# US 11,298,027 B2 · Photoacoustic remote sensing (PARS) > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,298,027 B2 - Document ID: US11298027B2 - Status: Granted - Kind: B2 - Application number: 16/847,182 - Filed: 2020-04-13 - Published: 2020-07-30 - Granted: 2022-04-12 - Earliest claimed: 2014-10-22 - Assignees: Illumisonics Inc. - Applicants: Illumisonics Inc. - Inventors: Parsin Haji Reza; Roger Zemp - Web page: https://patentgrep.com/patent/US11298027B2 ## CPC - A61B 5/0095: {by applying light and detecting acoustic waves, i.e. photoacoustic measurements} - G01N 21/1702: {with opto-acoustic detection, e.g. for gases or analysing solids} - G01N 21/1717: {with a modulation of one or more physical properties of the sample during the optical investigation, e.g. electro-reflectance} - G01N 2021/1706: {in solids} - G01N 2021/1725: {Modulation of properties by light, e.g. photoreflectance} - G01N 2201/06113: Coherent sources; lasers - G01N 2201/08: Optical fibres; light guides - G01N 2201/0846: Fibre interface with sample, e.g. for spatial resolution - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract A photoacoustic remote sensing system (PARS) for imaging a subsurface structure in a sample has an excitation beam configured to generate ultrasonic signals in the sample at an excitation location; an interrogation beam incident on the sample at the excitation location, a portion of the interrogation beam returning from the sample that is indicative of the generated ultrasonic signals; an optical system that focuses at least one of the excitation beam and the interrogation beam with a focal point that is below the surface of the sample; and a detector that detects the returning portion of the interrogation beam. ## Claims ### Claim 1 A method of visualizing details in a sample, the method comprising the steps of: generating signals in the sample at an excitation location using an excitation beam of light, the excitation beam being focused below a surface of the sample; interrogating the sample with an interrogation beam of light directed toward the excitation location of the sample, the interrogation beam being focused below the surface of the sample; and detecting a portion of the interrogation beam returning from the sample. ### Claim 2 (depends on 1) The method of claim 1, wherein the portion of the interrogation beam returning from the sample is indicative of the generated signals. ### Claim 3 (depends on 2) The method of claim 2, wherein the portion of the interrogation beam returning from the sample encodes the generated signals as one or more of intensity variations, polarization variations, phase variations, fluorescence variations, variations in nonlinear scattering, or variations in nonlinear absorption. ### Claim 4 (depends on 2) The method of claim 2, wherein the generated signals are ultrasonic and/or thermal signals. ### Claim 5 (depends on 2) The method of claim 2, wherein the generated signals are photoacoustic and/or initial pressure signals. ### Claim 6 (depends on 1) The method of claim 1, further comprising forming an image based on the returning portion of the interrogation beam. ### Claim 7 (depends on 1) The method of claim 1, wherein the excitation beam is pulsed, continuous, or intensity-modulated, and the interrogation beam is pulsed, continuous, or intensity-modulated. ### Claim 8 (depends on 1) The method of claim 1, further comprising: focusing the excitation beam at a first focal point below the surface of the sample; and focusing the interrogation beam at a second focal point below the surface of the sample. ### Claim 9 (depends on 8) The method of claim 8, wherein the first and second focal points are greater than 1 μm below the surface of the sample. ### Claim 10 (depends on 1) The method of claim 1, wherein detecting a portion of the interrogation beam returning from the sample includes detecting with an interferometer. ### Claim 11 (depends on 1) The method of claim 1, further including using an additional imaging system selected from optical coherence tomography, optical resolution photoacoustic microscopy, common photoacoustic microscopy, fluorescence microscopy, two-photon fluorescence microscopy, confocal fluorescence microscopy, Coherent-Anti-Raman-Stokes microscopy, Raman microscopy, or other photoacoustic systems. ### Claim 12 (depends on 1) The method of claim 1, used in one or more of the following applications: imaging of blood oxygen saturation; imaging of tumor hypoxia; imaging of wound healing, burn diagnostics, or surgery; imaging of microcirculation; blood oxygenation parameter imaging; estimating blood flow in vessels flowing into and out of a region of tissue; imaging of molecularly-specific targets; imaging angiogenesis for pre-clinical tumor models; clinical imaging of micro- and macro-circulation and pigmented cells; imaging of the eye; augmenting or replacing fluorescein angiography; imaging dermatological lesions; imaging melanoma; imaging basal cell carcinoma; imaging hemangioma; imaging psoriasis; imaging eczema; imaging dermatitis; imaging Mohs surgery; imaging to verify tumor margin resections; imaging peripheral vascular disease; imaging diabetic and/or pressure ulcers; burn imaging; plastic surgery; microsurgery; imaging of circulating tumor cells; imaging melanoma cells; imaging lymph node angiogenesis; imaging response to photodynamic therapies; imaging response to photodynamic therapies having vascular ablative mechanisms; imaging response to chemotherapeutics; imaging response to anti-angiogenic drugs; imaging response to radiotherapy; estimating oxygen saturation using multi-wavelength photoacoustic excitation; estimating venous oxygen saturation where pulse oximetry cannot be used; estimating cerebrovenous oxygen saturation and/or central venous oxygen saturation; estimating oxygen flux and/or oxygen consumption; imaging vascular beds and depth of invasion in Barrett's esophagus and/or colorectal cancers; functional imaging during brain surgery; assessment of internal bleeding and/or cauterization verification; imaging perfusion sufficiency of organs and/or organ transplants; imaging angiogenesis around islet transplants; imaging of skin-grafts; imaging of tissue scaffolds and/or biomaterials to evaluate vascularization and/or immune rejection; imaging to aid microsurgery; guidance to avoid cutting blood vessels and/or nerves; imaging of contrast agents in clinical or pre-clinical applications; identification of sentinel lymph nodes; non- or minimally-invasive identification of tumors in lymph nodes; imaging of genetically-encoded reporters, wherein the genetically-encoded reporters include tyrosinase, chromoproteins, and/or fluorescent proteins for pre-clinical or clinical molecular imaging applications; imaging actively or passively targeted optically absorbing nanoparticles for molecular imaging; imaging of blood clots; staging an age of blood clots; replacing a catheterization procedure; gastroenterological applications; single-excitation pulse imaging over an entire field of view; imaging of tissue; imaging of cells; imaging of scattered light from object surfaces; imaging of absorption-induced changes of scattered light; or non-contact imaging of optical absorption. ### Claim 13 A method of visualizing details in a sample, the method comprising the steps of: directing an excitation beam, using one or more lasers, toward an excitation location below a surface of the sample, to generate signals in the sample; directing an interrogation beam, using the one or more lasers, toward the excitation location of the sample; and directing detection of a portion of the interrogation beam returning from the sample that is indicative of the generated signals. ### Claim 14 (depends on 13) The method of claim 13, wherein the portion of the interrogation beam returning from the sample is indicative of the generated signals, wherein the generated signals are ultrasonic signals, thermal signals, photoacoustic signals, and/or initial pressure signals. ### Claim 15 (depends on 14) The method of claim 14, wherein the portion of the interrogation beam returning from the sample encodes the generated signals as one or more of intensity variations, polarization variations, phase variations, fluorescence variations, variations in nonlinear scattering, or variations in nonlinear absorption. ### Claim 16 (depends on 13) The method of claim 13, further including using an additional imaging system selected from optical coherence tomography, optical resolution photoacoustic microscopy, common photoacoustic microscopy, fluorescence microscopy, two-photon fluorescence microscopy, confocal fluorescence microscopy, Coherent-Anti-Raman-Stokes microscopy, Raman microscopy, or other photoacoustic systems. ### Claim 17 (depends on 13) The method of claim 13, used in one or more of the following applications: imaging of blood oxygen saturation; imaging of tumor hypoxia; imaging of wound healing, burn diagnostics, or surgery; imaging of microcirculation; blood oxygenation parameter imaging; estimating blood flow in vessels flowing into and out of a region of tissue; imaging of molecularly-specific targets; imaging angiogenesis for pre-clinical tumor models; clinical imaging of micro- and macro-circulation and pigmented cells; imaging of the eye; augmenting or replacing fluorescein angiography; imaging dermatological lesions; imaging melanoma; imaging basal cell carcinoma; imaging hemangioma; imaging psoriasis; imaging eczema; imaging dermatitis; imaging Mohs surgery; imaging to verify tumor margin resections; imaging peripheral vascular disease; imaging diabetic and/or pressure ulcers; burn imaging; plastic surgery; microsurgery; imaging of circulating tumor cells; imaging melanoma cells; imaging lymph node angiogenesis; imaging response to photodynamic therapies; imaging response to photodynamic therapies having vascular ablative mechanisms; imaging response to chemotherapeutics; imaging response to anti-angiogenic drugs; imaging response to radiotherapy; estimating oxygen saturation using multi-wavelength photoacoustic excitation; estimating venous oxygen saturation where pulse oximetry cannot be used; estimating cerebrovenous oxygen saturation and/or central venous oxygen saturation; estimating oxygen flux and/or oxygen consumption; imaging vascular beds and depth of invasion in Barrett's esophagus and/or colorectal cancers; functional imaging during brain surgery; assessment of internal bleeding and/or cauterization verification; imaging perfusion sufficiency of organs and/or organ transplants; imaging angiogenesis around islet transplants; imaging of skin-grafts; imaging of tissue scaffolds and/or biomaterials to evaluate vascularization and/or immune rejection; imaging to aid microsurgery; guidance to avoid cutting blood vessels and/or nerves; imaging of contrast agents in clinical or pre-clinical applications; identification of sentinel lymph nodes; non- or minimally-invasive identification of tumors in lymph nodes; imaging of genetically-encoded reporters, wherein the genetically-encoded reporters include tyrosinase, chromoproteins, and/or fluorescent proteins for pre-clinical or clinical molecular imaging applications; imaging actively or passively targeted optically absorbing nanoparticles for molecular imaging; imaging of blood clots; staging an age of blood clots; replacing a catheterization procedure; gastroenterological applications; single-excitation pulse imaging over an entire field of view; imaging of tissue; imaging of cells; imaging of scattered light from object surfaces; imaging of absorption-induced changes of scattered light; or non-contact imaging of optical absorption. ### Claim 18 A method of visualizing details in a sample, the method comprising the steps of: generating, using one or more light sources, an excitation beam for directing to below a surface of the sample to generate signals; generating, using the one or more light sources, an interrogation beam for directing to below the surface of the sample; and detecting a portion of the interrogation beam returning from the sample that is indicative of the generated signals. ### Claim 19 (depends on 18) The method of claim 18, wherein the portion of the interrogation beam returning from the sample is indicative of the generated signals, wherein the generated signals are ultrasonic signals, thermal signals, photoacoustic signals, and/or pressure, wherein the portion of the interrogation beam returning from the sample encodes the generated signals as one or more of intensity variations, polarization variations, phase variations, fluorescence variations, variations in nonlinear scattering, or variations in nonlinear absorption. ### Claim 20 (depends on 18) The method of claim 18, further including using an additional imaging system selected from optical coherence tomography, optical resolution photoacoustic microscopy, common photoacoustic microscopy, fluorescence microscopy, two-photon fluorescence microscopy, confocal fluorescence microscopy, Coherent-Anti-Raman-Stokes microscopy, Raman microscopy, or other photoacoustic systems.