opsins and methods of using the same
US9238150B2 (en) 2005-07-22 2016-01-19 The Board Of Trustees Of The Leland Stanford Junior University Optical tissue interface method and apparatus for stimulating cells
US9284353B2 (en) 2007-03-01 2016-03-15 The Board Of Trustees Of The Leland Stanford Junior University Mammalian codon optimized nucleotide sequence that encodes a variant opsin polypeptide derived from Natromonas pharaonis (NpHR)
US9365628B2 (en) 2011-12-16 2016-06-14 The Board Of Trustees Of The Leland Stanford Junior University Opsin polypeptides and methods of use thereof
US9522288B2 (en) 2010-11-05 2016-12-20 The Board Of Trustees Of The Leland Stanford Junior University Upconversion of light for use in optogenetic methods
US9636380B2 (en) 2013-03-15 2017-05-02 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic control of inputs to the ventral tegmental area
US9693692B2 (en) 2007-02-14 2017-07-04 The Board Of Trustees Of The Leland Stanford Junior University System, method and applications involving identification of biological circuits such as neurological characteristics
US9992981B2 (en) 2010-11-05 2018-06-12 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic control of reward-related behaviors
US10035027B2 (en) 2007-10-31 2018-07-31 The Board Of Trustees Of The Leland Stanford Junior University Device and method for ultrasonic neuromodulation via stereotactic frame based technique
US10052497B2 (en) 2005-07-22 2018-08-21 The Board Of Trustees Of The Leland Stanford Junior University System for optical stimulation of target cells
US10071261B2 (en) 2009-05-01 2018-09-11 Wayne State University Light therapy treatment
US10086012B2 (en) 2010-11-05 2018-10-02 The Board Of Trustees Of The Leland Stanford Junior University Control and characterization of memory function
US10188872B2 (en) 2006-01-30 2019-01-29 Pthera LLC Light-emitting device and method for providing phototherapy to the brain
US10220092B2 (en) 2013-04-29 2019-03-05 The Board Of Trustees Of The Leland Stanford Junior University Devices, systems and methods for optogenetic modulation of action potentials in target cells
US10307609B2 (en) 2013-08-14 2019-06-04 The Board Of Trustees Of The Leland Stanford Junior University Compositions and methods for controlling pain
US10426970B2 (en) 2007-10-31 2019-10-01 The Board Of Trustees Of The Leland Stanford Junior University Implantable optical stimulators
WO2019210304A1 (en) * 2018-04-27 2019-10-31 University Of Minnesota Device for treatment of traumatic brain injury and related systems and methods
US10568516B2 (en) 2015-06-22 2020-02-25 The Board Of Trustees Of The Leland Stanford Junior University Methods and devices for imaging and/or optogenetic control of light-responsive neurons
US10568307B2 (en) 2010-11-05 2020-02-25 The Board Of Trustees Of The Leland Stanford Junior University Stabilized step function opsin proteins and methods of using the same
US10711242B2 (en) 2008-06-17 2020-07-14 The Board Of Trustees Of The Leland Stanford Junior University Apparatus and methods for controlling cellular development
US10758743B2 (en) 2001-11-01 2020-09-01 Pthera LLC Method for providing phototherapy to the brain
US10974064B2 (en) 2013-03-15 2021-04-13 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic control of behavioral state
US11103723B2 (en) 2012-02-21 2021-08-31 The Board Of Trustees Of The Leland Stanford Junior University Methods for treating neurogenic disorders of the pelvic floor
US11294165B2 (en) 2017-03-30 2022-04-05 The Board Of Trustees Of The Leland Stanford Junior University Modular, electro-optical device for increasing the imaging field of view using time-sequential capture

Families Citing this family (118)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL124722A0 (en) * 1998-06-02 1999-01-26 Oron Amir Ischemia laser treatment
US20130274837A1 (en) * 1998-10-23 2013-10-17 Babak Nemati Systems and Methods to Enhance Optical Transparency of Biological Tissues for Photobiomodulation
US10315042B2 (en) 2001-11-01 2019-06-11 Pthera LLC Device and method for providing a synergistic combination of phototherapy and a non-light energy modality to the brain
US10683494B2 (en) 2001-11-01 2020-06-16 Pthera LLC Enhanced stem cell therapy and stem cell production through the administration of low level light energy
US9993659B2 (en) 2001-11-01 2018-06-12 Pthera, Llc Low level light therapy for enhancement of neurologic function by altering axonal transport rate
US20030144712A1 (en) * 2001-12-20 2003-07-31 Jackson Streeter, M.D. Methods for overcoming organ transplant rejection
US10695577B2 (en) * 2001-12-21 2020-06-30 Photothera, Inc. Device and method for providing phototherapy to the heart
US7316922B2 (en) * 2002-01-09 2008-01-08 Photothera Inc. Method for preserving organs for transplant
US20040153130A1 (en) * 2002-05-29 2004-08-05 Amir Oron Methods for treating muscular dystrophy
US20040132002A1 (en) * 2002-09-17 2004-07-08 Jackson Streeter Methods for preserving blood
US20060223155A1 (en) * 2002-11-01 2006-10-05 Jackson Streeter Enhancement of in vitro culture or vaccine production in bioreactors using electromagnetic energy
US7344555B2 (en) 2003-04-07 2008-03-18 The United States Of America As Represented By The Department Of Health And Human Services Light promotes regeneration and functional recovery after spinal cord injury
US8821559B2 (en) * 2004-08-27 2014-09-02 Codman & Shurtleff, Inc. Light-based implants for treating Alzheimer's disease
USRE47266E1 (en) 2005-03-14 2019-03-05 DePuy Synthes Products, Inc. Light-based implants for treating Alzheimer's disease
US7288108B2 (en) * 2005-03-14 2007-10-30 Codman & Shurtleff, Inc. Red light implant for treating Parkinson's disease
CA2603443C (en) 2005-03-31 2019-01-08 The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. Light as a replacement for mitogenic factors on progenitor cells
US20090216299A1 (en) * 2005-04-06 2009-08-27 Borad Of Trustees Of Michigan State University System for Low-Level Laser Radiation
US20130079759A1 (en) 2005-04-14 2013-03-28 Robert S. Dotson Ophthalmic Phototherapy Device and Associated Treatment Method
US20080269730A1 (en) 2005-04-14 2008-10-30 Dotson Robert S Ophthalmic Phototherapy Device and Associated Treatment Method
US7351253B2 (en) * 2005-06-16 2008-04-01 Codman & Shurtleff, Inc. Intranasal red light probe for treating Alzheimer's disease
US20060287696A1 (en) * 2005-06-21 2006-12-21 Wright David W Heat and light therapy treatment device and method
US20080288007A1 (en) * 2005-10-28 2008-11-20 United Laboratories & Manufacturing, Llc Hygienic-Therapeutic Multiplex Devices
US7819907B2 (en) * 2005-10-31 2010-10-26 Codman & Shurtleff, Inc. Device and method for fixing adjacent bone plates
US8033284B2 (en) 2006-01-11 2011-10-11 Curaelase, Inc. Therapeutic laser treatment
US20070179570A1 (en) * 2006-01-30 2007-08-02 Luis De Taboada Wearable device and method for providing phototherapy to the brain
US10695579B2 (en) 2006-01-30 2020-06-30 Pthera LLC Apparatus and method for indicating treatment site locations for phototherapy to the brain
US10357662B2 (en) 2009-02-19 2019-07-23 Pthera LLC Apparatus and method for irradiating a surface with light
US7739813B2 (en) * 2006-04-17 2010-06-22 Eric Beaton Telescoping boom for excavating apparatus
US11684510B2 (en) 2006-04-20 2023-06-27 University of Pittsburgh—of the Commonwealth System of Higher Education Noninvasive, regional brain thermal stimuli for the treatment of neurological disorders
US9492313B2 (en) 2006-04-20 2016-11-15 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Method and apparatus of noninvasive, regional brain thermal stimuli for the treatment of neurological disorders
US8425583B2 (en) 2006-04-20 2013-04-23 University of Pittsburgh—of the Commonwealth System of Higher Education Methods, devices and systems for treating insomnia by inducing frontal cerebral hypothermia
US9211212B2 (en) 2006-04-20 2015-12-15 Cerêve, Inc. Apparatus and method for modulating sleep
WO2007124012A1 (en) 2006-04-20 2007-11-01 University Of Pittsburgh Method and apparatus of noninvasive, regional brain thermal stimuli for the treatment of neurological disorders
JP2008029804A (en) * 2006-06-27 2008-02-14 Family Co Ltd Massage machine
US20080033412A1 (en) * 2006-08-01 2008-02-07 Harry Thomas Whelan System and method for convergent light therapy having controllable dosimetry
US7850720B2 (en) * 2006-09-23 2010-12-14 Ron Shefi Method and apparatus for applying light therapy
WO2008067455A2 (en) * 2006-11-30 2008-06-05 Stryker Corporation System and method for targeted activation of a pharmaceutical agent within the body cavity that is activated by the application of energy
US20080221211A1 (en) * 2007-02-02 2008-09-11 Jackson Streeter Method of treatment of neurological injury or cancer by administration of dichloroacetate
US9358292B2 (en) 2007-04-08 2016-06-07 Immunolight, Llc Methods and systems for treating cell proliferation disorders
US8968221B2 (en) * 2007-04-17 2015-03-03 Bwt Property, Inc. Apparatus and methods for phototherapy
AU2013101152B4 (en) * 2007-04-23 2014-05-08 Transdermal Cap, Inc. Phototherapy light cap
CN101795634A (en) * 2007-04-23 2010-08-04 透皮帽公司 Phototherapy light cap
WO2008156803A2 (en) * 2007-06-19 2008-12-24 Jesseph Jerry M Apparatus and method for the treatment of breast cancer with particle beams
WO2009026382A1 (en) * 2007-08-20 2009-02-26 Kopell, Brian, H. Systems and methods for treating neurological disorders by light stimulation
US9180308B1 (en) 2008-01-18 2015-11-10 Ricky A. Frost Laser device for intracranial illumination via oral or nasal foramina access
US9320914B2 (en) 2008-03-03 2016-04-26 DePuy Synthes Products, Inc. Endoscopic delivery of red/NIR light to the subventricular zone
US9907976B2 (en) 2011-07-08 2018-03-06 Immunolight, Llc Phosphors and scintillators for light stimulation within a medium
EP2291224A2 (en) * 2008-03-18 2011-03-09 PhotoThera, Inc. Method and apparatus for irradiating a surface with continuous-wave or pulsed light
EP3300744A1 (en) 2008-04-04 2018-04-04 Immunolight, Llc. Non-invasive systems and methods for in-situ photobiomodulation
NZ589537A (en) * 2008-04-25 2013-09-27 Inix Ltd Laser hair-loss treatment device
US8882685B2 (en) 2008-05-27 2014-11-11 Bwt Property, Inc. Apparatus and methods for phototherapy
US20110160814A2 (en) * 2008-09-19 2011-06-30 Apira Science, Inc. Phototherapy apparatus for hair, scalp and skin treatment
US8192473B2 (en) * 2008-09-19 2012-06-05 Apira Science, Inc. Phototherapy apparatus for hair, scalp and skin treatment
US8447409B2 (en) * 2008-10-15 2013-05-21 Cochlear Limited Electroneural interface for a medical implant
JP2012510316A (en) * 2008-11-29 2012-05-10 バイオレイズ テクノロジー,インク. Non-contact handpiece for laser tissue cutting
US20100185041A1 (en) * 2009-01-20 2010-07-22 Lee Richard H Cylindrical magnetic field projection method
US20100198281A1 (en) * 2009-01-30 2010-08-05 C.Y. Joseph Chang, MD, PA Methods for treating disorders of perceptual integration by brain modulation
US20100198316A1 (en) * 2009-02-04 2010-08-05 Richard Toselli Intracranial Red Light Treatment Device For Chronic Pain
WO2010134007A2 (en) 2009-05-19 2010-11-25 Ramot At Tel Aviv University Ltd. Low-level energy laser therapy
GB2470927A (en) * 2009-06-10 2010-12-15 Dezac Group Ltd Phototherapy apparatus with skin temperature control
US20110060292A1 (en) * 2009-08-14 2011-03-10 Stat Medical Devices, Inc. Pen needle storage device with integral removal and/or installation system
US8747446B2 (en) 2009-10-12 2014-06-10 Chung-Yang Chen Hair restoration caring device
US20110087310A1 (en) * 2009-10-12 2011-04-14 Wellmike Enterprise Co., Ltd. Hair-growth caring apparatus
US20120059440A1 (en) * 2009-11-25 2012-03-08 Theradome Inc. Portable light hair restoration helmet
US20110144725A1 (en) 2009-12-11 2011-06-16 Bwt Property, Inc. Phototherapy Apparatus With Interactive User Interface
KR101009462B1 (en) * 2010-03-18 2011-01-19 주식회사 루트로닉 Phototherapeutic apparatus
US9308046B2 (en) * 2010-05-18 2016-04-12 Candela Corporation Reduction of pain through lower fluence rates and longer treatment times
US20120078328A1 (en) * 2010-09-27 2012-03-29 Marc Vancraeyenest System and apparatus for treatment of biological cellular structure with electromagnetic wave energy and electromagnetic field energy sources
US9782605B2 (en) * 2010-10-22 2017-10-10 Sharp Laboratories Of America, Inc. Adaptive therapeutic light control system
US9403030B2 (en) * 2011-03-27 2016-08-02 Ramot At Tel-Aviv University Ltd. Low level laser therapy for alzheimer's disease
EP2550993B1 (en) * 2011-03-29 2014-12-10 Valkee Oy Devicefor altering dopamine Level
US20130172659A1 (en) * 2011-12-31 2013-07-04 Oron Zachar Electromagnetic Deep Tissue Excitation
US9352170B1 (en) 2012-01-31 2016-05-31 Christina Davis Spectral light therapy for autism spectral disorders
USD722383S1 (en) 2012-05-01 2015-02-10 Carol Cole Company Skin clearing and toning device
US9883824B2 (en) 2012-08-20 2018-02-06 Taiwan Biophotonic Corporation Detecting device
EP2892615B1 (en) 2012-09-10 2018-11-28 Dermal Photonics Corporation Systems for treating dermatological imperfections
CA2896950C (en) 2013-01-02 2021-10-19 Cereve, Inc. Systems for enhancing sleep
US8909344B2 (en) 2013-03-07 2014-12-09 Jeffrey Edward Arle Head worn brain stimulation device and method
US10376707B2 (en) * 2014-03-14 2019-08-13 Igea S.P.A. Method for the treatment of ischemic stroke by applying an electromagnetic field
USD739541S1 (en) 2014-05-12 2015-09-22 Carol Cole Company Skin clearing and toning device
FR3024355A1 (en) 2014-07-30 2016-02-05 Jean Tien EQUIPMENT FOR THE APPLICATION OF ACTIVE ELEMENTS ON THE SKULL OF A PATIENT
US10668305B2 (en) 2014-08-26 2020-06-02 Elwha Llc Garment system including at least one therapeutic stimulation delivery device and related methods
US10456604B2 (en) 2014-08-26 2019-10-29 Elwha Llc Garment system including at least one therapeutic stimulation delivery device and related methods
KR102609797B1 (en) 2014-09-09 2023-12-06 루미테라 인코포레이티드 Multi-wavelength phototherapy devices, systems, and methods for the non-invasive treatment of damaged or diseased tissue
KR20170084106A (en) 2014-10-20 2017-07-19 렉싱턴 인터내셔널 유한회사 Light emitting hands free device
US9907975B1 (en) 2014-11-19 2018-03-06 Roger D. Porter Therapeutic laser treatment and transdermal stimulation of stem cell differentiation
US11123366B1 (en) 2014-12-15 2021-09-21 Children's Hospital Of Orange County Methods, materials, and systems for treating injuries to the central nervous system using light emitting nanoparticles
USD752237S1 (en) 2015-03-03 2016-03-22 Carol Cole Company Skin toning device
WO2017019839A1 (en) 2015-07-28 2017-02-02 Photonmd, Llc Phototherapy devices for treatment of dermatological disorders of the scalp
BR122020024964B1 (en) 2015-07-28 2024-01-16 Know Bio, Llc METHODS AND DEVICES FOR REDUCING THE PRESENCE, CONCENTRATION OR GROWTH OF PATHOGENS IN OR ON TISSUE OF LIVING MAMMALS
CN106693200B (en) * 2015-12-29 2023-08-01 深圳市智连众康科技有限公司 Intelligent hair growing device and system
US10729914B2 (en) * 2016-01-04 2020-08-04 Jacob Zabara Electromagnetic radiation treatment
USD804047S1 (en) 2016-04-08 2017-11-28 Lexington International, Llc Curved light emitting hands free device
USD802211S1 (en) 2016-04-08 2017-11-07 Lexington International, Llc Stand for light emitting hands free device
KR101801473B1 (en) 2016-06-30 2017-11-27 부산대학교 산학협력단 Apparatus for brain imaging using bundled light elements
FR3065165A1 (en) * 2017-04-14 2018-10-19 Regenlife TRANSCUTANEOUS IRRADIATION DEVICE AND APPLICATION TO THE TREATMENT OF NEURODEGENERATIVE DISEASES
EP4115942A1 (en) 2017-06-30 2023-01-11 Lungpacer Medical Inc. System for prevention, moderation, and/or treatment of cognitive injury
US10525278B2 (en) * 2017-08-15 2020-01-07 Hair Group, LLC Light based therapy devices and methods
CN107693962B (en) * 2017-08-31 2019-09-17 深圳先进技术研究院 A kind of wear-type ultrasonic conducting device
CN108245306A (en) * 2017-12-01 2018-07-06 武汉市海沁医疗科技有限公司 A kind of therapeutic equipment fixing bracket
USD854699S1 (en) 2018-05-15 2019-07-23 Carol Cole Company Elongated skin toning device
KR102540352B1 (en) 2018-07-30 2023-06-07 삼성전자주식회사 Refrigerator
CN109464748B (en) * 2018-11-29 2021-05-11 合肥和正医疗科技有限公司 Knee massager
CN109303982B (en) * 2018-11-29 2021-06-29 合肥和正医疗科技有限公司 Infrared mounting structure of knee massager
CN110141796A (en) * 2019-05-23 2019-08-20 深圳市恒康泰医疗科技有限公司 Cerebral apoplexy, Alzheimer's disease rehabilitation system
WO2020243161A1 (en) * 2019-05-28 2020-12-03 The Trustees Of Columbia University In The City Of New York System, method, computer-accessible medium and apparatus for near infrared optical neural applications
US20220362576A1 (en) * 2019-06-17 2022-11-17 Zhejiang Brainhealth Medical Technology Co., Ltd. Phototherapy device and phototherapy instrument used for irradiation of the head, and therapy method thereof
CN110665126B (en) * 2019-10-09 2021-01-12 丹阳慧创医疗设备有限公司 Equipment and system for transcranial light regulation and control
USD949355S1 (en) 2019-10-15 2022-04-19 JelikaLite, LLC Head wearable light therapy device
CN110975167A (en) * 2019-12-19 2020-04-10 中国科学院苏州生物医学工程技术研究所 Hair growth instrument with imaging system
CN110947100B (en) * 2019-12-20 2023-03-31 武汉资联虹康科技股份有限公司 Method for positioning and correcting magnetic stimulation beat optical fiber
USD953553S1 (en) 2020-02-19 2022-05-31 Carol Cole Company Skin toning device
US11147984B2 (en) 2020-03-19 2021-10-19 Know Bio, Llc Illumination devices for inducing biological effects
CN111420293A (en) * 2020-04-15 2020-07-17 西安蓝极医疗电子科技有限公司 Device for treating brain diseases based on semiconductor laser external irradiation technology
USD957664S1 (en) 2020-07-29 2022-07-12 Carol Cole Company Skin toning device
EP4188539A1 (en) * 2020-08-03 2023-06-07 Mindlight, LLC Enhanced treatment of brain disorders utilizing coordinated negative suppressive stimulation and related devices designed to achieve treatment
US11654294B2 (en) 2021-03-15 2023-05-23 Know Bio, Llc Intranasal illumination devices
IL307537A (en) 2021-04-08 2023-12-01 Niraxx Inc Photobiomodulation therapy garment, methods and uses

Citations (93)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1856969A (en) * 1927-09-06 1932-05-03 Siemens Ag Apparatus for treating living cells by means of rays of light
US3375755A (en) * 1965-10-19 1968-04-02 James A. Hunt Control device for automating sequential machine operation
US3810367A (en) * 1970-07-16 1974-05-14 W Peterson Container for cooling, storage, and shipping of human organ for transplant
US4076393A (en) * 1975-12-15 1978-02-28 The United States Of America As Represented By The Secretary Of The Navy Thermal stress-relieving coupling member and support
US4315514A (en) * 1980-05-08 1982-02-16 William Drewes Method and apparatus for selective cell destruction
US4633872A (en) * 1983-11-08 1987-01-06 Hgm, Incorporated Laser optical delivery apparatus
US4798215A (en) * 1984-03-15 1989-01-17 Bsd Medical Corporation Hyperthermia apparatus
US5282797A (en) * 1989-05-30 1994-02-01 Cyrus Chess Method for treating cutaneous vascular lesions
US5304212A (en) * 1987-06-26 1994-04-19 Brigham And Women's Hospital Assessment and modification of a human subject's circadian cycle
US5401270A (en) * 1990-12-19 1995-03-28 Carl-Zeiss-Stiftung Applicator device for laser radiation
US5405368A (en) * 1992-10-20 1995-04-11 Esc Inc. Method and apparatus for therapeutic electromagnetic treatment
US5500009A (en) * 1990-11-15 1996-03-19 Amron, Ltd. Method of treating herpes
US5501655A (en) * 1992-03-31 1996-03-26 Massachusetts Institute Of Technology Apparatus and method for acoustic heat generation and hyperthermia
US5511563A (en) * 1991-06-21 1996-04-30 Diamond; Donald A. Apparatus and method for treating rheumatoid and psoriatic arthritis
US5601526A (en) * 1991-12-20 1997-02-11 Technomed Medical Systems Ultrasound therapy apparatus delivering ultrasound waves having thermal and cavitation effects
US5616140A (en) * 1994-03-21 1997-04-01 Prescott; Marvin Method and apparatus for therapeutic laser treatment
US5617258A (en) * 1995-10-25 1997-04-01 Plc Medical Systems, Inc. Non-reusable lens cell for a surgical laser handpiece
US5621091A (en) * 1986-07-25 1997-04-15 The Children's Medical Center Corporation Probes for and nucleic acid encoding the muscular dystrophy protein, dystrophin
US5622168A (en) * 1992-11-18 1997-04-22 John L. Essmyer Conductive hydrogels and physiological electrodes and electrode assemblies therefrom
US5627140A (en) * 1995-05-19 1997-05-06 Nec Research Institute, Inc. Enhanced flux pinning in superconductors by embedding carbon nanotubes with BSCCO materials
US5709645A (en) * 1996-01-30 1998-01-20 Comptronic Devices Limited Independent field photic stimulator
US5720894A (en) * 1996-01-11 1998-02-24 The Regents Of The University Of California Ultrashort pulse high repetition rate laser system for biological tissue processing
US5728090A (en) * 1995-02-09 1998-03-17 Quantum Devices, Inc. Apparatus for irradiating living cells
US5755752A (en) * 1992-04-24 1998-05-26 Segal; Kim Robin Diode laser irradiation system for biological tissue stimulation
US5871521A (en) * 1995-08-25 1999-02-16 Matsushita Electric Industrial Co., Ltd. Laser probe for medical treatment
US5879376A (en) * 1995-07-12 1999-03-09 Luxar Corporation Method and apparatus for dermatology treatment
US5902741A (en) * 1986-04-18 1999-05-11 Advanced Tissue Sciences, Inc. Three-dimensional cartilage cultures
WO1999062599A1 (en) * 1998-06-02 1999-12-09 Amir Oron Ischemia laser treatment
US6030767A (en) * 1997-01-21 2000-02-29 The American National Red Cross Intracellular and extracellular decontamination of whole blood and blood components by amphiphilic phenothiazin-5-ium dyes plus light
US6042531A (en) * 1995-06-19 2000-03-28 Holcomb; Robert R. Electromagnetic therapeutic treatment device and methods of using same
US6046046A (en) * 1997-09-23 2000-04-04 Hassanein; Waleed H. Compositions, methods and devices for maintaining an organ
US6045575A (en) * 1997-09-10 2000-04-04 Amt, Inc. Therapeutic method and internally illuminated garment for the management of disorders treatable by phototherapy
US6060306A (en) * 1995-06-07 2000-05-09 Advanced Tissue Sciences, Inc. Apparatus and method for sterilizing, seeding, culturing, storing, shipping and testing replacement cartilage tissue constructs
US6063108A (en) * 1997-01-06 2000-05-16 Salansky; Norman Method and apparatus for localized low energy photon therapy (LEPT)
US6179830B1 (en) * 1996-07-24 2001-01-30 J. Morita Manufacturing Corporation Laser probe
US6179771B1 (en) * 1998-04-21 2001-01-30 Siemens Aktiengesellschaft Coil arrangement for transcranial magnetic stimulation
US6187210B1 (en) * 1997-06-30 2001-02-13 The Regents Of The University Of California Epidermal abrasion device with isotropically etched tips, and method of fabricating such a device
US6198958B1 (en) * 1998-06-11 2001-03-06 Beth Israel Deaconess Medical Center, Inc. Method and apparatus for monitoring a magnetic resonance image during transcranial magnetic stimulation
US6197020B1 (en) * 1996-08-12 2001-03-06 Sublase, Inc. Laser apparatus for subsurface cutaneous treatment
US6210317B1 (en) * 1998-07-13 2001-04-03 Dean R. Bonlie Treatment using oriented unidirectional DC magnetic field
US6210425B1 (en) * 1999-07-08 2001-04-03 Light Sciences Corporation Combined imaging and PDT delivery system
US6214035B1 (en) * 1999-03-23 2001-04-10 Jackson Streeter Method for improving cardiac microcirculation
US6221095B1 (en) * 1996-11-13 2001-04-24 Meditech International Inc. Method and apparatus for photon therapy
US6238424B1 (en) * 1996-06-07 2001-05-29 Biolight Patent Holding Ab Device for external treatment with pulsating light of high duty cycle
US6238425B1 (en) * 1996-06-07 2001-05-29 Biolight Patent Holding Ab Device for external medical treatment with monochromatic light
US6344050B1 (en) * 1998-12-21 2002-02-05 Light Sciences Corporation Use of pegylated photosensitizer conjugated with an antibody for treating abnormal tissue
US20020018834A1 (en) * 1997-04-01 2002-02-14 Vaughan Nicholas John Cooking method and apparatus
US20020029071A1 (en) * 2000-03-23 2002-03-07 Colin Whitehurst Therapeutic light source and method
US6358272B1 (en) * 1995-05-16 2002-03-19 Lutz Wilden Therapy apparatus with laser irradiation device
US6363285B1 (en) * 2000-01-21 2002-03-26 Albert C. Wey Therapeutic sleeping aid device
US6364907B1 (en) * 1998-10-09 2002-04-02 Qlt Inc. Method to prevent xenograft transplant rejection
US6379939B1 (en) * 2000-07-18 2002-04-30 Rachel Lubart Method for increasing the fertilizing capability of sperm cells
US6379376B1 (en) * 1996-11-25 2002-04-30 Rachel Lubart Device for light irradiation onto tissue
US6379295B1 (en) * 1997-09-26 2002-04-30 Gilson Woo Treatment of afflictions, ailments and diseases
US6395016B1 (en) * 1996-07-28 2002-05-28 Biosense, Inc. Method of treating a heart using cells irradiated in vitro with biostimulatory irradiation
US6397107B1 (en) * 1998-04-27 2002-05-28 Bokwang Co., Ltd. Apparatus for embolic treatment using high frequency induction heating
US20030021124A1 (en) * 2000-02-23 2003-01-30 Jens Elbrecht Handpiece for radiating light onto skin surface during a medical or cosmetic skin treatment
US20030023283A1 (en) * 1998-11-30 2003-01-30 Mcdaniel David H. Method and apparatus for the stimulation of hair growth
US6514220B2 (en) * 2001-01-25 2003-02-04 Walnut Technologies Non focussed method of exciting and controlling acoustic fields in animal body parts
US6537301B1 (en) * 1995-03-23 2003-03-25 Tsutomu Kamei Method of noninvasively enhancing immunosurveillance capacity and apparatus for applying pulsed light to at least forehead
US6537302B1 (en) * 1999-01-20 2003-03-25 Biolight Patent Holding Ab Means for external medical treatment by means of light
US6551308B1 (en) * 1997-09-17 2003-04-22 Laser-Und Medizin-Technologie Gmbh Berlin Laser therapy assembly for muscular tissue revascularization
US6676655B2 (en) * 1998-11-30 2004-01-13 Light Bioscience L.L.C. Low intensity light therapy for the manipulation of fibroblast, and fibroblast-derived mammalian cells and collagen
US20040015214A1 (en) * 2001-11-09 2004-01-22 Simkin Guillermo O. Photodynamic therapy for the treatment of hair loss
US20040014199A1 (en) * 2002-01-09 2004-01-22 Jackson Streeter Method for preserving organs for transplant
US6689062B1 (en) * 1999-11-23 2004-02-10 Microaccess Medical Systems, Inc. Method and apparatus for transesophageal cardiovascular procedures
US20040030325A1 (en) * 2001-12-05 2004-02-12 Nicholas Cahir Removable attachments for laser emitting devices
US6692517B2 (en) * 1999-01-15 2004-02-17 Cynosure, Inc. Optical radiation treatment for enhancement of wound healing
US20040036975A1 (en) * 2001-12-10 2004-02-26 Michael Slatkine Method and apparatus for improving safety during exposure to a monochromatic light source
US20040044384A1 (en) * 2002-09-03 2004-03-04 Leber Leland C. Therapeutic method and apparatus
US6702837B2 (en) * 2002-04-23 2004-03-09 Phillip Gutwein Therapeutic light device
US20040073278A1 (en) * 2001-09-04 2004-04-15 Freddy Pachys Method of and device for therapeutic illumination of internal organs and tissues
US20040093042A1 (en) * 2002-06-19 2004-05-13 Palomar Medical Technologies, Inc. Method and apparatus for photothermal treatment of tissue at depth
US20050009161A1 (en) * 2002-11-01 2005-01-13 Jackson Streeter Enhancement of in vitro culture or vaccine production using electromagnetic energy treatment
US20050005626A1 (en) * 2003-07-08 2005-01-13 Mcmahon Richard Cooling device for pain relief
US20050024853A1 (en) * 2003-07-30 2005-02-03 Mellen Thomas-Benedict Modularized light processing of body components
US6866678B2 (en) * 2002-12-10 2005-03-15 Interbational Technology Center Phototherapeutic treatment methods and apparatus
US20050107851A1 (en) * 2002-11-01 2005-05-19 Taboada Luis D. Device and method for providing phototherapy to the brain
US6899723B2 (en) * 1999-01-15 2005-05-31 Light Sciences Corporation Transcutaneous photodynamic treatment of targeted cells
US7041094B2 (en) * 1999-03-15 2006-05-09 Cutera, Inc. Tissue treatment device and method
US7054676B2 (en) * 2001-04-24 2006-05-30 Duke University MR-compatible methods and systems for cardiac monitoring and gating
US20070066996A1 (en) * 2003-03-17 2007-03-22 Katzman Daniel E Modafinil-based neurorehabilitation of impaired neurological function associated with brian injury
US7217266B2 (en) * 2001-05-30 2007-05-15 Anderson R Rox Apparatus and method for laser treatment with spectroscopic feedback
US20070114872A1 (en) * 2005-11-23 2007-05-24 Daewood Electronics Corporation Rotor for use in induction motor
US20080033412A1 (en) * 2006-08-01 2008-02-07 Harry Thomas Whelan System and method for convergent light therapy having controllable dosimetry
US20080051858A1 (en) * 2001-06-26 2008-02-28 Photomed Technologies, Inc. Therapeutic methods using electromagnetic radiation
US7344555B2 (en) * 2003-04-07 2008-03-18 The United States Of America As Represented By The Department Of Health And Human Services Light promotes regeneration and functional recovery after spinal cord injury
US20080077199A1 (en) * 2006-09-23 2008-03-27 Ron Shefi Method and apparatus for applying light therapy
US7351253B2 (en) * 2005-06-16 2008-04-01 Codman & Shurtleff, Inc. Intranasal red light probe for treating Alzheimer's disease
US20090054955A1 (en) * 2007-08-20 2009-02-26 Kopell Brian H Systems and Methods for Treating Neurological Disorders by Light Stimulation
US20090088680A1 (en) * 2005-07-22 2009-04-02 Alexander Aravanis Optical tissue interface method and apparatus for stimulating cells
US20090112280A1 (en) * 2007-10-30 2009-04-30 Neuropace, Inc. Systems, methods and devices for a skull/brain interface
US20110060266A1 (en) * 2001-11-01 2011-03-10 Photothera, Inc. Enhanced stem cell therapy and stem cell production through the administration of low level light energy

Family Cites Families (273)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4110023A1 (en) 1991-03-27 1992-10-01 Ringsdorff Werke Gmbh SHOCK ABSORBER PISTON FROM UNEQUAL, JOINTED PARTS
US3283147A (en) * 1962-05-09 1966-11-01 Emik A Avakian Energy-projecting and scanning apparatus
DE1491830B1 (en) 1968-06-19 1970-06-18 Saba Gmbh Circuit arrangement for a device to calm down and induce sleep in sleep-disturbed people
US3735755A (en) * 1971-06-28 1973-05-29 Interscience Research Inst Noninvasive surgery method and apparatus
US4343301A (en) * 1979-10-04 1982-08-10 Robert Indech Subcutaneous neural stimulation or local tissue destruction
GB2071500B (en) 1980-02-27 1984-03-21 Nath G Coagulator
US4343215A (en) 1980-09-11 1982-08-10 The United States Of America As Represented By The Secretary Of The Treasury Perforating cylinder
HU186081B (en) 1981-09-02 1985-05-28 Fenyo Marta Process and apparatus for stimulating healing of pathologic points on the surface of the body first of all of wounds, ulcera and other epithelial lesions
JPS5844784A (en) 1981-09-11 1983-03-15 Nippon Sekigaisen Kogyo Kk Laser device
FR2514257B1 (en) 1981-10-09 1986-08-01 Ceskoslovenska Akademie Ved APPARATUS FOR STIMULATING ACUPUNCTURE POINTS BY LIGHT RADIATION
DE3200584A1 (en) 1982-01-12 1983-07-21 geb. Budwig Johanna Dr. 7290 Freudenstadt Budwig Method for controlling the energy level, especially of the pi electrons, in water by means of a red-light laser in such a way that the water treated in this way can be used for preserving transplants
IT1171078B (en) 1983-07-04 1987-06-10 Adriano Tessiore ELECTROMECHANICAL IRRADIANT EQUIPMENT, FOR THE TREATMENT OF HAIR LEATHER, AGAINST Baldness
JPS60232176A (en) * 1984-04-20 1985-11-18 ジユデイス ウオーカー エム.デイ. Treatment apparatus by laser beam
US4669466A (en) * 1985-01-16 1987-06-02 Lri L.P. Method and apparatus for analysis and correction of abnormal refractive errors of the eye
US4850351A (en) 1985-05-22 1989-07-25 C. R. Bard, Inc. Wire guided laser catheter
EP0214712B1 (en) 1985-07-31 1992-09-02 C.R. Bard, Inc. Infrared laser catheter apparatus
SE455920B (en) * 1986-01-29 1988-08-22 Hans Wiksell TUMOR HYPERTERMY TREATMENT DEVICE
DE3603156A1 (en) * 1986-02-03 1987-08-06 Zeiss Carl Fa DEVICE FOR THERAPEUTIC RADIATION OF ORGANIC TISSUE WITH LASER RADIATION
JPS633873A (en) * 1986-06-23 1988-01-08 富士電機株式会社 Laser remedy device
JPS63130075A (en) * 1986-11-19 1988-06-02 富士電機株式会社 Laser medical treatment device
IL82830A (en) * 1987-06-09 1992-03-29 Simeone Rochkind Apparatus for inducing functional regeneration of nerve fibres at an injured site of the spinal cord
US5503637A (en) * 1987-06-26 1996-04-02 Light Sciences, Inc. Apparatus for producing and delivering high-intensity light to a subject
US5259380A (en) * 1987-11-04 1993-11-09 Amcor Electronics, Ltd. Light therapy system
US4930504A (en) * 1987-11-13 1990-06-05 Diamantopoulos Costas A Device for biostimulation of tissue and method for treatment of tissue
US5054470A (en) * 1988-03-02 1991-10-08 Laboratory Equipment, Corp. Ultrasonic treatment transducer with pressurized acoustic coupling
US4951653A (en) * 1988-03-02 1990-08-28 Laboratory Equipment, Corp. Ultrasound brain lesioning system
US5053006A (en) 1988-04-19 1991-10-01 Watson Brant D Method for the permanent occlusion of arteries
US4998930A (en) 1988-08-03 1991-03-12 Phototherapeutic Systems Intracavity laser phototherapy method
US5125925A (en) 1988-08-03 1992-06-30 Photoradiation Systems Intracavity laser catheter with sensing fiber
US4951482A (en) * 1988-12-21 1990-08-28 Gilbert Gary L Hypothermic organ transport apparatus
US5167610A (en) 1989-05-25 1992-12-01 Matsushita Electric Works, Ltd. Sleep inducing system
CA2021506A1 (en) * 1989-08-17 1991-02-18 Abraham R. Liboff Electromagnetic treatment therapy for stroke victims
US5447528A (en) 1989-10-30 1995-09-05 Gerardo; Ernesto Method of treating seasonal affective disorder
US5047006A (en) 1989-11-06 1991-09-10 Howard Brandston Personal integrating sphere system
US5037374A (en) * 1989-11-29 1991-08-06 Carol Mark P Stereotactic-guided radiation therapy system with variable-length compensating collimator
IE911318A1 (en) 1990-04-23 1991-10-23 Yeda Res & Dev Use of a tumor necrosis factor for facilitating nerve¹regeneration
JPH0423634A (en) 1990-05-18 1992-01-28 Mitsubishi Electric Corp Line error rate monitor device
US6196226B1 (en) * 1990-08-10 2001-03-06 University Of Washington Methods and apparatus for optically imaging neuronal tissue and activity
US5265598A (en) 1990-08-27 1993-11-30 Energy Spectrum Foundation Phototherapy method
US5125395A (en) 1990-09-12 1992-06-30 Adair Edwin Lloyd Deflectable sheath for optical catheter
DE4108328A1 (en) 1991-03-14 1992-09-17 Durango Holding Gmbh Therapy treatment radiation appts. - has control circuit determining duration of IR, visible or UV radiation from matrix of elements e.g. LEDs
US5540737A (en) * 1991-06-26 1996-07-30 Massachusetts Institute Of Technology Minimally invasive monopole phased array hyperthermia applicators and method for treating breast carcinomas
US5951596A (en) 1991-07-01 1999-09-14 Laser Biotherapy Inc Biological tissue stimulation by optical energy
US5445146A (en) * 1995-03-31 1995-08-29 Bellinger; Gary J. Biological tissue stimulation by low level optical energy
US5217455A (en) 1991-08-12 1993-06-08 Tan Oon T Laser treatment method for removing pigmentations, lesions, and abnormalities from the skin of a living human
US5640978A (en) * 1991-11-06 1997-06-24 Diolase Corporation Method for pain relief using low power laser light
US5344418A (en) * 1991-12-12 1994-09-06 Shahriar Ghaffari Optical system for treatment of vascular lesions
IL100545A (en) 1991-12-29 1995-03-15 Dimotech Ltd Apparatus for photodynamic therapy treatment
DE4213053A1 (en) * 1992-04-21 1993-10-28 Matthias Dr Ing Herrig Laser radiation application device for brain tumour therapy - has radiation element at distal end of flexible light conductor enclosed by cooled hermetically sealed outer sheath
GB9208653D0 (en) 1992-04-22 1992-06-10 Unilever Plc Cosmetic composition and process for making it
US5267294A (en) * 1992-04-22 1993-11-30 Hitachi Medical Corporation Radiotherapy apparatus
US5807881A (en) * 1992-05-27 1998-09-15 Quadra Logic Technologies, Inc. Method for selectively reducing activated leukocyte cell population
KR100300618B1 (en) 1992-12-25 2001-11-22 오노 시게오 EXPOSURE METHOD, EXPOSURE DEVICE, AND DEVICE MANUFACTURING METHOD USING THE DEVICE
US5368555A (en) 1992-12-29 1994-11-29 Hepatix, Inc. Organ support system
FR2706132B1 (en) * 1993-06-07 1995-09-01 Atea Device for treating brain lesions by gamma radiation, and corresponding treatment device.
US5445608A (en) * 1993-08-16 1995-08-29 James C. Chen Method and apparatus for providing light-activated therapy
US5958761A (en) * 1994-01-12 1999-09-28 Yeda Research And Developement Co. Ltd. Bioreactor and system for improved productivity of photosynthetic algae
SE504298C2 (en) 1994-01-20 1996-12-23 Biolight Patent Holding Ab Device for wound healing by light
SE502784C2 (en) 1994-01-20 1996-01-15 Biolight Patent Holding Ab Device for medical treatment is externalized by light
US5358503A (en) * 1994-01-25 1994-10-25 Bertwell Dale E Photo-thermal therapeutic device and method
IL108772A0 (en) 1994-02-24 1994-05-30 Amcor Ltd Treatment of rhinitis by biostimulative illumination
US5474528A (en) * 1994-03-21 1995-12-12 Dusa Pharmaceuticals, Inc. Combination controller and patch for the photodynamic therapy of dermal lesion
US6156028A (en) 1994-03-21 2000-12-05 Prescott; Marvin A. Method and apparatus for therapeutic laser treatment of wounds
US5989245A (en) 1994-03-21 1999-11-23 Prescott; Marvin A. Method and apparatus for therapeutic laser treatment
US5464436A (en) 1994-04-28 1995-11-07 Lasermedics, Inc. Method of performing laser therapy
US5603728A (en) 1994-06-20 1997-02-18 Pachys; Freddy Scalp cooling/heating apparatus
US5762867A (en) * 1994-09-01 1998-06-09 Baxter International Inc. Apparatus and method for activating photoactive agents
US5540727A (en) 1994-11-15 1996-07-30 Cardiac Pacemakers, Inc. Method and apparatus to automatically optimize the pacing mode and pacing cycle parameters of a dual chamber pacemaker
JPH10509873A (en) 1994-11-29 1998-09-29 ザ ユニバーシティ オブ クイーンズランド Remedies
US6107325A (en) * 1995-01-17 2000-08-22 Qlt Phototherapeutics, Inc. Green porphyrins as immunomodulators
US5595568A (en) * 1995-02-01 1997-01-21 The General Hospital Corporation Permanent hair removal using optical pulses
US5735844A (en) * 1995-02-01 1998-04-07 The General Hospital Corporation Hair removal using optical pulses
US5643334A (en) * 1995-02-07 1997-07-01 Esc Medical Systems Ltd. Method and apparatus for the diagnostic and composite pulsed heating and photodynamic therapy treatment
US5769878A (en) 1995-03-23 1998-06-23 Kamei; Tsutomu Method of noninvasively enhancing immunosurveillance capacity
US20030181961A1 (en) 1995-03-23 2003-09-25 Tsutomu Kamei Method of noninvasively enhancing immunosurveillance capacity and apparatus for applying pulsed light to at least a portion of a user's temporal region
US5849585A (en) 1995-05-10 1998-12-15 Genetech, Inc. Isolating and culturing Schwann cells
US5683382A (en) 1995-05-15 1997-11-04 Arrow International Investment Corp. Microwave antenna catheter
US5571152A (en) 1995-05-26 1996-11-05 Light Sciences Limited Partnership Microminiature illuminator for administering photodynamic therapy
CA2222741C (en) 1995-06-06 2002-05-28 Vincent Chow Multi-phasic microphotodiode retinal implant and adaptive imaging retinal stimulation system
US5849029A (en) * 1995-12-26 1998-12-15 Esc Medical Systems, Ltd. Method for controlling the thermal profile of the skin
US5964749A (en) * 1995-09-15 1999-10-12 Esc Medical Systems Ltd. Method and apparatus for skin rejuvenation and wrinkle smoothing
AU7262496A (en) 1995-10-13 1997-04-30 Nordson Corporation Flip chip underfill system and method
AT403990B (en) 1995-11-24 1998-07-27 Nagypal Tibor Dipl Ing Dr DEVICE FOR THE PHOTODYNAMIC TREATMENT OF LIVING BEINGS OR. ORGANS THE SAME
DE19545259A1 (en) 1995-11-24 1997-05-28 Mannesmann Ag Method and device for producing thin metal strands
US20040010300A1 (en) * 1996-02-13 2004-01-15 Leonardo Masotti Device and method for biological tissue stimulation by high intensity laser therapy
US5842477A (en) 1996-02-21 1998-12-01 Advanced Tissue Sciences, Inc. Method for repairing cartilage
US6253097B1 (en) 1996-03-06 2001-06-26 Datex-Ohmeda, Inc. Noninvasive medical monitoring instrument using surface emitting laser devices
US5707396A (en) 1996-04-25 1998-01-13 Institute National De La Sante De La Recherche Medicale (Inserm) Method of arresting degeneration of the substantia nigra by high frequency stimulation of subthalamic nucleus
US5711316A (en) 1996-04-30 1998-01-27 Medtronic, Inc. Method of treating movement disorders by brain infusion
US5824024A (en) 1996-05-03 1998-10-20 Dial; Daniel Christoper Illumination devices and methods for treating light deficiency and mood disorders
US5983141A (en) 1996-06-27 1999-11-09 Radionics, Inc. Method and apparatus for altering neural tissue function
JP3183831B2 (en) 1996-07-12 2001-07-09 ヒロセ電機株式会社 Lamp socket
WO1998004321A1 (en) 1996-07-28 1998-02-05 Biosense Inc. Electromagnetic cardiac biostimulation
US5820626A (en) * 1996-07-30 1998-10-13 Laser Aesthetics, Inc. Cooling laser handpiece with refillable coolant reservoir
AU3314297A (en) 1996-09-04 1998-03-12 Esc Medical Systems Ltd. Device and method for cooling skin during laser treatment
US5817008A (en) * 1996-10-31 1998-10-06 Spacelabs Medical, Inc. Conformal pulse oximetry sensor and monitor
US5928945A (en) 1996-11-20 1999-07-27 Advanced Tissue Sciences, Inc. Application of shear flow stress to chondrocytes or chondrocyte stem cells to produce cartilage
US20010003800A1 (en) 1996-11-21 2001-06-14 Steven J. Frank Interventional photonic energy emitter system
US6517532B1 (en) 1997-05-15 2003-02-11 Palomar Medical Technologies, Inc. Light energy delivery head
US6653618B2 (en) 2000-04-28 2003-11-25 Palomar Medical Technologies, Inc. Contact detecting method and apparatus for an optical radiation handpiece
US6015404A (en) * 1996-12-02 2000-01-18 Palomar Medical Technologies, Inc. Laser dermatology with feedback control
US6162211A (en) 1996-12-05 2000-12-19 Thermolase Corporation Skin enhancement using laser light
US5899857A (en) * 1997-01-07 1999-05-04 Wilk; Peter J. Medical treatment method with scanner input
US5830208A (en) 1997-01-31 1998-11-03 Laserlite, Llc Peltier cooled apparatus and methods for dermatological treatment
US5810801A (en) 1997-02-05 1998-09-22 Candela Corporation Method and apparatus for treating wrinkles in skin using radiation
US6107608A (en) * 1997-03-24 2000-08-22 Micron Technology, Inc. Temperature controlled spin chuck
US5993442A (en) 1997-03-25 1999-11-30 Termuno Kabushiki Kaisha Medical laser irradiation apparatus
US5916518A (en) * 1997-04-08 1999-06-29 Allison Engine Company Cobalt-base composition
US6117128A (en) * 1997-04-30 2000-09-12 Kenton W. Gregory Energy delivery catheter and method for the use thereof
US6235015B1 (en) * 1997-05-14 2001-05-22 Applied Optronics Corporation Method and apparatus for selective hair depilation using a scanned beam of light at 600 to 1000 nm
EP0991372B1 (en) 1997-05-15 2004-08-04 Palomar Medical Technologies, Inc. Apparatus for dermatology treatment
US6161048A (en) * 1997-06-26 2000-12-12 Radionics, Inc. Method and system for neural tissue modification
US6273885B1 (en) 1997-08-16 2001-08-14 Cooltouch Corporation Handheld photoepilation device and method
EP1009483B1 (en) 1997-08-25 2005-12-21 Advanced Photodynamic Technologies, Inc. Treatment device for topical photodynamic therapy
US6149679A (en) 1997-09-15 2000-11-21 Adm Tronics Ulimited, Inc. Corona discharge beam treatment of neuro-cerebral disorders
US5954762A (en) * 1997-09-15 1999-09-21 Di Mino; Alfonso Computer-controlled servo-mechanism for positioning corona discharge beam applicator
GB9721506D0 (en) 1997-10-10 1997-12-10 Virulite Limited Treatment of diseases
AU2606399A (en) 1998-02-23 1999-09-06 Laser Research International, Inc. Therapeutic cluster laser device
CA2323479A1 (en) * 1998-03-12 1999-09-16 Palomar Medical Technologies, Inc. System for electromagnetic radiation of the skin
US6213998B1 (en) 1998-04-02 2001-04-10 Vanderbilt University Laser surgical cutting probe and system
US6074411A (en) 1998-04-04 2000-06-13 Lai; Ming Multiple diode laser apparatus and method for laser acupuncture therapy
US6306130B1 (en) 1998-04-07 2001-10-23 The General Hospital Corporation Apparatus and methods for removing blood vessels
US6264649B1 (en) * 1998-04-09 2001-07-24 Ian Andrew Whitcroft Laser treatment cooling head
RU2145247C1 (en) 1998-04-10 2000-02-10 Жаров Владимир Павлович Photomatrix therapeutic device for treatment of extended pathologies
US6223071B1 (en) 1998-05-01 2001-04-24 Dusa Pharmaceuticals Inc. Illuminator for photodynamic therapy and diagnosis which produces substantially uniform intensity visible light
US6391023B1 (en) * 1998-05-28 2002-05-21 Pearl Technology Holdings, Llc Thermal radiation facelift device
US6440121B1 (en) 1998-05-28 2002-08-27 Pearl Technology Holdings, Llc. Surgical device for performing face-lifting surgery using radiofrequency energy
DE19823947A1 (en) * 1998-05-28 1999-12-02 Baasel Carl Lasertech Method and device for superficial heating of tissue
US6432101B1 (en) 1998-05-28 2002-08-13 Pearl Technology Holdings, Llc Surgical device for performing face-lifting using electromagnetic radiation
US6084242A (en) 1998-07-06 2000-07-04 Brown, Jr. Doyle S. Method and device for stimulating the immune system and generating healing at the cellular level
US6574501B2 (en) * 1998-07-13 2003-06-03 Childrens Hospital Los Angeles Assessing blood brain barrier dynamics or identifying or measuring selected substances or toxins in a subject by analyzing Raman spectrum signals of selected regions in the eye
US6059820A (en) 1998-10-16 2000-05-09 Paradigm Medical Corporation Tissue cooling rod for laser surgery
US7901400B2 (en) * 1998-10-23 2011-03-08 Covidien Ag Method and system for controlling output of RF medical generator
US6530919B1 (en) 1998-10-30 2003-03-11 Redfield, Inc. Infrared coagulator with disposable tip light guide
GB9826157D0 (en) 1998-11-27 1999-01-20 British Telecomm Announced session control
US6663659B2 (en) 2000-01-13 2003-12-16 Mcdaniel David H. Method and apparatus for the photomodulation of living cells
US9192780B2 (en) 1998-11-30 2015-11-24 L'oreal Low intensity light therapy for treatment of retinal, macular, and visual pathway disorders
US20020198577A1 (en) 1998-11-30 2002-12-26 Jaillet Peter D. Apparatus and method for changing critical brain activity using light and sound
US6299632B1 (en) 1998-11-30 2001-10-09 Peter Jaillet Method for changing critical brain activity using light and sound
AU1671600A (en) * 1998-12-12 2000-07-03 Virulite Limited Electromagnetic radiation therapy
US6449466B1 (en) 1998-12-30 2002-09-10 Samsung Electronics Co., Ltd. Adaptive digital pre-distortion correction circuit for use in a transmitter in a digital communication system and method of operation
US6157854A (en) * 1999-01-13 2000-12-05 Bales Scientific Inc. Photon irradiation human pain treatment monitored by thermal imaging
US6454789B1 (en) 1999-01-15 2002-09-24 Light Science Corporation Patient portable device for photodynamic therapy
US20030166156A1 (en) * 1999-01-19 2003-09-04 Sheppard Paul O. Zsig67: a member of the human secretin-glucagon-VIP hormone family
SE515992C2 (en) 1999-01-20 2001-11-05 Biolight Patent Holding Ab Light emitting organs for medical treatment are externalized by light
US7107997B1 (en) 1999-03-16 2006-09-19 Jeffrey Warren Moses Method and apparatus for increasing angiogenic, growth factor in heart muscle
US6267779B1 (en) 1999-03-29 2001-07-31 Medelaser, Llc Method and apparatus for therapeutic laser treatment
US6733492B2 (en) * 1999-05-31 2004-05-11 Nidek Co., Ltd. Laser treatment apparatus
US6290713B1 (en) * 1999-08-24 2001-09-18 Thomas A. Russell Flexible illuminators for phototherapy
US20040082862A1 (en) 2002-07-10 2004-04-29 Britton Chance Examination and imaging of brain cognitive functions
US6524324B1 (en) * 1999-11-05 2003-02-25 Scimed Life Systems, Inc. Method and apparatus for demand injury in stimulating angiogenesis
WO2001037717A2 (en) 1999-11-26 2001-05-31 Applied Spectral Imaging Ltd. System and method for functional brain mapping
US7066929B1 (en) * 1999-12-02 2006-06-27 Radiancy Inc. Selective photothermolysis
CA2393535A1 (en) * 1999-12-07 2001-06-14 Krasnow Institute Adaptive electric field modulation of neural systems
US6743222B2 (en) 1999-12-10 2004-06-01 Candela Corporation Method of treating disorders associated with sebaceous follicles
US6277974B1 (en) * 1999-12-14 2001-08-21 Cogent Neuroscience, Inc. Compositions and methods for diagnosing and treating conditions, disorders, or diseases involving cell death
EP1244390B1 (en) 1999-12-30 2006-08-16 Pearl Technology Holdings, LLC Face-lifting device
US6542524B2 (en) 2000-03-03 2003-04-01 Charles Miyake Multiwavelength laser for illumination of photo-dynamic therapy drugs
US6436094B1 (en) 2000-03-16 2002-08-20 Laserscope, Inc. Electromagnetic and laser treatment and cooling device
US6692486B2 (en) 2000-05-10 2004-02-17 Minnesota Medical Physics, Llc Apparatus and method for treatment of cerebral aneurysms, arterial-vascular malformations and arterial fistulas
US7083610B1 (en) 2000-06-07 2006-08-01 Laserscope Device for irradiating tissue
DE10029580C1 (en) 2000-06-15 2002-01-10 Ferton Holding Sa Device for removing body stones with an intracorporeal lithotripter
US6447537B1 (en) 2000-06-21 2002-09-10 Raymond A. Hartman Targeted UV phototherapy apparatus and method
US20020068927A1 (en) * 2000-06-27 2002-06-06 Prescott Marvin A. Method and apparatus for myocardial laser treatment
US6471716B1 (en) * 2000-07-11 2002-10-29 Joseph P. Pecukonis Low level light therapy method and apparatus with improved wavelength, temperature and voltage control
WO2002003872A2 (en) * 2000-07-11 2002-01-17 Johns Hopkins University Application of photochemotherapy for the treatment of cardiac arrhythmias
US6421562B1 (en) * 2000-07-17 2002-07-16 Jesse Ross Alternative treatment of a nonsurgically treatable intracranial occlusion
US6402678B1 (en) * 2000-07-31 2002-06-11 Neuralieve, Inc. Means and method for the treatment of migraine headaches
WO2002013906A1 (en) 2000-08-16 2002-02-21 Vanderbilt University Methods and devices for optical stimulation of neural tissues
US6602275B1 (en) * 2000-09-18 2003-08-05 Jana Sullivan Device and method for therapeutic treatment of living organisms
US6571735B1 (en) * 2000-10-10 2003-06-03 Loy Wilkinson Non-metallic bioreactor and uses
US7463916B2 (en) 2000-10-16 2008-12-09 Hitachi Medical Corporation Optical measurement apparatus for living body
AU2002245163A1 (en) 2000-10-20 2002-07-24 Photomedex Controlled dose delivery of ultraviolet light for treating skin disorders
AU2002232892B2 (en) 2000-10-24 2008-06-26 Intrexon Corporation Method and device for selectively targeting cells within a three -dimensional specimen
US7668586B2 (en) 2000-11-02 2010-02-23 Cornell Research Foundation, Inc. In vivo multiphoton diagnostic detection and imaging of a neurodegenerative disease
JP2002165893A (en) * 2000-12-01 2002-06-11 Nidek Co Ltd Laser treatment device
WO2002062420A1 (en) 2001-01-22 2002-08-15 SØRENSEN, Svein Photodynamic stimulation device and methods
ITMO20010008A1 (en) * 2001-01-29 2002-07-29 Laserwave Srl DEVICE FOR SKIN TREATMENTS
DE60225783T2 (en) * 2001-02-06 2009-04-09 Qlt Inc., Vancouver PHOTODYNAMIC THERAPY WITH REDUCED IRRADIATION THICKNESS
US7753943B2 (en) 2001-02-06 2010-07-13 Qlt Inc. Reduced fluence rate PDT
US8034803B2 (en) * 2001-02-06 2011-10-11 Qlt Inc. Photodynamic therapy of occult age-related macular degeneration
JP4027049B2 (en) 2001-02-28 2007-12-26 株式会社ニデック Laser therapy device
US6746473B2 (en) * 2001-03-02 2004-06-08 Erchonia Patent Holdings, Llc Therapeutic laser device
US7101384B2 (en) 2001-03-08 2006-09-05 Tru-Light Corporation Light processing of selected body components
DE10123926A1 (en) 2001-03-08 2002-09-19 Optomed Optomedical Systems Gmbh irradiation device
WO2002092509A1 (en) 2001-05-11 2002-11-21 Rhodia Chimie Thickening precipitated silica granules obtained by granulation and use thereof as thickening agent in dental composition
US6638272B2 (en) 2001-06-04 2003-10-28 Cynosure, Inc Cooling delivery guide attachment for a laser scanner apparatus
US6666878B2 (en) * 2001-06-06 2003-12-23 Inca Asset Management S.A. Method and device stimulating the activity of hair follicles
US6770069B1 (en) 2001-06-22 2004-08-03 Sciton, Inc. Laser applicator
US20040158300A1 (en) 2001-06-26 2004-08-12 Allan Gardiner Multiple wavelength illuminator having multiple clocked sources
US6832111B2 (en) 2001-07-06 2004-12-14 Hosheng Tu Device for tumor diagnosis and methods thereof
US6685702B2 (en) * 2001-07-06 2004-02-03 Rodolfo C. Quijano Device for treating tissue and methods thereof
US9993659B2 (en) 2001-11-01 2018-06-12 Pthera, Llc Low level light therapy for enhancement of neurologic function by altering axonal transport rate
US7534255B1 (en) * 2003-01-24 2009-05-19 Photothera, Inc Low level light therapy for enhancement of neurologic function
US8308784B2 (en) 2006-08-24 2012-11-13 Jackson Streeter Low level light therapy for enhancement of neurologic function of a patient affected by Parkinson's disease
US10315042B2 (en) 2001-11-01 2019-06-11 Pthera LLC Device and method for providing a synergistic combination of phototherapy and a non-light energy modality to the brain
US20030109906A1 (en) * 2001-11-01 2003-06-12 Jackson Streeter Low level light therapy for the treatment of stroke
JP4283467B2 (en) 2001-11-12 2009-06-24 株式会社日立製作所 Biological measurement probe and biological optical measurement apparatus using the same
US6936043B2 (en) 2001-11-13 2005-08-30 Minu, Llc Method to treat age-related macular degeneration
WO2003042376A1 (en) 2001-11-15 2003-05-22 Photothera, Inc. Methods for preparing artificial cartilage
US20030125783A1 (en) 2001-12-18 2003-07-03 Ceramoptec Industries, Inc. Device and method for wound healing and debridement
US20030144712A1 (en) * 2001-12-20 2003-07-31 Jackson Streeter, M.D. Methods for overcoming organ transplant rejection
US20030212442A1 (en) 2001-12-21 2003-11-13 Jackson Streeter Low level light therapy for the treatment of myocardial infarction
US10695577B2 (en) 2001-12-21 2020-06-30 Photothera, Inc. Device and method for providing phototherapy to the heart
JP2003252127A (en) 2001-12-28 2003-09-10 Pioneer Electronic Corp Drive control device and drive control method
US20030181962A1 (en) 2002-02-19 2003-09-25 Jackson Streeter Low power energy therapy methods for bioinhibition
US7081128B2 (en) * 2002-03-04 2006-07-25 Hart Barry M Phototherapy device and method of use
US6742815B2 (en) * 2002-05-08 2004-06-01 Dormont Manufacturing Company Fluid line connector assembly
US20040153130A1 (en) * 2002-05-29 2004-08-05 Amir Oron Methods for treating muscular dystrophy
US20050159793A1 (en) * 2002-07-02 2005-07-21 Jackson Streeter Methods for treating macular degeneration
US6872221B2 (en) * 2002-08-05 2005-03-29 Larry Robert Lytle Therapeutic low level laser apparatus and method
US20040132002A1 (en) * 2002-09-17 2004-07-08 Jackson Streeter Methods for preserving blood
US20070219604A1 (en) 2006-03-20 2007-09-20 Palomar Medical Technologies, Inc. Treatment of tissue with radiant energy
WO2004033040A1 (en) 2002-10-07 2004-04-22 Palomar Medical Technologies, Inc. Apparatus for performing photobiostimulation
US20060223155A1 (en) 2002-11-01 2006-10-05 Jackson Streeter Enhancement of in vitro culture or vaccine production in bioreactors using electromagnetic energy
US7100615B1 (en) 2002-11-25 2006-09-05 Cms-Dental Aps Low level laser therapy system
US20040116909A1 (en) 2002-12-11 2004-06-17 Ceramoptec Industries Inc. Multipurpose diode laser system for ophthalmic laser treatments
US7354432B2 (en) 2003-01-17 2008-04-08 Mcw Research Foundation, Inc. Red to near-infrared photobiomodulation treatment of the visual system in visual system disease or injury
US20040153131A1 (en) 2003-02-04 2004-08-05 Yorke John A. Apparatus and method for hair retention and regeneration
ES2570987T3 (en) 2003-02-25 2016-05-23 Tria Beauty Inc Dermatological treatment device, based on diode laser and autonomous
US7402167B2 (en) 2003-03-03 2008-07-22 Mikhail Nemenov Portable laser and process for producing controlled pain
US20040220513A1 (en) 2003-03-04 2004-11-04 Jackson Streeter Low level light therapy for the enhancement of hepatic functioning
US7037326B2 (en) * 2003-03-14 2006-05-02 Hee-Young Lee Skin cooling device using thermoelectric element
AU2004226378A1 (en) * 2003-03-27 2004-10-14 The General Hospital Corporation Method and apparatus for dermatological treatment and fractional skin resurfacing
US20050015122A1 (en) * 2003-06-03 2005-01-20 Mott Christopher Grey System and method for control of a subject's circadian cycle
US7311723B2 (en) 2003-07-11 2007-12-25 University Of Washington Scanning laser device and methods of use
US7166070B2 (en) * 2003-08-29 2007-01-23 Lawlis G Frank Method and apparatus for acoustical stimulation of the brain
US7044960B2 (en) * 2003-09-17 2006-05-16 Medivance Incorporated Method and apparatus for providing non-invasive ultrasound heating of the preoptic anterior hypothalamus
US7282060B2 (en) 2003-12-23 2007-10-16 Reliant Technologies, Inc. Method and apparatus for monitoring and controlling laser-induced tissue treatment
US20050143792A1 (en) 2003-12-24 2005-06-30 Harvey Jay Hair treatment method
WO2005065565A1 (en) 2003-12-31 2005-07-21 Palomar Medical Technologies, Inc. Dermatological treatment with vusualization
ITVI20040131A1 (en) 2004-05-26 2004-08-26 Milone Francesco Ferro DEVICE FOR THE EMISSION OF INTERMITTENT LIGHT IMPULSES
US8308717B2 (en) 2004-06-21 2012-11-13 Seilex Ltd Thermal energy applicator
US20080033513A1 (en) * 2004-07-15 2008-02-07 Meddynamics Ltd. Directed Energy for Point Oriented Medical Treatment
US7127266B2 (en) * 2004-09-17 2006-10-24 Nextel Communications Inc. System and method for efficient media resource allocation
AU2005307870A1 (en) 2004-11-15 2006-05-26 Christopher Decharms Stimulation of neural tissue with light
US7274847B2 (en) 2004-11-16 2007-09-25 Biotex, Inc. Light diffusing tip
US7686839B2 (en) 2005-01-26 2010-03-30 Lumitex, Inc. Phototherapy treatment devices for applying area lighting to a wound
US7288108B2 (en) 2005-03-14 2007-10-30 Codman & Shurtleff, Inc. Red light implant for treating Parkinson's disease
CA2603443C (en) 2005-03-31 2019-01-08 The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. Light as a replacement for mitogenic factors on progenitor cells
US20070260231A1 (en) 2005-04-21 2007-11-08 Ondine International, Ltd. Optical probe for delivery of light
US8204600B2 (en) 2005-11-22 2012-06-19 Mayo Foundation For Medical Education And Research Detecting and treating nervous system disorders
US8033284B2 (en) 2006-01-11 2011-10-11 Curaelase, Inc. Therapeutic laser treatment
US7559945B2 (en) 2006-01-13 2009-07-14 Clarimedix Inc. Multi-spectral photon therapy device and methods of use
US7575589B2 (en) 2006-01-30 2009-08-18 Photothera, Inc. Light-emitting device and method for providing phototherapy to the brain
US20090254154A1 (en) 2008-03-18 2009-10-08 Luis De Taboada Method and apparatus for irradiating a surface with pulsed light
US20070179570A1 (en) 2006-01-30 2007-08-02 Luis De Taboada Wearable device and method for providing phototherapy to the brain
US10695579B2 (en) 2006-01-30 2020-06-30 Pthera LLC Apparatus and method for indicating treatment site locations for phototherapy to the brain
US10357662B2 (en) 2009-02-19 2019-07-23 Pthera LLC Apparatus and method for irradiating a surface with light
RU2297860C1 (en) 2006-02-07 2007-04-27 Иван Васильевич Максимович Method for endovascular treatment of alzheimer's disease
WO2007099545A2 (en) 2006-03-03 2007-09-07 Alma Lasers Ltd. Method and apparatus for light-based hair removal
US20070255355A1 (en) 2006-04-06 2007-11-01 Palomar Medical Technologies, Inc. Apparatus and method for skin treatment with compression and decompression
US8926676B2 (en) 2006-04-11 2015-01-06 Advanced Neuromodulation Systems, Inc. Systems and methods for applying signals, including contralesional signals, to neural populations
US9067060B2 (en) * 2006-04-20 2015-06-30 Joseph Neev Skin treatment and hair treatment device with protruding guards
US8057464B2 (en) 2006-05-03 2011-11-15 Light Sciences Oncology, Inc. Light transmission system for photoreactive therapy
JP2010507425A (en) 2006-10-25 2010-03-11 パンテック バイオソリューションズ アクチェンゲゼルシャフト Chip member for laser light emitting element
US20080119830A1 (en) 2006-10-31 2008-05-22 Ramstad Paul O Disposable tip for laser handpiece
US20080140164A1 (en) 2006-12-06 2008-06-12 Clrs Technology Corporation Light emitting therapeutic devices and methods
US8152727B2 (en) 2006-12-11 2012-04-10 Chidicon Medical Center Method for assessment of color processing mechanism in the human brain for diagnosis and treatment
US20080221211A1 (en) 2007-02-02 2008-09-11 Jackson Streeter Method of treatment of neurological injury or cancer by administration of dichloroacetate
ES2629612T3 (en) 2007-03-06 2017-08-11 Novocure Ltd. Cancer treatment using electromagnetic fields in combination with photodynamic therapy
US20100331928A1 (en) 2007-05-11 2010-12-30 Clarimedix Visible light modulation of mitochondrial function in hypoxia and disease
US20090112278A1 (en) 2007-10-30 2009-04-30 Neuropace, Inc. Systems, Methods and Devices for a Skull/Brain Interface
DE102008005940A1 (en) 2008-01-24 2009-08-06 Fontaine Helmut La abrading
US9320914B2 (en) 2008-03-03 2016-04-26 DePuy Synthes Products, Inc. Endoscopic delivery of red/NIR light to the subventricular zone
EP2291224A2 (en) 2008-03-18 2011-03-09 PhotoThera, Inc. Method and apparatus for irradiating a surface with continuous-wave or pulsed light
US20090270776A1 (en) 2008-04-28 2009-10-29 Hung-Chu Chang Massage Chair With Function of Stress Relaxation and Sleep Inducing
CA2731064A1 (en) 2008-07-17 2010-01-21 Lockheed Martin Corporation Method and apparatus for neural-signal capture to drive neuroprostheses or control bodily function
WO2010031777A2 (en) 2008-09-16 2010-03-25 El.En. S.p.A Device and method for regenerative therapy by high intensity laser therapy
US7848035B2 (en) 2008-09-18 2010-12-07 Photothera, Inc. Single-use lens assembly
KR101051025B1 (en) 2008-12-23 2011-07-26 한국과학기술연구원 Brain stimulation and measurement apparatus and method of manufacturing the same
US8790382B2 (en) * 2009-08-04 2014-07-29 Yonatan Gerlitz Handheld low-level laser therapy apparatus
US20110190745A1 (en) * 2009-12-04 2011-08-04 Uebelhoer Nathan S Treatment of sweat glands

Patent Citations (100)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1856969A (en) * 1927-09-06 1932-05-03 Siemens Ag Apparatus for treating living cells by means of rays of light
US3375755A (en) * 1965-10-19 1968-04-02 James A. Hunt Control device for automating sequential machine operation
US3810367A (en) * 1970-07-16 1974-05-14 W Peterson Container for cooling, storage, and shipping of human organ for transplant
US4076393A (en) * 1975-12-15 1978-02-28 The United States Of America As Represented By The Secretary Of The Navy Thermal stress-relieving coupling member and support
US4315514A (en) * 1980-05-08 1982-02-16 William Drewes Method and apparatus for selective cell destruction
US4633872A (en) * 1983-11-08 1987-01-06 Hgm, Incorporated Laser optical delivery apparatus
US4798215A (en) * 1984-03-15 1989-01-17 Bsd Medical Corporation Hyperthermia apparatus
US5902741A (en) * 1986-04-18 1999-05-11 Advanced Tissue Sciences, Inc. Three-dimensional cartilage cultures
US5621091A (en) * 1986-07-25 1997-04-15 The Children's Medical Center Corporation Probes for and nucleic acid encoding the muscular dystrophy protein, dystrophin
US5304212A (en) * 1987-06-26 1994-04-19 Brigham And Women's Hospital Assessment and modification of a human subject's circadian cycle
US5282797A (en) * 1989-05-30 1994-02-01 Cyrus Chess Method for treating cutaneous vascular lesions
US5500009A (en) * 1990-11-15 1996-03-19 Amron, Ltd. Method of treating herpes
US5401270A (en) * 1990-12-19 1995-03-28 Carl-Zeiss-Stiftung Applicator device for laser radiation
US5511563A (en) * 1991-06-21 1996-04-30 Diamond; Donald A. Apparatus and method for treating rheumatoid and psoriatic arthritis
US5601526A (en) * 1991-12-20 1997-02-11 Technomed Medical Systems Ultrasound therapy apparatus delivering ultrasound waves having thermal and cavitation effects
US5501655A (en) * 1992-03-31 1996-03-26 Massachusetts Institute Of Technology Apparatus and method for acoustic heat generation and hyperthermia
US5755752A (en) * 1992-04-24 1998-05-26 Segal; Kim Robin Diode laser irradiation system for biological tissue stimulation
US6033431A (en) * 1992-04-24 2000-03-07 Segal; Kim Robin Diode laser irradiation system for biological tissue stimulation
US5405368A (en) * 1992-10-20 1995-04-11 Esc Inc. Method and apparatus for therapeutic electromagnetic treatment
US5622168A (en) * 1992-11-18 1997-04-22 John L. Essmyer Conductive hydrogels and physiological electrodes and electrode assemblies therefrom
US5616140A (en) * 1994-03-21 1997-04-01 Prescott; Marvin Method and apparatus for therapeutic laser treatment
US5728090A (en) * 1995-02-09 1998-03-17 Quantum Devices, Inc. Apparatus for irradiating living cells
US6537301B1 (en) * 1995-03-23 2003-03-25 Tsutomu Kamei Method of noninvasively enhancing immunosurveillance capacity and apparatus for applying pulsed light to at least forehead
US6358272B1 (en) * 1995-05-16 2002-03-19 Lutz Wilden Therapy apparatus with laser irradiation device
US5627140A (en) * 1995-05-19 1997-05-06 Nec Research Institute, Inc. Enhanced flux pinning in superconductors by embedding carbon nanotubes with BSCCO materials
US6060306A (en) * 1995-06-07 2000-05-09 Advanced Tissue Sciences, Inc. Apparatus and method for sterilizing, seeding, culturing, storing, shipping and testing replacement cartilage tissue constructs
US6042531A (en) * 1995-06-19 2000-03-28 Holcomb; Robert R. Electromagnetic therapeutic treatment device and methods of using same
US5879376A (en) * 1995-07-12 1999-03-09 Luxar Corporation Method and apparatus for dermatology treatment
US6027495A (en) * 1995-07-12 2000-02-22 Esc Medical Systems Ltd. Method and apparatus for dermatology treatment
US5871521A (en) * 1995-08-25 1999-02-16 Matsushita Electric Industrial Co., Ltd. Laser probe for medical treatment
US5617258A (en) * 1995-10-25 1997-04-01 Plc Medical Systems, Inc. Non-reusable lens cell for a surgical laser handpiece
US5720894A (en) * 1996-01-11 1998-02-24 The Regents Of The University Of California Ultrashort pulse high repetition rate laser system for biological tissue processing
US5709645A (en) * 1996-01-30 1998-01-20 Comptronic Devices Limited Independent field photic stimulator
US6238424B1 (en) * 1996-06-07 2001-05-29 Biolight Patent Holding Ab Device for external treatment with pulsating light of high duty cycle
US6238425B1 (en) * 1996-06-07 2001-05-29 Biolight Patent Holding Ab Device for external medical treatment with monochromatic light
US6179830B1 (en) * 1996-07-24 2001-01-30 J. Morita Manufacturing Corporation Laser probe
US6395016B1 (en) * 1996-07-28 2002-05-28 Biosense, Inc. Method of treating a heart using cells irradiated in vitro with biostimulatory irradiation
US6197020B1 (en) * 1996-08-12 2001-03-06 Sublase, Inc. Laser apparatus for subsurface cutaneous treatment
US6221095B1 (en) * 1996-11-13 2001-04-24 Meditech International Inc. Method and apparatus for photon therapy
US6379376B1 (en) * 1996-11-25 2002-04-30 Rachel Lubart Device for light irradiation onto tissue
US6063108A (en) * 1997-01-06 2000-05-16 Salansky; Norman Method and apparatus for localized low energy photon therapy (LEPT)
US6030767A (en) * 1997-01-21 2000-02-29 The American National Red Cross Intracellular and extracellular decontamination of whole blood and blood components by amphiphilic phenothiazin-5-ium dyes plus light
US20020018834A1 (en) * 1997-04-01 2002-02-14 Vaughan Nicholas John Cooking method and apparatus
US6187210B1 (en) * 1997-06-30 2001-02-13 The Regents Of The University Of California Epidermal abrasion device with isotropically etched tips, and method of fabricating such a device
US6045575A (en) * 1997-09-10 2000-04-04 Amt, Inc. Therapeutic method and internally illuminated garment for the management of disorders treatable by phototherapy
US6551308B1 (en) * 1997-09-17 2003-04-22 Laser-Und Medizin-Technologie Gmbh Berlin Laser therapy assembly for muscular tissue revascularization
US6046046A (en) * 1997-09-23 2000-04-04 Hassanein; Waleed H. Compositions, methods and devices for maintaining an organ
US6379295B1 (en) * 1997-09-26 2002-04-30 Gilson Woo Treatment of afflictions, ailments and diseases
US6179771B1 (en) * 1998-04-21 2001-01-30 Siemens Aktiengesellschaft Coil arrangement for transcranial magnetic stimulation
US6397107B1 (en) * 1998-04-27 2002-05-28 Bokwang Co., Ltd. Apparatus for embolic treatment using high frequency induction heating
US6537304B1 (en) * 1998-06-02 2003-03-25 Amir Oron Ischemia laser treatment
WO1999062599A1 (en) * 1998-06-02 1999-12-09 Amir Oron Ischemia laser treatment
US6198958B1 (en) * 1998-06-11 2001-03-06 Beth Israel Deaconess Medical Center, Inc. Method and apparatus for monitoring a magnetic resonance image during transcranial magnetic stimulation
US6210317B1 (en) * 1998-07-13 2001-04-03 Dean R. Bonlie Treatment using oriented unidirectional DC magnetic field
US6364907B1 (en) * 1998-10-09 2002-04-02 Qlt Inc. Method to prevent xenograft transplant rejection
US6676655B2 (en) * 1998-11-30 2004-01-13 Light Bioscience L.L.C. Low intensity light therapy for the manipulation of fibroblast, and fibroblast-derived mammalian cells and collagen
US20030023283A1 (en) * 1998-11-30 2003-01-30 Mcdaniel David H. Method and apparatus for the stimulation of hair growth
US6344050B1 (en) * 1998-12-21 2002-02-05 Light Sciences Corporation Use of pegylated photosensitizer conjugated with an antibody for treating abnormal tissue
US6899723B2 (en) * 1999-01-15 2005-05-31 Light Sciences Corporation Transcutaneous photodynamic treatment of targeted cells
US6692517B2 (en) * 1999-01-15 2004-02-17 Cynosure, Inc. Optical radiation treatment for enhancement of wound healing
US6537302B1 (en) * 1999-01-20 2003-03-25 Biolight Patent Holding Ab Means for external medical treatment by means of light
US7041094B2 (en) * 1999-03-15 2006-05-09 Cutera, Inc. Tissue treatment device and method
US6214035B1 (en) * 1999-03-23 2001-04-10 Jackson Streeter Method for improving cardiac microcirculation
US6210425B1 (en) * 1999-07-08 2001-04-03 Light Sciences Corporation Combined imaging and PDT delivery system
US6689062B1 (en) * 1999-11-23 2004-02-10 Microaccess Medical Systems, Inc. Method and apparatus for transesophageal cardiovascular procedures
US6363285B1 (en) * 2000-01-21 2002-03-26 Albert C. Wey Therapeutic sleeping aid device
US20030021124A1 (en) * 2000-02-23 2003-01-30 Jens Elbrecht Handpiece for radiating light onto skin surface during a medical or cosmetic skin treatment
US20020029071A1 (en) * 2000-03-23 2002-03-07 Colin Whitehurst Therapeutic light source and method
US6379939B1 (en) * 2000-07-18 2002-04-30 Rachel Lubart Method for increasing the fertilizing capability of sperm cells
US6514220B2 (en) * 2001-01-25 2003-02-04 Walnut Technologies Non focussed method of exciting and controlling acoustic fields in animal body parts
US7054676B2 (en) * 2001-04-24 2006-05-30 Duke University MR-compatible methods and systems for cardiac monitoring and gating
US7217266B2 (en) * 2001-05-30 2007-05-15 Anderson R Rox Apparatus and method for laser treatment with spectroscopic feedback
US20080051858A1 (en) * 2001-06-26 2008-02-28 Photomed Technologies, Inc. Therapeutic methods using electromagnetic radiation
US20040073278A1 (en) * 2001-09-04 2004-04-15 Freddy Pachys Method of and device for therapeutic illumination of internal organs and tissues
US20110060266A1 (en) * 2001-11-01 2011-03-10 Photothera, Inc. Enhanced stem cell therapy and stem cell production through the administration of low level light energy
US20100105977A1 (en) * 2001-11-01 2010-04-29 Luis De Taboada Method for providing phototherapy to the brain
US20100094384A1 (en) * 2001-11-01 2010-04-15 Luis De Taboada System and method for providing phototherapy to the brain
US20040015214A1 (en) * 2001-11-09 2004-01-22 Simkin Guillermo O. Photodynamic therapy for the treatment of hair loss
US20040030325A1 (en) * 2001-12-05 2004-02-12 Nicholas Cahir Removable attachments for laser emitting devices
US20040036975A1 (en) * 2001-12-10 2004-02-26 Michael Slatkine Method and apparatus for improving safety during exposure to a monochromatic light source
US20040014199A1 (en) * 2002-01-09 2004-01-22 Jackson Streeter Method for preserving organs for transplant
US6702837B2 (en) * 2002-04-23 2004-03-09 Phillip Gutwein Therapeutic light device
US20040093042A1 (en) * 2002-06-19 2004-05-13 Palomar Medical Technologies, Inc. Method and apparatus for photothermal treatment of tissue at depth
US7351252B2 (en) * 2002-06-19 2008-04-01 Palomar Medical Technologies, Inc. Method and apparatus for photothermal treatment of tissue at depth
US20040044384A1 (en) * 2002-09-03 2004-03-04 Leber Leland C. Therapeutic method and apparatus
US20050107851A1 (en) * 2002-11-01 2005-05-19 Taboada Luis D. Device and method for providing phototherapy to the brain
US20050009161A1 (en) * 2002-11-01 2005-01-13 Jackson Streeter Enhancement of in vitro culture or vaccine production using electromagnetic energy treatment
US6866678B2 (en) * 2002-12-10 2005-03-15 Interbational Technology Center Phototherapeutic treatment methods and apparatus
US20070066996A1 (en) * 2003-03-17 2007-03-22 Katzman Daniel E Modafinil-based neurorehabilitation of impaired neurological function associated with brian injury
US7344555B2 (en) * 2003-04-07 2008-03-18 The United States Of America As Represented By The Department Of Health And Human Services Light promotes regeneration and functional recovery after spinal cord injury
US20080103562A1 (en) * 2003-04-07 2008-05-01 Anders Juanita J Method for regeneration and functional recovery after spinal cord injury using phototherapy
US20050005626A1 (en) * 2003-07-08 2005-01-13 Mcmahon Richard Cooling device for pain relief
US20050024853A1 (en) * 2003-07-30 2005-02-03 Mellen Thomas-Benedict Modularized light processing of body components
US7351253B2 (en) * 2005-06-16 2008-04-01 Codman & Shurtleff, Inc. Intranasal red light probe for treating Alzheimer's disease
US20090088680A1 (en) * 2005-07-22 2009-04-02 Alexander Aravanis Optical tissue interface method and apparatus for stimulating cells
US20070114872A1 (en) * 2005-11-23 2007-05-24 Daewood Electronics Corporation Rotor for use in induction motor
US20080033412A1 (en) * 2006-08-01 2008-02-07 Harry Thomas Whelan System and method for convergent light therapy having controllable dosimetry
US20080077199A1 (en) * 2006-09-23 2008-03-27 Ron Shefi Method and apparatus for applying light therapy
US20090054955A1 (en) * 2007-08-20 2009-02-26 Kopell Brian H Systems and Methods for Treating Neurological Disorders by Light Stimulation
US20090112280A1 (en) * 2007-10-30 2009-04-30 Neuropace, Inc. Systems, methods and devices for a skull/brain interface

Cited By (116)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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US9795803B2 (en) 2003-01-24 2017-10-24 Pthera LLC Low level light therapy for enhancement of neurologic function
US8025687B2 (en) 2003-01-24 2011-09-27 Photothera, Inc. Low level light therapy for enhancement of neurologic function
US8167921B2 (en) 2003-01-24 2012-05-01 Jackson Streeter Low level light therapy for enhancement of neurologic function
US9101690B2 (en) 2005-07-22 2015-08-11 The Board Of Trustees Of The Leland Stanford Junior University Light-activated cation channel and uses thereof
US10627410B2 (en) 2005-07-22 2020-04-21 The Board Of Trustees Of The Leland Stanford Junior University Light-activated cation channel and uses thereof
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US9360472B2 (en) 2005-07-22 2016-06-07 The Board Of Trustees Of The Leland Stanford Junior University Cell line, system and method for optical-based screening of ion-channel modulators
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US9238150B2 (en) 2005-07-22 2016-01-19 The Board Of Trustees Of The Leland Stanford Junior University Optical tissue interface method and apparatus for stimulating cells
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US20080085265A1 (en) * 2005-07-22 2008-04-10 Schneider M B System for optical stimulation of target cells
US20070261127A1 (en) * 2005-07-22 2007-11-08 Boyden Edward S Light-activated cation channel and uses thereof
US20090099038A1 (en) * 2005-07-22 2009-04-16 Karl Deisseroth Cell line, system and method for optical-based screening of ion-channel modulators
US10569099B2 (en) 2005-07-22 2020-02-25 The Board Of Trustees Of The Leland Stanford Junior University System for optical stimulation of target cells
US10451608B2 (en) 2005-07-22 2019-10-22 The Board Of Trustees Of The Leland Stanford Junior University Cell line, system and method for optical-based screening of ion-channel modulators
US10422803B2 (en) 2005-07-22 2019-09-24 The Board Of Trustees Of The Leland Stanford Junior University Light-activated cation channel and uses thereof
US9829492B2 (en) 2005-07-22 2017-11-28 The Board Of Trustees Of The Leland Stanford Junior University Implantable prosthetic device comprising a cell expressing a channelrhodopsin
US8926959B2 (en) 2005-07-22 2015-01-06 The Board Of Trustees Of The Leland Stanford Junior University System for optical stimulation of target cells
US10052497B2 (en) 2005-07-22 2018-08-21 The Board Of Trustees Of The Leland Stanford Junior University System for optical stimulation of target cells
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US11179572B2 (en) 2006-01-30 2021-11-23 Pthera LLC Light-emitting device and method for providing phototherapy to the brain
US10188872B2 (en) 2006-01-30 2019-01-29 Pthera LLC Light-emitting device and method for providing phototherapy to the brain
US8308784B2 (en) 2006-08-24 2012-11-13 Jackson Streeter Low level light therapy for enhancement of neurologic function of a patient affected by Parkinson's disease
US8864805B2 (en) 2007-01-10 2014-10-21 The Board Of Trustees Of The Leland Stanford Junior University System for optical stimulation of target cells
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US9284353B2 (en) 2007-03-01 2016-03-15 The Board Of Trustees Of The Leland Stanford Junior University Mammalian codon optimized nucleotide sequence that encodes a variant opsin polypeptide derived from Natromonas pharaonis (NpHR)
US9855442B2 (en) 2007-03-01 2018-01-02 The Board Of Trustees Of The Leland Stanford Junior University Method for optically controlling a neuron with a mammalian codon optimized nucleotide sequence that encodes a variant opsin polypeptide derived from natromonas pharaonis (NpHR)
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US9757587B2 (en) 2007-03-01 2017-09-12 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic method for generating an inhibitory current in a mammalian neuron
US8845704B2 (en) 2007-05-11 2014-09-30 Clarimedix Inc. Visible light modulation of mitochondrial function in hypoxia and disease
US10426970B2 (en) 2007-10-31 2019-10-01 The Board Of Trustees Of The Leland Stanford Junior University Implantable optical stimulators
US10035027B2 (en) 2007-10-31 2018-07-31 The Board Of Trustees Of The Leland Stanford Junior University Device and method for ultrasonic neuromodulation via stereotactic frame based technique
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US11273319B2 (en) 2008-03-18 2022-03-15 Pthera LLC Method and apparatus for irradiating a surface with pulsed light
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US9249200B2 (en) 2008-04-23 2016-02-02 The Board Of Trustees Of The Leland Stanford Junior University Expression vector comprising a nucleotide sequence encoding a Volvox carteri light-activated ion channel protein (VChR1) and implantable device thereof
US9394347B2 (en) 2008-04-23 2016-07-19 The Board Of Trustees Of The Leland Stanford Junior University Methods for treating parkinson's disease by optically stimulating target cells
US8603790B2 (en) 2008-04-23 2013-12-10 The Board Of Trustees Of The Leland Stanford Junior University Systems, methods and compositions for optical stimulation of target cells
US9878176B2 (en) 2008-04-23 2018-01-30 The Board Of Trustees Of The Leland Stanford Junior University System utilizing Volvox carteri light-activated ion channel protein (VChR1) for optical stimulation of target cells
US10350430B2 (en) 2008-04-23 2019-07-16 The Board Of Trustees Of The Leland Stanford Junior University System comprising a nucleotide sequence encoding a volvox carteri light-activated ion channel protein (VCHR1)
US8815582B2 (en) 2008-04-23 2014-08-26 The Board Of Trustees Of The Leland Stanford Junior University Mammalian cell expressing Volvox carteri light-activated ion channel protein (VChR1)
US9453215B2 (en) 2008-05-29 2016-09-27 The Board Of Trustees Of The Leland Stanford Junior University Cell line, system and method for optical control of secondary messengers
US8962589B2 (en) 2008-05-29 2015-02-24 The Board Of Trustees Of The Leland Stanford Junior University Cell line, system and method for optical control of secondary messengers
US8729040B2 (en) 2008-05-29 2014-05-20 The Board Of Trustees Of The Leland Stanford Junior University Cell line, system and method for optical control of secondary messengers
US20160015996A1 (en) * 2008-06-17 2016-01-21 The Board Of Trustees Of The Leland Stanford Junior University Methods, systems and devices for optical stimulation of target cells using an optical transmission element
US9084885B2 (en) 2008-06-17 2015-07-21 The Board Of Trustees Of The Leland Stanford Junior University Methods, systems and devices for optical stimulation of target cells using an optical transmission element
US20110172653A1 (en) * 2008-06-17 2011-07-14 Schneider M Bret Methods, systems and devices for optical stimulation of target cells using an optical transmission element
US10711242B2 (en) 2008-06-17 2020-07-14 The Board Of Trustees Of The Leland Stanford Junior University Apparatus and methods for controlling cellular development
US8956363B2 (en) * 2008-06-17 2015-02-17 The Board Of Trustees Of The Leland Stanford Junior University Methods, systems and devices for optical stimulation of target cells using an optical transmission element
US10583309B2 (en) 2008-07-08 2020-03-10 The Board Of Trustees Of The Leland Stanford Junior University Materials and approaches for optical stimulation of the peripheral nervous system
US9308392B2 (en) 2008-07-08 2016-04-12 The Board Of Trustees Of The Leland Stanford Junior University Materials and approaches for optical stimulation of the peripheral nervous system
US9101759B2 (en) 2008-07-08 2015-08-11 The Board Of Trustees Of The Leland Stanford Junior University Materials and approaches for optical stimulation of the peripheral nervous system
US8149526B2 (en) 2008-09-18 2012-04-03 Photothera, Inc. Single use lens assembly
US10071259B2 (en) 2008-09-18 2018-09-11 Pthera, Llc Optical assembly
US9458208B2 (en) 2008-11-14 2016-10-04 The Board Of Trustees Of The Leland Stanford Junior University Optically-based stimulation of target cells and modifications thereto
US8716447B2 (en) 2008-11-14 2014-05-06 The Board Of Trustees Of The Leland Stanford Junior University Optically-based stimulation of target cells and modifications thereto
US9309296B2 (en) 2008-11-14 2016-04-12 The Board Of Trustees Of The Leland Stanford Junior University Optically-based stimulation of target cells and modifications thereto
US10071132B2 (en) 2008-11-14 2018-09-11 The Board Of Trustees Of The Leland Stanford Junior University Optically-based stimulation of target cells and modifications thereto
US10064912B2 (en) 2008-11-14 2018-09-04 The Board Of Trustees Of The Leland Stanford Junior University Optically-based stimulation of target cells and modifications thereto
US20110066213A1 (en) * 2009-05-01 2011-03-17 Maik Huttermann Light therapy treatment
US8945196B2 (en) 2009-05-01 2015-02-03 Wayne State University Light therapy treatment
US9610460B2 (en) 2009-05-01 2017-04-04 Wayne State University Light therapy treatment
US10071261B2 (en) 2009-05-01 2018-09-11 Wayne State University Light therapy treatment
US11020604B2 (en) 2009-05-01 2021-06-01 Wayne State University Light therapy treatment
US20110040356A1 (en) * 2009-08-12 2011-02-17 Fredric Schiffer Methods for Treating Psychiatric Disorders Using Light Energy
US8303636B2 (en) 2009-08-12 2012-11-06 Fredric Schiffer Methods for treating psychiatric disorders using light energy
US8574279B2 (en) 2009-08-12 2013-11-05 Joulesafe, Llc Methods for treating psychiatric disorders using light energy
US9359449B2 (en) 2010-03-17 2016-06-07 The Board Of Trustees Of The Leland Stanford Junior University Light-sensitive ion-passing molecules
US9249234B2 (en) 2010-03-17 2016-02-02 The Board Of Trustees Of The Leland Stanford Junior University Light-sensitive ion-passing molecules
US9604073B2 (en) 2010-03-17 2017-03-28 The Board Of Trustees Of The Leland Stanford Junior University Light-sensitive ion-passing molecules
US9079940B2 (en) 2010-03-17 2015-07-14 The Board Of Trustees Of The Leland Stanford Junior University Light-sensitive ion-passing molecules
US20110313234A1 (en) * 2010-06-21 2011-12-22 Yen-Lung Lin Electromagnetic stimulation device and method thereof
US10252076B2 (en) 2010-11-05 2019-04-09 The Board Of Trustees Of The Leland Stanford Junior University Upconversion of light for use in optogenetic methods
US9968652B2 (en) 2010-11-05 2018-05-15 The Board Of Trustees Of The Leland Stanford Junior University Optically-controlled CNS dysfunction
US10086012B2 (en) 2010-11-05 2018-10-02 The Board Of Trustees Of The Leland Stanford Junior University Control and characterization of memory function
US9421258B2 (en) 2010-11-05 2016-08-23 The Board Of Trustees Of The Leland Stanford Junior University Optically controlled CNS dysfunction
US9992981B2 (en) 2010-11-05 2018-06-12 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic control of reward-related behaviors
US10196431B2 (en) 2010-11-05 2019-02-05 The Board Of Trustees Of The Leland Stanford Junior University Light-activated chimeric opsins and methods of using the same
US9340589B2 (en) 2010-11-05 2016-05-17 The Board Of Trustees Of The Leland Stanford Junior University Light-activated chimeric opsins and methods of using the same
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US8932562B2 (en) 2010-11-05 2015-01-13 The Board Of Trustees Of The Leland Stanford Junior University Optically controlled CNS dysfunction
US10568307B2 (en) 2010-11-05 2020-02-25 The Board Of Trustees Of The Leland Stanford Junior University Stabilized step function opsin proteins and methods of using the same
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WO2019210304A1 (en) * 2018-04-27 2019-10-31 University Of Minnesota Device for treatment of traumatic brain injury and related systems and methods
US11857801B2 (en) * 2018-04-27 2024-01-02 Regents Of The University Of Minnesota Device for treatment of traumatic brain injury and related systems and methods

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