# US 12,765,778 B2 · System and a method to distinguish between benign and malignant breast tumors > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,765,778 B2 - Document ID: US12765778B2 - Status: Granted - Kind: B2 - Application number: 18/727,127 - Filed: 2023-01-04 - Published: 2025-03-27 - Granted: 2026-10-20 - Earliest claimed: 2022-01-07 - Assignees: Agency for Science, Technology and Research; National University Hospital (Singapore) Pte Ltd - Applicants: Agency for Science, Technology and Research; National University Hospital (Singapore) Pte Ltd - Inventors: Malini Olivo; Yong Geng Goh; Ghayathri Balasundaram; Mohesh Moothanchery; Renzhe Bi; Ruochong Zhang - Web page: https://patentgrep.com/patent/US12765778B2 ## CPC - A61B 5/0095: {by applying light and detecting acoustic waves, i.e. photoacoustic measurements} - G06T 7/0012: {Biomedical image inspection} - G16H 30/20: for handling medical images, e.g. DICOM, HL7 or PACS - G06T 2207/10132: Ultrasound image - G06T 2207/30068: Mammography; Breast - G06T 2207/30096: Tumor; Lesion - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) - G06T: IMAGE DATA PROCESSING OR GENERATION, IN GENERAL - G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA ## Abstract An ex vivo method and system of identifying a state of a tumor margin in a sample. An ultrasound image and a photoacoustic image are generated, where the system includes a probe configured to deliver a pulsed laser from a laser source to a sample, where the laser source is operable to generate the pulsed laser. Furthermore, there are arrays coupled to the probe, where one of the arrays includes transducing elements arranged thereon which are operable to transmit and collect ultrasound signals, and where one of the arrays includes transducing elements arranged thereon which are operable to collect photoacoustic signals. Additionally, the system includes a data acquisition module which converts the ultrasound signals and the photoacoustic signals into the ultrasound image and the photoacoustic image, respectively. ## Claims ### Claim 1 An ex vivo method of identifying a state of a tumor margin in a sample, the method comprising: operating a system to generate an ultrasound image and a photoacoustic image, wherein the system comprises: a probe configured to deliver a pulsed laser from a laser source to a sample, wherein the laser source is operable to generate the pulsed laser; arrays coupled to the probe, wherein one of the arrays, which is a linear array, comprises transducing elements arranged thereon which are operable at a frequency of 7 MHz to 10 MHz to transmit and collect ultrasound signals, and wherein one of the arrays, which is a linear array configured adjacent to a curved array, comprises dual-frequency transducing elements arranged thereon which are operable to collect photoacoustic signals, wherein the dual-frequency comprises a range of 2 MHz to 5 MHz and 7 MHz to 10 MHz; and a data acquisition module which converts the ultrasound signals and the photoacoustic signals into the ultrasound image and the photoacoustic image, respectively, identifying from the photoacoustic image the presence or absence of lipids and observing for a pattern and distribution of the lipids, identifying from the photoacoustic image the presence or absence of collagen and observing for a pattern and distribution of the collagen; identifying from the photoacoustic image the presence or absence of hemoglobin and observing for a pattern and distribution of the hemoglobin; and comparing from the photoacoustic image an intensity of the collagen, or collagen and hemoglobin with an intensity of tissue proximal to the collagen, or collagen and hemoglobin. ### Claim 2 (depends on 1) The ex vivo method of claim 1, wherein the state of the tumor margin is negative, positive, or comprises a dye. ### Claim 3 (depends on 1) The ex vivo method of claim 1, wherein operating the system comprises operating the laser source to generate the pulsed laser having: a wavelength ranging from 600 nm to 2000 nm, a wave period of 10 ns or less, or a frequency of 1 to 100 Hz. ### Claim 4 (depends on 1) The ex vivo method of claim 1, wherein operating the system comprises having the laser source configured at an angle to the probe to deliver the pulsed laser to the sample, or having the laser source deliver the pulsed laser to the sample via a fiber, wherein one end of the fiber is configured at an angle to the probe. ### Claim 5 (depends on 1) The ex vivo method of claim 1, wherein operating the system comprises operating the probe in heavy water or having the probe incorporated with heavy water. ### Claim 6 (depends on 1) The ex vivo method of claim 1, wherein the arrays comprise one array having a planar surface configured between and adjacent to two arrays each having a curved surface, or wherein operating the system comprises operating transducing elements arranged on the planar surface at a higher frequency than or same frequency as transducing elements arranged on the curved surface. ### Claim 7 (depends on 1) The ex vivo method of claim 1, wherein observing for the pattern and distribution of the collagen further comprises observing the thickness of the collagen. ### Claim 8 (depends on 1) The ex vivo method of claim 1, further comprising: observing the presence or absence of vascularity extension from a tumor; or observing for heterogeneity of the issue from the ultrasound image; or correlating the ultrasound image and the photoacoustic image to a histopathological microscopic image. ### Claim 9 A method of determining a state of a tumor, the method comprising: operating a system to generate an ultrasound image and a photoacoustic image, wherein the system comprises: a probe configured to deliver a pulsed laser from a laser source to a sample, wherein the laser source is operable to generate the pulsed laser; arrays coupled to the probe, wherein one of the arrays, which is a linear array, comprises transducing elements arranged thereon which are operable at a frequency of 7 MHz to 10 MHz to transmit and collect ultrasound signals, and wherein one of the arrays, which is a linear array configured adjacent to a curved array, comprises dual-frequency transducing elements arranged thereon which are operable to collect photoacoustic signals, wherein the dual-frequency comprises a range of 2 MHz to 5 MHz and 7 MHz to 10 MHz; and a data acquisition module which converts the ultrasound signals and the photoacoustic signals into the ultrasound image and the photoacoustic image, respectively, identifying from the ultrasound image the presence or absence of an abnormal tissue or a lesion; identifying from the photoacoustic image the presence or absence of lipids and observing for a pattern and distribution of the lipids, identifying from the photoacoustic image the presence or absence of water and observing for a pattern and distribution of the water; identifying from the photoacoustic image the presence or absence of collagen and observing for a pattern and distribution of the collagen; identifying from the photoacoustic image the presence or absence of hemoglobin and observing for a pattern and distribution of the hemoglobin; and comparing from the photoacoustic image an intensity of the collagen, or collagen and hemoglobin with an intensity of tissue proximal to the collagen, or collagen and hemoglobin. ### Claim 10 (depends on 9) The method of claim 9, wherein the state of the tumor is benign, malignant, or indeterminate. ### Claim 11 (depends on 9) The method of claim 9, wherein the tumor is a breast cancer tumor. ### Claim 12 (depends on 9) The method of claim 9, wherein operating the system comprises operating the laser source to generate the pulsed laser having: a wavelength ranging from 600 nm to 2000 nm, a wave period of 10 ns or less, or a frequency of 1 to 100 Hz. ### Claim 13 (depends on 9) The method of claim 9, wherein operating the system comprises having the laser source configured at an angle to the probe to deliver the pulsed laser to the sample, or having the laser source deliver the pulsed laser to the sample via a fiber, wherein one end of the fiber is configured at an angle to the probe. ### Claim 14 (depends on 9) The method of claim 9, wherein operating the system comprises operating the probe in heavy water or having the probe incorporated with heavy water. ### Claim 15 (depends on 9) The method of claim 9, wherein the arrays comprise one array having a planar surface configured between and adjacent to two arrays each having a curved surface, or wherein operating the system comprises operating transducing elements arranged on the planar surface at a higher frequency than or same frequency as transducing elements arranged on the curved surface. ### Claim 16 (depends on 9) The method of claim 9, further comprising: observing for heterogeneity of the tissue from the ultrasound image; or correlating the ultrasound image and the photoacoustic image to a histopathological microscopic image. ### Claim 17 A system operable to generate an ultrasound image and a photoacoustic image, wherein the system comprises: a probe configured to deliver a pulsed laser from a laser source to a sample, wherein the laser source is operable to generate the pulsed laser; arrays coupled to the probe, wherein one of the arrays, which is a linear array, comprises transducing elements arranged thereon which are operable at a frequency of 7 MHz to 10 MHz to transmit and collect ultrasound signals, and wherein one of the arrays, which is a linear array configured adjacent to a curved array, comprises dual-frequency transducing elements arranged thereon which are operable to collect photoacoustic signals, wherein the dual-frequency comprises a range of 2 MHz to 5 MHz and 7 MHz to 10 MHz; and a data acquisition module which converts the ultrasound signals and the photoacoustic signals into the ultrasound image and the photoacoustic image, respectively. ### Claim 18 (depends on 17) The system of claim 17, wherein the laser source is configured at an angle to the probe to deliver the pulsed laser to the sample, or the laser source delivers the pulsed laser to the sample via a fiber, wherein one end of the fiber is configured at an angle to the probe. ### Claim 19 (depends on 17) The system of claim 17, wherein the probe is operable in heavy water or the probe is incorporated with heavy water. ### Claim 20 (depends on 17) The system of claim 17, wherein the arrays comprise one array having a planar surface configured between and adjacent to two arrays each having a curved surface, and/or wherein the transducing elements arranged on the planar surface are operable at a higher frequency than or same frequency as the transducing elements arranged on the curved surface.