# US 2012/0083691 A1 · Diagnostic Imaging for Age-Related Macular Degeneration (AMD) Using Second Harmonic Generation (SHG) Techniques > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2012/0083691 A1 - Document ID: US20120083691A1 - Status: Published application - Kind: A1 - Application number: 13/278,012 - Filed: 2011-10-20 - Published: 2012-04-05 - Earliest claimed: 2006-05-25 - Inventors: Josef Bille - Web page: https://patentgrep.com/patent/US20120083691A1 ## CPC - A61F 9/00825: {for photodisruption} - A61B 3/1225: {using coherent radiation} - A61N 5/062: {Photodynamic therapy, i.e. excitation of an agent} - A61B 3/152: {for aligning} - A61F 2009/00863: {Retina} - A61F: FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS (dental prosthetics A61C) - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) - A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B) ## Abstract A system for treating age-related macular degeneration includes an agent with non-centro symmetric molecules_for marking a region of diseased tissue. An optical assembly focuses the laser beam to a plurality of focal points in the region of diseased tissue, each focal point having a volumetric measurement of about 2 μm×2 μm×20 μm. Due to an increased concentration of photons in the relatively small volume of each focal point, two photons interact with a single molecule of the marking agent, within a very short interval of time (e.g. 10−13 sec). The resultant excited electron state (e.g. 3 eV) is sufficient to induce the marking agent to convert oxygen in a manner that causes the oxygen to kill the diseased tissue. Also, an interaction between photons and a non-centro symmetric molecule in the marking agent will cause a Second Harmonic Generation (SHG) response that can be used for imaging purposes. ## Claims ### Claim 1 A method for diagnostically identifying diseased tissue, during a therapeutic treatment of the diseased tissue, which comprises the steps of: introducing a marking agent into the blood stream of a patient, wherein the marking agent includes non-centro symmetric molecules; allowing the marking agent to permeate the diseased tissue; focusing a pulsed laser beam to a focal spot within the diseased tissue, wherein individual pulses in the laser beam have a pulse duration less than about 150 fs and the focal spot is characterized by a point spread function (PSF) approximately 2 μm×2 μm×20 μm in size, and wherein an interaction of photons in a laser pulse with a non-centro symmetric molecule of the marking agent in the PSF generates a Second Harmonic Generation (SHG) response signal; and detecting the SHG response signal to verify a positioning of the focal spot in the diseased tissue. ### Claim 2 (depends on 1) A method as recited in claim 1 wherein the non-centro symmetric molecule is verteporfin. ### Claim 3 (depends on 1) A method as recited in claim 1 wherein the diseased tissue is macula in a retina of a patient. ### Claim 4 (depends on 1) A method as recited in claim 1 wherein the wavelength of the laser beam “λ” is approximately 800 nm. ### Claim 5 (depends on 4) A method as recited in claim 4 wherein the wavelength of the SHG signal response “λs” is 400 nm. ### Claim 6 (depends on 1) A method as recited in claim 1 wherein the non-centro symmetric molecules provoke the SHG response signal. ### Claim 7 (depends on 1) A method as recited in claim 1 further comprising the step of creating an excited electron state with two-photon excitation fluorescence in the PSF to convert oxygen in the marking agent and kill the diseased tissue in the PSF. ### Claim 8 (depends on 7) A method as recited in claim 7 wherein the detecting step and the creating step are accomplished simultaneously. ### Claim 9 (depends on 1) A method as recited in claim 1 further comprising the step of moving the focal spot of the laser beam to a plurality of focal spots, in sequence, through the diseased tissue. ### Claim 10 A method for therapeutic treatment of a diseased tissue, which comprises the steps of: providing a marking agent, wherein the marking agent includes non-centro symmetric molecules; introducing the marking agent into the blood stream of a patient; allowing the marking agent to permeate the diseased tissue; focusing a pulsed laser beam to a focal spot within the diseased tissue, wherein individual pulses in the laser beam have a pulse duration less than about 150 fs and the focal spot is characterized by a point spread function (PSF) approximately 2 μm×2 μm×20 μm in size; causing photons in a laser pulse to interact with a non-centro symmetric molecule of the marking agent in the PSF to generate a Second Harmonic Generation (SHG) response signal; detecting the SHG response signal from the causing step to verify a positioning of the focal spot in the diseased tissue; and enabling photons in the laser pulse to interact for a two-photon excitation fluorescence in the PSF to create an excited electron state, wherein the excited electron state induces the marking agent to convert oxygen to kill the diseased tissue. ### Claim 11 (depends on 10) A method as recited in claim 10 wherein the causing step and the enabling step are accomplished simultaneously. ### Claim 12 (depends on 10) A method as recited in claim 10 wherein the diseased tissue is macula in a retina of a patient. ### Claim 13 (depends on 10) A method as recited in claim 10 wherein the wavelength of the laser beam “λ” is approximately 800 nm. ### Claim 14 (depends on 10) A method as recited in claim 10 further comprising the step of moving the focal spot of the laser beam to a plurality of focal spots, in sequence, through the diseased tissue. ### Claim 15 (depends on 10) A method as recited in claim 10 wherein the allowing step is accomplished as a consequence of a compromise of a blood-brain barrier in the eye of a patient. ### Claim 16 A system for performing a therapeutic treatment of diseased tissue which comprises: a means for introducing a marking agent into the blood stream of a patient to permeate the diseased tissue with the marking agent, wherein the marking agent includes non-centro symmetric molecules; and a means for focusing a pulsed laser beam to a focal spot within the diseased tissue, wherein individual pulses in the laser beam have a pulse duration less than about 150 fs and the focal spot is characterized by a point spread function (PSF) approximately 2 μm×2 μm×20 μm in size, and wherein an interaction of photons in a laser pulse with a non-centro symmetric molecule of the marking agent in the PSF generates a detectable Second Harmonic Generation (SHG) response signal to verify a position of the focal spot in the diseased tissue, and the interaction of photons in the laser pulse enables a two-photon excitation fluorescence in the PSF to create an excited electron state, wherein the excited electron state induces the marking agent to convert oxygen to kill the diseased tissue. ### Claim 17 (depends on 16) A system as recited in claim 16 wherein the diseased tissue is macula in a retina of a patient. ### Claim 18 (depends on 16) A system as recited in claim 16 wherein the wavelength of the laser beam “λ” is approximately 800 nm. ### Claim 19 (depends on 16) A system as recited in claim 16 wherein the focal spot (PSF) of the laser beam is moved to a plurality of focal spots, in sequence, through the diseased tissue. ### Claim 20 (depends on 16) A system as recited in claim 16 wherein the diseased tissue is macula in a retina of a patient, and wherein the wavelength of the laser beam “λ” is approximately 800 nm.