WO2004109312A2 - Procede pour transporter un gaz noble hyperpolarise - Google Patents

Procede pour transporter un gaz noble hyperpolarise Download PDF

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Publication number
WO2004109312A2
WO2004109312A2 PCT/DE2004/000974 DE2004000974W WO2004109312A2 WO 2004109312 A2 WO2004109312 A2 WO 2004109312A2 DE 2004000974 W DE2004000974 W DE 2004000974W WO 2004109312 A2 WO2004109312 A2 WO 2004109312A2
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WO
WIPO (PCT)
Prior art keywords
noble gas
hyperpolarized
xenon
hyperpolarized noble
solvent
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/DE2004/000974
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German (de)
English (en)
Other versions
WO2004109312A3 (fr
Inventor
Stephan Appelt
Daniel Gembris
Jürgen HESSER
Horst Halling
Richard Patzak
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Forschungszentrum Juelich GmbH
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Forschungszentrum Juelich GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
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Publication of WO2004109312A2 publication Critical patent/WO2004109312A2/fr
Publication of WO2004109312A3 publication Critical patent/WO2004109312A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • G01R33/282—Means specially adapted for hyperpolarisation or for hyperpolarised contrast agents, e.g. for the generation of hyperpolarised gases using optical pumping cells, for storing hyperpolarised contrast agents or for the determination of the polarisation of a hyperpolarised contrast agent

Definitions

  • the invention relates to a method for transporting a hyperpolarized noble gas.
  • the invention also relates to a magnetic resonance examination.
  • a method is known from WO 99/53332 in which a hyperpolarized noble gas present in the gas phase is inhaled for imaging a lung and is used as a contrast agent for the oxygenation state.
  • a method for increasing the relaxation time of a hyperpolarized noble gas in contact with a physiological liquid is known from US Pat. No. 6,426,058 B1.
  • the noble gas was dissolved in an artificial physiological solution in which the relaxation time of the noble gas is longer than the relaxation time of the noble gas in blood.
  • Walls of the devices containing them and rapidly lose their polarization when transported to the sample.
  • Hyperpolarized noble gases dissolved in a solvent can be detected longer than in the gas phase, but are then distributed in an uncontrolled manner on or in the sample.
  • the object of the invention is to provide a transport method, in particular for magnetic resonance examinations, in which the hyperpolarized noble gas is passed locally to a sample to be examined without losing the hyperpolarization.
  • the basic idea is the loss-free transport of the hyperpolarized noble gas in the device with the steps: a tubular device with a predetermined inner diameter and length for transporting the noble gas is selected such that the relaxation time of the noble gas is greater than the transit time in the device,
  • the hyperpolarized noble gas is transported in a targeted manner in the device to a destination.
  • Dissolving in a suitable solvent reduces the diffusion of the hyperpolarized noble gas compared to the hyperpolarized noble gas in the gas phase.
  • the diffusion coefficient of the noble gas is reduced.
  • the choice of a suitable tubular device ensures that the hyperpolarized noble gas does not hit the walls of the device on average during the transit time, since the relaxation time is longer than the transit time due to the reduced diffusion.
  • the noble gas is passed to the sample to be examined without loss, that is to say in the hyperpolarized state.
  • hyperpolarized noble gas can stay in solution longer without bumping against the walls of the hose than in the gas phase.
  • the tubular device can have a suitable tip via which the hyperpolarized noble gas is passed to the sample to be examined.
  • the hyperpolarized noble gas can be used for magnetic resonance examinations over a longer period of time and can be directed very directly to or into the examination site.
  • the location of the examination can also be difficult to access.
  • samples can also be examined in their hard-to-reach places, which due to the described processes relating to the relaxation time and the loss of polarization due to wall contact have so far not been and are not accessible for magnetic resonance examinations.
  • the long period over which the hyperpolarization of the noble gas is maintained means, in particular, a period of five to ten minutes and even longer.
  • hyperpolarized 129 xenon can be selected as the noble gas.
  • a solvent with few para- and even fewer ferromagnetic substances is selected in order to keep the depolarization of the hyperpolarized spins as low as possible.
  • the hyperpolarized noble gas is dissolved in a solvent that is deuterated, so that the dipolar noble gas deuteron relaxation is significantly less than the dipolar noble gas proton relaxation.
  • a solvent that is deuterated so that the dipolar noble gas deuteron relaxation is significantly less than the dipolar noble gas proton relaxation.
  • the hyperpolarized noble gas can be selected as the aerosol in the present case. It can e.g. B. by means of a suitable pump atomizer on or on the sample to be examined.
  • a lipophilic solvent can also be chosen, e.g. B. edible oil or perflurocarbon (PFC).
  • PFC perflurocarbon
  • the substances can in particular be deuterated.
  • the hyperpolarized noble gas dissolved in the solvent can also be transported high density, so that more noble gas per unit time can be transported in the tubular device.
  • a hyperpolarized noble gas which is present in solution in this way can be used as a contrast medium for magnetic resonance examinations.
  • hyperpolarized noble gas is brought locally via devices having PFA and / or polyimide compounds with spaces for receiving the noble gas into or onto an object to be examined and is detected as an imaging method by means of magnetic resonance examinations.
  • the devices having PFA and / or polyimide compounds advantageously, compared to other materials such as glass, stainless steel, titanium etc., advantageously maintain the hyperpolarization of the noble gas.
  • a hyperpolarized noble gas is first dissolved in a solvent.
  • a device for transporting the noble gas with predetermined dimensions is then selected such that the relaxation time of the noble gas is greater than the transport time in the device.
  • the hyperpolarized noble gas is transported to a destination in the device.
  • Hyperpolarized 129 xenon is generated in a rubidium flow polarizer by optical pumping and used to examine a pipe system or an oil separator.
  • the hyperpolarized 129 xenon is dissolved in ethanol as a solvent.
  • a tube with a millimeter diameter is selected.
  • the 129 xenon is transported locally to the location of the sample to be examined in the tube.
  • the diffusion coefficient of hyperpolarized xenon dissolved in ethanol is approx. 2 * 10 cm s " , that of gaseous 129 xenon, on the other hand, 6 * 10 ⁇ 2 cm 2 s _1 .
  • 129 xenon can therefore be used in a hose with a millimeter inside diameter the formula for the free path length for three dimensions
  • the methods according to the invention can in particular also be used for the therapy and / or diagnosis of diseases such as cardiovascular, gastrointestinal, tooth and throat diseases and vasoconstrictions.
  • hyperpolarized 129 xenon as a noble gas, in contrast to other contrast media such as 3 He and other, has other fundamental advantages for therapeutic tables and diagnostic purposes.
  • the xenon dissolves in blood and can be absorbed by various types of tissue.
  • Hyperpolarized 129 xenon is then detected using magnetic resonance or magnetic resonance tomography.
  • Spectroscopic 129 Xe imaging is also possible with this.
  • Magnetic resonance tomography can generally generate both projection images and three-dimensional volume images. The concentration of the 129 xenon should be so small that the effect as an anesthetic does not occur in patients.
  • catheter interventions on the heart are among the most common interventions in cardiology. Around 600,000 of these are currently performed annually in Germany alone. The tendency for such interventions is increasing worldwide. Around 200,000 interventions are so-called PTCAs.
  • PTCA Percutane Transluminare Coronary Angioplasty
  • the so-called catheter treatment using PTCA was developed in 1977 and in many cases represents an alternative to bypass surgery.
  • Hyperpolarized 129 xenon is first generated in a rubidium flow polarizer by optical pumping.
  • Devices for polarizing xenon are now portable due to their size and weight and can be installed near a tomograph.
  • 129 xenon is dissolved in ethanol to achieve a high density at room temperature and normal pressure.
  • After transporting the hyperpolarized 129 xenon to the examination site uses magnetic resonance tomography as an imaging method.
  • the hyperpolarized 129 xenon is injected into the veins via a catheter and detected using magnetic resonance tomography, and its advance is checked during the procedure.
  • the catheter is advanced from the groin to the entrances to the coronary arteries.
  • the catheter is latched into the entrance to the coronary arteries and from there a guide wire to the constriction point in the
  • the hyperpolarized 129 xenon is introduced into a balloon of a catheter which is closed at the end for a dilation of a vessel and followed online for the dilation of the vessel. Dilatation is observed without polarized 129 xenon coming into contact with tissue. However, it is also conceivable both to carry out a dilation and to enrich tissue with polarized 129 xenon.
  • the catheter open at the end has a guide wire with a balloon at the end of the guide wire.
  • Polarized 129 xenon can be directed into the dewebe as well as into the balloon via suitable connections.
  • the catheter can have at least one planar, e.g. B. have a meandering micro-coil.
  • micro coils are used to record magnetic resonance spectra with high resolution in time.
  • the microcoil (s) is / are attached to the outer skin of the catheter, e.g. B. glued. They can be surrounded by a biocompatible outer shell.
  • the micro coil sends out signals that cause transverse magnetization of the 129 xenon present in the tissue.
  • the decrease in the transverse magnetization of the 1 9 xenon is measured by the micro coil over time. After Fourier transformation one gets one
  • cylindrical micro-coils can also be arranged in the tip.
  • the imaging can take place without losses in terms of the signal-to-noise ratio (SNR, signal-to-noise ratio) at comparatively low B 0 field strengths, that is to say with field strengths of clearly less than 1.5 Tesla, especially with field strengths of approx. 0.2 Tesla (low-field scanner).
  • SNR signal-to-noise ratio
  • a narrowed vessel is achieved with an inflatable balloon (balloon dilation).
  • a balloon catheter is moved over the guide wire, which is dilated in the constriction site and thus widens the vein.
  • a stent i.e. a stable wire mesh, is used to support the opening and keeps the wire open.
  • stents can now be installed as vascular supports in the area of a vasoconstriction that keep the vessel artificially open.
  • stents are catheter brought to the narrowed place in the coronary artery.
  • the vascular network is expanded either with the balloon catheter or with the support's self-expanding technique.
  • Vascular supports are increasingly being used successfully, particularly to improve long-term results after balloon dilatation.
  • the method according to the invention has many advantages.
  • the contrast medium used is not iodine, as was previously the case with PTCA and coupled x-ray transmission, but hyperpolarized 129 xenon, which is dissolved in ethanol as a solvent.
  • a catheter can be used as a tubular device, the 129 xenon being guided very quickly and practically without loss locally to the area of the heart to be examined.
  • magnetic resonance procedures enable a three-dimensional display of the coronary arteries. This makes the process much safer because the risk of perforation of the wires is reduced.
  • the reaction options for complications are expanded by the three-dimensional representation.
  • the radiation dose no longer places a burden on the patient.
  • iodine infarctions and the risk of allergic reactions to iodine up to anaphylactic shock are excluded.
  • the hyperpolarized noble gas can also in difficult to access places such.
  • B. inside human or animal bodies are transported and used by means of magnetic resonance methods for diagnostic and / or therapeutic purposes.
  • a catheter comprising PFA and / or polyimide
  • the PFA catheter is connected to a polarizer or buffer for 129 xenon via a polyimide connector.
  • the areas of PFA and / or polyimide in contact with the hyperpolarized noble gas maintain the hyperpolarization of the xenon for 10 minutes and longer.
  • Local application in catheterization means that in particular parts of organs with polarized 129 xenon can be examined.
  • hyperpolarized noble gas such as 129 xenon as contrast medium
  • functional imaging and thus the imaging of physiological processes can also be carried out particularly advantageously with magnetic resonance tomography.
  • Hyperpolarized noble gas such as 129 xenon can advantageously have a degree of polarization of up to 40% and, in a Tesla, has a signal-to-noise ratio that is about 5-6 orders of magnitude higher than thermally polarized xenon. The consequence of this is that a higher spatial and temporal resolution of the magnetic resonance examination is made possible.
  • the data generated by magnetic resonance methods are collected particularly advantageously at low field strengths of 0.02 to 0.5 Tesla. In this case, superconductors for generating the B 0 field can be dispensed with.
  • Expensive high-field superconductors can advantageously be dispensed with, since only normal conductor or permanent magnets are used.
  • the k-space Frier-transformed object space
  • the k-space can also be scanned by an increasing number of readouts, which enables fast spectroscopic imaging and / or an additional increase in the SNR by averaging measured values of a k-space point ,
  • the maximum achievable (Rayleigh) resolution ⁇ x scales with -, where ⁇ f stands for the line width.
  • a long T2 time also proves to be advantageous here.
  • the volume field-of-view
  • the signal excitation should be limited to this volume by targeted administration of hyperpolarized 129 xenon.
  • the signal only comes from the area to be examined, which means that volume selection based on the pulse sequence is not necessary. This proves to be advantageous because it is associated with a certain degree of inaccuracy due to residual signal contributions from the environment.
  • the method is also suitable for the visual highlighting of vascular deposits (plaques) in arteries and for differentiating between different deposits, e.g. B. hard and soft plaques, which is made possible by the so-called chemical shift. This is based on a shift in the resonance frequency due to electrical currents in the electron shell of the xenon, which lead to a change in the B_0 field strength at the nucleus.
  • the use of diffusion-weighted pulse sequences has proven to be useful. Due to the long Tl times of xenon, the nuclear spins can scan a spatially wide area, which can result in improvements in inversion calculations to determine microstructural features. With the- This in turn enables a more precise characterization of the plaques.
  • An inverse keyhole method can prove to be particularly useful for examining the vascular deposits.
  • the scanning of the k-space is not aimed at the k-space center (more frequent or denser scanning in this area), but at the k-space periphery, which co - dated.
  • FOV x where ⁇ k x indicates the distance between successive k-space points, f the Larmor frequency divided by 2 ⁇ , G x the gradient strength, ⁇ t the time interval between successive sampling points and FOV x the width of the field-of-view.
  • ⁇ is 42.5MHz / T and for 129 Xe 11.78MHz / T.
  • the transition from protons to Xe atoms at a constant sampling rate and constant gradient strength is therefore associated with a tenfold increase in spatial resolution (42.5 ⁇ 2 / ll .78 A 2).
  • the diagnosis of dental diseases is another exemplary embodiment.
  • La-c shows magnetic resonance imaging using hyperpolarized 129 xenon dissolved in ethanol. The measurements were carried out with a 4.3 Tesla NMR spectrometer equipped with a Imaging unit and a 55 MHz xenon birdcage resonator with 20 mm inner diameter.
  • Figures la-c show axial slice images of the tooth, which were obtained with a FLASH sequence and a resolution of 64 x 64 voxels. In the illustration, dark gray tones stand for higher signal intensities, light gray tones for low signal intensities. Since the xenon does not penetrate the dentin, the dentin has low signal values. In the event of caries, cavities are created that absorb xenon and are therefore visible.
  • Xe-MR imaging can advantageously be transferred to the examination of teeth in vivo. Due to the hyperpolarization of the xenon, the measurements can be carried out at low B_0 field strengths, so that the entire measuring arrangement can be miniaturized to such an extent that it can be accommodated in the oral cavity. In order to transport the hyperpolarized 129 xenon to the site of the examination without loss, it is transported to the tooth using PFA syringes or hoses.

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  • Physics & Mathematics (AREA)
  • Condensed Matter Physics & Semiconductors (AREA)
  • General Physics & Mathematics (AREA)
  • Magnetic Resonance Imaging Apparatus (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Sampling And Sample Adjustment (AREA)

Abstract

L'invention concerne un procédé permettant de transporter un gaz noble hyperpolarisé, qui comprend les étapes suivantes : un dispositif tubulaire de diamètre intérieur prédéterminé et de longueur appropriée pour transporter le gaz noble, est sélectionné de sorte que le temps de relaxation du gaz noble soit supérieur au temps de transit dans le dispositif ; le gaz noble hyperpolarisé est transporté à destination, de manière ciblée dans le dispositif. L'invention concerne également un procédé de résonance magnétique pour analyse locale d'un échantillon.
PCT/DE2004/000974 2003-05-27 2004-05-11 Procede pour transporter un gaz noble hyperpolarise Ceased WO2004109312A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10324353.4 2003-05-27
DE2003124353 DE10324353A1 (de) 2003-05-27 2003-05-27 Verfahren zum Transport eines hyperpolarisierten Edelgases

Publications (2)

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WO2004109312A2 true WO2004109312A2 (fr) 2004-12-16
WO2004109312A3 WO2004109312A3 (fr) 2005-03-24

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DE102009026897A1 (de) * 2009-06-10 2010-12-16 Sirona Dental Systems Gmbh Sensor sowie Magnetfeldeinheit zur Verwendung innerhalb eines Magnetresonanztomographie-Systems oder eines Magnetresonanzspektroskopie-Systems
NL1043064B1 (en) * 2018-10-31 2020-06-02 Stefan Golkowsky Dr "methods and devices for imaging pulmonary and/or cardiac vasculature"

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FI982069A7 (fi) * 1996-03-29 1998-11-10 Lawrence Berkeley Nat Laboratory NMR:n ja MRI:n tehostaminen hyperpolaroitujen jalokaasujen läsnä olles sa
DE19619471C1 (de) * 1996-05-14 1997-10-16 Siemens Ag Kernspintomographiegerät mit Vorpolarisation
WO2002001242A2 (fr) * 2000-06-28 2002-01-03 The Regents Of The University Of Minnesota Procedes d'imagerie permettant de visualiser des cellules vivantes implantees
GB0110392D0 (en) * 2001-04-27 2001-06-20 Oxford Instr Plc Method and apparatus for magnetic resonance imaging

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WO2004109312A3 (fr) 2005-03-24
DE10324353A1 (de) 2005-01-13

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