Apparatus for non-invasive imaging oxygen distribution in multi-dimensions

• US 6,274,086 B1
• Filed: 10/30/1998
• Issued: 08/14/2001
• Est. Priority Date: 12/16/1996
• Status: Expired due to Term

• Current Assignee: Oxygen Enterprises, Ltd.
• Original Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Inventors: Vinogradov, Sergei A., Wilson, David F.
• Primary Examiner(s): SNAY, JEFFREY R
• Application Number:
  US09/183,235
• Time in Patent Office: 1,019 Days
• Field of Search: 600/310, 600/311, 600/312, 422/82.07, 422/82.08, 436/68
• US Class Current: 422/82.08
• CPC Class Codes: A61B 2562/146 for optical coupling
• 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 5/14556 by fluorescence A61B5/14555 takes precedence
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/6833 Adhesive patches
• CPC Class Codes: A61B 5/6848 Needles
• CPC Class Codes: C07D 487/22 in which the condensed system contains four or more hetero rings
• CPC Class Codes: C07H 15/26 Acyclic or carbocyclic radicals, substituted by hetero rings
• CPC Class Codes: G01N 2021/6432 Quenching
• CPC Class Codes: G01N 21/64 Fluorescence; Phosphorescence
• CPC Class Codes: G01N 21/6408 with measurement of decay time, time resolved 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 21/6456 Spatial resolved fluorescence measurements; Imaging
• CPC Class Codes: G01N 21/6458 Fluorescence microscopy fluorescence microscopes per se G02B21/0076 and G02B21/16
• CPC Class Codes: G01N 31/225 for oxygen, e.g. including dissolved oxygen

Abstract

A detection device for three-dimensional tissue oxygen measurement in animals and humans comprising an array of fiber optics effective for transmitting emitted phosphorescent light, and further comprising an array of phosphorescent detectors and an excitation light emitter, forming a matrix and effective for sequential introduction of pulses of excitation light from a plurality of sites in said matrix.

Claims

1. A detection device for tissue oxygen measurement in animals and humans comprising:

an array of fiber optic means effective for transmitting excitation light;

an array of fiber optic means effective for collecting and transmitting emitted phosphorescent light;

an array of phosphorescent detection means;

wherein the arrays form a matrix means, by which pulses of excitation light are sequentially introduced from, and phosphorescence detected at, a plurality of sites within the matrix.

2. The device of claim 1, wherein tissue oxygen is measured two-dimensionally.

3. The method of claim 1, wherein tissue oxygen is measured three-dimensionally.

4. The detection device of claim 1, wherein said device is used in conjunction with an oxygen-quenchable phosphorescence emitting oxygen sensor.

5. The detection device of claim 2, wherein said oxygen sensor comprises an absorption band at a wavelength of greater than about 400 nm.

6. The detection device of claim 5, wherein said sensor comprises an emission band at a wavelength of greater than about 400 nm.

7. The detection device of claim 6, wherein said absorption and emission bands are located in the range from about 400 nm to about 1000 nm.

8. The detection device of claim 5, wherein said absorption band ranges from about 400 to about 700 nm.

9. The device of claim 4, wherein said sensor comprises porphyrin.

10. The detection device of claim 9, wherein said porphyrin comprises metalloporphyrin.

11. The detection device of claim 10, comprising an oxygen sensor compound which is capable of phosphorescing and which has the formula:

wherein;

R₁ is substituted or unsubstituted aryl;

R₂ and R₃ are independently hydrogen or are linked together to form substituted or unsubstituted aryl; and

M is H₂ or a metal.

12. The detection device of claim 11, wherein the oxygen sensor compound M is a metal selected from the group consisting of Zn, Al, Sn, Y, La, Lu, Pd, Pt and derivatives thereof.

13. The detection device of claim 12, wherein the derivatives of the oxygen sensor compound comprise LuOH, YOH, LaOH or AlOH.

14. The detection device of claim 11, wherein R₂ and R₃ of the oxygen sensor compound are linked together to form an aryl system.

15. The detection device of claim 14, wherein the oxygen sensor compound of the aryl system comprises phenyl, naphthyl or anthryl.

16. The detection device of claim 15, wherein R₁ of the oxygen sensor compound comprises substituted phenyl.

17. The detection device of claim 16, wherein the oxygen sensor compound is Pd-meso-tetra-(4-carboxy-phenyl) porphine.

18. The detection device of claim 4, wherein oxygen measurement in human or animal tissue comprises a porphyrin chromophore capable of releasing absorbed energy as phosphorescent light and a dendrimer, and wherein the porphyrin chromophore comprises the core of the dendrimer.

19. The detection device of claim 18, wherein the absorption spectrum of the chromophore phosphorescent probe exhibits strong light absorption in the near infrared region of the spectrum, at which point on the spectrum, natural tissue chromophores exhibit relatively weak absorption.

20. The detection device of claim 18, wherein the absorption spectrum of the chromophore of the phosphorescent probe exhibits strong light absorption between 600 nm to about 720 nm.

21. The detection device of claim 18, wherein the absorption spectrum of the chromophore of the phosphorescent probe exhibits strong light absorption between 610 nm to about 720 nm.

22. The detection device of claim 18, wherein the porphyrin chromophore of the phosphorescent probe comprises a functionally derivatized metalloporphyrin.

23. The detection device of claim 22, wherein the formula for the functionally derivatized metalloporphyrin of the porphyrin chromophore of the phosphorescent probe is

wherein R₁ is a hydrogen atom or a substituted or unsubstituted aryl;

R₂ and R₃ are independently hydrogen or are linked together to form substituted or unsubstituted aryl; and

M is H₂ or a metal.

24. The detection device of claim 23, wherein M of the metalloporphyrine compound is a metal selected from the group consisting of Zn, Al, Sn, Y, La, Lu, Pd, Pt and derivatives thereof.

25. The detection device of claim 22, wherein the porphyrin chromophore compound is selected from the group consisting of tetrabenzoporphyrin, tetranapthoporphyrin, tetraanthraporphyrin and derivatives thereof.

26. The detection device of claim 25, wherein a derivative of the porphyrin chromophore compound is a meso-tetraphenylated compound.

27. The detection device of claim 25, wherein the porphyrin chromophore compound is tetrabenzoporphyrin.

28. The detection device of claim 25, wherein the metal of the porphyrin chromophore compound is selected from the group consisting of Zn, Al, Sn, Y, La, Lu, Pd, Pt and derivatives thereof.

29. The detection device of claim 28, wherein the metalloporphyrin chromophore is tetraphenyltetrabenzoporphyrin.

30. The detection device of claim 28, wherein the metallopophyrin chromophore is (Lu) tetraphenyltetranapthoporphyrin.

31. The detection device of claim 28, wherein the metalloporphyrin chromophore compound is meso-tetra-(4-carboxylphenyl) porphyrin.

32. The detection device of claim 28, wherein the metallopophyrin chromophore compound is mesotetra-phenyltetrabenzoporphyrin.

33. The detection device of claim 28, wherein the metalloporphyrin chromophore compound is a first, second, third, fourth or fifth generation dendrimer cages.

34. The detection device of claim 23, wherein the dendrimer of the metalloporphyrin chromophore compound comprises polyglutamate dendritic.