Induced fluorescence spectroscopy blood perfusion and pH monitor and method

• US 5,456,252 A
• Filed: 09/30/1993
• Issued: 10/10/1995
• Est. Priority Date: 09/30/1993
• Status: Expired due to Term

• Current Assignee: Cedars-Sinai Medical Center (Cedars Sinai Health System)
• Original Assignee: Cedars-Sinai Medical Center (Cedars Sinai Health System)
• Inventors: Vari, Sandor G., Papazoglou, Theodore, Grundfest, Warren S.
• Primary Examiner(s): Smith, Ruth S.
• Application Number:
  US08/129,406
• Time in Patent Office: 740 Days
• Field of Search: 128/633, 128/634, 128/664, 128/665, 128/666, 356/326, 356/328
• US Class Current: 600/301
• CPC Class Codes: G01N 2021/6417 Spectrofluorimetric devices
• CPC Class Codes: G01N 2021/6484 Optical fibres
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence
• CPC Class Codes: Y10S 128/925 Neural network

Abstract

A medical monitor, and related method, determines a pre-existing physiological property of an organ of a patient by monitoring fluorescent light produced by constituents associated with the metabolic and structural condition of the organ. The monitor illuminates the organ with ultraviolet excitation light that induces some constituents of the organ to fluoresce, with the fluorescent light being monitored and processed to determine pre-existing physiological properties of the organ. A sensor monitors the return light, which includes fluorescent light produced by the fluorescent constituents of the organ, and generates first and second electrical signals indicative of the intensity of light at two wavelength. One wavelength is associated with the fluorescence of collagen, a constituent associated with organ'"'"'s structural properties, and the other wavelength is a associated with the fluorescence of NADH, a constituent associated with the organ'"'"'s metabolism. A processor then processes the first and second electrical signals to determine the localized pH of the organ. A fiber-optic waveguide is used to guide the excitation light from the laser light source to the organ and the return light from the organ to the sensor. In another aspect of the invention, the sensor generates a third electrical signal associated with the fluorescence of elastin, a constituent associated with the organ'"'"'s structural properties. The processor processes the first, second and third electrical signals to determine the perfusion or oxygenation of the organ.

Claims

1. Apparatus for determining a pre-existing physiological property of an organ having constituents including NADH and collagen, comprising:

a light source emits excitation light that is directed at an organ to produce return light from the organ, such return light including fluorescent light produced by any constituents present in the organ;

a sensor, responsive to the return light, that monitoring the return light and generates a first signal indicative of the intensity of return light within a first wavelength band associated with the fluorescence of NADH and generates a second signal indicative of the intensity of return light within a second wavelength band associated with the fluorescence of collagen; and

a processor associated with the sensor processes the first and second signals and produces an output signal, based on the first and second signals, that represents the physiological property.

2. Apparatus for determining a pre-existing physiological property of an organ as defined in claim 1, wherein the output signal produced by the processor represents the pH of the organ.

3. Apparatus for determining a pre-existing physiological property of an organ as defined in claim 1, wherein:

the excitation light produced by the light source has a wavelength between about 250 nanometers and about 450 nanometers;

the first wavelength band is centered around a wavelength that is about 190 nanometers longer than the wavelength of the excitation wavelength; and

the second wavelength band is centered around a wavelength that is about 100 nanometers longer than the wavelength of the excitation wavelength; and

the output signal produced by the processor represents the acidity or alkalinity of the organ.

4. Apparatus for determining a pre-existing physiological property of an organ as defined in claim 3, wherein:

the excitation light produced by the light source has a wavelength centered at about 308 nanometers;

the first wavelength band is between about 485 and 505 nanometers; and

the second wavelength band is between about 400 and 420 nanometers.

5. Apparatus for determining a pre-existing physiological property of an organ as defined in claim 1, wherein:

the excitation light produced by the light source has a wavelength centered at about 308 nanometers;

the first wavelength band is centered at about 495 nanometers;

the second wavelength band is centered at about 410 nanometers; and

the output signal produced by the processor represents the acidity or alkalinity of the organ.

6. Apparatus for determining a pre-existing physiological property of an organ as defined in claim 1, wherein the processor produces the output signal in accordance with a ratio defined by the formula:

space="preserve" listing-type="equation">R.sub.pH =I.sup.NADH /I.sup.COLLAGEN

where R_pH is a ratio that represents the acidity or alkalinity of the organ, I^NADH is the intensity of light within the first wavelength band, and I^COLLAGEN is the intensity of light within the second wavelength band.

7. Apparatus for determining a pre-existing physiological property of an organ as defined in claim 1, wherein:

the constituents further include elastin;

the sensor generates a third signal indicative of the intensity of return light within a third wavelength band associated with the fluorescence of elastin; and

the processor further receives the third signal from the sensor and processes the first, second and third signals such that the output signal is based also on the third signal and represents the blood perfusion of the organ.

8. Apparatus for determining a pre-existing physiological property of an organ as defined in claim 7, wherein:

the excitation light produced by the light source has a wavelength between about 250 nanometers and about 450 nanometers;

the first wavelength band is centered around a wavelength that is about 190 nanometers longer than the wavelength of the excitation wavelength;

the second wavelength band is centered around a wavelength that is about 100 nanometers longer than the wavelength of the excitation wavelength; and

the third wavelength band is centered around a wavelength that is about 70 nanometers longer than the wavelength of the excitation wavelength.

9. Apparatus for determining a pre-existing physiological property of an organ as defined in claim 7, wherein:

the excitation light produced by the light source has a wavelength centered at about 308 nanometers;

the first wavelength band is between about 485 and 505 nanometers;

the second wavelength band is between about 400 and 420 nanometers; and

the third wavelength band is between about 365 and 385 nanometers.

10. Apparatus for determining a pre-existing physiological property of an organ as defined in claim 7, wherein:

the excitation light produced by the light source has a wavelength centered at about 308 nanometers;

the first wavelength band is centered at about 495 nanometers;

the second wavelength band is centered at about 410 nanometers; and

the third wavelength band is centered at about 375 nanometers.

11. Apparatus for determining a pre-existing physiological property of an organ as defined in claim 7, wherein the processor produces the output signal in accordance with a ratio defined by the formula:

space="preserve" listing-type="equation">R.sub.PERFUSION =(I.sup.ELASTIN -I.sup.COLLAGEN)/(I.sub.NADH -I.sup.COLLAGEN)

where R_PERFUSION is a ratio that represents the blood perfusion of the organ, I^NADH is the intensity of light within the first wavelength band, I^COLLAGEN is the intensity of light within the second wavelength band, and I^ELASTIN is the intensity of light within the third wavelength band.

12. Apparatus for determining a pre-existing physiological property of an organ as defined in claim 1, further including a waveguide, associated with the light source, that transmitts the excitation light from the light source to the organ and that transmitts the return light from the organ to the sensor.

13. Apparatus for determining a pre-existing physiological property of an organ as defined in claim 12, and further comprising a probe for housing the waveguide.

14. Apparatus for determining a pre-existing physiological property of an organ as defined in claim 1, further comprising:

a first fiber-optic waveguide, associated with the light source, that transmitts the excitation light from the light source to the organ; and

a second fiber-optic waveguide, associated with the sensor, that collects the return light and transmitts it from the organ to the sensor.

15. Apparatus for determining a pre-existing physiological property of an organ as defined in claim 1, further including:

a first fiber-optic waveguide, associated with the light source, that transmitts the excitation light from the light source to the organ and that collects the return light from the organ;

a second fiber-optic waveguide, associated with the sensor, for transmitting the return light to the sensor; and

means for transmitting the return light from the first waveguide to the second waveguide, the means including a lens.

16. Apparatus for determining a pre-existing physiological property of an organ as defined in claim 1, wherein the sensor includes:

a first detector that detects the return light within the first wavelength band and generate the first signal; and

a second detector that detects the return light within the second wavelength band and generate the second signal.

17. Apparatus for determining a pre-existing physiological property of an organ as defined in claim 1, wherein the sensor includes:

a spectrograph having an array of detectors, the spectrograph resolving the return light such that each detector of the array detects a different spectral wavelength of the return light and generates a separate electrical signal representing the intensity of light in its wavelength; and

an optical analyzer, associated with the spectrograph, that analyzes the plurality of electrical signals received from the spectrograph and generates the first and second signals.

18. Apparatus for determining a pre-existing physiological property of an organ as defined in claim 1, wherein the sensor comprises:

a dichroic filter, within an optical path of the return light, that rejects return light having a wavelength equal to the wavelength of the excitation light and transmits the return light within the first and second wavelength bands;

a stop having a slit aperture, wherein a portion of the return light that is transmitted through the dichroic filter passes through the slit;

a grating that spreads the return light that passes through the slit such that the return light is spread along an axis by a distance proportional to the wavelength of the return light; and

first and second electro-optical detectors that generate the first and second electrical signals, respectively, the first electro-optical detector located along the axis at a distance corresponding to the first wavelength band and the second electro-optical detector located along the axis at a distance corresponding to the second wavelength band.

19. Apparatus for determining a pre-existing physiological property of an organ as defined in claim 1, wherein the processor includes an artificial neural network.

20. A method of determining a pre-existing physiological property of an organ having constituents including NADH and collagen comprising:

directing excitation light at the organ to cause the organ to produce return light, such return light including fluorescent light produced by constituents present in the organ;

monitoring the return light and generating first and second signals, the first signal indicative of the intensity of the return light within a first wavelength band associated with the fluorescence of NADH and the second signal indicative of the intensity of return light within a second wavelength band associated with the fluorescence of collagen; and

processing the first and second signals to produce an output signal, based on the first and second signals, that represents the physiological property of the organ.

21. A method for determining a pre-existing physiological property of an organ as defined in claim 20, wherein the output signal produced by the processor represents the pH of the organ.

22. A method of determining a pre-existing physiological property of an organ as defined in claim 20, wherein:

the excitation light used in the step of directing has a wavelength between about 250 nanometers and about 450 nanometers;

the first wavelength band used in the step of monitoring is about 190 nanometers longer than the wavelength of the excitation wavelength; and

the second wavelength band used in the step of monitoring is about 100 nanometers longer than the wavelength of the excitation wavelength; and

the outside signal produced in the step of processing represents the acidity or alkalinity of the organ.

23. A method of determining a pre-existing physiological property of an organ as defined in claim 20, wherein:

the excitation light used in the step of directing has a wavelength centered at about 308 nanometers;

the first wavelength band used in the step of monitoring is between about 485 and 505 nanometers; and

the second wavelength band used in the step of monitoring is between about 400 and 420 nanometers.

24. A method of determining a pre-existing physiological property of an organ as defined in claim 20, wherein:

the excitation light used in the step of directing has a wavelength centered at about 308 nanometers;

the first wavelength band used in the step of monitoring is centered at about 495 nanometers;

the second wavelength band used in the step of monitoring is centered at about 410 nanometers; and

the output signal produced in the step of processing represents the acidity or alkalinity of the organ.

25. A method of determining a pre-existing physiological property of an organ as defined in claim 20, wherein the step of processing includes the step of determining a ratio defined by the formula:

space="preserve" listing-type="equation">R.sub.pH =I.sup.NADH /I.sup.COLLAGEN

where R_pH is a ratio that represents the acidity or alkalinity of the organ, I^NADH is the intensity of light within the first wavelength band, and I^COLLAGEN is the intensity of light within the second wavelength band.

26. A method of determining a pre-existing physiological property of an organ as defined in claim 20, wherein:

the pre-existing physiological property is the perfusion of the organ and the constituents further include elastin;

the step of monitoring further comprises the step of generating a third signal indicative of the intensity of return light within a third wavelength band associated with the fluorescence of elastin; and

the step of processing includes processing the first, second, and third signals to produce an output signal that represents the perfusion of the organ.

27. A method of determining a pre-existing physiological property of an organ as defined in claim 26, wherein:

the excitation light used in the step of directing has a wavelength between about 250 nanometers and about 450 nanometers;

the first wavelength band used in step of monitoring is about 190 nanometers longer than the wavelength of the excitation wavelength;

the second wavelength band used in step of monitoring is about 100 nanometers longer than the wavelength of the excitation wavelength; and

the third wavelength band used in step of monitoring is about 70 nanometers longer than the wavelength of the excitation wavelength.

28. A method of determining a pre-existing physiological property of an organ as defined in claim 26, wherein:

the excitation light used in the step of directing has a wavelength centered at about 308 nanometers;

the first wavelength band used in step of monitoring is between about 485 and 505 nanometers;

the second wavelength band used in step of monitoring is between about 400 and 420 nanometers; and

the third wavelength band used in step of monitoring is between about 365 and 385 nanometers.

29. A method of determining a pre-existing physiological property of an organ as defined in claim 26, wherein:

the excitation light used in the step of directing has a wavelength centered at about 308 nanometers;

the first wavelength band used in step of monitoring is centered at about 495 nanometers;

the second wavelength band used in step of monitoring is centered at about 410 nanometers; and

the third wavelength band used in step of monitoring is centered at about 375 nanometers.

30. A method of determining a pre-existing physiological property of an organ as defined in claim 26, wherein the step of processing includes the step of causing the output signal to assume a value in accordance with a ratio defined by the formula:

space="preserve" listing-type="equation">R.sub.PERFUSION =(I.sup.ELASTIN -I.sup.COLLAGEN)/I.sub.NADH -I.sup.COLLAGEN)

where R_PERFUSION is a ratio that represents the blood perfusion of the organ, I^NADH is the intensity of light within the first wavelength band, I^COLLAGEN is the intensity of light within the second wavelength band, and I^ELASTIN is the intensity of light within the third wavelength band.

31. A method of determining a pre-existing physiological property of an organ as defined in claim 20, wherein the step of directing excitation light at an organ further comprises the step of guiding the excitation light from the light source to the organ.

32. A method of determining a pre-existing physiological property of an organ as defined in claim 20, wherein the step of monitoring the return light further comprises the step of guiding the return light from the organ to the sensor.

33. A method of determining a pre-existing physiological property of an organ as defined in claim 32, wherein the step of monitoring the return light further comprises the step of resolving the return light into its different spectral wavelengths to detect the light within the respective first and second wavelength bands.

34. Apparatus for determining the acidity or alkalinity of tissues of an organ, the tissues having constituents including NADH and collagen, comprising:

a light source that emits excitation light;

a first fiber-optic waveguide that transmits the excitation light from the light source to the tissues to cause the tissues to produce return light, such return light including fluorescent light produced by any compounds present in the tissues;

a second fiber-optic waveguide that transmits the return light from the tissues;

a sensor, associated with the second waveguide, for monitoring the return light, wherein the sensor generates a first signal indicative of the intensity of return light within a first wavelength band associated with the fluorescence of NADH and generates a second signal indicative of the intensity of return light within a second wavelength band associated with the fluorescence of collagen; and

a processor that processes the first and second signals and produces an output signal that represents the acidity or alkalinity of the tissues.

35. Apparatus for determining the perfusion of the tissues of an organ, the tissues having constituents including NADH, collagen and elastin, comprising:

a light source that emits excitation light;

a first fiber-optic waveguide that transmits the excitation light from the light source to the tissues to cause the tissues to produce return light, such return light including fluorescent light produced by any compounds present in the tissues;

a second fiber-optic waveguide that transmits the return light from the tissues;

a sensor, associated with the waveguide, for monitoring the return light;

wherein the sensor generates a first signal indicative of the intensity of return light within a first wavelength band associated with the fluorescence of NADH, generates a second signal indicative of the intensity of return light within a second wavelength band associated with the fluorescence of collagen, and generates a third signal indicative of the intensity of return light within a third wavelength band associated with the fluorescence of elastin; and

a processor that processes the first, second, and third signals and produce an output signal that represents the blood perfusion of the tissues.

36. Apparatus for determining a pre-existing physiological property of an organ'"'"'s tissues which include metabolic and structural constituents, comprising:

a light source that emits excitation light;

a first fiber-optic waveguide that transmits the excitation light from the light source to the tissues of an organ to cause the tissues to produce return light, such return light including fluorescent light produced by any compounds present in the tissues;

a second fiber-optic waveguide that transmits the return light from the tissues;

a sensor, responsive to the return light transmitted by the second waveguide, wherein the sensor monitors the return light and generates a first signal indicative of the intensity of return light within a first wavelength band associated with the fluorescence of a metabolic constituent, and generates a second signal indicative of the intensity of return light within a second wavelength band associated with the fluorescence of a structural constituent; and

a processor that processes the first and second signals and produces an output signal that represents the physiological property.

37. Apparatus for determining a pre-existing physiological property of an organ having constituents including NADH and collagen, comprising:

a light source that emits excitation light which is directed at an organ to produce return light from the organ, such return light including fluorescent light produced by any constituents present in the organ;

a sensor having at least one output terminal for transmitting signals produced by the sensor in response to the return light, wherein the sensor monitors the return light and generates a first signal indicative of the intensity of return light within a first wavelength band associated with the fluorescence of NADH and generates a second signal indicative of the intensity of return light within a second wavelength band associated with the fluorescence of collagen; and

a processor having at least one input terminal and an output terminal, wherein the processor receives the first and second signals from the sensor using the at least one input terminal, processes the first and second signals, and produces an output signal at the output terminal, that represents the physiological property.