Method and devices for laser induced fluorescence attenuation spectroscopy (LIFAS)

• US 6,697,657 B1
• Filed: 06/28/2000
• Issued: 02/24/2004
• Est. Priority Date: 07/07/1997
• Status: Expired due to Fees

• Current Assignee: Cedars-Sinai Medical Center (Cedars Sinai Health System)
• Original Assignee: Cedars-Sinai Medical Center (Cedars Sinai Health System)
• Inventors: Marmarelis, Vasilis Z., Grundfest, Warren S., Shehada, Ramez E. N.
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US09/605,176
• Time in Patent Office: 1,336 Days
• Field of Search: 600/310, 600/317, 600/322, 600/323, 600/329, 600/476, 600/477, 356/300, 356/311, 356/317, 356/318
• US Class Current: 600/323
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• 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 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/7267 involving training the classification device
• CPC Class Codes: G01N 2021/6484 Optical fibres
• CPC Class Codes: G01N 21/49 within a body or fluid
• CPC Class Codes: G01N 21/6402 Atomic fluorescence; Laser induced fluorescence
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence
• CPC Class Codes: G01N 2201/06193 Secundary in-situ sources, e.g. fluorescent particles

Abstract

Methods and devices for Laser Induced Fluorescence Attenuation Laser Induced Fluorescence Attenuation Spectroscopy (LIFAS) Spectrocopy, including, in particular, methods and devices for the detection of ischemia and hypoxia in biological tissue. The LIFAS method and apparatus preferably include a source adapted to emit radiation that is directed at a sample volume in a sample to produce return light from the sample, such return light including modulated return light resulting from modulation by the sample, a first sensor, displaced by a first distance from the sample volume for monitoring the return light and generating a first signal indicative of the intensity of return light, a second sensor, displaced by a second distance from the sample volume for monitoring the return light and generating a second signal indicative of the intensity of return light, and a processor associated with the first sensor and the second sensor and adapted to process the first and second signals so as to determine the modulation of the sample. The methods and devices of the inventions are particularly well-suited for determining the wavelength-dependent attenuation of a sample and using the attenuation to restore the intrinsic laser induced fluorescence of the sample. In turn, the attenuation and intrinsic laser induced fluorescence can be used to determined a characteristic of interest, such as the ischemic or hypoxic condition of biological tissue.

Claims

1. A method for determining the oxygenation of a sample, comprising:

determining the transmittance of the sample at a plurality of wavelengths;

determining the wavelength of peak transmittance in the 450-500 nm range;

comparing the wavelength of peak transmittance to the wavelength of peak transmittance of a sample having a known level of oxygenation; and

determining the oxygenation of the sample using the result of the comparing step.

2. A spectroscopic method for the detection of ischemia in a biological sample, comprising:

determining a shape of a fluorescence spectrum of a biological sample;

identifying a main lobe of the fluorescence spectrum in the wavelength range 350-450 nm;

determining the symmetry of the main lobe;

comparing the symmetry of the main lobe to the symmetry of the main lobe of a sample having a known level of ischemia; and

detecting ischemia in the biological sample using the result of the comparing step.

3. The method of claim 2, wherein the symmetry of the main lobe is determined using skewness.

4. The method of claim 3, wherein a small skewness value indicates that the lobe is symmetric.

5. A method for determining the oxygenation of a biological sample, comprising:

determining the intrinsic fluorescence of the sample;

detecting a fluorescence spectrum of the instrinsic fluorescence in the 450-500 nm range;

comparing the fluorescence spectrum of the intrinsic fluorescence in the 450-500 nm range of the sample with the fluorescence spectrum of the intrinsic fluorescence in the 450-500 nm range of a sample having a known level of oxygenation; and

determining the oxygenation of the sample using the result of the comparing step.

6. A method for detecting ischemia in a biological sample, comprising:

determining the intrinsic fluorescence of the sample;

detecting a fluorescence spectrum of the instrinsic fluorescence in the 450-500 nm range;

comparing the fluorescence spectrum of the intrinsic fluorescence in the 450-500 nm range of the sample with the fluorescence spectrum of the intrinsic fluorescence in the 450-500 nm range of a sample having a known level of ischemia; and

detecting ischemia in the sample using the result of the comparing step.