DE102019216759A1 - Method for operating an NMR spectrometer and an NMR spectrometer - Google Patents

Abstract

A method for operating a mobile NMR spectrometer is proposed, a static magnetic field B0 being generated during an NMR spectroscopy measurement using a magnetic device of the mobile NMR spectrometer and an excitation signal B1 being generated using a magnetic field-sensitive detection device of the mobile NMR spectrometer According to the invention, an influence of location-dependent magnetic field changes and / or location-independent magnetic field changes acting during the NMR spectroscopy measurement, in particular from during the acquisition of the at least one nuclear magnetic resonance signal, on the at least one acquired nuclear magnetic resonance signal after the NMR spectroscopy measurement has been carried out, in particular after detection of the at least one nuclear magnetic resonance signal, compensated during an evaluation of the at least one nuclear magnetic resonance signal. Furthermore, a mobile NMR spectrometer is proposed.

Description

State of the art

From the prior art, transportable, that is, in principle movable due to their size and weight, NMR measuring devices with spectroscopic resolution are known, see for example from “Benchtop NMR spectrometers in academic teaching”, Susanne D. Riegel, Garett M. Leskowitz, Application Chemistry, Nanalysis Corp., Canada (DOI: 10.1016 / j.trac.2016.01.001). Such NMR spectrometers work on the basis of an initial calibration in which a magnetic field that is as homogeneous as possible B0 is adjusted, for example by so-called "active shimming" using electromagnetic coils. Before and during the NMR spectroscopy measurements following the calibration, it must be ensured that the NMR spectrometer remains stationary, ie stationary, and thus the magnetic field B0 does not change at the location of the measurement sample due to a change in 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 µT) (cf. "Spin Dynamics" Malcolm H. Levitt, Wiley 2008 ). Moving the NMR spectrometer would destroy a calibration that was carried out beforehand.

Furthermore, compact NMR spectrometers are known, for example from "Scalable NMR spectroscopy with semiconductor chips", Dongwan Ha, Jeffrey Paulsen, Nan Sun, Yi-Qiao Song, Donhee Ham, Proceedings of the National Academy of Sciences August 2014 (DOI: 10.1073 / pnas.1402015111). Even with such compact NMR spectrometers, a mobile application - while maintaining a (almost) perfectly homogeneous, unchangeable magnetic field for 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 BO field.

Disclosure of the invention

According to a first aspect of the invention, this is based on a method for operating a mobile NMR spectrometer, with a static magnetic field during an NMR spectroscopy measurement on a measurement sample by means of a magnetic device of the mobile NMR spectrometer B0 is generated and an excitation signal is generated by means of a magnetic field-sensitive detection device of the mobile NMR spectrometer B1 sent and at least one nuclear magnetic 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 prevented on the at least one acquired nuclear magnetic resonance signal using sensor data from at least one sensor and / or is compensated.

An NMR spectrometer is to be understood as a measuring device which has 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. Furthermore, further, in particular external, components can be included which are necessary and / or useful for measuring NMR spectra by means of the NMR spectrometer. Such components can represent, for example, an input 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 mode of operation of the NMR spectrometer is based on the nuclear physical effect, in which the atomic nucleus of a measurement sample is placed in the magnetic field B0 electromagnetic alternating fields in the form of the excitation signal B1 absorb and then emit in the form of the nuclear magnetic resonance signal. The nuclear magnetic 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, especially static, first magnetic field B0 . In particular, the nuclear spins of the atomic nuclei in the measurement sample are generated by the first magnetic field B0 aligned. Becomes energy in the form of an electromagnetic excitation signal B1 , in particular an electromagnetic alternating field, for example a pulsed magnetic field, irradiated onto the atomic nuclei, which is in resonance with the Larmor precession whose nuclear spins are in resonance (energy quanta), the atomic nuclei can orient their spins relative to the static magnetic field B0 change 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. Equivalently, the emission of energy quanta leads to a return of the excited nuclear spins to another, Lower energy level, for the emission of an electromagnetic alternating field, which can be detected as a nuclear magnetic resonance signal by means of a device for detecting a change in the magnetic field, in particular by means of the magnetic field-sensitive detection device. Excitation of atomic nuclei should in particular mean that the energy and irradiation duration of the irradiated 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 B0 Field (transverse magnetization). Furthermore, it is assumed in the following that in particular variable magnetic fields are coupled with electric fields (cf. Maxwell's equations), so that no distinction is made between electric field and magnetic field. For the excitation of nuclear magnetic resonance effects, 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 B0 in the test sample to be examined. The magnet device is set up to generate a magnetic field B0 to provide or generate a magnetic field strength of more than 0.1 Tesla, in particular of more than 1.5 Tesla and very particularly of more than 5 Tesla. The magnetic field B0 extends in a volume in and / or around the magnet device. The static magnetic field generated by the magnet device B0 serves to align the nuclear spins of the atomic nuclei present in the measurement sample (in the said volume) in the sense that the nuclear spins are located on the magnetic field lines of the static magnetic field due to their magnetic nuclear spin moment B0 align, especially precessing around the magnetic field lines of the magnetic field. In one embodiment of the NMR spectrometer, 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 B0 can be generated. Using a permanent magnet, a cost-effective and permanently functional magnet device can be realized which - in contrast to the use of an electromagnet - does not require a further energy source for its operation. They are particularly suitable for realizing a static magnetic field B0 Particularly strong permanent magnets, made from ferrites or from iron-cobalt-nickel alloy or from neodymium-iron-boron or samarium-cobalt alloy. The nuclear spins are excited as a result of the irradiation of energy in the form of an excitation signal generated by means of the magnetic field-sensitive detection device B1 , ie in the form of an electromagnetic field, in particular an electromagnetic alternating field, for example a pulsed magnetic field in at least a portion of the measurement sample that is also affected by the static magnetic field B0 is interspersed. Characterize the electromagnetic fields B0 and B1 a sensitive area of the NMR spectrometer in its overlapping field 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 the acquisition of the at least one nuclear magnetic resonance signal. In one embodiment of the NMR spectrometer, 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”). In this way, at least two RF coils are provided in the NMR spectrometer. An RF coil (high frequency coil) can in particular be operated at a frequency in the mega-Hertz range. For example, the frequency is below 900 mega-hertz, in particular below 200 mega-hertz and very particularly below 50 mega-hertz. Alternatively or additionally, the magnetic field-sensitive detection device comprises a single RF coil for sending the excitation signal B1 and for receiving the nuclear magnetic resonance signal. In this way, a particularly compact NMR spectrometer can be realized. It is also conceivable to design one or more RF coils in such a way that they can excite nuclear spins at several frequencies and receive nuclear magnetic resonance signals (broadband NMR). In this way, nuclear magnetic resonance signals from different atomic nuclei (for example 13C, 1H or the like) can be excited and received. “Magnetic field sensitive” is understood to mean 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 is to 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 fulfill the function.

In this document, “NMR 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 the context of NMR spectroscopy assumes that there is an influence of a location-dependent and / or location-independent and / or also a static inhomogeneity of the magnetic field B0 on the resonance frequency is particularly small in order to make an actual effect of binding states and thus a molecular structure of the measurement sample measurable. Here, in technical terminology, NMR spectroscopy (differentiation between the Larmor frequencies of nuclei in different bond states / molecules) 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 µT), 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 must B0 have an extremely high field homogeneity. In particular, location-dependent magnetic field deviations (inhomogeneities of the magnetic field) in 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. In particular, a movement can take place relative to an external magnetic field, for example to the earth's magnetic field. In particular, a speed of movement - up to which the “mobile” NMR spectrometer can carry out meaningful 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 a Cars built in), especially greater than 100 m / s (for example built in an airplane). Alternatively or in addition, in particular, repetitive movements such as vibrations or periodically executed movements, for example a translational and / or rotational movement of a wristwatch worn on the wrist, can also be understood as a mobile application. The mobile NMR spectrometer is therefore set up to enable correct operation even in the presence of changes in the magnetic field - i.e. under the influence of magnetic field inhomogeneities - and to continue to record nuclear magnetic resonance signals in such high quality that a determined time signal is Fourier transformed and the frequency components contained are evaluated according to frequency and amplitude can.

(ortsabhängig) innerhalb des Messvolumens unterschiedliche Änderungen aufweist. Hierbei ändert sich sowohl die Homogenität als auch die Verteilung der Feldstärke des Magnetfelds innerhalb des Messvolumens - und somit in der Messprobe. Diese ortsabhängigen Magnetfeldänderungen stellen den allgemeineren Fall dar. Ortsabhängige Magnetfeldänderungen können, neben oben genannten Effekten, insbesondere auch durch Einfluss inhomogener externer Magnetfelder oder durch starke Temperaturgradienten innerhalb der Magnetvorrichtung entstehen.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 expression “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 to be understood in particular as global (ie non-local or non-location-dependent) magnetic field changes ΔB ₀ (t), in which the strength of the magnetic field changes B0 in the measurement volume - and thus in the measurement sample - changes over time, regardless of location. The strength of the magnetic field changes accordingly B0 at every point within the measurement volume by the same amount. 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 while the NMR spectrometer is moving relative to the earth's magnetic field and under the influence of temperature changes, in particular temperature changes acting on the magnetic device. In contrast to this, “location-dependent magnetic field changes” are to be understood as meaning in particular locally limited or locally different - ie non-global - magnetic field changes ΔB ₀ (t, r) in which the magnetic field is present B0 depending on the position $\overrightarrow{\text{r}}$

(depending on location) 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 through the influence of inhomogeneous external magnetic fields or through strong temperature gradients within the magnetic device.

Furthermore, in a further aspect of the invention (third aspect, see below) there is an influence of a time-independent magnetic field inhomogeneity of the static magnetic field B0 on the at least one detected nuclear magnetic resonance signal is conceivable and can be used when evaluating the at least one Nuclear magnetic resonance signal are compensated. Further explanations on this aspect of the invention can be found below.

Furthermore, a combinatorial or superimposed influence of location-dependent magnetic field changes and / or location-independent magnetic field changes and / or static magnetic field inhomogeneities can also be compensated according to the proposed method according to the invention. This includes the most general case of temporally and spatially arbitrary magnetic field changes ΔB ₀ (r, t), i.e. dynamic magnetic field inhomogeneities in which the magnetic field changes B0 both over time and location-dependent (locally) changes, with the magnetic field B0 itself already has magnetic field inhomogeneities.

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 in the order of magnitude of approx. ± 50 ppm assuming a magnetic field B0 of 1 Tesla (for example, an influence of this magnitude can occur as a result of a rotation of the NMR spectrometer relative to the earth's magnetic field). In contrast, in a further example, 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 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”) occurs, and then at an evaluation is compensated. In particular, a period of time can also be understood in which excitation pulses ( B1 , so-called “pulse duration”) and magnetic resonance signals are recorded (so-called “acquisition time”). It is also conceivable to prevent and / or compensate during an entire pulse sequence and / or during an evaluation for the time frame of an entire pulse sequence, comprising a plurality of emitted excitation pulses and recorded nuclear magnetic resonance signals as well as relaxation times in between (so-called “relaxation recovery”). The nuclear magnetic resonance signal describes the signal from which the so-called free induction decay (FID) can be determined. 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 enables, compared to the prior art known NMR spectrometers, NMR spectroscopy measurements also 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 to be carried out sensibly by preventing and / or compensating and / or compensating for influences occurring during an evaluation. This means that 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. Consequently, the method makes it possible to reduce, in particular to minimize, and thus to compensate or completely avoid influences of the abovementioned strengths on the resonance frequency to be detected or on the already detected resonance frequency. 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 compensate for an influence of location-dependent and / or location-independent magnetic field changes that are active during the NMR spectroscopy measurement, in particular of location-dependent and / or location-independent magnetic field changes on 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. In the following, embodiments of the method that are implemented in hardware and / or in software are presented. In particular, 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. To carry out the method, the processor device can also use at least one memory 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.

• - magnetfeldsensitive Sensoren wie beispielsweise Kompass, Magnetfeldsensor, Fluxgate-Magnetometer und Hall-Sensor;
• - kapazitive Sensoren;
• - positionssensitive und/oder lagesensitive Sensoren wie beispielsweise GPS, Positionssensor, Odometriesensor und Einschlagwinkelsensor für ein Lenkrad oder Steuerrad;
• - geschwindigkeitssensitive und/oder beschleunigungssensitive Sensoren wie beispielsweise Gyroskop, Inertialsensorik und Beschleunigungssensoren;
• - temperatursensitive Sensoren wie beispielsweise IR-Sensor, Bolometer und Thermoelement;
• - abstandssensitive Sensoren wie beispielsweise Laserentfernungsmesser, Ultraschallsensoren und Radar, ...
• - drucksensitive Sensoren,
• - optische Sensoren,
• - spannungssensitive und/oder stromsensitive Sensoren

oder eine Kombination derer.In one embodiment of the method, 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;
• - capacitive sensors;
• 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;
• - temperature-sensitive sensors such as IR sensors, bolometers and thermocouples;
• - Distance-sensitive sensors such as laser range finders, ultrasonic sensors and radar, ...
• - pressure sensitive sensors,
• - optical sensors,
• - voltage-sensitive and / or current-sensitive sensors

or a combination of these.

In one embodiment, the acquisition of the sensor data takes place in a time-resolved manner during or essentially parallel to the duration of the acquisition of the nuclear magnetic resonance signal. Further sensors that allow a movement of the NMR spectrometer to be detected are conceivable and accessible to the person skilled in the art. In this way, an influence of a location-dependent and / or location-independent change in the magnetic field can be determined by measurement technology in a particularly simple manner, 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. In one embodiment, 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. For example, 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 by means of 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. Alternatively, the other atomic species can be measured at the same time as 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.

In one embodiment of the method, 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. In one embodiment, 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 magnetic field change. For example, it is conceivable that 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. In principle, a one-dimensional (length-resolving), two-dimensional (surface-resolving) or three-dimensional (volume-resolving) arrangement of sensors in the form of a 1D, 2D or 3D array is conceivable. By choosing 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.

It should be noted that the at least one sensor of the embodiments described can be assigned to the NMR spectrometer (internal or external) or can also be implemented as a sensor external to the NMR spectrometer. For example, it is conceivable to carry out the method using sensor data from a GPS sensor of a ship, the GPS sensor being connected for signaling purposes to a control device carrying out the method.

In one embodiment of the method, the influence for a future point in time is determined, in particular calculated in advance (“anticipated”), by extrapolation, in particular from already acquired sensor data, to this future point in time. In this way, 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). For example, an influence of a location-dependent and / or location-independent magnetic field change 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 or based on a mathematical extrapolation of the sensor data a mathematical extrapolation of the time-dependent influence determined from it - a statement for the future can be derived. For example, linear magnetic field changes over time, quadratic magnetic field changes over time and / or periodic magnetic field changes can be detected and anticipated. In particular, an influence of a change in the magnetic field can be anticipated or calculated in advance using sensors which can be used to derive a statement about a position, a speed, an acceleration or a temperature of the NMR spectrometer. For example, using a spatially resolved geomagnetic field map ("declination map") in conjunction with a change in position of the NMR spectrometer - measured using sensor data from a GPS sensor - a change in the geomagnetic field can be estimated and also calculated (extrapolated) in advance, assuming inertia in locomotion.

In one embodiment of the method, the influence is determined, 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 magnetic resonance signal. In particular, an undisturbed reference nuclear magnetic resonance signal is known. In this way, a known reference spectrum, for example that of a known substance, can be used to detect the influence of a change in the magnetic field 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 FID, can be used to calculate or model the influence. In particular, any mathematical optimization models can be used to determine the influence as a mathematical parameter δ _n or as a correction function (a mathematical parameter δ _n is equated here in the effect to a correction function). The proposed embodiment is based on the knowledge that a parameter δ _n 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 of the measurement sample . In other words, 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.

In one embodiment of the method, 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. In an alternative or additional embodiment, 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. Again, as an alternative or in addition, the measurement sample is subjected to a reference NMR spectroscopy measurement on a predefined, in particular predefinable, NMR-active core. In one embodiment, 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 a reference sample added to the measurement 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.

In one embodiment of the method, the influence, in particular after the NMR spectroscopy measurement has been carried out, in particular after the acquisition of the at least one nuclear magnetic resonance signal, is compensated for during an evaluation of the at least one nuclear magnetic resonance signal. 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. In particular, no special precautions are necessary for active compensation on the NMR spectrometer. Furthermore, the method can be designed in this way preferably in a computer-implemented manner.

In one embodiment of the method, the influence is compensated by calculating the at least one acquired 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 of the nuclear spins. In this context, “offsetting” denotes a computational operation for correcting the acquired nuclear magnetic resonance signal by means of the correction function, wherein 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. In particular, 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 taken into account so that the undisturbed, unaffected nuclear magnetic resonance signal can be reconstructed from the measured nuclear magnetic resonance signal.

(ortsabhängige Magnetfeldänderung), als ΔB₀(t) (ortsunabhängige Magnetfeldänderung) oder auch als $\mathrm{\Delta }{\mathrm{{\rm B}}}_0\left(\overrightarrow{\text{r}}\text{,t}\right)$

(statische Inhomogenität) bezeichnet werden. Die Magnetfeldänderungen $\mathrm{\Delta }{\mathrm{{\rm B}}}_0\left(\overrightarrow{\text{r}}\text{,t}\right)$

können auch als resultierende Frequenzänderungen $\mathrm{\delta }\left(\overrightarrow{\text{r}}\text{,t}\right)$

des Kernspinresonanzspektrums verstanden werden. Die Begriffe werden daher synonym verwendet. Eine Änderung des Magnetfelds B0 während der Erfassung des Kernspinresonanzsignals (während der „acquisition time“, siehe oben) ändert die Präzessionsfrequenz aller Kernspins.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 methods 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 changes in the magnetic field can generally be called $\mathrm{\Delta }{\mathrm{{\rm B}}}_0\left(\overrightarrow{\text{r}}\text{, t}\right)$

(location-dependent magnetic field change), as ΔB ₀ (t) (location-independent magnetic field change) or as $\mathrm{\Delta }{\mathrm{{\rm B}}}_0\left(\overrightarrow{\text{r}}\text{, t}\right)$

(static inhomogeneity). The magnetic field changes $\mathrm{\Delta }{\mathrm{{\rm B}}}_0\left(\overrightarrow{\text{r}}\text{, t}\right)$

can also be called resulting frequency changes $\mathrm{\delta }\left(\overrightarrow{\text{r}}\text{, t}\right)$

of the nuclear magnetic resonance spectrum can be understood. The terms are therefore used synonymously. A change in the magnetic field B0 During the acquisition of the nuclear magnetic resonance signal (during the "acquisition time", see above) the precession frequency of all nuclear spins changes.

kann vereinfacht wie folgt beschrieben werden: Aus einem jeden Volumenelement V_n der Messprobe kann ein Signalanteil FID_n(t) empfangen werden. Diese Einzelsignale sind mit einer lokalen Empfindlichkeit S_n(r̅) der magnetfeldsensitiven Detektions-Vorrichtung, beispielsweise einer Empfangsspule, gewichtet und erfahren je nach lokaler Magnetfeldänderung eine Frequenzverschiebung $\mathrm{\delta }\left(\overrightarrow{\text{r}}\text{,t}\right)$

(hier diskretisiert als δ_n(t)) gemäß: $$\begin{array}{l}\text{FID}\left(\text{t}\right)={\displaystyle \sum _{\text{n}=1}^{\text{N}}{\text{FID}}_{\text{n}}\left(\text{t}\right)}={\displaystyle \sum _{\text{n}=1}^{\text{N}}{\text{S}}_{\text{n}}\cdot {\text{FID}}_{\text{hom}}\left(\text{t}\right)\cdot \text{exp}\left(\text{i}{\mathrm{\delta }}_{\text{n}}\left(\text{t}\right)\text{t}\right)}\\ ={\text{FID}}_{\text{hom}}\left(\text{t}\right)\cdot {\displaystyle \sum _{\text{n}=1}^{\text{N}}{\text{S}}_{\text{n}}\cdot \text{exp}\left(\text{i}{\mathrm{\delta }}_{\text{n}}\left(\text{t}\right)\text{t}\right)}\text{,}\end{array}$$

wobei ein FID einer bestimmten Substanz in einem homogenen Magnetfeld B0 vereinfacht beschrieben werden kann durch: $${\text{FID}}_{\text{hom}}\left(\text{t}\right)={\displaystyle \sum _{\text{k}}{\text{a}}_{\text{k}}\cdot \text{exp}\left\{\text{i}{\mathrm{\varpi }}_{\text{k}}\text{t}\right\}}\cdot \text{exp}\left\{-\text{t}/{\text{T}}_2\right\}\text{.}$$

The general case of location-dependent changes in the magnetic field $\mathrm{\Delta }{\mathrm{{\rm B}}}_0\left(\overrightarrow{\text{r}}\text{, t}\right)$

can be described in simplified form as follows: 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 (r̅) of the magnetic field-sensitive detection device, for example a receiving coil, and experience a frequency shift depending on the local change in the magnetic field $\mathrm{\delta }\left(\overrightarrow{\text{r}}\text{, t}\right)$

(here discretized as δ _n (t)) according to: $$\begin{array}{l}\text{FID}\left(\text{t}\right)={\displaystyle \sum _{\text{n}=1}^{\text{N}}{\text{FID}}_{\text{n}}\left(\text{t}\right)}={\displaystyle \sum _{\text{n}=1}^{\text{N}}{\text{S.}}_{\text{n}}\cdot {\text{FID}}_{\text{hom}}\left(\text{t}\right)\cdot \text{exp}\left(\text{i}{\mathrm{\delta }}_{\text{n}}\left(\text{t}\right)\text{t}\right)}\\ ={\text{FID}}_{\text{hom}}\left(\text{t}\right)\cdot {\displaystyle \sum _{\text{n}=1}^{\text{N}}{\text{S.}}_{\text{n}}\cdot \text{exp}\left(\text{i}{\mathrm{\delta }}_{\text{n}}\left(\text{t}\right)\text{t}\right)}\text{,}\end{array}$$

being an FID of a given substance in a homogeneous magnetic field B0 can be simplified by: $${\text{FID}}_{\text{hom}}\left(\text{t}\right)={\displaystyle \sum _{\text{k}}{\text{a}}_{\text{k}}\cdot \text{exp}\left\{\text{i}{\mathrm{\varpi }}_{\text{k}}\text{t}\right\}}\cdot \text{exp}\left\{-\text{t}/{\text{T}}_2\right\}\text{.}$$

The signal is made up of the characteristic frequencies ω _{k of} the differently bound nuclei in the test sample and their weightings a _k as well as an attenuation caused by the so-called T2 decay. The Fourier transformation of FID _hom (t) corresponds to the undisturbed NMR spectrum of the measurement sample.

bzw. δ_n(t) rekonstruiert werden.The desired NMR spectrum, as it would be detectable without the influence of the magnetic field change and / or without the influence of the static magnetic field inhomogeneity - i.e. FID _hom (t) - can be obtained from the actually recorded nuclear magnetic resonance signal FID (t) with knowledge of the coil sensitivities S _n and the influence the change in the magnetic field $\mathrm{\Delta }{\mathrm{{\rm B}}}_0\left(\overrightarrow{\text{r}}\text{, t}\right)$

or δ _n (t) can be reconstructed.

In the case of a location-independent change in the magnetic field and assuming a spatially constant coil sensitivity S _n = 1, the following applies: $$\begin{array}{l}{\text{FID}}_{\text{drift}}\left(\text{t}\right)={\displaystyle \sum _{\text{k}}{\text{a}}_{\text{k}}\cdot \text{exp}}\left\{\text{i}\left[{\mathrm{\varpi }}_{\text{k}}+\mathrm{\delta }\left(\text{t}\right)\text{t}\right]\right\}\cdot \text{exp}\left\{-{\text{t / t}}_2\right\}\\ ={\text{FID}}_{\text{hom}}\left(\text{t}\right)\cdot \text{exp}\left\{\text{i}\mathrm{\delta }\left(\text{t}\right)\text{t}\right\}\text{.}\end{array}$$

The time-dependent frequency δ (t) describes a time-dependent change in the Larmor frequency during the FID due to the time-dependent one Change in magnetic field. With knowledge of the time-dependent phase shift in the FID - for example by measuring as explained above - the undisturbed nuclear magnetic resonance signal FID _hom (t) can be reconstructed arithmetically using the above formula.

For the case of a temporally constant (static) magnetic field inhomogeneity (see third aspect of the invention) and also assuming a spatially constant coil sensitivity S _n = 1, the following applies: $$\begin{array}{l}{\text{FID}}_{\text{inhom}}\left(\text{t}\right)={\displaystyle \sum _{\text{n}=1}^{\text{N}}{\displaystyle \sum _{\text{k}}{\text{a}}_{\text{k}}\cdot \text{exp}\left\{\text{i}\left[{\mathrm{\varpi }}_{\text{k}}+{\mathrm{\delta }}_{\text{n}}\right]\text{t}\right\}\cdot \text{exp}\left\{-{\text{t / t}}_2\right\}}}\\ ={\text{FID}}_{\text{hom}}\left(\text{t}\right)\cdot {\displaystyle \sum _{\text{n}=1}^{\text{N}}\text{exp}\left\{\text{i}{\mathrm{\delta }}_{\text{n}}\text{t}\right\}}\end{array}$$

Similarly, with knowledge of the cumulative, location-dependent phase shift - for example by measuring the location-dependent magnetic field inhomogeneity as explained above - the undisturbed nuclear magnetic resonance signal FID _hom (t) can be reconstructed mathematically according to the above formula.

In one embodiment of the method, 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. In this way, the influence can be weakened (ie reduced by at least one order of magnitude) by active countermeasures and preferably completely compensated for. In particular, the influence can be compensated particularly well if it is known (ie dimension, direction) on the basis of the proposed evaluation. In one embodiment, the influence is achieved by controlling and / or regulating and / or adapting an electromagnetic superimposition field B2 actively compensated. In one embodiment, the influence is actively compensated by energizing a compensation coil. As an alternative or in addition to this, the influence can be actively compensated for by changing the magnetic device mechanically. A mechanical change in the magnet device includes, for example, a change in a distance between magnets, mechanical distortion (compression, shear, torsion or the like) of magnets or the like. As an alternative or in addition, it is conceivable to move the mobile NMR spectrometer by means of suitable mounting in such a way that the influence of the change in the magnetic field is actively counteracted. For example, by rotating the NMR spectrometer in opposite directions by means of a motorized stage, a change in the magnetic field that acts while driving in a curve can be counteracted. It is thus possible to use the static magnetic field generated by means of the magnet device B0 continue to be kept constant and, in particular, homogeneous. In particular, these exemplary embodiments are particularly suitable in the case of a location-independent change in the magnetic field. Alternatively or additionally, 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 are superimposed on the magnetic field B0 the magnetic device the magnetic field B0 make homogeneous in the measurement volume and compensate for the influence of a change in the magnetic field. While methods from the prior art require a preliminary calibration in order to carry out active shiming, 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. In particular, based on an anticipation of a change in the magnetic field (see above), a particularly precise compensation can be achieved in real time.

In one embodiment of the method, 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 change and / or a location-independent magnetic field change is relatively small, in particular negligible, with the NMR spectroscopy measurement , in particular the acquisition of the at least one nuclear magnetic resonance signal, is carried out at this point in time. In this context, “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. Alternatively or additionally, it is conceivable to define “relatively low” by means of a threshold value, for example in such a way that the influence during the duration of the acquisition of the nuclear magnetic resonance signal is so much reduced that it does not exceed 50 ppm, in particular not more than 15 ppm, entirely in particular is not more than 1 ppm. According to the invention, 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. In one exemplary embodiment, the times could be calculated using suitable algorithms, in particular using methods of self-learning methods, in particular using methods of artificial intelligence. For example, it is conceivable that the pitching movement of a deep-sea tanker is by Detect acceleration sensors and extrapolate those points in time from the sensor data at which the ship is at the reversal points of the pitching movement. If an NMR spectroscopy measurement is then carried out at these points in time of the reversal points, the influence of a magnetic field change can advantageously be kept low.

In a second aspect of the invention, this is based on a method for operating a mobile NMR spectrometer, with a static magnetic field during an NMR spectroscopy measurement by means of a magnetic device of the mobile NMR spectrometer B0 is generated and an excitation signal is generated by means of a magnetic field-sensitive detection device of the mobile NMR spectrometer B1 sent and at least one nuclear magnetic resonance signal is detected. According to the invention, 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, on the at least one acquired nuclear magnetic resonance signal after performing the NMR spectroscopy measurement, in particular after acquiring the at least one nuclear magnetic resonance signal, compensated in an evaluation of the at least one nuclear magnetic resonance signal.

The aspects and definitions discussed above, in particular for the NMR spectrometer and its mode of operation, for the magnetic device, for the magnetic field-sensitive detection device, for NMR spectroscopy, for the term “mobile”, for the expression “during the NMR spectroscopy measurement”, for the control device , to magnetic field changes, in particular location-independent and location-dependent magnetic field changes, as well as to the influence of these magnetic field changes and their order of magnitude, can apply analogously to the second aspect of the invention. According to the proposed method according to the second aspect of the invention, however, it is now conceivable that the 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, on the at least one acquired nuclear magnetic resonance signal without the use of Sensor data of a sensor is compensated.

A combinatorial or superimposed influence of location-dependent magnetic field changes and / or location-independent magnetic field changes and / or static magnetic field inhomogeneities can also be compensated according to the proposed method according to the invention according to the second aspect.

“During an evaluation” is to be understood as meaning that the a-posteriori compensation takes place within the framework of the evaluation, processing or analysis of the at least one recorded nuclear magnetic resonance signal. Consequently, under this aspect of the invention, the nuclear magnetic 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 method according to the invention according to the second aspect of the invention enables, compared to the prior art known NMR spectrometers, NMR spectroscopy measurements also under the influence of location-dependent and / or location-independent magnetic field changes during the NMR spectroscopy measurement, in particular during the acquisition of the nuclear magnetic resonance signal to be carried out sensibly by compensating for any influences occurring "a posteriori" when evaluating the nuclear magnetic resonance signals. This means that the nuclear magnetic resonance signals determined during the evaluation after the compensation has been carried out 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. In particular, this enables unrestricted, i.e. high-quality, NMR spectroscopy measurements with a moving - mobile - NMR spectrometer. Furthermore, 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. In particular, no special precautions are necessary for active compensation on the NMR spectrometer. Furthermore, the method can be designed in this way preferably in a computer-implemented manner.

In one embodiment of the method, the influence is determined, in particular calculated or evaluated, using the at least one detected nuclear magnetic resonance signal. In this way, 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.

In one embodiment of the method, the influence is compensated for by offsetting the at least one acquired nuclear magnetic resonance signal with a correction function. 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. In particular, 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.

In one embodiment of the method, 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 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. In this way, a particularly efficient method can be specified in which the correction function is calculated by numerical adaptation. In particular, any mathematical optimization models (for example parameter variation, “least square” method or the like) can be used to adapt the correction function.

In one embodiment of the method, the correction function is determined from the at least one nuclear magnetic resonance signal, in particular calculated or evaluated, in that a low-frequency interference and / or a linear change and / or a non-linear change in a time profile of the phase of the at least one nuclear magnetic resonance signal is determined, wherein the correction function is chosen 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. Here, low-frequency refers to a frequency range from 0 Hz (magnetic field change as drift) to 1 kHz (vibrations). In this way, unusual phase profiles - for example periodic fluctuations or linear increases or the like on which the phase profile is based - can serve as the basis for determining a low-frequency interference and / or a linear and / or non-linear change. In particular, it is conceivable to determine a location-independent change in the magnetic field as a linear, quadratic, cubic or periodic change in phase from an FID curve of a detected nuclear magnetic resonance signal. In addition, assumptions relating to the typical movement of the NMR spectrometer can be incorporated into the determination of the correction function, for example a periodicity with regard to the movement of an NMR spectrometer moved on the arm, a periodicity with regard to the movement of an NMR spectrometer moved in the ship, frequencies of a vibration due to it movement of the NMR spectrometer in a car or the like. With these assumptions, a disturbance can be compensated for particularly precisely and efficiently.

In one embodiment of the method, the correction function is determined using a plurality of, in particular sequentially or parallel, acquired nuclear magnetic resonance signals by determining at least one, in particular time-dependent, difference between the acquired nuclear magnetic resonance signals, the correction function being selected in such a way that when the nuclear magnetic resonance signals are offset with the correction function, the at least one, in particular time-dependent, difference is minimized, in particular becomes zero. In particular, 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, from the comparison of 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. strongly broadened peaks), can be applied to these and these can consequently be corrected. In particular, the nuclear magnetic resonance signals of the plurality corrected in this way can be used and averaged as part of an overall measurement. In one embodiment of the method, to determine, in particular time-dependent, differences, a signal-to-noise ratio, a line width of 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 or a positional relationship (such as in the case of multiplets caused by coupling) of at least one peak, a ratio of a maximum amplitude to an amplitude at the end of an FID curve and / or a partial or entire FID curve of the nuclear magnetic resonance signals is evaluated.

In one embodiment of the method, at least one recorded nuclear magnetic resonance signal is excluded from the plurality of recorded nuclear magnetic resonance signals when determining the correction function. In this way, when calculating a Fourier transform of a summed up signal - in which, in principle, FIDs of a plurality of acquired nuclear magnetic resonance signals are summed up - individual ones Nuclear magnetic resonance signals are specifically excluded from the summation 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.

In one embodiment of the method, 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. In particular, it is conceivable to use 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). In particular, an evaluation of a nuclear magnetic resonance signal with respect to a plurality of, in particular previous, further nuclear magnetic resonance signals allows an advantageous evaluation of individual nuclear magnetic resonance signals even in the case of dynamic magnetic field changes. For example, a threshold value with regard to a change in the position of a peak can be approx. 1% (corresponding to 0.1 ppm at 10 ppm spectral width) or 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, then in one embodiment the nuclear magnetic resonance signal is excluded from the evaluation.

In a third aspect of the invention, this is based on a method for operating an NMR spectrometer, with a static magnetic field during an NMR spectroscopy measurement on a measurement sample by means of a magnetic device of the mobile NMR spectrometer B0 is generated and an excitation signal is generated by means of a magnetic field-sensitive detection device of the NMR spectrometer B1 sent and at least one nuclear magnetic resonance signal is detected. According to the invention, there is an influence of a magnetic field inhomogeneity of the static magnetic field B0 compensated for the at least one detected nuclear magnetic resonance signal during an evaluation of the at least one nuclear magnetic resonance signal.

zu verstehen, bei der das Magnetfeld B0 je nach Position $\overrightarrow{\text{r}}$

innerhalb des Messvolumens unterschiedliche Beträge aufweist. Die Magnetfeldinhomogenität bleibt dabei während der NMR-Spektroskopiemessung statisch, d.h. zeitlich unveränderlich. Statische Magnetfeldinhomogenitäten können beispielsweise bei Verwendung einer an sich inhomogenen Magnet-Vorrichtung vorliegen. Ferner kann ein ursprünglich homogenes Magnetfeld inhomogen werden, beispielsweise durch das Einbringen einer Probe in das Messvolumen, durch Überlagerung mit inhomogenen, insbesondere externen, Magnetfeldern (z.B. auf Grund magnetischer Objekte in der Nähe des NMR-Spektrometers), oder durch Alterung oder starke Temperaturgradienten innerhalb der Magnet-Vorrichtung. Eine Kompensation des Einflusses derartiger statischer Magnetfeldinhomogenitäten ermöglicht es, NMR-Spektroskopiemessungen mit einer prinzipiell inhomogenen Magnet-Vorrichtung und/oder unter Einfluss von während einer NMR-Spektroskopiemessung wirkenden ortsabhängigen Magnetfeldänderungen durchzuführen.The aspects and definitions discussed above, in particular for the NMR spectrometer and its mode of operation, for the magnetic device, for the magnetic field-sensitive detection device, for NMR spectroscopy, for the expression “during the NMR spectroscopy measurement”, for the control device, for magnetic field inhomogeneities, as well as for The influence of these magnetic field inhomogeneities and its magnitude can apply analogously to the third aspect of the invention. According to the proposed method according to the third aspect of the invention, however, it is now conceivable that the influence of static, ie time-independent, magnetic field inhomogeneities on an NMR spectroscopy measurement can be compensated. According to a third aspect of the invention, there is an influence of a time-independent magnetic field inhomogeneity of the static magnetic field B0 compensated for the at least one detected nuclear magnetic resonance signal during an evaluation of the at least one nuclear magnetic resonance signal. A magnetic field inhomogeneity is in particular a static magnetic field inhomogeneity $\mathrm{\Delta }{\mathrm{{\rm B}}}_0\left(\overrightarrow{\text{r}}\text{, t}\right)$

to understand when the magnetic field B0 depending on the position $\overrightarrow{\text{r}}$

has different amounts 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. Furthermore, 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 within 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 location-dependent magnetic field changes acting during an NMR spectroscopy measurement.

Here, too, “during an evaluation” is to be understood as meaning that the a-posteriori compensation takes place within the framework of the evaluation, processing or analysis of the at least one recorded nuclear magnetic resonance signal. So it must Nuclear magnetic resonance signal under this aspect of the invention have been measured beforehand in order to subsequently compensate for the influence of the change in the magnetic field during the evaluation.

In one embodiment of the method, the influence is compensated for using a BO field distribution map (which can also be referred to as an inhomogeneity map or a frequency shift map). A particularly simple and efficient compensation can be carried out in this way. The BO field distribution map is provided to a control device performing the method. In particular, it is conceivable that the BO field distribution map is known from the construction of the magnetic device. For example, 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 has a linear field gradient in a third dimension. In this case, 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 method. In one embodiment of the method, the BO field distribution map is determined, in particular recorded or measured, using spatially resolved sensor data, the sensor data being recorded 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. In principle, a one-dimensional (length-resolving), two-dimensional (surface-resolving) or three-dimensional (volume-resolving) arrangement of the sensors in the form of a 1D, 2D or 3D array is conceivable. By choosing the number and spatial arrangement of the sensors, in particular those sensitive to magnetic fields, it is possible to determine a linear, quadratic or cubic resolution of the influence of a static magnetic field inhomogeneity. It should be noted that the B0 field distribution map can be refined by interpolating sensor data. In one embodiment of the method, the BO 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, very particularly 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. This phase difference is a measure for the local Larmor frequency and thus for the local frequency shift. A local field strength distribution can thus be determined from the difference between the at least two images. In one embodiment, the BO field distribution map is determined immediately before and / or after the magnetic resonance signal is detected. “Immediately” here means that a time interval between the NMR spectroscopy measurement and the acquisition of the BO field distribution map is less than 60 seconds, in particular less than 20 seconds, and in particular less than 1 second. 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.

In one embodiment of the method, the influence is determined, in particular recorded or measured, using a reference NMR spectroscopy measurement that has been carried out. In particular, an undisturbed reference nuclear magnetic resonance signal is known. In this way, 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 explained above - be used to calculate or model the influence. In the case of a static magnetic field inhomogeneity and assuming a spatially constant coil sensitivity S _n = 1, the following applies: $$\begin{array}{l}{\text{FID}}_{\text{inhom}}\left(\text{t}\right)={\displaystyle \sum _{\text{n}=1}^{\text{N}}{\displaystyle \sum _{\text{k}}{\text{a}}_{\text{k}}\cdot \text{exp}\left\{\text{i}\left[{\mathrm{\varpi }}_{\text{k}}+{\mathrm{\delta }}_{\text{n}}\right]\text{t}\right\}\cdot \text{exp}\left\{-{\text{t / t}}_2\right\}}}\\ ={\text{FID}}_{\text{hom}}\left(\text{t}\right)\cdot {\displaystyle \sum _{\text{n}=1}^{\text{N}}\text{exp}\left\{\text{i}{\mathrm{\delta }}_{\text{n}}\text{t}\right\}}\end{array}$$

With knowledge of the accumulated, location-dependent phase shift - for example by measuring the location-dependent magnetic field inhomogeneity as explained above - the undisturbed nuclear magnetic resonance signal FID _hom (t) can be reconstructed mathematically according to this formula. Alternatively, any mathematical optimization models can be used to determine the influence as a mathematical parameter δ _n or as a correction function. The proposed embodiment is based on the knowledge that a parameter δ _n 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. In one embodiment of the method, the reference NMR spectroscopy measurement is carried out on a separate sample from the measurement sample Reference sample carried out. In particular, it is conceivable to measure the reference sample at the same point at which the measurement sample is also measured. This can be achieved, for example, by means of a folding mechanism in the measurement volume, the reference sample being automatically folded away when the measurement sample is inserted. In an alternative or additional embodiment, 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. Again, as an alternative or in addition, the measurement sample is subjected to a reference NMR spectroscopy measurement on a predefined, in particular predefinable, NMR-active core. In one embodiment, 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 a reference sample added to the measurement 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.

In one embodiment of the method, the influence is compensated for by offsetting the at least one acquired nuclear magnetic resonance signal with a correction function. Regarding 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. In particular, 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.

In one embodiment of the method, 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. In particular, it is conceivable that the influence by controlling and / or regulating and / or adapting an electromagnetic superimposition field B2 is actively compensated. These embodiments have already been discussed in connection with the embodiments according to the first aspect of the invention.

It should be pointed out that the embodiments according to the first aspect of the invention, the second aspect of the invention and the third aspect of the invention can be implemented individually or in combination with one another. The invention consequently makes it possible, in contrast to NMR spectrometers known from the prior art, to carry out NMR spectroscopy measurements also 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, this enables unrestricted, i.e. high-quality, NMR spectroscopy measurements with a moving - mobile - NMR spectrometer. 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. It should also be noted that “a posteriori” compensation can in principle also be combined with active compensation. In addition, it should be noted that compensation according to one of the proposed embodiments (first, second or third aspect of the invention) can also be combined with passive shielding of the NMR spectrometer (passive compensation), for example with a layer of μ surrounding the NMR spectrometer -Metal or an RF cage surrounding the NMR spectrometer or the like. In particular, good shielding can prevent the influence of a change in the magnetic field and simplify the method described. In particular, reducing magnetic field changes through active and / or passive compensation can considerably facilitate an “a posteriori” compensation. Active and passive compensation methods can be used, for example, 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.

In a further aspect of the invention there is an, in particular mobile, NMR spectrometer with a magnetic device for generating a static magnetic field B0 as well as with a magnetic field-sensitive detection device for emitting an excitation signal B1 and proposed for the acquisition of a nuclear magnetic resonance signal. According to the invention, the NMR spectrometer has a control device which is set up to perform 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 Invention to carry out. The statements made with regard to the method according to the invention can be transferred 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, and also in environments with magnetic field fluctuations and / or temperature fluctuations.

In particular, a vehicle comprising the proposed NMR spectrometer is proposed. 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. Furthermore, a mobile data processing device such as a smartphone or a mobile, personal device (“personal device”) comprising the proposed NMR spectrometer is proposed. Furthermore, an implant comprising the proposed NMR spectrometer is proposed.

In a further aspect, a computer program is proposed. The computer program is set up to carry out one of the aforementioned methods. The computer program comprises instructions which cause a processor device to carry out a corresponding method.

Furthermore, a computer-readable storage medium is proposed on which the computer program is deposited, in particular stored. Storage media per se are known to a person skilled in the art.

Figure list

The invention is explained in more detail in the following description on the basis of exemplary embodiments shown in the drawings. The drawing, the description and the claims contain numerous features in combination. The person skilled in the art will expediently also consider the features individually and combine them into meaningful further combinations. The same or similar reference symbols in the figures designate the same or similar elements.

• 1 ein perspektivische Darstellung einer Ausgestaltung des erfindungsgemäßen mobilen NMR-Spektrometers,
• 2 ein Verfahrensdiagramm eines Ausführungsbeispiels des Verfahrens gemäß erstem Aspekt der Erfindung,
• 3 ein Verfahrensdiagramm eines weiteren Ausführungsbeispiels des Verfahrens gemäß erstem Aspekt der Erfindung,
• 4 ein Verfahrensdiagramm eines weiteren Ausführungsbeispiels des Verfahrens gemäß erstem Aspekt der Erfindung,
• 5 ein Verfahrensdiagramm eines Ausführungsbeispiels des Verfahrens gemäß zweitem Aspekt der Erfindung,
• 6 ein Verfahrensdiagramm eines Ausführungsbeispiels des Verfahrens gemäß drittem Aspekt der Erfindung,
• 7 ein Verfahrensdiagramm eines alternativen Ausführungsbeispiels des Verfahrens gemäß drittem Aspekt der Erfindung,
• 8 schematische Darstellung der Kompensation von Kernspinresonanzsignalen gemäß einem der erfindungsgemäßen Verfahren.

Show it:

• 1 a perspective view of an embodiment of the mobile NMR spectrometer according to the invention,
• 2 a method diagram of an embodiment of the method according to the first aspect of the invention,
• 3 a method diagram of a further embodiment of the method according to the first aspect of the invention,
• 4th a method diagram of a further embodiment of the method according to the first aspect of the invention,
• 5 a method diagram of an embodiment of the method according to the second aspect of the invention,
• 6th a method diagram of an embodiment of the method according to the third aspect of the invention,
• 7th a method diagram of an alternative embodiment of the method according to the third aspect of the invention,
• 8th schematic representation of the compensation of nuclear magnetic resonance signals according to one of the methods according to the invention.

Description of the exemplary embodiments

1 shows a view of an exemplary embodiment of a mobile, here hand-held, NMR spectrometer according to the invention 10 in perspective view. The exemplary NMR spectrometer 10 has a housing 12th on. In the case 12th is an input device 14th in the form of actuators 14 ' , suitable for switching the NMR spectrometer on and off 10 , for starting and configuring a measurement process and for entering work parameters. It is also in the housing 12th an output device 16 for the output of determined information as well as for the output of working parameters in the form of a screen 16 ' intended. The NMR spectrometer 10 has a handle for transport and guidance 18th . For the energy supply of the NMR spectrometer 10 instructs the NMR spectrometer 10 an energy storage device (not shown in more detail here) in the form of rechargeable batteries. The NMR spectrometer 10 in particular has a magnet device 20th to generate a magnetic field B0 on, a magnetic field sensitive detection device 22nd for sending out an excitation signal B1 and for detecting a nuclear magnetic resonance signal and a control device 24 to control the NMR spectrometer 10 and for evaluating by means of the magnetic field-sensitive detection device 22nd detected measurement signals, in particular nuclear magnetic resonance signals. The magnet device 20th is realized as a permanent magnet. The magnetic field sensitive detection device 22nd is implemented as an RF coil. The NMR spectrometer 10 is designed in such a way that there is a nuclear magnetic resonance spectrum of a measurement sample 30th can accommodate. The NMR spectrometer 10 also has four magnetic field sensitive sensors 26th in a square array- Arrangement are positioned and thus register an influence of a location-dependent change in the magnetic field by direct measurement of the magnetic field. The control device 24 has control electronics comprising means for communication with the other components of the NMR spectrometer 10 on, for example means for controlling and regulating the magnetic field-sensitive detection device 22nd and to control magnetic field sensitive sensors 26th . The control device 24 comprises in particular a processor device (not shown here), a memory unit and a computer program stored in the memory unit. The computer program is set up, a method as described in 2-6 is illustrated, to execute and comprises instructions that 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 aspects of the invention. The control device 24 is set up to measure the influence of location-dependent magnetic field changes acting during an NMR spectroscopy measurement as well as location-independent magnetic field changes and static magnetic field inhomogeneities by means of the magnetic device 20th generated magnetic field B0 on by means of the magnetic field-sensitive detection device 22nd to compensate detected nuclear magnetic resonance signals.

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, respectively.

In 2 is a process diagram 100 shown, the one embodiment of the method according to the first aspect of the invention for operating a mobile NMR spectrometer 10 reproduces. The procedure is used to operate the mobile NMR spectrometer 10 as in 1 shown, wherein during an NMR spectroscopy measurement on a measurement sample 30th by means of the magnet device 20th of the mobile NMR spectrometer 10 a static magnetic field B0 is generated as well as by means of a magnetic field-sensitive detection device 22nd an excitation signal B1 sent and at least one nuclear magnetic resonance signal is detected. In a first process step 102 is by means of the magnet device 20th the static magnetic field B0 generated, which is maintained over a period of time in which at least the process steps 104 and 106 are executed. In process step 104 the sensor data of the four magnetic field sensitive sensors 26th 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 the process step 106 is performed. As an alternative or in addition to this determination of the influence - for example to increase the accuracy by averaging - it is conceivable to use a temporally at least during the period in which the method step 106 is carried out, to determine the reference NMR spectroscopy measurement carried out (not shown here by itself) and to use it 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). In particular, based on both detection methods (sensor data from sensors and sensor data from reference NMR spectroscopy measurement), an average value of the influence can be formed and the accuracy in determining the influence can be increased in this way. In process step 106 is by means of the magnetic field-sensitive detection device 22nd of the mobile NMR spectrometer 10 an excitation signal B1 and a nuclear magnetic resonance signal is recorded from the measurement sample. In the exemplary embodiment shown here, the change in the magnetic field is determined after the NMR spectroscopy measurement has been carried out (ie after process steps 106 ) compensated for the evaluation of the nuclear magnetic resonance signals. This is done in process step 108 initially from the in process step 104 recorded sensor data the (superimposed) influence of location-dependent and location-independent magnetic field changes and magnetic field inhomogeneities of the magnetic field acting during the NMR spectroscopy measurement B0 determined on the at least one detected nuclear magnetic resonance signal and calculates a correction function, the correction function taking into account the magnetic field changes 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 shift of the nuclear spins. In sub-steps 110 the influence is then compensated by offsetting with the calculated correction function. In principle, the method can be carried out repeatedly.

In 3 is a process diagram 200 shown, the another embodiment of the method according to the first aspect of the invention for operating a mobile NMR spectrometer 10 reproduces. In a first process step 202 is by means of the magnet device 20th the static magnetic field B0 generated, which is maintained over a period of time in which at least the process steps 204 and 206 are executed. In process step 204 the sensor data of the four magnetic field sensitive sensors 26th read out continuously in order to determine the influence of a location-independent change in the magnetic field by averaging the sensor data. Sensor data are time-dependent during the continuous readout and from this a time-dependent influence of the change in the magnetic field is determined. At the same time - based on the time-dependent course of the influence that has already been recorded - a for the time at which the method step is carried out 206 effective influence "into the future" is extrapolated, so that the influence is then known for this point in time and as the basis of the active compensation at least during the execution of the process step 206 can be used. In process step 206 is by means of the magnetic field-sensitive detection device 22nd of the mobile NMR spectrometer 10 an excitation signal B1 and a nuclear magnetic resonance signal is recorded from the measurement sample. At the same time takes place in process step 208 by, in particular continuously, adapting the energization of a compensation coil, a compensation of the extrapolated influence of the magnetic field change. It should be pointed out that the method here can run in a continuous loop, shown by the dashed arrow.

In 4th is a process diagram 300 shown, the another embodiment of the method according to the first aspect of the invention for operating a mobile NMR spectrometer 10 reproduces. In a first process step 302 is by means of the magnet device 20th the static magnetic field B0 generated, which is maintained over a period of time in which at least the process steps 304 to 308 are executed. In process step 304 the sensor data of a magnetic field sensitive sensor 26th read out continuously 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 magnetic field change are determined. In process step 306 using the sensor data, 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, process step 308 by means of the magnetic field sensitive detection device 22nd of the mobile NMR spectrometer 10 an excitation signal B1 and a nuclear magnetic resonance signal is recorded from the measurement sample. By adjusting the point in time at which the influence of the change in the magnetic field is small, the influence on the acquired nuclear magnetic resonance signal can be avoided (and thus compensated). This Procedure can also be carried out repeatedly.

In 5 is a process diagram 400 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 in 1 shown, wherein during an NMR spectroscopy measurement on a measurement sample 30th by means of the magnet device 20th of the mobile NMR spectrometer 10 a static magnetic field B0 is generated as well as by means of a magnetic field-sensitive detection device 22nd an excitation signal B1 sent and at least one nuclear magnetic resonance signal is detected. In a first process step 402 is by means of the magnet device 20th the static magnetic field B0 generated, which is maintained over a period of time in which at least the process steps 404 and 406 are executed. In process step 404 is by means of the magnetic field-sensitive detection device 22nd of the mobile NMR spectrometer 10 an excitation signal B1 and a nuclear magnetic resonance signal is recorded from the measurement sample. In process step 406 an influence of location-dependent and / or location-independent magnetic field changes acting during the measurement of the at least one nuclear magnetic resonance signal during the NMR spectroscopy measurement on the at least one acquired nuclear magnetic resonance signal is compensated for when evaluating the at least one nuclear magnetic resonance signal and using the at least one acquired nuclear magnetic resonance signal. The influence is compensated for by offsetting the at least one recorded nuclear magnetic resonance signal with a correction function. This is done in sub-process step 410 the correction function is determined from the at least one nuclear magnetic resonance signal by a deviation being determined 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 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. Alternatively or in addition to process step 410 is in process step 412 the correction function is determined from the at least one nuclear magnetic resonance signal 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 against the correction function, the low-frequency disturbance is minimized, in particular zero becomes. Alternatively or in addition to procedural steps 410 and 412 is in process step 414 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 in such a way that when the magnetic resonance signals are offset against the correction function, the at least one difference is minimized, in particular becomes zero . To determine the at least one difference, a position of at least one peak in the NMR spectrum is evaluated. This procedure can also be carried out repeatedly.

In 6th is a process diagram 500 shown that an embodiment of a method according to the third aspect of the invention for operating a (here mobile) NMR spectrometer 10 reproduces. The method is used to operate a - not necessarily mobile - NMR spectrometer 10 as in 1 shown, wherein during an NMR spectroscopy measurement on a measurement sample 30th by means of the magnet device 20th of the mobile NMR spectrometer 10 a static magnetic field B0 is generated as well as by means of a magnetic field-sensitive detection device 22nd an excitation signal B1 sent and at least one nuclear magnetic resonance signal is detected. In a first process step 502 is by means of the magnet device 20th the static magnetic field B0 generated, which is maintained over a period of time in which at least the process steps 504 and 506 are executed. In process step 504 the sensor data of the four magnetic field sensitive sensors 26th read out and created a BO field distribution map from it. The BO field distribution map shows the influence of a static magnetic field inhomogeneity of the magnetic field B0 depending on location again. Alternatively, in a further exemplary embodiment, in method step 504 the B0 field distribution map can also be determined by means of an imaging gradient system. In process step 506 is by means of the magnetic field-sensitive detection device 22nd of the mobile NMR spectrometer 10 an excitation signal B1 and a nuclear magnetic resonance signal is recorded from the measurement sample. In the embodiment shown here, the influence of the magnetic field inhomogeneity of the static magnetic field is B0 compensated for the at least one detected nuclear magnetic resonance signal during an evaluation of the at least one nuclear magnetic resonance signal. This is done in process step 508 Based on the BO field distribution map, 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.

In 7th is a process diagram 600 shown that a procedure 500 reproduces alternative embodiment of a method according to the third aspect of the invention. In a first process step 602 is by means of the magnet device 20th the static magnetic field B0 generated, which is maintained over a period of time in which at least the process steps 604 and 606 are executed. In process step 604 an influence of the magnetic field inhomogeneity is determined using a reference NMR spectroscopy measurement that has been carried out. In this exemplary embodiment, the reference NMR spectroscopy measurement is carried out on a reference sample that is separate from the measurement sample. In process step 606 is by means of the magnetic field-sensitive detection device 22nd of the mobile NMR spectrometer 10 an excitation signal B1 and a nuclear magnetic resonance signal is recorded from the measurement sample. In the exemplary embodiment shown here, 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. This is done in process step 608 initially from the in process step 604 detected sensor data determines the influence of the magnetic field inhomogeneity acting during the NMR spectroscopy measurement on the at least one detected nuclear magnetic resonance signal and calculates a correction function, the correction function taking into account 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 shift of the nuclear spins. In sub-steps 610 the influence is then compensated by offsetting with the calculated correction function. This procedure can also be carried out repeatedly.

8th shows a schematic representation of the compensation of nuclear magnetic resonance signals according to one of the methods according to the invention. In 8a an uncompensated NMR spectrum is shown, which, 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 B0 to the in 8b shown undisturbed NMR spectrum can be compensated. In this exemplary embodiment, the FID of the nuclear magnetic resonance signal disturbed by the influence was multiplied by a phase factor exp {-iδ (t) t} in order to obtain the undisturbed (compensated) FID and thus the undisturbed NMR spectrum: $$\begin{array}{l}{\text{FID}}_{\text{drift}}\left(\text{t}\right)={\displaystyle \sum _{\text{k}}{\text{a}}_{\text{k}}\cdot \text{exp}}\left\{\text{i}\left[{\mathrm{\varpi }}_{\text{k}}+\mathrm{\delta }\left(\text{t}\right)\text{t}\right]\right\}\cdot \text{exp}\left\{-{\text{t / t}}_2\right\}\\ ={\text{FID}}_{\text{hom}}\left(\text{t}\right)\cdot \text{exp}\left\{\text{i}\mathrm{\delta }\left(\text{t}\right)\text{t}\right\}\text{.}\end{array}$$

This compensation by means of the correction function “exp {-iδ (t) t}” presupposes that the location-independent change in the magnetic field (expressed here as a frequency change δ (t)) has been measured or evaluated using one of the previous examples.

QUOTES INCLUDED IN THE DESCRIPTION

This list of the documents listed by the applicant was generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Non-patent literature cited

• "Benchtop NMR spectrometers in academic teaching", Susanne D. Riegel, Garett M. Leskowitz, Application Chemistry, Nanalysis Corp., Canada [0001]
• "Spin Dynamics" Malcolm H. Levitt, Wiley 2008 [0001]
• "Scalable NMR spectroscopy with semiconductor chips", Dongwan Ha, Jeffrey Paulsen, Nan Sun, Yi-Qiao Song, Donhee Ham, Proceedings of the National Academy of Sciences August 2014 [0002]

Claims (10)

Method for operating a mobile NMR spectrometer, wherein a static magnetic field B0 is generated during an NMR spectroscopy measurement by means of a magnetic device of the mobile NMR spectrometer and an excitation signal B1 is sent and at least one by means of a magnetic field-sensitive detection device of the mobile NMR spectrometer Nuclear magnetic resonance signal is detected, characterized in that an influence of location-dependent magnetic field changes and / or location-independent magnetic field changes acting during the NMR spectroscopy measurement, in particular from during the detection of the at least one nuclear magnetic resonance signal, on the at least one detected nuclear magnetic resonance signal after performing the NMR spectroscopy measurement, in particular after 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. Procedure according to Claim 1 , characterized in that the influence is determined using the at least one detected nuclear magnetic resonance signal. Method according to one of the Claims 1 - 2 , characterized in that the influence is compensated for by offsetting the at least one detected nuclear magnetic resonance signal with a correction function. Procedure according to Claim 3 , characterized in that the correction function is determined from the at least one nuclear magnetic resonance signal, • 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 an 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 the deviation is minimized, in particular becomes zero, when the at least one nuclear magnetic resonance signal is offset against the correction function. Method according to one of the Claims 3 - 4th , characterized in that the correction function is determined from the at least one nuclear magnetic resonance signal, • 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 it is 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 change and / or the non-linear change in the phase is minimized, in particular becomes zero. Method according to one of the Claims 3 - 5 , characterized in that the correction function is determined using a plurality of, in particular sequentially or parallel, acquired nuclear magnetic resonance signals, • by determining at least one difference between the acquired nuclear magnetic resonance signals, • wherein the correction function is selected such that when offsetting the nuclear magnetic resonance signals with the Correction function that minimizes at least one difference, in particular becomes zero. Procedure according to Claim 6 , characterized in that, to determine differences, a signal-to-noise ratio, a height of at least one peak, an area of at least one peak, a line width of at least one peak, a position of at least one peak, a positional relationship of at least one peak, a ratio from a maximum amplitude to an amplitude at the end of an FID curve and / or a partial or entire FID curve of the nuclear magnetic resonance signals is evaluated. Procedure according to Claim 6 - 7th , characterized in that at least one recorded nuclear magnetic resonance signal is excluded from the plurality of recorded nuclear magnetic resonance signals when determining the correction function. Procedure according to Claim 8 , characterized in that 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. Mobile NMR spectrometer with a magnetic device for generating a static magnetic field B0 and with a magnetic field-sensitive detection device for emitting an excitation signal B1 and for detecting at least one nuclear magnetic resonance signal, characterized in that the NMR spectrometer has a control device which is set up for this purpose , a method according to one of the Claims 1 - 9 to execute.

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