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AssigneeThe Regents of the University of California
InventorsThomas Gentry, Ryan Morton, Tyson Kim
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Methods, systems and adaptors for multiphoton imaging of, and laser-tissue interactions with, non-transparent tissue, such as ocular and periocular tissue, are provided. Aspects of the present invention include methods of imaging a structure through non-transparent tissue, such as ocular or periocular tissue, comprising: deploying an excitation source to transmit light energy to a structure through non-transparent tissue, such as ocular or periocular tissue, detecting light emitted from the structure via multiphoton excitation through the non-transparent tissue, such as ocular or periocular tissue, and imaging the structure based on the detected light. Aspects of the present invention further include methods of treating tissue, such as ocular or periocular tissue or dermatologic tissue, by manipulating an imaged structure, including, for example, providing non-incisional therapy, photo-tissue interactions, multi-photon-mediated damage, such as thermal damage, photo-disruption, photo cross-linking, blood vessel coagulation or ablating tissue. Aspects of the present invention further include methods of imaging dermatologic tissues or providing dermatologic treatments. Aspects of the present invention further include methods of providing cosmetic treatments. Aspects of the present invention further include methods of guiding delivery of gene therapy or cellular therapy in ocular or periocular tissue. Also provided are systems and adaptors for performing the methods described herein.
A method of imaging a structure through non-transparent tissue, the method comprising:
A method of manipulating a structure through non-transparent tissue, the method comprising:
The method of any of the previous claims, wherein the non-transparent tissue comprises non-transparent ocular or periocular tissue.
The method of any of the previous claims, wherein the non-transparent tissue comprises one or more of:
The method of any of the previous claims, wherein the non-transparent tissue comprises light-scattering tissue or light-absorbing tissue.
The method of any of the previous claims, wherein the non-transparent tissue comprises pigmented uveal tissues.
The method of any of the previous claims, wherein the structure comprises one or more of:
The method of any of the previous claims, wherein the structure comprises one or more of:
The method of any of the previous claims, wherein the structure is present in front of (relative to the excitation source) a retinal pigment epithelium (RPE).
The method of any of the previous claims, wherein the structure comprises light-scattering tissue.
The method of any of the previous claims, wherein the structure comprises light-absorbing tissue.
The method of any of the previous claims, wherein the method further comprises introducing fluorescent dye into the structure.
The method of any of the previous claims, wherein the method further comprises labeling blood plasma present in the structure with a fluorescent dye.
The method of any of the previous claims, further comprising imaging the structure over a specified volume.
The method of any of the previous claims, further comprising imaging the structure over a specified period of time.
The method of any of the previous claims, wherein the method is a method of imaging cellular dynamics or imaging neuronal activity or imaging a corneal nerve or imaging aspects of a central nervus system.
The method of any of the previous claims, wherein the method further comprises utilizing an invasive probe to image aspects of a central nervus system, optionally, further comprising thinning a region of a skull to image aspects of a central nervus system.
The method of any of the previous claims, wherein the method further comprises visualizing nerve structures or pain receptors and, optionally, utilizing imaged nerve structures or pain receptors to mitigate pain.
The method of any of the previous claims, wherein the method is a method of imaging neuronal activity, optionally with calcium indicators;
The method of any of the previous claims, wherein the excitation source comprises one or more laser systems.
The method of any of the previous claims, wherein the excitation source comprises one or more laser systems configured to emit light energy with average power output great than 100 Watts.
The method any of the previous claims, wherein the excitation source comprises one or more laser systems that utilize dispersion compensation.
The method of any of the previous claims, wherein the excitation source comprises one or more laser systems comprise a usable power band of 350 nm to 5,000 nm.
The method of any of the previous claims, wherein the excitation source comprises a first laser.
The method of any of the previous claims, wherein the excitation source comprises a second laser.
The method of any of the previous claims, wherein the excitation source comprises a third component.
The method of any of the previous claims, wherein deploying an excitation source comprises translating the excitation source over a predetermined area.
The method of any of the previous claims, wherein deploying an excitation source comprises articulating the excitation source around the non-transparent tissue.
The method of any of the previous claims, wherein the excitation source comprises a pulsed laser.
The method of any of the previous claims, wherein deploying an excitation source comprises deploying one or more of the following optical components:
The method of any of the previous claims, wherein light emitted from the structure via multiphoton excitation comprises stimulated light.
The method of any of the previous claims, wherein light emitted via multiphoton excitation comprises light emitted from endogenous fluorophores present in the structure or from exogenous fluorophores present in the structure.
The method of any of the previous claims, wherein endogenous or exogenous fluorophores present in the structure emit one or more of ultra-violet, blue, green, red or far red light.
The method of any of the previous claims, wherein light emitted from the structure comprises light emitted via two-photon excitation (2PEF) and further comprises a second harmonic generation (SHG) signal.
The method of any of the previous claims, wherein light emitted from the structure comprises light emitted via three-photon excitation (3PEF) and further comprises a third harmonic generation (THG) signal.
The method of any of the previous claims, wherein deploying an excitation source to transmit light energy to a structure comprises spatially guiding the excitation source to transmit light energy through the non-transparent tissue.
The method of any of the previous claims, further comprising employing an adaptive optics technique.
The method of any of the previous claims, further comprising employing an adaptive optics technique applied to light transmitted from the excitation source.
The method of any of the previous claims, further comprising employing an adaptive optics technique configured to increase efficiency of multiphoton excitation.
The method of any of the previous claims, further comprising employing an adaptive optics technique configured to improve a resolution of the imaged structure.
The method of any of the previous claims, further comprising employing an adaptive optics technique comprising one or more of:
The method of any of the previous claims, further comprising employing an adaptive optics technique comprising direct wavefront sensing comprising employing a Shack-Hartman sensor and a deformable mirror.
The method of any of the previous claims, further comprising employing an adaptive optics technique configured to improve spatiotemporal resolution.
The method of any of the previous claims, further comprising employing velocity analysis by particle tracking and cross-correlation analysis.
The method of any of the previous claims, further comprising employing velocity analysis by particle tracking and cross-correlation analysis comprising measuring blood flow, wherein measuring blood flow, optionally, comprises measuring choroid blood flow.
The method of any of the previous claims, further comprising velocity analysis by particle tracking and cross-correlation analysis comprising employing line-scanning particle image velocimetry (LS-PIV).
The method of any of the previous claims, further comprising utilizing an imaged structure to perform flow analysis.
The method of any of the previous claims, further comprising performing flow analysis, wherein the flow analysis comprises analysis of fluid flow within the structure.
The method of any of the previous claims, comprising utilizing multi-core processors or parallel processing units to perform flow analysis, wherein the multi-core processors or parallel processing units optionally comprise graphics processing units (GPUS).
The method of any of the previous claims, further comprising performing flow analysis substantially in real time.
The method of any of the previous claims, further comprising performing flow analysis, wherein the flow analysis comprises generating a velocity map of fluid flow within the structure.
The method of any of the previous claims, further comprising deploying sensors configured to collect back-scattered light emitted from the structure via multiphoton excitation through the non-transparent tissue.
The method of any of the previous claims, further comprising deploying sensors configured to collect light other than back-scattered light emitted from the structure via multiphoton excitation through the non-transparent tissue.
The method of any of the previous claims, further comprising imaging at subcellular resolution.
The method of any of the previous claims, further comprising using imaging of the structure to detect or diagnose disease;
The method of any of the previous claims, further comprising manipulating an imaged structure.
The method of any of the previous claims, further comprising manipulating an imaged structure comprising using the excitation source to manipulate the structure.
The method of any of the previous claims, further comprising manipulating the structure, wherein manipulating the structure comprises using the excitation source for one or more of:
The method of any of the previous claims, wherein manipulating a structure, optionally, by using the excitation source for photo-tissue interactions, comprises providing treatment of tumors or cancerous tissue or cancerous cells.
The method of any of the previous claims, wherein manipulating a structure, optionally, by using the excitation source for photo-tissue interactions, comprises configuring the excitation source for photo-disruption;
The method of any of the previous claims, wherein manipulating an imaged structure comprises ablating the structure;
The method of any of the previous claims, further comprising using the excitation source to treat glaucoma, optionally, comprising increasing outflow of aqueous humor.
The method of any of the previous claims, further comprising manipulating the imaged structure using the excitation source to prevent or treat retinal breaks, wherein the retinal break is, optionally, a peripheral retinal break.
The method of any of the previous claims, further comprising using the excitation source for non-incisional therapy comprising using the excitation source to prevent or treat retinal breaks, wherein the retinal break is, optionally, a peripheral retinal break.
The method of any of the previous claims, further comprising preventing or treating retinal breaks comprising transscleral imaging or transscleral treatment.
The method of any of the previous claims, further comprising preventing or treating retinal breaks comprising identifying and providing photocoagulation therapy to the retina.
The method of any of the previous claims, further comprising using the excitation source for non-incisional therapy comprising:
The method of any of the previous claims, further comprising manipulating the imaged structure using the excitation source to optically cross-link scleral tissue.
The method of any of the previous claims, wherein the method is a method for prevention of myopia.
The method of any of any of the previous claims, further comprising manipulating the imaged structure using the excitation source to visualize extraocular muscle function.
The method of any of the previous claims, further comprising performing targeted alternation of extraocular muscle function.
The method of any of any of the preceding claims, further comprising visualizing orbital fat.
The method of any of the preceding claims, further comprising performing targeted thermal or photocoagulation therapy of orbital fat.
The method of any of the preceding claims, further comprising visualizing palpebral tissues.
The method of any of the preceding claims, further comprising manipulating the imaged structure by performing targeted alternation of palpebral tissues.
The method of any of the preceding claims, further comprising using the excitation source to manipulate the structure employing an adaptive optics technique.
The method of any of the preceding claims, further comprising using the excitation source to manipulate the structure employing an adaptive optics technique configured to increase efficiency of manipulating the imaged structure using the excitation source.
The method of any of the preceding claims, further comprising using the excitation source to manipulate the structure employing an adaptive optics technique configured to improve an accuracy of the excitation source.
The method of any of the preceding claims, further comprising using the excitation source to manipulate the structure employing an adaptive optics technique configured to improve the accuracy of the excitation source with respect to an aspect of the structure.
The method of any of the preceding claims, further comprising using the excitation source to manipulate the structure employing an adaptive optics technique configured to improve the accuracy of the manipulation of the imaged structure.
The method of any of the preceding claims, further comprising using the excitation source to manipulate the structure employing an adaptive optics technique, wherein the adaptive optics technique comprises one or more of:
The method of any of the preceding claims, further comprising using the excitation source to manipulate the structure employing an adaptive optics technique, wherein the adaptive optics technique is configured to improve spatiotemporal resolution.
The method of any of the preceding claims, further comprising using the excitation source to manipulate dermatologic tissue, optionally, comprising one or more of:
The method of any of the preceding claims, further comprising using the excitation source to manipulate a tear duct, optionally, to facilitate fluid flow within the tear duct.
The method of any of the preceding claims, further comprising using the excitation source to manipulate the structure to mitigate ocular tissue redness.
The method of any of the preceding claims, further comprising using the excitation source to manipulate the structure to deliver therapy to the structure.
The method of any of previous claims, wherein the method is a method of guiding delivery of gene therapy.
The method of any of the previous claims, further comprising guiding positioning of an intraocular implant based on imaging the structure.
The method of any of the previous claims, further comprising predicting effective placement of intraocular implant based on imaging the structure.
The method of any of the previous claims, further comprising imaging one or more of sulcas or capsular bag region.
The method of any of the previous claims, further comprising guiding positioning of an intraocular implant based on imaging the structure while implanting the intraocular implant.
The method of any of the previous claims, further comprising evaluating a position of an implanted intraocular implant based on imaging the structure.
The method of any of the previous claims, further comprising evaluating an effective lens position (ELP) of an implanted intraocular implant based on imaging the structure.
The method of any of the previous claims, wherein the method is a method of transscleral imaging;
The method of any of the previous claims, wherein the method is a method of imaging through light-scattering tissue;
The method of any of the previous claims, wherein the method is a method of quantification of blood flow, optionally, comprising one or more of:
The method of any of the previous claims, wherein the method is a method of deploying multi-photon excitation microscopy on non-transparent tissue, optionally comprising ocular or periocular tissue.
The method of any of the previous claims, wherein the method is a method of deploying multi-photon excitation microscopy through non-transparent tissue, optionally comprising ocular or periocular tissue.
The method of any of the previous claims, wherein the method is a method of deploying multi-photon excitation microscopy comprising one or more of:
The method of any of the previous claims, wherein the method is a method of imaging living tissue, optionally comprising ocular or periocular tissue.
The method of any of the previous claims, wherein the method is a method of imaging a subject.
The method of any of the previous claims, wherein the method is a method of imaging a subject with one or more of:
The method of any of the previous claims, wherein the method is a method of imaging a human subject.
The method of any of the previous claims, wherein the method is a method of delivering therapy.
The method of any of the previous claims, wherein the method is a method of providing cosmetic treatment.
The method of any of the previous claims, wherein the method is a method of providing cosmetic dermatologic treatment, optionally, comprising one or more of:
The method of any of the previous claims, further comprising manipulating the structure by performing controlled cutting of tissue, wherein the tissue is, optionally, dermatologic tissue.
The method of any of the previous claims, wherein the method is a method of performing a skin biopsy procedure.
The method of any of the previous claims, further comprising manipulating the structure by disrupting cancerous tissue or one or more cancer cells or ablating cancerous tissue or ablating one or more cancer cells or ablating melanoma or ablating skin melanoma.
The method of any of the previous claims, wherein the method is a method of affecting tissue shape, optionally, comprising the shape of one or more fat deposits;
The method of any of the previous claims, wherein the method is a method of tissue sculpting;
The method of any of the previous claims, further comprising using the excitation source to perforate the structure, optionally, in connection with providing thermal treatment to tissue.
The method of any of the preceding claims, further comprising deploying an adaptor for coupling an optical system to non-transparent tissue.
The method of any of the preceding claims, further comprising deploying a system for imaging a structure through non-transparent tissue.
An adaptor for coupling an optical system to non-transparent tissue, the adaptor comprising:
An immersion media for biological imaging comprising an immersion gel.
A kit comprising:
A kit comprising:
Dependencies are inferred from the claim text.