EP1763680A1 - Method and device for high-resolution nuclear magnetic resonance spectroscopy using a hyperpolarised medium - Google Patents
Method and device for high-resolution nuclear magnetic resonance spectroscopy using a hyperpolarised mediumInfo
- Publication number
- EP1763680A1 EP1763680A1 EP05749200A EP05749200A EP1763680A1 EP 1763680 A1 EP1763680 A1 EP 1763680A1 EP 05749200 A EP05749200 A EP 05749200A EP 05749200 A EP05749200 A EP 05749200A EP 1763680 A1 EP1763680 A1 EP 1763680A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- medium
- sample
- chemical shift
- xenon
- magnetic field
- 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.)
- Withdrawn
Links
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
- G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
- G01R33/46—NMR spectroscopy
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N24/00—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects
- G01N24/08—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects by using nuclear magnetic resonance
-
- 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
- G01R33/24—Arrangements or instruments for measuring magnetic variables involving magnetic resonance for measuring direction or magnitude of magnetic fields or magnetic flux
Definitions
- the present invention relates to a method and a device for analyzing a sample by detecting a chemical shift in a medium which has been caused by the presence of a sample. From the prior art it is known to carry out such an analysis with the aid of high-resolution Kernspinresonanz ⁇ or to perform NMR spectroscopy.
- Nuclear magnetic resonance is the measurement of a precessing nuclear spin ensemble which oscillates with the Larmor precession frequency around a homogeneous magnetic field. The excitation of the precession is carried out by a resonant high-frequency field. In addition to nuclear spin tomography (imaging), nuclear magnetic resonance is particularly useful for highly resolved structure determination used in NMR spectroscopy,
- the test tube enclosed by a test tube in which the high frequency (RF) alternating magnetic field H 1 is generated to excite the nuclear magnetic resonance in the sample by means of a radio frequency generator, zwi ⁇ tween the poles of a large magnet of the NMR spectrometer brought ,
- This provides a stable, homogeneous magnetic field ' B 0 , which is perpendicular to the direction of the alternating magnetic field.
- Resonance occurs when the frequency of the exciting RF field in accordance with the prescending nuclear spins.
- the Larmor frequency is determined by the magnetic field acting at the nuclear location, which, however, does not coincide exactly with the externally applied magnetic field B 0.
- the applied magnetic field is weakened by magnetic fields of the shell electrons and the fields of neighboring nuclei the local effective field strength in normal cases is less than the applied field strength B 0 (diamagnetic atoms or, substances).
- reinforcement of the field can also take place at the location of the core plots (paramagnetic atoms or substances). This effect, referred to as shielding, leads to a change in frequency (chemical shift) in the NMR spectrum of the medium under investigation.
- the chemical shift depends on the chemical and physical environment of the considered nucleus. Therefore, the determination of the chemical shift in a medium caused by the presence or addition of a sample makes it possible to draw conclusions about the sample and thus an analysis of the sample.
- nuclei Because of their frequent occurrence, the most frequently investigated nuclei are protons ( 1 H-NMR) Furthermore, it is usual to examine 2 H, 13 C, 9 F, and 31 P nuclei.
- a disadvantage of the known proton spectroscopy method is that strong magnetic fields of more than 0.1 T have to be applied, so that on the one hand a resonance is detected in the spectrum or the chemical shift in the spectrum is so great that it is resolvable. For small magnetic fields, the signal - to - noise ratio is low. It is particularly disadvantageous that the strong magnetic fields can only be produced comparatively expensive since they must have sufficiently high homogeneity and temporal constancy, which in general can only be achieved by superconducting magnets or expensive unwieldy electromagnets. In addition to the high cost, the operation of such magnets also requires considerable maintenance costs, Furthermore, it limits the transportability of such equipment considerably.
- NMR spectroscopy The classical field of application of NMR spectroscopy is chemical structure elucidation, which is of great importance in connection with the analysis of proteins and other macromolecular substances and is used, for example, in the pharmaceutical and petroleum industries. Living tissue can also be measured by means of NMR spectroscopy. With the aid of electronic computational methods, NMR cross-sectional images of plants, animals and humans can be produced which represent the distribution of the "freely mobile" hydrogen atoms and thus detect tissue structures and organs Let NEN (magnetic resonance imaging),
- the method according to the invention for analyzing a sample provides that a hyperpolarized medium is added to a sample and the chemical shift caused in the hyperpolarized medium by the sample is determined. It is used to determine the chemical shift öie ⁇ Lamorfrequenz of
- the medium for example, the gas is passed to the sample and dissolved, for example, in the sample.
- the dissolution of the medium in the sample succeeds before all, if the sample is a liquid, It is now the Larmor frequency of the medium, so for example, the dissolved gas measured.
- the difference of the Larmor frequencies sfeilf a measure of the sought chemical shift,
- the hyperpolarization can be carried out continuously or discontinuously. Suitable for this purpose are in principle all known processes (inter alia DNP, PHIP),
- Hyperpolarization is achieved particularly efficiently by means of optical spin exchange pumps, in particular by means of high-pressure polarizers and / or transportable polarizers, which make mobility possible.
- the signal-to-noise ratio can thus be improved by several tens of powers
- Xenon is preferred as the medium.
- Xenon also has the advantage that it can be dissolved in a particularly suitable manner in many liquids such as petroleum.
- Weak magnetic fields according to the invention are in particular fields having a thickness of less than 200 G. For example, there are very weak fields in the range of 0.001 T, ie 1 0 Gaus.
- the advantages of determining the chemical shift in the case of weak fields are that corresponding devices can be manufactured and maintained at comparatively low costs (for example, in comparison to superconducting magnets).
- a shield is not required in the inventive method.
- An artificial, weak magnetic field B 0 can be achieved, for example, with simple electromagnets that can be operated at low current intensities. Further advantages are that the T2 and T2 * times can be very long and susceptibility artifacts practically do not occur. The latter is a big problem with high magnetic fields,
- an excitation of the nuclear spins for determining the chemical shift can advantageously take place with a DC current pulse, as a result of which the electronics for exciting the core pin can be kept simple. Further, upon excitation with a DC pulse, the Skln effect advantageously disappears.
- the excitation of the nuclear spins can then also be carried out by conductive materials (for example metal tubes) and in difficult environments.
- a magnetic field is typically sufficiently weak if the DC magnetic pulse is at least twice, preferably at least three times as large as the static magnetic field.
- the DC magnetic pulse is preferably rectangular.
- hyperpolarized xenon is added to the sample, for example the polarization of the xenon can be achieved by optical spin exchange pumping using Rb vapor and natural xenon gas, for example hyperpolar ⁇ sated xenon gas using a jet polarizer, as disclosed in DE 102004002640.8 DE, be produced.
- Xe ⁇ non has the advantage that in this element, the chemical shift is particularly pronounced, for example, it is 1 88 ppm when dissolved in toluene xenon, Further, xenon has the Advantageous, that it can be immersed, for example, in contrast to 3 He in a liquid sample with different solubilities.
- the nuclear magnetic resonance or Larmorfrequenz of z. Xenon gas is used as a comparison when xenon is the medium.
- This nuclear magnetic resonance of xenon gas which acts as a reference line in the spectrum, is preferably measured simultaneously with the lamor frequency of the xenone dissolved in the sample so as to make it meaningful Results went to.
- a detection coil for xenon and xenon dissolved in the sample liquid can be provided in the gas phase.
- the nuclear magnetic resonance of 3 He is measured.
- the xenon gas line can be used as a reference.
- the measurement of the chemical shift of xenon can be particularly difficult in the earth's magnetic field in that the exact position of the xenon gas line on the temperature and the particle density, ie the pressure of the xenon gas depends and that in many cases the xenon gas line with the xenon - Liquid line overlaps when the T 2 time of xenon becomes shorter than 10 seconds.
- 3 He is also advantageously hyperpolarized beforehand, in particular by spin exchange optical pumping.
- the nuclear spin resonance signal ie the Larmor frequency of 3 He-GaS, is a comparatively good reference since the exact position the 3 He line in the spectrum negligibly depends on the temperature and density of the 3 He gas and in the Earth's magnetic field the line width of the 3 He spectrum is extremely small (T 2 ⁇ T OOOs or longer).
- the resonance in the terrestrial magnetic field of 3 He (about 1.6 kHz) in the spectrum is so far away from xenon (about 600 Hz) that the 3He line and the Xe line do not overlap and thus do not overlap disturbingly disadvantageous,
- the nuclear magnetic resonance ie the Larmor frequency of xenon in a sample and 3 He is measured simultaneously.
- This can be achieved by two separate measuring arrangements (two sample volumes, two resonant circuits, two ejection electronics) for 3 He-GaS and for xenon in the sample .
- the simultaneous measurement of the signals has the further advantage that disturbances and fluctuations in the magnetic field or mechanical rotational movements of the measuring device can be calculated out.
- the signal of the 3 He gas or the xenon-containing sample liquid can be used to determine the absolute magnetic field accurately be used.
- the two Larmor frequencies are subtracted from one another to determine the chemical shift and then the result is divided by the Larmor frequency of the medium.
- FIG. 1 illustrates that the chemical shift, ie the distance between the resonance peaks of the solution dissolved in toluene
- (a) additionally shows that the line width of the resonance is scaled by B 0 . Therefore, it is also possible to separate the two resonance lines (xenon gas and xenon in the liquid) down to the ground magnetic field.
- oxygen-free toluene is used here.
- the xenon T 1 -T 2 time is approximately 1 00 s
- the line width of the xenon-toluene line is about 1 0 mHz
- the chemical shift between xenon and xenon in toluene in Erd ⁇ magnetic field is about 0, 1 2 Hz ie the two lines are clearly separated from each other in the magnetic field.
- the limit at which the two lines are just separated is 45 mG (about 1/10 of the earth's field). The chemical shift makes it possible to draw conclusions about the Type of solvent and its temperature.
Landscapes
- Physics & Mathematics (AREA)
- High Energy & Nuclear Physics (AREA)
- General Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Condensed Matter Physics & Semiconductors (AREA)
- Magnetic Resonance Imaging Apparatus (AREA)
Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102004032080A DE102004032080A1 (en) | 2004-07-02 | 2004-07-02 | Method and apparatus for high-resolution NMR spectroscopy |
PCT/EP2005/052512 WO2006003065A1 (en) | 2004-07-02 | 2005-06-01 | Method and device for high-resolution nuclear magnetic resonance spectroscopy using a hyperpolarised medium |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1763680A1 true EP1763680A1 (en) | 2007-03-21 |
Family
ID=35058060
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP05749200A Withdrawn EP1763680A1 (en) | 2004-07-02 | 2005-06-01 | Method and device for high-resolution nuclear magnetic resonance spectroscopy using a hyperpolarised medium |
Country Status (5)
Country | Link |
---|---|
US (1) | US20070229072A1 (en) |
EP (1) | EP1763680A1 (en) |
JP (1) | JP2008504541A (en) |
DE (1) | DE102004032080A1 (en) |
WO (1) | WO2006003065A1 (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7741844B2 (en) * | 2007-05-07 | 2010-06-22 | General Electric Company | Method and system for magnetic resonance imaging using labeled contrast agents |
US8508222B2 (en) | 2008-01-23 | 2013-08-13 | Koninklijke Philips N.V. | Nuclear magnetic resonance spectroscopy using light with orbital angular momentum |
CN104458785B (en) * | 2014-12-12 | 2016-09-07 | 中国科学院武汉物理与数学研究所 | A kind of NMR spectrum spectral peak alignment and spectral peak extracting method |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997037239A1 (en) * | 1996-03-29 | 1997-10-09 | Lawrence Berkeley National Laboratory | Enhancement of nmr and mri in the presence of hyperpolarized noble gases |
US6845262B2 (en) * | 2000-03-29 | 2005-01-18 | The Brigham And Women's Hospital, Inc. | Low-field MRI |
US7126332B2 (en) * | 2001-07-20 | 2006-10-24 | Baker Hughes Incorporated | Downhole high resolution NMR spectroscopy with polarization enhancement |
US7541806B2 (en) * | 2006-06-24 | 2009-06-02 | Forschungszentrum Julich Gmbh | Method for molecule examination by NMR spectroscopy |
-
2004
- 2004-07-02 DE DE102004032080A patent/DE102004032080A1/en not_active Withdrawn
-
2005
- 2005-06-01 JP JP2007518572A patent/JP2008504541A/en not_active Withdrawn
- 2005-06-01 EP EP05749200A patent/EP1763680A1/en not_active Withdrawn
- 2005-06-01 US US11/571,372 patent/US20070229072A1/en not_active Abandoned
- 2005-06-01 WO PCT/EP2005/052512 patent/WO2006003065A1/en active Application Filing
Non-Patent Citations (1)
Title |
---|
See references of WO2006003065A1 * |
Also Published As
Publication number | Publication date |
---|---|
US20070229072A1 (en) | 2007-10-04 |
JP2008504541A (en) | 2008-02-14 |
DE102004032080A1 (en) | 2006-01-26 |
WO2006003065A1 (en) | 2006-01-12 |
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RIN1 | Information on inventor provided before grant (corrected) |
Inventor name: PATZAK, RICHARD Inventor name: GEMBRIS, DANIEL DR. Inventor name: SIELING, ULRICH Inventor name: HAESING, FRIEDRICH, WOLFGANG Inventor name: APPELT, STEPHAN PROF. DR. Inventor name: HALLING, HORST PROF. DR. |
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RIN1 | Information on inventor provided before grant (corrected) |
Inventor name: APPELT, STEPHAN PROF. DR. Inventor name: HAESING, FRIEDRICH, WOLFGANG Inventor name: PATZAK, RICHARD Inventor name: SIELING, ULRICH Inventor name: GEMBRIS, DANIEL DR. Inventor name: HALLING, HORST PROF. DR. |
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