CONFOCAL PHOTOACOUSTIC MICROSCOPY WITH OPTICAL LATERAL RESOLUTION

• US 20100268042A1
• Filed: 10/24/2008
• Published: 10/21/2010
• Est. Priority Date: 10/25/2007
• Status: Active Grant

• Current Assignee: Washington University In St Louis
• Original Assignee: Washington University In St Louis
• Inventors: Wang, Lihong, Maslov, Konstantin
• Granted Patent: US 8,454,512 B2
• Time in Patent Office: Days
• US Class Current: 600/322
• CPC Class Codes: A61B 2090/306 using optical fibres
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• CPC Class Codes: A61B 5/0068 Confocal scanning
• CPC Class Codes: A61B 5/0082 adapted for particular medical purposes
• CPC Class Codes: A61B 5/0095 by applying light and detecting acoustic waves, i.e. photoacoustic measurements
• CPC Class Codes: A61B 5/02007 Evaluating blood vessel condition, e.g. elasticity, compliance
• CPC Class Codes: A61B 5/14542 for measuring blood gases A61B5/14551 takes precedence
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/444 Evaluating skin marks, e.g. mole, nevi, tumour, scar
• CPC Class Codes: A61B 5/4848 Monitoring or testing the effects of treatment, e.g. of medication
• CPC Class Codes: A61B 8/485 involving measuring strain or elastic properties
• CPC Class Codes: G01N 21/1702 with opto-acoustic detection, e.g. for gases or analysing solids
• CPC Class Codes: G01N 2291/02836 Flow rate, liquid level
• CPC Class Codes: G01N 2291/02872 Pressure
• CPC Class Codes: G01N 29/0681 by acoustic microscopy, e.g. scanning acoustic microscopy
• 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: G02B 21/0028 specially adapted for specific applications, e.g. for endoscopes, ophthalmoscopes, attachments to conventional microscopes
• CPC Class Codes: G02B 21/008 Details of detection or image processing, including general computer control

Abstract

A confocal photoacoustic microscopy system includes a laser configured to emit a light pulse, a focusing assembly configured to receive the light pulse and to focus the light pulse into an area inside an object, an ultrasonic transducer configured to receive acoustic waves emitted by the object in response to the light pulse, and an electronic system configured to process the acoustic waves and to generate an image of the area inside the object. The focusing assembly is further configured to focus the light pulse on the object in such a way that a focal point of the focusing assembly coincides with a focal point of the at least one ultrasonic transducer.

Claims

1. A method for noninvasively imaging a scattering medium, said method comprising:

focusing at least one light pulse into a predetermined area inside an object using a focusing assembly;

transforming absorbed optical energy into an acoustic wave, the acoustic wave emitted by the object in response to the light pulse;

detecting the acoustic wave using at least one transducer positioned such that the transducer and the focusing assembly are coaxial and confocal; and

creating an image of the predetermined area inside the object based on a signal generated by the transducer representative of the acoustic wave.

2. A method according to claim 1, wherein focusing at least one light pulse comprises focusing the at least one light pulse using a focusing optical system such that the at least one light pulse converges at a focal point of the transducer.

3. A method according to claim 2, wherein focusing at least one light pulse further comprises reducing the focal point of the focusing optical system to facilitate increasing a spatial resolution.

4. A method according to claim 1, wherein creating an image comprises recording and digitizing the received acoustic wave so that the predetermined area inside the object may be imaged.

5. A confocal photoacoustic imaging apparatus comprising:

a focusing assembly configured to receive at least one light pulse and to focus the light pulse into an area inside an object;

at least one transducer configured to receive acoustic waves emitted by the object in response to the light pulse, said at least one transducer positioned such that said at least one transducer and said focusing assembly are coaxial; and

a processor configured to record and process the received acoustic waves.

6. A confocal photoacoustic imaging apparatus according to claim 5, wherein said focusing assembly comprises an optical assembly of lenses and mirrors configured to focus the at least one light pulse on the object in such a way that a focal point of said focusing assembly coincides with a focal point of said at least one ultrasonic transducer.

7. A confocal photoacoustic imaging apparatus according to claim 5, wherein said focusing assembly focusing assembly is positioned on an XYZ translation stage in order to perform raster scanning along a surface of the object with simultaneous adjustment of an axial position of said apparatus to compensate for a curvature of the surface of the object.

8. A confocal photoacoustic imaging apparatus according to claim 5, wherein said focusing assembly comprises an optical microscope objective lens configured to focus the at least one light pulse into a nearly diffraction-limited point.

9. A confocal photoacoustic imaging apparatus according to claim 5, wherein said focusing assembly comprises an objective lens configured to form an image of a small pinhole on the area inside the object.

10. A confocal photoacoustic imaging apparatus according to claim 5, wherein said focusing assembly comprises an oscillating mirror configured to scan an optical focus rapidly within a larger focal area than a focal area of said at least one transducer.

11. A confocal photoacoustic microscopy system comprising:

a laser configured to emit at least one light pulse;

a focusing assembly configured to receive the at least one light pulse and to focus the light pulse into an area inside an object;

at least one ultrasonic transducer configured to receive acoustic waves emitted by the object in response to the light pulse, wherein said focusing assembly is further configured to focus the at least one light pulse on the object in such a way that a focal point of said focusing assembly coincides with a focal point of said at least one ultrasonic transducer; and

an electronic system configured to process the acoustic waves and to generate an image of the area inside the object.

12. A confocal photoacoustic microscopy system according to claim 11, wherein said focusing assembly focusing assembly is positioned on an XYZ translation stage in order to perform raster scanning along a surface of the object with simultaneous adjustment of an axial position of said apparatus to compensate for a curvature of the surface of the object

13. A confocal photoacoustic microscopy system according to claim 11, wherein said focusing assembly comprises an optical microscope objective lens configured to focus the at least one light pulse into a nearly diffraction-limited point.

14. A confocal photoacoustic microscopy system according to claim 11, wherein said focusing assembly comprises an objective lens configured to form an image of a small pinhole on the area inside the object.

15. A confocal photoacoustic microscopy system according to claim 11, wherein said focusing assembly comprises a single-mode optical fiber configured to emit a focused at least one light pulse.

16. A confocal photoacoustic microscopy system according to claim 11, wherein said focusing assembly comprises an oscillating mirror configured to scan an optical focus rapidly within a larger focal area than a focal area of said at least one transducer.

17. A confocal photoacoustic microscopy system according to claim 11, wherein said electronic system is configured to record the acoustic waves and to display the recorded acoustic waves versus a corresponding position of said focusing assembly in order to generate the image.

18. A confocal photoacoustic microscopy system according to claim 17, wherein said electronic system comprises a motor controller configured to synchronize data acquisition and object scanning with the at least one light pulse at programmed locations of the laser focus with respect to the object.

19. A method for determining a ratio of hemoglobin absorption within a biological tissue using a handheld device, said method comprising:

focusing at least one light pulse into a predetermined area inside an object using at least one excitation wavelength, wherein a fluorescence signal is based on at least a local excitation optical fluence and properties of fluorophores in the predetermined area;

receiving a photoacoustic signal emitted by the object in response to the at least one light pulse, the photoacoustic signal being a product of the local excitation optical fluence, an optical absorption coefficient of hemoglobin, and an acoustic detection sensitivity;

determining the ratio of hemoglobin absorption based on a hemoglobin absorption coefficient that is based at least partially on the fluorescence signal and the photoacoustic signal.

20. A method for determining an oxygen metabolic rate (MRO2) within a biological tissue using a handheld device, said method comprising:

focusing at least one light pulse into a predetermined area inside an object;

receiving acoustic waves emitted by the object in response to the at least one light pulse; and

determining the MRO2 based on an area of an incoming vessel within the predetermined area, a mean flow velocity of blood in an incoming vessel, and a total concentration of hemoglobin, wherein the area of the incoming vessel and the mean flow velocity may are based on measurements obtained by one of ultrasound imaging, optical coherence tomography, and flow imaging technologies, and wherein the total concentration of hemoglobin is based on measurements obtained by the at least one light pulse.