Methods and compositions for detecting and imaging a gas in an animal by nuclear magnetic resonance

Claim 3

A method according to claim 1 wherein said element is fluorine.

Claim 4

A method according to claim 2 wherein said fluorine is derived from a perfluorocarbon or derivative thereof.

Claim 5

A method according to claim 3 wherein said perfluorocarbon or derivative thereof is introduced into said animal.

Claim 6

A method according to claim 3 wherein said perfluorocarbon or derivative thereof is RES-phobic.

Claim 7

A method according to claim 3 wherein said perfluorocarbon or derivative thereof is in aqueous media.

Claim 8

A method according to claim 6 wherein said perfluorocarbon is selected from the group consisting of perfluoro(methylcyclohexane), perfluoro-1-methyldecalin [also known as perfluoro(decahydro-a-methylnaphthalene)], perfluoro(1,3-dimethylcyclohexane), perfluoro(decahydronaphthalene), and perfluoro(decahydrodimethylnaphthalene), or mixtures thereof, perfluorinated bicyclononane, perfluorinated bicyclooctane, perfluorinated adamantane hydrocarbon, perfluoromethyladamantane and perfluorodimethylbicyclo[3.3.1.]nonane, perfluorodimethyladamantane and perfluorotrimethylbicyclo[3.3.1.]nonane, perfluorotetrahydrodicyclopentadiene, perfluorinated bicyclononane, perfluorinated bicyclooctane, perfluorinated adamantane hydrocarbon, perfluoromethyladamantane and perfluorodimethylbicyclo[3.3.1]nonane, perfluorodimethyladamantane and perfluorotrimethylbicyclo[3.3.1.]nonane, and perfluorotetrahydrodicyclopentadiene and perfluorobicyclo[5.3.1]decane, and perfluorotributylamine (FC47), perfluorodecaline (PP5), perfluorotetrahydrofuran (FC80), perfluoroether (PID) [(CF 3 ) 2 CFOCF 2 (CF 2 ) 2 CF 2 OCF(CF 3 ) 2 ], perfluoroether (PIID) [(CF 3 ) 2 CFOCF 2 (CF 2 ) 6 CF 2 OCF(CF 3 ) 2 ], ##STR3## perfluoropolymer (E4) [CF 3 CHF(OCF 2 CF) 3 OCF 2 CF 2 CF 3 ], perfluoroetherpolyer (Fomblin Y/01), perfluorododecane, perfluorobicyclo[4.3.0]nonane, perfluorotrimethylcyclohexane, perfluoroisopropylcyclohexane, perfluoroendotetrahydrodicyclopentadiene, perfluorobicyclo]5.3.0.]decane, perfluorotetramethylcyclohexane, perfluoro-1-methyl-4-isopropylcyclohexane, perfluoro-n-butylcyclohexane, perfluorodimethylbicyclo[3.3.1]nonane, perfluoro-1-methyl adamantane, perfluoro-1-methyl-4-t-butycyclohexane, perfluorodecahydroacenaphthlene, perfluorotrimethylbicyclo[3.3.1.]nonane, perfluoro-n-undecane, perfluorotetradecahydrophenanthrene, perfluoro-1,3,5,7-tetramethyladamantane, perfluorododecahydrofluorene, perfluoro-1,3-dimethyl adamantane, perfluoro-o-octylcyclohexane, perfluoro-7-methyl bicyclo[4.3.0.]nonane, perfluoro-p-diisopropylcyclohexane, and perfluoro-m-diisopropylcyclohexane.

Claim 9

A method according to claim 3 wherein said perfluorocarbon or derivative thereof is a perfluorocyclocarbon.

Claim 10

A method according to claim 8 wherein said perfluorocyclocarbon is selected from the group consisting of perfluoro(methylcyclohexane), perfluoro(1,3-dimethylcyclohexane), perfluoro(decahydronaphthalene), perfluoro(decahydro-1-methylnaphthalene) and perfluoro(decahydrodimethylnaphthalene), or mixtures thereof, perfluorinated bicyclononane, perfluorinated bicyclooctane, perfluorinated adamantane hydrocarbon, perfluoromethyladamantane and perfluorodimethylbicyclo[3.3.1.]nonane, perfluorodimethyladamantane and perfluorotrimethylbicyclo[3.3.1.]nonane, perfluorotetrahydrodicyclopentadiene and perfluorobicyclo[5.3.0.]decane, perfluorotetrahydrodicyclopentadiene, perfluorinated bicyclononane, perfluorinated bicyclooctane, perfluorinated adamantane hydrocarbon, perfluoromethyladamantane and perfluorotrimethylbicyclo[3.3.1.]nonane, and perfluorotetrahydrodicyclopentadiene and perfluorobicyclo[5.3.0.]decane.

Claim 11

A method according to claim 1 wherein said element is selected from the group consisting of carbon-13, chlorine-35, chlorine-37, deuterium, magnesium-25, nitrogen-14, nitrogen-15, oxygen-17, phosphorous-31, platinum-195, potassium-39, proton, silicon-29, sodium-23, and xenon-129.

Claim 12

A method according to claim 1 wherein said detected gas is a mixture of gases.

Claim 13

A method according to claim 1 wherein said gas is a blood gas.

Claim 14

A method according to claim 1 wherein said gas is a tissue gas.

Claim 15

A method according to claim 1 wherein said gas is a paramagnetic gas.

Claim 16

A method according to claim 1 wherein said gas is a foreign gas introduced into said animal.

Claim 17

A method according to claim 15 wherein said foreign gas is an anesthetic gas.

Claim 18

A method according to claim 1 wherein said gas is detected continuously.

Claim 19

A method according to claim 1 wherein said detected signals are determined for at least one region in said animal.

Claim 20

A method according to claim 1 wherein said detected signals in at least one said region is further processed to reconstruct at least one projection of said gas in said animal.

Claim 21

A method according to claim 19 wherein said projection is reconstructed into a one, two, or three dimensional projection.

Claim 22

A method according to claim 19 wherein said projection is an image.

Claim 23

A method according to claim 21 wherein said image is reconstructed from chemical shifts, relaxation times or spin-spin couplings.

Claim 24

A method according to claim 1 wherein said method is used to determine a gaseous physiological state in said animal.

Claim 25

A method according to claim 1 wherein said method is used to monitor a gaseous physiological state in said animal.

Claim 26

A method of claim 1 wherein the NMR technique is NMR relaxation time.

Claim 27

A method according to claim 25 wherein said relaxation time is NMR T 1 or T 2 .

Claim 28

A method of claim 25 wherein the relaxation time corresponds to the identity of the gas.

Claim 29

A method of claim 25 wherein the relaxation time corresponds to the amount of the gas.

Claim 30

A method of claim 1 wherein the NMR technique is selected from the class consisting of NMR spin-spin coupling or NMR chemical shift.

Claim 31

A method of claim 29 wherein the spin-spin coupling or chemical shift corresponds to the identity of the gas.

Claim 32

A method of claim 29 wherein the spin-spin coupling or chemical shift corresponds to the amount of the gas.

Claim 33

A method of claim 1 further comprising the steps of detecting a second radio-frequency signal derived from an element independent of the animal and uninfluenced by the gas, the element being detected independent of the animal is similar to the element being detected of the animal, and comparing the detected signals as a further determination of the gas.

Claim 34

A method of claim 1 wherein the gas is oxygen.

Claim 35

A method of claim 1 wherein the gas is selected from the class consisting of carbon dioxide, hydrogen, helium, nitrogen, nitrous oxide, or any combination thereof.

Claim 36

An NMR method for detecting indirectly a dissolved gas in an area of interest in an animal comprising introducing into the animal a perfluorocarbon or derivative thereof for providing fluorine into the area of interest, the fluorine being influenced by the dissolved gas in the area of interest, subjecting the animal to an NMR spectrometer, detecting the influenced fluorine in the area of interest with an NMR technique to obtain an NMR parameter, and observing the NMR parameter as a function of the dissolved gas in the area of interest in the animal.

Claim 37

An NMR method for detecting indirectly a dissolved gas in an area of interest in an animal comprising introducing into the animal a perfluorocarbon or derivative thereof for providing fluorine into the area of interest, the fluorine being influenced by the dissolved gas in the area of interest, subjecting the animal to an NMR spectrometer, detecting the influenced fluorine in the area of interest with an NMR technique to obtain an NMR parameter, and observing the NMR parameter as a function of the dissolved gas in the area of interest in the animal.

Claim 38

A method of claim 35 wherein the area of interest is blood or tissue of an animal.

Claim 39

A method of claim 35 wherein the dissolved gas is selected from the class consisting of oxygen, carbon dioxide, hydrogen, helium, nitrogen, nitrous oxide or any combination thereof.

Claim 40

A method of claim 35 wherein the perfluorocarbon or derivative thereof is in an aqueous media.

Claim 41

A method of claim 35 wherein the perfluorocarbon or derivative thereof is a perfluorocyclocarbon.

Claim 42

A method of claim 35 wherein the NMR technique is selected from the class consisting of NMR relaxation time, NMR chemical shift or NMR spin-spin coupling.

Claim 43

A method of claim 40 wherein the NMR relaxation time is NMR T 1 or NMR T 2 .

Claim 44

A method of claim 35 wherein the NMR parameter is further processed to reconstruct a one, two, or three dimensional projection.

Claim 45

A method of claim 42 wherein the projection is an image.

Claim 46

A method of claim 35 wherein the dissolved gas is a paramagnetic gas.

Claim 47

An NMR method for detecting indirectly dissolved oxygen gas in blood of an animal comprising introducing into the animal a perfluorocarbon or derivative thereof for providing fluorine into the blood of the animal, the fluorine being influenced by the dissolved oxygen gas in the blood, subjecting the animal to an NMR spectrometer, detecting the influenced fluorine in the blood of the animal utilizing NMR relaxation time technique, and obtaining the NMR relaxation time as a result of said detection whereby the NMR relaxation time is a function of the dissolved oxygen gas in the blood of the animal.

Claim 48

An NMR method for detecting indirectly dissolved oxygen gas in blood of an animal comprising introducing into the animal a perfluorocarbon or derivative thereof for providing fluorine into the blood of the animal, the fluorine being influenced by the dissolved oxygen gas in the blood, subjecting the animal to an NMR spectrometer, detecting the influenced fluorine in the blood of the animal utilizing NMR relaxation time technique, and obtaining the NMR relaxation time as a result of said detection whereby the NMR relaxation time is a function of the dissolved oxygen gas in the blood of the animal.

Claim 49

A method of claim 45 wherein the perfluorocarbon or derivative thereof is in an aqueous media.

Claim 50

A method of claim 45 wherein the perfluorocarbon or derivative thereof is a perfluorocyclocarbon.

Claim 51

A method of claim 45 wherein the NMR relaxation time is NMR T 1 or NMR T 2 .

Claim 52

A method of claim 45 wherein the NMR relaxation time is further processed to reconstruct a one, two, or three dimensional projection.

Claim 53

A method of claim 49 wherein the projection is an image.

Claim 54

An NMR method of detecting indirectly an anesthetic gas in an animal comprising subjecting the animal having an element influenced by the anesthetic gas to an NMR spectrometer, and detecting a radio-frequency signal derived from the nuclear magnetic resonance of the influenced element utilizing an NMR technique as a determination of the anesthetic gas.

Claim 55

An NMR method of detecting indirectly an anesthetic gas in an animal comprising subjecting the animal having an element influenced by the anesthetic gas to an NMR spectrometer, and detecting a radio-frequency signal derived from the nuclear magnetic resonance of the influenced element utilizing an NMR technique as a determination of the anesthetic gas.

Claim 56

An NMR method of detecting indirectly and continuously a gas in an animal comprising subjecting the animal having an element influenced by the gas to an NMR spectrometer, and detecting continuously a radio-frequency signal derived from the nuclear magnetic resonance of the influenced element utilizing an NMR technique as a determination of the gas.

Claim 57

An NMR method of detecting indirectly and continuously a gas in an animal comprising subjecting the animal having an element influenced by the gas to an NMR spectrometer, and detecting continuously a radio-frequency signal derived from the nuclear magnetic resonance of the influenced element utilizing an NMR technique as a determination of the gas.