Methods and devices for phototherapy

Abstract

An implantable light therapy device includes: a power receiver element configured to receive power from an external power transmitter; a light delivery element powered by the power receiver and configured to deliver light therapy to a target treatment area; and a tether element coupled to the light delivery element and the power receiver element. The tether element is configured to deliver power between the power receiver element and the light delivery element.

Description

[0001] Priority claim

[0002] This application claims the benefit of U.S. Provisional Patent Application No. 62 / 923,738, filed on October 21, 2019; the entire contents of which are incorporated herein by reference. Background Art

[0003] Light delivery as a therapeutic tool is integral to human existence. Light from the sun helps regulate our circadian rhythms and produces critical vitamin D in our skin throughout the day. Light is used in therapeutic form to treat conditions of the eyes and skin, or to reduce bilirubin levels to treat neonatal jaundice. Light delivery can be used to treat many other conditions. BRIEF DESCRIPTION OF THE DRAWINGS

[0004] In the accompanying drawings, which are not necessarily drawn to scale, similar reference numerals may describe similar components in different views. Similar reference numerals with different letter suffixes may represent different instances of similar components. The accompanying drawings generally illustrate various embodiments discussed in this document by way of example and not by way of limitation.

[0005] Figure 1 A light illumination system is shown.

[0006] Figure 2 A light illumination system is shown coupled to a patient's head.

[0007] Figure 3 A light illumination system is shown coupled to a patient's head.

[0008] Figure 4 An example of electronic components in a housing is shown.

[0009] Figure 5 An example of an illumination element is shown.

[0010] FIG. 6A to FIG. 6D Examples of optical light guide shapes are shown.

[0011] Figure 7 An example of an illumination element disposed on a customizable substrate is shown.

[0012] Figure 8 Another example of an optical light guide shape is shown.

[0013] 9A to 9D An example of a custom light guide that can be coupled to an illumination element is shown.

[0014] Fig.10 Another example of an illumination element is shown.

[0015] Fig.11The use of a planar immersion lens is shown.

[0016] Fig.12 The use of multiple light sources in an illumination system is shown.

[0017] Fig.13 An example of a light source control device is shown.

[0018] Fig.14 An example of an irradiation system that may also include electrical stimulation of the target treatment area is shown.

[0019] Fig.15A An example of a reinforcement substrate is shown.

[0020] Fig. 15B The tumor cavity is shown Fig.15A enhanced substrate.

[0021] Fig.16 Another example of a reinforcement substrate is shown.

[0022] Fig.17 The use of additional support elements in the tumor cavity is shown.

[0023] Fig.18 Another example of an additional support element in a tumor cavity is shown.

[0024] Fig.19 A second port for coupling the illumination element to an external light source is shown.

[0025] FIG. 20A to FIG. 20B The use of multiple light sources in an illumination element and the resulting illumination pattern are shown.

[0026] Fig.21 An example of a method of treating a tumor is shown. DETAILED DESCRIPTION

[0027] Light delivery as a therapeutic tool is integral to human existence. Light from the sun helps regulate our circadian rhythms and produces critical vitamin D in our skin throughout the day. Light is used in therapeutic forms to treat conditions of the eyes and skin, or to reduce bilirubin levels to treat neonatal jaundice. Recently, light has been viewed as a potential source of new treatments paired with light-activated drugs, resulting in new advances in skin cancer as well as some internal tumors and other conditions.

[0028] The main challenge in using light to treat internal diseases is that light cannot penetrate very far into the body. Light is absorbed by the skin and tissue, which limits the penetration depth of visible and near-infrared (NIR) wavelengths to 3 mm to 5 mm. Applying light therapy to tumors or stimulating neurons to treat movement disorders may require light at depths of 10 cm to 25 cm, less, or even greater, and an implantable light source adjacent to the target treatment area is the only practical way for light to reach such depths in the human body.

[0029] The present disclosure describes novel powering, light delivery, and integration aspects of implantable phototherapy devices, systems, and methods of use. Implants may also be designed to deliver monotherapy and / or in combination with other forms of stimulation and / or therapeutic agents other than light, and in doing so deliver innovative combination therapies. Implants may also be modified to include sensing features, such as to adjust the therapeutic dose in response to the patient's physiological state.

[0030] Figure 1 An example of a light irradiation system 100 is shown, which can be used to deliver phototherapy in the patient's body, such as for treating tumors deep in the body (e.g., glioblastoma in the brain). Although the examples disclosed herein are mainly related to implanting the device into the brain as a treatment for brain cancer, this is not intended to be limiting, and those skilled in the art will understand that the device can be implanted in any other part of the body to deliver phototherapy in the body as part of the treatment for other conditions. Therefore, the device and system described herein can be surgically implanted into a tumor cavity created by resection of a tumor, or the device and system described herein can be placed in a natural body cavity adjacent to the diseased area or in a natural tissue (e.g., by direct implantation into the tissue) without the need for surgical modification. In either case, light can be used to activate various therapeutic agents that help fight tumors or provide other therapeutic effects to treat diseases, thereby providing local therapy. For example, in photodynamic therapy, light can be used to activate therapeutic agents (also called photosensitizers) absorbed by cells, which causes the generation of reactive oxygen species (ROS), which are toxic to host cells and cause cell death, such as in tumors, which is well reported in patents and scientific literature. The generation of ROS can be quantified by titration methods known in the art.The wavelength of light must overlap with the activation spectrum of the photosensitizer.

[0031] The illumination system includes a power receiver element, which may include a wireless coil 101 and a housing 200. The system may also include a tether line 300 and a light source (also referred to as a light element or illumination element or light source) 400.

[0032] The power receiver element in this example or any example may or may not include any energy storage device (e.g., a battery, capacitor, or other storage element). If there is no storage device, treatment is provided only when the external power source is activated. If an energy storage device is included, the device can be turned on as needed, and the irradiation element is powered by the energy storage device. The wireless coil 101 is configured to receive radio frequency energy from an external transmitter coil in an external power source, and may have one or more turns of wire covered by an insulator. The turns may be in any geometric shape, such as a circular or spiral coil, and the coil may be made of any material that is conductive to electromagnetic energy. The wireless coil may optionally be made of a flexible printed circuit board or printed circuit board with a metal or conductive trace having a circular or other coil pattern. The size of the coil is suitable for wireless power transmission through tissue, such as any depth through the patient's scalp, such as less than about 5cm, 4cm, 3cm, 2cm, or 1cm, and the coil can tolerate changes in the thickness of the intervening tissue. The wireless transmitter and receiver may optionally be capable of two-way authentication so that only approved devices can work together and send power to the implanted device. Optionally, secure cryptographic techniques may be used to ensure that the device cannot be activated by unauthorized users or transmitters.

[0033] The wireless coil 101 may be electrically and mechanically coupled to an optional housing 200 such that energy captured by the coil 101 is delivered to the housing 200, which includes various electronics for managing power and controlling the duty cycle of the light source 400. The electronics in the housing may be mounted on a printed circuit board.

[0034] The housing can be any size or shape and can be formed from any number of materials (e.g., titanium or any biocompatible material). Wires from the coil 101 or tether 300 can be coupled to the housing via a ceramic feedthrough. Additional disclosure regarding the electronic components in the housing 200 is provided later in this specification.

[0035] The tether line 300 is operably coupled to the housing 200, the electronics in the housing 200, and the light source 400. The tether ensures that the light source 400 remains coupled to the housing and can be formed of any material having the appropriate strength for the tether and being conductive. The tether line can be welded to an electronic feedthrough in a hermetically sealed housing (sometimes also referred to as a "can") that encapsulates the power supply electronics. The tether 300 can be several wires extending linearly between the housing and the irradiation element, or the wires can be coiled, spirally wound, braided, twisted together, or in any configuration, and have sufficient length to ensure that the housing can be anchored in one position and the light source can be set in a desired position. The tether can include multiple wires passing through a multi-lumen tube to form a single filament, or the tether can have more than one filament.

[0036] Light source 400 may be a single light source or may include multiple light sources. For example, multiple light sources may be included in the light source and configured to be adjusted to various intensities and may all have the same or different wavelengths of light that may be controlled together or independently of each other. The wavelength may be selected to maximize the photoactivation of the therapeutic agent.

[0037] Figure 2 shows a device coupled to the patient's skull 1000. Figure 1 A phototherapy system is provided. Here, the phototherapy system includes a power receiver element having a coil 101 for receiving RF energy from an external power source and a housing 200 containing electronic components for controlling the device. A tether 300 operably couples the housing to an irradiation element that is disposed in a tissue cavity in the patient's brain after tumor resection. The irradiation element is not visible in this view. The tether may be coiled 301 along any portion of its length to absorb excess slack or provide strain relief. In this example, the power receiver element is attached to the patient's skull using techniques known in the art (e.g., using sutures, staples, adhesives, or using fasteners such as screws) so that the power receiver element is disposed below the scalp. The tether is also disposed between the scalp and the skull. A burr hole may be drilled through the skull to allow the tether and irradiation element to pass through the skull into a tissue cavity where the irradiation element may be attached to the tissue to secure the irradiation element in a desired position where it will irradiate the target treatment tissue to provide therapy, such as activation of a drug to reduce or eliminate tumor cells that may remain or may recur after resection. The burr hole may be the same as the burr hole used to provide access for the surgeon during tumor resection, or the burr hole may be a separate burr hole. In this example, the power receiver element may be placed behind the ear as shown, or the power receiver may be placed anywhere along the skull.

[0038] Optionally, a fastener such as a clip or grommet (not shown) can be used to help secure the tether as it passes through an opening in the skull that may have sharp edges. The fastener helps hold the tether in place so that it cannot be pulled out, and provides cable management to prevent the tether from becoming tangled. The fastener can be formed of any biocompatible material such as a polymer, silicone, metal, etc.

[0039] Figure 3 Shows Figure 1A phototherapy system and an external power source 700 that wirelessly provides radio frequency power to the phototherapy system. The phototherapy system includes a power receiver element, which includes a coil 101 for receiving radio frequency energy (RF) energy from a power source 700 (here, an RF wireless transmitter). The power receiver element also includes a housing 200 containing electronic components for controlling the phototherapy system. Fasteners 201 such as screws can be used to secure the housing to a skull 1000 under the scalp. A tether 300 electrically couples the housing and the electronic components in the housing to an irradiation element (not shown), which is disposed in a cavity of brain tissue formed after tumor resection. The bone plate 500 can be repositioned in the drill hole to help close the skull, and a grommet 510 or a clip can be used to help secure the tether to the skull and prevent damage to the tether. The tether can be coiled or unfolded. Here, the power receiver element is positioned on one side of the patient's head, approximately at eye height.

[0040] Figure 4 An example of a housing 200 that can be used for any example of a light therapy system disclosed herein is shown. Some electronic components that can be disposed in the housing to help control the light therapy system include a rectifier 210 such as a full-wave bridge rectifier, the rectifier including four diodes arranged to convert alternating current (AC) received from the coil 101 to direct current (DC). A DC / DC converter 220 can be coupled to the rectifier and convert power or voltage levels from one level to another, and the DC / DC converter can be operably coupled to an illumination driver 240 that drives an illumination element (not shown) that can be one or more light sources such as light emitting diodes. A microcontroller 230 can also be included in the housing to control the system. An impedance matching network 102 can couple the coil to the rectifier to ensure maximum power transfer and minimize losses. The impedance matching network can include capacitors or can have active electronic devices to tune resonance. The housing can also include a temperature measurement component 250 that helps monitor the temperature from a sensor disposed at a target treatment site (not shown) to ensure that the temperature at the light source is not excessive and does not cause tissue damage. The temperature measurement component 250 can also monitor the temperature of the receiver electronics to ensure that overheating is avoided. The housing can be formed of any biocompatible material, such as titanium, and provides an airtight seal for the electronics. The housing can serve as a heat sink, or a separate heat sink (not shown) can also be included in the housing. Electrical leads leaving the housing form a tether 300 that is coupled to the radiation source.

[0041] Figure 5An example of an irradiation element 400 that can be coupled to a tether 300 and can be used in any example of an irradiation system is shown. The tether enables power to be delivered from a power receiver element to the irradiation element, and optionally also electrically couples an optional temperature sensor to the electronics in the housing. The tether also provides mechanical coupling between the irradiation element 400 and the power receiver element so that both the irradiation element 400 and the power receiver element remain coupled together. Here, the irradiation element 400 includes one or more flexible substrates 430 such as a flexible printed circuit board (PCB), which can be shaped in any desired configuration to conform to the target treatment area. Polyimide is an example of a suitable PCB material. The target treatment area can be a cavity created after a tumor is removed from the brain, so the substrate should be formable into a three-dimensional shape. In addition, the flexible substrate, once formed, helps support the tissue around the cavity to prevent the tissue from collapsing inward, which can prevent some tissue from being irradiated. Here, multiple illumination elements 420 are coupled to a flexible substrate, and the substrate is bent into an inverted square U-shaped configuration (or a U-shaped staple with two vertical legs and a horizontal strip connecting the legs), so that one illumination element 420 is on each leg of the U-shape, and one illumination element is on the horizontal connector between the legs of the U-shape. This ensures that the light emitted from the illumination elements will be radially outward and evenly distributed in several different directions to illuminate the target treatment area. The illumination elements 420 can be one or more LEDs that can be controlled independently of each other or together. The LEDs can emit a single wavelength of light or several wavelengths of light, and the intensity of the light and the duty cycle of how long the LED is on and how long the LED is off can be adjusted. The PCB can include other electronic components that help control the light source and automatically direct power from the tether to each LED continuously in the desired cycle. This enables the light intensity to be increased or decreased as needed to control the illumination of different areas of the tumor cavity. When the LED cycles, more intense light exposure is followed by a dark period, which can increase the activation of the photosensitizer while giving oxygen in the tissue time to recover between illumination cycles when the cavity is in the dark. The light source and substrate may be encapsulated 410 in a protective device and a material that acts as a light guide to help deliver the light to the target treatment area. For example, the encapsulation 410 may be formed of silicone or another translucent material that acts as a light guide to deliver the light, or the encapsulation may help diffuse the light. The encapsulation may be any shape, including a flat sheet, a square box, a rectangular box, a circle, a cylinder, a sphere, an oval, etc., and is selected to fit into the tumor cavity.

[0042] An optional temperature sensor 251 (e.g., a thermistor) may also be coupled to the flexible substrate to enable temperature monitoring at the target treatment area, since light can generate heat and overheating is undesirable and may damage tissue. If too much heat is generated, the light source can be turned off. As mentioned above, the illumination element 420 and the temperature sensor 251 may optionally be encapsulated in a material that protects the light source and sensor and provides the desired optical properties for delivering light from the illumination element to the target treatment area. For example, the encapsulation material may be optically transparent, or the encapsulation material may contain a diffusing material or a reflective material such as titanium dioxide particles (not shown). The seal may then also act as a light guide or waveguide to ensure minimal light loss during transmission. The seal may have a primary layer for protecting the light and facilitating heat dissipation. An optional secondary layer of the seal may be provided, the secondary layer of the seal acting as a light guide and facilitating light distribution to the target treatment area. Examples of multilayer encapsulation are disclosed herein, any of which may be used for any example of an illumination element.

[0043] FIG. 6A to FIG. 6D Examples of optical light guide shapes that can be used for any of the illumination elements disclosed herein are shown. The light guide can be integral to the seal surrounding the light source, or the light guide can be disposed on top of the seal. The light guide can be formed of the same material as the encapsulation layer, or a different material can be used. The optical light guide shape helps distribute light to the target treatment area with minimal light loss, and is shaped to fit into the cavity left after tumor resection to ensure that all tissue in the target treatment area is irradiated, thereby activating the therapeutic agent. Additionally, the optical light guide can physically or mechanically support the tissue and help prevent tissue collapse, which also helps ensure that all tissue in the target treatment area is irradiated.

[0044] Fig. 6A A cloud-shaped optical light guide 451 is shown. The cloud shape may include a plurality of protrusions extending radially outward. A light source and a temperature sensor may be disposed in the cloud.

[0045] Figure 6B An optical light guide is shown comprising a central spherical ball 453 with spokes extending radially outward. The spokes may be linear spokes or take any other form and may help anchor the optical light guide in the tissue as well as support the tissue and direct light directly to the target treatment area. A light source and temperature sensor may be disposed in the optical light guide.

[0046] Figure 6C A star-shaped polygonal optical light guide 452 is shown. The star comprises a plurality of arms extending radially outward, and each arm may taper radially outward and terminate in a narrow tip. A light source and a temperature sensor may be disposed in the star.

[0047] Fig.6DAn eye-shaped optical light guide 454 is shown. The optical light guide may have a wide arcuate middle portion and opposite sides taper to narrower portions. A light source and a temperature sensor may be disposed in the optical light guide.

[0048] Figure 7 An example of an illumination element with multiple light sources is shown, where LEDs 420 are disposed on a substrate 430 such as a flexible PCB. The illumination element is coupled to a tether 300 so that the illumination element can receive power from a power receiver element, and an optional temperature sensor (not shown) can be operably coupled to the electronic components in the housing. The illumination element can be coupled to a flat sheet of planar material or wallpaper 455, which is formed of an optical material that can act as a light guide to help distribute light to the target treatment area. The wallpaper may also be referred to as a conformal stretched cavity paper (CTCP) capsule. The flat planar material can be bent and trimmed / cut to the size of the target treatment area and secured to the target treatment area. The entire flat planar material may be trimmable, or only certain portions may be trimmable. Clearly mark areas that should not be trimmed (e.g., areas adjacent to the LEDs). The flat planar material can then be coupled to the tissue in the cavity left after tumor resection using techniques such as adhesives, sutures, friction fit, or other techniques known in the art. If an adhesive is used, light such as ultraviolet light (UV) can be introduced into the wallpaper and distributed by the wallpaper to the target treatment area to help cure the adhesive (eg, cyanoacrylate). The light can be provided by an external light source, which will be discussed below.

[0049] Wallpaper may be desirable as surgical cavity dynamics following brain metastasis resection and their impact on postoperative radiosurgery in patients with glioblastoma multiforme (GBM) are known to be a challenge. Patients with symptomatic brain metastases are typically treated with a surgical resection procedure followed by postoperative stereotactic radiosurgery to the surgical cavity to improve local control. Based on many brain metastasis expert panels, there is currently no clear consensus on the timing or start date of radiation therapy simulation for these patients. As an illustrative example of the challenges faced today, some have suggested that delayed radiation therapy (4 to 6 weeks postoperatively) appears to have a theoretical advantage in addressing surgical cavity collapse, which could thereby reduce the target volume.

[0050] There have been numerous studies demonstrating retrospective evaluation of surgical cavity changes in patients treated with surgery and postoperative radiation. The rate of parenchymal cavity collapse (>2 cm^3) at a mean of 24 days postoperatively in this cohort appears to be between 21% and 31%. Therefore, some caregivers have concluded that delaying radiation therapy beyond two weeks after surgery does not provide the benefit of a smaller target volume. It seems evident that a significant portion of the surgical cavity changes volume significantly during the time period including 3 to 4 weeks postoperatively for a range of reasons including edema control, healing, fibrosis, etc. This has been evaluated as an opportunity to reduce the treatment volume by delaying postoperative radiation.

[0051] However, treatment delays will have profound consequences for these at-risk patients. Given known cavity dynamics and cavity collapse, there remains a need to maximize sustained light coverage of the surgical cavity margins throughout the treatment cycle. The combination of a light source embedded in the CTCP capsule ensures that cavity margin surfaces do not otherwise escape irradiation.

[0052] Such a CTCP capsule may include a multi-material matrix that will be used to pave the inner edge of the resection cavity with light. The multi-material matrix includes various materials, each of which has specific properties to maximize the conformal paving effect and in some cases is used as a waveguide. The base of the matrix can be a flexible biocompatible material that uniformly conforms to the shape of the cavity edge but does not hinder light transmission or flux. The matrix is ​​used as a support for various standard or custom elements, including a span of a higher tensile strength material to maximize the expansion effect of the CTCP capsule. Such expansion characteristics will offset the tendency of cavity collapse, thereby ensuring uniform, consistent and personalized distribution of light activation and light guidance. In some cases, the support function of the base matrix is ​​not limited to the element that offsets cavity collapse. In some cases, the multi-material matrix can include a support or anchoring light element itself to optimize the placement of various light components and system performance. Such a capsule can be personalized. In some examples, a higher tensile span is used as one or more slats. Each slat can be individually controlled to optimize paving. The multi-material matrix can be molded or impregnated with an optimized polymer material. In some cases, the material of higher tensile strength can be embedded in the base of the matrix or protrude from the base of the matrix with the span of one or more cavity expansion materials. In some cases, the cavity expansion material can anchor or suspend one or more light elements or multiple light systems, or it can not anchor or suspend one or more light elements or multiple light systems. Such customization may occur when implanted or when working as a modular surgical kit. Such examples can include various multi-material matrices of various shapes, sizes and structures. Some CTCP capsules can include one or more radioactive markers to help, for example, visualize using CT and / or MR scanning. Such methods will help to distinguish capsules from surrounding tissues, tumor tissues, and will enable the migration or separation of wallpaper and / or irradiation elements to be determined.

[0053] Due to known surgical cavity collapse or contraction, some excision cavities may also have bending and are difficult to reach recesses. Such customized CTCP capsules can be personalized to cope with this challenging cavity condition and dynamics. Various adhesives, gels, fiber meshes and waveguides can also be adopted to optimize CTCP capsules. Light sources can be embedded in CTCP. CTCP materials can be overmolded on LEDs and printed circuit boards. Capsules can be closed, partially closed, modular combinations of various capsule elements, and / or can comprise one or more pre-configured holes.

[0054] The multi-material matrix can be a combination of multiple different materials and / or one or more material thicknesses. The multi-material matrix can be a combination of multiple different materials configured to expand for use as an implantable balloon, as will be described in more detail below. The CTCP paving kit can include a pre-configured assembly of various components designed to enable a caregiver to optimize the CTCP capsule according to the patient's needs.

[0055] Figure 8 Another example of a light guide that can be integrated with or coupled to an illumination element is shown. Here, the illumination element includes one or more light sources 420 (e.g., LEDs) mounted to a flexible or rigid PCB substrate 430. The LEDs are powered via a tether 300. The light guide 456 can include a spherical center portion with a plurality of spokes extending radially outward, or the light guide 456 can include a flat, planar circular center portion with a plurality of planar spokes extending radially outward. The spokes are formed of an optical material that helps deliver light to the target treatment area with minimal light loss, and the spokes also help support tissue in the cavity formed after tumor resection, thereby preventing the cavity from collapsing. This helps ensure irradiation of the target treatment area. The spokes can be any shape including flat, planar rectangular arms, rounded cylindrical arms, or any other shape.

[0056] 9A to 9D An example of a custom light guide that can be coupled to an illumination element is shown.

[0057] exist Fig.9A In the embodiment of the present invention, a tether 300 delivers power to a light source enclosed in a standard shape 401 such as a sphere or a square. The light source is implanted in a cavity 1100 formed after a tumor is removed from the brain of a patient's skull 1000. In some cases, it may be beneficial to provide an additional light-guiding element that is customizable to any shape and easily coupled to the encapsulation to help support the tissue in the cavity 1100 and facilitate the delivery of light to the target treatment area. Fig.9A In the embodiment of the present invention, an external light guide 460, which is customized to fit the cavity, is coupled to the illumination element, thereby forming an external oval light guide. The external light guide can be snap-fitted, adhesively bonded or otherwise coupled to the internal main light element.

[0058] FIG. 9B to FIG. 9D Examples of light guides that may be snapped onto, bonded to, or otherwise coupled to light elements are shown.

[0059] exist Fig. 9B In the example, the spherical light guide 461 has a smaller hemispherical recessed area sized to accommodate the light element. The light element is inserted into the recessed area and then adhesively bonded or snapped into place. In this example, the light element is coupled to the light guide 461 off-center, however the light element can also be set in the center of the spherical light guide.

[0060] Fig. 9C A cloud-like light guide 462 is shown having a hemispherical recessed area sized to accommodate a light element. The light element is inserted into the recessed area and then adhesively bonded or snapped into place. The cloud-like light guide may include a plurality of protrusions extending radially outward.

[0061] Fig.9D A rectangular light guide 463 is shown with linear sides and an arcuate or scalloped top and bottom. The light guide includes a hemispherical recessed area sized to accommodate a light element. The light element is inserted into the recessed area and then adhesively bonded or snapped into place.

[0062] Those skilled in the art will understand that 9A to 9D The examples in are not intended to be limiting, and any shape of light guide may be coupled to the illumination element to support tissue in the tumor cavity and ensure that light is delivered to the target treatment area.

[0063] Fig.10 Another example of an irradiation element that can be used to conform to a tumor cavity 1100 after tumor resection is shown. Here, an irradiation element of a package 401 having any of the configurations described herein is coupled to a tether 300 and powered by electricity from the tether 300. The irradiation element in package 401 may include one or more light sources coupled to a substrate such as a flexible or rigid PCB. The irradiation element is coupled to an expandable member 470, such as a balloon, rather than the solid seal previously described above. The expandable member is plastic, so that when the expandable member is radially expanded, it will conform to the wall of the tumor cavity and provide uniform support, thereby helping to ensure that the target treatment area is irradiated with light. In addition, in order to adapt to changes in the tumor cavity, the radially expandable member can be adjusted by further expansion or by contracting it. The expandable member can be expanded using a fluid such as a liquid or a gas. Contrast material can also be used so that the balloon can be visualized using radiographic imaging.

[0064] Fig.11The use of a planar immersion lens 600 that can be disposed on a substrate is shown. The planar immersion lens 600 can be disposed between an external power source (not shown) and a power receiver element 700 in the irradiation system and helps focus energy onto the receiver to efficiently transmit energy. The substrate can be ridged or flexible and can be disposed adjacent to or attached to the skull 1000 and close to the power receiver element. Here, the irradiation system can be any example disclosed herein and includes a wireless receiver 700 that is disposed in a tumor cavity after tumor resection or attached to the skull 1000. The wireless receiver 700 includes an antenna coil 710 that is used to receive energy from an external energy source and the energy is focused onto the coil by an immersion lens. The irradiation element, which can include one or more light sources such as LEDs, is powered by the power delivered to the coil. The light source can be encapsulated in a seal 720 that helps diffuse the light and also helps keep the implant in place in the tumor cavity 1100. Any seals and light guides disclosed herein can also be used in this example of the irradiation system.

[0065] Fig.12 The use of multiple light sources in an irradiation system is shown. Here, the irradiation element includes multiple light sources 420 oriented to provide directional light output. In this example, three light sources 420 (e.g., LEDs) are oriented so that light is emitted radially outward and in different directions relative to adjacent light sources. Here, light is emitted at 3:00 o'clock, 6:00 o'clock, and 9:00 o'clock. The tether 300 delivers power to the light source. The irradiation element is disposed in a tumor cavity 1100 formed after a tumor is removed from the brain of the patient's skull 1000. The light source can be independently controlled to guide the light, and the light intensity and on / off timing are also independently adjusted. Some electronic devices 480 can be disposed on a substrate 430 that holds the light source 420. The substrate 430 can be a printed circuit board. The irradiation element can be encapsulated 410 in an optical material that, for example, facilitates light delivery by helping to diffuse the light or effectively transmit the light and providing a protective covering for the light source. Any seal or light guide described herein can be used as a seal. Having multiple light sources enables different light treatments to be provided.

[0066] Fig.13 It is shown that it can be used in this article such as Fig.12 An example of a light source control device 480 for any example of an illumination system described in the invention. When multiple light sources are used, the light source control device 480 controls the illumination of the target tissue and is capable of independently controlling the light sources. The control device 480 includes an oscillator 481 and a multiplexer 482 that cycles through the multiplexers at a desired switching frequency. Fig.13Each of the four LEDs 483 shown. In an alternative example, a microcontroller 484 may control the oscillator 481 and the multiplexer 482. A tether 300 connects the control device to the power receiver element. The electrical components may be mounted on the PCB 430. The control device 480 may also be in the housing instead of the illumination element.

[0067] Fig.14 An example of an irradiation system that may also include electrical stimulation of a target treatment area is shown. Here, an irradiation system is set in a tumor cavity 1100 after a tumor is removed from the brain of a patient's skull 1000. The irradiation system can be any system disclosed herein and can include a tether 300 for providing power to an irradiation element 420, which can have one or more light sources coupled to a substrate such as a PCB 430. The light source and substrate can be encapsulated 410 in a material that protects the device and facilitates delivery of light to the target treatment area, for example by acting as a light guide or by diffusing the light. The encapsulation can be any packaging example or light guide disclosed herein, and can also help secure the device to the tumor cavity. Extending from the PCB is a conductor 801 attached to an electrode 800, which is exposed to the side of the irradiation element and can provide electrical stimulation (deep brain stimulation) to the target treatment area by direct contact with brain tissue or by conduction through interstitial fluid in the resection cavity. Thus, light therapy and electrical stimulation can be provided simultaneously. An irradiation system (e.g. Fig.14 Electrodes for tissue stimulation, whether in the brain or elsewhere in the body, can be used with any of the examples of the phototherapy systems described herein. Additionally, the phototherapy system with electrodes is not limited to implantation in a tumor cavity formed following tumor resection. The phototherapy system can be placed in any tissue where phototherapy and / or electrical stimulation will be delivered to treat any disease or condition.

[0068] Fig.15A An example of a reinforced substrate that can be used with any of the examples of the light and / or electrical stimulation systems disclosed herein is shown. For any substrate used in these examples, such as a substrate on which a light source is mounted, or a light guide substrate, it may be advantageous to use a substrate with reinforcements in the substrate to provide a stiffer substrate or a substrate that can be bent, flexed, or otherwise shaped to fit a target treatment area and retain that shape. Here, the substrate is similar to Figure 7The substrate 455 in the embodiment of the present invention is a flat planar substrate that can be trimmed to a desired size and shape to fit a target treatment area. The substrate can be formed of a material having reinforcement features, or the reinforcement features can be built into the substrate. For example, here, a two-dimensional grid of ribs 457 can be formed in the substrate to provide the desired reinforcement properties. This helps the substrate maintain its shape once it is set in the tumor cavity created after tumor resection. The irradiation element 430 (which can be any irradiation element disclosed herein) can be positioned anywhere along the substrate, and the tether 300 is coupled to the irradiation element 430 to supply power. The reinforcement features can be formed of different materials (e.g., different polymers) having different mechanical properties (e.g., Young's modulus, durometer, etc.) compared to the base substrate.

[0069] Fig. 15B Shows Fig.15A A device having reinforcement features in a substrate implanted in a tumor cavity 1100 in a skull 1000. A tether 300 provides power to an irradiation element (not shown in this view) coupled to a substrate having a reinforcement member or stiffening member. The substrate is formed as a partially closed ring in two dimensions or as a partially closed sphere in three dimensions to support and conform to tissue and irradiate tissue. The substrate acts as a light guide to help irradiate the target treatment area.

[0070] Fig.16 A reinforcing substrate (eg, a closed ring in two dimensions or a closed sphere in three dimensions) is shown. Fig.15A Here, power is delivered via tether 300 to an illumination element (not shown, and which may be any illumination element disclosed herein) disposed on a reinforcing substrate 458 in a tumor cavity 1100 in a skull 1000. The reinforcing substrate may be coupled to Fig.15A The ends may be held juxtaposed to each other in a closed configuration, either the same or different as shown in FIG, and due to reinforcements in the base plate that maintain the desired shape or due to the use of an adhesive. This helps to hold the base plate in the desired configuration to support the tumor cavity to ensure proper irradiation of the target treatment area.

[0071] Fig.17 The use of additional support elements in a tumor cavity 1100 in a patient's skull 1000 is shown. Figure 7 , FIG. 15A to FIG. 15B and Fig.16The wallpaper substrate concept described in the can be used for additional support elements disposed in the tumor cavity to help support tissue in the target treatment area and also to help distribute light to the target treatment area. Here, the tether 300 provides power to the illumination element, which can be any illumination element disclosed herein. The illumination element can be encapsulated in a material, and the combination of the illumination element and the seal can be coupled to a flat planar substrate 457 that can be shaped and trimmed to fit in the tumor cavity. The flat planar substrate 457 can be any flat planar substrate described herein, and can be optically transparent to ensure that light passes through the flat planar substrate. Here, the wallpaper is formed as a partially closed ring in two dimensions, or as a partial sphere in three dimensions. In some cases, it may be beneficial to provide additional support elements 459, which help support tissue in the tumor cavity and prevent collapse, and the additional support elements can also be formed of optical materials to form light guides that help distribute light to the target treatment area. The support element can be a thin sheet of planar material that is trimmed and shaped to fit the tumor cavity, or the support element can be prefabricated into various desired shapes. The support element can then be secured to the tissue in the tumor cavity using techniques known in the art (e.g., using sutures, adhesives, or other techniques). Additional support elements can also act as spacers between the tissue and the illumination element, or as optical instruments to help deliver light to the tissue.

[0072] Fig.18 Another example of using an additional support element 490 in a tumor cavity 1100 in a patient's skull 1000 is shown. Again, the tether 300 provides power to the illumination element, which can be any illumination element disclosed herein. Multiple additional support elements 490 can be coupled together (as indicated by the arrows) to form a fully closed ring or a partially open ring (in two dimensions) or a fully closed sphere or a partially open sphere (in three dimensions), which creates a rigid or semi-rigid structure that supports the tissue in the tumor cavity and prevents the tissue from collapsing inward. Thus, customization can be performed during surgery, ensuring that the light provided by the illumination element can illuminate the entire target treatment area and support the cavity. The support elements can be snapped together, press-fitted together, adhesively coupled together, or using coupling mechanisms known in the art to form any desired shape, and these support elements can be formed of optical materials used to help distribute light to the target treatment area.

[0073] Fig.19 A second port is shown for coupling the illumination element to an external light source. Here, the tether 300 is coupled to the tether 300 as shown above. Figure 7The irradiation element (not shown) in the flat planar substrate 455 is described. The tether 300 delivers power to the irradiation element, which delivers light to the target treatment area via the flat planar substrate 455. As described above, the flat planar substrate 455 can be shaped and trimmed to conform to the target treatment area, and the flat planar substrate can be adhesively bonded to the tissue. In some cases, such as when cyanoacrylate is used, light can be used to help cure the adhesive. Therefore, the external light source 1300 can provide the required curing light such as ultraviolet light via a port 1210 that can be releasably coupled to the external light source. Then, the light is delivered to the flat planar substrate via the optical fiber 1200, which then delivers the light to the target treatment area, thereby facilitating the curing of the adhesive. Once the substrate 455 is adhesively bonded to the tissue, the external light source can be turned off and the external light source can be decoupled and removed from the second port 1210. The port 1210 and the optical fiber 1200 can remain coupled to the flat planar substrate 455, or the port and the optical fiber can also be removed. Other components that can be adhesively bonded, such as a substrate, may also be adhesively bonded and cured using an external light source coupled to the light input port 1210 and delivered to the flat planar substrate via the optical fiber 1200 for irradiating and curing the adhesive. Figure 17 to Figure 18 Auxiliary support elements in, around (e.g. Figure 5 Packaging of irradiation components FIG. 6A to FIG. 6D The shape of the optical light guide in 9A to 9D In other examples, the second light port can be used to introduce light into the target treatment area via the substrate 455 using an external light source to illuminate a biological agent, chemical or other agent that reacts to light.

[0074] FIG. 20A to FIG. 20B The use of multiple light sources in an illumination element and the resulting illumination pattern providing the desired illumination control is shown.

[0075] A uniform light source may not be the best solution for asymmetrically distributed disease in human tissue. Depending on the individual patient and the details of the anatomy and tumor, there may be areas in the surgical cavity that are more likely to contain residual tumor. In order to focus the photodynamic therapy (PDT) effect, it may be beneficial to concentrate the light to these areas. Clinical trials using intraoperative PDT have shown a direct relationship between input light (flux, joules / cm^2) and clinical outcomes. In a single application (as part of a longer series of treatments), examples of the devices disclosed herein can deliver customized light output, with greater emphasis / output on areas with greater tumor risk.

[0076] The total amount of light available in an implanted device is limited, primarily due to wireless power transfer limitations and tissue heating limitations. Therefore, optimal use of light sources is desirable and can be achieved in a device that can control the output of multiple light sources in a variable combination of light sources such as with on and off configurations.

[0077] Furthermore, this configuration can be applied not only to on and off configurations, but also to control individual LED light outputs within defined ranges. This can be controlled by firmware embedded within the implanted PCB or housing, which will direct the power output of the individual light sources in the implant. User control of this can be achieved through a user interface designed to control the power delivery and output means. The planning of this "prescription" for each patient can be similar to the spatial and temporal planning of radiation therapy, combined with a priori imaging of the tumor location in the patient.

[0078] exist Fig. 20A In the embodiment of the present invention, the tether 300 is coupled to an illumination element, which in this example includes four independently controllable light sources 420, here LEDs. The LEDs are mounted in a substrate 430 such as a flexible PCB, and the assembly can be packaged in any manner, as previously described. Because the LEDs can be independently controlled, the LEDs can be turned on or off as needed to direct light in a desired direction for a desired amount of time.

[0079] Fig. 20B The intensity of light emitted by four LEDs in all four directions when emitting light in a direction away from the center of the PCB 430 is shown. Each direction has a leaf-shaped pattern that shows the illumination pattern of each LED and the intensity of the emitted light. With the total power provided by the tether fixed, the intensity of each LED is higher when only a single LED is activated at a time. Therefore, the illumination can be directed in the desired direction and the light intensity can also be controlled.

[0080] Example of usage

[0081] Fig.21 An example of a method of treating a tumor is shown. Treatment may be determined by a team of physicians and surgeons, which may include a neurosurgeon, a neuroradiologist, and a neuro-oncologist. Any of the irradiation devices and optional features disclosed herein may be used according to the following method of use. This example relates to the treatment of brain cancer, but this is not intended to be limiting, and one skilled in the art will appreciate that other diseases and conditions may also be treated.

[0082] MRI (magnetic resonance imaging) scans can be used to determine the size and shape of the tumor, and based on this information, a device of appropriate size can be selected. Other imaging techniques known in the art, such as computed tomography (CT), positron emission tomography (PET), radiographic imaging, etc., can also be used. The irradiation dose can also be determined based on the bioavailability of the photosensitizer delivered to the target tissue and the effective light flux and timing. In some examples, artificial intelligence (AI) or AI classifiers can be used at least as a pattern recognition tool to detect and guide physicians to optimize targeted therapy, thereby improving patient outcomes. Dosages include photosensitizer drug doses and frequency, as well as light flux from implantable phototherapy devices. Depending on the patient's condition and the expected severity of any remaining tumor cells in the tumor margin, the initial dose may be higher or lower.

[0083] The craniotomy typically removes a circular bone segment of 5 cm to 10 cm diameter from the skull and enables access to the patient's brain. After the tumor is removed 2102, the device is implanted 2104 in the tumor cavity formed after the craniotomy and tumor removal surgery, where a large portion of the glioblastoma tumor or other diseased tissue is removed by a neurosurgeon using standard surgical procedures. The light source portion of the device is fixed in place by a neurosurgeon using methods known in the art (including any of these methods described herein). The light source can include a thin flexible sheet or wallpaper that is glued to the cavity and solidified in place. The surgeon can trim the thin flexible sheet or wallpaper to fit the tumor size and shape 2106 of an individual patient.

[0084] The surgeon can adhesively bond or otherwise secure the device into the tumor cavity using cyanoacrylate, fibrin glue, or a similar biocompatible tissue adhesive 2108. The device is capable of "self-curing" by emitting the wavelength of light required by the adhesive (glue). The LED emitter can be built into the device, or an external curing light can be coupled to the light guide so that the curing light can go where it is needed. For example, in the case of an adhesive (such as a UV curing adhesive) that is cured by light, then the light source itself can be its own source of curing light. The device can have an attachment that connects to a point on the light source, and the curing light can be sent to the adhesive by the light source, such as previously described above with respect to Fig.19 The example described.

[0085] If trimming is required, the surgeon can trim the light guide shape of the light source with surgical scissors or other cutting instruments to better fit the corresponding tumor cavity of the patient. The light source can contain visual markings indicating areas that should not be cut.

[0086] The placement of the illuminating element is at the discretion of the neurosurgeon, but should ensure that the light is directed to the target treatment area that contains residual tumor or is likely to experience recurrence. For dendritic and invasive GBM tumors, an additional margin of up to about 2 cm from the known margin may be a good margin. For smaller tumors, the light element can be attached so that all luminal surfaces are irradiated.

[0087] The device 2110 can then be tested to visually check that the light source is working and in the correct position.

[0088] The tether can extend to the outside of the skull, and the wireless power portion of the device is fixed in place anywhere outside the skull and under the scalp (e.g., behind the ear). The tether can also be fixed to the skull so that it will not be pulled out by the patient. A clip or grommet can be attached to the skull adjacent to the craniotomy opening, and the tether can be fixed with a clip or grommet to protect the wire from the sharp edges around the craniotomy and also to keep the tether in place. Excess wire can be wound around the clip or grommet. If necessary, additional sutures, screws, adhesives, etc. can be used to help fix the tether and coil. A recessed area in the skull can be formed to help accommodate the tether, coil, or housing to prevent or minimize bulging. The coil can be set on the same side as the craniotomy, or the coil can be set on the side of the contralateral side. Once the device is implanted and fixed to the skull, the skull can be closed, and the scalp can also be closed.

[0089] Optionally, the irradiation system may include radiopaque markers adjacent to the irradiation elements to allow the surgeon or physician to visualize and confirm placement of the device in the patient's tumor cavity using imaging techniques known in the art (e.g., MRI, PET, x-ray, etc.).

[0090] After recovery from surgery, photodynamic therapy 2112 is activated by powering the wireless power portion of the implant via an external transmitter in the clinic. The implant can control the level of power it receives and direct most of that power to the light source. The transmitter will monitor the dosage under observation by the operator. Each course of treatment will require sufficient dosage for effective photodynamic therapy. Since the course of treatment may be only a few hours at most, patients can use regular phototherapy courses to control the recurrence of their tumors for months or even years. An example of a duty cycle can include one minute of irradiation and thirty seconds of no irradiation, and then repeat. This helps reduce heat and can also enable tissues to be reoxygenated between light cycles. The power receiving element in any example of the device may include a clock oscillator so that it can manage the cycling of the light source. The energy transmitter is able to reprogram the power receiver element to change the timing of light delivery.

[0091] The fractionation of the dose can occur over several days, distinguishing this method from a one-time treatment.

[0092] Use of the disclosed devices and methods enables efficient transfer of large amounts of power to the device while still allowing the optical device to be located in the center of the brain that is not easily reached by traditional wireless power methods.

[0093] Phototherapy can optionally be combined with imaging and mapping to help guide irradiation. Since the irradiation element can include multiple light sources, light can be directed to the desired direction so that if an area with more tumor cells is identified or an area with more tumor cells is expected, phototherapy can be directed in that direction. In addition, phototherapy can be combined with algorithms and tumor recurrence modeling to direct light to the area of ​​interest, where the dose is also predicted by computer modeling. The devices, systems, and methods described herein can be used with any photosensitizer that provides the desired diagnostic or therapeutic effect. Examples of photosensitizers are described below. Brain imaging techniques known in the art are then used to monitor patients' adverse reactions to photodynamic therapy or photosensitizer drugs at regular intervals (e.g., every 3 to 6 months) to look for tumor recurrence. Patient doses and treatments can be adjusted as needed.

[0094] Possible opportunities for personalized treatment may occur at various times during a patient's treatment, including during resection, during the approximately 6-week recovery period following resection, during the approximately 6-week period of combined TMZ (temozolomide) chemotherapy and radiation therapy, and during the 6-month follow-up period. The use of phototherapy may be used alone or in conjunction with any of these time periods and treatments to provide enhanced results.

[0095] Wavelength of light

[0096] The wavelength of light delivered by the illumination element is selected based on the wavelength required to activate the photosensitizer and the depth of tissue penetration. For example, light in the red to near infrared wavelength range of about 600 nm to 940 nm may have sufficient tissue penetration in brain tissue. This wavelength may be used for any example of the device disclosed herein.

[0097] Examples of photosensitizers

[0098] Any photosensitizer that can have a therapeutic effect when exposed to light can be used in any example of the irradiation system described herein. Examples of photosensitizers include, but are not limited to, methyl aminolevulinate hydrochloride; paldeporfin potassium; talaporfin sodium; SGX-301; fimaporfin + gemcitabine; redaporfin; aminolevulinic acid + artemisinin; CTT-1700; IVX-MES; IVX-PDT; IVXP-02; JL-103; photobacteria; YC-9; ADC + fimaporfin; bleomycin sulfate + fimaporfin; levometorfin; methyl aminolevulinate hydrochloride; lutetium motexafin; patoporfin; SL-017; Vangiolux; deuterated phospholipin; small molecules that activate ABCB1 for graft-versus-host disease; recombinant peptides targeting EGFR for oncology; small molecules targeting eNOS; nNOS and NO synthase for oncology; epirubicin hydrochloride + fimaporfin; porfimer sodium; temoporfin; palladium bacterial pheophytin; rotaporfin; verteporfin; and 5-aminolevulinic acid.

[0099] These photosensitizers can be used with light in the treatment of various cancers and other diseases, including but not limited to: basal cell carcinoma (e.g., basal cell epithelioma); squamous cell carcinoma; actinic (e.g., solar) keratosis; skin cancer; solid tumors; prostate cancer; esophageal cancer; transitional cell carcinoma (urothelial carcinoma); biliary tract cancer (e.g., cholangiocarcinoma); bronchial cancer; kidney cancer (e.g., renal cell carcinoma); renal cell cancer; choroidal neovascularization; brain tumors; gliomas; neurofibromas; head and neck cancer; hepatocellular carcinoma; metastatic colorectal cancer; nasal Pharyngeal cancer; pancreatic cancer; benign prostatic hyperplasia; age-related macular degeneration; coronary heart disease; cutaneous vascular malformations; peripheral arterial disease (PAD); peripheral vascular disease (PVD); mycosis fungoides; psoriasis; glioblastoma multiforme (e.g., GBM); inflammatory bowel disease; colorectal cancer; malignant mesothelioma; ovarian cancer; viral infections; colon cancer; graft-versus-host disease (GVHD); carcinoma; sarcoma; acne vulgaris; coronary artery disease (CAD) (e.g., ischemic heart disease); breast cancer; non-small cell lung cancer; small cell lung cancer; and bladder cancer.

[0100] experiment

[0101] A sample device having a coil for receiving RF energy, a rectifier for converting the AC power of the received power into DC power, and an LED was tested. The LED emits light with a wavelength of about 630 nm, and the flux (energy density) was measured to be about 120 J / cm^2. The radiated power was measured using an optical power meter over a drive current range of about 0.1 mA to about 20 mA. Based on reported literature, the extrapolated necrotic death depth for this flux level was estimated to be about 10 mm to 20 mm.

[0102] The subject of photosensitizer drug activation is well known in the art. Effective application of photodynamic therapy requires light at an optimal wavelength for photosensitizer (PS) drug activation, sufficient intensity, and sufficient duration to deliver a minimum light flux (Joules per square centimeter of area).

[0103] When demonstrating efficacy against tumors in preclinical and clinical testing, known experimental protocols have used light flux as a control parameter (i.e., PS activation threshold or target). Therefore, since the examples of the irradiation systems disclosed herein deliver discrete amounts of light flux consistent with those known in the art, effective activation of PS must be followed. In some examples, the target light flux is 90 J / cm^2 to 500 J / cm^2. In some examples, the target light flux is optimized to 100 J / cm^2 to 200 J / cm^2.

[0104] Fractional or rhythmic PDT (mPDT) has attracted considerable attention in the PDT research community. For PS activation, mPDT can achieve the same dosage, but over a longer period of time at low light intensity. Scientific literature reports that after a 10-day period in an animal model, there are promising results with a light intensity of <100uW / cm^2, 1000 times lower than that of a typical PDT scheme. By using a much longer period of time (1000x), the product of intensity multiplied by time remains constant.

[0105] Other literature suggests that fluence rate (W / cm^2) does have an effect, showing that at the same amount of dose, higher intensities kill tumor cells more deeply. This can also lead to more normal cell death, but it does support the concept of a "threshold" for photosensitizer activation.

[0106] Other studies have reported that other flux rates are possible. Flux rates of 20 J / cm^2 to 400 J / cm^2 have been used (mostly between 100 J / cm^2 and 200 J / cm^2), and there is some evidence that higher flux rates correspond to better results.

[0107] Based on the data contained in these references, implanted phototherapy devices treat targets with a light flux of 100 J / cm^2. When distributed over many hours or even days, the instantaneous power required to deliver this energy can be on the order of mW or tens of mW (e.g., 7 mW / cm^2 over 4 hours). Additional details can be found in Brendan J. Quirk et al., "Photodynamic therapy (PDT) for malignant brain tumors——Where do we stand" Photodiagnosis and Photodynamic Therapy 12.3 (2015): 530-544. And Tudge, SH et al., Modulation of light delivery in photodynamic therapy of brain tumours, Journal of Clinical Neuroscience, 1999 6(3), 227-232; and Yamagishi's Tissue-adhesive wirelessly powered optoelectronic device for metronomic photodynamic cancer therapy, Nature Biomedical Engineering, January 2019; the entire contents of which are incorporated herein by reference.

[0108] Notes and Examples

[0109] The following non-limiting examples detail certain aspects of the subject matter to address challenges and provide the benefits discussed herein, among others.

[0110] Example 1 is an implantable phototherapy device comprising: a power receiver element configured to receive power from an external power transmitter; a light delivery element powered by the power provided by the power receiver and configured to deliver phototherapy to a target treatment area; and a tether element operably coupled to the light delivery element and the power receiver element, the tether element being configured to deliver the power from the power receiver element to the light delivery element.

[0111] Example 2 is the apparatus of Example 1, wherein the power receiver element comprises a coil configured to receive the power from the external power transmitter, and wherein the power comprises radio frequency energy.

[0112] Example 3 is a device as described in any of Examples 1 to 2, wherein the power receiver element includes a sealed housing operably coupled to the tether, and the device also includes an electronic component disposed in the sealed housing, the electronic component being configured to control the power delivered to the light delivery element.

[0113] Example 4 is a device as described in any of Examples 1 to 3, wherein the light delivery element includes a light source encapsulated in an optical material, the optical material is configured to protect the light source, and wherein the optical material facilitates transmission of light from the light delivery element to the target treatment area.

[0114] Example 5 is the device of any of Examples 1 to 4, further comprising an optical light guide coupled to the light delivery element, the optical light guide being shaped to facilitate delivery of light from the light delivery element to the target treatment area.

[0115] Example 6 is the device of any of Examples 1 to 5, wherein the light delivery element comprises a plurality of light sources disposed on a substrate, and wherein the substrate is configured to be shaped to match the target treatment area.

[0116] Example 7 is the device of any of Examples 1 to 6, wherein the substrate is a light guide configured to direct light to the target treatment area, and wherein the substrate is configured to be trimmed into a desired shape to fit the target treatment area.

[0117] Example 8 is the apparatus of any of Examples 1 to 7, wherein the light delivery element comprises a plurality of light sources configured to be independently controllable relative to each other.

[0118] Example 9 is the apparatus of any of Examples 1 to 8, wherein the light delivery element further comprises a temperature sensor configured to measure a temperature at the target treatment area.

[0119] Example 10 is the device of any one of Examples 1 to 9, wherein the light delivery element is disposed in a radially expandable member having an expansion structure and a contraction structure, wherein, in the expansion structure, the radially expandable member conforms to the target treatment area.

[0120] Example 11 is a device as described in any of Examples 1 to 10, wherein the light delivery element further comprises a port configured to releasably receive an optical fiber, the optical fiber being optically coupled to an external light source, and wherein light from the external light source is delivered to the light delivery element via the optical fiber for irradiating the target treatment area.

[0121] Example 12 is a light therapy system comprising the apparatus of any one of Examples 1 to 11, and is the apparatus of any one of Examples 1 to 10, wherein the external power transmitter is configured to wirelessly transmit power to the power receiver element.

[0122] Example 13 is the system of Example 12, further comprising a planar immersion lens disposed between the external power transmitter and the power receiver element, the planar immersion lens being configured to focus energy from the external power transmitter toward the power receiver element.

[0123] Example 14 is the system of any of Examples 12 to 13, further comprising an electrode configured to provide electrical stimulation to the target treatment area.

[0124] Example 15 is the system of any of Examples 12 to 14, further comprising at least one support element configured to juxtapose and support tissue in the target treatment area.

[0125] Example 16 is the system of any of Examples 12 to 15, further comprising a photosensitizer.

[0126] Example 17 is a method for delivering light therapy to a target treatment area of ​​a patient, the method comprising: providing an implantable light therapy device, the implantable light therapy device comprising a power receiver element, a light delivery element, and a tether element; implanting the light therapy device at the target treatment area of ​​the patient; wirelessly transmitting power from an external power transmitter to the power receiver element; transmitting the power from the power receiver element to the light delivery element via the tether; and illuminating the target treatment area with light from the light delivery element.

[0127] Example 18 is the method of Example 17, wherein wirelessly transmitting power from an external power transmitter to the power receiver element includes receiving radio frequency energy with a coil.

[0128] Example 19 is the method of any one of Examples 17 to 18, wherein the irradiating comprises irradiating the target treatment area with a plurality of independently controllable light emitting elements.

[0129] Example 20 is the method of any of Examples 17 to 19, wherein wirelessly transmitting the power comprises transmitting the power from the external power transmitter and focusing the power toward the power receiver element with a planar immersion lens.

[0130] Example 21 is the method of any of Examples 17 to 20, further comprising electrically stimulating tissue in the target treatment area with energy provided by an electrode adjacent to the light delivery element.

[0131] Example 22 is the method of any of Examples 17 to 21, wherein the target treatment area includes the patient's brain.

[0132] Example 23 is the method described in any one of Examples 17 to 22, releasably coupling an optical fiber to the light delivery element; inputting light from an external light source into the light delivery element via the optical fiber; and irradiating the target tissue with light from the external light source.

[0133] Example 24 is a method described in any of Examples 17 to 23, wherein the light delivery element includes a plurality of light sources disposed on a substrate, the method further comprising: shaping the substrate to conform to the target treatment area and directing light in multiple directions to irradiate the target treatment area.

[0134] Example 25 is the method of any of Examples 17 to 24, further comprising trimming the substrate to a desired size or shape to fit the target treatment area.

[0135] Example 26 is the method of any one of Examples 17 to 25, further comprising measuring the temperature at the target treatment area with a temperature sensor.

[0136] Example 27 is the method of any of Examples 17 to 26, wherein the light delivery element comprises a plurality of light sources encapsulated in an optical material, the optical material being a light guide that directs light from the plurality of light sources to the target treatment area.

[0137] Example 28 is the method of any of Examples 17 to 27, wherein the light delivery element is disposed in a radially expandable member, the method further comprising radially expanding the radially expandable member to be juxtaposed with and conform to the target treatment area.

[0138] Example 29 is the method of any of Examples 17 to 28, further comprising positioning a support element in the target treatment area to help support tissue in the target treatment area to ensure that the tissue is irradiated.

[0139] In Example 30, the apparatus, system, or method of any one or any combination of Examples 1 to 29 can optionally be configured such that all of the listed elements or options are available for use or selection.

[0140] The above detailed description includes reference to the accompanying drawings, which form a part of the detailed description. The accompanying drawings show specific embodiments in which the present invention can be put into practice by way of illustration. These embodiments are also referred to as "examples" in this article. Such examples may include elements other than the elements shown or described. However, the inventors also consider examples in which only these elements shown or described are provided. In addition, the inventors also consider examples using any combination or arrangement of these elements (or one or more aspects thereof) shown or described with respect to a specific example (or one or more aspects thereof) or with respect to other examples (or one or more aspects thereof) shown or described herein.

[0141] In the event of an inconsistency in usage between this document and any document incorporated by reference, the usage in this document controls.

[0142] In this document, as is common in patent literature, the terms "a" or "an" are used to include one or more than one, regardless of any other instance or usage of "at least one" or "one or more." In this document, unless otherwise indicated, the term "or" is used to refer to a non-exclusive or, such that "A or B" includes "A but not B," "B but not A," and "A and B." In this document, the terms "including" and "in..." are used as the plain English equivalents of the respective terms "comprising" and "wherein." In addition, in the appended claims, the terms "including" and "comprising" are open-ended, that is, systems, devices, articles, combinations, formulations, or processes that include elements other than those listed after such terms in a claim are still considered to fall within the scope of the claim. In addition, in the appended claims, the terms "first," "second," and "third," etc. are used merely as labels and are not intended to impose numerical requirements on their objects.

[0143] The above description is intended to be illustrative, not restrictive. For example, the above examples (or one or more aspects of the examples) can be used in combination with each other. For example, a person of ordinary skill in the art can use other embodiments after consulting the above description. An abstract is provided to allow the reader to quickly determine the essence of the technical disclosure. The submitted abstract should be understood as not being used to interpret or limit the scope or meaning of the claims. In addition, in the above specific embodiments, various features can be combined together to organize the present disclosure. This should not be interpreted to mean that: for any claim, the disclosed features that are not claimed for protection are all necessary. Instead, the subject matter of the invention may be less than all the features of a specific disclosed embodiment. Therefore, the attached claims are thus incorporated into the specific embodiments as examples or embodiments, wherein each claim is independently a separate embodiment, and it is expected that such embodiments can be combined with each other in various combinations or arrangements. The scope of the present invention should be determined with reference to the attached claims and the full range of equivalents given by such claims.

Claims

1. An implantable phototherapy device comprising: a power receiver element configured to receive power from an external power transmitter; a light delivery element powered by said power provided by said power receiver element and configured to deliver light therapy to a target treatment area; a tether element operably coupled to the light delivery element and the power receiver element, the tether element being configured to deliver the power from the power receiver element to the light delivery element; as well as a radially expandable member having an expanded configuration and a collapsed configuration, wherein, in the expanded configuration, the radially expandable member conforms to and provides uniform support for the target treatment area such that the target treatment area is illuminated by the phototherapy, and Therein, the light delivery element is arranged in the radially expandable member.

2. The device according to claim 1, wherein: The power receiver element comprises a coil configured to receive the power from the external power transmitter, and wherein the power comprises radio frequency energy.

3. The device according to claim 1, wherein: The power receiver element includes a sealed housing operably coupled to the tether, the device further including electronic components disposed in the sealed housing, the electronic components configured to control the power delivered to the light delivery element.

4. The device according to claim 1, wherein: The light delivery element includes a light source encapsulated in an optical material, the optical material being configured to protect the light source, and wherein the optical material facilitates transmission of light from the light delivery element to the target treatment area.

5. The device of claim 1, further comprising an optical light guide coupled to the light delivery element, the optical light guide being shaped to facilitate delivery of light from the light delivery element to the target treatment area.

6. The device according to claim 1, wherein: The light delivery element includes a plurality of light sources disposed on a substrate, and wherein the substrate is configured to be shaped to match the target treatment area.

7. The device according to claim 6, wherein: The substrate is a light guide configured to direct light to the target treatment area, and wherein the substrate is configured to be trimmed into a desired shape to fit the target treatment area.

8. The device according to claim 1, wherein: The light delivery element includes a plurality of light sources configured to be independently controllable relative to each other.

9. The device according to claim 1, wherein: The light delivery element also includes a temperature sensor configured to measure the temperature at the target treatment area.

10. The device according to claim 1, wherein: The light delivery element also includes a port configured to releasably receive an optical fiber, the optical fiber being optically coupled to an external light source, and wherein light from the external light source is delivered to the light delivery element via the optical fiber for irradiating the target treatment area.

11. A light therapy system, comprising: The implantable phototherapy device of claim 1; as well as An external power transmitter configured to wirelessly transmit power to the power receiver element.

12. The system of claim 11, further comprising a planar immersion lens disposed between the external power transmitter and the power receiver element, the planar immersion lens being configured to focus energy from the external power transmitter toward the power receiver element.

13. The system of claim 11, further comprising electrodes configured to provide electrical stimulation to the target treatment area.

14. The system of claim 11, further comprising at least one support element configured to juxtapose and support tissue in the target treatment area.

15. The system of claim 11, further comprising a photosensitizer.

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