Granted Patent B2

US 12,631,562 · App. 18/560,514 · Granted May 19, 2026

Inventors: Parsin Haji Reza (Waterloo, CA); Kevan Bell (Waterloo, CA); Benjamin Eccelstone (Waterloo, CA); Vladimir Pekar (Waterloo, CA); Nicholas Pellegrino (Waterloo, CA); Paul Fieguth (Waterloo, CA); James Alexander Tummon Simmons (Waterloo, CA); James Tweel (Waterloo, CA)

Assignee: ILLUMISONICS INC.

G01N21/6456A61B5/0071G01N21/47G06V10/56G06V10/762G06V20/698

Abstract

Claims (132)

1 . A method of visualizing details in a sample, comprising:

generating radiative and non-radiative signals in the sample at an excitation location using an excitation beam, the excitation beam being focused below a surface of the sample;

interrogating the sample with an interrogation beam directed toward the excitation location of the sample, the interrogation beam being focused below the surface of the sample;

detecting light from the sample, the detected light including a portion of the interrogation beam returning from the sample, wherein the detected light is indicative of the generated radiative and the non-radiative signals; and

determining a value using a function based on the detected generated radiative signals and the non-radiative signals.

2 . The method of claim 1 , wherein the returned portion of the interrogation beam is indicative of the generated non-radiative signals, and a portion of the detected light that excludes the returned portion of the interrogation beam and the excitation beam is indicative of the generated radiative signals.

3 . The method of claim 1 , further comprising detecting local optical scattering from the sample.

4 . A method of visualizing details in a sample, comprising:

generating radiative and non-radiative signals in the sample at an excitation location using an excitation beam, the excitation beam being focused below a surface of the sample;

interrogating the sample with an interrogation beam directed toward the excitation location of the sample, the interrogation beam being focused below the surface of the sample;

detecting light from the sample, the detected light including a portion of the interrogation beam returning from the sample, wherein the detected light is indicative of the generated radiative and the non-radiative signals, wherein detecting the light includes detecting the generated radiative and non-radiative signals over time; and

determining an evolution time of the detected generated radiative and non-radiative signals.

5 . The method of claim 4 , wherein generating radiative and non-radiative signals in the sample occurs at a plurality of regions in the sample, and the method further comprises identifying regions among the plurality of regions that belong to cell nuclei based on the determined evolution time.

6 . The method of claim 4 , further comprising determining, based on the determined evolution time, at least one of:

a thermal diffusivity of the sample,

a conductivity of the sample,

a speed of sound in the sample,

a temperature of the sample,

a density of the sample,

a heat capacity of the sample,

an acoustic impedance of the sample,

a tissue type of the sample, or

molecular information of the sample.

7 . The method of claim 4 , further comprising:

determining an average pre-excitation signal,

determining an average post-excitation signal based on a predetermined portion of the detected signals over time,

determining an amplitude based on a difference between the determined average pre-excitation signal and the determined average post-excitation signal.

8 . The method of claim 1 , wherein the value is a ratio of the detected generated radiative signals to the non-radiative signals.

9 . The method of claim 1 , further comprising redirecting a portion of the returned interrogation beam and detecting an interaction with the sample.

10 . The method of claim 1 , wherein a wavelength of the excitation beam is configured such that the sample absorbs two or more photons simultaneously, wherein a sum of energy of the two or more photons is equal to a predetermined energy or absorption.

11 . A method of visualizing details in a sample, comprising:

generating radiative and non-radiative signals in the sample at an excitation location using an excitation beam, the excitation beam being focused below a surface of the sample;

interrogating the sample with an interrogation beam directed toward the excitation location of the sample, the interrogation beam being focused below the surface of the sample; and

detecting light from the sample, the detected light including a portion of the interrogation beam returning from the sample, wherein the detected light is indicative of the generated radiative and the non-radiative signals,

wherein a wavelength of the excitation beam is configured such that the sample absorbs two or more photons simultaneously, wherein the wavelength is equal to twice a predetermined wavelength.

12 . The method of claim 11 , wherein the predetermined wavelength is a wavelength in the ultraviolet (UV) range.

13 . The method of claim 11 , wherein the predetermined wavelength is a wavelength in the UVC range.

14 . The method of claim 1 , further comprising:

clustering the detected generated radiative and non-radiative signals based on shape using a clustering algorithm to determine features of the sample; and

determining cluster centroids based on the clustered signals and determining an image based on the clustered signals, including determining one or more colors based on the clustered signals.

15 . The method of claim 1 , wherein interrogating the sample with an interrogation beam includes moving the interrogation beam over the sample to interrogate the sample over a plurality of regions over time.

16 . The method of claim 15 , further comprising estimating non-modulated scattering caused by the movement of the interrogation beam over spatial variations of the sample.

17 . The method of claim 1 , further comprising measuring or storing a plurality of filtered-instances of one of the generated signals, wherein the plurality of filtered-instances include an unfiltered instance of the signal and a filtered instance of the signal.

18 . The method of claim 1 , further comprising:

determining a first image based on the detected generated radiative signals;

determining a second image based on the detected generated non-radiative signals;

comparing the first and second images; and

determining one or more modifications to a final image of the sample based on the comparison.

19 . A method of visualizing details in a sample, comprising:

generating radiative and non-radiative signals in the sample at an excitation location using an excitation beam, the excitation beam being focused below a surface of the sample;

interrogating the sample with an interrogation beam directed toward the excitation location of the sample, the interrogation beam being focused below the surface of the sample; and

detecting light from the sample, the detected light including a portion of the interrogation beam returning from the sample, wherein the detected light is indicative of the generated radiative and the non-radiative signals, wherein the interrogation beam includes a chirped-pulse; and

spatially separating various wavelength components of the interrogation beam.

20 . The method of claim 1 , wherein detecting the light from the sample is performed using a plurality of detectors.

21 . The method of claim 1 , wherein the excitation beam is focused in an area that is smaller than an area in which the detection beam is focused.

22 . A method of visualizing details in a sample, comprising:

generating radiative and non-radiative signals in the sample at an excitation location using an excitation beam, the excitation beam being focused below a surface of the sample;

interrogating the sample with an interrogation beam directed toward the excitation location of the sample, the interrogation beam being focused below the surface of the sample; and

detecting light from the sample, the detected light including a portion of the interrogation beam returning from the sample, wherein the detected light is indicative of the generated radiative and the non-radiative signals,

wherein the method is 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;

non-destructive testing of materials;

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.

23 . A photoabsorption remote sensing system for imaging features in a sample, comprising:

an excitation light source configured to generate signals in the sample at an excitation location, the excitation light source being focused below a surface of the sample;

an interrogation light source configured to interrogate the sample and directed toward the excitation location of the sample, the interrogation light source being focused below the surface of the sample, wherein a portion of the interrogation light source returning from the sample is indicative of generated signals;

a detection source configured to detect light from the sample, wherein the detection source is configured to detect a portion of the interrogation light source returning from the sample, the returned portion of the interrogation light source being indicative of generated signals; and

a processor configured to analyze the generated signals as a function of time and determine an image, the image being indicative of features in the sample.

24 . A photoabsorption remote sensing system for imaging features in a sample, comprising:

an excitation light source configured to generate signals in the sample at an excitation location, the excitation light source being focused below a surface of the sample;

an interrogation light source configured to interrogate the sample and directed toward the excitation location of the sample, the interrogation light source being focused below the surface of the sample; and

a detection source configured to detect light from the sample, wherein the detection source is configured to detect a portion of the interrogation light source returning from the sample, the returned portion of the interrogation light source being indicative of at least some of the generated signals; and

a processor configured to analyze the generated signals as a function of time and determine an image, the image being indicative of features in the sample.

Assignments (1)

Continuity (6)

References Cited (84)