Method and apparatus for dynamically monitoring multiple in vivo tissue chromophores

• US 20050228246A1
• Filed: 04/12/2005
• Published: 10/13/2005
• Est. Priority Date: 04/13/2004
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Cerussi, Albert E., Brenner, Matthew, Tromberg, Bruce J., Lee, Jangwoen
• Granted Patent: US 7,248,909 B2
• Time in Patent Office: Days
• US Class Current: 600/310
• CPC Class Codes: A61B 5/14551 for measuring blood gases
• CPC Class Codes: A61B 5/14552 Details of sensors specially adapted therefor
• CPC Class Codes: A61B 5/412 Detecting or monitoring sepsis
• CPC Class Codes: G01N 21/31 Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry G01N21/72 takes precedence
• CPC Class Codes: G01N 21/359 using near infrared light
• CPC Class Codes: G01N 21/49 within a body or fluid
• CPC Class Codes: G01N 2201/08 Optical fibres; light guides

Abstract

A device and method utilizes a broadband diffuse optical spectroscopy (DOS) system to dynamically calculate the concentrations of multiple chromophores in vivo using a non-invasive probe. The device and method permit dynamic monitoring of multiple in vivo tissue chromophores non-invasively with sensitivities necessary for effective therapeutic monitoring. The device includes a probe containing first and second source optical fibers as well as first and second detector optical fibers. The probe is placed adjacent to a sample of interest and detects reflected light which is passed to a proximally located detector and spectrometer. The concentrations of multiple chromophores are determined in real time. In a preferred embodiment, the multiple tissue chromophores include at least two of methemoglobin (MetHb), deoxyhemoglobin (Hb-R), oxyhemoglobin (Hb-O₂), water (H₂O), and methylene blue (MB). The device and method can be used quantify and monitor methemoglobin formation in subjects suffering from methemoglobinemia.

Claims

1. A method of monitoring the concentrations of multiple chromophores in a subject comprising the steps of:

providing a broadband diffuse optical spectroscopy device, the device having a first light source emitting light at a plurality of wavelengths, the first light source being optically coupled to a first source optical fiber, and a second light source comprising a broadband light source, the second light source being optically coupled to a second source optical fiber, a first detector optical fiber being optically coupled to a detector, and a second detector optical fiber being optically coupled to a spectrometer, the first and second source optical fibers and the first and second detector optical fibers terminating in a probe;

placing the probe adjacent to the subject;

radiating the subject with light from the first light source;

detecting intensity-modulated diffuse reflectance signals using the detector;

determining absorption and reduced scattering coefficients at each wavelength of the first light source;

radiating the subject with radiation from the second light source;

acquiring broadband reflectance measurements using the spectrometer;

determining absolute reflectance spectra based on the broadband reflectance measurements and the absorption and reduced scattering coefficients;

calculating μ

_a spectra from the absolute reflectance spectra; and

determining the concentration of the multiple chromophores based on wavelength-dependent extinction coefficient spectra of each chromophore.

2. The method of claim 1, wherein the concentrations of multiple chromophores in the subject is monitored in vivo.

3. The method of claim 1, wherein the first source optical fiber comprises a bundle of optical fibers.

4. The method of claim 1, wherein the probe is secured to the surface of the subject.

5. The method of claim 1, wherein the multiple chromophores are selected from the group consisting of MetHb, Hb-R, Hb-O₂, H₂O, and MB.

6. The method of claim 1, wherein the multiple chromophores are selected from the group consisting of Hb-R, Hb-O₂, H₂O, and cytochrome-c oxidase.

7. The method of claim 1, wherein the concentrations of multiple chromophores are determined in real time.

8. The method of claim 1, wherein the radiation from the first and second light sources exits the probe in a direction perpendicular to a surface of the probe.

9. The method of claim 1, wherein the first light source comprises a plurality of laser diodes.

10. The method of claim 1, further comprising the step of displaying the concentrations of the multiple chromophores on a computer display connected to the broadband diffuse optical spectroscopy device.

11. A broadband diffuse optical spectroscopy device for monitoring the concentrations of multiple chromophores in vivo comprising:

first and second light sources, the first light source emitting light at a plurality of wavelengths and the second light source comprising a broadband light source;

a first source optical fiber coupled at a proximal end to the first light source and terminating in a probe at a distal end;

a second source optical fiber coupled at a proximal end to the second light source and terminating in the probe at a distal end;

a first detector optical fiber coupled at a proximal end to a detector and terminating in the probe at a distal end;

a second detector optical fiber coupled at a proximal end to a spectrometer and terminating in the probe at a distal end; and

a computer interfacing with the detector and the spectrometer, the computer calculating the concentrations of the multiple chromophores based on intensity-modulated diffuse reflectance signals detected at the detector and steady-state reflectance measurements made by the spectrometer.

12. The device of claim 11, wherein the probe is located on a distal end of a positioning member.

13. The device of claim 11, wherein the computer modulates the intensity of light emitted from the first light source.

14. The device of claim 11, further comprising a network analyzer for identifying the phase and amplitude of an optical signal detected by the detector.

15. The device of claim 11, wherein the detector comprises an avalanche photo diode (APD) detector.

16. The device of claim 11, wherein the distal ends of the first and second source optical fibers and the first and second detector optical fibers terminate in a substantially planar surface of the probe.

17. The device of claim 16, wherein the substantially planar surface is oriented generally planar to the long axis of the probe.

18. The device of claim 16, wherein the substantially planar surface is oriented generally perpendicular to the long axis of the probe.

19. A method of monitoring methemoglobinemia in a subject comprising the steps of:

providing a broadband diffuse optical spectroscopy device, the device having a first light source emitting light at a plurality of wavelengths and second light source comprising a broadband light source, first and second source optical fibers optically coupled, respectively, to the first and second light sources, first and second detector optical fibers optically coupled, respectively, to a detector and a spectrometer;

radiating the subject with light from the first light source;

detecting intensity-modulated diffuse reflectance signals using the detector;

determining absorption and reduced scattering coefficients at each wavelength of the first light source;

radiating the subject with radiation from the second light source;

acquiring broadband reflectance measurements using the spectrometer;

determining absolute reflectance spectra based on the broadband reflectance measurements and the absorption and reduced scattering coefficients;

calculating μ

_a spectra from the absolute reflectance spectra; and

determining the concentration of at least two chromophores selected from the group consisting of methemoglobin, deoxyhemoglobin, oxyhemoglobin, water, and methylene blue based on wavelength-dependent extinction coefficient spectra.

20. The method of claim 19, wherein the concentrations of the at least two chromophores are displayed on a display in real time.