WO2019207815A1

WO2019207815A1 - Method for enhancing magnetic resonance sensitivity by quantum coding

Info

Publication number: WO2019207815A1
Application number: PCT/JP2018/037504
Authority: WO
Inventors: 誠根耒; 北川　勝浩; 晃徳香川; 直規一条; 太香典杉山; 靖森田; 剛志村田; 祐士中村
Original assignee: 国立大学法人大阪大学; 学校法人名古屋電気学園
Priority date: 2018-04-24
Filing date: 2018-10-09
Publication date: 2019-10-31
Also published as: JP2021126132A

Abstract

Provided is a method for enhancing magnetic resonance sensitivity where measurement is directed toward an enhanced-polarization liquid comprising molecules that have a plurality of nuclear spins, wherein the method comprises: a step for placing the plurality of nuclear spins in an environmentally-sensitive entangled state in a state where the molecules have been arranged in a uniform external magnetic field; a step for performing sensing with the plurality of nuclear spins in the entangled state; a step for decoding the plurality of nuclear spins where sensing has been executed by an operation corresponding to the reverse process of the step for placing same in the entangled state; a step for executing spin amplification; and a step for executing NMR measurement. Due to this configuration, detection sensitivity can be enhanced in NMR measurement.

Description

Magnetic resonance sensitivity enhancement by quantum coding

The present invention relates to a method for increasing the sensitivity of magnetic resonance by quantum coding that can improve the detection sensitivity of nuclear magnetic resonance signals in NMR spectroscopy, MRI, and the like.

NMR spectroscopy is an indispensable tool for chemical analysis, and MRI is an essential tool for medical diagnosis. In recent years, dynamic nuclear polarization (hereinafter also referred to as DNP (Dynamic Nuclear Polarization)), which is one of the methods capable of improving these sensitivities, has been actively studied.

In NMR spectroscopy and MRI, nuclear spins in materials (hereinafter also simply referred to as nuclear spins) are precisely controlled under a strong static magnetic field, and from electromagnetic wave signals (NMR signals) modulated by interactions between nuclear spins, etc. Read out a wealth of information at the molecular level. The sensitivity of the NMR signal is proportional to the polarization rate, but the Zeeman energy of the nuclear spin is very low even under a strong magnetic field of several T (tesla) to several tens of T applied by the superconducting magnet. Since this Zeeman energy is 5 orders of magnitude smaller than the thermal energy at room temperature, the ratio of the spin direction to the direction of the static magnetic field (polarization rate) is 10 ⁻⁵ to 10 ⁻⁶ (0.001 to 0. The ratio of nuclear spins contributing to the detection signal out of the resonating nuclear spins is extremely small. Therefore, in order to improve the sensitivity of NMR spectroscopy and MRI, it is important to increase the nuclear spin polarization. “High polarization” generally refers to a case where the polarization rate of a nuclear spin is about 100 times or more than the polarization rate at room temperature, but in this specification, the polarization rate of a nuclear spin. Is a state that exceeds the polarization rate at room temperature.

Application of visualization of chemical response (especially metabolism) in real time using Dissolution DNP method in which the sample is dissolved in an aqueous solution after increasing the nuclear spin polarization rate by DNP and injected into a test tube or body imitating cells Has attracted attention (see Non-Patent Document 1). In consideration of this application, the detection sensitivity (SN (signal / noise) ratio, hereinafter simply referred to as “sensitivity”) of the NMR signal is input by the number K of nuclear spins in one molecule in a normal method. It is proportional to the total number N of molecules and the polarization rate P of nuclear spins (sensitivity ∝ K × N × P). Usually, the polarization rate P is very small as described above, but if the DNP is increased to nearly 100%, the sensitivity can be increased by 10,000 times or more. On the other hand, when sending highly sensitive molecules into a living body, the total number N of molecules needs to be limited to a lethal dose or less, and the sensitivity of this method is limited by the molecules used, and the application range is limited.

It has been known that if a multi-body spin system encoded in a specific entangled state is used as a sensor, precise sensing can be performed with sensitivity that cannot be achieved by classical technology. The following Non-Patent Documents 2 to 5 report the results of sensing using large-scale entanglement in a cooled atomic gas or unsampled molecular spin system with the development of quantum control technology.

In actual applications, the number of sensors (ie, the total number of molecules) N can be increased by increasing the sensitivity without using the entangled state. In many cases, however, the number of sensors N is limited for some reason. So, the ultimate high sensitivity is realized by entanglement sensing. For example, as described above, entanglement sensing is an important technique for in vivo metabolic imaging in which the total N of the sensor is strongly limited by the lethal dose.

In vivo metabolic imaging, which has been actively researched in the fields of NMR spectroscopy and MRI in recent years, has been highly polarized to about several tens of percent as Dissolution DNP, as disclosed in Non-Patent Documents 6 and 7. It was established by the development of a technique for producing an aqueous solution of molecules with nuclear spins. In this method, a molecule having a highly polarized nuclear spin is injected into a test tube or living body imitating a cell before the highly polarized state is broken by spin lattice relaxation. The state of metabolism is imaged in real time from changes in signal intensity and frequency measured by MRI and MRSI (Magnetic Resonance Spectroscopic Imaging).

Consider the sensitivity of metabolic imaging. Here, first, a molecule belonging to the model molecular system shown in FIG. 1 in which only one observable nuclear spin S (for example, a nucleus having a spin quantum number (hereinafter also simply referred to as a spin) ½) exists is used. Think about the sensitivity when In FIG. 1, the bond between the atom having the nuclear spin S and another atom is shown by a line segment, and the other atom itself bonded to the atom having the nuclear spin S is not shown. Note that FIG. 1 shows a connection relationship between atoms and does not show a three-dimensional structure.

For convenience, the pure state with a polarization rate of 100% is assumed to be the initial state. Consider an ideal case where there is no decoherence of the state at the time of detection and the fidelity of the gate operation is 100%. The quantum state of 1/2 nuclear spin is expressed as P.I. A. M.M. Introduced by Dirac, it is represented by a ket (| 導入>), which is a standard notation for describing quantum states in quantum mechanics. | 0> represents a state in which the direction of nuclear spin is the same direction as the external magnetic field, and | 1> represents a state in which the direction of nuclear spin is opposite to the external magnetic field.

The measurement protocol is shown in FIG. In FIG. 2, the state of the nuclear spin is shown at the left end, and the operations shown in order from the left to the right are executed. First, a nuclear spin is brought into a coherent state by a Hadamard gate H. This is realized by irradiating molecules arranged in a uniform external magnetic field with RF pulses (resonance frequency) of a predetermined pulse sequence including π / 2 pulse, π pulse, etc. in NMR measurement (non-resonance). (See Patent Documents 12 and 13). Thereby, the nuclear spin | 0> becomes a coherent state (overlapping state of two eigenstates) of (| 0> + | 1>) / 2 ^1/2 . Subsequently, when held for a predetermined time, the nuclear spin is affected by a perturbation magnetic field (change from a uniform magnetic field) due to the environment (hereinafter also referred to as sensing), and an offset is generated in the resonance frequency to be measured. As a result, the nuclear spin undergoes φ rotation about the Z axis (magnetic field direction), and the state of the nuclear spin changes to (| 0> + e ^iφ | 1>) / 2 ^1/2 . Subsequently, a detection operation 100 for detecting NMR signals is performed. COSφ is obtained as the expected value of the measurement signal. From this result, φ can be estimated and the frequency shift can be read.

In the measurement, thermal noise exists in the detection circuit. Therefore, even if accumulated many times using the latest detection technology, if there are no more than 10 ⁶ molecules, the signal does not exceed thermal noise in one measurement, and φ cannot be estimated. A typical detection circuit requires many orders of magnitude more molecules. At the time of detection, quantum noise is added to the state of the nuclear spin, but since the number of molecules is large, the quantum noise is many orders of magnitude smaller than the signal and the thermal noise of the detector.

Non-Patent Documents 2 and 3 disclose techniques for improving the sensitivity of NMR signals for molecules belonging to the model molecular system shown in FIG. In the model molecular system shown in FIG. 3, there are a plurality (K) of nuclear spins, of which only one nuclear spin S can be observed, and the remaining nuclear spin I (for example, the spin quantum number is 0) is not observable. Note that FIG. 3 shows a connection relationship between atoms and does not show a three-dimensional structure.

The measurement protocol is shown in Fig. 4. The meaning of the notation in FIG. 4 is the same as in FIG. At the left end, the initial state of K nuclear spins (one nuclear spin S and the remaining nuclear spin I) is shown. The uppermost stage is the initial state of the observable nuclear spin S.

First, the observable nuclear spin S is made into a coherent state of (| 0> + | 1>) / 2 ^1/2 by the Hadamard gate H. For this purpose, as described above, π / 2 pulses or the like are irradiated to molecules arranged in a uniform external magnetic field. Next, an encoding operation 102 for applying a control NOT gate (hereinafter also referred to as a CNOT gate) from the nuclear spin S to all the nuclear spins I is performed. This is performed by applying an RF pulse (resonance frequency) of a predetermined pulse sequence including a π / 2 pulse, a π pulse, etc., which is a rotation operation around the X axis or the Y axis (Non-Patent Documents 12 and 13). reference). As a result, the state of K nuclear spins is changed to (| 00... 0> + | 11... 1>) / 2 ^1/2 entangled GHZ state (Greenberger-Horne-Zeilinger state). Become. Subsequently, a sensing operation 104 is performed. As a result, all nuclear spins S and I are subjected to φ rotation, and the state of K nuclear spins is (| 00... 0> + e ^iKφ | 11... 1>) / 2 ^1/2 . change. Finally, when the decoding operation 106 is performed by the control NOT gate, the state of K nuclear spins becomes (| 0> + e ^iKφ | 1>) | 00... 0> / 2 ^1/2 . Accordingly, the rotation phase felt by the observable nuclear spin S is K times that of the protocol of FIG. 2, and the signal intensity is K times by the detection operation 108 for detecting the NMR signal. The protocol of FIG. 4 and the protocol of FIG. 2 have the same thermal noise of the detection circuit and the quantum noise of the observable nucleus, and therefore the sensitivity to the change in φ that can be estimated is better for the protocol of FIG. 4 than for the protocol of FIG. And up to K times higher.

Also, Non-Patent Documents 4 and 5 disclose techniques for improving the sensitivity of NMR signals targeting molecules belonging to the model molecular system shown in FIG. In the model molecular system shown in FIG. 5, there are a plurality (K) of nuclear spins, all of which are observable nuclear spins S. In addition, FIG. 5 shows the connection relationship between atoms, and does not show a three-dimensional structure.

The measurement protocol is shown in FIG. The meaning of the notation in FIG. 6 is the same as in FIG. At the left end, the initial state of K nuclear spins S is shown. In FIG. 6, all nuclear spins S are (| 0> + e ^iφ | 1>) / 2 ^1/2 , and the signal is K times stronger than the protocol of FIG.

US Pat. No. 7,474,095 US Pat. No. 8,980,225 US Pat. No. 9,642,924 JP 2017-15443 A

When measuring the molecule belonging to the model molecular system shown in FIG. 5 using the protocol of FIG. 6, the signal intensity is considered to be K times that of the protocol of FIG. Sensitivity is not K times. In other words, the thermal noise of the detection circuit is the same as when the number of observable nuclear spins is one, but since the number of observable nuclear spins is K, the quantum noise is K ^1/2 times. Therefore, when the thermal noise is smaller than the quantum noise as in the case of detecting using light (when the quantum noise is the main), the sensitivity is K ^1/2 compared to the measurement situation in the protocol of FIG. It is only doubled. That is, when quantum noise is taken into account, one observable nuclear spin out of K nuclear spins is used in comparison with the protocol of FIG. 6 which uses a molecule in which all K nuclear spins are observable nuclear spins S. The protocol of FIG. 4 using molecules with S is rather K ^1/2 times more sensitive.

Further, when thermal noise is more dominant than quantum noise as in NMR measurement, the sensitivity of the protocol of FIG. 4 is K times higher than that of FIG. 2 as in the protocol of FIG. Sensitivity. Therefore, until now, it was thought that the protocol of FIG. 4 was sufficient for NMR measurement. However, it is preferable to further improve the sensitivity in NMR measurement. In particular, as described above, regarding in vivo metabolic imaging, since the total number N of detection target molecules to be sent into the living body must be limited to a lethal dose or less, it is desired to further improve sensitivity.

Therefore, an object of the present invention is to provide a method for increasing the sensitivity of magnetic resonance by quantum coding that can improve the detection sensitivity of nuclear magnetic resonance signals in NMR measurements such as NMR spectroscopy and MRI.

The magnetic resonance sensitization method according to the first aspect of the present invention is a magnetic resonance sensitization using a liquid containing a plurality of nuclear spins and a highly polarized molecule as a measurement target. It is a chemical method. This magnetic resonance sensitization method is based on a quantum coding step in which a plurality of nuclear spins are entangled in an environmentally sensitive state with molecules placed in a uniform external magnetic field, and a plurality of entangled nuclear spins. A sensing step for executing sensing for a predetermined time, a quantum decoding step for decoding a plurality of nuclear spins for which the sensing step has been executed by an operation corresponding to an inverse process of the quantum encoding step, and a quantum decoding step are executed. An amplification step for performing spin amplification on the plurality of nuclear spins, and a measurement step for performing NMR measurement on the plurality of nuclear spins on which the amplification step has been performed.

Thereby, the detection sensitivity of nuclear magnetic resonance signals can be improved in NMR measurements such as NMR spectroscopy and MRI.

Preferably, the quantum coding step applies a Hadamard gate to one specific nuclear spin among a plurality of nuclear spins in a state in which the molecule is placed in an external magnetic field, thereby making the specific nuclear spin coherent. And applying a control NOT gate to the plurality of nuclear spins using a specific nuclear spin in a coherent state for initial control, and bringing the plurality of nuclear spins into an entangled state, and the quantum decoding step includes: , Applying a control NOT gate to the plurality of nuclear spins for which the sensing step is performed using a specific nuclear spin for initial control, and decoding.

More preferably, the magnetic resonance sensitization method is a step executed between the quantum decoding step and the amplification step, wherein the Hadamard is applied to a specific nuclear spin of the plurality of nuclear spins on which the quantum decoding step is executed. A step that is executed between a Z-axis displacement step that applies a gate to displace a specific nuclear spin in the XY plane in the Z-axis direction, and an amplification step and a measurement step, and the amplification step is executed. An XY displacement step of applying a Hadamard gate to each of the plurality of nuclear spins to displace it in the XY plane. The amplification step is performed on the plurality of nuclear spins on which the Z-axis displacement step has been performed, and the measurement step is performed on the plurality of nuclear spins on which the XY displacement step has been performed.

Thereby, the detection sensitivity of the nuclear magnetic resonance signal can be further improved.

More preferably, the magnetic resonance sensitization method further includes a quantum insensitive encoding step that is performed before the coherentization step, and makes the highly polarized molecule less susceptible to relaxation.

Thereby, since a highly polarized state is maintained, the detection sensitivity of the nuclear magnetic resonance signal can be further improved.

Preferably, the molecule is a molecule highly polarized by triplet DNP, a molecule used for metabolic imaging, a molecule used for quantum computer research, a molecule to which quantum insensitive coding is applied, or a quantum sensitive code It is a molecule to which the crystallization is applied, and has a plurality of nuclei having a nuclear spin 1/2.

This makes it possible to widely apply the magnetic resonance sensitization method.

According to the present invention, detection sensitivity of nuclear magnetic resonance signals can be improved in NMR measurements such as NMR spectroscopy and MRI. According to the present invention, if the NMR measurement, signal is ^doubled K for the case of the protocol shown in FIG. 2, the thermal noise is equal magnification. Therefore, when one molecule contains K detectable nuclear spins, K times higher sensitivity can be realized as compared with the conventional protocol shown in FIGS.

If the quantum noise is more dominant than thermal noise, according to the present invention, the signal is ^doubled K, since the quantum noise becomes ^1/2 K, of the conventional protocol shown in FIG. 4 In comparison, K ^1/2 times higher sensitivity can be realized. In comparison with the conventional protocol shown in FIG. 6, even when the quantum noise is more dominant than the thermal noise, K times higher sensitivity can be realized.

Currently, PET (Positron Emission Tomography) is mainly used to determine the effects of cancer treatment, and it takes several weeks to determine the effects. By applying this magnetic resonance sensitization method to MRI, it is expected that the effect can be immediately determined in many hospitals. Moreover, metabolic imaging using fluorescence is difficult to apply to the deep part of the human body. On the other hand, by applying this magnetic resonance sensitivity enhancement method, metabolic imaging in the deep part of the human body by MRI becomes possible. Further, by applying this magnetic resonance sensitization method to an NMR spectrometer, real-time visualization of the state of protein folding, the state of polymerization of a polymer material, and the like becomes possible.

It is a model molecular system diagram which shows typically the molecule | numerator used for NMR measurement. It is a block diagram which shows the protocol of the NMR measurement with respect to the molecule | numerator which belongs to the model molecular system shown in FIG. FIG. 2 is a model molecular system diagram different from FIG. 1 schematically showing molecules used for NMR measurement. It is a block diagram which shows the protocol of the NMR measurement with respect to the molecule | numerator which belongs to the model molecular system shown in FIG. FIG. 4 is a model molecular diagram different from FIGS. 1 and 3 schematically showing molecules used for NMR measurement. It is a block diagram which shows the protocol of the NMR measurement with respect to the molecule | numerator which belongs to the model molecular system shown in FIG. It is a flowchart which shows the magnetic resonance sensitivity enhancement method which concerns on embodiment of this invention. It is a block diagram which shows schematic structure of the NMR apparatus for enforcing the magnetic resonance sensitivity enhancement method which concerns on embodiment of this invention. It is a block diagram which shows the protocol of the NMR measurement performed using a highly polarized liquid. FIG. 6 is a model molecular system diagram different from FIG. 5, schematically showing molecules to be subjected to the magnetic resonance sensitization method according to the embodiment of the present invention.

In the following embodiments, the same reference numerals are assigned to the same parts. Their names and functions are also the same. Therefore, detailed description thereof will not be repeated.

With reference to FIG. 7, the magnetic resonance high-sensitivity method according to the embodiment of the present invention will be described. The molecule to be measured includes a plurality (K) of nuclear spins (1/2 spin) detectable by NMR measurement, and belongs to the model molecular system shown in FIG. 5, for example. For example, trimethyl phosphate (hereinafter also referred to as TMP) represented by the chemical formula (CH ₃ O) ₃ PO disclosed in Non-Patent Document 2. The stable phosphorus ( ³¹ P) nucleus and hydrogen ( ¹ H) nucleus both have nuclear spins with a spin quantum number of 1/2, and are nuclear spins capable of NMR measurement.

In step 300, a nuclear spin (spin is 1/2) of a molecule to be measured by NMR spectroscopy, MRI or the like is highly polarized to generate a liquid (hereinafter referred to as a highly polarized liquid). For high polarization, known methods such as DNP using a thermal equilibrium state at a cryogenic temperature, a method using Dissolution DNP disclosed in Patent Document 4, or a method using parahydrogen disclosed in Non-Patent Document 8 are used. A method may be used. The triplet DNP (see Patent Document 4) can increase the polarization rate to about 10 ³ times at room temperature.

In step 302, quantum insensitive encoding is performed on the highly polarized liquid generated in step 300. That is, when a molecule having a highly polarized nuclear spin is sent into the body, the polarization rate decreases due to molecular rotation or the like. To suppress this, encoding is performed in a decoherence-free state. Quantum insensitive coding is an operation that makes nuclear spins in a coherent state and makes relaxation difficult. For example, the initial state | 00> of two nuclear spins is converted to | 01> − | 10>. For example, known methods disclosed in Patent Documents 2 to 4 and Non-Patent Documents 9 and 10 may be used.

In step 304, the highly polarized liquid that has been insensitively encoded in step 302 is supplied to the target and placed in the NMR measurement apparatus. For example, when performing NMR spectroscopy, a highly polarized liquid is placed in the NMR spectrometer (between the pole pieces of the magnet). When performing metabolic imaging, a highly polarized liquid is injected into a living body (animal or person) with a syringe or the like and placed in the gantry of the MRI apparatus. As a result, the highly polarized liquid is disposed in a space in which a uniform magnetic field is formed.

FIG. 8 shows the configuration of an NMR apparatus for NMR spectroscopy. The NMR apparatus 200 generates an RF pulse for irradiating the magnetic field forming unit 202, the cavity 204 disposed between the magnetic poles of the magnetic field forming unit 202, and the sample (highly polarized liquid) 206 disposed in the cavity 204. An RF wave source 208 and an amplification unit 210 that amplifies an RF pulse output from the RF wave source 208 are included. Further, the NMR apparatus 200 includes an NMR signal detection unit 212 for detecting an NMR signal, an NMR analysis unit 214 for analyzing the NMR signal detected by the NMR signal detection unit 212, and a control unit 216 for controlling each unit. Including.

The magnetic field forming unit 202 is, for example, an electromagnet, and is supplied with a current from a power source (not shown), and forms a static magnetic field having a uniform direction and strength in a region where the sample 206 is disposed. The RF wave source 208 is controlled by the control unit 216 to generate and output an RF pulse having a predetermined frequency for a predetermined period at a predetermined timing. The NMR signal detection unit 212 is a coil for detecting an NMR signal. The coil constituting the NMR signal detection unit 212 detects a magnetic field change in a direction orthogonal to the magnetic field formed by the magnetic field formation unit 202. Under the control of the control unit 216, the NMR analysis unit 214 measures the NMR signal using the NMR signal detection unit 212, and performs known NMR analysis. The resonance frequency of the NMR signal detection unit 212 is adjusted to be equal to the NMR frequency corresponding to the magnetic field strength by an adjustment component such as a capacitor.

In step 306, one of the nuclear spins of a particular kind of atoms contained in each molecule of high polarized poling liquid (e.g., ^{31 P} if TMP) by applying the Hadamard gate respect, the nuclear spin coherent Put it in a state. Specifically, molecules arranged in a uniform magnetic field are irradiated with an RF pulse of a predetermined pulse sequence including a π / 2 pulse, a π pulse, and the like by the RF wave source 208 and the amplification unit 210 (Non-Patent Document). 12 and 13). As a result, the nuclear spin | 0> becomes a coherent state of (| 0> + | 1>) / 2 ^1/2 .

In step 308, the control NOT against the specific types of atoms became coherent state ⁽¹ H if TMP) remaining nuclear spins in the same molecule nuclear spins ⁽³¹ P if TMP) in step 306 Apply gate sensitive quantum coding. This is performed by applying an RF pulse of a predetermined pulse sequence including a π / 2 pulse, a π pulse, and the like, which is a rotation operation around the X axis or the Y axis, by the RF wave source 208 and the amplifying unit 210 (non-null). (See Patent Documents 12 and 13). As a result, the plurality of nuclear spins (spin 1/2) constituting each molecule of the highly polarized liquid are in an entangled state sensitive to the environment such as a spin NOON state, a GHZ state, a spin squeezed state, and the like.

In step 310, the highly polarized liquid in the entangled state is held for a predetermined time, and each nuclear spin (spin 1/2) is caused to sense an environmental change (perturbation of magnetic field strength). As a result, all nuclear spins undergo φ rotation.

In step 312, quantum sensitive decoding is performed by applying a control NOT gate to the highly polarized liquid. The quantum sensitive decoding is an operation for returning the sensitive decoding state to an original state, and is an operation corresponding to the reverse process of the quantum sensitive encoding in Step 308. As a result, the plurality of nuclear spins return from the entangled state to the original state. Specifically, the quantum sensitive decoding is the same operation as the quantum sensitive coding in step 308.

In step 314, a Hadamard gate is applied to the highly polarized liquid that has been quantum sensitively decoded in step 312. Specifically, the Hadamard gate is applied in the same manner as in Step 306 to the nuclear spin of a specific kind of atom ( ³¹ P if TMP) to which the Hadamard gate is applied in Step 306. As a result, the nuclear spin in the XY plane is displaced in the Z-axis direction, the expected value of the measured value of the nuclear spin of a specific type of atom is cos (Kφ), and the remaining nuclear spin is | 0>. In other words, the phase of the nuclear spin of a specific type of atom is greatly changed by the influence of the environment.

In step 316, spin amplification is performed on the highly polarized liquid to which the Hadamard gate is applied in step 314, and the amount of phase change of the specific type of nuclear spin whose phase has changed greatly in step 314 is changed to another nuclear spin. make a copy. Specifically, a control NOT gate is applied from the specific kind of nuclear spin whose phase has changed greatly in step 314 to the remaining nuclear spin. For spin amplification, a known method disclosed in Non-Patent Document 11 may be used.

In step 318, a Hadamard gate is applied to each of the plurality of nuclear spins included in the molecule of the highly polarized liquid. By applying a Hadamard gate, the Z component of all nuclear spins is converted to an X component.

In step 320, NMR measurement is performed. That is, the NMR signal is measured by a signal detection probe (NMR signal detection unit 212 in FIG. 8).

As described above, by performing quantum insensitive encoding and spin amplification on a highly polarized liquid, NMR measurement (NMR spectroscopy, metabolic imaging, etc.) with higher sensitivity than before can be performed. Hereinafter, the improvement in sensitivity will be specifically described.

FIG. 9 shows the above steps 306 to 320 in the same manner as FIG. 2, FIG. 4 and FIG. 9, operations corresponding to the steps in FIG. 7 are denoted by the same reference numerals as in FIG. 9 is compared with FIG. 4, the operations in steps 306 to 312 are the same as the operations in FIG. 4 (excluding the detection operation 108).

In the protocol of FIG. 4, as described above, the signal strength is K times that of the protocol of FIG. On the other hand, in the protocol of FIG. 9, at the stage where the operation of step 314 is executed, the expected value of the measured value of the nuclear spin of a specific type of atom becomes cos (Kφ), and the signal for the protocol of FIG. The strength is thought to be K times. Furthermore, in the protocol of FIG. 9, the amount of phase change of a specific kind of nuclear spin is copied to (K−1) other nuclear spins by the spin amplification in step 316. Therefore, the signal intensity obtained by the NMR measurement in the operation of step 320 following the operation of step 318 is K × K = K ² times for the protocol of FIG. 2 and K times for the protocol of FIG. Become. Similarly, in the protocol of FIG. 9, the signal strength is K times that of the protocol of FIG. That is, when the thermal noise is larger than the quantum noise, the sensitivity of the protocol in FIG. 9 is K times the sensitivity of each protocol in FIG. 4 and FIG.

In the system in which the quantum noise is larger than the thermal noise, the quantum noise of the protocol of FIG. 9 is K ^1/2 times the same as the protocol of FIG. 6, so the sensitivity of the protocol of FIG. ^Is K ^3/2 (= K ² / K ^1/2 ) times, and K ^1/2 times the sensitivity of the protocol of FIG. Also in this case, the sensitivity of the protocol of FIG. 9 is K times higher than the sensitivity of the protocol of FIG.

In the above description, the case where the Hadamard gate is applied in step 314 to convert the X component of the nuclear spin into the Z component has been described, but step 314 may not be performed. That is, after step 312, spin amplification in step 316 may be performed on the X component of the nuclear spin. In that case, the NMR measurement in step 320 may be performed without performing step 318 of applying a Hadamard gate to each of the nuclear spins.

In the above description, a case has been described in which a plurality of nuclear spins constituting a molecule are entangled using a Hadamard gate and a control NOT gate, but the present invention is not limited to this. The method of bringing a plurality of nuclear spins into an entangled state may be a method other than the combination of a Hadamard gate and a control NOT gate. For example, it may be a numerical optimization pulse that expresses a unitary evolution that generalizes a combination of a Hadamard gate and a control NOT gate. As a numerical optimization method, for example, a method disclosed in Non-Patent Document 14 may be used.

The molecule to which the magnetic resonance sensitization method according to the present embodiment is applied is not limited to the model molecular system shown in FIG. For example, a cyclic model molecular system as shown in FIG. 10 or a model molecular system partially including a ring may be used. Although it is preferably a symmetric model molecular system, it may be an asymmetric model molecular system as long as the above-described CNOT gate can be configured.

The magnetic resonance sensitization method according to the present embodiment is
(1) a molecule highly polarized by triplet DNP and a molecule used for metabolic imaging,
(2) molecules used in quantum computer research,
(3) a molecule to which quantum insensitive coding is applied, and
(4) numerator to which quantum sensitive coding is applied,
It is applicable to.

The molecule (1) is, for example, a molecule in which an atom at an appropriate position in benzoic acid, p-terphenyl, naphthalene, benzophenone, or the like is substituted with an isotope having a nuclear spin of 1/2. The molecule (2) is a molecule in which, for example, pyruvate, choline, glucose, or the like, an atom at an appropriate position is substituted with an isotope of nuclear spin 1/2. The molecule (3) is a molecule in which, for example, in diacetylene, glutamate, or the like, an atom at an appropriate position is substituted with an isotope of nuclear spin 1/2. The molecule (4) is a molecule in which, for example, trimethylphosphate (trimethyl phosphate: TMP) or tetramethylsilane or the like, an atom at an appropriate position is substituted with a nuclear spin 1/2 isotope.

The case where the magnetic resonance sensitization method according to the present embodiment is applied to the NMR measurement of TMP is specifically shown. As described above, the operations of quantum sensitive coding (step 308), quantum sensitive decoding (step 312), and spin amplification (step 316) are performed in a uniform static magnetic field (for example, magnetic field strength of 11.7 T) and the resonance frequency. This is performed by pulse irradiation of radio waves (RF waves). When the magnetic field strength is 11.7 T, the resonance frequency of ³¹ P of TMP is 202 MHz, and the CNOT gate is implemented by weak pulse irradiation at a frequency that resonates with only one end spectrum split by J-bonding. To do. It is also realized by pulse irradiation that the Z magnetization of the nuclear spin is brought down to the XY plane. At this time, it is realized by double resonance strong pulse irradiation in which ¹ H (resonance frequency is 500 MHz at a magnetic field intensity of 11.7 T) and ³¹ P nuclear spins all fall down. Resonance irradiation in a magnetic field is enabled by using an NMR probe. The irradiation pulse is generated by an NMR spectrometer, amplified by a high-power amplifier, and irradiated to an NMR probe (the NMR probe of an NMR apparatus can be used for RF irradiation and detection of an NMR signal).

As mentioned above, although this invention was demonstrated by describing embodiment, above-described embodiment is an illustration and this invention is not necessarily restricted only to above-described embodiment. The scope of the present invention is indicated by each claim in the scope of the claims, taking into account the description of the detailed description of the invention, and includes all modifications within the meaning and scope equivalent to the words described therein. .

According to the present invention, the detection sensitivity of nuclear magnetic resonance signals can be improved in NMR measurements such as NMR spectroscopy and MRI.

100, 108 Detecting operation 102 Encoding operation 104 Sensing operation 106 Decoding operation 200 NMR device 202 Magnetic field forming unit 204 Cavity 206 Sample 208 RF wave source 210 Amplifying unit 212 NMR signal detecting unit 214 NMR analyzing unit 216 Control unit

Claims

A magnetic resonance sensitization method for measuring a liquid containing a plurality of nuclear spins and a highly polarized molecule to be subjected to NMR measurement,
A quantum encoding step of placing the plurality of nuclear spins in an entangled state sensitive to an environment with the molecules arranged in a uniform external magnetic field;
A sensing step of performing sensing by the plurality of nuclear spins in the entangled state for a predetermined time;
A quantum decoding step of decoding the plurality of nuclear spins on which the sensing step has been performed by an operation corresponding to an inverse process of the quantum encoding step;
An amplification step of performing spin amplification on the plurality of nuclear spins on which the quantum decoding step has been performed;
And a measurement step of performing NMR measurement on the plurality of nuclear spins on which the amplification step has been performed.
The quantum encoding step includes:
A coherent step of applying a Hadamard gate to a specific nuclear spin of one of the plurality of nuclear spins to place the specific nuclear spin in a coherent state in a state where the molecule is arranged in the external magnetic field;
Applying a control NOT gate to the plurality of nuclear spins using the specific nuclear spin in the coherent state for initial control, and bringing the plurality of nuclear spins into the entangled state;
The quantum decoding step includes a step of applying a control NOT gate to the plurality of nuclear spins on which the sensing step has been performed using the specific nuclear spins for initial control, and performing decoding. The method for increasing the sensitivity of magnetic resonance according to claim 1.
XY between the quantum decoding step and the amplification step, applying a Hadamard gate to the specific nuclear spins of the plurality of nuclear spins for which the quantum decoding step was performed, XY A Z-axis displacement step for displacing the specific nuclear spin in the plane in the Z-axis direction;
An XY displacement step that is performed between the amplification step and the measurement step, and applies a Hadamard gate to each of the plurality of nuclear spins on which the amplification step has been performed to displace them in the XY plane. And further including
The amplification step is performed on the plurality of nuclear spins on which the Z-axis displacement step is performed,
The method according to claim 2, wherein the measuring step is performed on the plurality of nuclear spins on which the XY displacement step has been performed.
4. The method according to claim 2, further comprising a quantum insensitive encoding step that is performed before the coherent step and makes the highly polarized molecule less susceptible to relaxation. The method for increasing the sensitivity of magnetic resonance described in 1.
The molecule is a molecule highly polarized by triplet DNP, a molecule used for metabolic imaging, a molecule used for quantum computer research, a molecule to which quantum insensitive coding is applied, or a quantum sensitive coding 5. The magnetic resonance sensitization method according to claim 1, wherein the molecule is a molecule having a plurality of nuclei having a nuclear spin of 1/2.