Pulsed ultrasound modulated optical tomography with increased optical/ultrasound pulse ratio

• US 10,299,682 B1
• Filed: 12/15/2017
• Issued: 05/28/2019
• 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, Sobek, Daniel
• Primary Examiner(s): Santos Rodriguez, Joseph M
• Application Number:
  US15/844,398
• Publication Number:
  US 20190150744A1
• Time in Patent Office: 529 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. Multiple pulses of the sample light are delivered into the anatomical structure for each pulse of the ultrasound delivered into the target voxel. Reference light is combined with the signal light and background light to generate an interference light pattern, which is sequentially modulated to generate different interference light patterns, which are detected.

Claims

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

an acoustic assembly configured for delivering ultrasound into a target voxel in 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, wherein a duration of each pulse of the ultrasound delivered into the target voxel is within a decorrelation time of the target voxel, and wherein multiple pulses of the sample light are sequentially delivered into the anatomical structure for each pulse of the ultrasound delivered into the target voxel, the controller further configured for operating the interferometer to sequentially modulate the interference light pattern to generate a plurality of different interference light patterns;

at least one detector configured for detecting the different interference light patterns; and

a processor configured for determining a physiologically-dependent optical parameter of the target voxel based on the detected interference light patterns.

2. The UOT system of claim 1, wherein the at least one detector comprises an array of detectors configured for respectively detecting spatial components of each different interference light pattern, wherein the processor is configured for determining the physiologically-dependent optical parameter of the target voxel based on the detected spatial components.

3. The UOT system of claim 2, wherein each detector, in response to external trigger signals generated by the controller, is configured for respectively storing a plurality of values in a plurality of data storing bins representative of the respective spatial components of the interference light patterns, wherein the processor is configured for determining the physiologically-dependent optical parameter of the target voxel based on the plurality of values stored in the data storing bins of each detector.

4. 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.

5. The UOT system of claim 1, wherein the physiologically-dependent optical parameter is the level of water concentration or relative water concentration of brain matter.

6. The UOT system of claim 5, wherein the wavelength of the sample light is in the range of 950-1080 nanometers.

7. The UOT system of claim 1, wherein the anatomical structure is a head, the system further comprising a wearable unit configured for being affixed to the head, the wearable unit comprising the acoustic assembly and the interferometer.

8. The UOT system of claim 1, wherein the target voxel comprises brain matter, and the processor is configured for determining whether or not neural activity exists within the target voxel based on the determined physiologically-dependent optical parameter.

9. 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.

10. The UOT system of claim 9, wherein the interferometer is configured for phase modulating the interference light pattern by respectively setting different phases between sequential pulses of the sample light and the reference light.

11. The UOT system of claim 10, wherein the different phases are 0, π

/2, π

, and 3π

/2.

12. The UOT system of claim 1, wherein the pulses of the sample light are identical.

13. The UOT system of claim 12, wherein the interferometer comprises:

at least one 1×

N fiber splitter configured for splitting a single optical pulse into an N number of identical light pulses;

an N number of optical fibers configured for propagating the N number of identical light pulses, wherein the N number of optical fibers are of different lengths, such that the N number of identical light pulses are temporally spaced apart;

at least one N×

1 fiber coupler configured for temporally combining the N number of identical light pulses; and

a single optical fiber for propagating the N number of temporally combined identical light pulses as the sample light pulses.

14. The UOT system of claim 1, wherein the interferometer is configured for combining the reference light with the signal light using a homodyne technique.

15. The UOT system of claim 14, 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 using the homodyne technique.

16. 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.

17. The UOT system of claim 16, 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.

18. The UOT system of claim 3, wherein each of the interference light patterns comprises a speckle light pattern.

19. The UOT system of claim 18, wherein the spatial components comprise speckle grains of the speckle light pattern.

20. The UOT system of claim 3, wherein the array of detectors is configured for respectively detecting spatial components of each different interference light pattern, and storing the plurality of values for all of the interference patterns in the plurality of data storing bins within 10 milliseconds.

21. The UOT system of claim 3, wherein the array of detectors is configured for respectively detecting spatial components of each different interference light pattern, and storing the plurality of values for all of the interference patterns in the plurality of data storing bins within 1 microsecond to 1 millisecond.

22. The UOT system of claim 3, wherein the processor is configured for reconstructing the amplitude of the signal light using the plurality of values stored in each of the data storing bins, and determining the physiologically-dependent optical parameter of the target voxel based on the reconstructed amplitude of the signal light.

23. The UOT system of claim 3, wherein each value respectively stored in each of the data storing bins is an intensity of the spatial component of the respective interference light pattern, the processor is configured for using the plurality of values stored in each of the data storing bins to extract a product of the amplitude of the signal light and a known amplitude of the reference light, and determining the amplitude of the signal light from the extracted product.

24. The UOT system of claim 1, wherein the target voxel is less than one mm³, and the acoustic assembly is configured for focusing the ultrasound onto the target voxel.

25. The UOT system of claim 3, further comprising a lock-in camera that includes the array of detectors and the corresponding data storing bins.

48. The UOT system of claim 3, wherein the controller is configured for synchronizing operation of the acoustic assembly, the interferometer, and the array of detectors, such that the different interference light patterns are detected at specific points on a cycle of the ultrasound.

50. The UOT system of claim 1, wherein the multiple pulses of the sample light have the same wavelength.

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

delivering ultrasound into a target voxel in 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, wherein a duration of each pulse of the ultrasound delivered into the target voxel is within a decorrelation time of the target voxel, and wherein multiple pulses of the sample light are sequentially delivered into the anatomical structure for each pulse of the ultrasound delivered into the target voxel;

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;

detecting the different interference light patterns; and

determining a physiologically-dependent optical parameter of the target voxel based on the detected interference light patterns.

27. The method of claim 26, wherein spatial components of each different interference light pattern are respectively detected, wherein the physiologically-dependent optical parameter of the target voxel is determined based on the detected spatial components.

28. The method of claim 27, further comprising, in response to external trigger signals, respectively storing a plurality of values in a plurality of data storing bins representative of the respective spatial components of the interference light patterns, wherein the physiologically-dependent optical parameter of the target voxel is determined based on the plurality of values stored in the data storing bins of each detector.

29. The method of claim 26, wherein the physiologically-dependent optical parameter is the level of deoxygenated and/or oxygenated hemoglobin concentration or relative abundance.

30. The method of claim 26, wherein the physiologically-dependent optical parameter is the level of water concentration or relative water concentration of brain matter.

31. The method of claim 30, wherein the wavelength of the sample light is in the range of 950-1080 nanometers.

32. The method of claim 26, wherein the biological tissue is brain matter.

33. The method of claim 32, further comprising determining whether or not neural activity exists within the target voxel based on the determined physiologically-dependent optical parameter.

34. The method of claim 26, wherein the interference light pattern is sequentially modulated by phase modulating the interference light pattern.

35. The method of claim 34, wherein the interference light pattern is phase modulated by respectively setting different phases between sequential pulses of the sample light and the reference light.

36. The method of claim 35, wherein the different phases are 0, π

/2, π

, and 3π

/2.

37. The method of claim 26, wherein the pulses of the sample light are identical.

38. The method of claim 26, wherein the reference light is combined with the signal light using a homodyne technique.

39. The method of claim 38, further comprising frequency shifting the sample light by the frequency of the ultrasound, such that the reference light is combined with the signal light using the homodyne technique.

40. The method of claim 26, further comprising generating source light, and splitting the source light into the sample light and the reference light.

41. The method of claim 26, wherein each of the interference light patterns comprises a speckle light pattern.

42. The method of claim 41, wherein the spatial components comprise speckle grains of the speckle light pattern.

43. The method of claim 28, wherein the spatial components of each different interference light pattern are respectively detected and the plurality of values for all of the interference patterns are stored in the plurality of data storing bins within 10 milliseconds.

44. The method of claim 28, wherein the spatial components of each different interference light pattern are respectively detected and the plurality of values for all of the interference patterns are stored in the plurality of data storing bins within 1 microsecond to 1 millisecond.

45. The method of claim 28, further comprising reconstructing the amplitude of the signal light using the plurality of values stored in each of the data storing bins, wherein the physiologically-dependent optical parameter of the target voxel is determined based on the reconstructed amplitude of the signal light.

46. The method of claim 28, wherein each value respectively stored in each of the data storing bins is an intensity of the spatial component of the respective interference light pattern, wherein the plurality of values stored in each of the data storing bins are used to extract a product of the amplitude of the signal light and a known amplitude of the reference light, and the amplitude of the signal light is determined from the extracted product.

47. The method of claim 26, wherein the target voxel is less than one mm³, and wherein the ultrasound is focused on the target voxel.

49. The method of claim 28, further comprising 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.

51. The method of claim 26, wherein the multiple pulses of the sample light have the same wavelength.