Overpolarization method and device

Abstract

The present invention relates to an inversion chamber (2) comprising at least one magnetization means, called at least one internal magnetization means (11, 12), which is at least partially located inside a magnetic shielding part (5) and which at least partially surrounds an inversion part (33), said magnetization means being configured to generate an inversion magnetic field, the main component of the inversion magnetic field being along the direction Z, which is inverted as it travels inside the inversion part (33), and inside the inversion part (33), as the solution flows at a non-zero speed from the chamber inlet to the chamber outlet inside the inversion part (33), to transfer the hyperpolarization from a first nuclear spin species to a second nuclear spin species (with scalar coupling between said nuclear spins). The present invention also relates to a device comprising this chamber and to a method implemented by said device.

Description

[Technical Field]

[0001] The present invention relates to an inversion chamber, a hyperpolarization device comprising such a chamber, and a method implemented by such a device.

[0002] Such a device allows a user to hyperpolarize solutions quickly and easily.The field of the invention relates more particularly, but not exclusively, to the field of hyperpolarized solutions for medical imaging. [Background technology]

[0003] Dynamic nuclear polarisation (DNP) methods are known from GE HEALTHCARE AS, for example as described in WO200826937.

[0004] hyperpolarization 13 The production of metabolites by C is enabling new applications in magnetic resonance imaging (MRI).

[0005] hyperpolarization 13 C-pyruvate is used in magnetic resonance imaging (MRI) applications. 13 C-pyruvate can be obtained by dissolution dynamic nuclear polarization (dDNP). The most common method is 13 Use the trityl radical as a polarizing agent to directly polarize C. 13 C can be prepared for MRI using trityl radicals at SpinLab (GE Healthcare). When using trityl radicals, preparation time for hyperpolarized samples exceeds 60 minutes.

[0006] 1 The H nuclei are polarized and the polarization is transferred to the solid state by cross polarization. 13 It is also possible to move to C. This method is fast (less than 20 minutes) but relies on the use of highly sophisticated equipment. WO2013153101 by BRUKER BIOSPIN AG describes such a method. Summary of the Invention

Problems to be Solved by the Invention

[0007] The object of the present invention is to propose a hyperpolarization device or method that combines two technical advantages that are quick and simple to implement and thus could not be combined in the prior art, and a chamber for such a hyperpolarization device or method.

Means for Solving the Problems

[0008] This object is achieved by a hyperpolarization method including 〇 a first nuclear spin species that is hyperpolarized and has a first magnetic rotation ratio, and 〇 a second nuclear spin species having a second magnetic rotation ratio being supplied in a liquid state solution, the solution is supplied to an inversion chamber such that the solution circulates through a conduit in the form of a solution flow, and a part of the conduit called the inversion part passes through the inversion chamber, the inversion chamber includes an inlet through which the solution flow enters and an outlet through which the solution flow exits, the inversion chamber preferably includes a magnetic shielding part surrounding the inversion part so as to isolate the inversion part from the ambient magnetic field around the magnetic shielding part, the method further includes -(preferably at least partially located inside the magnetic shielding part) generating an inversion magnetic field by at least one magnetization means called at least one internal magnetization means and the main component of the inversion magnetic field is along the direction Z and reverses as it progresses inside the inversion part, generating the inversion magnetic field to move the hyperpolarization from the first nuclear spin species to the second nuclear spin species inside the inversion part while the solution flows from the chamber inlet to the chamber outlet at a non-zero speed inside the inversion part.

[0009] The nuclear spins of both nuclear spin species are preferably coupled by scalar spin-spin coupling in one or more molecules of the solution.

[0010] The inversion part can be a straight line.

[0011] At least one internal magnetization means may include a pair of internal magnetization means that at least partially surround, border, or are around the inversion part within the magnetic shielding part. Each internal magnetization means - Can generate a magnetic field that is constant over time and opposite to the magnetic field of the other internal magnetization means, and the overall magnetic field of these two internal magnetization means preferably inverses inside the inversion part, and / or at the center of the inversion part, and / or - Comprises an internal solenoid or can be an internal solenoid. Thus, at least one internal magnetization means at least partially includes a pair of internal solenoids within the magnetic shielding part, and the pair of internal solenoids: 〇 Preferably, currents having opposite rotation directions are supplied, and / or 〇 Preferably, have opposite leakage magnetic fields.

[0012] At least one internal magnetization means may at least partially surround the inversion part within the magnetic shielding part and include a plurality of internal solenoids connected by a current splitting bridge. The internal solenoids are divided into two internal solenoid assemblies, and the two internal solenoid assemblies - Have currents supplied with opposite rotation directions, and / or - Have opposite leakage magnetic fields.

[0013] Preferably, there is no gap between the two internal solenoid assemblies.

[0014] The current splitting bridge may include a resistor that can be changed via an adjustment interface. The method according to the present invention preferably includes changing the resistor of the splitting bridge via this interface to adjust or optimize the magnetic field inversion profile.

[0015] The method according to the invention may include the use of magnetization means called external inlet magnetization means, which at least partially extend outside the magnetic shielding part and at least to the inlet of the inversion chamber, and magnetization means called external outlet magnetization means, which at least partially extend outside the magnetic shielding part and at least to the outlet of the inversion chamber. Each external magnetization means maintains an input magnetic field at the inlet of the inversion chamber and an output magnetic field at the outlet of the inversion chamber within the conduit.

[0016] Preferably, each external magnetization means surrounds, borders or is around at least a part of at least one internal magnetization means.

[0017] Preferably, - The upstream magnetization means 〇 In the area that is both outside the magnetic shielding part and outside the external inlet magnetization means, and 〇 In the area that is both outside the magnetic shielding part and inside the external inlet magnetization means continuously surrounds the conduit between them, and / or - The downstream magnetization means 〇 In the area that is both outside the magnetic shielding part and outside the external outlet magnetization means, and 〇 In the area that is both outside the magnetic shielding part and inside the external outlet magnetization means continuously surrounds the conduit between them.

[0018] Each external inlet magnetization means or external outlet magnetization means - While passing through each respective external inlet magnetization means or external outlet magnetization means, a part of the conduit surrounded by each respective upstream magnetization means or downstream magnetization means, and - Surrounds, borders or is around the joining area between a part of the conduit that is surrounded, bordered or has at least one internal magnetization means around it and passes through the magnetic shielding part through each of the inlet or outlet of the inversion chamber. It can surround, border or be around the joining area.

[0019] Each external magnetization means may comprise, or be, an external solenoid.

[0020] Each external magnetization means may comprise, or be, an external solenoid, and each external solenoid is preferably supported around the conduit by an external support part, surrounds the conduit, and the external support part - on the conduit side, does not contact the conduit, and / or - on the side of each external solenoid, comprises reliefs configured to accommodate and dispose the windings of each external solenoid.

[0021] At least one internal magnetization means may be at least one internal solenoid.

[0022] At least one internal magnetization means may be at least one internal solenoid, and each internal solenoid is at least partially supported by an inversion part and at least partially surrounds the inversion part via an internal support part, and the internal support part - on the conduit side, contacts the conduit, and / or - on the side of each internal solenoid, comprises reliefs configured to accommodate and dispose the windings of each internal solenoid along the conduit.

[0023] According to the method of the present invention, after passing through the inversion chamber, it may further include supplying a solution through the conduit to a nuclear magnetic resonance (NMR) spectrometer or a magnetic resonance imaging (MRI) device.

[0024] The inversion magnetic field may have a single component within the inversion part, and this single component extends in the Z direction and inverts as it progresses through the inversion part.

[0025] The supply of the solution to the inversion chamber may include supplying the solution from a DNP (dynamic nuclear polarization) device connected to the conduit and / or from any other device capable of generating and / or supplying a solution containing both spin species.

[0026] The inversion section and / or the conduit is preferably a capillary having a maximum dimension perpendicular to the solution flow of less than 5 mm.

[0027] In the inversion section, the inversion magnetic field is preferably between 0 mT and 0.1 mT in absolute value along the direction Z.

[0028] The first nuclear spin species can have a higher magnetic gyration ratio than the second nuclear spin species.

[0029] According to another aspect of the present invention, an inversion chamber is proposed, the inversion chamber comprising: - an inlet configured such that a solution flow in a liquid state containing 〇 a first nuclear spin species that is hyperpolarized and has a first magnetic gyration ratio, and 〇 a second nuclear spin species having a second magnetic gyration ratio enters the chamber through this inlet; - an outlet configured such that the solution flow exits the chamber through this outlet; and the inlet and the outlet are configured such that the solution flows along the solution flow in the conduit, and a portion of the conduit called the inversion section passes through the inversion chamber, the chamber further comprising: - preferably, a magnetic shielding portion surrounding the inversion section, the magnetic shielding portion isolating the inversion section from the ambient magnetic field around the magnetic shielding portion; - at least one magnetization means, preferably at least partially located inside the magnetic shielding portion, called at least one internal magnetization means; The at least one magnetization means is configured to generate an inversion magnetic field, the main component of the inversion magnetic field is along the direction Z, and as it progresses inside the inversion section, it reverses, generating an inversion magnetic field, such that in the inversion section, while the solution flows at a non-zero velocity from the chamber inlet to the chamber outlet inside the inversion section, the hyperpolarization is transferred from the first nuclear spin species to the second nuclear spin species.

[0030] The nuclear spins of both nuclear spin species are preferably coupled by scalar spin-spin coupling in one or more molecules of the solution.

[0031] The inversion part can be a straight line.

[0032] At least one internal magnetization means may comprise a pair of internal magnetization means that at least partially surround, border, or are around the inversion part, at least partially within the magnetic shielding part. Each internal magnetization means - can be configured to generate a magnetic field that is constant over time and opposite to the magnetic field of the other internal magnetization means, and the totality of the magnetic fields of these two internal magnetization means preferably invert within the inversion part, preferably at the center of the inversion part, and / or - may comprise an internal solenoid or be an internal solenoid, and thus at least one internal magnetization means comprises a pair of internal solenoids at least partially within the magnetic shielding part, preferably, 〇 The chamber may further comprise a power supply configured to supply currents in opposite rotational directions to the two internal solenoids, and / or 〇 The two opposing internal solenoids have leakage magnetic fields.

[0033] At least one internal magnetization means may comprise a plurality of internal solenoids that at least partially surround the inversion part and are connected by a current splitting bridge, at least partially within the magnetic shielding part. The internal solenoids are divided into two internal solenoid assemblies, and the chamber further comprises a power supply configured to supply power to the two internal solenoid assemblies, - The power supply is performed by currents having opposite rotational directions, and / or - The power supply is such that the leakage magnetic fields of the two internal solenoid assemblies are opposite to each other.

[0034] The inversion chamber according to the present invention may not have a gap between the two internal solenoid assemblies.

[0035] The current splitting bridge may comprise a resistor that can be changed via an adjustment interface, said adjustment interface being configured to change the resistor of the splitting bridge via this interface and to adjust or optimize the magnetic field inversion profile.

[0036] The inversion chamber according to the invention, referred to as external inlet magnetization means, may include magnetization means that at least extend to the inlet of the inversion chamber at least partially outside the magnetic shielding, and external outlet magnetization means, referred to as magnetization means that at least extend to the outlet of the inversion chamber at least partially outside the magnetic shielding, and each external magnetization means maintains an input magnetic field at the inlet of the inversion chamber and an output magnetic field at the outlet of the inversion chamber within the conduit.

[0037] Each external magnetization means can surround, border or be around at least a part of at least one internal magnetization means.

[0038] The inversion chamber according to the invention - 〇 An area that is both outside the magnetic shielding and outside the external inlet magnetization means, and 〇 An area that is both outside the magnetic shielding and inside the external inlet magnetization means Upstream magnetization means that continuously surround the conduit between, and / or - 〇 An area that is both outside the magnetic shielding and outside the external outlet magnetization means, and 〇 An area that is both outside the magnetic shielding and inside the external outlet magnetization means Downstream magnetization means that continuously surround the conduit between may further be provided.

[0039] Each external inlet magnetization means or external outlet magnetization means - While passing through each respective external inlet magnetization means or external outlet magnetization means, a part of the conduit surrounded by each respective upstream magnetization means or downstream magnetization means, and - Surrounded by, bordered by, or having at least one internal magnetization means surrounding it, and being part of a conduit that penetrates a magnetic shielding portion through each of the inlet or outlet of the inversion chamber It can surround, border, or be around the joint area between it and

[0040] Each external magnetization means comprises, or can be, an external solenoid.

[0041] Each external solenoid is supported around the conduit via an external support component and can surround the conduit, and the external support component - On the conduit side, it does not contact the conduit, and / or - On the side of each external solenoid, it comprises a relief portion configured to accommodate and arrange the windings of each external solenoid.

[0042] At least one internal magnetization means can be at least one internal solenoid.

[0043] Each internal solenoid is at least partially supported by an inversion portion and can at least partially surround the inversion portion via an internal support component, and the internal support component - On the conduit side, it contacts the conduit, and / or - On the side of each internal solenoid, it comprises a relief portion configured to accommodate and arrange the windings of each internal solenoid along the conduit.

[0044] The inversion chamber according to the present invention can be configured such that the inversion magnetic field has a single component that extends in the direction Z within the inversion portion and reverses as it progresses through the inversion portion.

[0045] The inversion portion and / or the conduit can be a capillary having a maximum dimension perpendicular to the solution flow of less than 5 mm.

[0046] The inversion chamber according to the present invention can be configured such that in the inversion portion, the inversion magnetic field is between at least 0 mT and 0.1 mT in absolute value along the direction Z.

[0047] The first nuclear spin species can have a higher magnetic gyration ratio than the second nuclear spin species.

[0048] According to another aspect of the present invention, a hyperpolarization device is proposed, the hyperpolarization device comprising - an inversion chamber according to the present invention, and - a device configured to deliver a solution to the inlet of the inversion chamber through a conduit and.

[0049] The device according to the present invention may further comprise a nuclear magnetic resonance (NMR) spectrometer or a magnetic resonance imaging (MRI) device connected to the outlet of the inversion chamber via a conduit.

[0050] The device configured to supply the solution is - a dynamic nuclear polarization device DNP connected to the conduit, and / or - any other device capable of generating and / or supplying a solution containing both spin species and.

[0051] Other advantages and features will become apparent from the following accompanying drawings upon reading the detailed description of the completely non-limiting embodiments and implementations.

Brief Description of the Drawings

[0052]

Figure 1

Figure 2a

Figure 2b

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9a

Figure 9b

Figure 10a

Figure 10b

Embodiments for Carrying Out the Invention

[0053] These embodiments are in no way limiting, and in particular, if the selection of one feature provides a technical advantage or is sufficient to distinguish the present invention from the prior art, it is possible to consider variants of the present invention that include only one selection of the disclosed features (even if the selection is independent within a clause that includes other features), independent of the other features disclosed below. This selection includes at least one preferred functional feature having no structural details and / or only a part of the structural details, provided that the part is sufficient to provide a technical advantage or to distinguish the present invention from the prior state of the art.

[0054] First, with reference to FIGS. 1 to 4, a first embodiment of the overpolarization device 100 according to the present invention including a first embodiment of the inversion chamber 2 according to the present invention will be described.

[0055] The device 100 includes an inversion chamber 2, and the inversion chamber 2 - An inlet, 〇 A first nuclear spin species that is overpolarized and has a first magnetic rotation ratio (preferably having the advantage of being very rapidly overpolarized upstream of the chamber 2 by DNP 1 H), and 〇 A second nuclear spin species having a second magnetic rotation ratio (preferably having the advantage that the relaxation time is 1 longer than that of the H nuclear spin 13 C)[[ID=3,2]] An inlet configured such that a stream of solution 1 enters the chamber 2 in a liquid state through this inlet, including - An outlet configured such that the stream of solution 1 leaves the chamber 2 through this outlet comprising, both of said nuclear spin species being coupled by scalar spin-spin coupling in one or more molecules of Solution 1, said inlet and outlet are configured such that this Solution 1 circulates as a solution flow within conduit 3, and a portion of conduit 3 called the inversion portion 33 passes through inversion chamber 2.

[0056] As used herein, the term "spin" or "nuclear spin" means the spin of an atomic nucleus (possibly within a molecule) performed by the atomic nucleus.

[0057] Chamber 2 further comprises a magnetic shielding portion 5 surrounding the inversion portion 33, and the magnetic shielding portion 5 is configured to isolate the inversion portion 33 from the ambient magnetic field around the magnetic shielding portion 5.

[0058] As shown in FIGS. 2a and 3, this shielding portion 5 preferably comprises a plurality of layers (preferably concentric) for greater efficiency.

[0059] The inlet to chamber 2 corresponds to the inlet of conduit 3 that enters the magnetic shielding portion 5 from outside chamber 2.

[0060] The outlet from chamber 2 corresponds to the outlet of conduit 3 that exits the magnetic shielding portion 5 from inside chamber 2.

[0061] Chamber 2 further comprises at least one magnetization means 11, 12, and at least one magnetization means 11, 12 is at least partially located inside the magnetic shielding part 5, and is called at least one internal magnetization means 11, 12, and surrounds at least a part of the inversion part 33, or borders it, or is around at least a part of the inversion part 33. At least one internal magnetization means 11, 12 is configured to generate an inversion magnetic field 6 within the inversion part 33, the main component of the inversion magnetic field 6 is along the direction Z, and (along the axis S and the direction Z) as it travels from the inlet to the outlet of chamber 2 through the inside of the inversion part 33, it preferably inverts once (in the inversion plane 71), and while the solution 1 flows within the inversion part 33, it does not immobilize the solution 1 within the inversion part 33, that is, in a state where the solution 1 flows at a non-zero speed from the chamber inlet to the chamber outlet within the inversion part 33, and transfers the hyperpolarization from the first nuclear spin species to the second nuclear spin species within the inversion part 33.

[0062] In this specification, inversion is used to mean that the main component changes direction (while maintaining the same direction Z).

[0063] In this specification, the concept of the inversion magnetic field 6 whose main component is along the direction Z preferably means that when the magnetic field 6 has a component transverse to the main component, this transverse component is always - 10% of the main component in the inversion direction Z, and / or -(for example, when the scalar coupling is 1 H- 13 C pair is about 100 - 200 Hz) 1 μT, or even more (for example, in the case of a 10 - 20 Hz coupling) always less than 0.1 μT It should be understood to mean remaining less than. The maximum transverse magnetic field linearly reduces the effective transfer due to the scalar coupling strength between nuclear spins at any point of the solution 1 within the part 33.

[0064] Chamber 2 is configured such that the reversing magnetic field 6 has, preferably, a single component in the reversing portion 33, and this single component is solely in the Z direction (i.e., the component orthogonal to Z is zero or negligible compared to the main component), and it reverses as it progresses through the reversing portion 33.

[0065] At least one internal magnetization means 11, 12 - At the inlet side of chamber 2, at least one internal inlet magnetization means 11, and - At the outlet side of chamber 2, at least one internal outlet magnetization means 12 are provided.

[0066] In this specification, the magnetization means preferably means an electromagnet, a permanent magnet, an assembly of electromagnets, an assembly of permanent magnets, or an assembly of electromagnet(s) and permanent magnet(s).

[0067] In this specification, a solenoid is interpreted to mean the conductive wire of an electromagnet, which is wound in multiple loops or turns and through which a current flows (or is configured to flow).

[0068] In this specification, the magnetic shielding part or shield 5 means a preferably metallic shield in any form (continuous (sheet, plate, etc.) and / or discontinuous (grid, lattice, etc.)), which is configured to isolate the interior of the shield 5 from a temporally continuous magnetic field or a low temporal frequency magnetic field located around the shield 5, and preferably, - The Tesla value of the temporally continuous magnetic field located around the shield 5 and having a value of 100 microtesla or less around the shield 5 is reduced by at least one-tenth, preferably at least one-tenth, 5 and / or 6 - It has a shielding coefficient of at least 10, preferably at least 10. 5 6 has.

[0069] In this specification, solution 1 refers to a liquid or liquid mixture that may optionally contain suspended solid particles.​​

[0070] In this embodiment, the inversion portion 33 is linear and extends longitudinally along the S axis.

[0071] In this embodiment, the directions S and Z coincide.

[0072] In this embodiment, at least one of the internal magnetization means 11, 12 comprises a pair of internal magnetization means 11, 12 that at least partially surround, border, or are at least partially around the inversion portion 33 within the magnetic shielding portion 5.

[0073] Along the S axis (and direction Z), - at least one internal inlet magnetization means 11 and - at least one internal outlet magnetization means 12 there is a gap 13 therebetween.

[0074] This enables the solution flow 1 to be made faster in the present embodiment 100 (since the magnetic field profile 6 is closer to ideal, a faster flow rate can be selected while maintaining efficient movement).

[0075] More precisely, each of the internal magnetization means 11 and 12 - a portion that surrounds, borders, or is around a part of the inversion portion 33 inside the shielding portion 5, and - a portion that is outside the shielding portion 5 (but inside one of the external magnetization means 41, 42 to be described later) and surrounds, borders, or is around another part of the inversion portion 33 comprises.

[0076] The inversion portion 33 corresponds to a part of the conduit 3 that is surrounded, bordered, or has the at least one internal magnetization means 11, 12 around it.

[0077] Each internal magnetization means includes an internal solenoid. Thus, at least one of the internal magnetization means 11, 12 includes a pair of anti-parallel internal solenoids 11, 12 with windings centered on the same axis S, at least partially inside the magnetic shielding portion 5.

[0078] The chamber 2 is configured with at least one power source (not shown, preferably located outside the shielding portion 5) to supply currents i1 in opposite rotational directions (preferably of equal intensity) to the two internal solenoids 11, 12, and preferably further includes a single common power source, such that the leakage magnetic fields of the two internal solenoids 11, 12 are opposite to each other. This current i1 is constant over time.

[0079] The advantage of a common power source is greater simplicity and a more stable reversing magnetic field 6.

[0080] Each internal magnetization means 11, 12 is configured to generate a magnetic field that is constant over time (i.e., for each solenoid 11 or 12).

[0081] Each internal magnetization means 11 or 12 is configured to generate a magnetic field opposite to that of each of the other internal magnetization means 12 or 11 (i.e., for each of the other solenoids 12 or 11), such that the overall magnetic fields of these two internal magnetization means (i.e., the two solenoids 11, 12) reverse along the direction S, preferably at the center of the inversion portion 33 and the gap 13 (in the inversion plane 71 orthogonal to the portion 33) inside the inversion portion 33.

[0082] The chamber 2 - Magnetization means known as external entrance magnetization means 41, at least partially outside the magnetic shielding portion 5 and extending at least to the entrance of the inversion chamber 2, where the external entrance magnetization means 41 can be both outside and inside the shielding portion 5, but is preferably only outside the shielding portion 5, - known as external exit magnetization means 42, at least partially outside the magnetic shielding portion 5, and extending at least to the exit to the inversion chamber 2, the external exit magnetization means 42 can be both outside and inside the shielding portion 5, but preferably is only outside the shielding portion 5, magnetization means further comprises.

[0083] Each external magnetization means 41 or 42 is configured to maintain an input magnetic field (constant over time) at the inlet to the inversion chamber 2 and an output magnetic field (constant over time) at the exit from the inversion chamber 2 within the conduit 3.

[0084] Both the input magnetic field and the output magnetic field are typically at least 4 mT in the direction Z which is their main direction.

[0085] Both the input magnetic field and the output magnetic field ensure that polarization is not lost due to rotation of the non-adiabatic magnetic field (e.g., due to the combined influence of the ambient magnetic field and the magnetic shielding portion 5).

[0086] Each external magnetization means 41, 42 surrounds, borders or is at least partially around at least a part of at least one of the internal magnetization means 11, 12, preferably at least outside the shielding portion 5, preferably only outside the shielding portion 5.

[0087] The external inlet magnetization means 41 surrounds, borders or is at least partially around a part of the solenoid 11 located outside the shielding portion.

[0088] The external exit magnetization means 42 surrounds, borders or is at least partially around a part of the solenoid 12 located outside the shielding portion.

[0089] The device 100 is - The area that is both outside the magnetic shielding part 5 and outside the external inlet magnetization means 41, and - The area that is both outside the magnetic shielding part 5 and inside the external inlet magnetization means 41 An upstream magnetization means or solenoid 51 that continuously surrounds the conduit 3 between them, and - The area that is both outside the magnetic shielding part 5 and outside the external outlet magnetization means 42, and - The area that is both outside the magnetic shielding part 5 and inside the external outlet magnetization means 42 A downstream magnetization means or solenoid 52 that continuously surrounds the conduit 3 between them It further comprises.

[0090] Each magnetization means 51 or 52 is designed to maintain a (constant over time) magnetic field in the respective conduits 3 upstream and downstream of the chamber 2.

[0091] Each external inlet magnetization means 41 or external outlet magnetization means 42 respectively - While passing through the respective external inlet magnetization means 41 or external outlet magnetization means 42, it is surrounded, bordered, or the respective upstream magnetization means 51 or downstream magnetization means 52 are in the vicinity of the part of the conduit 3 surrounded by them, and - It is surrounded, bordered, or at least one internal magnetization means 11, 12 are in the vicinity, preferably the part of the conduit 3 that passes through the magnetic shielding part 5 through each of the inlet or outlet of the inversion chamber 2 Surrounds, borders, or is in the vicinity of the joining area 61 at the inlet to the chamber 2 or the joining area 62 at the outlet from the chamber 2 between them.

[0092] Each external magnetization means comprises or is an external solenoid, and thus the chamber 2 comprises a pair of anti-parallel external solenoids 41, 42 with windings preferably centered on the same axis S at least partially outside the magnetic shielding part 5.

[0093] Chamber 2 is configured with at least one power supply (not shown, preferably located outside the shielding part 5) that supplies currents i2 in opposite rotational directions (preferably of equal intensity) to two external solenoids 41, 42, and preferably further includes a common power supply. This current i2 is constant over time.

[0094] The current i1 in solenoid 11 rotates in the same direction as the current i2 in solenoid 41.

[0095] The current i1 in solenoid 12 rotates in the same direction as the current i2 in solenoid 42.

[0096] The advantage of the common power supply is greater simplicity and a more stable reversing magnetic field 6.

[0097] Each external solenoid 41 or 42 is supported around conduit 3 via an external support part 8, surrounding the conduit 3, and the external support part 8 - On the side of the conduit 3, it does not contact the conduit (however, it surrounds only a part of the upstream solenoid 51 or the downstream solenoid 52, only a part of at least one internal solenoid 11, 12, and the joining area 61 or 62), and - On the side of each external solenoid 41 or 42, it has a relief part configured to accommodate and arrange the windings of the external solenoid 41 or 42 (the relief part is wound in the form of a winding around the external support part 8).

[0098] As already described, at least one internal magnetization means 11, 12 includes at least one internal solenoid 11, 12.

[0099] Each internal solenoid 11, 12 is at least partially supported by the reversing part 33 and at least partially surrounds the reversing part 33 via an internal support part 9, and the internal support part 9 - On the side of the conduit 3, it contacts the conduit 3, and - On the side of each of the internal solenoids 11, 12, there is provided a relief portion configured to accommodate and arrange the windings of the internal solenoid 11 or 12 along the conduit 3, particularly along the inversion portion 33 (the relief portion is wound in the form of a winding around the internal support part 9).

[0100] The inversion portion 33 and / or the conduit 3 is a capillary tube having a maximum dimension perpendicular to the solution flow 1 (i.e., perpendicular to the axis S) of less than 5 mm. This enables better control of the magnetic field 6. The reason is that (in the cross-sectional plane perpendicular to the portion 33), the transverse component of the magnetic field 6 may become larger the farther away from the center of the portion 33.

[0101] The chamber 2 is configured such that in the inversion portion 33, the inversion magnetic field 6 is included between at least 0 mT and 0.1 mT, or even between at least 0 mT and 0.2 mT, in absolute value along the direction Z. The intensity of the magnetic field 6 in the portion 33 preferably has at least one value that is 10 times greater than the ratio (coupling J of the two spin species) / (difference in the magnetic gyromagnetic ratios of the two spin species).

[0102] The chamber is configured such that in the inversion portion 33, the inversion magnetic field 6 reverses between at least the value +B max in the direction along the Z axis and the value +B max in the opposite direction along the Z axis, and B max is equal to at least 0.1 mT or at least 0.2 mT.

[0103] As part of the method of using the device 100, the first nuclear spin species preferably has a higher magnetic gyromagnetic ratio than the second nuclear spin species.

[0104] In addition to the chamber 2 just described, the hyperpolarization device 100 comprises a device 18 configured to supply the solution 1 to the inlet (i.e., upstream) of the inversion chamber 2 via the conduit 3.

[0105] The device 18 is - Preferably, a dynamic nuclear polarization (DNP) device 18, preferably a dissolution dynamic nuclear polarization (dDNP) device, and / or - Any other device 18 capable of generating and / or supplying a solution containing both species of nuclear spins is provided.

[0106] The device 100 further comprises a nuclear magnetic resonance (NMR) spectrometer 19 or a magnetic resonance imaging (MRI) device 19 connected via the conduit 3 to the outlet (i.e., downstream) of the inversion chamber 2.

[0107] The device 100 further comprises means (not shown) for purifying the solution 1, e.g., one or more polarization matrices, e.g., a HYPOP polarization matrix, for purifying the solution 1 by removing trace amounts of the polarizing agent, downstream of the chamber 2, i.e., between the chamber 2 and the device 19.

[0108] The polarization transfer from one nucleus to the other is complete if it is adiabatic, i.e., sufficiently slow. The minimum time τ trans for the adiabatic transition can be calculated by the Landau-Zener theory in the simple case where the magnetic field strength 6 changes linearly with time as the two coupled spins (a first nuclear spin species and a second nuclear spin species of different gyromagnetic ratios, preferably coupled by scalar coupling and preferably within the same molecule) move within the portion 33 (the magnetic field 6 being constant with time at each fixed point within the portion 33),

[0109]

Equation

[0110] and can be described as, where the magnetic field 6 is +B max at time t = 0 (typically at the inlet to the chamber 2), and trans -B max at time t = τ (typically at the outlet of the chamber 2), and B max the value of the magnetic field is subject to the condition

[0111]

Number

[0112] is given by, where J IS , γ I and γ S are the scalar coupling between spins in Hz units and the magnetic gyromagnetic ratio in T -1 Hz units. To obtain the numerical values under this condition,

[0113]

Number

[0114] can be selected, and this numerical value ranges from 0.3 to 63 μT for a pair of 1 H and 13 C spins having typical couplings (each between 1 and 200 Hz). The Landau-Zener theory shows that the minimum transfer time (see Equation 1) for an adiabatic transition in a linear magnetic field profile from +B max to -B max is given by the condition

[0115]

Number

[0116] is given by, and to obtain the numerical values under this condition,

[0117]

Number

[0118] can be selected, and the numerical value ranges from 0.05 to 10 s for a pair of 1 H and 13 C spins having typical couplings (each between 1 and 200 Hz).

[0119] It should be noted that the movement can be significantly reduced when a non-linear magnetic field profile is employed. A constant adiabatic profile (i.e., a profile that enables the fastest possible adiabatic transition) can be calculated numerically. A pair of solenoids 11, 12 with opposite leakage magnetic fields aligned along the same axis S enables approaching this ideal profile at a certain distance between the solenoids (distance D with reference numeral 13 in Fig. 3). This distance 13 and the currents flowing through the solenoids 11, 12 may be affected.

[0120] In this way, based on the magnetic field 6 as well as the two spin species and their coupling, it is possible to easily calculate and optimize the flow rate of the solution 1 in the section 33, and thus the residence time in the section 33.

[0121] The profile of the magnetic field 6 experienced by a pair of coupled nuclear spins in the solution 1 as a function of time depends on the following: - The profile of the magnetic field 6 in space (constant in time). The magnetic field 6 depends on the arrangement of various internal inlet magnetization means 11 and outlet magnetization means 12, and possibly, if the magnetization means are not permanent magnets, on the current flowing through the magnetization means. The magnetic field profile 6 along the position S is calculated using the formula for a conventional ideal solenoid and can be optimized by optimizing the current i1. - The flow rate of the solution flow 1. The flow rate of the solution flow 1 can be calculated and optimized by simply adjusting a pump or valve or any other known means for adjusting the flow rate of the solution flow 1 as already described.

[0122] Therefore, summarizing this embodiment of the present invention, - The magnetic shielding portion 5 shields the geomagnetic field and the magnetic field generated by devices around the chamber 2. - The internal magnetization means 11, 12 bring about a spatial inversion of the magnetic field 6. - The external magnetization means 41, 42 act to maintain a sufficient magnetic field at the inlet and outlet of the inversion chamber 2. - The conduit 3 (which is a capillary) is itself surrounded by coils or magnetization means 51, 52 (wound around the conduit 3 or held by an adhesive) and maintains a sufficient magnetic field throughout the entire movement of the solution from the device 18 to the chamber 2 and then from the chamber 2 to the destination 19 of the solution.

[0123] Typically, a device or method according to the present invention uses dDNP to polarize a first spin species 1 H and then transfers this polarization to a second spin species 13 C in the liquid state. In the case of the present invention, the inversion is achieved by moving the solution 1 through the magnetic field profile 6 in the space. Further, the present invention makes a highly selective use of DNP or dDNP to prepare a hyperpolarized 1 H solution upstream of the chamber 2.

[0124] A device or method according to the present invention enables the generation of a hyperpolarized 13 C metabolic solution in less than 20 minutes and does not require complex equipment. This is because the generation of a solution containing 1 H nuclei hyperpolarized by DNP is faster, simpler, and more straightforward than the generation of 13 C directly (e.g., by cross-polarization), and the polarized transfer from 1 H to 13 C (or 15 N or 31 P) in the continuous flow within the chamber 2 is quite fast, simple, and interruption-free. Different from cross-polarization, the addition of the inversion chamber 2 according to the present invention does not require any major modification to the polarizer and only requires adding inexpensive equipment at the outlet of the polarizer.

[0125] Typically, a hyperpolarized 13 C solution is rapidly (in less than 20 minutes) generated in the case of a molecule in which a 13 C nucleus is bound to at least one 1 H nucleus. The present invention 1A general protocol for the production of solution 1 in which H is hyperpolarized by dissolution dynamic nuclear polarization (dDNP) is used. Next, the polarization is reversed in a controlled manner through a magnetic field profile 6 by the transport of solution 1, in solution 1, in the liquid state 1 from 13 H to 1 C. This magnetic field profile 6 is obtained by the use of a magnetic shielding section 5 that cancels out the ambient magnetic field (the residual magnetic field is in the nT range), and the magnetic shielding section 5 comprises a pair of anti-parallel constant current solenoid coils 11, 12, or more generally, a pair of internal inlet magnetization means 11 and outlet magnetization means 12, or at least one internal magnetization means 11, 12. Each coil 11, 12 generates a constant opposite magnetic field 6. The capillaries 3, 33 pass through the solenoids 11, 12 and the magnetic shielding section 5 so that when solution 1 is pushed into the capillaries 3, 33, the molecules are subjected to the reversal of the magnetic field 6 over time. 13 The scalar coupling (J coupling) between the nucleus of H and

[0126] the nucleus of C enables the polarization transfer. The theory of this transfer is well established and enables the optimization of the magnetic field profile of the hyperpolarized molecules. This "in-flow" transfer, which means that solution 1 is not fixed, enables rapid transfer and minimizes losses due to relaxation. 13 C) is enabled.

[0127] 13 For polarizing the nuclear spins of C formate and 13 C pyruvate, experiments were conducted using the device shown in FIG. 3. A rapid increase in the polarization of these molecules was observed, and a final polarization of several percent was measured by liquid magnetic resonance.

[0128] Next, with reference to FIGS. 1 and 5 to 7, a second embodiment of the overpolarization device 200 according to the present invention, which includes a second embodiment of the inversion chamber 2 according to the present invention, will be described. Only the differences from the first embodiment of the chamber 2 and the device 100 already described will be explained.

[0129] Device 200 is more accurate than device 100.

[0130] In the present embodiment, at least one of the internal magnetization means 11, 12 includes a plurality of internal solenoids 11, 12 at least partially within the magnetic shielding portion 5, and the plurality of internal solenoids 11, 12 at least partially surround the inversion portion 33 and are electrically interconnected by a current splitting bridge 20.

[0131] The internal solenoids 11, 12 are two internal solenoid assemblies 110, 120, namely, - A first assembly 110 of internal inlet solenoids 11, all of which are on the inlet side of the chamber 2, - A second assembly 120 of internal outlet solenoids 12, all of which are on the outlet side of the chamber 2 are separated into.

[0132] Each pair of adjacent internal solenoids 11 (of the assembly 110) is electrically connected by a current splitting bridge 20 (and only by this bridge 20), preferably having no intermediate space between these internal solenoids 11, but having no direct electrical contact between these adjacent solenoids 11 (i.e., the winding of one solenoid 11 does not continue to the winding of another adjacent solenoid 11).

[0133] Each pair of adjacent internal solenoids 12 (of the assembly 120) is electrically connected by a current splitting bridge 20 (and only by this bridge 20), preferably having no intermediate space between these internal solenoids 12, but having no direct electrical contact between these adjacent solenoids 12 (i.e., the winding of one solenoid 12 does not continue to the winding of another adjacent solenoid 12).

[0134] The first assembly 110 is electrically connected to the second assembly 120. The first assembly 110 and the second assembly 120 are connected to the same power supply 21, but the rotational direction of the current of each solenoid 11 of the assembly 110 is opposite to the rotational direction of the current of each solenoid 12 of the assembly 120.

[0135] The assembly 110 includes the same number of solenoids 11 as the assembly 120 includes solenoids 12.

[0136] The chamber 2 further includes at least one power supply, preferably a common power supply, configured to supply currents i1 in opposite rotational directions (preferably of the same intensity) to the two internal solenoid assemblies 110, 120, such that the leakage magnetic fields of the two internal solenoid assemblies 110, 120 are opposite to each other and i1 is constant over time.

[0137] The advantage of the common power supply is greater simplicity and a more stable reversing magnetic field 6.

[0138] The two assemblies 110 and 120 are antiparallel.

[0139] The windings of the solenoids 11 and 12 are centered on the same axis S.

[0140] The chamber has no gap between the two assemblies 110, 120 of the internal solenoids 11, 12, i.e., the first assembly 110 is flush with the second assembly 120, and possibly only a simple mechanical gap remains.

[0141] In the present embodiment 200, this enables faster movement and minimizes losses due to relaxation during movement.

[0142] Each bridge 20 includes a pair of resistors 23.

[0143] The current-splitting bridge 20 comprises a resistor 23 that can be changed via an adjustment interface, and the adjustment interface is configured to change the resistor 23 of the splitting bridge 20 via this interface so as to adjust or optimize the magnetic field reversal profile 6.

[0144] As the adjustable resistor 23 and the adjustment interface, any type of variable resistor technology can be used, for example, using a potentiometer or rheostat of any kind that is controlled from outside the display device 5 by analog and / or digital means, touch screen, etc.

[0145] The spatial profile of the magnetic field 6 - the current i1 of each solenoid 11 and / or 12, and / or - the (equal or different) values of the various resistors 23 can be refined by adjusting.

[0146] Even when the resistor 23 is not adjusted, the device 200 is more accurate than the device 100.

[0147] All the resistors 23 of all the bridges 20 are assembled, for example, on a single printed circuit board integrated inside the shielding part 5.

[0148] The external inlet magnetization means 41 surrounds, borders, or is around a part of the assembly 110 located outside the shielding part.

[0149] The external outlet magnetization means 42 surrounds, borders, or is around a part of the assembly 120 located outside the shielding part.

[0150] Accordingly, the chamber 2 of the device 200 corresponds to the chamber 2 of the device 100, - the solenoid 11 of the device 100 is replaced by the assembly 110 of the device 200 and the bridge 20 of the device 200, - The solenoid 12 of the device 100 is replaced by the assembly 120 of the device 200 and the bridge 20 of the device 200.

[0151] In a variant of the embodiment shown in FIGS. 5 to 7, - The portion 33 is V-shaped, and the reversal of the magnetic field 6 occurs at the tip of the V, and the tip of the V defines the separation boundary between the two assemblies 110 and 120, and / or - Although less convenient, there is a separation between the assemblies 110 and 120.

[0152] The two embodiments described with reference to FIGS. 1 to 7 can be generalized by replacing the term "solenoid" with "magnetization means" (or "electromagnet", "permanent magnet", "assembly of electromagnets", "assembly of permanent magnets" or "assembly of electromagnet(s) and permanent magnet(s)"). In the case of permanent magnet(s), the means for supplying power to the solenoid described above is no longer necessary.

[0153] Next, with reference to FIGS. 1 and 8, a third embodiment of the overpolarization device 300 according to the present invention including a third embodiment of the inversion chamber 2 according to the present invention will be described. Only the differences from the first embodiment of the chamber 2 and the device 100 already described will be explained.

[0154] In this embodiment, the inversion portion 33 is not linear.

[0155] In this embodiment, the first portion and the second portion of the inversion portion 33 form a right angle, but generally, they can form any angle.

[0156] The internal inlet magnetization means 11 includes or is an internal inlet solenoid 11 surrounding a part of the first portion of the portion 33.

[0157] The means 11 generates a magnetic field in the first portion of the portion 33, and this magnetic field is parallel to Z and the extending direction of the first portion of the portion 33.

[0158] The chamber 2 comprises means for supplying a direct current to the solenoid 11.

[0159] The internal outlet magnetization means 12 comprises or is a group 12 of permanent magnet(s) and / or Helmholtz coil(s), the group 12 surrounding a part of the second part of the portion 33 and being configured to emit a magnetic field orthogonal to a part of the portion 33 surrounded by the group 12.

[0160] The means 12 generates, in the second part of the portion 33, a magnetic field which is parallel to Z and orthogonal to the extending direction of the second part of the portion 33.

[0161] Thus, the magnetic field 6 reverses in the direction Z as the solution flow 1 passes through the portion 33.

[0162] In a non-illustrated variant of FIG. 8, - a non-linear portion 33, - an internal inlet magnetization means 11 which comprises or is a group 11 of permanent magnet(s) and / or Helmholtz coil(s), the internal inlet magnetization means 11 surrounding a part of the first part of the portion 33 and being configured to emit a magnetic field orthogonal to a part of the portion 33 surrounded by the internal inlet magnetization means 11 in the first part of the portion 33, - an internal outlet magnetization means 12 which comprises or is an internal outlet solenoid 12, the internal outlet magnetization means 12 surrounding a part of the second part of the portion 33 and generating a magnetic field parallel to Z and to the extending direction of the second part of the portion 33 in the second part of the portion 33 should be noted.

[0163] Next, a fourth embodiment of the polarization device 400 according to the invention, comprising a fourth embodiment of the inversion chamber 2 according to the invention, will be described with reference to FIGS. 1 and 9. Only the differences of these embodiments from the third embodiment of the chamber 2 and the device 300 already described will be described.

[0164] Therefore, referring to FIG. 9, in a variant of FIG. 8, - a straight portion 33, - an internal inlet magnetization means 11 comprising or being a group 11 of permanent magnet(s) and / or Helmholtz coil(s), surrounding a part of the first part of the portion 33 and configured to emit a magnetic field orthogonal to a part of the portion 33 surrounded by the internal inlet magnetization means 11 in the portion 33, - an internal outlet magnetization means 12 comprising or being a group 12 of permanent magnet(s) and / or Helmholtz coil(s), surrounding a part of the second part of the portion 33 and configured to emit a magnetic field orthogonal to a part of the portion 33 surrounded by the internal outlet magnetization means 12 in the portion 33 but in a direction opposite to the magnetic field of the means 11, is noted.

[0165] Furthermore, in the case of FIGS. 8 to 10, - the device according to the invention comprises an intermediate inlet magnetization means 81 between the inlet of the chamber 2 and the internal magnetization means 11 (or at least one internal magnetization means 11) (in the case of the variant of FIG. 8 where the means 11 and 12 are exchanged), and / or - the device according to the invention comprises an intermediate outlet magnetization means 82 between the outlet of the chamber 2 and the internal magnetization means 12 (or at least one internal magnetization means 12) (in the case of FIGS. 8, 9 and 10). It should be noted.

[0166] Each of the means 81 and 82 surrounds, borders or is around at least a part of the portion 33.

[0167] Each of the means 81 and 82 comprises a solenoid.

[0168] The intermediate magnetization means 81 is configured to maintain, within the conduit 3, an intermediate input magnetic field that is parallel (constant over time) to the chamber 2 through the inlet in the longitudinal direction of the conduit 3, between the magnetic field of the means 41 within the conduit 3 and the magnetic field of the means(s) 11 within the portion 33.

[0169] The intermediate magnetization means 82 is configured to maintain, within the conduit 3, an intermediate output magnetic field that is parallel (constant over time) to the chamber 2 through the outlet in the longitudinal direction of the conduit 3, between the magnetic field of the means 42 within the conduit 3 and the magnetic field of the means(s) 12 within the portion 33.

[0170] The functions of the means 81 and 82 are to ensure that the direction of the magnetic field affected by the spin is constant. Without these functions, the success of the polarization transfer method by the device according to the present invention in FIGS. 8, 9, and 10 risks being too dependent on the orientation of the shielding portion 5 related to the spatial and ambient magnetic fields.

[0171] A magnetic field direction that changes by 90° in the middle of space (and thus time) is not a problem if the change is slow enough (adiabatic). An example of adiabatic conditions is

[0172]

Number

[0173] where a is the angle of the magnetic field B(t) at time t and y is the lowest magnetic rotation ratio of the two spins. Mathematically, this results in

[0174]

Number

[0175] which results in.

[0176] Note that none of the embodiments of the device according to the present invention or the chamber according to the present invention just described with reference to FIGS. 1 to 10 comprise means for emitting microwaves (i.e., electromagnetic radiation having a frequency above 1 GHz or between 1 GHz and 300 GHz) into the chamber and / or part 2.

[0177] Next, a fifth embodiment of the hyperpolarization device 500 according to the present invention, comprising a fifth embodiment of the inversion chamber 2 according to the present invention, will be described with reference to FIGS. 1 and 10. Only the differences from the first embodiment of the chamber 2 and the device 100 already described will be explained for these embodiments.

[0178] Therefore, referring to FIG. 10, - a straight portion 33, - an internal inlet magnetization means 11 comprising a group 11 of permanent magnet(s) and / or Helmholtz coil(s) or being the group 11, surrounding a part of the first part of the portion 33 or being around a part of the first part of the portion 33, and configured to emit a magnetic field parallel to a part of the conduit 33 surrounded by the internal inlet magnetization means 11, - an internal outlet magnetization means 12 comprising a group 12 of permanent magnet(s) and / or Helmholtz coil(s) or being the group 12, surrounding a part of the second part of the portion 33 or being around a part of the second part of the portion 33, and configured to emit a magnetic field parallel to a part of the conduit 33 surrounded by the internal outlet magnetization means 12 It should be noted that there may be.

[0179] Next, various embodiments of the method according to the present invention, implemented in various embodiments of the hyperpolarization devices 100, 200, 300, 400, 500 according to the present invention, will be described with reference to FIGS. 1 to 10.

[0180] In all devices 100, 200, 300, 400 and 500, the hyperpolarization method according to the present invention comprises supplying the solution 1 in a liquid state, said solution 1 being 〇 Having a first magnetic rotation ratio, a first nuclear spin species that is hyperpolarized (e.g., 1 H hydrogen nucleus), and 〇 Having a second magnetic rotation ratio, a second nuclear spin species that is not hyperpolarized (e.g., carbon 13 C, nitrogen 15 N or phosphorus 31 P nucleus) is included.

[0181] Two nuclear spin species in one or more molecules of solution 1 that are coupled by scalar spin-spin coupling are also referred to as "J-couplings" by those skilled in the art. This coupling is a permanent coupling (without chemical exchange).

[0182] Solution 1 is supplied to the inversion chamber 2 such that this solution 1 circulates through the conduit 3 as solution flow 1, and a portion of the conduit 3 called the inversion portion 33 passes through the inversion chamber 2.

[0183] The inversion chamber 2 includes an inlet through which the solution flow 1 enters and an outlet through which the solution flow 1 exits.

[0184] The inversion chamber 2 includes a magnetic shielding portion 5 that surrounds the inversion portion 33, and the magnetic shielding portion 5 isolates the inversion portion 33 from the ambient magnetic field around the magnetic shielding portion 5.

[0185] In devices 100, 200, 300, 400, and 500, the method according to the invention further comprises generating an inversion magnetic field 6 in section 33 by means of at least one magnetization means, the at least one magnetization means being located at least partially inside the magnetic shield 5 and being referred to as at least one internal magnetization means 11, 12, surrounding, delimiting, or being around at least a part of the inversion section 33, the main component of the inversion magnetic field 6 being along the direction Z, preferably reversing once while traveling through the inside of the inversion section 33, and while the solution 1 flows through the inversion section 33 from the inlet of the chamber 2 to the outlet of the chamber 2 at a non-zero velocity of the solution 1, i.e., without fixing the solution 1 in the inversion section 33, causing the hyperpolarization to move from the first nuclear spin species to the second nuclear spin species in the inversion section 33. This is a "crossing-avoiding" movement, and the possibility can be calculated using the Landau-Zener theory.

[0186] As already shown, the inversion section 33 may or may not be straight.

[0187] The main component of the inversion magnetic field 6 in the direction Z may be orthogonal, parallel (or even oblique in some variants) to the direction in which the solution 1 flows through section 33. The direction Z is constant, but the direction of the solution flow 1 in section 33 may vary, for example, through bends, curves, or corners in section 33.

[0188] In the case of device 100 or 500, - Each internal magnetization means 11, 12 generates a magnetic field that is constant over time and opposite to the magnetic field of the other internal magnetization means, and the overall magnetic field of these two internal magnetization means reverses inside the inversion section 33, preferably at the center of the inversion section 33. - The two internal magnetization means 11, 12 are supplied with a current i1 in opposite rotational directions, and their leakage magnetic fields are opposite to each other.

[0189] A preferred solution to achieving the ideal magnetic field profile 6 is the use of internal magnetization means 11 and 12 (or 110 and 120), which are symmetric (preferably with respect to the plane 71 orthogonal to the preferably straight portion 33), as in the case of devices 100, 200 and 500, and face each other around or along the portion 33 inside the shield 5.

[0190] In the case of device 200, - Two internal solenoid assemblies (110, 120) are supplied with a current i1 in opposite rotational directions, and their leakage magnetic fields are opposite to each other, - The method optionally includes varying the resistor 23 of the split bridge 20 via an adjustment interface in order to adjust or optimize the magnetic field inversion profile 6.

[0191] In the case of devices 100, 200, 300, 400 and 500, - Supplying the solution 1 to the inversion chamber 2 〇 preferably supplying the solution 1 from a dynamic nuclear polarization device (18) DNP, preferably dDNP, connected to the conduit 3, and / or 〇 supplying the solution 1 from any other device 18 capable of generating and / or supplying a solution containing both nuclear spin species comprises - The external inlet magnetization means 41 or the external outlet magnetization means 42 maintains respectively the input magnetic field at the inlet of the inversion chamber 2 or the output magnetic field at the outlet of the inversion chamber 2 within the conduit 3, - The two external magnetization means 41, 42 are supplied with a current i2 having opposite rotational directions, - The method preferably includes purifying the solution 1 by means of a purification means, for example one or more polarization matrices, downstream of the chamber 2, i.e. between the chamber 2 and the device 19. - The method further includes supplying the solution 1 via the conduit 3 to a nuclear magnetic resonance (NMR) spectrometer 19 or a magnetic resonance imaging (MRI) device 19 after passing through the inversion chamber 2.

[0192] The method includes, for example, 13 13C hyperpolarization for MRI detection of prostate cancer, or NMR drug screening, NMR chemical or biological kinetics, and metabolomics studies, metabolite (or 1 other low gyromagnetic ratio nuclei bound to 1H nuclei) 13 13C hyperpolarization.

[0193] For example, the transfer was performed under the following experimental conditions: - Polarization device used: Device 100 - Upstream and downstream conduits 3 of chamber 2: Teflon capillary tubes having an outer diameter of 3.2 mm and an inner diameter of 1.6 mm (circular cross-section) and surrounded by 0.5 mm copper wire (solenoid 51 or 52) wound and adhered. A current of 2 A supplied by the laboratory power supply passed through the copper wire (solenoid 51 or 52) and generated a magnetic field of about 4 mT in the upstream and downstream capillaries of chamber 2. - Composition of solution 1 at the inlet of chamber 2: 100 μL of DNP sample (composition: 0.43 M 13 sodium 13C formate, 0.44 M [3- 13 13C]-sodium pyruvate, 0.44 M [2- 13 13C] sodium pyruvate, 0.45 M [1- 13 13C] sodium pyruvate, and 50 mM TEMPOL dissolved in 1:3:6 H2O:D2O:D8-glycerol v / v / v) 1 1H spins were hyperpolarized in an 18 d DNP polarizer at 1.2 K and 7.05 T. The 1 1H polarization of the sample before dissolution was about 50%. ([[]]END]] 1 Weak 13 13C polarization of the sample (acquired while the 13 13C polarization in the liquid is solely 1To ensure that it is derived from the movement from H, it was reduced to 0% by a series of radio frequency pulses before dissolution. The sample was dissolved in 5 mL of D2O pressurized up to 6 bar and heated to 9 bar and 175 °C, and then transferred to an NMR tube placed in a benchtop NMR spectrometer (reference numeral 19 in FIG. 1) operating at 1.88 Tesla in 1.8 s using a rapid transfer injection system (for example, refer to "An automated system for fast transfer and injection of hyperpolarized solutions", Ceillier et al., Journal of Magnetic Resonance Open, Volumes 8 - 9, December 2021, 100017). The velocity of the solution during transfer was about 5 m.s -1 The conduit for transferring the solution from the polarizer to the benchtop spectrometer passed through an inversion chamber placed as close as possible to the outlet of the dDNP polarizer so as to minimize the loss of 1 H polarization. - All solenoids 11, 12 were made of copper wire, with a wire diameter of 0.5 mm, a coil diameter of 12 mm, 112 windings, a solenoid length of 7.3 cm, separated by 10.4 cm, and supplied with a current i1 of 0.05 ampere. - All solenoids 41, 42 were made of copper wire, with a wire diameter of 0.5 mm, a coil diameter of 1.8 cm, 107 windings, a solenoid length of 70 cm, and supplied with a current i2 of 1 ampere. - All solenoids 51, 52 were made of copper wire, with a wire diameter of 0.5 mm, a coil diameter of 3.2 mm, more than 2000 windings, a solenoid length of more than 100 cm, and supplied with a current of 2 amperes. - The support 8 is made of a 3D printed resin (transparent resin) having grooves for arranging copper wires as accurately as possible. - The support 9 is made of a 3D printed resin (transparent resin) having grooves for arranging copper wires as accurately as possible. - The conduits 3, 33 are made of a 3D printed substrate, have square holes (4 mm on each side), and capillaries (or conduits) 3, 33 having an outer diameter of 3.2 mm (circular cross-section) and an inner diameter of 1.6 mm (circular cross-section) pass through these holes. - The shielding part 5 is made of mu-metal, has four concentric layers with a thickness of about 1 mm, and has a length of 32.6 cm along the axis S (MS-IL, Twinleaf). - The distances D, 13 are 7.3 cm.

[0194] The obtained magnetic field is shown in Figure 4.

[0195] The C polarization obtained in the liquid state at the end of this experiment for the four molecules present in the solution is shown in the following table. The experiment was repeated twice ("Inversion #1", "Inversion #2"). Furthermore, two control experiments were conducted. 13 - In the "No inversion #1" experiment, the solution was passed through the inversion chamber, but the coil was connected so that the magnetic field did not invert (the magnetic field decreased to a value in the pT range and then increased again). - In the "No inversion #2" experiment, the solution was not passed through the inversion chamber.

[0196]

Table 1

[0197] Assuming the magnetic field profile of this inversion chamber and this solution velocity, numerical spin dynamics simulations predict that the polarization transfer from H to C must be a total for C formate and [3- 1 H to 13 C. On the other hand, the transfer is expected to be almost zero for [2- 13 C]-pyruvate and [l- 13 C]-pyruvate molecules because the J coupling (for a given magnetic field profile) is too weak. The experimental results of the inventors confirm these predictions. 13 C]-pyruvate and [l- 13 C]-pyruvate molecules. The experimental results of the inventors confirm these predictions.

[0198] The two control experiments show non-zero transfer despite the absence of magnetic field inversion. This is probably due to the nuclear Overhauser effect (NOE) during transfer in the liquid. This transfer is 1H and 13 Since the distance between the nuclear spins of H and C is too large, [2- 13 C]-pyruvate and [1- 13 C]-pyruvate molecules do not occur.

[0199] The details of the implementation form of device 200 differ from those of the implementation form of device 100 in the following points: - All solenoids 11 and 12 are made of copper wire, with a wire diameter of 0.5 mm, a coil diameter of 4 cm, wound 62 times, and a solenoid length of 3 cm. - The current source 21 supplies a current I of 4000 pA to the 13 13 C-formate molecule at the inlet of the current divider 20, or supplies a current I of 30 μA to the 1- 13 C-pyruvate. - The assembly 110 includes 12 solenoids 11 having 12 current dividers 20 (more than those shown in FIG. 6). - The assembly 120 includes 12 solenoids 12 having 12 current dividers 20 (more than those shown in FIG. 6). - Each solenoid 11 or 12 associated with the current divider 20 having resistors R1 and R2 has a current i1 = I(R2 / (R1 + R2)) flowing through the solenoid 11 or 12. - Each pair of R1 / R2 is different so that each solenoid portion 11 or 12 provides an optimal magnetic field 6. Each resistor is set to a default value of 1000 ohms for R2 and R1 with values increasing towards the center of portion 33 (increasing values from left to right for the bridge 20 in the case of assembly 110 and increasing values from right to left in the case of assembly 120). Typically, each resistor R1 has values of 4 ohms, 20 ohms, 44 ohms, 70 ohms, 90 ohms, 125 ohms, 166 ohms, 220 ohms, 302 ohms, 454 ohms, 768 ohms, 2000 ohms for the 12 bridges 20 from left to right in the case of assembly 110 and from right to left in the case of assembly 120.

[0200] The method according to the present invention is [2-13 C]-pyruvate or [1- 13 It is applicable to Solution 1 containing a molecule having a J-coupling such as C]-pyruvate.

[0201] The method according to the present invention is a strong J-coupling ([3- 13 Solution 1 containing a molecule having C]-pyruvate, J = 125 Hz), or [2- 13 C]-pyruvate or [1- 13 It is applicable to Solution 1 containing other molecules more interesting for in vivo use such as C]-pyruvate, and more efficiently has a longer shielding part 5 (with a length on the order of 1 m).

[0202] Naturally, the present invention is not limited to the examples just described, and numerous adjustments can be made to these examples without departing from the scope of the present invention.

[0203] The inversion part 33 can be of any shape, linear, curved, or a combination of curved (s) and / or linear (s).

[0204] Naturally, the various features, forms, deformations, and embodiments of the present invention can be combined with each other in various combinations as long as they are not incompatible or exclusive of each other. In particular, all the deformations and embodiments described above can be combined with each other.

Claims

Claim 1 A method of hyperpolarization, the hyperpolarization method comprising: - Supplying a solution (1) in a liquid state containing - A first nuclear spin species that is hyperpolarized and has a first magnetic rotation ratio, and - A second nuclear spin species having a second magnetic rotation ratio Both of the nuclear spin species are coupled by scalar spin-spin coupling in one or more molecules of the solution (1), The solution (1) is supplied to an inversion chamber (2) such that the solution (1) circulates in the form of a solution flow within a conduit (3). A part of the conduit (3) called an inversion part (33) passes through the inversion chamber (2). The inversion chamber (2) has an inlet through which the solution flow enters and an outlet through which the solution flow exits, The inversion chamber (2) is provided with a magnetic shielding part (5) surrounding the inversion part (33), and the inversion part (33) is isolated from the ambient magnetic field around the magnetic shielding part (5), The method further comprises: - Generating an inversion magnetic field (6) by at least one magnetization means called at least one internal magnetization means (11, 12) that is at least partially located inside the magnetic shielding part (5), The main component of the inversion magnetic field (6) is along the direction Z, and it reverses as it travels inside the inversion part (33). By generating the inversion magnetic field (6), within the inversion part (33), while the solution flows at a non-zero speed from the chamber inlet to the chamber outlet within the inversion part (33), a method of hyperpolarization for transferring hyperpolarization from the first nuclear spin species to the second nuclear spin species. Claim 2 At least one of the internal magnetization means (11, 12) comprises a pair of internal magnetization means (11, 12) that are at least partially within the magnetic shielding part (5) and at least partially surround, border, or are around the inversion part (33), Each of the internal magnetization means (11, 12) generates a magnetic field that is constant over time and opposite to the magnetic field of the other internal magnetization means. The overall magnetic field of the two internal magnetization means reverses inside the inversion part (33), preferably at the center of the inversion part (33). The method according to claim 1. Claim 3 At least one of the internal magnetization means (11, 12) comprises a plurality of internal solenoids (11, 12) at least partially within the magnetic shielding portion (5), the plurality of internal solenoids (11, 12) at least partially surround the inversion portion (33), and are connected by a current splitting bridge (20), the internal solenoids (11, 12) are separated into two internal solenoid assemblies (110, 120), the two internal solenoid assemblies (110, 120) are supplied with currents in opposite rotational directions, and the leakage magnetic fields of the two internal solenoid assemblies (110, 120) are opposite to each other. The method according to claim 1, characterized in that.

4. The method according to claim 3, characterized in that there is no gap between the two assemblies (110, 120) of the internal solenoids (11, 12).

5. The current splitting bridge (20) comprises a variable resistor (23) via an adjustment interface, and the method comprises changing the resistor (23) of the splitting bridge (20) via the interface to adjust or optimize the magnetic field inversion profile (6). The method according to claim 3 or 4, characterized in that it comprises.

6. The method further comprises magnetization means called external inlet magnetization means (41) at least partially outside the magnetic shielding portion (5) and extending at least to the inlet of the inversion chamber (2), and magnetization means called external outlet magnetization means (42) at least partially outside the magnetic shielding portion and extending at least to the outlet of the inversion chamber (2), and each said external magnetization means maintains an input magnetic field at the inlet of the inversion chamber (2) and an output magnetic field at the outlet of the inversion chamber (2) within the conduit (3). The method according to any one of claims 1 to 5, characterized in that.

7. Each said external magnetization means (41, 42) surrounds, borders or is around at least a part of at least one of the internal magnetization means (11, 12). The method according to claim 6, characterized in that.

8. Each of the external magnetization means includes an external solenoid or is an external solenoid. Each of the external solenoids (41, 42) is supported by an external support component (8) around the conduit (3), surrounds the conduit (3), and the external support component (8) - On the side of the conduit (3), it does not contact the conduit, - On the side of each of the external solenoids (41, 42), it is characterized by including a relief portion configured to accommodate and arrange the windings of each of the external solenoids (41, 42). The method according to claim 6 or 7.

9. At least one of the internal magnetization means is at least one internal solenoid. Each of the internal solenoids (11, 12) is at least partially supported by the inversion portion (33) and at least partially surrounds the inversion portion (33) via an internal support component (9). The internal support component (9) - On the side of the conduit (3), it contacts the conduit (3), - On the side of each of the internal solenoids (11, 12), it is characterized by including a relief portion configured to accommodate and arrange the windings of each of the internal solenoids (11, 12) along the conduit (3). The method according to any one of claims 1 to 8.

10. The supply of the solution (1) to the inversion chamber (2) includes supplying the solution (1) from a dynamic nuclear polarization DNP device (18) connected to the conduit (3). The method according to any one of claims 1 to 9.

11. The inversion portion (33) and / or the conduit (3) is a capillary having a maximum dimension perpendicular to the solution flow (1) of less than 5 mm. The method according to any one of claims 1 to 10.

12. In the inversion portion (33), the inversion magnetic field (6) is included in the range of at least 0 mT to 0.1 mT in absolute value along the direction Z. The method according to any one of claims 1 to 11.

13. An overpolarization device including an inversion chamber, wherein the inversion chamber (2) - is an inlet, and 〇 A solution (1) flow in a liquid state including a first nuclear spin species that is overpolarized and has a first magnetic rotation ratio, and 〇 A second nuclear spin species having a second magnetic rotation ratio is configured such that the solution (1) flow enters the chamber (2) through the inlet. - An outlet configured such that the solution (1) flow exits the chamber (2) through the outlet and both of the nuclear spin species are coupled by scalar spin-spin coupling in one or more molecules of the solution (1), the inlet and the outlet are configured such that the solution (1) flows along the solution flow in the conduit (3), and a portion of the conduit (3) called the inversion portion (33) passes through the inversion chamber (2), the chamber (2) is - A magnetic shielding portion (5) surrounding the inversion portion (33), the magnetic shielding portion (5) isolating the inversion portion (33) from the ambient magnetic field around the magnetic shielding portion (5), - At least one magnetization means, at least partially located inside the magnetic shielding portion (5), called at least one internal magnetization means (11, 12) and the internal magnetization means (11, 12) is configured to generate an inversion magnetic field (6), the main component of the inversion magnetic field (6) is along the direction Z, and it reverses as it progresses inside the inversion portion (33), and the inversion magnetic field (6) is generated so that, in the inversion portion (33), while the solution flows through the inversion portion (33) from the chamber inlet to the chamber outlet at a non-zero velocity, the hyperpolarization is transferred from the first nuclear spin species to the second nuclear spin species, The hyperpolarization device further comprises a device (18) configured to supply the solution (1) to the inlet of the inversion chamber (2) through the conduit (3). **Claim 14** The device according to claim 13, characterized in that the device (18) configured to supply the solution (1) comprises a dynamic nuclear polarization, i.e., a DNP device (18) connected to the conduit (3).

Images