Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
  • G01R33/00—Arrangements or instruments for measuring magnetic variables
  • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
  • G01R33/28—Details of apparatus provided for in groups G01R33/44 - G01R33/64
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K49/00—Preparations for testing in vivo
  • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
  • A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
  • A61K49/1806—Suspensions, emulsions, colloids, dispersions
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K49/00—Preparations for testing in vivo
  • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
  • A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
  • A61K49/1806—Suspensions, emulsions, colloids, dispersions
  • A61K49/1815—Suspensions, emulsions, colloids, dispersions compo-inhalant, e.g. breath tests
• • C—CHEMISTRY; METALLURGY
  • C01—INORGANIC CHEMISTRY
  • C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
  • C01B23/00—Noble gases; Compounds thereof
  • C01B23/001—Purification or separation processes of noble gases
  • C01B23/0036—Physical processing only
  • C01B23/0089—Physical processing only by absorption in liquids
• • C—CHEMISTRY; METALLURGY
  • C01—INORGANIC CHEMISTRY
  • C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
  • C01B2210/00—Purification or separation of specific gases
  • C01B2210/0029—Obtaining noble gases
  • C01B2210/0037—Xenon

Definitions

• the invention relates to a method for enriching hyperpolarized atomic nuclei and an apparatus for carrying out the method.
• Electrons understood. For example, 100 percent polarization means that all nuclei or electrons are oriented in the same way. A magnetic moment is associated with the polarization of nuclei or electrons.
• hyperpolarized 129 Xe is inhaled or injected into a human. 10 to 15 seconds later, the polarized xenon accumulates in the brain. Magnetic resonance tomography is used to determine the distribution of the noble gas in the brain. The result is used for further analyzes.
• the choice of a polarized noble gas depends on the application. 129 Xe shows a large chemical shift. Xenon z. B. adsorbed on a surface, its resonance frequency changes significantly. Xenon also dissolves in lipophilic liquids. If such properties are desired, xenon is used.
• the noble gas helium hardly dissolves in liquids.
• the 3 He isotope is therefore used regularly when cavities are affected. A person's lungs is an example of such a cavity.
• noble gases have other valuable properties.
• the isotopes 83 Kr, 21 Ne and 131 Xe have a quadrupole moment, which is interesting, for example, for experiments in basic research or in surface physics.
• these noble gases are very expensive, so that they are unsuitable for applications in which larger quantities are used.
• a gas stream consisting of a mixture of 1% 129 Xe and N 2 and 98% 4 He is enriched in a container with Rb vapor and passed through a sample cell.
• a laser circularly polarized light is provided, that is light in which the angular momentum or the spin of the photons are all in the same
• the Rb atoms are optically pumped species with the laser beam ( ⁇ ⁇ 795 nm, Rb Dl line) optically pumped longitudinally to a magnetic field, thus polarizing the electron spins of the Rb atoms.
• the angular momentum of the photons is transferred to the free electrons of the alkali atoms transferred.
• the spins of the electrons of the alkali atoms therefore show a large deviation from the thermal equilibrium.
• the alkali atoms are consequently polarized.
• the collision of an alkali atom with a noble gas atom transfers the polarization of the electron spin from the alkali atom to the noble gas atom. This creates polarized noble gas.
• the polarization of the electron spin of the alkali atoms generated by the optical pumping of alkali atoms is thus transferred from the alkali electron to the nuclear spin of the noble gases by spin exchange.
• Alkali atoms are used because they have a large optical dipole moment which interacts with the light. Furthermore, alkali atoms each have a free electron, so that no disadvantageous interactions between two and more electrons per atom can occur.
• the partial pressure of He in the gas mixture is up to 10 bar. This is very high compared to the other partial pressures (xenon or nitrogen). This relatively high partial pressure means that polarized atoms only rarely reach the sample wall of the glass cell and lose their polarization there, for example due to interaction with paramagnetic centers. With increasing partial pressure of the 4 He, the probability decreases that polarized atoms adversely hit the cell wall.
• the heavy noble gas atoms e.g. B. Xenon atoms
• the partial pressure of the xenon gas in the gas mixture must be correspondingly low.
• Even with a xenon Partial pressure in the gas mixture of 0.1 bar requires laser powers of around 100 watts in order to achieve a polarization of the alkali atoms of around 70 percent in the entire sample volume.
• the nuclear spin polarization build-up times are between 20 and 40 seconds due to the high spin exchange cross section. Due to the very high rubidium-spin destruction rate for rubidium-xenon impacts, the xenon partial pressure in optical spin-exchange pumps must not exceed the values specified so that a sufficiently high rubidium polarization can be maintained. Therefore 4 He is used as a buffer gas for line broadening in such polarizers.
• Glass sample cells are used, which are blown from one piece and in which the noble gas atoms or the atomic nuclei are optically pumped.
• the sample cell is located in a static magnetic field B0 of some 10 Gauss, which is generated by coils, in particular a so-called Helmholtz coil pair.
• the direction of the magnetic field runs parallel to the cylinder axis of the sample cell or parallel to the beam direction of the laser.
• the magnetic field is used to guide the polarized atoms.
• the rubidium atoms which are highly polarized by the light of the laser, collide with the xenon atoms in the glass cell and give up their polarization to the xenon atoms.
• Typical values of partial pressures at the output of a polarizer are p He ⁇ 7 bar, p N2 ⁇ 0.07 bar, p Xe ⁇ 0.07 bar with a numerical particle density of Rb of ⁇ 10 14 cm -3 .
• its partial pressure during the polarization is reduced to a few by means of spin exchange optical pumps. wa limited to 0.1 bar.
• the Xe density in the gas must be increased for the enrichment.
• a method for the enrichment of hyperpolarized 129 Xe is known from EP 0 890 066 B1.
• the gas mixture which comprises hyperpolarized 129 Xe
• the reservoir is cooled, for example with liquid N 2, to a temperature which causes the xenon to condense to the frozen form, so that it is enriched in the reservoir from the flowing starting gas in frozen form.
• the rubidium is deposited at the outlet of the sample cell due to the high melting point compared to the melting points of the other gases on the wall.
• the polarized 129 Xe or the residual gas mixture is passed on from the sample cell to a freezer unit. This consists of a glass bulb, the end of which is immersed in liquid nitrogen.
• the glass bulb is in a magnetic field with a strength of up to approx. 1 Tesla.
• a magnetic field of the order of about 1 T must be applied, since the relaxation time of the polarized Xe ice is only a few minutes with weaker magnetic fields and at a temperature of the liquid N 2 , so that considerable portions of the polarization disintegrate again with long enrichment times.
• Longer relaxation times (Tl ⁇ a few hours) can only be achieved if the Xe ice is additionally enriched / stored at the temperature of the liquid He at about 4 K.
• the object of the invention is to provide an inexpensive method for enriching hyperpolarized atomic nuclei.
• the method provides for the hyperpolarized atomic nuclei flowing in a gas mixture to be dissolved in a solvent cooled below 293 K.
• Solubility is defined as the density of the hyperpolarized gas in the solvent in relation to the density of the hyperpolarized gas in the gas space above it at a given temperature and pressure. The solubility is also called the Ostwald coefficient.
• the solvent has an Ostwald coefficient of at least 2 for the hyperpolarized atomic nuclei below room temperature. With falling temperatures, the solubility or the Ostwald coefficient increases to values of up to 200. Above room temperature, the Ostwald coefficient can advantageously assume a value less than 1.
• the method according to the invention is in no way limited to the enrichment of hyperpolarized atomic nuclei. Rather, it was recognized that the method can always be used when a specific component to be enriched in a gas mixture dissolves particularly well in a solvent cooled below 293 K compared to other constituents of the mixture.
• An example of this is the enrichment of the carbon isotopes 12 C and 13 C from a mixture with N 2 and 0 2 . After being dissolved in a solvent cooled below room temperature, the carbon isotopes are enriched and separated from the N 2 and 0 2 . 12 C and 13 C are then separated by isotope separation. Every valuable gas can be enriched from a mixture and, if necessary, separated through further process steps.
• the method has the advantage that it is inexpensive and easy to use.
• a lipophilic solvent with high viscosity will be selected for the process.
• toluene with an Ostwald coefficient of about 5 under standard conditions (293 K, 1 bar) or ethanol with an Ostwald coefficient of about 2.5 under standard conditions is chosen as the solvent for hyperpolarized 129 Xe.
• Pentane, acetone, methanol and butanol are generally suitable solvents for the enrichment of hyperpolarized noble gases.
• the solvent can be chosen according to the temperature.
• the solvent is also present in the liquid phase at low temperatures of, for example, 180 K.
• the melting point of the solvent is reduced in comparison to the pure solvent without the hyperpolarized atomic nucleus.
• Hyperpolarized atomic nuclei are accordingly dissolved in the solvent at lower temperatures than is to be expected according to the prior art. This effect is used for enrichment, since the solubility increases rapidly at lower temperatures.
• Olive oil and benzene as solvents also have a high Ostwald coefficient.
• the solvent With a suitable choice of the solvent, there is a desired increase in the solubility and thus an enrichment of the hyperpolarized atomic nuclei in the solvent.
• the solvent includes, for example, ethanol and / or toluene.
• ethanol for example, ethanol and / or toluene.
• a high solubility for hyperpolarized atomic nuclei was demonstrated in the context of the invention. It is conceivable to use these solvents to enrich other components from a gas mixture, such as. B. 13 C to use.
• T ⁇ relaxation time in the solvent is chosen greater than the residence time in the solvent during the process.
• deuterated solvents such as. B. C 6 D 5 CD 3 (toluene) or CD 3 CD 2 OD (ethanol) in which the relaxation time of the hyperpolarized atomic nuclei is greater than 100 seconds.
• a hyperpolarized noble gas is advantageously dissolved in the solvent from the gas stream of a polarizer in a chamber in which the solvent is either cooled or is still being cooled. Accordingly, other gases to be enriched are passed into such a chamber.
• the method optionally provides for a component to be enriched, e.g. B of a hyperpolarized noble gas to cause degassing from the solvent.
• a component to be enriched e.g. B of a hyperpolarized noble gas to cause degassing from the solvent.
• the solvent can be passed from the cooling chamber into a further chamber with degassing means. It is conceivable to carry out the redemption and degassing in one and the same chamber if the chamber has cooling and heating means.
• the volume of the chambers, in particular the chamber in which the degassing takes place, is chosen so large that in the case of
• the tu time of hyperpolarized atomic nuclei is determined, among other things, by their interaction with the inner wall of the chamber.
• Ti times of more than 1 hour can be achieved.
• a fundamental T ⁇ time (Xe-Xe interaction) of 56 h / [amagat] can be used as a basis for Xe gas.
• hyperpolarized atomic nuclei can therefore be enriched and stored longer than with the known methods.
• the solvent can be passed into chambers specially provided for this purpose. This procedure enables a pump effect and, for enrichment, a further increase in density of the component to be enriched to be achieved.
• the flow of the solvent can be controlled continuously or semi-continuously by controlling the pressure in the chambers or in pressure equalization containers or stores.
• the method has the advantage that, depending on the solvent, only small amounts of N 2 are dissolved in the storage medium. In contrast, considerable amounts of N 2 are frozen out in the known freezing-out process.
• a device for carrying out a method accordingly comprises at least one chamber with means for degassing the enriched component, which is dissolved in a solvent in the chamber.
• the chamber has z. B. heating coils and / or means for training ultrasound.
• the device also has at least one means for forming a magnetic field with a maximum strength of 0.04 Tesla, e.g. B. a Helmholtz coil.
• a magnetic field with a maximum strength of 0.04 Tesla e.g. B. a Helmholtz coil.
• expensive and heavy magnets no longer have to be used to generate strong magnetic fields for the hyperpolarized atomic nuclei.
• the chamber also has means for degassing. if necessary, means for cooling.
• the temperature of the solvent can be set to, for example, about 180 K during the enrichment, compared to 77 K in the case of condensed Xe ice.
• the temperatures required in the enrichment process according to the invention with solvents can therefore with standard cooling processes and agents such.
• B. can be achieved with Peltier elements. This advantageously enables a compact structure of the device according to the invention for mobile systems.
• the device has at least one chamber in which the hyperpolarized atomic nuclei or other components to be enriched are dissolved, and a further second chamber connected to this chamber.
• the cold solvent with the gas enriched in it is passed from the first to the second chamber, where it is degassed.
• the second chamber then has the means for degassing from the solvent.
• the device optionally has a storage for the enriched gas e.g. a hyperpolarized noble gas.
• the storage tank is connected to the chamber or chambers in which the degassing takes place.
• the enriched, possibly hyperpolarized gas is fed into the storage.
• the solvent on the other hand, is disposed of or returned to the cooling chamber with cooling.
• the device has at least two cascaded tete units each from a chamber in which the component to be enriched, for. B. a hyperpolarized noble gas is dissolved in a cooled solvent, and a further chamber in which it is degassed again.
• a hyperpolarized noble gas is dissolved in a cooled solvent
• a further chamber in which it is degassed again.
• the solvents cooled below 293 K can be used not only for enrichment but also for storing and transporting a component to be enriched, e.g. B. a certain hyperpolarized noble gas can be used.
• the once enriched gases, in particular hyperpolarized noble gases, are of particular interest even in the cooled solvent itself.
• the method according to the invention is not limited to the advantages mentioned. In many applications, it is necessary e.g. B. hyperpolarized 129 Xe dissolved in a liquid from the outset to make it available to the objects or substances to be examined, eg. B. to get to complex molecules or to study the diffusion of liquids in porous structures.
• the thawing step from the Xe ice is advantageously omitted in the method according to the invention.
• a cooled solvent with a dissolved hyperpolarized noble gas is therefore a direct contrast medium for magnetic resonance tomography examinations.
• Chilled ethanol or toluene with dissolved 129 Xe may again be mentioned as an example.
• a cold solvent with hyperpolarized atomic nuclei, or 13 C, 235 U or 238 U, in which the solvent has a temperature of less than 293 K is therefore of particular interest.
• the solvent can also include pentane or other solvents. Such a solvent can
• FIG. 2 shows a device for carrying out the method according to the invention.
• a device for enrichment can be seen, for example, in FIG. 2.
• a gas mixture 1 with hyperpolarized atomic nuclei flows from a polarizer (not shown) into a first chamber 2, which contains a cooled solvent.
• Chamber 2 has means for cooling the solvent.
• the solvent with the gas mixture is cooled to a temperature i of e.g. 180 K.
• the gas components are enriched according to their solubility in the solvent and thus separated from one another.
• the components of the mixture that are not required are discharged via valve 3.
• the solvent enriched with the hyperpolarized atomic nuclei is passed via a connecting line from the chamber 2 into another chamber 5.
• Chamber 5 comprises degassing means, such as a device for generating ultrasound and / or a heater. The solvent is thus degassed by heat and / or ultrasound in the chamber 5.
• Chamber 5 thus represents a degassing chamber 5 for the hyperpolarized atomic nuclei from the solvent.
• the hyperpolarized In the atomic nuclei above the solvent a gas pressure of the originally dissolved gas entered.
• the gas pressure is determined by the partial pressure of the hyperpolarized atomic nuclei (gas component) in the solvent chamber 2 and the ratio of the solubilities of this gas component in the solvent at the temperatures Ti in chamber 2 and T 2 in chamber 5.
• the degassing chamber 5, into which the solvent is passed, has a sufficiently large volume that a long Tx relaxation time of the hyperpolarized nuclei is ensured.
• the volume is measured so that a gas pressure of about 2 bar is established.
• the process of solution and degassing can be repeated, as shown in FIG. 2 by means of solid lines.
• the gas with the hyperpolarized atomic nuclei is passed into chamber 6 and cooled there to the temperature T x .
• the temperature T x After enrichment in the solvent, it is passed into chamber 8 at a temperature T 2 for degassing.
• Chamber 8 again has a sufficient volume.
• Chamber 6 like chamber 2 for cooling, is provided with a cooling unit 7 for cooling the solvent.
• the respective temperatures Ti and T 2 in the chambers 2, 6 and 5, 8 can, but need not necessarily, be identical. Rather, the chambers can be provided with heaters and means for generating ultrasound, depending on the application.
• the degassed hyperpolarized atomic nuclei are passed from the chamber 8 into a memory 9.
• the inner walls of the memory 9 are lined with PFA or monochlorosilane in order to extend the relaxation time of the hyperpolarized atomic nuclei.
• all chambers and connecting lines of the device can be designed in this way.
• the solvent is passed into a waste container 14 and disposed of, or temporarily stored in a container 10 for reuse. Transport can be controlled by gas pressure.
• the solvent is, for. B. in the container 10 exposed to pressure equalization.
• the waste container 14 is arranged behind the chamber or chambers 5, 8 for degassing.
• the solvent is then fed back into the chamber 2 via a cooling coil 11 via the connecting line 12.
• a storage container 13 with solvent is arranged in front of the cooling coil 11, so that used solvent can be replaced and pre-cooled to the intended temperature Ti.
• the entire process can be controlled continuously or semi-continuously by controlling the pressure in the accumulator 9 and in the surge tank 10.
• the method can be controlled at least partially discontinuously via the valves shown. Additional valves, not shown, can be arranged, for. B. behind chamber 8 before the branch to waste bin 14th
• a magnetic field of less than 0.01 T is sufficient to store the gas in storage 9.
• Helmholtz coils are arranged in a suitable manner for this purpose and are part of the device.
• 129 Xe densities can be set at different temperatures in the solvent (toluene / ethanol): Level 1 Level 2 (Chamber 2) (Chamber 6)
• T 240K, pXe, Sol -0.7 bar -3.5 bar
• T 200K, pXe, Sol -2.1 bar -10 bar

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• 2004
  • 2004-01-19 DE DE102004002639A patent/DE102004002639A1/de not_active Withdrawn
  • 2004-12-08 WO PCT/DE2004/002689 patent/WO2005068359A2/de not_active Ceased
  • 2004-12-08 US US10/586,569 patent/US20070156046A1/en not_active Abandoned
  • 2004-12-08 EP EP04802897A patent/EP1706355A2/de not_active Withdrawn
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