Methods of photoacoustic imaging

• US 6,662,040 B1
• Filed: 12/10/1999
• Issued: 12/09/2003
• Est. Priority Date: 06/16/1997
• Status: Expired due to Fees

• Current Assignee: GE Healthcare As (GE Healthcare Technologies, Inc.)
• Original Assignee: Amersham Health (General Electric Company)
• Inventors: Coffey, Steven Blair, Henrichs, Paul Mark, Gunther, Wolfgang Hans Heinrich, McIntire, Gregory Lynn, Hollister, Kenneth Robert, Eriksen, Marten, Rongved, Pal, Snow, Robert Allen
• Primary Examiner(s): Lateef, Marvin M.
• Assistant Examiner(s): Lin, Jeoyuh
• Application Number:
  US09/458,008
• Time in Patent Office: 1,460 Days
• Field of Search: 600/310, 600/312, 600/321, 600/329, 600/407, 600/410, 600/436, 600/437, 600/458, 600/473, 600/476, 600/431, 424/82.05, 424/9.52, 424/9.6, 424/9.2, 424/9.3
• US Class Current: 600/431
• CPC Class Codes: A61B 6/508 for non-human patients
• CPC Class Codes: A61K 41/00 Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
• CPC Class Codes: A61K 49/00 Preparations for testing in vivo
• CPC Class Codes: A61K 49/0002 General or multifunctional contrast agents, e.g. chelated agents
• CPC Class Codes: A61K 49/0034 Indocyanine green, i.e. ICG, cardiogreen
• CPC Class Codes: A61K 49/0078 microemulsion, nanoemulsion
• CPC Class Codes: A61K 49/0084 liposome, i.e. bilayered vesicular structure
• CPC Class Codes: A61K 49/0091 Microparticle, microcapsule, microbubble, microsphere, microbead, i.e. having a size or diameter higher or equal to 1 micrometer
• CPC Class Codes: A61K 49/0404 containing barium sulfate
• CPC Class Codes: A61K 49/0438 Organic X-ray contrast-enhancing agent comprising an iodinated group or an iodine atom, e.g. iopamidol
• CPC Class Codes: A61K 49/0466 Liposomes, lipoprotein vesicles, e.g. HDL or LDL lipoproteins, phospholipidic or polymeric micelles
• CPC Class Codes: Y10S 977/949 Radiation emitter using nanostructure

Abstract

The invention relates to a method of generating an image of an animate human or non-human animal body or part thereof. The method comprises administering to said body a physiologically tolerable contrast agent comprising a radiation absorbing component and/or a pressure inducing component, exposing said body to radiation, detecting pressure waves generated in said body by said radiation and generating an optoacoustic image therefrom of at least a part of said body containing the administered contrast agent.

Claims

1. A method of generating an image of an animate human or non-human animal body or part thereof, said method comprising administering to said body a physiologically tolerable contrast agent comprising a pressure inducing component, exposing said body to radiation, detecting pressure waves generated in said body by said radiation and generating an optoacoustic image therefrom of at least a part of said body containing the administered contrast agent.

26. A method as claimed in claim 1 wherein radiation with a wavelength of 300-1300 nm is used.

27. A method as claimed in claim 26 wherein radiation with a wavelength of 600-1300 nm is used.

28. A method as claimed in claim 26 wherein radiation with a wavelength of 625-1200 nm is used.

29. A method as claimed in claim 26 wherein radiation with a wavelength of 650-1000 nm is used.

30. A method as claimed in claim 1 wherein X-ray or gamma ray radiation with a wavelength of less than 0.1 μ

m is used.

31. A method as claimed in claim 30 wherein the contrast agent is in the form of a suspension of solid or liquid particles in a physiologically acceptable liquid.

32. A method as claimed in claim 31 wherein the particles have diameters of 100 to 500 nm.

33. A method as claimed in claim 30 wherein the contrast agent is in the form of a solid or liquid material encapsulated into micelles or liposomes.

34. A method as claimed in claim 1 wherein microwave radiation with a frequency of from 0.3 GHz to 30 GHz is used.

35. A method as claimed in claim 34 wherein the contrast agent is in the form of a suspension of superparamagnetic particles in a physiologically acceptable liquid.

36. A method as claimed in claim 35 wherein the particles have diameters of 5 to 30 nm.

37. A method as claimed in claim 1 wherein short pulses of radiation are used.

38. A method as claimed in claim 1 wherein said contrast agent comprises an active targeting ligand.

39. A method as claimed in claim 38 wherein the active targeting ligand is capable of binding to a dihydrofolate reductase receptor.

40. A method as claimed in claim 1 wherein said pressure-inducing component is a gas precursor.

41. A method as claimed in claim 40 wherein said gas precursor is selected from graphite, aminomalonates, carbonates, bicarbonates, physiologically acceptable diazonium compounds, carbonate esters containing groupings of the type —

CO—

O—

CR¹R²—

O—

CO—

OR³, and β

-ketoacids.

42. A Method as claimed in claim 1 wherein said pressure-inducing component is an oil-in-water emulsion droplet.

43. A method as claimed in claim 42 wherein said emulsion droplet comprises a light-absorbing, lipophilic dye.

44. A method as claimed in claim 43 wherein said light-absorbing particles comprise particles of graphite and/or surface-modified pigment particles.

45. A method as claimed in claim 42 wherein said emulsion droplet contains hydrophobic light-absorbing particles.

46. A method as claimed in claim 1 wherein said contrast agent comprises at least one chromophoric group attached to a surfactant molecule.

47. A method as claimed in claim 1 wherein said pressure-inducing component is a gas.

48. A method as claimed in claim 47 wherein said gas is xenon or a perfluorocarbon.

2. A method of generating an image of an animate human or non-human animal body or part thereof, said method comprising administering to said body a physiologically tolerable contrast agent comprising a pressure inducing component and a radiation absorbing component, exposing said body to radiation, detecting pressure waves generated in said body by said radiation and generating an optoacoustic image therefrom of at least a part of said body containing the administered contrast agent.

3. A method as claimed in claim 2 wherein X-ray or gamma ray radiation with a wavelength of less than 0.1 μ

m is used.

4. A method as claimed in claim 3 wherein said radiation absorbing component comprises an element with atomic number greater than 20.

5. A method as claimed in claim 4 wherein said radiation absorbing component comprises an element selected from barium, tungsten, iodine, bromine, bismuth and lanthanide elements.

6. A method as claimed in claim 4 wherein said radiation absorbing component includes a highly iodinated aromatic compound.

7. A method as claimed in claim 3 wherein said radiation absorbing component includes an iodinated compound containing at least one atom of iodine per molecule.

8. A method as claimed in claim 7 wherein said radiation absorbing component includes an iodinated compound containing at least three atoms of iodine per molecule.

9. A method as claimed in claim 7 wherein said radiation absorbing component includes an iodinated compound containing at least six atoms of iodine per molecule.

10. A method as claimed in claim 3 wherein the radiation absorbing component is in the form of a suspension of solid particles in a physiologically acceptable liquid.

11. A method as claimed in claim 10 wherein the particles have diameters of 100 to 500 nm.

12. A method as claimed in claim 3 wherein the radiation absorbing component is in the form of a solid, liquid or gaseous material encapsulated into micelles or liposomes.

13. A method as claimed in claim 12 wherein the gaseous material is xenon.

14. A method as claimed in claim 3 wherein the contrast agent is in the form of a suspension of particles of a ceramic material selected from Co₂O₃, MnO₂, NiO and CuO, in a physiologically acceptable liquid.

15. A method as claimed in claim 2 wherein said radiation absorbing component includes a dye compound.

16. A method as claimed in claim 15 wherein said dye compound is selected from the group comprising cyanine dyes, squarylium dyes, croconium, phthalocyanine dyes, naphthalocyanine dyes, xanthene dyes, dibenzxanthene dyes, merocyanine dyes, triphenylmethane dyes or porphyrins.

17. A method as claimed in claim 15 wherein said dye compound has the formula I:

wherein

each Z₁ is independently selected from the group consisting of;

hydrogen,

a methyl group optionally substituted with a substituent selected from the group consisting of hydroxyl, carboxyl, sulfonate, phosphonate, and poly(alkylene oxidyl) such as ω

-hydroxypoly(ethylene oxidyl) and ω

-methoxypoly(ethylene oxidyl) the molecular weights of which can be up to about 50,000,

an ethyl group optionally substituted with one or two substituents selected from the group consisting of hydroxyl, carboxyl, sulfonate, phosphonate, and poly(alkylene oxidyl) such as ω

-hydroxypoly(ethylene oxidyl) and ω

-methoxypoly(ethylene oxidyl) the molecular weights of which can be up to about 50,000,

an ethylene group optionally substituted with one or two substituents selected from the group consisting of hydroxyl, carboxyl, sulfonate, phosphonate, and poly(alkylene oxidyl) such as ω

-hydroxypoly(ethylene oxidyl) and ω

-methoxypoly-(ethylene oxidyl) the molecular weights of which can be up to about 50,000,

a C_3-16 alkyl group, the alkyl portion of which is optionally substituted as defined above,

a C_1-16 alkoxyl ether group, the alkyl portion of which is optionally substituted as defined above,

a C_1-16 carboxyalkyl estergroup, the alkyl portion of which is optionally substituted as defined above,

a C_1-16 oxycarbonylalkyl ester group, the alkyl portion of which is optionally substituted as defined above,

a C_1-16 carbonylaminoalkyl amide group, the alkyl portion of which is optionally substituted as defined above,

a C_1-16 aminocarbonylalkyl amide group, the alkyl portion of which is optionally substituted as defined above,

a carboxylic acid group which may be a carboxylate group,

a sulfonate group,

a hydroxyl group,

a phosphate group,

a C_1-16 sulfonamidoalkyl group, the alkyl portion of which is optionally substituted as defined above,

a C_1-16 aminosulfonylalkyl group, the alkyl portion of which is optionally substituted as defined above,

a C_1-16 aminocarbonylaminoalkyl urea group, the alkyl portion of which is optionally substituted as defined above,

a C_1-16 aminothiocarbonylaminoalkyl thiourea group, the alkyl portion of which is optionally substituted as defined above,

a phenyl-C_1-16-alkyl group, the alkyl portion of which is optionally substituted as defined above,

a phenoxy-C_1-16-alkyl group, the alkyl portion of which is optionally substituted as defined above,

a C_1-16 phenyloxyalkyl group, the alkyl portion of which is as defined above,

an oxyphenoxy-C_1-16-alkyl group, the alkyl portion of which is optionally substituted as defined above,

a poly(alkylene oxidyl) group such as hydroxypoly(ethylene oxidyl) and methoxypoly(ethylene oxidyl) with a molecular weight up to about 50,000,

and an annulated aromatic ring which comprises a benz[e]aromatic ring, a benz[f]aromatic ring, or a benz[g]aromatic ring, where e, f, and g are defined relative to the indole structure as a template and each of which ring may be substituted by C_1-16 alkyl, C_1-16 alkoxyl, carboxyl, sulfonate, sulfonamido, phenyl, poly(alkylene oxidyl) or phenoxyl groups as defined above;

each R₁′

is independently selected from the group consisting of methyl and a C_2-16 alkyl group including a substituted alkyl group where alkyl is optionally substituted as defined above,

each X is independently selected from the group consisting of O, N—

R₁′

, S, Se, Te, CH═

CH, and (CH₃)₂C; and

Q₁ is selected from the group consisting of;

(CH═

CH)_n where n has a value of 1 to 6,

where Z₂ is selected from the group consisting of H, chloro, O-alkyl, S-alkyl, where alkyl is optionally substituted as defined above, O-poly(alkylene oxidyl), S-poly(alkylene oxidyl), where poly(alkylene oxidyl) is as defined above and also includes poly(alkylene oxide) groups to which another dye is attached at the w-end, O-phenyl, S-phenyl, wherein the phenyl groups may be substituted with alkyl groups optionally substituted as defined above, O-alkyl groups as defined above, S-alkyl groups as defined above, aminothiocarbonylaminoalkyl groups, and aminothiocarbonylamino-phenyl groups, and

where Z₃ is selected from the group consisting of H, carboxylate, and carboxyalkyl where alkyl is as defined above, carbonylaminoalkyl where alkyl is as defined above, and carbonylaminophenyl where phenyl is as defined above, and

and Z⁻

is a physiologically tolerable counterion.

18. A method as claimed in claim 17 wherein the physiological counterion is I, Br, Cl or OAc.

19. A method as claimed in claim 15 wherein said dye compound has the formula II:

wherein

n is an integer having a value of 1 to 6;

each R₁, which may be the same or different, represents a hydrogen atom or a solubilizing group, or adjacent R₁ substituents together with the ring carbons to which they are attached may form a ring structure, which may be a 5 or 6-membered ring;

each R₂, which may be the same or different, represents a hydrogen atom or a lipophilic group, alternatively, each R₂ may be an optionally unsaturated C_2-8 alkyl group which is attached to one or more solubilizing groups;

each X, which may be the same or different, each represents O, S, —

CH═

CH—

or C(R₃)₂ in which each R₃, which may be the same or different, represents a hydrogen atom or a methyl or ethyl group;

Z is a physiologically tolerable counterion.

20. A method as claimed in claim 19 wherein the physiological counterion is I, Br, or Cl.

21. A kit of parts for a method as claimed in claim 2 comprising both a radiation absorbing component according to claim 15 and a pressure-inducing component selected from a gas, a gas precursor or an oil-in-water emulsion droplet, said components being suitable for separate, administration (simultaneously or sequentially) to an animate human or non-human animal.

22. A kit of parts for a method as claimed in claim 2 comprising both a radiation absorbing component according to claiml 4 and a pressure-inducing component selected from a gas, a gas precursor or an oil-in-water emulsion droplet, said components being suitable for separate, administration (simultaneously or sequentially) to an animate human or non-human animal.

23. A kit of parts for a method as claimed in claim 2 comprising both a radiation absorbing component according to claim 7 and a pressure-inducing component selected from a gas, a gas precursor or an oil-in-water emulsion droplet, said components being suitable for separate, administration (simultaneously or sequentially) to an animate human or non-human animal.

24. A kit of parts for a method as claimed in claim 2 comprising both a radiation absorbing component according to claim 10 and a pressure-inducing component selected from a gas, a gas precursor or an oil-in-water emulsion droplet, said components being suitable for separate, administration (simultaneously or sequentially) to an animate human or non-human animal.

25. A kit of parts for a method as claimed in claim 2 comprising both a radiation absorbing component according to claim 12 and a pressure-inducing component selected from a gas, a gas precursor or an oil-in-water emulsion droplet, said components being suitable for separate, administration (simultaneously or sequentially) to an animate human or non-human animal.