EP4052058A1 - Procédé de correction de l'influence de variations du champ magnétique pour des mesures effectuées au moyen d'un spectromètre rmn mobile - Google Patents

Procédé de correction de l'influence de variations du champ magnétique pour des mesures effectuées au moyen d'un spectromètre rmn mobile

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Publication number
EP4052058A1
EP4052058A1 EP20775858.2A EP20775858A EP4052058A1 EP 4052058 A1 EP4052058 A1 EP 4052058A1 EP 20775858 A EP20775858 A EP 20775858A EP 4052058 A1 EP4052058 A1 EP 4052058A1
Authority
EP
European Patent Office
Prior art keywords
magnetic field
magnetic resonance
nuclear magnetic
resonance signal
influence
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.)
Pending
Application number
EP20775858.2A
Other languages
German (de)
English (en)
Inventor
Reiner Krapf
Jens Hoffmann
Andreas Graessl
Carolin SCHLAWNE
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.)
Robert Bosch GmbH
Original Assignee
Robert Bosch 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.)
Filing date
Publication date
Priority claimed from DE102019216755.1A external-priority patent/DE102019216755A1/de
Priority claimed from DE102019216761.6A external-priority patent/DE102019216761A1/de
Priority claimed from DE102019216759.4A external-priority patent/DE102019216759A1/de
Application filed by Robert Bosch GmbH filed Critical Robert Bosch GmbH
Publication of EP4052058A1 publication Critical patent/EP4052058A1/fr
Pending 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
    • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/46—NMR spectroscopy
    • G01R33/4625—Processing of acquired signals, e.g. elimination of phase errors, baseline fitting, chemometric analysis
    • 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
    • G01R33/38—Systems for generation, homogenisation or stabilisation of the main or gradient magnetic field
    • G01R33/3808—Magnet assemblies for single-sided MR wherein the magnet assembly is located on one side of a subject only; Magnet assemblies for inside-out MR, e.g. for MR in a borehole or in a blood vessel, or magnet assemblies for fringe-field MR
    • 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
    • G01R33/38—Systems for generation, homogenisation or stabilisation of the main or gradient magnetic field
    • G01R33/387—Compensation of inhomogeneities
    • 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
    • G01R33/38—Systems for generation, homogenisation or stabilisation of the main or gradient magnetic field
    • G01R33/387—Compensation of inhomogeneities
    • G01R33/3875—Compensation of inhomogeneities using correction coil assemblies, e.g. active shimming
    • 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

Definitions

  • NMR measuring devices with spectroscopic resolution are known, cf. for example from “Benchtop NMR spectrometers in academic teaching”, Susanne D. Riegel, Garett M. Leskowitz , Application Chemistry, Nanalysis Corp., Canada (D0l: 10.1016 / j.trac.2016.01.001).
  • Such NMR spectrometers work on the basis of an initial calibration in which a magnetic field BO that is as homogeneous as possible is adjusted, for example by so-called “active shimming” using electromagnetic coils.
  • the NMR spectrometer Before and during the NMR spectroscopy measurements following the calibration, it must be ensured that the NMR spectrometer remains stationary, i.e. stationary, and that the magnetic field BO at the location of the measurement sample does not change due to a change in the position of the NMR spectrometer.
  • the requirements for temporally and spatially unchangeable magnetic fields, in particular for field homogeneity, are extremely high in NMR spectrometers in order to be able to resolve differences in resonance frequencies of only a few ppm ("parts per million", corresponding to only a few mT) ( see “Spin Dynamics” Malcolm H. Levitt, Wiley 2008). Moving the NMR spectrometer would make a calibration carried out beforehand unnecessary.
  • compact NMR spectrometers are known, for example from “Scalable NMR spectroscopy with semiconductor chips", Dongwan Ha, Jeffrey Paulsen,
  • a mobile application - while maintaining an (almost) perfectly homogeneous, unchangeable magnetic field during the duration of an NMR spectroscopy measurement - is not feasible according to the current state of the art.
  • This circumstance prevents an actually mobile use, ie an NMR spectroscopy measurement while the NMR spectrometer is moving, of compact NMR spectrometers, for example as "wearables" (e.g. smart watch), implants, sensors in vehicles, airplanes, ships or the like , but also use in disturbed environments such as in industry and manufacturing, where other machines and systems can induce magnetic field inhomogeneities and / or magnetic field changes in the B0 field.
  • wearables e.g. smart watch
  • this is based on a method for operating a mobile NMR spectrometer, a static magnetic field B0 being generated during an NMR spectroscopy measurement on a measurement sample by means of a magnetic device of the mobile NMR spectrometer and by means of a magnetic field sensitive Detection device of the mobile NMR spectrometer sends an excitation signal B1 and at least one nuclear spin resonance signal is detected. It is proposed that an influence of location-dependent magnetic field changes and / or location-independent magnetic field changes acting during the NMR spectroscopy measurement, in particular during the acquisition of the at least one nuclear magnetic resonance signal, be determined and determined using at least one sensor using sensor data prevented and / or compensated.
  • An NMR spectrometer is to be understood as a measuring device which comprises at least one magnetic device for generating a static magnetic field B0 and a magnetic field-sensitive detection device for emitting an excitation signal B1 and for detecting a nuclear magnetic resonance signal.
  • components can be included which are necessary and / or necessary for measuring NMR spectra by means of the NMR spectrometer are useful.
  • Such components can represent, for example, an input device and / or an output device, a control device (which is also to be understood as an evaluation device), an energy supply device or the like.
  • the functioning of the NMR spectrometer is based on the nuclear physical effect, in which the atomic nuclei of a measurement sample absorb electromagnetic alternating fields in the magnetic field BO in the form of the excitation signal B1 and then emit them in the form of the nuclear magnetic resonance signal.
  • the nuclear spin resonance is based on the precession (Larmor precession) of nuclear spins of the atomic nuclei in the examined sample around the magnetic field lines of the constant, in particular static, first magnetic field BO. In particular, the nuclear spins of the atomic nuclei in the measurement sample are aligned by the first magnetic field BO.
  • an electromagnetic excitation signal Bl in particular an electromagnetic alternating field, for example a pulsed magnetic field
  • the atomic nuclei can orient their spins relative to the static Change magnetic field BO by absorbing this energy.
  • the irradiated excitation signal B1 therefore serves to excite the nuclear spins, which change their nuclear spin states while absorbing energy.
  • the emission of energy quanta as a result of a return of the excited nuclear spins to a different, lower energy level leads to the emission of an electromagnetic alternating field, which is generated as a nuclear magnetic resonance signal by means of a device for detecting a magnetic field change, in particular by means of the magnetic field-sensitive detection device can be captured.
  • Excitation of atomic nuclei is to be understood in particular as meaning that the energy and duration of the radiation of the electromagnetic fields, in particular alternating fields, cause a change in the direction of magnetization of the nuclear spins of the atomic nuclei, in particular a magnetization component orthogonal to the direction of the magnetic field BO field (transverse magnetization).
  • the energy transmitted by incident electromagnetic radiation is particularly important. This energy can advantageously be transmitted by means of pulsed electromagnetic fields.
  • the magnetic device of the NMR spectrometer is used to generate the static magnetic field BO in the test sample to be examined.
  • the magnet device is set up to provide or generate a magnetic field BO with a magnetic field strength of more than 0.1 Tesla, in particular of more than 1.5 Tesla and, in particular, of more than 5 Tesla.
  • the magnetic field BO extends in a volume in and / or around the magnet device.
  • the static magnetic field BO generated by the magnetic device serves to align the nuclear spins of the atomic nuclei present in the measurement sample (in said volume) in the sense that the nuclear spins align themselves to the magnetic field lines of the static magnetic field BO due to their magnetic nuclear spin moment, esp special precess around the magnetic field lines of the magnetic field.
  • the magnet device has at least one electromagnet (in particular resistive or superconducting) and / or at least one permanent magnet, by means of which the static magnetic field BO can be generated.
  • an inexpensive and permanently functional magnet device can be implemented which - in contrast to the use of an electromagnet - does not need another energy source for its operation.
  • Particularly strong permanent magnets made from ferrite or from iron-cobalt-nickel alloy or from neodymium-iron-boron or samarium-cobalt alloy are particularly suitable for realizing a static magnetic field BO.
  • the nuclear spins are excited as a result of the irradiation of energy in the form of an excitation signal B1 generated by means of the magnetic field-sensitive detection device, ie in the form of an electromagnetic field, in particular an alternating electromagnetic field, for example a pulsed magnetic field in at least a portion of the measurement sample, which is also penetrated by the static magnetic field BO.
  • the electromagnetic fields BO and B1 characterize in their overlapping field a sensitive area of the NMR spectrometer at the point where the fields are perpendicular to one another.
  • the magnetic field-sensitive detection device is used to send an excitation signal B1 and to detect the at least one nuclear magnetic resonance signal.
  • the magnetic field sensitive detection device comprises at least one RF coil for sending the excitation signal B1 and at least one RF coil for receiving the nuclear magnetic resonance signal (ie the “echo signal”).
  • at least two RF coils are provided in the NMR spectrometer.
  • An RF coil (high frequency coil) can in particular be operated with a frequency in the megahertz range. For example, the frequency is below 900 mega-hertz, in particular below 200 mega-hertz and especially below 50 mega-hertz.
  • the magnetic field-sensitive detection device comprises a single RF coil for transmitting the excitation signal B1 and for receiving the nuclear magnetic resonance signal. In this way, a particularly compact NMR spectrometer can be realized.
  • Magnetic field sensitive is to be understood as meaning that the magnetic field sensitive detection device is indirectly magnetic field sensitive - for example using MEMS sensors, sensors based on nitrogen defects or the like - and / or directly magnetic field sensitive - for example by means of a magnetic field coil, a Hall Sensor or the like - measures.
  • Provided is to be understood in particular as specifically “programmed”, “designed” and / or “set up”.
  • the fact that an object is “intended” for a specific function should be understood in particular to mean that the object fulfills and / or executes this specific function in at least one application and / or operating state or is designed to perform the function fulfill.
  • NM R spectroscopy means that the determined nuclear magnetic resonance signals can be determined in such high quality that a determined time signal can be Fourier transformed and the frequency components contained can be evaluated according to frequency and amplitude. Such an evaluation in In the context of NMR spectroscopy, it is assumed that the influence of a location-dependent and / or location-independent and / or a static inhomogeneity of the magnetic field B0 on the resonance frequency is particularly small in order to be able to measure an actual effect of binding states and thus a molecular structure of the measurement sample do.
  • NMR spectroscopy differs from so-called NMR relaxometry or time-domain NMR. Differences in measured resonance frequencies amount to a few ppm (“parts per million”, ie a few mT), in particular to significantly less than 0.1 ppm (when measuring a spectral range of, for example, 10 ppm). In order to be able to resolve these frequency differences, the static magnetic field B0 must have an extremely high field homogeneity.
  • location-dependent magnetic field deviations in homogeneities of the magnetic field
  • the measurement volume must be limited to well below 0.1 ppm (depending on the desired spectral resolution) in order to resolve chemical shifts and thus to be able to carry out meaningful NMR spectroscopy measurements.
  • “Mobile” means that the NMR spectrometer is specially set up to carry out NMR spectroscopy measurements while it is in motion.
  • the movement can take place in the form of translational movements and / or rotational movements.
  • a movement can take place relative to an external magnetic field, for example the earth's magnetic field.
  • a speed of movement - up to which the "mobile" NMR spectrometer can carry out useful NMR spectroscopy measurements - is greater than 1 mm / s (for example installed in a ship), in particular greater than 1 m / s (for example in installed in a car), in particular greater than 100 m / s (for example installed in an airplane).
  • repetitive movements such as vibrations or periodically executed movements, for example a translational and / or rotational movement of a wrist watch worn on the wrist, can also be understood as a mobile application.
  • the mobile NMR spectrometer is consequently set up to operate correctly even in the presence of changes in the magnetic field - ie under the influence of magnetic field inhomogeneities that occur to enable and furthermore to record nuclear magnetic resonance signals in such a high quality that a determined time signal can be Fourier transformed and the frequency components contained can be evaluated according to frequency and amplitude.
  • Changes in the magnetic field are time-dependent and, in principle, can be differentiated into location-independent changes in the magnetic field and location-dependent changes in the magnetic field.
  • the term “change in magnetic field” denotes a change in the electromagnetic field (see comment on Maxwell's equations above), in particular a change in the magnetic component of the electromagnetic field.
  • “Location-independent magnetic field changes” are in particular global (ie non-local or non-location-dependent) magnetic field changes AB 0 (t) in which the strength of the magnetic field B0 in the measurement volume - and thus in the measurement sample - varies over time changes regardless of location.
  • the strength of the magnetic field B0 changes by the same amount at every point within the measurement volume.
  • the spatial homogeneity of the magnetic field B0 does not change, only its strength.
  • Possible causes for a location-independent change in the magnetic field are, for example, slow, uniform heating or cooling of the magnetic device or a rotation of the magnetic device with respect to the orientation of the earth's magnetic field.
  • a prevention and / or compensation of the influence of such location-independent magnetic field changes consequently makes it possible to carry out NMR spectroscopy measurements during a movement of the NMR spectrometer relative to the earth's magnetic field as well as under the influence of temperature changes, in particular temperature changes acting on the magnetic device.
  • location-dependent magnetic field changes are to be understood as meaning in particular locally limited or locally different - ie non-global - magnetic field changes AB 0 (t, r) in which the magnetic field B0 depending on the position? (location-dependent) has different changes within the measurement volume. This changes both the homogeneity and the distribution of the field strength of the magnetic field within the measurement volume - and thus in the measurement sample. These location-dependent magnetic field changes represent the more general case. Location-dependent magnetic field changes can arise, in addition to the effects mentioned above, in particular also from the influence of inhomogeneous external magnetic fields or from strong temperature gradients within the magnetic device.
  • an influence of a time-independent magnetic field inhomogeneity of the static magnetic field BO on the at least one detected nuclear magnetic resonance signal is conceivable and can be compensated when evaluating the at least one nuclear magnetic resonance signal. Further explanations on this aspect of the invention can be found below.
  • a combinatorial or superimposed influence of location-dependent magnetic field changes and / or location-independent magnetic field changes and / o the static magnetic field inhomogeneities can also be compensated according to the proposed method according to the invention.
  • the influence of location-independent magnetic field changes that act during the NMR spectroscopy measurement, in particular during the acquisition of the nuclear magnetic resonance signal, can in one example be of the order of magnitude of approx Order of magnitude as a result of a rotation of the NMR spectrometer relative to the earth's magnetic field).
  • location-independent changes in the magnetic field for example as a result of heating of the magnet device, can also have a much higher influence of, for example, 1200 ppm / K for NdFeB magnets or, for example, 350 ppm / K for SmC magnets.
  • During the NMR spectroscopy measurement is to be understood as preventing and / or compensating and / or measuring and / or compensating for an influence that acts at least during a period in which the acquisition of the at least one nuclear magnetic resonance signal (so-called “acquisition time”) takes place is compensated later in an evaluation.
  • acquisition time a period in which the acquisition of the at least one nuclear magnetic resonance signal
  • a time period can also be understood in which excitation pulses (B1, so-called “pulse duration”) are emitted and magnetic resonance signals are recorded (so-called “acquisition time”).
  • the nuclear magnetic resonance signal describes the signal from which the so-called free induction decay (FID) can be determined.
  • FID free induction decay
  • An NMR spectrum can in turn be determined from the free induction decay by Fourier transformation.
  • the method according to the invention according to the first aspect of the invention makes it possible, compared to NMR spectrometers known from the prior art, NMR spectroscopy measurements also under the influence of location-dependent and / or location-independent acting during the NMR spectroscopy measurement, in particular during the acquisition of the nuclear magnetic resonance signal To carry out changes in the magnetic field sensibly by preventing and / or compensating and / or compensating for influences occurring during an evaluation.
  • the determined nuclear magnetic resonance signals can still be determined in such high quality that a determined time signal can be Fourier transformed and the frequency components contained can be evaluated according to frequency and amplitude.
  • the method makes it possible to reduce influences of the above-mentioned strength on the resonance frequency to be detected or on the already detected resonance frequency, in particular to minimize them, and thus to compensate for them or to avoid them entirely.
  • An actual influence of binding states and thus a molecular structure of the measurement sample can advantageously also be measured and sensibly evaluated during a mobile - moving or moving - use of the NMR spectrometer. In particular, this enables unrestricted, i.e. high-quality, NMR spectroscopy measurements with a moving - mobile - NMR spectrometer.
  • a control device carrying out the method is set up to have an influence of location-dependent effects acting during the NMR spectroscopy measurement, in particular during the acquisition of the nuclear magnetic resonance signal and / or to compensate for location-independent magnetic field changes to nuclear magnetic resonance signals detected by means of the magnetic field-sensitive detection device.
  • the method can be implemented, at least partially, in the form of software or in a mixture of software and hardware.
  • embodiments of the method that are implemented in hardware and / or in software are presented.
  • the method can, at least in part, represent a computer-implemented method that is carried out by means of a processor device, in particular a processor device of the control device.
  • the processor device can also use at least one storage device in which the method is stored, at least in part, as a machine-readable computer program.
  • the computer program contains instructions which, when executed by the processor device, cause the processor device to, at least partially, execute the method for operating the mobile NMR spectrometer.
  • the influence of a change in the magnetic field is determined using sensor data that is recorded, in particular measured, by at least one sensor, the sensor being selected from a list of sensors which includes:
  • Magnetic field-sensitive sensors such as compass, magnetic field sensor, fluxgate magnetometer and Hall sensor;
  • position-sensitive and / or position-sensitive sensors such as GPS, position sensors, odometry sensors and steering angle sensors for a steering wheel or steering wheel;
  • - speed-sensitive and / or acceleration-sensitive sensors such as gyroscope, inertial sensors and acceleration sensors;
  • thermocouples such as IR sensors, bolometers and thermocouples
  • Distance-sensitive sensors such as laser rangefinders, ultrasonic sensors and radar, ...
  • the acquisition of the sensor data takes place time-resolved during or essentially parallel to the duration of the acquisition of the nuclear magnetic resonance signal.
  • Further sensors which allow the detection of a movement of the NMR spectrometer are conceivable and accessible to the person skilled in the art.
  • an influence of a location-dependent and / or location-independent change in the magnetic field can be determined in a particularly simple manner by measurement technology, with the sensor data in particular being processable at any time in order to prevent and / or compensate for a disruptive influence on a measurement result of the NMR spectroscopy measurement.
  • a magnetic field-sensitive sensor for example a magnetic field probe in the form of an RF coil (so-called “NMR field probes”), can be arranged in or on the measurement volume and provide sensor data on the influence of a magnetic field change.
  • the provision can in particular take place continuously or at least quasi-continuously.
  • the magnetic field-sensitive sensor can measure and provide a time profile of a magnetic field strength, an influence of a location-independent change in the magnetic field being determined from this profile. It is also conceivable to record sensor data on a separate receiving channel of the detection device using a reference sample or on the measurement sample itself, in which the Larmor frequency of the reference sample is continuously measured by evaluating the measurement data.
  • the separate receiving channel of the detection device can mean the measurement of the nuclear magnetic resonance signal of a different type of atom than for the NMR spectroscopy measurement.
  • the other atomic species can be measured simultaneously with the actual NMR spectroscopy measurement on the same channel by means of a broadband receiver. If the Larmor frequency is known at any time, the influences on the nuclear magnetic resonance signal can be compensated for at any time.
  • the influence is ascertained, in particular acquired or measured, using spatially resolved sensor data, the sensor data being acquired spatially resolved by means of a plurality of sensors arranged in a distributed manner.
  • several magnetic field sensitive sensors for example magnetic field probes in the form of RF Coils (“field probes”) can be arranged in or around the measurement volume and provide sensor data on a location-dependent influence of a change in the magnetic field.
  • RF Coils RF Coils
  • a plurality of magnetic field-sensitive sensors each record a time profile of the magnetic field strength during the NMR spectroscopy measurement at their respective measurement location. With this sensor data, the influence of a location-dependent change in the magnetic field can be modeled and used for later compensation of an FID.
  • a one-dimensional (length-resolving), two-dimensional (surface-resolving) or three-dimensional (volume-resolving) arrangement of sensors in the form of an ID, 2D or 3D array is conceivable.
  • the number and spatial arrangement of the sensors it is consequently possible to determine a linear, quadratic or cubic resolution of the influence of a location-dependent change in the magnetic field and to model a compensation in different spatial dimensions.
  • the at least one sensor of the executed embodiments can be assigned to the NMR spectrometer (internal or external) or can also be implemented as a sensor external to the NMR spectrometer.
  • the NMR spectrometer internal or external
  • the influence for a future point in time is determined by extrapolation, in particular from already recorded sensor data, to this future point in time, in particular calculated in advance (“anticipated”).
  • an estimate of the influence of a magnetic field change for the future can be carried out based on an influence that has already been determined, in particular based on already existing sensor data (for example sensor data that were recorded in previous minutes, seconds up to previous milliseconds).
  • an influence of a location-dependent and / or location-independent change in the magnetic field as a result of a movement and / or rotation of the mobile NMR spectrometer in relation to the earth's magnetic field can be measured by sensors of the above list for the past and from this - based on a mathematical extrapolation of the sensor data or Based on a mathematical extrapolation of the determined time-dependent influence - a statement for the future can be derived.
  • linear magnetic field changes over time square magnetic field changes over time and / or periodic magnetic field changes can be detected and anticipated.
  • an influence of a magnetic field change can be anticipated or calculated in advance.
  • a change in the geomagnetic field can be estimated and also calculated in advance (extrapolated ) become.
  • the influence is ascertained, in particular recorded or measured, using a reference NMR spectroscopy measurement carried out essentially in parallel with the NMR spectroscopy measurement, in particular essentially in parallel with the acquisition of the at least one nuclear spin resonance signal.
  • a reference NMR spectroscopy measurement carried out essentially in parallel with the NMR spectroscopy measurement, in particular essentially in parallel with the acquisition of the at least one nuclear spin resonance signal.
  • an undisturbed reference nuclear magnetic resonance signal is known.
  • a known reference spectrum for example that of a known substance, can be used to detect the influence of a magnetic field change and / or in principle also an inhomogeneous magnetic field (see below in the third aspect of the invention) during the NMR spectroscopy measurement.
  • the disturbed reference nuclear magnetic resonance signal measured by means of the reference NMR spectroscopy measurement, in particular a reference FI D can be used to calculate or model the influence.
  • any mathematical optimization models can be used to determine the influence as a mathematical parameter d h or as a correction function (a mathematical parameter d h is here equated in effect to a correction function).
  • the proposed embodiment is based on the knowledge that a parameter d h determined by means of a reference NMR spectroscopic measurement or a determined correction function for carrying out the compensation is transferred to a further, essentially parallel measured, NMR spectroscopic measurement of the measurement sample and can be applied.
  • the influence acting on the reference nuclear magnetic resonance signal is assumed to be identical to the influence acting on the nuclear magnetic resonance signal of the measurement sample.
  • the reference NMR spectroscopy measurement is carried out on a reference sample that is separate from the measurement sample. If the material of the measurement sample is known, it is conceivable to design or select the reference sample accordingly. In principle, it is conceivable to keep various reference samples available in order to be able to select a suitable reference sample for the compensation in an application.
  • the reference NMR spectroscopy measurement is carried out on the measurement sample (which is actually of interest) after a marker material has been added to the measurement sample.
  • the measurement sample is subjected to a reference NMR spectroscopy measurement on a predefined, in particular predeterminable, NMR-active core.
  • the reference spectrum can thus be taken from the measurement sample itself (for example measured on a 1H, 13C, 14N, 15N, 19F or another NMR-active nucleus of the measurement sample) or from a separate reference sample or from one added to the measurement sample Reference sample (marker material), the latter being known in principle, ie its undisturbed NMR spectrum is known. It is also conceivable to use several reference spectra on several cores, for example using several RF coils, to measure the influence of location-dependent changes in the magnetic field. As a result, a number of mathematical equations for finding the correction function sought can advantageously be increased.
  • a reference spectrum determined in this way represents, in particular, the FID of a known substance.
  • the influence, in particular after the NMR spectroscopy measurement has been carried out, in particular after the detection of the at least one nuclear magnetic resonance signal, is compensated for during an evaluation of the at least one nuclear magnetic resonance signal.
  • a particularly effective and structurally simple “a posteriori” compensation can be achieved by means of software-based correction of the at least one nuclear magnetic resonance signal take place by calculating the influence of the location-dependent and / or location-independent magnetic field change.
  • no special precautions are necessary for active compensation on the NMR spectrometer.
  • the method can preferably be designed in this way in a computer-implemented manner.
  • the influence is compensated for by calculating the at least one detected nuclear magnetic resonance signal with a correction function, the correction function taking into account a location-dependent change in the magnetic field in the form of a location-dependent phase shift of the nuclear spins and / or a location-independent magnetic field change in the form of a location-independent phase shift in the nuclear spins.
  • offset denotes a computational operation for correcting the acquired nuclear magnetic resonance signal by means of the correction function, whereby the offsetting can take place, for example, by multiplication or also convolution with the correction function. In this way, a particularly efficient, computer-implemented method can be specified.
  • the proposed method allows the influence in the form of a correction function to be included as a known variable in a mathematical equation describing the nuclear magnetic resonance signal and thus to be taken into account, so that the undisturbed, uninfluenced nuclear magnetic resonance signal can be reconstructed from the measured nuclear magnetic resonance signal.
  • a possible implementation of the method is explained below, in which the detected nuclear magnetic resonance signals in the form of FIDs are corrected or compensated for by the influence of a magnetic field change when the nuclear magnetic resonance signals are evaluated.
  • the proposed implementation applies equally to the proposed method according to the first aspect of the invention, the second aspect of the invention and the third aspect of the invention. It is assumed that the influence of a location-independent and / or a location-dependent change in the magnetic field is known - for example, it was measured using sensors as described above.
  • the influence of the magnetic field changes can generally be referred to as AB 0 (r, t) (location-dependent magnetic field change), AB 0 (t) (location-independent magnetic field change) or also as DB 0 (G) (static inhomogeneity).
  • the magnetic field changes AB 0 (r, t) can also be used as resulting frequency changes 6 (r, t) of the nuclear magnetic resonance spectrum can be understood.
  • the terms are therefore used synonymously.
  • a change in the magnetic field BO during the acquisition of the nuclear magnetic resonance signal (during the “acquisition time”, see above) changes the precession frequency of all nuclear spins.
  • a signal component FID n (t) can be received from each volume element V n of the measurement sample. These individual signals are weighted with a local sensitivity S n (r) of the magnetic field-sensitive detection device, for example a receiving coil, and experience a frequency shift 6 (r, t) (here discretized as 6 n (t) depending on the local change in the magnetic field) ) according to: where an FID of a certain substance in a homogeneous magnetic field B0 can be described in a simplified way by:
  • the signal is made up of the characteristic frequencies ⁇ o k of the differently bound nuclei in the test sample and their weightings a k as well as an attenuation due to the so-called T2 decay.
  • the Fourier transformation of FI Dhom (t) corresponds to the undisturbed NMR spectrum of the test sample.
  • the time-dependent frequency 5 (t) describes a time-dependent change in the lar- mor frequency during the FID due to the time-dependent magnetic field change.
  • the influence during the NMR spectroscopy measurement in particular during the acquisition of the at least one nuclear magnetic resonance signal, is actively compensated, in particular prevented, as a function of the determined influence.
  • the influence can be weakened (ie reduced by at least one order of magnitude) by active counter-control and preferably completely compensated for.
  • the influence can be compensated particularly well if it is known (ie dimension, direction) on the basis of the proposed evaluation.
  • the influence is actively compensated for by controlling and / or regulating and / or adapting an electromagnetic superimposition field B2.
  • the influence is actively compensated by energizing a compensation coil.
  • the influence can be actively compensated for by mechanical changes to the magnetic device.
  • a mechanical change in the magnet device includes, for example, changing a distance between magnets, mechanical distortion (compression, shear, torsion or the like) of magnets or the like.
  • by rotating the NMR spectrometer in opposite directions by means of a motorized stage a change in the magnetic field acting in a curve while driving can be counteracted. It is thus possible, please include to keep the static magnetic field B0 generated by means of the magnet device constant and, in particular, homogeneous.
  • these exemplary embodiments are particularly suitable in the case of a location-independent change in the magnetic field.
  • the influence of a location-dependent change in the magnetic field can also be implemented by means of a plurality of electromagnets, for example small coils (“shim coils”), by what is known as “active shimming”.
  • a suitable electric current is applied to the individual electromagnets in order to generate correction fields which, in superposition with the magnetic field B0 of the magnetic device, make the magnetic field B0 homogeneous in the measurement volume and compensate for the influence of a change in the magnetic field.
  • the method according to the invention allows the compensation to be carried out continuously or at least quasi continuously, in particular in real time.
  • Compensation in real time means, in particular, that the processing time until the compensation is carried out is less than 60 seconds, in particular less than 20 seconds, in particular less than 1 second.
  • a particularly precise compensation can be achieved in real time.
  • the influence is avoided and / or compensated by using the sensor data to determine a point in time at which the influence of a location-dependent magnetic field changes and / or a location-independent magnetic field change is relatively small, in particular negligible, the NMR spectroscopy measurement, in particular the acquisition of the at least one nuclear magnetic resonance signal, being carried out at this point in time.
  • “relatively low” is to be understood as the fact that the point in time is selected, in particular anticipated, at which the influence is least effective.
  • a movement pattern can be recognized by means of the sensor data and points in time can be identified from the movement pattern and calculated in advance at which a particularly small or negligible influence can be foreseen, ie extrapolated.
  • the calculation of the points in time could be implemented with suitable algorithms, in particular with methods of self-learning processes, in particular with methods of artificial intelligence.
  • this is based on a method for operating a mobile NMR spectrometer, a static magnetic field B0 being generated during an NMR spectroscopy measurement by means of a magnetic device of the mobile NMR spectrometer and by means of a magnetic field-sensitive detection device of the mobile NMR spectrometer, an excitation signal B1 is sent and at least one nuclear magnetic resonance signal is detected.
  • a combinatorial or superimposed influence of location-dependent magnetic field changes and / or location-independent magnetic field changes and / o the static magnetic field inhomogeneities can also be compensated for according to the proposed method according to the invention according to the second aspect.
  • the inventive method according to the second aspect of the invention it makes it possible compared to the prior art known NMR spectrometers, NMR spectroscopy measurements also under the influence of during the NMR spectroscopy measurement, in particular during the acquisition of the Nuclear magnetic resonance signal, effective location-dependent and / or location-independent magnetic field changes to be sensibly carried out by compensating for influences occurring "a posteriori" when evaluating the nuclear magnetic resonance signals.
  • This means that the nuclear magnetic resonance signals determined during the evaluation after performing the compensation can still be determined in such high quality that a determined time signal can be Fourier transformed and the frequency components contained can be evaluated according to frequency and amplitude.
  • An actual influence of binding states and thus a molecular structure of the measurement sample can advantageously also be measured and sensibly evaluated during a mobile - moving or moving - use of the NMR spectrometer.
  • unrestricted, ie qualitatively high-quality, NMR spectroscopy measurements with a moving - mobile - NMR spectrometer are made possible in this way.
  • a particularly effective and structurally simple “a posteriori” compensation can take place by means of software-based correction of the at least one nuclear magnetic resonance signal by calculating the influence of the location-dependent and / or location-independent magnetic field change.
  • no special precautions are necessary for active compensation on the NMR spectrometer.
  • the method can be designed in this way preferably in a computer-implemented manner.
  • the influence is determined, in particular calculated or evaluated, using the at least one detected nuclear magnetic resonance signal.
  • the influence can also be determined from the nuclear magnetic resonance signal without further recording the influence of a change in the magnetic field by means of sensors using suitable data evaluation methods.
  • the influence is compensated for by offsetting the at least one acquired nuclear magnetic resonance signal with a correction function.
  • a correction function refers to the advantages with regard to the correction function, reference is made to the above text passages in connection with the correction function according to the first aspect of the invention, which apply analogously here.
  • the proposed exemplary embodiments and functions also apply here.
  • the invention is based on the knowledge that the correction function determined by evaluation can then be used to compensate for the influence on the at least one detected nuclear magnetic resonance signal.
  • the correction function is determined from the at least one nuclear magnetic resonance signal, in particular calculated or evaluated, by comparing a characteristic property of the at least one nuclear magnetic resonance signal, in particular a position and / or a line shape of a peak in the nuclear magnetic resonance signal, with a, in particular - Their predetermined or predeterminable expected value with respect to the characteristic property, in particular a target position and / or a target line shape of the peak, a deviation is determined, the correction function being selected such that when the at least one nuclear magnetic resonance signal is offset against the correction function, the Deviation is minimized, in particular becomes zero.
  • a particularly efficient method can be specified in which the correction function is calculated by numerical adaptation.
  • any mathematical optimization models for example parameter variation, “least square” method or the like
  • the correction function is determined from the at least one nuclear magnetic resonance signal, in particular calculated or evaluated, by determining a low-frequency interference and / or a linear change and / or a non-linear change in a time curve of the phase of the at least one nuclear magnetic resonance signal , the correction function being selected such that when the at least one nuclear magnetic resonance signal is offset against the correction function, the low-frequency interference and / or the linear and / or non-linear changes in the phase are minimized, in particular zero.
  • low-frequency denotes a frequency range from 0 Hz (magnetic field change as drift) to 1 kHz (vibrations).
  • phase profiles - for example periodic fluctuations or linear increases or the like on which the phase profile is based - can be used as the basis for determining a low-frequency interference and / or a linear ren and / or non-linear change.
  • a location-independent change in the magnetic field as a linear, quadratic, cubic or periodic change in the phase from a Fl D curve of a detected nuclear magnetic resonance signal.
  • the correction function is determined using a plurality of, in particular sequentially or parallel, acquired nuclear spin resonance signals by determining at least one, in particular time-dependent, difference between the acquired nuclear magnetic resonance signals, the correction function being selected such that at Offsetting the nuclear spin resonance signals with the correction function of at least one, in particular time-dependent, difference is minimized, in particular becomes zero.
  • the determination of the correction function can also be based on a plurality of differences in order to advantageously increase the quality of the correction function. In this way, by comparing nuclear magnetic resonance signals, in particular with undisturbed nuclear magnetic resonance signals as the expected value, a correction function can be determined which, in the case of only slightly disturbed nuclear magnetic resonance signals (e.g.
  • a signal-to-noise ratio, a line width for at least one peak, a position of at least one peak, a height (intensity) of at least one peak, an area of at least one peak is used to determine, in particular time-dependent, differences Peaks or a positional relationship (such as in the case of multiplets caused by coupling) at least one peak, a ratio of a maximum amplitude to an amplitude at the end of a Fl D curve and / or a partial or entire Fl D curve of the nuclear magnetic resonance signals is evaluated.
  • At least one recorded nuclear magnetic resonance signal is excluded from the plurality of recorded nuclear magnetic resonance signals when determining the correction function.
  • a Fourier transform of a summed signal - in which, in principle, FIDs of a plurality of recorded nuclear magnetic resonance signals are summed up - individual nuclear magnetic resonance signals can be specifically excluded from the summation in order to achieve an improved signal-to-noise ratio.
  • This is particularly advantageous when a temporary influence of a magnetic field change with a duration in the time domain of one or a few individual detected nuclear magnetic resonance signals acts, the influence leading to a strong change in the information content in the corresponding nuclear magnetic resonance signal.
  • a nuclear magnetic resonance signal is excluded if there is an unexpected deviation of the nuclear magnetic resonance signal from the further nuclear magnetic resonance signals of the plurality of detected nuclear magnetic resonance signals.
  • An unexpected deviation can be recognized by comparing the FIDs of the K spin resonance signals or the Fourier-transformed NMR spectra. For example, a signal-to-noise ratio of at least one peak in a respective NMR spectrum, a line width of at least one peak, a position of at least one peak, a height (intensity) or area (integrated intensity) of at least one peak or a positional relationship for each detected nuclear magnetic resonance signal of the plurality can be compared and excluded from the evaluation in the event of an unexpected deviation.
  • a threshold value observation in order to specifically exclude nuclear magnetic resonance signals from the evaluation based on a percentage deviation.
  • the threshold value observation can relate, for example, to a predefined, in particular predeterminable, expected value and / or to the respective further nuclear magnetic resonance signals of the plurality (mutual deviation).
  • a Evaluation of a nuclear magnetic resonance signal with respect to several, in particular preceding, further nuclear magnetic resonance signals allows an advantageous evaluation of individual nuclear magnetic resonance signals even in the case of dynamic magnetic field changes.
  • a threshold value with regard to a change in position of a peak can be approx.
  • 1% corresponding to 0.1 ppm at 10 ppm spectral width
  • a threshold value with regard to an integrated intensity (area integral) of a peak can be approx. 10%. If an individual nuclear magnetic resonance signal deviates by more than this threshold value from the other nuclear magnetic resonance signals, in one embodiment the nuclear magnetic resonance signal is excluded from the evaluation.
  • this is based on a method for operating an NMR spectrometer, a static magnetic field B0 being generated during an NMR spectroscopy measurement on a measurement sample by means of a magnetic device of the mobile NMR spectrometer and by means of magnetic field-sensitive detection -
  • the device of the NMR spectrometer sends an excitation signal B1 and at least one nuclear magnetic resonance signal is detected.
  • an influence of a magnetic field inhomogeneity of the static magnetic field B0 on the at least one detected nuclear magnetic resonance signal is compensated for when the at least one nuclear magnetic resonance signal is evaluated.
  • a magnetic field inhomogeneity is to be understood in particular as a static magnetic field inhomogeneity DB 0 (G) ZU, in which the magnetic field B0 has different amounts depending on the position r within the measurement volume.
  • the magnetic field inhomogeneity remains static during the NMR spectroscopy measurement, ie it does not change over time.
  • Static magnetic field inhomogeneities can be present, for example, when using an inherently inhomogeneous magnet device.
  • an originally homogeneous magnetic field can become inhomogeneous, for example due to the introduction of a sample into the measurement volume, due to superimposition with inhomogeneous, in particular external, magnetic fields (e.g. due to magnetic objects in the vicinity of the NMR spectrometer), or due to aging or strong temperature gradients inside the magnet device. Compensation for the influence of such static magnetic field inhomogeneities makes it possible to carry out NMR spectroscopy measurements with a principally inhomogeneous magnetic device and / or under the influence of the location-dependent magnetic field changes acting during an NMR spectroscopy measurement.
  • the nuclear spin resonance signal must have been measured beforehand in order to subsequently compensate for the influence of the change in the magnetic field during the evaluation.
  • the influence is compensated for using a B0 field distribution map (which can also be referred to as an inhomogeneity map or a frequency shift map).
  • a B0 field distribution map (which can also be referred to as an inhomogeneity map or a frequency shift map).
  • the B0 field distribution map is provided to a control device performing the method.
  • the B0 field distribution map is known from the construction of the magnetic device.
  • a so-called “single-sided” magnet device can be constructed in such a way that the magnetic field B0 is homogeneous in two spatial dimensions and in a third dimension has a linear field gradient.
  • the BO field distribution map can already have been determined during the manufacture of the magnet by means of simulation or by measurement and stored for provision in this process.
  • the B0 field distribution map is determined, in particular recorded or measured, using spatially resolved sensor data, the sensor data being spatially resolved by means of a plurality of distributed magnetic field-sensitive sensors.
  • Magnetic field-sensitive sensors have already been discussed above - the statements also apply here.
  • a one-dimensional (length-resolving), two-dimensional (surface-resolving) or three-dimensional (volume-resolving) arrangement of the sensors in the form of an ID, 2D or 3D array is conceivable.
  • the B0 field distribution map can be refined by interpolating sensor data.
  • the B0 field distribution map is determined by means of an imaging gradient system.
  • Such gradient systems are known in principle for imaging MRT measuring systems. It is conceivable to generate a magnetic field gradient in a defined spatial direction by means of one, in particular two, in particular by means of three coils. At least two (for example three-dimensional) images of a sample, in particular the measurement sample, are recorded, the measurements differing in their echo time TE, ie the time between the excitation pulse and signal recording. The phase difference between the two images is evaluated, ie how much the phase of the nuclear spins has changed at each location of the sample within the echo time difference.
  • the B0 field distribution map is determined immediately before and / or after the magnetic resonance signal is detected. “Immediately” means that a time interval between the NMR spectroscopy measurement and the recording of the B0 field distribution map is less than 60 seconds, in particular less than 20 seconds, and in particular less than 1 second amounts to. In particular, it is conceivable to use the gradient system to record the BO field distribution map directly in the presence of the measurement sample, ie on the measurement sample.
  • the influence is determined, in particular recorded or measured, using a reference NMR spectroscopy measurement that has been carried out.
  • a reference NMR spectroscopy measurement that has been carried out.
  • an undisturbed reference nuclear magnetic resonance signal is known.
  • a known reference spectrum for example a known substance, can be used to detect the influence of an inhomogeneous magnetic field.
  • the disturbed reference nuclear magnetic resonance signal measured by means of the reference NMR spectroscopy measurement, in particular a reference FID can - as already stated above - be used to calculate or model the influence.
  • the undisturbed nuclear magnetic resonance signal FID hom (t) can be reconstructed mathematically using this formula.
  • any mathematical models to specific optimization are used to influence a mathematical parameter to determine d h or as a correction function.
  • the proposed embodiment is based on the knowledge that a parameter d h determined by means of a reference NMR spectroscopic measurement or a determined correction function for performing the compensation can be transferred and applied to a further, essentially parallel measured NMR spectroscopic measurement .
  • the reference NMR spectroscopy measurement is carried out on a reference sample that is separate from the measurement sample.
  • the reference sample is measured at the same point at which the measurement sample is also measured. This can be, for example can be achieved by means of a folding mechanism in the measurement volume, the reference sample being automatically folded away when the measurement sample is inserted.
  • the reference NMR spectroscopy measurement is carried out on the measurement sample (actually to be measured) after a marker material has been added to the measurement sample.
  • the measurement sample is subjected to a reference NMR spectroscopy measurement on a predefined, in particular predeterminable, NMR-active core.
  • the reference spectrum can thus be taken from the measurement sample itself (for example measured on a 1H, 13C, 14N, 15N, 19F or another NMR-active nucleus of the measurement sample) or from a separate reference sample or from one added to the measurement sample Reference sample (marker material). It is also conceivable to use several reference spectra on several cores, in particular with several RF coils, to measure the influence of location-dependent changes in the magnetic field. As a result, a number of mathematical equations for finding the correction function sought can advantageously be increased.
  • the influence is compensated for by offsetting the at least one acquired nuclear magnetic resonance signal with a correction function.
  • a correction function refers to the advantages with regard to the correction function, reference is made to the above text passages in connection with the correction function according to the first aspect of the invention, which apply analogously here.
  • the proposed exemplary embodiments and functions also apply here.
  • the invention is based on the knowledge that the correction function determined by evaluation can then be used to compensate for the influence on the at least one detected nuclear magnetic resonance signal.
  • the influence during the NMR spectroscopy measurement in particular during the acquisition of the at least one nuclear magnetic resonance signal, is actively compensated as a function of the determined influence.
  • the influence is actively compensated for by controlling and / or regulating and / or adapting an electromagnetic superimposition field B2.
  • the invention consequently makes it possible, compared to NMR spectrometers known from the prior art, to carry out NMR spectroscopy measurements even under the influence of location-dependent and / or location-independent magnetic field changes that act during the NMR spectroscopy measurement, in particular during the acquisition of the nuclear magnetic resonance signal.
  • This can be done using sensors (first aspect of the invention) and / or solely using the at least one detected nuclear magnetic resonance signal (second aspect of the invention).
  • the invention also allows NMR spectroscopy measurements to be carried out in inhomogeneous magnetic fields (third aspect of the invention). In particular, unrestricted, ie high-quality, NMR spectroscopy measurements with a moving - mobile - NMR spectrometer are made possible in this way.
  • Such an NMR spectrometer can advantageously be operated in association with moving objects, for example on people (implants, wearables) in vehicles, aircraft, ships or the like, as well as in environments with magnetic field fluctuations and / or temperature fluctuations.
  • an “a posteriori” compensation can in principle also be combined with an active compensation.
  • compensation according to one of the proposed embodiments can also be combined with passive shielding of the NMR spectrometer (passive compensation), for example with a layer surrounding the NMR spectrometer made of m-metal or an NMR spectrometer surround the RF cage or the like.
  • passive compensation for example with a layer surrounding the NMR spectrometer made of m-metal or an NMR spectrometer surround the RF cage or the like.
  • good shielding can prevent the influence of a change in the magnetic field and simplify the method described.
  • reducing magnetic field changes through active and / or passive compensation can considerably facilitate an “a posteriori” compensation.
  • Active and passive compensation methods can, for example, be used in such a way that a controlled, linear, “slow” BO field change occurs, which enables a simplified “a posteriori” compensation within the framework of a proposed evaluation.
  • a particularly mobile NMR spectrometer with a magnetic device for generating a static magnetic field B0 and with a magnetic field-sensitive detection device for sending an excitation signal B1 and for detecting a nuclear magnetic resonance signal is proposed.
  • the NMR spectrometer has a control device which is set up to carry out one of the methods according to the invention according to the first aspect of the invention and / or according to the second aspect of the invention and / or according to the third aspect of the invention.
  • the statements made with regard to the method according to the invention can be applied analogously to the NMR spectrometer, in particular to the control device.
  • Such an NMR spectrometer can advantageously be operated in association with moving objects, for example on people (implants, wearables), in vehicles, aircraft, ships or the like, as well as in environments with magnetic field fluctuations and / or temperature fluctuations.
  • a vehicle comprising the proposed NMR spectrometer.
  • the vehicle can be, for example, a car, a truck, a construction machine, an agricultural machine, a ship, a submarine, a drone, an aircraft, a spaceship, a bicycle or the like.
  • a mobile data processing device such as a smartphone or a mobile personal device (“personal device”) comprising the proposed NMR spectrometer is proposed.
  • an implant comprising the proposed NMR spectrometer is proposed.
  • a computer program is proposed.
  • the computer program is set up to execute one of the aforementioned methods.
  • the computer program comprises instructions which cause a processor device to execute a corresponding method.
  • Figure 1 is a perspective view of an embodiment of the inventive mobile NMR spectrometer
  • FIG. 2 shows a process diagram of an exemplary embodiment of the process according to the first aspect of the invention
  • FIG. 3 shows a process diagram of a further exemplary embodiment of the method according to the first aspect of the invention
  • FIG. 4 shows a process diagram of another exemplary embodiment of the method according to the first aspect of the invention
  • FIG. 5 shows a process diagram of an exemplary embodiment of the method according to the second aspect of the invention
  • FIG. 6 shows a process diagram of an exemplary embodiment of the process according to the third aspect of the invention.
  • FIG. 7 shows a process diagram of an alternative exemplary embodiment of the process according to the third aspect of the invention.
  • FIG. 8 shows a schematic representation of the compensation of nuclear magnetic resonance signals in accordance with one of the methods according to the invention.
  • FIG. 1 shows a view of an exemplary embodiment of a fiction, contemporary mobile, here hand-held, NMR spectrometer 10 in a perspective representation.
  • the exemplary NMR spectrometer 10 has a housing 12.
  • an input device 14 in the form of actuating elements 14 ', suitable for switching the NMR- Spectrometer 10, for starting and configuring a measurement process and for entering working parameters, housed.
  • an output device 16 for outputting ascertained information and for outputting work parameters in the form of a screen 16 'is provided in the housing 12.
  • the NMR spectrometer 10 has a handle 18 for transporting and guiding it.
  • the NMR spectrometer 10 has an energy storage device (not shown in detail here) in the form of rechargeable batteries.
  • the NMR spectrometer 10 has in particular a magnetic device 20 for generating a magnetic field B0, a magnetic field-sensitive detection device 22 for emitting an excitation signal Bl and for detecting a nuclear magnetic resonance signal, and a control device 24 for controlling the NMR spectrometer 10 and for evaluating by means of the magnetic field-sensitive detection device 22 recorded measurement signals, in particular nuclear magnetic resonance signals.
  • the magnet device 20 is implemented as a permanent magnet.
  • the magnetic field-sensitive detection device 22 is implemented as an RF coil.
  • the NMR spectrometer 10 is designed in such a way that it can record a nuclear magnetic resonance spectrum of a measurement sample 30.
  • the NMR spectrometer 10 also has four magnetic field-sensitive sensors 26, which are positioned in a square array arrangement and thus register an influence of a location-dependent change in the magnetic field by measuring the magnetic field directly.
  • the control device 24 has control electronics comprising means for communication with the other components of the NMR spectrometer 10, for example means for controlling and regulating the magnetic field-sensitive detection device 22 and for activating magnetic field-sensitive sensors 26
  • the computer program is set up to execute a method as shown in FIGS. 2-6 and comprises instructions which cause the processor device to execute the corresponding method.
  • the control device 24 is thus set up here to carry out a method according to the first, second and third aspect of the invention.
  • the control device 24 is set up to control the influence of location-dependent magnetic field changes acting during an NMR spectroscopy measurement and of location-independent magnetic field changes. to compensate changes and static magnetic field inhomogeneities of the magnetic field BO generated by means of the magnetic device 20 to magnetic field-sensitive detection device 22 detected magnetic resonance signals.
  • FIGS. 2-6 each show an exemplary embodiment of a method for operating a mobile NMR spectrometer 10 according to the first, second and third aspects of the invention.
  • FIG. 2 shows a method diagram 100 which reproduces an exemplary embodiment of the method according to the first aspect of the invention for operating a mobile NMR spectrometer 10.
  • the method is used to operate the mobile NMR spectrometer 10 as shown in Figure 1, with a static magnetic field B0 being generated during an NMR spectroscopy measurement on a measurement sample 30 by means of the magnetic device 20 of the mobile NMR spectrometer 10 and by means of magnetic field-sensitive detection Device 22 is sent an excitation signal B1 and at least one nuclear magnetic resonance signal is detected.
  • the magnetic device 20 is used to generate the static magnetic field B0, which is maintained over a period of time in which at least method steps 104 and 106 are carried out.
  • the sensor data of the four magnetic field-sensitive sensors 26 are continuously read out in order to determine the influence of location-dependent (sensors each output different sensor data) and location-independent magnetic field changes (sensors each output the same sensor data) in a spatially resolved manner.
  • the continuous reading takes place over a period of time in which at least method step 106 is carried out.
  • this determination of the influence for example to increase the accuracy by averaging - it is conceivable to determine the influence using a reference NMR spectroscopy measurement carried out at least during the period in which method step 106 is carried out (here not shown separately) and used for compensation.
  • the reference NMR spectroscopy measurement can be carried out, for example, on a reference sample separate from the measurement sample (also not shown here).
  • a mean value of the influence can be formed and an accuracy in the determination of the influence can be increased in this way.
  • an excitation signal B1 is sent by means of the magnetic field-sensitive detection device 22 of the mobile NMR spectrometer 10 and a nuclear spin resonance signal is recorded from the measurement sample.
  • the change in the magnetic field after the NMR spectroscopy measurement has been carried out ie after method steps 106) is compensated for in the evaluation of the nuclear magnetic resonance signals.
  • the (superimposed) influence of location-dependent and location-independent magnetic field changes and magnetic field inhomogeneities of the magnetic field B0 on the at least one recorded nuclear magnetic resonance signal is determined from the sensor data recorded in method step 104 and a correction function is calculated, with the correction function takes into account the changes in the magnetic field and the magnetic field inhomogeneity in the form of a location-dependent phase shift of the nuclear spins or in the form of a location-independent phase shifts of the nuclear spins.
  • the influence is then compensated for by offsetting with the calculated correction function. In principle, the process can be carried out repeatedly.
  • FIG. 3 shows a process diagram 200 which reproduces a further exemplary embodiment of the process according to the first aspect of the invention for operating a mobile NMR spectrometer 10.
  • the magnetic device 20 In a first method step 202, the magnetic device 20 generates the static magnetic field B0, which is maintained over a period of time in which at least method steps 204 and 206 are carried out.
  • the sensor data of the four magnetic field-sensitive sensors 26 are continuously read out in order to determine the influence of a location-independent change in the magnetic field by averaging the sensor data. During the continuous readout, time-dependent sensor data and, from this, a time-dependent influence of the magnetic field change are determined.
  • an influence “into the future” effective for the time at which method step 206 is carried out is extrapolated, so that the Influence is then known for this point in time and can be used as the basis for the active compensation at least during the execution of method step 206.
  • an excitation signal B1 is sent by means of the magnetic field-sensitive detection device 22 of the mobile NMR spectrometer 10 and a nuclear magnetic resonance signal is recorded from the measurement sample.
  • the extrapolated influence of the magnetic field change is compensated by, in particular continuously, adapting the current supply to a compensation coil. It should be pointed out that the method here can run in a continuous loop, shown by the dashed arrow.
  • FIG. 4 shows a process diagram 300 which reproduces a further exemplary embodiment of the process according to the first aspect of the invention for operating a mobile NMR spectrometer 10.
  • the magnetic device 20 generates the static magnetic field B0, which is maintained over a period of time in which at least method steps 304 to 308 are carried out.
  • the sensor data of a magnetic field-sensitive sensor 26 are continuously read out in order to determine the influence of a location-independent change in the magnetic field from the sensor data. During the continuous readout, time-dependent sensor data and, from this, a time-dependent influence of the change in the magnetic field are determined.
  • a point in time is determined at which the influence of the location-independent change in the magnetic field is (presumably) relatively small, in particular negligible. If this point in time is reached, an excitation signal B1 is sent in method step 308 by means of the magnetic field-sensitive detection device 22 of the mobile NMR spectrometer 10 and a nuclear magnetic resonance signal is recorded from the measurement sample.
  • an excitation signal B1 is sent in method step 308 by means of the magnetic field-sensitive detection device 22 of the mobile NMR spectrometer 10 and a nuclear magnetic resonance signal is recorded from the measurement sample.
  • a method diagram 400 is shown that an embodiment of a method according to the second aspect of the invention for operating a mobile NMR spectrometer 10 reproduces.
  • the method is used to operate a mobile NMR spectrometer 10 as shown in Figure 1, with a static magnetic field B0 being generated during an NMR spectroscopy measurement on a measurement sample 30 by means of the magnetic device 20 of the mobile NMR spectrometer 10 and by means of a magnetic field sensitive Detection device 22 sends an excitation signal B1 and at least one nuclear magnetic resonance signal is detected.
  • the magnetic device 20 generates the static magnetic field B0, which is maintained over a period of time in which at least method steps 404 and 406 are carried out.
  • an excitation signal B1 is sent by means of the magnetic field-sensitive detection device 22 of the mobile NMR spectrometer 10 and a nuclear magnetic resonance signal is recorded from the measurement sample.
  • a nuclear magnetic resonance signal is recorded from the measurement sample.
  • an influence of location-dependent and / or location-independent magnetic field changes acting during the NMR spectroscopy measurement, in particular during the acquisition of the at least one nuclear magnetic resonance signal, on the at least one acquired nuclear magnetic resonance signal when evaluating the at least one nuclear magnetic resonance signal and using the at least one he captured magnetic resonance signal compensated. The influence is compensated for by calculating the at least one recorded nuclear magnetic resonance signal with a correction function.
  • the correction function is determined from the at least one nuclear magnetic resonance signal in sub-method step 410 by determining a deviation from a comparison of a position of a peak in the nuclear magnetic resonance signal with an expected value, in particular a target position, the correction function being selected in such a way that when the at least - At least one nuclear magnetic resonance signal with the correction function, the deviation is minimized, in particular becomes zero.
  • the correction function is determined from the at least one nuclear magnetic resonance signal in method step 412 by determining a low-frequency disturbance of a temporal course of the phase of the at least one nuclear magnetic resonance signal, the correction function being selected such that when the at least one nuclear magnetic resonance signal is offset with the correction function, the low frequency interference is minimized, in particular becomes zero.
  • the correction function is determined using a plurality of, in particular sequentially acquired, nuclear magnetic resonance signals by determining at least one difference between the acquired nuclear magnetic resonance signals, the correction function being selected such that when the nuclear magnetic resonance signals are offset against the correction function, the at least one difference is minimized, in particular special zero becomes.
  • a position of at least one peak in the NMR spectrum is evaluated. This process can also be carried out repeatedly.
  • FIG. 6 shows a method diagram 500 that shows an exemplary embodiment of a method according to the third aspect of the invention for operating a (here mobile) NMR spectrometer 10.
  • the method is used to operate a - not necessarily mobile - NMR spectrometer 10 as shown in Figure 1, a static magnetic field B0 being generated during an NMR spectroscopy measurement on a measurement sample 30 by means of the magnetic device 20 of the mobile NMR spectrometer 10 and by means of a magnetic field-sensitive detection device 22, an excitation signal B1 is sent and at least one nuclear spin resonance signal is detected.
  • the magnetic device 20 In a first method step 502, the magnetic device 20 generates the static magnetic field B0, which is maintained over a period of time in which at least method steps 504 and 506 are carried out.
  • the sensor data of the four magnetic field-sensitive sensors 26 are read out and a B0 field distribution map is created therefrom.
  • the B0 field distribution map shows the influence of a static magnetic field inhomogeneity of the magnetic field B0 as a function of location.
  • the B0 field distribution map can also be determined by means of an imaging gradient system.
  • an excitation signal Bl ge is sent by means of the magnetic field-sensitive detection device 22 of the mobile NMR spectrometer 10 and a nuclear magnetic resonance signal is recorded from the measurement sample.
  • the influence of the magnetic field inhomogeneity of the static magnetic field B0 on the at least one detected nuclear magnetic resonance signal is determined when the at least one nuclear magnetic resonance signal is evaluated compensated.
  • a correction function is set up, by means of which the at least one nuclear magnetic resonance signal is compensated for the influence of the magnetic field inhomogeneity. This procedure can also be carried out repeatedly.
  • FIG. 7 shows a method diagram 600 that reproduces an exemplary embodiment of a method in accordance with the third aspect of the invention that is alternative to method 500.
  • the magnetic device 20 In a first method step 602, the magnetic device 20 generates the static magnetic field BO, which is maintained over a period of time in which at least method steps 604 and 606 are carried out.
  • an influence of the magnetic field inhomogeneity is determined using a reference NMR spectroscopy measurement that has been carried out.
  • the reference NMR spectroscopy measurement is carried out on a reference sample that is separate from the measurement sample.
  • an excitation signal B1 is sent by means of the magnetic field-sensitive detection device 22 of the mobile NMR spectrometer 10 and a nuclear magnetic resonance signal is recorded from the measurement sample.
  • the change in the magnetic field after the NMR spectroscopy measurement has been carried out is compensated for in the evaluation of the nuclear magnetic resonance signals.
  • the influence of the magnetic field inhomogeneity acting during the NMR spectroscopy measurement on the at least one recorded nuclear magnetic resonance signal is first determined from the sensor data recorded in method step 604, and a correction function is calculated . taken into account in the form of a location-independent phase shift of the nuclear spins.
  • the influence is then compensated for by offsetting with the calculated correction function. This procedure can also be carried out repeatedly.
  • FIG. 8 shows a schematic representation of the compensation of nuclear magnetic resonance signals in accordance with one of the methods according to the invention.
  • Figure 8a is a uncompensated NMR spectrum is shown, which can be compensated for, for example, by means of an “a posteriori” compensation regarding the influence of a location-dependent or location-independent magnetic field change or regarding the influence of a static magnetic field inhomogeneity of the magnetic field BO in relation to the undisturbed NMR spectrum shown in FIG. 8b can.

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  • High Energy & Nuclear Physics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • General Life Sciences & Earth Sciences (AREA)
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  • Engineering & Computer Science (AREA)
  • Signal Processing (AREA)
  • Magnetic Resonance Imaging Apparatus (AREA)

Abstract

L'invention concerne un procédé de fonctionnement d'un spectromètre RMN mobile (10), un champ magnétique statique B0 étant produit sur un échantillon de mesure (30) pendant une mesure de spectroscopie RMN au moyen d'un dispositif magnétique du spectromètre RMN mobile (20), et un signal d'excitation B1 est transmis au moyen d'un dispositif de détection sensible au champ magnétique du spectromètre RMN mobile (22) et au moins un signal de résonance magnétique nucléaire est saisi. Selon l'invention, une influence des variations du champ magnétique dépendant de l'emplacement et/ou des variations du champ magnétique indépendants de l'emplacement qui se produisent pendant la mesure de spectroscopie RMN, en particulier pendant la capture dudit au moins un signal de résonance magnétique nucléaire, sur ledit au moins un signal de résonance magnétique nucléaire capturé est déterminée à l'aide des données de capteur d'au moins un capteur (26) et est évitée et/ou compensée. L'invention concerne également un spectromètre RMN mobile (10).
EP20775858.2A 2019-10-30 2020-09-21 Procédé de correction de l'influence de variations du champ magnétique pour des mesures effectuées au moyen d'un spectromètre rmn mobile Pending EP4052058A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
DE102019216755.1A DE102019216755A1 (de) 2019-10-30 2019-10-30 Verfahren zum Betrieb eines NMR-Spektrometers sowie NMR-Spektrometer
DE102019216761.6A DE102019216761A1 (de) 2019-10-30 2019-10-30 Verfahren zum Betrieb eines NMR-Spektrometers sowie NMR-Spektrometer
DE102019216759.4A DE102019216759A1 (de) 2019-10-30 2019-10-30 Verfahren zum Betrieb eines NMR-Spektrometers sowie NMR-Spektrometer
PCT/EP2020/076259 WO2021083580A1 (fr) 2019-10-30 2020-09-21 Procédé de correction de l'influence de variations du champ magnétique pour des mesures effectuées au moyen d'un spectromètre rmn mobile

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EP4052058A1 true EP4052058A1 (fr) 2022-09-07

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CN113960505B (zh) * 2021-10-28 2022-08-09 中国地质大学（武汉） 一种多传感器协同测量的互干扰抑制方法及存储介质

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5382904A (en) * 1992-04-15 1995-01-17 Houston Advanced Research Center Structured coil electromagnets for magnetic resonance imaging and method for fabricating the same
DE102015226168A1 (de) * 2015-12-21 2017-06-22 Robert Bosch Gmbh Verwendung eines Messgeräts zur Untersuchung von Bestandteilen eines menschlichen oder tierischen Körpers
US11439313B2 (en) * 2016-05-16 2022-09-13 Bitome, Inc. Small form factor digitally tunable NMR in vivo biometric monitor for metabolic state of a sample
DE102017210700A1 (de) * 2017-06-26 2018-12-27 Robert Bosch Gmbh Verfahren zum automatisierten Quantifizieren eines Analyten sowie NMR-Messgerät zur Durchführung des Verfahrens
US20210141036A1 (en) * 2017-07-06 2021-05-13 Terence Cosgrove Portable nmr probe and nmr apparatus

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