Methods, arrangements and systems for obtaining information associated with an anatomical sample using optical microscopy

• US 9,777,053 B2
• Filed: 02/08/2007
• Issued: 10/03/2017
• Est. Priority Date: 02/08/2006
• Status: Active Grant

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Yun, Seok-Hyun
• Primary Examiner(s): Santos Rodriguez, Joseph M
• Application Number:
  US11/672,571
• Publication Number:
  US 20070233056A1
• Time in Patent Office: 3,890 Days
• Field of Search: 606 32, 356479, 385 12, 600322
• CPC Class Codes: A61B 3/102 for optical coherence tomography [OCT]
• CPC Class Codes: A61B 3/117 for examining the anterior chamber or the anterior chamber angle, e.g. gonioscopes
• 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 5/0066 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 5/0075 by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy A61B5/0071 takes precedence
• CPC Class Codes: A61B 5/0084 for introduction into the body, e.g. by catheters A61B5/1459 takes precedence
• CPC Class Codes: A61B 5/0086 using infrared radiation
• CPC Class Codes: A61B 5/0095 by applying light and detecting acoustic waves, i.e. photoacoustic measurements
• CPC Class Codes: A61B 5/0097 by applying acoustic waves and detecting light, i.e. acoustooptic measurements
• CPC Class Codes: A61B 5/4088 Diagnosing of monitoring cognitive diseases, e.g. Alzheimer, prion diseases or dementia
• CPC Class Codes: A61B 5/412 Detecting or monitoring sepsis
• CPC Class Codes: A61B 5/413 Monitoring transplanted tissue or organ, e.g. for possible rejection reactions after a transplant
• CPC Class Codes: C07K 14/70503 Immunoglobulin superfamily
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C07K 2319/32 fusions with soluble part of a cell surface receptor, "decoy receptors"
• CPC Class Codes: C07K 2319/70 containing domain for protein-protein interaction
• CPC Class Codes: G01B 9/02091 Tomographic interferometers, e.g. based on optical coherence
• CPC Class Codes: G01J 3/4412 Scattering spectrometry particle sizing by light scattering G01N15/0205; optical velocimetry of particles G01P5/20, G01P5/26
• CPC Class Codes: G01N 2021/1725 Modulation of properties by light, e.g. photoreflectance
• CPC Class Codes: G01N 2021/638 : Brillouin effect, e.g. stimulated Brillouin effect
• CPC Class Codes: G01N 21/1717 : with a modulation of one or more physical properties of the sample during the optical investigation, e.g. electro-reflectance
• CPC Class Codes: G01N 21/4795 : spatially resolved investigating of object in scattering medium in vivo A61B
• CPC Class Codes: G01N 21/636 : using an arrangement of pump beam and probe beam; using the measurement of optical non-linear properties; non-linear optics per se G02F1/35
• CPC Class Codes: G01N 2201/06 : Illumination; Optics
• CPC Class Codes: G01N 2201/0612 : Laser diodes
• CPC Class Codes: G01N 2800/042 : Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
• CPC Class Codes: G01N 2800/387 : Down syndrome; Trisomy 18; Trisomy 13
• CPC Class Codes: G01N 2800/7023 : (Hyper)proliferation
• CPC Class Codes: G01N 2800/7028 : Cancer
• CPC Class Codes: G02B 21/0052 : Optical details of the image generation

Abstract

Arrangements and methods are provided for obtaining information associated with an anatomical sample. For example, at least one first electro-magnetic radiation can be provided to the anatomical sample so as to generate at least one acoustic wave in the anatomical sample. At least one second electro-magnetic radiation can be produced based on the acoustic wave. At least one portion of at least one second electro-magnetic radiation can be provided so as to determine information associated with at least one portion of the anatomical sample. In addition, the information based on data associated with the second electro-magnetic radiation can be analyzed. The first electro-magnetic radiation may include at least one first magnitude and at least one first frequency. The second electro-magnetic radiation can include at least one second magnitude and at least one second frequency. The data may relate to a first difference between the first and second magnitudes and/or a second difference between the first and second frequencies. The second difference may be approximately between −100 GHz and 100 GHz, excluding zero.

Claims

1. An apparatus, comprising:

at least one first arrangement configured to provide at least one first electro-magnetic radiation to a live biological sample so as to generate at least one acoustic wave in the biological sample, wherein at least one second electro-magnetic radiation is produced from the biological sample based on the at least one acoustic wave;

at least one second arrangement configured to receive at least one portion of the at least one second electro-magnetic radiation;

at least one third arrangement configured to determine information associated with a biomechanical property of at least one portion of the biological sample based on a measurement of at least one of a magnitude or frequency of a spectral peak in a spectrum of the at least one second electro-magnetic radiation; and

an electro-magnetic radiation source configured to provide at least one third electro-magnetic radiation to the biological sample,

wherein the at least one first electro-magnetic radiation includes at least one first frequency, wherein the at least one second electro-magnetic radiation includes at least one second frequency of the spectral peak, wherein the at least one third electro-magnetic radiation includes at least one third frequency, and wherein the second frequency is different from the first frequency and is different from the third frequency and is determined as a function of the first and third frequencies.

2. The apparatus according to claim 1, wherein the biological sample is at least one of an organ, a tissue or cell.

3. The apparatus, according to claim 1, further comprising at least one fourth arrangement configured to generate an image of the at least one portion of the biological sample as a function of data associated with the at least one second electro-magnetic radiation.

4. The apparatus according to claim 3, further comprising at least one fifth arrangement configured to translate the at least one first electro-magnetic radiation across the biological sample.

5. The apparatus according to claim 4, wherein the at least one fifth arrangement includes at least one lens, and wherein the at least one lens focuses the at least one first electro-magnetic radiation and collects the at least one second electro-magnetic radiation.

6. The apparatus according to claim 3, wherein the at least one first electro-magnetic radiation includes at least one first frequency, wherein the at least one second electro-magnetic radiation includes at least one second frequency, and wherein the data relates to a difference between the first and second frequencies.

7. The apparatus according to claim 6, wherein the second difference is between −

100 GHz and 100 GHz, excluding zero.

8. The apparatus according to claim 1, wherein the at least one second arrangement includes a spectral filter which facilitates a determination of the spectrum of the at least one second electro-magnetic radiation.

9. The apparatus according to claim 4, wherein the at least one fifth arrangement is at least one of a catheter, an endoscope, a laparoscope, or an ophthalmic visualization device.

10. The apparatus according to claim 1, wherein the biomechanical property comprises stiffness or electrostriction.

11. The apparatus according to claim 1, wherein the biological sample is a living subject.

12. The apparatus according to claim 1, wherein the at least one first electro-magnetic radiation has a center wavelength which is between 0.5-1.8 μ

m.

13. The apparatus according to claim 12, wherein the at least one first electro-magnetic radiation has a line width which is smaller than 100 MHz.

14. The apparatus according to claim 12, wherein the at least one first electro-magnetic radiation has a form of a plurality of pulses, and wherein the duration of each of the pulses is longer than 10 ns.

15. The apparatus according to claim 1, wherein the at least one first electro-magnetic radiation includes at least two first electro-magnetic radiations, wherein a first one of the at least two first electro-magnetic radiations has a first frequency, and a second one of the at least two first electro-magnetic radiations has a second frequency, and wherein a difference between the first and second frequencies is between zero and 100 GHz.

28. The apparatus according to claim 3, wherein the at least one acoustic wave is originated from a vacuum fluctuation.

29. The apparatus according to claim 1, wherein the at least one first electro-magnetic radiation is provided to the biological sample in-vivo.

31. The apparatus according to claim 1, wherein the third arrangement is further configured to determine information associated with a difference in the biomechanical property between first and second portions of the biological sample based on a first Brillouin frequency shift associated with electro-magnetic radiation received from the first portion and a second Brillouin frequency shift associated with electro-magnetic radiation received from the second portion.

32. The apparatus according to claim 31, wherein the biomechanical property is stiffness.

16. An apparatus, comprising:

at least one first arrangement configured to provide at least one first electro-magnetic radiation to a live anatomical sample so as to generate at least one acoustic wave in the anatomical sample, wherein at least one second electro-magnetic radiation is provided from the anatomical sample based on the at least one acoustic wave;

at least one second arrangement configured to receive at least one portion of the at least one second electro-magnetic radiation;

at least one third arrangement configured to determine information associated with a biomechanical property of at least one portion of the anatomical sample based on a measurement of at least one of a magnitude or frequency of a spectral peak in a spectrum of the at least one second electro-magnetic radiation; and

at least one fourth arrangement configured to generate an image of the at least one portion of the anatomical sample based on data associated with the measurement,

wherein the at least one first electro-magnetic radiation includes at least one first frequency, wherein the at least one second electro-magnetic radiation includes at least one second frequency which is different from the at least one first frequency, and wherein the data relates to a difference between the first and second frequencies, wherein the difference between the first and second frequencies is between −

100 GHz and 100 GHz, and wherein the at least one first electro-magnetic radiation has a form of a plurality of pulses, and wherein a duration of each of the pulses is longer than 10 ns.

17. The apparatus according to claim 16, further comprising at least one fifth arrangement configured to translate the at least one first electro-magnetic radiation across the anatomical sample.

18. The apparatus according to claim 17, wherein the at least one fifth arrangement includes at least one lens, and wherein the at least one lens focuses the at least one first electro-magnetic radiation and collects the at least one second electro-magnetic radiation.

19. The apparatus according to claim 16, wherein the at least one second arrangement includes a spectral filter which facilitates a determination of the spectrum of the at least one second electro-magnetic radiation.

20. The apparatus according to claim 16, wherein the biomechanical property comprises stiffness or electrostriction.

21. The apparatus according to claim 16, wherein the anatomical sample is a living subject.

22. The apparatus according to claim 16, wherein the at least one first electro-magnetic radiation has a center wavelength which is between 0.5 and 1.8 μ

m.

23. The apparatus according to claim 22, wherein the at least one first electro-magnetic radiation has a line width which is smaller than 100 MHz.

24. The apparatus according to claim 16, wherein the at least one first electro-magnetic radiation includes at least two first electro-magnetic radiations, wherein a first one of the at least two first electro-magnetic radiations has a first frequency, and a second one of the at least two first electro-magnetic radiations has a second frequency, and wherein a difference between the first and second frequencies is between zero and 100 GHz.

25. An apparatus comprising:

at least one first arrangement configured to provide at least one first electro-magnetic radiation to a live anatomical sample so as to generate at least one acoustic wave in the anatomical sample, wherein at least one second electro-magnetic radiation is provided from the anatomical sample based on the at least one acoustic wave;

at least one second arrangement configured to receive at least one portion of the at least one second electro-magnetic radiation;

at least one third arrangement configured to determine information associated with a biomechanical property of at least one portion of the anatomical sample based on a measurement of at least one of a magnitude or frequency of a spectral peak in a spectrum of the at least one second electro-magnetic radiation; and

at least one fourth arrangement configured to generate an image of the at least one portion of the anatomical sample based on data associated with the measurement,

wherein the at least one first electro-magnetic radiation includes at least one first frequency, wherein the at least one second electro-magnetic radiation includes at least one second frequency which is different from the at least one first frequency, and wherein the data relates to a difference between the first and second frequencies, wherein the difference between the first and second frequencies is between −

100 GHz and 100 GHz, wherein at least one third electro-magnetic radiation which has at least one third frequency is provided to the sample, and wherein the second frequency is different from the first frequency and is different from the third frequency and is determined as a function of the first and third frequencies.

33. The apparatus according to claim 25, wherein the biomechanical property comprises stiffness or electrostriction.

26. A method for obtaining information associated with a live biological sample, comprising:

providing at least one first electro-magnetic radiation to the live biological sample so as to generate at least one acoustic wave in the biological sample, wherein at least one second electro-magnetic radiation is produced from the biological sample based on the at least one acoustic wave;

receiving at least one portion of at least one second electro-magnetic radiation; and

determining information associated with a biomechanical property of at least one portion of the biological sample based on a measurement of at least one of a magnitude or frequency of a spectral peak in a spectrum of the at least one second electro-magnetic radiation,

wherein the at least one first electro-magnetic radiation includes at least one first frequency, wherein the at least one second electro-magnetic radiation includes at least one second frequency of the spectral peak, wherein at least one third electro-magnetic radiation includes at least one third frequency and is further provided to the biological sample, and wherein the second frequency is different from the first frequency and is different from the third frequency and is determined as a function of the first and third frequencies.

34. The method according to claim 26, wherein the biomechanical property comprises stiffness or electrostriction.

35. The method according to claim 26, further including determining information associated with a difference in the biomechanical property between first and second portions of the biological sample based on a first Brillouin frequency shift associated with electro-magnetic radiation received from the first portion and a second Brillouin frequency shift associated with electro-magnetic radiation received from the second portion.

36. The method according to claim 35, wherein the biomechanical property is stiffness.

27. A method for obtaining information associated with a live anatomical sample, comprising:

providing at least one first electro-magnetic radiation to the live anatomical sample so as to generate at least one acoustic wave in the anatomical sample, wherein at least one second electro-magnetic radiation is provided from the anatomical sample based on the at least one acoustic wave;

receiving at least one portion of the at least one second electro-magnetic radiation;

determining information associated with a biomechanical property of at least one portion of the anatomical sample based on a measurement of at least one of a magnitude or frequency of a spectral peak in a spectrum of the at least one second electro-magnetic radiation; and

generating an image of the at least one portion of the anatomical sample based on data associated with the measurement,

wherein the at least one first electro-magnetic radiation includes at least one first frequency, wherein the at least one second electro-magnetic radiation includes at least one second frequency which is different from the at least one first frequency, and wherein the data relates to a difference between the first and second frequencies, wherein the difference between the first and second frequencies is between −

100 GHz and 100 GHz, and wherein the at least one first electro-magnetic radiation has a form of a plurality of pulses, and wherein a duration of each of the pulses is longer than 10 ns.

37. The method according to claim 27, wherein the biomechanical property comprises stiffness or electrostriction.

30. A method for obtaining information associated with a live anatomical sample, comprising:

providing at least one first electro-magnetic radiation to the live anatomical sample so as to generate at least one acoustic wave in the anatomical sample, wherein at least one second electro-magnetic radiation is provided from the anatomical sample based on the at least one acoustic wave;

receiving at least one portion of the at least one second electro-magnetic radiation;

determining information associated with a biomechanical property of at least one portion of the anatomical sample based on a measurement of at least one of a magnitude or frequency of a spectral peak in a spectrum of the at least one second electro-magnetic radiation; and

generating an image of the at least one portion of the anatomical sample based on the data associated with the measurement,

wherein the at least one first electro-magnetic radiation includes at least one first frequency, wherein the at least one second electro-magnetic radiation includes at least one second frequency which is different from the at least one first frequency, and wherein the data relates to a difference between the first and second frequencies, wherein the difference between the first and second frequencies is between −

100 GHz and 100 GHz, wherein at least one third electro-magnetic radiation includes at least one third frequency and is provided to the anatomical sample, and wherein the second frequency is different from the first frequency and is different from the third frequency and is determined as a function of the first and third frequencies.

38. The method according to claim 30, wherein the biomechanical property comprises stiffness or electrostriction.