Pulsed ultrasound modulated optical tomography using lock-in camera

• US 10,335,036 B2
• Filed: 12/15/2017
• Issued: 07/02/2019
• Est. Priority Date: 11/22/2017
• Status: Active Grant

• Current Assignee: Hi LLC (Cybin, Inc.)
• Original Assignee: Hi LLC (Cybin, Inc.)
• Inventors: Yang, Changhuei, Marblestone, Adam, Alford, Jamu
• Primary Examiner(s): Santos Rodriguez, Joseph M
• Application Number:
  US15/844,370
• Publication Number:
  US 20190150743A1
• Time in Patent Office: 564 Days
• CPC Class Codes: A61B 2562/04 Arrangements of multiple sensors of the same type
• CPC Class Codes: A61B 2576/026 for the brain
• CPC Class Codes: A61B 5/0042 for the brain
• CPC Class Codes: A61B 5/0066 Optical coherence imaging
• CPC Class Codes: A61B 5/0073 by tomography, i.e. reconstruction of 3D images from 2D projections A61B5/0066 takes precedence
• CPC Class Codes: A61B 5/0097 by applying acoustic waves and detecting light, i.e. acoustooptic measurements
• CPC Class Codes: A61B 5/14553 specially adapted for cerebral tissue
• CPC Class Codes: A61B 5/4064 Evaluating the brain A61B5/031, A61B5/369, A61B5/14553 take precedence
• CPC Class Codes: A61B 5/4875 Hydration status, fluid retention of the body
• CPC Class Codes: A61B 5/6803 Head-worn items, e.g. helmets, masks, headphones or goggles
• CPC Class Codes: A61B 5/6814 Head
• CPC Class Codes: A61B 5/7278 Artificial waveform generation or derivation, e.g. synthesising signals from measured signals A61B5/327 takes precedence
• CPC Class Codes: G01B 9/02002 using two or more frequencies
• CPC Class Codes: G01B 9/0201 using temporal phase variation
• CPC Class Codes: G01B 9/02031 With non-optical systems, e.g. tactile
• CPC Class Codes: G01N 2021/1706 in solids
• CPC Class Codes: G01N 2021/3129 Determining multicomponents by multiwavelength light
• CPC Class Codes: G01N 21/1702 with opto-acoustic detection, e.g. for gases or analysing solids
• CPC Class Codes: G01N 21/45 using interferometric methods; using Schlieren methods
• CPC Class Codes: G01N 21/4795 spatially resolved investigating of object in scattering medium in vivo A61B
• CPC Class Codes: G01N 29/2418 : using optoacoustic interaction with the material, e.g. laser radiation, photoacoustics photoacoustic cells G01N21/1702; measuring characteristics of vibrations by using radiation-sensitive means G01H9/00; acousto-optical conversion techniques for short-range imaging G01S15/8965; sound-producing devices using laser bundle G10K15/046
• CPC Class Codes: G16H 30/40 : for processing medical images, e.g. editing

Abstract

A system and method of performing ultrasound modulated optical tomography. Ultrasound is delivered into a target voxel in an anatomical structure, and sample light is delivered into the anatomical structure, whereby a portion of the sample light passing through the target voxel is scattered by the biological tissue as signal light, and a portion of the sample light not passing through the target voxel is scattered by the anatomical structure as background light. The ultrasound and sample light are pulsed in synchrony, such that only the signal light is frequency shifted by the ultrasound. Reference light is combined with the signal light and background light to generate an interference light pattern, which is sequentially modulated to generate a plurality of different interference light patterns. Spatial components of each of the different interference light patterns are simultaneously detected and stored in bins.

Claims

1. An ultrasound modulated optical tomography (UOT) system, comprising:

an acoustic assembly configured for delivering ultrasound into a target voxel within an anatomical structure;

an interferometer configured for delivering sample light into the anatomical structure, whereby a portion of the sample light passing through the target voxel is scattered by the anatomical structure as signal light, and another portion of the sample light not passing through the target voxel is scattered by the anatomical structure as background light that combines with the signal light to create a sample light pattern, the interferometer further configured for combining reference light with the sample light pattern to generate an interference light pattern;

a controller configured for operating the acoustic assembly and the interferometer to pulse the ultrasound and the sample light in synchrony, such that only the signal light is frequency shifted by the ultrasound, the controller further configured for operating the interferometer to sequentially modulate the interference light pattern to generate a plurality of different interference light patterns;

a lock-in camera having an array of detectors configured for simultaneously detecting spatial components of each different interference light pattern, wherein each detector of the lock-in camera respectively stores a plurality of values in a plurality of bins of the lock-in camera representative of the respective spatial components of the interference light patterns, wherein the controller is configured for synchronizing operation of the acoustic assembly, the interferometer, and the array of detectors of the lock-in camera, such that the different interference light patterns are detected at specific points on a cycle of the ultrasound; and

a processor configured for determining a physiologically-dependent optical parameter of the target voxel based on the plurality of values stored in the bins of each detector.

2. The UOT system of claim 1, wherein the physiologically-dependent optical parameter is the level of deoxygenated and/or oxygenated hemoglobin concentration or relative abundance.

3. The UOT system of claim 1, wherein the target voxel comprises brain matter.

4. The UOT system of claim 3, wherein the processor is configured for determining neural activity within the target voxel based on the determined physiologically-dependent optical parameter.

5. The UOT system of claim 1, wherein the interferometer is configured for sequentially modulating the interference light pattern by phase modulating the interference light pattern.

6. The UOT system of claim 5, wherein the interferometer is configured for phase modulating the interference light pattern by setting different phases between the sample light and the reference light.

7. The UOT system of claim 6, wherein the different phases are 0, π

/2, π

, and 3π

/2.

8. The UOT system of claim 1, wherein the controller is configured for operating the acoustic assembly and the interferometer to pulse the ultrasound and the sample light in synchrony, such that only a single pulse of the sample light is delivered into the anatomical structure for each pulse of the ultrasound delivered into the target voxel.

9. The UOT system of claim 1, wherein the interferometer is configured for combining the reference light with the signal light in a homodyne manner.

10. The UOT system of claim 9, wherein the interferometer is further configured for frequency shifting the sample light by the frequency of the ultrasound, such that the reference light is combined with the signal light in the homodyne manner.

11. The UOT system of claim 1, wherein the interferometer comprises a light source configured for generating source light, a beam splitter configured for splitting the source light into the sample light and the reference light, and a light combiner configured for combining the reference light with the signal light and the background light to generate the interference light pattern.

12. The UOT system of claim 11, wherein the interferometer further comprises an optical phase shifter configured for setting a phase difference between the sample light and the reference light to phase modulate the interference light pattern.

13. The UOT system of claim 1, wherein each of the interference light patterns comprises a speckle light pattern.

14. The UOT system of claim 1, wherein the lock-in camera is configured for simultaneously detecting the spatial components of each different interference light pattern, and storing the plurality of values for all of the interference patterns in the plurality of bins within 10 milliseconds.

15. The UOT system of claim 1, wherein the array of detectors of the lock-in camera is configured for simultaneously detecting the spatial components of each different interference light pattern, and storing the plurality of values for all of the interference light patterns in the plurality of bins of the lock-in camera within 1 microsecond to 1 millisecond.

16. The UOT system of claim 1, wherein the processor is configured for reconstructing the amplitude of the signal light using the plurality of values stored in each of the bins of the lock-in camera, and determining the physiologically-dependent optical parameter of the target voxel based on the reconstructed amplitude of the signal light.

17. The UOT system of claim 1, wherein the target voxel is less than one mm³.

18. A method of performing pulsed ultrasound modulated optical tomography (UOT), comprising:

delivering ultrasound into a target voxel within an anatomical structure;

delivering sample light into the anatomical structure, whereby a portion of the sample light passing through the target voxel is scattered by the anatomical structure as signal light, and another portion of the sample light not passing through the target voxel is scattered by the anatomical structure as background light that combines with the signal light to create a sample light pattern;

pulsing the ultrasound and the sample light in synchrony, such that only the signal light is frequency shifted by the ultrasound;

combining reference light with the sample light pattern to generate an interference light pattern;

sequentially modulating the interference light pattern to generate a plurality of different interference light patterns;

simultaneously detecting spatial components of each different interference light pattern with a lock-in camera;

synchronizing the delivery of the ultrasound, the delivery of the sample light, and the detection of the different interference light patterns, such that the different interference light patterns are detected at specific points on a cycle of the ultrasound;

storing a plurality of values for each detected spatial component in a plurality of bins of the lock-in camera, the plurality of values being representative of the spatial component for the respective interference light patterns; and

determining a physiologically-dependent optical parameter of the target voxel based on the plurality of values stored in the bins.

19. The method of claim 18, wherein the wavelength of the sample light is in the range of 950-1080 nanometers.

20. The method of claim 18, wherein the target voxel comprises brain matter.

21. The method of claim 18, further comprising determining neural activity within the target voxel based on the determined physiologically-dependent optical parameter.

22. The method of claim 18, wherein the interference light pattern is sequentially modulating by phase modulating the interference light pattern.

23. The method of claim 22, wherein the interference light pattern is phase modulated by setting different phase differences between the sample light and the reference light.

24. The method of claim 23, wherein the ultrasound and the sample light are pulsed in synchrony, such that only a single pulse of the sample light is delivered into the anatomical structure for each pulse of the ultrasound delivered into the anatomical structure.

25. The method of claim 18, further comprising combining the reference light with the signal light in a homodyne manner.

26. The method of claim 25, further comprising frequency shifting the sample light by the frequency of the ultrasound, such that the reference light is combined with the signal light in the homodyne manner.

27. The method of claim 18, further comprising generating source light, and splitting the source light into the sample light and the reference light.

28. The method of claim 18, wherein each of the interference light patterns comprises a speckle light pattern.

29. The method of claim 18, further comprising reconstructing the amplitude of the signal light using the plurality of values stored in each of the bins of the lock-in camera, wherein the physiologically-dependent optical parameter of the target voxel is determined based on the reconstructed amplitude of the signal light.