Method and apparatus for monitoring metabolism in body organs in vivo

• US 4,223,680 A
• Filed: 03/05/1979
• Issued: 09/23/1980
• Est. Priority Date: 06/28/1977
• Status: Expired due to Term

• Current Assignee: Duke University
• Original Assignee: Duke University
• Inventors: Jobsis, Frans F.
• Primary Examiner(s): Kamm, William E.
• Application Number:
  US06/017,727
• Time in Patent Office: 568 Days
• Field of Search: 128/633, 128/634, 128/664, 128/665, 356/39, 356/43-45, 356/432
• US Class Current: 600/324
• 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 5/0073 by tomography, i.e. reconstruction of 3D images from 2D projections A61B5/0066 takes precedence
• 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 5/14553 specially adapted for cerebral tissue
• CPC Class Codes: A61B 5/6833 Adhesive patches
• CPC Class Codes: A61K 49/0004 Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions

Abstract

A spectrophotometric method, apparatus and reflectance technique is directed to non-invasive, harmless, continuous, atraumatic, in vivo, in situ monitoring of metabolism in a body organ utilizing measuring and reference wavelengths within the near infrared region, i.e., 700-1300 nm. Monitoring of oxidative metabolism is accomplished by monitoring oxygen sufficiency in an organ, normally an internal vital organ, e.g., the brain or heart, of a living human or animal body. Advantage is taken of the critical characteristic of cellular enzyme cytochrome a, a₃ within the optical path and within the radiated portion of the selected organ from which the light so reflected for absorbing the selected measuring wavelength and for light of this measuring wavelength, as well as at least one reference wavelength within the same defined infrared region and at a low, non-hazardous level of intensity to travel to the organ, be reflected and be detectable at a point spaced from the point of entry and at the end of a relatively long path, e.g., of several centimeters length, which may include substantial content of bone as well as soft tissue. The method corrects for skin blood flow effects, variations in laser diode output and variations in metabolic and circulatory parameters during measuring.

Claims

1. A spectrophotometric reflectance method for measuring local metabolism of a body organ such as the brain, in situ, in vivo, non-invasively, atraumatically, harmlessly, rapidly and continuously, said method comprising the steps:

(a) locating and fixing the body in a position appropriate to the measuring operation;

(b) selecting an optical transmission-reflectance path including said organ and extending for several centimeters between points of light entry and exit said points of light entry and exit being laterally spaced several centimeters apart and positioned on contiguous skin surface areas of the body;

(c) establishing a plurality of near-infrared light sources located external of the body and having light emissions of different wavelengths in the 700 to 1300 nanometer spectral range and of an intensity below the level damaging to the body and said organ but sufficient to be detectable by a light sensor after transmission through any skin, bone and tissue included in said path and scattering in and reflectance from said organ along said path, said emissions including at least one measuring wavelength and at least one reference wavelength within said spectral range, each said measuring wavelength being selected such that said organ exhibits a selective absorption therefor, the extent of which is dependent upon a specific state of metabolic activity of said organ;

(d) directing said light emissions at said measuring and reference wavelengths sequentially at said point of entry to be transmitted, reflected and scattered along said path and to said organ and receiving the light emissions reflected directly back from said skin, bone and tissue at or within a few millimeters of said point of entry as well as the light emissions reflected and scattered from said organ at a point several centimeters away from said point of entry and light sensor and circuit means adapted to produce and electrical output signal corrected for changes in blood volume of said skin, bone and tissue during the measuring cycle and representing the difference in absorption of said measuring and reference wavelengths by the organ as a function of the state of said metabolic activity; and

(e) converting said electrical output signal to a signal providing a substantially continuous and rapid measure of said activity.

2. The method of claim 1 wherein said organ is the brain.

3. The method of claim 1 including the step of receiving said light emissions reflected back from said skin, bone and tissue at said point of entry in light receptor means structurally combined with light transmission means connected to said light sources and removably secured to the body at said point of entry.

4. The method of claim 1 including the step of utilizing said light emissions reflected back from said skin, bone and tissue to correct for variations in output of said light sources during said measuring operation.

5. The method of claim 1 wherein said organ comprises the brain, said points of light entry and exit comprise spaced points on the head of the body having the brain organ being measured and including the step of sensing and electrically processing said light emissions reflected back at said point of entry in a manner enabling reflected and scattered light received at said exit point mainly from the skin and bone of the head to be discriminated from reflected and scattered light received at said more distant exit point from the gray and white matter of the brain whereby in said processing said signal is developed as indicative of oxygen sufficiency in said gray matter.

6. The method of claim 1 including at least two reference wavelengths comprising a contrabestic pair and processing the sum of the absorption changes at the two contrabestic wavelengths to produce a signal indicative of blood volume changes and using the difference of the absorption changes in said wavelengths to produce a signal indicative of changes in oxygenation of the blood in said organ.

7. The method of claim 1 wherein each respective said measuring wavelength is selected within an absorption band of a metabolite, enzyme or other cellular biochemical entity controlling said state of activity and wherein each said reference wavelength to which a respective measuring wavelength is referred is selected so as to be more distant from the peak of the respective said band within which such respective wavelength resides.

8. The method of claim 1 wherein said activity is one of cellular metabolism.

9. The method of claim 8 wherein said activity is that of the redox state of enzyme cytochrome a, a₃.

10. The method of claim 8 wherein said activity is that of hemoglobin oxygenation in said organ.

11. The method of claim 1 wherein said activity relates to local changes in blood volume in said organ.

12. The method of claim 1 including the step of periodically interrupting normal measuring of said metabolism by admitting an agent to said body in a manner enabling such agent to reach said organ and designed to effect a fluctuating change of the absorption properties within said organ over a period of time effecting a corresponding change in said electrical output signal during such time, and recording the intensity of said fluctuating change and the time interval between the beginning and end of said change in the output signal brought about by said agent within said organ as a measure of the blood flow rate to said organ.

13. The method of claim 12 wherein said agent comprises a dye agent.

14. The method of claim 12 wherein said agent comprises a gaseous agent.

15. The method of claim 1 wherein said activity is that of the redox state of enzyme cytochrome a, a₃ in said organ.

16. The method of claim 1 wherein said activity is that of hemoglobin oxygenation in said organ.

17. The method of claim 1 including at least two said reference wavelengths comprising a contrabestic pair or series.

18. A spectrophotometric reflectance apparatus for measuring in situ, in vivo, non-invasively, atraumatically, harmlessly, rapidly and continuously a local metabolic, oxygen dependent activity of a body organ such as the brain of a body where such activity bears a measurable relation to an oxygen dependent absorption characteristic of the organ for a particular wavelength of light transmitted therethrough, comprising:

(a) light source means including;

(i) a plurality of near-infrared light sources located external of the body and having light emissions of different wavelengths in the 700 to 1300 nanometer spectral range and of an intensity below the level damaging to the body and said organ but sufficient to be detectable by a light sensor after transmission through any skin, bone and tissue included in an optical transmission-reflectance path including said organ and extending for several centimeters between points of light entry and exit laterally spaced several centimeters apart and located on contiguous skin surface areas of the body and after scattering in and reflectance from said organ along said path, said emissions including at least one measuring wavelength and at least one reference wavelength within said spectral range, each said measuring wavelength being selected such that said organ exhibits a selective absorption therefor, the extent of which is dependent upon a specific state of a local metabolic, oxygen dependent activity of said organ;

(ii) means operatively associated with said light sources to produce emissions representing at least one said measuring wavelength and at least one said reference wavelength within said spectral range for transmission along said path to said organ and at levels of intensity below that which would be damaging to the body and said organ; and

(iii) light transmission means for receiving, transmitting and directing the output light emissions of said light sources at said measuring and reference wavelengths to a selected fixed light entry point on said body to be transmitted, reflected and scattered along said path and to said organ;

(b) first detector means fixed to said body proximate said entry point for receiving and transmitting the light emissions reflected directly back from said skin, bone and tissue at or within a few millimeters of said point of entry;

(c) second detector means fixed to said body at a fixed light exit point on said body and spaced several centimeters away from said fixed light entry point for receiving and transmitting the light emissions reflected and scattered from said organ;

(d) light sensor and circuit means connected to receive the light emission outputs of said first and second detector means and adapted to produce an electrical output signal corrected for changes in blood volume of said skin, bone and tissue during the measuring cycle and representing the difference in absorption of said measuring and reference wavelengths by the organ as a function of the state of said local metabolic oxygen dependent activity; and

(e) means for converting said electrical output signal to a signal providing a substantially continuous and rapid measure of said activity.

19. The apparatus of claim 18 wherein said means operatively associated with said light sources comprises means for sequentially operating said light sources.

20. The apparatus of claim 18 wherein said light transmission and first detector means are structurally combined and removably secured to the body at said point of entry.

21. The apparatus of claim 18 wherein said light sensor and circuit means include means for utilizing said light emissions reflected back from said skin, bone and tissue at said point of entry to correct for variations in output of said light sources during said measuring operation.

22. The apparatus of claim 18 wherein said organ comprises the brain in the head of said body, said points of light entry and exit comprise spaced points on the head and wherein said light sensor and circuit means include means adapted for sensing and electrically processing said light emissions reflected back at said point of entry in a manner enabling reflected and scattered light received at said exit point mainly from the skin, bone and tissue of the head to be discriminated from reflected and scattered light received at said more distant exit point from the gray and white matter of the brain whereby in said processing said signal is developed as indicative of oxygen sufficiency in said gray matter.

23. The apparatus of claim 18 wherein said light sources and said means for sequentially operating said light sources produce at least two reference wavelengths comprising a contrabestic pair and said light sensor and circuit means are adapted for processing the sum of the absorption changes at the two contrabestic wavelengths to produce a signal indicative of blood volume changes and being further adapted for using the difference of the absorption changes in said wavelengths to produce a signal indicative of changes in oxygenation of the blood in said organ.

24. The apparatus of claim 18 wherein said activity is one of cellular metabolism and said wavelengths operate in reference thereto.

25. The apparatus of claim 18 wherein said activity is one of cellular oxidative metabolism and said wavelengths operate in reference thereto.

26. The apparatus of claim 18 wherein said activity is that of the redox state of enzyme cytochrome a, a₃ and said wavelengths operate in reference thereto.

27. The apparatus of claim 18 wherein said activity is that of hemoglobin oxygenation in said organ and said wavelengths operate in reference thereto.

28. The apparatus of claim 18 wherein said activity is that of local changes in blood volume in said organ, including means for establishing a feedback voltage to maintain at some predetermined level the said reference signal corresponding to a selected said reference wavelength and monitoring said voltage as a measure of said volume.

29. The apparatus of claim 18 wherein said measured activity is that of the redox state of enzyme cytochrome a, a₃ in said organ.

30. The apparatus of claim 18 wherein said light sources and means for operating said light sources are adapted to produce a pair of said reference wavelengths comprising a contrabestic pair.