Techniques for determining NMR relaxation times and / or NMR spectra of probes

Abstract

The present invention relates to a method for determining the nuclear magnetic resonance relaxation time of a probe (P). The method comprises: a first step (S 1 ), by applying a longitudinal static magnetic field (B 0 ) polarizes the first nucleus (H) and the second nucleus (N); the second step (S 2 ), exchanging the polarization of the first nucleus (H) and the second nucleus (N) by irradiating a transverse magnetic field pulse of an exchange sequence (SWAP); the third step (S 3 ), transversely magnetizing the second nucleus (N) by irradiating at least one excitation pulse (EXC), and measuring the magnetization signal (FID) generated by the second nucleus (N); and a fourth step (S 4 ), determine the nuclear magnetic resonance relaxation time of the second nucleus (N) based on the measured magnetization signal (FID) of the second nucleus (N).

Description

Technical Field

[0001] The present invention relates to a method, an apparatus, a computer program, and a data carrier for determining at least one of a nuclear magnetic resonance relaxation time and a nuclear magnetic resonance spectrum of a probe, wherein the probe comprises a first atomic nucleus having a first gyromagnetic ratio and a second atomic nucleus having a second gyromagnetic ratio, and the first gyromagnetic ratio is greater than the second gyromagnetic ratio. Background Art

[0002] Nuclear magnetic resonance (NMR) spectroscopy is one of the most fundamental spectroscopic techniques for studying the electronic properties of substances in physics, chemistry, and biology. For example, areas of application of NMR relaxometry may involve the study of porous media in the oil industry, the structural analysis of solid fats and seed oils, or the testing of contrast agents in magnetic resonance imaging (MRI). Further applications involve the study of the physical and chemical properties of polymers, for example, determining their electron density, crystallinity, degree of polymerization, or the proportion of plasticizers and other additives.

[0003] In NMR spectroscopy, a strong static longitudinal magnetic field is applied to the probe, and the magnetic response signal of the probe is measured after exciting the probe with a specific sequence of transverse magnetic field excitation pulses. However, when the nuclei of the probe are excited with a small gyromagnetic ratio, the intensity of the detected magnetic response signal may be quite weak. In this case, it may be necessary to perform multiple excitation and measurement sequences to ensure an acceptable signal-to-noise ratio. Usually, between two such sequences, it is necessary to wait until the nuclei of the probe return to their equilibrium state in the applied static longitudinal magnetic field, i.e., before another excitation and measurement step can be performed. Therefore, in a typical experiment, determining the NMR relaxation time or the NMR spectrum may take a very long time, on the order of several hours or even days. Summary of the invention

[0004] The object of the present invention is to overcome these limitations and to provide a simple and practical method, an apparatus, a computer program, and a data carrier for determining NMR relaxation times and / or NMR spectra with high accuracy in a time-efficient manner.

[0005] This object of the invention is achieved by a method, an apparatus, a computer program, and a data carrier as described in claims 1, 13, 14, and 15. Advantageous developments and embodiments are described in the dependent claims.

[0006] The present invention relates to a method for determining the nuclear magnetic resonance relaxation time and / or the nuclear magnetic resonance spectrum of a probe, wherein the probe comprises a first atomic nucleus having a first gyromagnetic ratio and a second atomic nucleus having a second gyromagnetic ratio. The first gyromagnetic ratio is greater than the second gyromagnetic ratio.

[0007] Here and below, nucleus may refer to the nucleus of an isotope.

[0008] The method comprises the following steps:

[0009] In the first step, the first atomic nucleus and the second atomic nucleus are polarized by applying a longitudinal static magnetic field to the probe.

[0010] In a second step, the polarization of the first atomic nucleus and the second atomic nucleus are exchanged by irradiating at least one transverse magnetic field pulse of an exchange sequence.

[0011] In a third step, the second atomic nuclei are transversely magnetized by irradiating at least one excitation pulse and the generated magnetization signal is measured.

[0012] The fourth step is to determine the nuclear magnetic resonance relaxation time and / or the nuclear magnetic resonance spectrum according to the measured magnetization signal.

[0013] Advantageously, in the second step, the polarization of the first nucleus and the second nucleus is exchanged by irradiating at least one exchange sequence of transverse magnetic field pulses, the polarization of the first nucleus can be transferred to the second nucleus, and the polarization of the second nucleus can be transferred to the first nucleus, that is, at least one exchange sequence can correspond to a complete exchange operation of the polarization of the respective nuclei.

[0014] Therefore, the intensity of the magnetization signal of the second atomic nucleus measured in the third step can be significantly increased, because the stronger polarization of the first atomic nucleus in the longitudinal static magnetic field may have been transferred to the second atomic nucleus due to its larger gyromagnetic ratio. More specifically, according to the proposed method, the intensity of the magnetization signal may have been increased by a factor corresponding to the ratio of the first gyromagnetic ratio to the second gyromagnetic ratio. Therefore, the signal-to-noise ratio can also be significantly improved.

[0015] Furthermore, by irradiating at least one exchange sequence, the polarization of the second nucleus may also be transferred to the first nucleus, resulting in a complete exchange of the respective polarizations, thus enabling a more efficient reinitialization of the probe and significantly simplifying the proposed method, since fewer gradient pulses may be required and a smaller number of parameters need to be calibrated.

[0016] Furthermore, in order to achieve a complete exchange of polarizations of the first nucleus and the second nucleus by irradiating a transverse magnetic field pulse of an exchange sequence, the basic quantum mechanical structure of two interacting quantum systems (i.e., the first nucleus and the second nucleus) can be accurately considered when designing at least one exchange sequence, thereby improving the accuracy and precision of the proposed method.

[0017] Preferably, the atom corresponding to the first atomic nucleus and the atom corresponding to the second atomic nucleus are covalently bonded to form the molecule.

[0018] Illustratively, the first gyromagnetic ratio may be at least four times greater than the second gyromagnetic ratio.

[0019] The nuclear spins of the first atomic nucleus and the second atomic nucleus may interact with each other through a longitudinal spin-spin interaction, wherein the spin-spin interaction corresponds to the coupling between the nuclear spin components in the longitudinal direction of the static magnetic field applied in the first step.

[0020] Illustratively, the first nucleus may be a hydrogen isotope (e.g., 1 The second nucleus may be 15 N or 13 The probe may include an aqueous solution of isotopically enriched protein molecules.

[0021] When performing the second and third steps, the longitudinal static magnetic field applied to the probe in the first step may also be applied to the probe, so that the first atomic nuclei and the second atomic nuclei are continuously exposed to the longitudinal static magnetic field at least from the first step to the third step.

[0022] The second step may be performed after the first step is performed. The third step may be performed after the second step is performed. The fourth step may be performed after the third step is performed.

[0023] The applied static longitudinal magnetic field can lead to Zeeman energy splitting between the ground and excited states of nuclear spins. where the Zeeman energy splitting ΔE is proportional to the corresponding gyromagnetic ratio γ of the nucleus and the effective magnetic field B at the corresponding nucleus, and Where h is Planck's constant.

[0024] Due to chemical shielding of the electron density around the nucleus, the effective magnetic field B at the corresponding nucleus may be reduced relative to the applied static longitudinal magnetic field B0. Therefore, the resonance frequency ω = γB (also called Larmor frequency) may contain information about the electronic structure around the nucleus and is therefore also called chemical shift.

[0025] The polarization of a nucleus can be corresponded to the population difference between two Zeeman energy levels.

[0026] More specifically, the population difference may refer to the difference in the population of Zeeman levels in the presence of a longitudinal static magnetic field at thermal equilibrium, wherein the splitting ΔE of the Zeeman levels is caused by the interaction of nuclear dipoles with the longitudinal static magnetic field.

[0027] The difference in particle numbers can be expressed by the Boltzmann factor The calculation shows that, where N1 is the number of particles in the ground state, N2 is the number of particles in the excited state, k is the Boltzmann constant, and T represents the temperature. At room temperature, the Boltzmann factor can be expanded to the first order Therefore, a smaller gyromagnetic ratio γ may lead to a smaller population difference and, accordingly, a smaller magnetization signal intensity.

[0028] The corresponding Zeeman energy levels form an effective two-level quantum system, which can be manipulated (e.g., excited and de-excited) by irradiating a transverse magnetic field pulse. The irradiation of the transverse magnetic field pulse can then correspond to a spin 1 / 2 rotation corresponding to the two-level quantum system and representing the nuclear spin on a Bloch sphere with a specific magnetic field pulse rotation angle determined by the pulse duration.

[0029] Preferably, by irradiating at least one transverse magnetic field pulse of the exchange sequence in the second step, the nuclear spin or bulk magnetization of the first atomic nucleus and the nuclear spin or bulk magnetization of the second atomic nucleus can be realigned with the longitudinal static magnetic field immediately after the second step is performed and before the third step is performed. After irradiating the exchange sequence in the second step, the bulk transverse magnetization of the first atomic nucleus and the bulk transverse magnetization of the second atomic nucleus can be averaged to zero immediately. Therefore, after the second step, the first atomic nucleus and the second atomic nucleus may already be in their equilibrium or cooling state relative to the applied static longitudinal magnetic field, and can immediately and quickly perform transverse excitation in the second step and acquire magnetization signals in the third step.

[0030] The irradiation of at least one exchange sequence of transverse magnetic field pulses in the second step may include: irradiating a first sequence of transverse magnetic field pulses to excite the first atomic nucleus, and irradiating a second sequence of transverse magnetic field pulses to excite the second atomic nucleus. The pulse frequency of the first sequence of transverse magnetic field pulses may correspond to the Larmor frequency of the first atomic nucleus in the longitudinal static magnetic field. The pulse frequency of the second sequence of transverse magnetic field pulses may correspond to the Larmor frequency of the second atomic nucleus in the longitudinal static magnetic field. Therefore, the first sequence can excite the first atomic nucleus, and the second sequence can excite the second atomic nucleus. Most preferably, the transverse magnetic field pulses are resonant pulses, that is, the pulse frequency of the transverse magnetic field pulses can be equal to the corresponding Larmor frequency (under resonant excitation).

[0031] The first sequence of transverse magnetic field pulses and the second sequence of transverse magnetic field pulses may be irradiated simultaneously and / or synchronously. Specifically, the first sequence of transverse magnetic field pulses and the second sequence of transverse magnetic field pulses may be irradiated simultaneously and / or synchronously.

[0032] The time length of the first sequence of transverse magnetic field pulses and the time length of the second sequence of transverse magnetic field pulses may be the same.

[0033] Exemplarily, the time length of at least one exchange sequence, the time length of the first sequence and / or the time length of the second sequence can be equal to the inverse of the longitudinal spin-spin interaction strength between the first nucleus and the second nucleus (given in frequency units).

[0034] Preferably, each transverse magnetic field pulse of the first sequence may correspond to the transverse magnetic field pulse of the second sequence in terms of pulse center timing, magnetic field pulse rotation angle and / or magnetic field pulse oscillation direction. The magnetic field pulse oscillation direction may be perpendicular to the longitudinal direction of the static magnetic field applied in the first step. The magnetic field pulse rotation angle may correspond to the time width of the transverse magnetic field pulse. The time width of the transverse magnetic field pulse may be of the order of the reciprocal of the Larmor frequency (in appropriate units). The pulse center timing may correspond to the time when the maximum amplitude peak of the transverse magnetic field pulse leaves the pulse generator, for example, in the case of a Gaussian pulse shape. The transverse magnetic field pulse may also be a rectangular pulse.

[0035] In the following, for the sake of specificity, it may be assumed that the longitudinal static magnetic field is applied in the longitudinal z direction of the Cartesian coordinate system. However, this is only for the convenience of notation, and in general, the magnetic field can be applied in any spatial direction. (π a / 2) pulse refers to a transverse magnetic field pulse having a magnetic field pulse rotation angle of π / 2 and a magnetic field pulse oscillation direction corresponding to the transverse direction in the Cartesian coordinate system, wherein the lower index a can represent the transverse x direction (a=x), the transverse y direction (a=y), the transverse negative x direction (a=-x), or the transverse negative y direction (a=-y). Therefore, (π a / 2) pulse corresponds to half a Rabi cycle of a two-level quantum system, where the two-level quantum system is defined by the splitting of two Zeeman energy levels of the probe's nucleus induced by a static longitudinal magnetic field. a A pulse corresponds to a complete Rabi cycle. To determine the direction of each rotation, the right-hand rule can be used.

[0036] Exemplarily, irradiating at least one exchange sequence of transverse magnetic field pulses, irradiating the first sequence of transverse magnetic field pulses and / or irradiating the second sequence of transverse magnetic field pulses in the second step may include:

[0037] - irradiating a first transverse magnetic field pulse, wherein the first transverse magnetic field pulse is (π x / 2) Pulse,

[0038] - after irradiating the first transverse magnetic field pulse, irradiating the second transverse magnetic field pulse with a predetermined time delay, wherein the second transverse magnetic field pulse is π xpulse,

[0039] - after irradiating the second transverse magnetic field pulse, irradiating the third transverse magnetic field pulse with a predetermined time delay, wherein the third transverse magnetic field pulse is π x pulse,

[0040] - immediately after irradiating the third transverse magnetic field pulse, irradiating the fourth transverse magnetic field pulse without time delay, wherein the fourth transverse magnetic field pulse is (π -x / 2) Pulse,

[0041] - immediately after irradiating the fourth transverse magnetic field pulse, irradiating the fifth transverse magnetic field pulse without time delay, wherein the fifth transverse magnetic field pulse is (π y / 2) Pulse,

[0042] - after irradiating the fifth transverse magnetic field pulse, irradiating the sixth transverse magnetic field pulse with a predetermined time delay, wherein the sixth transverse magnetic field pulse is π x pulse,

[0043] - after irradiating the sixth transverse magnetic field pulse, irradiating the seventh transverse magnetic field pulse with a predetermined time delay, wherein the seventh transverse magnetic field pulse is (π -y / 2) pulse.

[0044] The at least one exchange sequence of transverse magnetic field pulses, the first sequence of transverse magnetic field pulses and / or the second sequence of transverse magnetic field pulses can also be further simplified by:

[0045] Optionally, the third transverse magnetic field pulse and the fourth transverse magnetic field pulse may be combined into a combined transverse magnetic field pulse and / or replaced by a combined transverse magnetic field pulse, the combined transverse magnetic field pulse being delayed by a predetermined time t D followed by a second transverse magnetic field pulse, wherein the combined transverse magnetic field pulse is (π x / 2) pulse.

[0046] Preferably, the predetermined time delay is t D =1 / (4 JHN ) is given by, and therefore corresponds to the longitudinal spin-spin interaction strength J between the first nucleus and the second nucleus HN It should be noted that the time width of the transverse magnetic field pulse is of the order of the inverse of the Larmor frequency and is therefore much smaller than the predetermined time delay, because the Larmor frequency is much larger than the longitudinal spin-spin interaction strength J HNTherefore, when determining the time length of the transverse magnetic field pulses of at least one exchange sequence, the time length of the transverse magnetic field pulses of the first sequence and / or the time length of the transverse magnetic field pulse sequence of the second sequence, the time width of the transverse magnetic field pulses can be ignored.

[0047] Most preferably, the exchange sequence in the second step comprises synchronously irradiating a first sequence of transverse magnetic field pulses and a second sequence of transverse magnetic field pulses. The first sequence may comprise a pulse sequence irradiating from the first transverse magnetic field pulse to the seventh transverse magnetic field pulse as described above, wherein each pulse frequency may correspond to the Larmor frequency of the first atomic nucleus, and / or each magnetic field pulse rotation angle may correspond to a half or full Rabi period of the first atomic nucleus. The second sequence may comprise a pulse sequence irradiating from the first transverse magnetic field pulse to the seventh transverse magnetic field pulse as described above, wherein each pulse frequency may correspond to the Larmor frequency of the second atomic nucleus, and / or each magnetic field pulse rotation angle may correspond to a half or full Rabi period of the second atomic nucleus.

[0048] Optionally, at least the second step and the third step may form a scanning sequence that is repeatedly performed, i.e., iteratively repeated in an iterative loop, so as to achieve an improved signal-to-noise ratio in determining the NMR relaxation time and / or the NMR spectrum in the fourth step. The iterative loop may terminate when a predetermined signal-to-noise ratio is reached.

[0049] The time delay between executing two scanning sequences may be equal to the thermal equilibrium time T of the first nucleus. eq , i.e. the time required to at least approximately equilibrate the first nucleus in the static longitudinal magnetic field.

[0050] Preferably, the time delay between performing two scanning sequences is greater than or equal to five times the longitudinal relaxation time of the first nuclei.

[0051] Most preferably, the time delay between performing two scanning sequences is less than five times the longitudinal relaxation time of the second nucleus.

[0052] Optionally, the longitudinal relaxation time of the first nucleus may be predetermined, estimated and / or measured.

[0053] Therefore, compared to the case where the time delay corresponds to the equilibrium time of the second nucleus, after measuring the magnetization signal of the second nucleus in the third step, a faster reinitialization can be achieved, and the second scanning sequence can be performed without further delay. In particular, after the nuclear spin of the first nucleus has been quickly balanced in the static longitudinal magnetic field, its polarization is fully restored and can be exchanged with the second nucleus or other nuclei, regardless of their state at the time. Therefore, the proposed method can allow a predetermined signal-to-noise ratio to be achieved with a smaller number of iterations and a smaller amount of time.

[0054] The probe may also include a third nucleus having a third gyromagnetic ratio. The nuclear spin of the third nucleus may interact with the nuclear spin of the first nucleus and / or the nuclear spin of the second nucleus through longitudinal spin-spin interaction. The third nucleus may be 15 N or 13 The nucleus of the C isotope.

[0055] Optionally, exchanging the polarization of the first atomic nucleus and the second atomic nucleus by irradiating at least one exchange sequence of transverse magnetic field pulses in the second step may include:

[0056] - exchanging the polarization of the first nucleus and the third nucleus by irradiating a transverse magnetic field pulse of a first exchange sequence, and

[0057] - exchanging the polarization of the third nucleus and the second nucleus by irradiating a transverse magnetic field pulse of a second exchange sequence, and

[0058] - exchanging the polarization of the first atomic nucleus and the third atomic nucleus by irradiating a transverse magnetic field pulse of a third exchange sequence.

[0059] The first exchange sequence, the second exchange sequence, and the third exchange sequence can be irradiated one after another in succession. The second exchange sequence can be irradiated immediately after the first exchange sequence without a time delay. The third exchange sequence can be irradiated immediately after the second exchange sequence without a time delay.

[0060] The first exchange sequence may include synchronously irradiating a first sequence of transverse magnetic field pulses and a second sequence of transverse magnetic field pulses. As further described above, the first sequence of the first exchange sequence may include a pulse sequence from the first transverse magnetic field pulse to the seventh transverse magnetic field pulse, wherein each pulse frequency may correspond to the Larmor frequency of the first atomic nucleus, and / or each magnetic field pulse rotation angle may correspond to a half or full Rabi period of the first atomic nucleus. As further described above, the second sequence of the first exchange sequence may include irradiating a pulse sequence from the first transverse magnetic field pulse to the seventh transverse magnetic field pulse, wherein each pulse frequency may correspond to the Larmor frequency of the third atomic nucleus and / or each magnetic field pulse rotation angle may correspond to a half or full Rabi period of the third atomic nucleus.

[0061] Then, the predetermined time delay of the first exchange sequence can be determined by t D =1 / (4J HC ) is given by, which can correspond to the longitudinal spin-spin interaction strength J between the first nucleus and the third nucleus. HC One quarter of the reciprocal of (in frequency units).

[0062] The second exchange sequence may include synchronously irradiating a first sequence of transverse magnetic field pulses and a second sequence of transverse magnetic field pulses. As further described above, the first sequence of the second exchange sequence may include a pulse sequence from the first transverse magnetic field pulse to the seventh transverse magnetic field pulse, wherein each pulse frequency may correspond to the Larmor frequency of the second atomic nucleus and / or each magnetic field pulse rotation angle may correspond to a half or full Rabi period of the second atomic nucleus. As further described above, the second sequence of the second exchange sequence may include irradiating a pulse sequence from the first transverse magnetic field pulse to the seventh transverse magnetic field pulse, wherein each pulse frequency may correspond to the Larmor frequency of the third atomic nucleus and / or each magnetic field pulse rotation angle may correspond to a half or full Rabi period of the third atomic nucleus.

[0063] The predetermined time delay of the second exchange sequence can be determined by t D =1 / (4J CN ) is given by, which can correspond to the longitudinal spin-spin interaction strength J between the second and third nuclei. CN One quarter of the reciprocal of (in frequency units).

[0064] The third exchange sequence may be the same as the first exchange sequence.

[0065] In this way, a complete exchange of polarization between the first nucleus and the second nucleus can be achieved indirectly via the third nucleus without the need for a predetermined time delay t between the transverse magnetic field pulses. D =1 / (4J HN ) irradiation exchange sequence.

[0066] In particular, the longitudinal spin-spin interaction strength J between the first nucleus and the second nucleus HN can be less than the longitudinal spin-spin interaction strength J between the first nucleus and the third nucleus HC and / or less than the longitudinal spin-spin interaction strength J between the second nucleus and the third nucleus CN In this case, exchanging the polarization between the first and second nuclei by a third nucleus is even more beneficial and time-efficient than directly exchanging the polarization between the first and second nuclei by irradiating only a single exchange sequence as described further above.

[0067] At least one excitation pulse in the third step may be (π y / 2) pulse or (π x / 2) pulse. The at least one excitation pulse may also include two excitation pulses separated by a time delay, wherein the two excitation pulses may form an excitation pulse sequence. The excitation pulse sequence in the third step may correspond to a saturation recovery pulse sequence or a reverse recovery pulse sequence. Based on the magnetization signal generated by the probe, the longitudinal relaxation time of the second atomic nucleus may be determined in the fourth step.

[0068] Alternatively, the excitation pulse sequence in the third step may also correspond to a Carr-Purcell-Meiboom-Gil (CPMG) pulse sequence. Based on the magnetization signal generated by the probe, the transverse relaxation time of the second atomic nucleus can be determined.

[0069] When iterating multiple scan sequences, the time delay of the corresponding excitation pulse sequence can also be changed from scan sequence to scan sequence, so as to measure the magnetization signal corresponding to different time delays of the excitation pulse sequence. Then, the nuclear magnetic relaxation time can be determined from the time decay of the magnetization signal as a function of the time delay of the excitation pulse sequence.

[0070] Additionally or alternatively, when iterating a plurality of scan sequences, the pulse phase of the excitation pulse or excitation pulse sequence may also vary, for example, alternate, from scan sequence to scan sequence.For example, the magnetic field pulse oscillation direction may alternate between the x-direction and the y-direction.

[0071] Exemplarily, in the first scanning sequence, the oscillation direction of the magnetic field pulse of the excitation pulse or the excitation pulse sequence in the third step may be the x-direction, and the magnetization signal measured in the third step of the first sequence may correspond to the transverse magnetization in the x-direction. In the second scanning sequence, the oscillation direction of the magnetic field pulse of the excitation pulse or the excitation pulse sequence in the third step may be the y-direction, and the magnetization signal measured in the third step of the first sequence may correspond to the transverse magnetization in the y-direction. By implementing such a phase cycle, i.e., changing the pulse phase from scanning sequence to scanning sequence, errors caused by inaccuracies in the pulse width setting can be eliminated. In particular, since the body magnetization of the first atomic nucleus and the second atomic nucleus can be exclusively oriented in the longitudinal direction of the static longitudinal magnetic field after performing the second step, such a phase cycle can be implemented in a particularly simple and efficient manner.

[0072] The nuclear magnetic resonance relaxation time determined in the fourth step may be the longitudinal relaxation time of the second nucleus or the transverse relaxation time of the second nucleus.

[0073] The NMR spectrum determined in the fourth step may be a one-dimensional or two-dimensional NMR spectrum of the second atomic nucleus, which may be obtained by Fourier transformation of the magnetization signal measured in the third step.

[0074] The NMR relaxation time may be determined from the damping of the free induction decay corresponding to the magnetization signal and / or from the width of one or more resonances in the NMR spectrum.

[0075] In another aspect, the present invention relates to an apparatus configured to determine the nuclear magnetic resonance relaxation time of a probe (P) and / or the nuclear magnetic resonance spectrum of the probe (P), wherein the probe (P) comprises a first atomic nucleus (H) having a first gyromagnetic ratio and a second atomic nucleus (N) having a second gyromagnetic ratio, and the first gyromagnetic ratio is greater than the second gyromagnetic ratio.

[0076] The device includes at least one static magnetic field generating unit, which is configured to polarize the first atomic nucleus and the second atomic nucleus by applying a longitudinal static magnetic field to the probe. The device also includes at least one electromagnetic pulse generating unit, which is configured to exchange the polarization of the first atomic nucleus and the second atomic nucleus by irradiating at least one transverse magnetic field pulse of an exchange sequence. The at least one electromagnetic pulse generating unit is also configured to transversely magnetize the second atomic nucleus by irradiating at least one excitation pulse of the transverse magnetic field pulse. The device also includes at least one signal receiving unit, which is configured to measure the magnetization signal generated by the at least one excitation pulse. The device also includes at least one electronic control and evaluation unit, which is configured to determine the nuclear magnetic resonance relaxation time and / or the nuclear magnetic resonance spectrum based on the measured magnetization signal.

[0077] Specifically, the present invention may relate to a device configured to perform a method having some or all of the above steps.

[0078] The present invention also relates to a computer program comprising computer-readable instructions, which, when executed by a computer, causes the computer to perform the method having some or all of the above steps.

[0079] When the computer program is run in the computing unit, the computer program (or sequence of instructions) can use software means to execute a method for determining the nuclear magnetic resonance relaxation time of the probe and / or the nuclear magnetic resonance spectrum of the probe. The computer program can be directly stored in an internal memory, a memory unit, or a data storage unit of at least one electronic control and evaluation unit.

[0080] The invention also relates to a computer readable data carrier on which the above-mentioned computer program is stored.The computer program product may be stored on a machine readable data carrier, preferably a digital storage medium.

[0081] In summary, a simple and practical method, apparatus, computer program, and data carrier are proposed for determining the NMR relaxation time and / or the NMR spectrum of a probe with high precision and time efficiency. The proposed method allows only a small number of pulses to be irradiated in a relatively short period of time and takes into account the quantum mechanical properties of the first, second and / or third nuclei. Furthermore, the proposed method may allow a smaller number of experimental parameters that need to be calibrated compared to existing protocols. BRIEF DESCRIPTION OF THE DRAWINGS

[0082] Exemplary embodiments of the present invention are illustrated in the accompanying drawings and will be referred to herein. Figure 1 The description will proceed to Figure 5.

[0083] In the figure:

[0084] Figure 1 A schematic diagram showing an embodiment of the device is shown,

[0085] Figure 2 A schematic flow chart showing an embodiment of the method is shown,

[0086] Figure 3 An example of an exchange pulse sequence is shown,

[0087] Figure 4a A saturation recovery pulse sequence is shown as an example of an excitation pulse sequence.

[0088] Figure 4b A reverse recovery pulse sequence is shown as an example of an excitation pulse sequence.

[0089] Figure 4c A CPMG pulse sequence is shown as an example of an excitation pulse sequence.

[0090] Figure 5a The diethyl phthalimidomalonate-2- 13 C- 15 N(ethylphthalimidomalonate-2- 13 C- 15 N) molecular structure,

[0091] Figure 5b shows the NMR spectrum determined based on the magnetization signal without prior exchange of polarization,

[0092] Figure 5c The NMR spectrum determined based on the magnetization signal without prior exchange of polarization is shown. DETAILED DESCRIPTION

[0093] Figure 1The schematic diagram of an embodiment of the device is shown. The device comprises a static magnetic field generating unit STATIC configured to polarize the first atomic nucleus H and the second atomic nucleus N by applying a longitudinal static magnetic field B0 to the probe P.

[0094] The device also includes an electromagnetic pulse generating unit PULSE configured to exchange the polarization of the first atomic nucleus H and the second atomic nucleus N by irradiating the transverse magnetic field pulse of the exchange sequence SWAP. The electromagnetic pulse generating unit PULSE is also configured to transversely magnetize the second atomic nucleus N by irradiating the transverse magnetic field pulse of the excitation pulse sequence EXC.

[0095] The device further comprises a signal receiving unit DECT configured to measure a magnetization signal FID of a second nucleus N generated by the irradiation excitation pulse sequence EXC.

[0096] The device further comprises an electronic control and evaluation unit CONTROL configured to determine the NMR relaxation time and the NMR spectrum from the measured magnetization signal FID of the second nucleus N.

[0097] The static magnetic field generating unit STATIC, the electromagnetic pulse generating unit PULSE, and the signal receiving unit DECT are electronically connected to the electronic control and evaluation unit CONTROL. The static magnetic field generating unit STATIC is configured to generate a magnetic field with a strength between 5 Tesla and 20 Tesla. The electromagnetic pulse generating unit PULSE comprises a magnetic excitation coil and is configured to generate radio frequency pulses as transverse magnetic field pulses. The signal receiving unit DECT comprises a magnetic receiving coil. The magnetic receiving coil of the signal receiving unit DECT is identical to the magnetic excitation coil of the electromagnetic pulse generating unit PULSE. The signal receiving unit DECT further comprises at least one amplifier configured to amplify the magnetization signal FID. The electronic control and evaluation unit CONTROL comprises a computer.

[0098] The following figure provides Figure 1 Repeated features are given the same reference numerals.

[0099] Figure 2 A schematic flow chart of an embodiment of a method for determining the NMR relaxation time and the NMR spectrum of a probe P is shown, wherein the probe P comprises a first nucleus H having a first gyromagnetic ratio and a second nucleus N having a second gyromagnetic ratio. The first gyromagnetic ratio is greater than the second gyromagnetic ratio.

[0100] The method comprises a first step S1, polarizing a first atomic nucleus H and a second atomic nucleus N by applying a longitudinal static magnetic field B0 to a probe P; a second step S2, exchanging the polarization of the first atomic nucleus H and the second atomic nucleus N by irradiating a transverse magnetic field pulse of an exchange sequence SWAP; a third step S3, transversely magnetizing the second atomic nucleus N by irradiating an excitation pulse sequence EXC, and measuring a magnetization signal FID generated by the second atomic nucleus N; and a fourth step S4, determining a nuclear magnetic resonance relaxation time T1(N) of the second atomic nucleus N and a nuclear magnetic resonance spectrum of the second atomic nucleus N according to the measured magnetization signal FID of the second atomic nucleus N.

[0101] The magnetization signal FID corresponds to the time-decaying transverse bulk magnetization of the second atomic nucleus, also called free induction decay. The magnetization signal FID induces a time-dependent current which is measured in a magnetic receiving coil of the signal receiving unit DECT.

[0102] The second step S2 and the third step S3 form a scanning sequence SCAN, which is iteratively repeated to obtain an improved signal-to-noise ratio when determining the nuclear magnetic relaxation time T1(N) and the nuclear magnetic spectrum of the second nucleus N in the fourth step S4.

[0103] The time delay between two scanning sequences SCAN, i.e., the time interval between the last transverse magnetic field pulse of the excitation pulse sequence EXC irradiated in the third step S3 of the first scanning sequence and the first transverse magnetic field pulse of the exchange sequence SWAP irradiated in the second step S2 of the second scanning sequence immediately after the first scanning sequence, corresponds to the thermal equilibrium time T of the first nucleus H eq . Figure 3 An embodiment of an exchange pulse sequence SWAP is shown. The transverse magnetic field pulses of the exchange sequence SWAP include transverse magnetic field pulses of a first sequence SEQ1 that excites the first atomic nucleus H and transverse magnetic field pulses of a second sequence SEQ2 that excites the second atomic nucleus N. Therefore, the pulse frequency of the transverse magnetic field pulses of the first sequence SEQ1 corresponds to the Larmor frequency of the first atomic nucleus H in the longitudinal static magnetic field B0. The pulse frequency of the transverse magnetic field pulses of the second sequence SEQ2 corresponds to the Larmor frequency of the second atomic nucleus N in the longitudinal static magnetic field B0. The transverse magnetic field pulses of the first sequence SEQ1 and the transverse magnetic field pulses of the second sequence SEQ2 are irradiated simultaneously and synchronously.

[0104] Hereinafter, for ease of reference, it is assumed that the longitudinal static magnetic field B0 is applied in the longitudinal z direction of the Cartesian coordinate system.

[0105] Then, each of the first sequence SEQ1 and the second sequence SEQ2 may comprise the following transverse magnetic field pulses:

[0106] - a first transverse magnetic field pulse P1, wherein the first transverse magnetic field pulse P1 is (π x / 2) Pulse,

[0107] - with a predetermined time delay t relative to the first transverse magnetic field pulse P1 D The second transverse magnetic field pulse P2 is π x pulse,

[0108] - has a predetermined time delay t relative to the second transverse magnetic field pulse P2 D The third transverse magnetic field pulse P3 is π x pulse,

[0109] - a fourth transverse magnetic field pulse P4 immediately following the third transverse magnetic field pulse P3 without a time delay, wherein the fourth transverse magnetic field pulse P4 is (π -x / 2) Pulse,

[0110] - a fifth transverse magnetic field pulse P5 immediately following the fourth transverse magnetic field pulse P4 without a time delay, wherein the fifth transverse magnetic field pulse P5 is (π y / 2) Pulse,

[0111] - after the fifth transverse magnetic field pulse P5 there is a predetermined time delay t D The sixth transverse magnetic field pulse P6 is π x Pulse, and

[0112] - after the sixth transverse magnetic field pulse P6 there is a predetermined time delay t D The seventh transverse magnetic field pulse P7 is (π -y / 2) pulse.

[0113] Therefore, each transverse magnetic field pulse of the first sequence SEQ1 corresponds to a transverse magnetic field pulse of the second sequence SEQ2 in terms of pulse centre timing, magnetic field pulse rotation angle, and magnetic field pulse oscillation direction.

[0114] The predetermined time delay is given by t D =1 / (4J HN ) is given by, and therefore corresponds to the longitudinal spin-spin interaction strength J between the first nucleus H and the second nucleus N HN One quarter of the reciprocal of (in frequency units).

[0115] In the following, the product operator form is used to describe the influence of each pulse of the exchange pulse sequence SWAP on the density matrix of the combined system including the first nucleus H and the second nucleus N.

[0116] The Hamiltonian (in units of frequency) describing the Larmor frequency contribution and the longitudinal coupling of the nuclear spins of the first nucleus H and the second nucleus N is as follows:

[0117] H=-ω H I z -ω N S z +2πJ I z S z , (1)

[0118] Among them, ω H =γ1B0 represents the Larmor frequency of the first nucleus with the first gyromagnetic ratio γ1, ω N =γ2B0 represents the Larmor frequency of the second nucleus with the second gyromagnetic ratio γ2, and J represents the frequency equal to J HN The longitudinal spin-spin interaction of z represents the z component of the nuclear spin operator of the first nucleus H, S z denotes the z-component of the nuclear spin operator of the second nucleus N. The quantum mechanical expectation value of the z-component of the nuclear spin operator then corresponds to the corresponding polarization.

[0119] Initially, i.e., before irradiating the exchange pulse sequence SWAP, the state of the combined system can be at least approximately described by the following density matrix:

[0120] ρ0=γ H I z +γ X S z ,, (2)

[0121] in, is a constant proportional to the first gyromagnetic ratio γ1, is a constant proportional to the second gyromagnetic ratio γ2. The above expression assumes thermal equilibrium at room temperature. In addition, for simplicity, the constant additive contribution to the density matrix that is simply proportional to the unit matrix is ​​omitted in the above expression.

[0122] By irradiating the first transverse magnetic field pulse P1 of the first sequence SEQ1 and the second sequence SEQ2, the state of the combined system described by the density matrix is ​​transformed into:

[0123] ρ1=-γ H I y -γ X S y . (3)

[0124] After waiting for the predetermined time delay t DAfterwards, the state of the combined system is transformed through unitary Hamiltonian dynamics:

[0125]

[0126] By irradiating the second transverse magnetic field pulse P2 of the first sequence SEQ1 and the second sequence SEQ2, the state of the combined system described by the density matrix is ​​transformed into:

[0127]

[0128] After waiting for the predetermined time delay t D Afterwards, the state of the combined system is transformed through normalized Hamiltonian dynamics as:

[0129]

[0130] By irradiating the third transverse magnetic field pulse P3 of the first sequence SEQ1 and the second sequence SEQ2, the state of the combined system described by the density matrix is ​​transformed into:

[0131] ρ5=γ H 2I x S z +γ X 2I z S x . (7)

[0132] By irradiating the fourth transverse magnetic field pulse P4 of the first sequence SEQ1 and the second sequence SEQ2, the state of the combined system described by the density matrix is ​​transformed into:

[0133] ρ6=γ H 2I x S y +γ X 2I y S x . (8)

[0134] By irradiating the fifth transverse magnetic field pulse P5 of the first sequence SEQ1 and the second sequence SEQ2, the state of the combined system described by the density matrix is ​​transformed into:

[0135] ρ7=-γ H 2I z S y -γ X 2I y S z . (9)

[0136] After waiting for the predetermined time delay t D Afterwards, the state of the combined system is transformed through normalized Hamiltonian dynamics as:

[0137]

[0138] By irradiating the sixth transverse magnetic field pulse P6 of the first sequence SEQ1 and the second sequence SEQ2, the state of the combined system described by the density matrix is ​​transformed into:

[0139]

[0140] After waiting for the predetermined time delay t D Afterwards, the state of the combined system is transformed through normalized Hamiltonian dynamics as:

[0141]

[0142] By irradiating the seventh transverse magnetic field pulse P7 of the first sequence SEQ1 and the second sequence SEQ2, the state of the combined system described by the density matrix is ​​transformed into:

[0143] ρ 11 =γ H S z +γ X I z . (13)

[0144] By comparing the state ρ0 of the combined system with the state ρ0 obtained after the irradiation exchange sequence SWAP 11 , it can be seen that the complete exchange of polarization has been achieved. In addition, after the irradiation of the seventh transverse magnetic field pulse P7, the nuclear spin of the first atomic nucleus H and the nuclear spin of the second atomic nucleus N are immediately realigned with the longitudinal static magnetic field B0.

[0145] Figure 4a A saturation recovery pulse sequence is shown as an exemplary embodiment of an excitation pulse sequence EXC, which is irradiated in a third step S3 so as to be able to measure a magnetization signal FID of a second atomic nucleus N generated by the excitation pulse sequence EXC. The saturation recovery pulse sequence includes two transverse magnetic field pulses, wherein the first transverse magnetic field pulse of the saturation recovery pulse sequence is (π x / 2) pulse, whose pulse frequency corresponds to the Larmor frequency of the second nucleus N, and the second transverse magnetic field pulse of the saturation recovery pulse sequence is also (π x / 2) pulses, whose pulse frequency corresponds to the Larmor frequency of the second atomic nucleus N. After irradiating the first transverse magnetic field pulse of the saturation recovery pulse sequence, the second transverse magnetic field pulse of the saturation recovery pulse sequence is irradiated with a time delay τ1. The saturation recovery pulse sequence is irradiated multiple times, each time with a different time delay τ1. Then, the longitudinal relaxation time T1(N) of the second atomic nucleus is determined from the time decay of the magnetization signal FID as a function of the time delay τ1.

[0146] Figure 4b FIG. 4 shows a reverse recovery pulse sequence as another exemplary embodiment of the excitation pulse sequence EXC irradiated in the third step S3. Figure 4a Compared with the saturation recovery pulse sequence shown in the figure, the first transverse magnetic field pulse of the reverse recovery pulse sequence is π x In addition, the longitudinal relaxation time T1(N) is determined by referring to Figure 4a Proceed as described.

[0147] Figure 4c A CPMG pulse sequence is shown as another exemplary embodiment of the excitation pulse sequence EXC irradiated in the third step S3. The first transverse magnetic field pulse of the CPMG pulse sequence is (π x / 2) pulse, followed by irradiation with a specific time delay τ,2τ,.. y Pulse series, such as Figure 4c In the fourth step S4, the transverse relaxation time T2(N) of the second nucleus N is determined in a standard manner based on the magnetization signal FID measured after irradiating a plurality of CPMG pulse sequences, each CPMG pulse sequence having a different characteristic time delay τ.

[0148] Figure 5 shows diethyl phthalimidomalonate-2- 13 C- 15 The molecular structure of N molecule. Benzene-d6 was used as solvent. Therefore, probe P includes isotopes corresponding to 1 The first atomic nucleus H of H corresponds to the isotope 15 N's second nucleus N, and the corresponding isotope 13 The longitudinal spin-spin interaction strength direction between the first nucleus H and the second nucleus N is J HN = 1.7 Hz. The longitudinal spin-spin interaction strength between the first nucleus H and the third nucleus C is J HC = 139 Hz. The longitudinal spin-spin interaction strength between the second nucleus N and the third nucleus C is J CN =13Hz.

[0149] Since the longitudinal spin-spin interaction strength J between the first nucleus H and the second nucleus N HN is smaller than the longitudinal spin-spin interaction strength J between the first nucleus H and the third nucleus C HC , and is less than the longitudinal spin-spin interaction strength J between the second nucleus N and the third nucleus C CN , it is advantageous to indirectly exchange the polarization between the first nucleus H and the second nucleus N through the third nucleus C, as described below.

[0150] This is achieved in an alternative embodiment by successively irradiating three exchange pulse sequences SWAP (i.e., a first exchange pulse sequence SWAP, a second exchange pulse sequence SWAP, and a third exchange pulse sequence SWAP), wherein each of the three exchange pulse sequences SWAP comprises a pulse sequence according to Figure 3 transverse magnetic field pulse.

[0151] More specifically, in an alternative embodiment, exchanging the polarization of the first atomic nucleus H and the second atomic nucleus N by irradiating at least one transverse magnetic field pulse of the exchange sequence SWAP in the second step S2 comprises:

[0152] - exchanging the polarization of the first atomic nucleus H and the third atomic nucleus C by irradiating a transverse magnetic field pulse of a first exchange sequence SWAP,

[0153] - exchanging the polarization of the third nucleus C and the second nucleus N by irradiating a transverse magnetic field pulse of a second exchange sequence SWAP,

[0154] - The polarization of the first atomic nucleus H and the third atomic nucleus C are exchanged by irradiating a transverse magnetic field pulse of the third exchange sequence SWAP.

[0155] The first exchange sequence SWAP, the second exchange sequence SWAP, and the third exchange sequence SWAP are irradiated successively. Figure 3 As shown, each of the first exchange sequence SWAP, the second exchange sequence SWAP, and the third exchange sequence SWPA includes synchronously irradiating transverse magnetic field pulses of the first sequence SEQ1 and transverse magnetic field pulses of the second sequence SEQ2.

[0156] The frequency of the transverse magnetic field pulses of the first sequence SEQ1 of the first exchange sequence SWAP corresponds to the Larmor frequency of the first nucleus H. The frequency of the transverse magnetic field pulses of the second sequence SEQ2 of the first exchange sequence SWAP corresponds to the Larmor frequency of the third nucleus C.

[0157] The frequency of the transverse magnetic field pulses of the first sequence SEQ1 of the second exchange sequence SWAP corresponds to the Larmor frequency of the second nucleus N. The frequency of the transverse magnetic field pulses of the second sequence SEQ2 of the second exchange sequence SWAP corresponds to the Larmor frequency of the third nucleus C.

[0158] The frequency of the transverse magnetic field pulses of the first sequence SEQ1 of the third exchange sequence SWAP corresponds to the Larmor frequency of the first nucleus H. The frequency of the transverse magnetic field pulses of the second sequence SEQ2 of the third exchange sequence SWAP corresponds to the Larmor frequency of the third nucleus C.

[0159] Then, the predetermined time delay t of the first exchange sequence SWAP D1 By D1 =1 / (4J HC ) is given. Then, the predetermined time delay t of the second exchange sequence SWAP is D2 By D2 =1 / (4J CN The predetermined time delay t of the third exchange sequence SWAP is given by D3 Yes D3 =t D1 .

[0160] Therefore, with reference Figure 3 Compared to the discussed direct exchange case using a single exchange sequence SWAP, the polarization of the first nucleus H and the polarization of the second nucleus N are exchanged faster via the third nucleus C.

[0161] Figure 5b The NMR spectrum determined in the fourth step S4 based on the magnetization signal FID obtained in the third step S3 is shown without the prior polarization exchange using the exchange sequence SWAP proposed in the second step S2, i.e., the second step S2 of the proposed method is not performed before performing the third step S3. More specifically, Figure 5b The NMR spectrum shown in is determined after 32 iterations of the third step S3 (using a reverse recovery pulse sequence with a time delay τ1 = 1 s as the excitation pulse sequence EXC) and by averaging the magnetization signal FID measured in each third step S3. Therefore, the time delay / equilibrium time between two third steps S3 in an iterative cycle is T eq = 1000s. The corresponding experiment lasted for about 9 hours in total. Finally, in the fourth step S4, Figure 5b The widths of the four Lorentzian shaped resonances of the NMR spectrum shown are used to determine the four results of the longitudinal relaxation times: T1(N)=(115±5)s, (119±6)s, (114±7)s, (124±3)s.

[0162] Figure 5c FIG. 4 shows an NMR spectrum determined from a magnetization signal FID with a prior polarization exchange, i.e. according to an embodiment of the proposed method. More specifically, Figure 5cThe NMR spectra shown in FIG. 1 are determined by averaging the magnetization signals FID measured in each third step S3 of the scanning sequence SCAN after only 4 iterations of the scanning sequence SCAN are performed using a reverse recovery pulse sequence with a time delay τ1=1 s as the excitation pulse sequence EXC. In each second step S2 of the scanning sequence SCAN, the magnetization signals FID measured in accordance with the reference are realized. Figure 5a The discussed embodiment indirectly exchanges polarization by irradiating the first, second, and third exchange sequences SWAP. Therefore, the time delay / equilibrium time between two scan sequences SCAN in an iterative cycle is Teq=10s. The corresponding experiment lasted about 1 minute in total. Finally, in the fourth step S4, from Figure 5c The widths of the four Lorentzian resonances of the NMR spectrum shown are used to determine the four results of the longitudinal relaxation times: T1(N) = (129±11) s, (101±3) s, (99±5) s, and (107±8) s.

[0163] Clearly, Figure 5a and 5b The NMR spectra and determined NMR relaxation times in are similar and have been obtained with comparable signal-to-noise ratios. Figure 5c The NMR spectra and the corresponding NMR relaxation times are determined in a more time-efficient and resource-efficient manner.

[0164] Of course, features of different embodiments which are disclosed only in the exemplary embodiment may be combined with one another and may also be claimed separately.

Claims

1. A method for determining the nuclear magnetic resonance relaxation time of a probe (P) and / or the nuclear magnetic resonance spectrum of a probe (P), wherein: The probe (P) comprises a first nucleus (H) having a first gyromagnetic ratio and a second nucleus (N) having a second gyromagnetic ratio, and the first gyromagnetic ratio is greater than the second gyromagnetic ratio, and the method comprises the following steps: The first step (S1) is to polarize the first atomic nucleus (H) and the second atomic nucleus (N) by applying a longitudinal static magnetic field B0 to the probe (P); A second step (S2) of exchanging the polarization of the first nucleus (H) and the second nucleus (N) by irradiating at least one exchange sequence (SWAP) of transverse magnetic field pulses, wherein the time length of the at least one exchange sequence (SWAP) is equal to the inverse of the longitudinal spin-spin interaction strength between the first nucleus (H) and the second nucleus (N); A third step (S3) is to transversely magnetize the second atomic nuclei (N) by irradiating at least one excitation pulse (EXC) and measuring the resulting magnetization signal (FID); The fourth step (S4) is to determine the NMR relaxation time and / or the NMR spectrum according to the measured magnetization signal (FID).

2. The method according to claim 1, characterized in that By irradiating the transverse magnetic field pulse of the at least one exchange sequence (SWAP) in the second step (S2), the nuclear spin of the first atomic nucleus (H) and the nuclear spin of the second atomic nucleus (N) are immediately realigned in the direction of the longitudinal static magnetic field B0 after executing the second step (S2) and before executing the third step (S3).

3. A method according to any one of the preceding claims, characterised in that The irradiating of the transverse magnetic field pulses of the at least one exchange sequence (SWAP) in the second step (S2) includes irradiating the transverse magnetic field pulses of the first sequence (SEQ1) to excite the first atomic nucleus (H), and irradiating the transverse magnetic field pulses of the second sequence (SEQ2) to excite the second atomic nucleus (N), wherein the pulse frequency of the transverse magnetic field pulses of the first sequence (SEQ1) corresponds to the Larmor frequency of the first atomic nucleus (H) in the longitudinal static magnetic field B0, and the pulse frequency of the transverse magnetic field pulses of the second sequence (SEQ2) corresponds to the Larmor frequency of the second atomic nucleus (N) in the longitudinal static magnetic field B0.

4. The method according to claim 3, characterized in that The transverse magnetic field pulses of the first sequence (SEQ1) and the transverse magnetic field pulses of the second sequence (SEQ2) are irradiated simultaneously and synchronously, and / or the time length of the transverse magnetic field pulses of the first sequence (SEQ1) is the same as the time length of the transverse magnetic field pulses of the second sequence (SEQ2).

5. The method according to claim 3, characterized in that: Each transverse magnetic field pulse of the first sequence (SEQ1) corresponds to a transverse magnetic field pulse of the second sequence (SEQ2) in terms of pulse center timing, magnetic field pulse rotation angle and / or magnetic field pulse oscillation direction.

6. The method according to claim 3, characterized in that The irradiating of the transverse magnetic field pulses of the at least one exchange sequence (SWAP), the irradiating of the transverse magnetic field pulses of the first sequence (SEQ1) and / or the irradiating of the transverse magnetic field pulses of the second sequence (SEQ2) in the second step (S2) comprises: irradiating a first transverse magnetic field pulse (P1), wherein the first transverse magnetic field pulse (P1) is π x / 2 pulse; After irradiating the first transverse magnetic field pulse (P1), a predetermined time delay t D irradiating a second transverse magnetic field pulse (P2), wherein the second transverse magnetic field pulse (P2) is π x pulse; After irradiating the second transverse magnetic field pulse (P2), the predetermined time delay t D irradiating a third transverse magnetic field pulse (P3), wherein the third transverse magnetic field pulse (P3) is π x pulse; After irradiating the third transverse magnetic field pulse (P3), a fourth transverse magnetic field pulse (P4) is irradiated immediately without time delay, wherein the fourth transverse magnetic field pulse (P4) is π -x / 2 pulse; After irradiating the fourth transverse magnetic field pulse (P4), a fifth transverse magnetic field pulse (P5) is irradiated immediately without time delay, wherein the fifth transverse magnetic field pulse (P5) is π y / 2 pulse; After irradiating the fifth transverse magnetic field pulse (P5), the predetermined time delay t D irradiating a sixth transverse magnetic field pulse (P6), wherein the sixth transverse magnetic field pulse (P6) is π x Pulse; and After irradiating the sixth transverse magnetic field pulse (P6), the predetermined time delay t D irradiating a seventh transverse magnetic field pulse (P7), wherein the seventh transverse magnetic field pulse (P7) is π -y / 2 pulse.

7. The method according to claim 6, characterized in that The predetermined time delay is t D =1 / (4J HN ), where J HN is the longitudinal spin-spin interaction strength between the first nucleus (H) and the second nucleus (N).

8. The method according to claim 1 or 2, characterized in that: At least the second step (S2) and the third step (S3) form a scanning sequence (SCAN) which is repeatedly performed before the fourth step (S4) is performed, so as to achieve an improved signal-to-noise ratio for determining the nuclear magnetic resonance relaxation time and / or the nuclear magnetic resonance spectrum in the fourth step (S4), wherein the time delay between performing two scanning sequences (SCAN) corresponds to the thermal equilibrium time T of the first atomic nucleus (H). eq .

9. The method according to claim 1 or 2, characterized in that: The first atomic nucleus (H) is 1 The nucleus of the H isotope and / or the second nucleus (N) is 15 N isotope or 13 The nucleus of the C isotope.

10. The method according to claim 1 or 2, characterized in that: The nuclear magnetic resonance relaxation time is the longitudinal relaxation time of the second atomic nucleus (N) or the transverse relaxation time of the second atomic nucleus (N); and / or The NMR spectrum is a one-dimensional NMR spectrum of the second atomic nucleus (N); and / or In the third step (S3), a plurality of excitation pulses (EXC) are irradiated, wherein the plurality of excitation pulses (EXC) correspond to a saturation recovery pulse sequence, a reverse recovery pulse sequence and / or a Carr-Purcell-Meiboom-Gil (CPMG) pulse sequence.

11. A method for determining the nuclear magnetic resonance relaxation time of a probe (P) and / or the nuclear magnetic resonance spectrum of a probe (P), wherein: The probe (P) comprises a first nucleus (H) having a first gyromagnetic ratio and a second nucleus (N) having a second gyromagnetic ratio, and the first gyromagnetic ratio is greater than the second gyromagnetic ratio, and the method comprises the following steps: The first step (S1) is to polarize the first atomic nucleus (H) and the second atomic nucleus (N) by applying a longitudinal static magnetic field B0 to the probe (P); A second step (S2) of exchanging the polarization of the first atomic nucleus (H) and the second atomic nucleus (N) by irradiating at least one transverse magnetic field pulse of an exchange sequence (SWAP); A third step (S3) is to transversely magnetize the second atomic nuclei (N) by irradiating at least one excitation pulse (EXC) and measuring the resulting magnetization signal (FID); The fourth step (S4) is to determine the NMR relaxation time and / or the NMR spectrum according to the measured magnetization signal (FID), wherein The probe (P) further comprises a third nucleus (C) having a third gyromagnetic ratio, and the step of exchanging the polarization of the first nucleus (H) and the second nucleus (N) by irradiating at least one transverse magnetic field pulse of an exchange sequence (SWAP) in the second step (S2) comprises: exchanging the polarization of the first atomic nucleus (H) and the third atomic nucleus (C) by irradiating a transverse magnetic field pulse of a first exchange sequence (SWAP); exchanging the polarization of the third atomic nucleus (C) and the second atomic nucleus (N) by irradiating a transverse magnetic field pulse of a second exchange sequence (SWAP); and The polarization of the first atomic nucleus (H) and the third atomic nucleus (C) are exchanged by irradiating a transverse magnetic field pulse of a third exchange sequence (SWAP), wherein: The longitudinal spin-spin interaction strength J between the first nucleus (H) and the second nucleus (N) is HN is less than the longitudinal spin-spin interaction strength J between the first atomic nucleus (H) and the third atomic nucleus (C) HC ; and / or The longitudinal spin-spin interaction strength J between the first nucleus (H) and the second nucleus (N) is HN is less than the longitudinal spin-spin interaction strength J between the second nucleus (N) and the third nucleus (C) CN .

12. A device configured to determine the nuclear magnetic resonance relaxation time of a probe (P) and / or the nuclear magnetic resonance spectrum of the probe (P), wherein: The probe (P) comprises a first nucleus (H) having a first gyromagnetic ratio and a second nucleus (N) having a second gyromagnetic ratio, the first gyromagnetic ratio being greater than the second gyromagnetic ratio, wherein the device comprises: at least one static magnetic field generating unit (STATIC), the at least one static magnetic field generating unit being configured to polarize the first atomic nuclei (H) and the second atomic nuclei (N) by applying a longitudinal static magnetic field B0 to the probe (P); at least one electromagnetic pulse generating unit (PULSE), the at least one electromagnetic pulse generating unit being configured to exchange polarization of the first atomic nucleus (H) and the second atomic nucleus (N) by irradiating at least one exchange sequence (SWAP) of transverse magnetic field pulses, wherein the time length of the at least one exchange sequence (SWAP) is equal to the inverse of the longitudinal spin-spin interaction strength between the first atomic nucleus (H) and the second atomic nucleus (N), and to transversely magnetize the second atomic nucleus (N) by irradiating at least one excitation pulse (EXC) of the transverse magnetic field pulses; at least one signal receiving unit (DECT) configured to measure a magnetization signal (FID) generated by the at least one excitation pulse (EXC); and At least one electronic control and evaluation unit (CONTROL) is configured to determine the NMR relaxation time and / or the NMR spectrum from the measured magnetization signal (FID).

13. A device configured to determine the nuclear magnetic resonance relaxation time of a probe (P) and / or the nuclear magnetic resonance spectrum of the probe (P), wherein: The probe (P) includes a first nucleus (H) having a first gyromagnetic ratio, a second nucleus (N) having a second gyromagnetic ratio, and a third nucleus (C) having a third gyromagnetic ratio, and the first gyromagnetic ratio is greater than the second gyromagnetic ratio, and The longitudinal spin-spin interaction strength J between the first nucleus (H) and the second nucleus (N) is HN is less than the longitudinal spin-spin interaction strength J between the first atomic nucleus (H) and the third atomic nucleus (C) HC ; and / or The longitudinal spin-spin interaction strength J between the first nucleus (H) and the second nucleus (N) is HN is less than the longitudinal spin-spin interaction strength J between the second nucleus (N) and the third nucleus (C) CN , Wherein, the device comprises: at least one static magnetic field generating unit (STATIC), the at least one static magnetic field generating unit being configured to polarize the first atomic nuclei (H) and the second atomic nuclei (N) by applying a longitudinal static magnetic field B0 to the probe (P); at least one electromagnetic pulse generating unit (PULSE), the at least one electromagnetic pulse generating unit being configured to exchange the polarization of the first atomic nucleus (H) and the second atomic nucleus (N) by irradiating the transverse magnetic field pulse of at least one exchange sequence (SWAP), wherein exchanging the polarization of the first atomic nucleus (H) and the second atomic nucleus (N) by irradiating the transverse magnetic field pulse of at least one exchange sequence (SWAP) comprises: exchanging the polarization of the first atomic nucleus (H) and the third atomic nucleus (C) by irradiating the transverse magnetic field pulse of the first exchange sequence (SWAP), and exchanging the polarization of the third atomic nucleus (C) and the second atomic nucleus (N) by irradiating the transverse magnetic field pulse of the second exchange sequence (SWAP), and exchanging the polarization of the first atomic nucleus (H) and the third atomic nucleus (C) by irradiating the transverse magnetic field pulse of the third exchange sequence (SWAP); and the at least one electromagnetic pulse generating unit (PULSE) is further configured to transversely magnetize the second atomic nuclei (N) by irradiating at least one excitation pulse (EXC) of a transverse magnetic field pulse; at least one signal receiving unit (DECT) configured to measure a magnetization signal (FID) generated by the at least one excitation pulse (EXC); and At least one electronic control and evaluation unit (CONTROL) is configured to determine the NMR relaxation time and / or the NMR spectrum from the measured magnetization signal (FID).

14. A computer program comprising instructions which, when executed by a computer, cause the computer to perform the steps of the method according to any one of claims 1 to 11.

15. A computer-readable data carrier having stored thereon the computer program according to claim 14.

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