NMR compositions for indirectly detecting a dissolved gas in an animal

• US 4,775,522 A
• Filed: 12/16/1985
• Issued: 10/04/1988
• Est. Priority Date: 03/04/1983
• Status: Expired due to Fees

• Current Assignee: Children'S Hospital Research Foundation
• Original Assignee: Children'S Hospital Research Foundation
• Inventors: Clark, Leland C. Jr.
• Primary Examiner(s): Jaworski, Francis J.
• Application Number:
  US06/808,999
• Time in Patent Office: 1,023 Days
• Field of Search: 128/653, 324/309, 424/9
• US Class Current: 424/9.37
• CPC Class Codes: A61B 5/145 Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissuemeasuring of blood pressure or blood flow A61B5/02; non-radiation detecting or locating of foreign bodies in blood A61B5/06
• CPC Class Codes: A61K 49/06 Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
• CPC Class Codes: A61K 49/1806 Suspensions, emulsions, colloids, dispersions
• CPC Class Codes: G01R 33/465 applied to biological material, e.g. in vitro testing
• CPC Class Codes: G01R 33/485 based on chemical shift information [CSI] or spectroscopic imaging, e.g. to acquire the spatial distributions of metabolites
• CPC Class Codes: G01R 33/5601 involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

A novel and improved method to detect and/or measure indirectly at least one gas, particularly dissolved gases, of an animal employing nuclear magnetic resonance techniques (NMR). The method examines an NMR spectrum to determine chemical shift relaxation times or spin-spin couplings for an element of an animal influenced by at least one gas of the animal. Uniquely, the gas detected according to the principles of this invention may be insensitive to present NMR techniques. Further, the present invention discloses a novel method to determine and monitor gaseous physiological states of an animal. Because of the unique and advantageous non-invasive, non-destructive and non-ionizing properties, the present invention may be employed in an animal continuously and in vivo. Still further, the present invention provides for the imaging of at least one-, two-, or three-dimensional projections reconstructed from a chemical shift, relaxation times, or spin-spin couplings for an element of an animal influenced by at least one gas in the animal. Novel compounds directed to providing radio-frequency reference signals in which chemical shifts may be determined therefrom are also disclosed.

Claims

1. An NMR composition suitable for introduction into an animal for detecting indirectly a dissolved gas in the animal with an NMR technique, said NMR composition comprising

a compound containing a sufficient amount of an element adapted for NMR detection with an NMR technique, the element being influenced by the dissolved gas when said NMR composition is introduced into the animal, and

an aqueous liquid mixed with said compound which forms said NMR composition whereby, when said NMR composition is introduced into the animal and the animal is subjected to an NMR spectrometer, a radio-frequency signal derived from the nuclear magnetic resonance of the influenced element can be detected with an NMR technique to generate an NMR parameter which is a function of the dissolved gas.

2. An NMR composition of claim 1 wherein said compound is a perfluorocarbon or derivative thereof and the element is flourine.

3. An NMR composition of claim 2 wherein said NMR composition is an emulsion.

4. An NMR composition of claim 3 wherein said perfluorocarbon or derivative thereof is a perfluorocyclocarbon.

5. An NMR composition of claim 3 wherein said aqueous liquid includes a surfactant.

6. An NMR composition of claim 5 wherein said surfactant is XMO-10.

7. An NMR composition of claim 1 wherein said compound is selected from a group of perfluorocarbon compounds comprising perfluorodecalin, perfluoromethyldecalin, perfluoroetherpolymer (Fomblin Y/01), perfluorotrimethylbicyclononane, perfluorotributylamine (FC-47), perfluorotripropylamine, perfluoro-1-3-dimethyladamantane and perfluorotrimethylbicyclo[3.3.1]nonane (DAWN), perfluoroether (PID) [(CF₃)₂ CFOCF₂ (CF₂)₂ CF₂ OCF(CF₃)₂ ], perfluoroether (PIID) [(CF₃)₂ CFOCF₂ (CF₂)₆ CF₂ OCF(CF₃)₂ ], ##STR3## perfluorohexane and perfluorooctylbromide.

8. An NMR composition of claim 3 wherein the emulsion is a perfluorocarbon emulsion comprising a perfluorocarbon in an amount on the order of 10% V/V and a surfactant in an amount of about 3-10% V/V.

9. An NMR composition of claim 3 wherein said surfactant is a pluronic surfactant.

10. An NMR composition of claim 1 wherein said compound is a perfluorocyclocarbon.

11. An NMR composition of claim 1 wherein the element is flourine.