Single-cell label-free photoacoustic flowoxigraphy in vivo

Patent metadata

Field	Value
Publication number	US-10433733-B2
Application number	US-201615148685-A
Country	US
Kind code	B2
Filing date	May 6, 2016
Priority date	Oct 25, 2007
Publication date	Oct 8, 2019
Grant date	Oct 8, 2019

Abstract

A method for obtaining a 3-D OR-PAM image of microvasculature within a region of interest of a subject is provided. The method includes: focusing a first light pulse at a first depth beneath a first surface position within the region of interest; receiving a first PA signal in response to the first light pulse; focusing a second light pulse at a second depth beneath the first surface position within the region of interest; receiving a second PA signal in response to the second light pulse; and forming the 3-D OR-PAM image by combining the first PA signal and the second PA signal.

First claim

What is claimed is:

1. A device for real-time spectral imaging of single moving red blood cells in a subject in vivo, the device comprising:
an isosbestic laser to deliver a series of isosbestic laser pulses at an isosbestic wavelength;
a non-isosbestic laser to deliver a series of non-isosbestic laser pulses at a non-isosbestic wavelength;
an optical fiber to direct the series of isosbestic laser pulses and the series of non-isosbestic laser pulses to an optical assembly;
the optical assembly to focus the series of isosbestic laser pulses and the series of non-isosbestic laser pulses into a beam with a beam cross-sectional diameter of less than 10 μm through an optical focus region;
a focused ultrasound transducer to detect acoustic signals generated within the optical focus region in response to the series of isosbestic and non-isosbestic laser pulses, the focused ultrasound transducer comprising an acoustic focus region that is aligned with the optical focus region; and
an acoustically transparent optical reflector to transmit acoustic signals from the acoustic focus region to the focused ultrasound transducer and to reflect the series of isosbestic and non-isosbestic laser pulses from the optical assembly to the optical focus region;
wherein each isosbestic laser pulse is delivered at a pulse separation period of 20 μs before or after each adjacent non-isosbestic laser pulse.

2. The device of claim 1 , wherein: the isosbestic wavelength is a wavelength with a hemoglobin absorbance that corresponds to an oxyhemoglobin absorbance; the isosbestic wavelength is chosen from 532 nm, 548 nm, 568 nm, 587 nm, and 805 nm; and the non-isosbestic wavelength is any wavelength with the hemoglobin absorbance that does not correspond to the oxyhemoglobin absorbance.

3. The device of claim 2 , wherein the isosbestic wavelength is 532 nm and the non-isosbestic wavelength is 560 nm.

4. The device of claim 1 , wherein the optical assembly comprises a pair of optical lenses comprising two achromatic doublets with a numerical aperture in water of 0.1.

5. The device of claim 1 , wherein the focused ultrasound transducer further comprises a central frequency of at least 10 MHz.

6. The device of claim 5 , wherein the central frequency is 50 MHz and the focused ultrasound transducer further comprises an axial spatial resolution of 15 μm.

7. The device of claim 5 , further comprising a linear scanner to move the optical assembly and the focused ultrasound transducer in a linear scanning pattern.

8. The device of claim 7 , wherein the linear scanner is a voice-coil scanner with a scanning rate of at least 100 linear scans per second.

9. The device of claim 1 , wherein the acoustically transparent optical reflector comprises a first prism and a second prism, wherein a first face of the first prism and a second face of the second prism are arranged on opposite sides of an aluminum layer forming a planar optical reflector aligned at an angle of 45° relative to an axis of the optical assembly.

10. A system for real-time spectral imaging of single moving red blood cells in a subject in vivo, the system comprising:
a dual wavelength light source module to produce a series of isosbestic laser pulses and a series of non-isosbestic laser pulses at a non-isosbestic wavelength;
an optical module to direct the series of isosbestic laser pulses and the series of non-isosbestic laser pulses through an optical focus region in a cylindrical beam with a beam cross-sectional diameter of less than 10 μm;
an ultrasound detection module to detect acoustic signals generated within the optical focus region in response to the series of isosbestic and non-isosbestic laser pulses, the ultrasound detection module comprising a focused ultrasound transducer, the focused ultrasound transducer comprising an acoustic focus region that is aligned with the optical focus region; and
an acoustically transparent optical reflector to transmit acoustic signals from the acoustic focus region to the focused ultrasound transducer and to reflect the series of isosbestic and non-isosbestic laser pulses from the optical module to the optical focus region;
wherein each isosbestic laser pulse is delivered at a pulse separation period of 20 μs before or after each adjacent non-isosbestic laser pulse.

11. The system of claim 10 , wherein the dual wavelength light source module comprises an isosbestic laser to produce the series of isosbestic laser pulses and a non-isosbestic laser to produce the series of non-isosbestic laser pulses.

12. The system of claim 10 , wherein: the isosbestic wavelength is a wavelength with a hemoglobin absorbance that corresponds to an oxyhemoglobin absorbance; the isosbestic wavelength is chosen from 532 nm, 548 nm, 568 nm, 587 nm, and 805 nm; and the non-isosbestic wavelength is any wavelength with the hemoglobin absorbance that does not correspond to the oxyhemoglobin absorbance.

13. The system of claim 12 , wherein the isosbestic wavelength is 532 nm and the non-isosbestic wavelength is 560 nm.

14. The system of claim 10 , wherein the optical module comprises an optical fiber operatively connected to the isosbestic laser and the non-isosbestic laser at a first end and operatively connected to a pair of optical lenses comprising two achromatic doublets with a numerical aperture in water of 0.1 at a second end opposite to the first end of the optical fiber.

15. The system of claim 10 , wherein the focused ultrasound transducer further comprises a central frequency of 50 MHz.

16. The system of claim 15 , further comprising a scanning module to move the optical module and the ultrasound detection module in a linear scanning pattern, wherein the scanning module comprises a voice-coil scanner with a scanning rate of at least 100 linear scans per second.

17. The system of claim 15 , wherein the system obtains images of the single moving red blood cells at an axial spatial resolution of 15 μm and a lateral spatial resolution of 3.4 μm.

18. The system of claim 15 , wherein the system simultaneously obtains one or more functional parameters of the single moving red blood cells using a pulse oximetry method, wherein the one or more functional parameters are chosen from: total hemoglobin concentration, oxygen saturation, gradient of oxygen saturation, flow speed, metabolic rate of oxygen, and any combination thereof.

Assignees

• Univ Washington

Inventors

• Wang Lihong
• Wang Lidai
• Maslov Konstantin

Classifications

• A61B5/0068

  Confocal scanning · CPC title

• A61B5/0059

  using light, e.g. diagnosis by transillumination, diascopy, fluorescence (photoacoustic A61B5/0093; optical measurement of heart rate A61B5/02416; optical measurement of blood flow A61B5/0261; optical measurement of analytes A61B5/1455) · CPC title

• A61B5/14542

  for measuring blood gases (A61B5/14551 takes precedence) · CPC title

• G01N21/1702

  with opto-acoustic detection, e.g. for gases or analysing solids · CPC title

• A61B2090/306

  using optical fibres · CPC title