Hyperpolarization method and apparatus

Abstract

A reversal chamber (2) comprising at least one magnetization device, referred to as at least one internal magnetization device (11, 12), located at least partially inside the magnetic shield (5) and at least partially surrounding a reversal portion (33), said at least one internal magnetization device being arranged for generating a reversal magnetic field (6), the main component of the magnetic field is reversed in the Z-direction and as it passes through the interior of the reversal portion (33) to, inside the reversal portion (33), generate a magnetic field in which the main component of the magnetic field is reversed during a non-zero velocity of the flow of solution in the reversal portion (33) from the inlet of the chamber to the outlet of the chamber. The hyperpolarization is transferred from a first type of nuclear spins to a second type of nuclear spins (by scalar coupling between the nuclear spins) inside said inversion portion (33). The invention also relates to a device comprising such a chamber and a method implemented by such a device.

Description

Technical Field

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

[0002] Such a device allows the user to hyperpolarize a solution in a simple and quick manner.The technical field of the invention is more particularly (but not limited to) the technical field of hyperpolarized solutions for medical imaging. Background Art

[0003] The method of dynamic nuclear polarization (DNP) is well known and is described, for example, in WO200826937 of GE HEALTHCARE AS.

[0004] Hyperpolarization 13 The generation of C metabolites allows new applications in magnetic resonance imaging (MRI).

[0005] Hyperpolarization 13 C-pyruvate is used in magnetic resonance imaging (MRI) applications. It can be obtained by solution dynamic nuclear polarization (dDNP). The most common method uses trityl radicals as polarizing agents to directly polarize 13 C. Hyperpolarized ions for MRI can be prepared using trityl radicals using SpinLab (GE Healthcare). 13 C. The time for preparing the hyperpolarized sample using trityl radicals exceeded 60 min.

[0006] It can also be polarized 1 H nuclei, and the transfer of this polarization to the solid state by cross polarization 13 C. This method is fast (less than 20 minutes) but requires very sophisticated instrumentation. This method is described in W02013153101 from BRUKER BIOSPIN AG.

[0007] The object of the present invention is to provide a hyperpolarization device or method which is both fast and simple to implement, thereby combining two technical advantages which cannot be combined in the prior art, and to provide a chamber for such a hyperpolarization device or method. Summary of the invention

[0008] This object is achieved by a hyperpolarization method, the method comprising supplying a liquid solution comprising: ○ a first type of nuclear spin having a first gyroscopic ratio and being hyperpolarized, and ○ a second type of nuclear spin having a second gyroscopic ratio; The solution is supplied to the inversion chamber so that it flows as a stream of solution in a conduit, a portion of which, referred to as the inversion portion, passes through the inversion chamber; the inversion chamber comprises an inlet through which the flow of said solution enters, and an outlet through which the flow of said solution exits; The reversal chamber preferably includes a magnetic shield surrounding the reversal portion so as to isolate the reversal portion from an ambient magnetic field around the magnetic shield; The method further comprises: - generating a reversal magnetic field by at least one magnetizing device, referred to as at least one internal magnetizing device, preferably located at least partially inside the magnetic shield, the main component of which is in the Z direction and which is reversed when passing through the interior of the reversal section, so as to transfer the hyperpolarized nuclear spins of the first type to the nuclear spins of the second type inside the reversal section when the flow of the solution flows at a non-zero speed in the reversal section from the inlet to the outlet of the chamber.

[0009] In one or more molecules in the solution, the types of nuclear spins are preferably coupled via scalar spin coupling.

[0010] The reverse portion may be straight.

[0011] The at least one internal magnetizing device may include a pair of internal magnetizing devices located at least partially inside the magnetic shield, the pair of internal magnetizing devices at least partially surrounding or framing the reversal portion or extending along the reversal portion. Each internal magnetizing device: - a magnetic field which is constant in time and opposite to the magnetic field of the other internal magnetization means can be generated, the sum of the magnetic fields of the two internal magnetization means being reversed inside the reversal section (preferably in the center of the reversal section), and / or - may include or may be an internal solenoid, whereby the at least one internal magnetizing means located at least partially within the magnetic shielding body comprises a pair of internal solenoids, the pair of internal solenoids: ○ preferably powered by currents of opposite rotational direction, and / or ○ Preferably have opposite stray magnetic fields.

[0012] The at least one internal magnetizing device may include a plurality of internal solenoids at least partially located inside the magnetic shield, the plurality of internal solenoids at least partially surrounding the reversing portion and connected by a shunt bridge, the internal solenoids being divided into two groups of internal solenoids, the two groups of internal solenoids: ○ powered by currents of opposite rotational direction, and / or ○ Have opposite leakage magnetic fields.

[0013] Preferably, there is no separation space between the two sets of inner solenoids.

[0014] The shunt bridge may comprise a variable resistor which is adjusted via an adjustment interface, and the method according to the invention preferably comprises changing the resistance of the shunt bridge via the interface in order to adjust or optimize the reversal distribution of the reversal magnetic field.

[0015] The method according to the invention may comprise the use of a magnetizing device at least partially located outside the magnetic shield, called an entrance external magnetizing device, extending at least as far as the entrance of the reversal chamber, and a magnetizing device at least partially located outside the magnetic shield, called an exit external magnetizing device, extending at least as far as the exit of the reversal chamber, each external magnetizing device maintaining an entrance magnetic field at the entrance of the reversal chamber and an exit magnetic field at the exit of the reversal chamber in the conduit.

[0016] Preferably, each outer magnetizing means at least partially surrounds or frames the at least one inner magnetizing means or extends along the at least one inner magnetizing means.

[0017] Preferably: - The upstream magnetizer surrounds the conduit continuously between the following two areas: ○ The area that is both outside the magnetic shield and outside the inlet external magnetizer, and ○ An area that is both outside the magnetic shield and inside the inlet external magnetizer, and / or - The upstream magnetizer surrounds the conduit continuously between the following two areas: ○ The area that is both outside the magnetic shield and outside the outlet external magnetizer, and ○ The area that is both outside the magnetic shield and inside the magnetizer outside the outlet.

[0018] Each respective inlet or outlet external magnetisation means may respectively surround or frame or extend along a junction area between: - the portion of the conduit penetrating into the respective inlet or outlet external magnetizing device and surrounded by the respective upstream or downstream magnetizing device, and - a portion of the conduit surrounded or framed by or extending along the at least one internal magnetizing device, said portion penetrating into the magnetic shield through the inlet or outlet of the respective inversion chamber.

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

[0020] Each external magnetizing means may comprise or may be an external solenoid, each external solenoid preferably encircling the conduit, carried around the conduit by an external support, said external support: - on the catheter side, without contact with the catheter, and / or - On each external solenoid side, comprising a protrusion arranged to receive and position the turns of each external solenoid.

[0021] The at least one internal magnetizing means may be at least one internal solenoid.

[0022] The at least one internal magnetizing device may be at least one internal solenoid, each internal solenoid at least partially surrounding the reversing portion, at least partially carried by the reversing portion via an internal support, the internal support: - on the catheter side, in contact with the catheter, and / or - On each internal solenoid side, comprising a protrusion arranged to receive and position the turns of each internal solenoid along the conduit.

[0023] The method according to the present invention may further include supplying the solution to a nuclear magnetic resonance (NMR) spectrometer or a magnetic resonance imaging (MRI) device through a conduit after the solution passes through the inversion chamber.

[0024] In the reversal section, the reversal magnetic field may have a single component that is along the Z direction and is reversed when passing through the reversal section.

[0025] Supplying the solution to the inversion chamber may include supplying the solution from a DNP (Dynamic Nuclear Polarization) device connected to the catheter and / or from any other device capable of making and / or supplying a solution containing two types of spins.

[0026] The inverted sections and / or conduits are preferably capillaries having a largest dimension perpendicular to the flow of the solution of less than 5 mm.

[0027] In the reversal portion, the absolute value of the reversal magnetic field in the Z direction is preferably at least 0 m to 0.1 mT.

[0028] The first type of nuclear spins may have a greater gyroscopic ratio than the second type of nuclear spins.

[0029] According to another aspect of the present invention, an inversion chamber is provided, comprising: - an inlet arranged for a flow of a liquid solution, the flow of the liquid solution comprising: ○ a first type of nuclear spin having a first gyroscopic ratio and being hyperpolarized, and ○ A second type of nuclear spin with a second gyromagnetic ratio, A flow of the solution enters the chamber through the inlet; - an outlet arranged for a flow of solution to leave the chamber through the outlet The inlet and the outlet are arranged so that the solution flows in the form of a stream of solution in a conduit, a portion of the conduit, referred to as the inversion portion, passing through the inversion chamber; The chamber further comprises: - a magnetic shield preferably surrounding the reversal portion so as to isolate the reversal portion from an ambient magnetic field surrounding the magnetic shield; at least one magnetizing device, referred to as at least one internal magnetizing device, preferably located at least partially inside the magnetic shield, arranged to generate a reversal magnetic field having a main component in the Z direction and reversing when passing through the interior of the inversion section, in order to transfer the hyperpolarization of the nuclear spins of the first type to the nuclear spins of the second type inside the inversion section during the flow of the solution at a non-zero speed in the inversion section from the inlet of the chamber until the outlet of the chamber.

[0030] In one or more molecules of the solution, the two types of nuclear spins are preferably coupled via scalar spin coupling.

[0031] The reverse portion may be straight.

[0032] The at least one internal magnetizing device may include a pair of internal magnetizing devices at least partially located within the magnetic shield, the pair of internal magnetizing devices at least partially surrounding or framing the reversal portion or extending along the reversal portion. Each internal magnetizing device: - can be arranged to generate a magnetic field which is constant in time and opposite to the magnetic field of the other internal magnetization means, so that the sum of the magnetic fields of the two internal magnetization means reverses inside the reversal section, preferably in the center of the reversal section, and / or - may include or may be an internal solenoid, whereby the at least one internal magnetizing means comprises a pair of internal solenoids at least partially located within the magnetic shield, the pair of internal solenoids preferably having: o The chamber may further comprise a power supply arranged to power the two internal solenoids with currents of opposite rotational directions, and / or ○ The leakage fields of the two inner solenoids are opposite.

[0033] The at least one internal magnetizing device may include a plurality of internal solenoids at least partially located inside the magnetic shield, the internal solenoids at least partially surrounding the reversing portion and connected by a shunt bridge, the internal solenoids being divided into two groups of internal solenoids, the chamber further comprising a power supply arranged to power the two groups of internal solenoids: - energizing the two sets of internal solenoids with currents rotating in opposite directions, and / or - Make the leakage magnetic fields of the two sets of internal solenoids opposite.

[0034] The reversal chamber according to the present invention may not include a separation space between the two sets of internal solenoids.

[0035] The shunt bridge may comprise a variable resistor which is adjusted by an adjustment interface arranged for varying the resistance of the shunt bridge via the interface in order to adjust or optimize the reversal profile of the reversal magnetic field.

[0036] The chamber according to the invention may further comprise a magnetising device, referred to as an entrance external magnetising device, which is at least partially located outside the magnetic shield and extends at least to the entrance of the reversal chamber, and a magnetising device, referred to as an exit external magnetising device, which is at least partially located outside the magnetic shield and extends at least to the exit of the reversal chamber, each external magnetising device being arranged to maintain an entrance magnetic field at the entrance of the reversal chamber and an exit magnetic field at the exit of the reversal chamber in the conduit.

[0037] Each outer magnetizing means may at least partially surround or frame the at least one inner magnetizing means or extend along the at least one inner magnetizing means.

[0038] The inversion chamber according to the present invention may further comprise: - An upstream magnetizing device which surrounds the conduit continuously between the following two areas: ○ The area that is both outside the magnetic shield and outside the inlet external magnetizer, and ○ An area that is both outside the magnetic shield and inside the inlet external magnetizer, and / or - A downstream magnetizer which surrounds the conduit continuously between the following two areas: ○ The area that is both outside the magnetic shield and outside the outlet external magnetizer, and ○ The area that is both outside the magnetic shield and inside the magnetizer outside the outlet.

[0039] Each respective inlet or outlet external magnetisation means may surround or frame or extend along the junction area between: - the portion of the conduit penetrating into the respective inlet or outlet external magnetizing device and surrounded by the upstream or downstream magnetizing device respectively, and - a portion of the conduit surrounded or framed by or extending along the at least one internal magnetizing device, said portion penetrating into the magnetic shield through the inlet or outlet of the respective inversion chamber.

[0040] Each external magnetising means may comprise or may be an external solenoid.

[0041] Each external magnetizing device may be carried around the catheter by an external support member surrounding the catheter, the external support member: - on the catheter side, without contact with the catheter, and / or - On each external solenoid side, comprising a protrusion arranged to receive and position the turns of each external solenoid.

[0042] The at least one internal magnetizing means may be at least one internal solenoid.

[0043] Each internal solenoid at least partially surrounds the reversing portion and may be at least partially carried by the reversing portion via an internal support member, the internal support member: - on the catheter side, in contact with the catheter, and / or - On each internal solenoid side, comprising a protrusion arranged to receive and position the turns of each internal solenoid along the conduit.

[0044] The reversal chamber according to the present invention may be arranged so that the reversal magnetic field has a single component in the reversal section along the Z direction and reversed while passing through the reversal section.

[0045] The inverted portion and / or conduit may be a capillary tube having a largest dimension perpendicular to the solution flow of less than 5 mm.

[0046] The reversal chamber according to the present invention may be arranged so that, in the reversal portion, the absolute value of the reversal magnetic field in the Z direction is at least 0 mT to 0.1 mT.

[0047] The first type of nuclear spins may have a greater gyroscopic ratio than the second type of nuclear spins.

[0048] According to another aspect of the present invention, a hyperpolarization device is provided, comprising: - an inversion chamber according to the invention, - means arranged for supplying a solution to the inlet of the inversion chamber via the conduit.

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

[0050] Equipment for supplying the solution may include: - Dynamic Nuclear Polarization (DNP) device connected to the catheter, and / or - Any other device capable of manufacturing and / or supplying a solution containing both types of spins. BRIEF DESCRIPTION OF THE DRAWINGS AND EMBODIMENTS

[0051] Other advantages and features of the invention will emerge from a reading of the detailed description of non-limiting implementations and embodiments and from the following drawings:

Figure 1

Figure 2

Figure 3

Figure 4

[0052]

Figure 5

Figure 6

Figure 7

Figure 8

Fig. 9

Fig.10

[0053] Since these embodiments are in no way limiting, variants of the invention comprising only a selection of features described or illustrated by subsequent isolation from other features described or illustrated (even if this selection is isolated in the statement comprising these other features) are particularly contemplated if the selection of features is sufficient to confer a technical advantage or to distinguish the invention from the prior art. This selection comprises at least one preferred functional feature without structural details and / or only with some structural details if only this part is sufficient to confer a technical advantage or to distinguish the invention from the prior art.

[0054] First, refer to Figures 1 to 4 A first embodiment of a hyperpolarization device 100 according to the invention is described, comprising a first embodiment of a reversal chamber 2 according to the invention.

[0055] The apparatus 100 comprises an inversion chamber 2, which comprises: - an inlet arranged for a flow of a liquid solution 1 comprising: ○ A first type of nuclear spin (preferably 1 H, which has the advantage of being hyperpolarized very rapidly by DNP upstream of chamber 2) and ○ A second type of nuclear spin with a second gyroscopic ratio (preferably 13 C, which has the advantage of 1 H nuclear spins have a longer relaxation time), and in one or more molecules of solution 1, the two types of nuclear spins are coupled via scalar spin coupling, The flow of the liquid solution enters chamber 2 through the inlet; - an outlet arranged for a flow of solution 1 to leave chamber 2 through the outlet The inlet and the outlet are arranged for the solution 1 to flow in the form of a stream of solution in a portion of the conduit 3 , referred to as the inversion portion 33 , which passes through the inversion chamber 2 .

[0056] In this specification, "spin" or "nuclear spin" refers to the spin of an atomic nucleus (possibly within a molecule) carried by the nucleus of an atom.

[0057] The reversal chamber 2 further comprises a magnetic shield 5 surrounding the reversal portion 33 , and the magnetic shield 5 is arranged to isolate the reversal portion 33 from an ambient magnetic field around the magnetic shield 5 .

[0058] like Figure 2 As shown in Figs. a and 3, for better efficiency, the shield 5 preferably comprises a plurality of layers (preferably concentric).

[0059] The inlet of the chamber 2 corresponds to the inlet of the duct 3 leading from the outside of the chamber 2 into the shield 5 .

[0060] The outlet of the chamber 2 corresponds to the outlet of the duct 3 leading from the interior of the chamber 2 to the outside of the shielding body 5 .

[0061] The chamber 2 further comprises at least one magnetizing device 11, 12, referred to as at least one internal magnetizing device 11, 12, which is at least partially located inside the magnetic shield 5 and at least partially surrounds or frames the inversion portion 33 or extends along the inversion portion 33. The at least one internal magnetizing device 11, 12 is arranged for generating a reversal magnetic field 6 in the portion 33, the main component of which preferably reverses only once (at the reversal plane 71) while passing through the interior of the inversion portion 33 along the Z direction and from the entrance to the exit of the chamber 2 (along the axis S and the Z direction), so as to transfer hyperpolarization from the first type of nuclear spins to the second type of nuclear spins inside the inversion portion 33 during the flow of the flow of the solution 1 in the inversion portion 33, without bringing the solution 1 to rest in the inversion portion 33 (i.e. the solution 1 has a non-zero velocity in the inversion portion 33 from the entrance of the chamber until the exit of the chamber).

[0062] In this specification, inversion means changing the direction of the principal component (while keeping the Z direction unchanged).

[0063] In this specification, a reversal magnetic field 6 having a main component along the Z direction preferably means that if the magnetic field 6 has a component transverse to the main component, the transverse component is always smaller than: - 10% of the principal component inverted along the Z direction, and / or - 1μT (for example, if a pair 1 H- 13The scalar coupling of C is about 100-200 Hz), and even always less than 0.1 μT (for example, for a coupling of 10-20 Hz), the maximum transverse field allowing effective transfer decreases linearly with the strength of the scalar coupling between nuclear spins at any point of solution 1 in portion 33.

[0064] The chamber 2 is arranged such that the reversal magnetic field 6 preferably has only a single component along the Z direction (ie the component perpendicular to Z is zero or negligible compared to the main component) in the reversal portion 33 and reverses when passing through the reversal portion 33 .

[0065] At least one internal magnetizing device 11, 12 comprises: - at least one inlet internal magnetizing device 11 on the inlet side of the chamber 2, - at least one outlet internal magnetizing device 12 on the outlet side of the chamber 2, In the present specification, the magnetizing device preferably refers to an electromagnet, a permanent magnet, an assembly of a plurality of electromagnets, an assembly of a plurality of permanent magnets, or an assembly of an electromagnet(s) and a permanent magnet(s).

[0066] In this specification, a solenoid refers to the wire of an electromagnet that is wound into a plurality of loops or turns and through which an electric current flows (or is arranged to flow).

[0067] In this specification, a magnetic shield or magnetic barrier 5 refers to a shield of any shape (continuous (sheet, plate, etc.) and / or discontinuous (grid, lattice, etc.)), preferably metal, and arranged to isolate the interior of the shield 5 from a time-continuous magnetic field or a low-temporal-frequency magnetic field located around the shield 5, preferably: - is arranged to reduce the Tesla value of a time-continuous magnetic field located around the shield 5 and having a value less than or equal to 100 microtesla around the shield 5 by at least 10 5 times, preferably at least 10 6 , and / or - Have at least 10 5 , preferably at least 10 6 Shielding factor.

[0068] In this specification, solution 1 refers to a liquid or a liquid mixture, which may contain suspended solid particles.

[0069] In the present embodiment, the reverse portion 33 is straight and extends longitudinally along the axis S.

[0070] In this embodiment, the S and Z directions coincide.

[0071] In this embodiment, the at least one internal magnetizing device 11 , 12 includes a pair of internal magnetizing devices 11 , 12 at least partially inside the magnetic shield 5 , and the pair of internal magnetizing devices at least partially surround or frame the reversal portion 33 or extend along the reversal portion 33 .

[0072] Along the axis S (and in the Z direction) there is a separation space 13 between: - at least one inlet internal magnetizing device 11, and - At least one outlet internal magnetizing device 12.

[0073] In the present embodiment 100, this enables a faster flow of solution 1 (the distribution of field 6 is closer to ideal, so higher flow rates can be chosen while maintaining efficient transfer).

[0074] More precisely, each internal magnetizing device 11 and 12 comprises: - a portion that is inside the shield 5 and surrounds or frames a portion of the inversion portion 33 or extends along a portion of the inversion portion 33, and - a portion that is outside the shield 5 (but inside one of the external magnetizing means 41 , 42 to be described later) and surrounds or frames another portion of the reversal portion 33 or extends along another portion of the reversal portion 33 .

[0075] The reversal portion 33 corresponds to the portion of the catheter 3 which is surrounded or framed by the at least one internal magnetizing device 11 , 12 or which extends along it.

[0076] Each internal magnetizing device comprises an internal solenoid, so at least one internal magnetizing device 11 , 12 comprises a pair of anti-parallel internal solenoids 11 , 12 at least partially within the magnetic shield 5 , the coils of which are centered on the same axis S.

[0077] The chamber 2 also includes at least one power source (not shown, and preferably located outside the shield 5), preferably a single common power source, which is arranged to pass currents i 1 The two inner solenoids 11, 12 are powered (preferably with the same strength) so that the leakage magnetic fields of the two inner solenoids 11, 12 are opposite. 1 is constant in time.

[0078] The advantage of a common power supply is that it is simpler and enables the inversion field 6 to be more stable.

[0079] Each respective internal magnetizing device 11 or 12 , ie each respective solenoid 11 or 12 , is respectively arranged to generate a magnetic field which is constant in time.

[0080] Each corresponding internal magnetizing device 11 or 12 (i.e. each corresponding solenoid 11 or 12) is arranged to generate a magnetic field opposite to the magnetic field of the other corresponding internal magnetizing device 12 or 11 (i.e. the other corresponding solenoid 12 or 11), so that the sum of the magnetic fields of the two internal magnetizing devices (i.e. the two solenoids 11, 12) is reversed inside the reversal portion 33 (in the reversal plane 71 perpendicular to the portion 33), preferably reversed along the S direction at the center of the reversal portion 33 and the separation space 13.

[0081] Room 2 also includes: - a magnetizing device, called an entrance external magnetizing device 41, which is at least partially located outside the magnetic shield 5 and extends at least to the entrance of the inversion chamber 2; the entrance external magnetizing device 41 can be both outside the shield 5 and inside the shield 5, but preferably only outside the shield 5, and - A magnetizing device, called the exit external magnetizing device 42, which is at least partially located outside the magnetic shielding body 5 and extends at least to the exit of the inversion chamber 2; the exit external magnetizing device 42 can be both outside the shielding body 5 and inside the shielding body 5, but preferably only outside the shielding body 5.

[0082] Each external magnetizing device 41 or 42 is arranged to maintain in the conduit 3 an entrance magnetic field (constant in time) at the entrance of the inversion chamber 2 and an exit magnetic field (constant in time) at the exit of the inversion chamber 2 .

[0083] Each of the entrance magnetic field and the exit magnetic field is typically at least 4 mT in the Z direction as its main direction.

[0084] Each of the inlet and outlet magnetic fields ensures that the polarization does not vanish due to rotation of the non-adiabatic field (eg caused by the combined effect of the ambient field and the magnetic shield 5 ).

[0085] Inside or outside the shielding body 5, preferably at least outside the shielding body 5, preferably only outside the shielding body 5, each external magnetizing device 41, 42 surrounds or frames a part of at least one internal magnetizing device 11, 12, or extends along a part of at least one internal magnetizing device 11, 12.

[0086] The inlet external magnetizing device 41 surrounds or frames the portion of the solenoid 11 located outside the shield body, or extends along the portion of the solenoid 11 located outside the shield body.

[0087] The outlet external magnetizing device 42 surrounds or frames the portion of the solenoid 12 located outside the shield body, or extends along the portion of the solenoid 12 located outside the shield body.

[0088] The device 100 further comprises: - Upstream magnetizing means or solenoid 51 which surrounds the conduit 3 continuously between the following two zones: o an area located both outside the magnetic shield 5 and outside the entrance external magnetizing device 41, and o an area both outside the magnetic shield 5 and inside the entrance external magnetizing device 41, and - A downstream magnetizing device or solenoid 52 which surrounds the conduit 3 continuously between the following two zones: ○ An area located both outside the magnetic shield 5 and outside the outlet external magnetizing device 42, and ○ The area located both outside the magnetic shield 5 and inside the outlet external magnetizing device 42.

[0089] Each magnetizing device 51 or 52 is arranged to maintain a magnetic field (constant in time) in the duct 3 , respectively upstream and downstream of the chamber 2 .

[0090] Each inlet external magnetizing device 41 surrounds or frames or extends along a junction area 61 between the following two areas at the inlet of the chamber 2, or each outlet external magnetizing device 42 surrounds or frames or extends along a junction area 62 between the following two areas at the outlet of the chamber 2: - a portion of the conduit 3 which penetrates the respective inlet external magnetizing device 41 or outlet external magnetizing device 42 and which the respective upstream magnetizing device 51 or downstream magnetizing device 52 surrounds or frames or extends along, and - a portion of the conduit 3 around which or along which at least one internal magnetizing device 11 , 12 surrounds or frames or extends, said portion preferably penetrating the magnetic shield 5 through the inlet or outlet, respectively, of the inversion chamber 2 .

[0091] Each external magnetizing device comprises or is an external solenoid, so the chamber 2 comprises, at least partially outside the magnetic shield 5 , a pair of antiparallel external solenoids 41 , 42 , the coils of which are preferably centered on the same axis S.

[0092] The chamber 2 further comprises at least one power source (not shown, and preferably located outside the shield 5), preferably a common power source, arranged to pass currents i 2 The two outer solenoids 41, 42 are powered (preferably with the same strength). The current i 2 is constant in time.

[0093] The current i in the solenoid 11 1 and the current i in the solenoid 41 2 The direction of rotation is the same.

[0094] The current i in the solenoid 12 1 and the current i in the solenoid 42 2 The direction of rotation is the same.

[0095] The advantage of a common power supply is that it is simpler and enables the inversion field 6 to be more stable.

[0096] Each external solenoid 41, 42 surrounds the conduit 3 and is carried around the conduit 3 by an external support 8, which: - on the conduit 3 side, not in contact with the conduit (but only around a portion of the upstream solenoid 51 or the downstream solenoid 52, only around a portion of at least one of the internal solenoids 11, 12 and the joining area 61 or 62), and On the side of each external solenoid 41 or 42 , it comprises turns of a coil arranged for receiving and positioning the external solenoid 41 or 42 (wound in the form of a coil around the external support 8 ).

[0097] As described above, the at least one internal magnetizing device 11 , 12 comprises at least one internal solenoid 11 , 12 .

[0098] Each internal solenoid 11, 12 is at least partially carried by the reversing portion 33 via an internal support 9, by at least partially surrounding the reversing portion 33, said internal support: - on the catheter 3 side, in contact with the catheter 3, and On the side of each internal solenoid 11 or 12 , it comprises a projection arranged for receiving and positioning the turns of the internal solenoid 11 or 12 (wound in the form of a coil around the internal support 9 ) along the duct 3 and in particular along the reversal 33 .

[0099] The inverted portion 33 and / or the conduit 3 is a capillary tube whose greatest dimension perpendicular to the flow of the solution 1 (i.e. perpendicular to the axis S) is less than 5 mm. This allows a better control of the field 6, since the lateral component of the field 6 is more likely to become large the further away from the center of the portion 33 (in a section plane perpendicular to the portion 33).

[0100] The chamber 2 is arranged so that in the inversion portion 33, the absolute value of the reversal magnetic field 6 in the Z direction is at least 0 mT to 0.1 mT, or even at least 0 mT to 0.2 mT. In the portion 33, the field 6 preferably has at least a value greater than 10 times the ratio (J coupling of the two types of spins) / (difference in the gyroscopic ratios of the two types of spins).

[0101] The chamber is arranged so that in the reversal section 33, the reversal magnetic field 6 is at least at a value +B along the direction Z. max To the value +B in the opposite direction along direction Z max Invert between, where Bmax At least equal to 0.1 mT, or at least equal to 0.2 mT.

[0102] In the case of the method using the device, the nuclear spins of the first type preferably have a higher gyromagnetic ratio than the nuclear spins of the second type.

[0103] In addition to the chamber 2 just described, the hyperpolarisation device 100 comprises means 18 arranged to supply the solution 1 at the inlet of the inversion chamber 2 , ie upstream, via the conduit 3 .

[0104] The device 18 comprises: - preferably a dynamic nuclear polarisation DNP device 18, preferably a dissolution dynamic nuclear polarisation dDNP device 18, connected to the catheter 3, and / or - Any other device 18 capable of producing and / or supplying a solution containing both types of nuclear spins.

[0105] The apparatus 100 further comprises a nuclear magnetic resonance (NMR) spectrometer 19 or a magnetic resonance imaging (MRI) apparatus 19 connected to the outlet (ie downstream) of the inversion chamber 2 via the conduit 3 .

[0106] The device 100 further comprises, downstream of the chamber 2 , ie between the chamber 2 and the device 19 , a purification device for the solution 1 (not shown), such as one or more polarization matrices, such as the HYPOP polarization matrix for purifying trace polarizing agents of the solution 1 .

[0107] If the transfer of polarization from one nucleus to another is adiabatic, in other words, if it is slow enough, then it is complete. For the simple case of two coupled spins (nuclear spins of the first and second type of different gyroscopic ratios coupled by scalar coupling, preferably within the same molecule), the minimum time τ for the adiabatic transition is τ for the simple case of the strength of the magnetic field 6 moving in the portion 33 (the field 6 being constant in time at every fixed point within the portion 33) varying linearly with time. trans It can be calculated by Landau-Zener theory, which can be written as [Formula.1]

[0108] Among them, the value of field 6 at time t=0 is +B max (usually at the entrance of chamber 2), at time t = τ trans The time value is -B max (Usually at the exit of Chamber 2). Field Bmax The value of is given by: [Formula 2]

[0109] in , and is the ratio of the spin (in Hz) to its magnetic gyrometry (in Hz.T -1 To obtain this value, choose [Formula 3]

[0110] For a pair with typical coupling 1 H and 13 C spins (1 to 200 Hz, respectively), which is 0.3 to 63 μT. Landau-Zener theory shows that in a linear magnetic field distribution, from +B max To-B max The minimum transfer time for the adiabatic transition of (see Eq. 1) is given by [Formula 4] .

[0111] To obtain the value under this condition, you can choose [Formula 5]

[0112] For a pair with typical coupling 1 H and 13 C spin (1 to 200 Hz, respectively), which is 0.05 to 10 s.

[0113] It should be noted that if a nonlinear field distribution is used, the transfer may be greatly reduced. A constant adiabatic distribution (i.e. a distribution that allows the fastest possible adiabatic transfer) can be calculated numerically. A pair of solenoids 11, 12 aligned along the same axis S and whose leakage magnetic fields are opposite to each other makes it possible to transfer the solenoids at a distance ( Figure 3 The distance D) in the figure with the reference numeral 13 is close to this ideal distribution. This distance 13 and the current flowing through the solenoids 11, 12 can be particularly utilized.

[0114] Therefore, the speed of the flow of solution 1 in portion 33 and its presence time in portion 33 can be easily calculated and optimized as a function of field 6 and the two types of spins and their coupling.

[0115] The distribution of the field 6 experienced by a pair of coupled nuclear spins of solution 1 as a function of time depends on: - The distribution of the field 6 in space (and constant in time) depends on the arrangement of the different inlet internal magnetizing means 11 and outlet internal magnetizing means 12 and possibly on the current flowing (if not permanent magnets). The distribution of the field 6 along the position S can be calculated with the help of the classical equations of an ideal solenoid and by optimizing the current i 1 and is optimized.

[0116] - The speed of the flow of solution 1 , which can be calculated and optimized as previously explained and simply regulated by a pump or a valve or any other known device regulating the speed of the flow of solution 1 .

[0117] Therefore, to summarize this embodiment of the invention: - the magnetic shield 5 enables shielding against the Earth's magnetic field and the magnetic fields generated by the equipment surrounding the room 2, - the internal magnetization means 11, 12 produce a spatial reversal of the field 6, - external magnetizing means 41, 42 for maintaining 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 a coil or magnetizing means 51 , 52 (wound and bonded to the conduit 3 ) to maintain a sufficient magnetic field throughout the transfer of the solution from the device 18 until the chamber 2 and then from the chamber 2 until its destination.

[0118] Typically, the apparatus or method according to the invention uses dDNP to polarize a first type of 1 H spin, and then this polarization is transferred to the second type of liquid 13 C spin. In the case of the present invention, the inversion is accomplished by moving the solution 1 through a distribution of the field 6 in space. Furthermore, the present invention very preferably uses DNP or dDNP to prepare the hyperpolarized 1 H solution 1.

[0119] The device or method according to the invention enables the generation of hyperpolarization in less than 20 minutes without the aid of complex instrumentation. 13 C metabolite solution, which is generated by DNP and contains hyperpolarized 1 The solution of H nuclei is directly generated 13 C (e.g. by cross polarization) and then in chamber 2 in the form of a continuous flow from 1 H 13 C (or 15 N or 31 P) Transferring polarization is very fast, simple and uninterrupted. Unlike cross polarization, adding a reversal chamber 2 according to the invention does not require extensive modifications of the polarizer, but only requires the addition of an inexpensive device at the outlet of the polarizer.

[0120] Usually, for 13 C core with at least one 1 H-nucleus coupled molecules can generate hyperpolarization quickly (<20 min) 13 C solution. The present invention uses a general scheme to produce solution 1, which 1 H is hyperpolarized by "dissolved dynamic nuclear polarization" (dDNP). The polarization in the liquid solution 1 is then changed from 1 HTransfer to 13 C. This field distribution 6 is obtained by using a magnetic shield 5 that eliminates the ambient field (residual magnetic field is of the order of nT) with a pair of antiparallel solenoid coils 11, 12 with constant current, or more generally with a pair of inlet internal magnetizing means 11 and outlet internal magnetizing means 12 or at least one internal magnetizing means 11, 12. Each coil 11, 12 generates a constant and opposite magnetic field 6. The capillary 3, 33 passes through the solenoid 11, 12 and the magnetic shield 5, so that when the solution 1 is pushed into the capillary 3, 33, the molecules are subjected to the reversal of the magnetic field 6 over time. 1 H nucleus and 13 Scalar coupling (J coupling) between C nuclei allows polarization transfer. The theory of this transfer is well established and makes it possible to optimize the distribution of the field for the molecule to be hyperpolarized. This transfer "in the form of a flow", i.e. without bringing the solution 1 to rest, allows a rapid transfer and minimizes losses due to relaxation.

[0121] Thus, the present invention enables the analysis of nuclear spins with low magnetic gyroscopic ratios (e.g. 13 C) polarized for MRI applications.

[0122] use Figure 3 The device according to the present invention was tested to 13 C-Formate and 13 The nuclear spins of C-pyruvate are polarized. A strong increase in the polarization of these molecules was observed, with the ultimate polarization of these molecules increasing by several percent as measured by liquid magnetic resonance.

[0123] Now refer to Figure 1 and 5 7 describe a second embodiment of a hyperpolarisation device 200 according to the invention comprising a second embodiment of a reversal chamber 2 according to the invention, which will be described only with respect to their differences from the first embodiment of the chamber 2 and the device 100 previously described.

[0124] Device 200 is more accurate than device 100 .

[0125] In this embodiment, the at least one internal magnetizing device 11 , 12 comprises a plurality of internal solenoids 11 , 12 at least partially inside the magnetic shield 5 , which at least partially surround the reversing portion 33 and are electrically connected to each other via the shunt bridge 20 .

[0126] The internal solenoids 11, 12 are divided into two groups 110, 120 of internal solenoids: - a first set 110 of inlet internal solenoids 11 are all located on the inlet side of chamber 2, - A second set 120 of outlet internal solenoids 12 are all located on the outlet side of chamber 2 .

[0127] Each pair of adjacent internal solenoids 11 (of the group 110) is electrically connected via a shunt bridge 20 (and only via the bridge 20), preferably with no intermediate space between these internal solenoids 11, but without direct electrical contact between these adjacent solenoids 11 (i.e., the coil of one solenoid 11 does not continue to wrap around the coil of another adjacent solenoid 11).

[0128] Each pair of adjacent internal solenoids 12 (of the group 120) is electrically connected via a shunt bridge 20 (and only via the bridge 20), preferably with no intermediate spaces between the internal solenoids 12, but without direct electrical contact between the adjacent solenoids 12 (i.e., the coil of one solenoid 12 does not continue to wrap around the coil of another adjacent solenoid 12).

[0129] The first group 110 is electrically connected to the second group 120 and to the same power source 21 , but the rotation direction of the current of each solenoid 11 of the group 110 is opposite to the rotation direction of the current of each solenoid 12 of the group 120 .

[0130] The group 110 includes the same number of solenoids 11 as the group 120 includes the same number of solenoids 12 .

[0131] The chamber 2 also comprises at least one power source, preferably a common power source, which is arranged to pass currents i 1 The two groups 110, 120 of internal solenoids are powered (preferably with the same strength) so that the leakage magnetic fields of the two groups 110, 120 of internal solenoids are opposite to each other. 1 Constant in time.

[0132] The advantage of a common power supply is that it is simpler and enables the inversion field 6 to be more stable.

[0133] The two groups 110 and 120 are anti-parallel.

[0134] The coils of the solenoid 11 and the solenoid 12 are centered on the same axis S. The chamber does not include a separation space between the two groups 110, 120 of solenoids 11, 12, that is, the first group 110 is adjacent to the second group 120, and only a simple mechanical gap may remain.

[0135] In the present embodiment 200, this enables a faster transfer and thus minimizes the losses caused by relaxation during the transfer.

[0136] Each bridge 20 includes a pair of resistors 23 .

[0137] The shunt bridge 20 comprises a variable resistor 23 which is adjusted by an adjustment interface arranged for varying the resistance 23 of the shunt bridge 20 via the interface in order to adjust or optimize the reversal profile of the reversal magnetic field 6 .

[0138] As adjustable resistor 23 and adjustment interface, any technical type of variable resistor may be used, for example any type of potentiometer or rheostat controlled from outside the shield 5 by analog and / or digital means, a touch screen or the like.

[0139] The spatial distribution of the field can be refined by adjusting the following factors: - the current i in each solenoid 11 and / or 12 1 , and / or - The value of the different resistors 23 (same or different).

[0140] Even without adjusting resistor 23 , device 200 is more accurate than device 100 .

[0141] All resistors 23 of the combination of bridge 20 are mounted on a single printed circuit, for example integrated inside shield 5 .

[0142] The inlet external magnetizing device 41 surrounds or frames or extends along the portion of the group 110 located outside the shielding body.

[0143] The exit external magnetizer 42 surrounds or frames or extends along the portion of the group 120 located outside the shield.

[0144] Chamber 2 of the apparatus 200 thus corresponds to chamber 2 of the apparatus 100, wherein: - The solenoid 11 of the device 100 is replaced by the group 110 and its bridge 20 of the device 200 The solenoid 12 of the device 100 is replaced by the group 120 of the device 200 and its bridge 20 .

[0145] exist Figures 5 to 7 In a variation of the embodiment: - the portion 33 is V-shaped, the reversal of the field 6 occurring at the tip of the V, the tip of the V defining the interval between the two groups 110 and 120, and / or - There is a separation between groups 110 and 120, even though this is less favorable.

[0146] Just described Figures 1 to 7 The two embodiments can be summarized by replacing the term "solenoid" with "magnetizing device" (or "electromagnet", "permanent magnet", "assembly of multiple electromagnets", "assembly of multiple permanent magnets", or "assembly of electromagnet(s) and permanent magnet(s)"). In the case of permanent magnet(s), the power supply device described above for the solenoid is no longer needed.

[0147] Now refer to Figures 1 to 8 A third embodiment of a hyperpolarisation device 300 according to the invention is described comprising a third embodiment of a reversal chamber 2 according to the invention, which will be described only with respect to their differences from the previously described first embodiment of the chamber 2 and the apparatus 100.

[0148] In the present embodiment, the reverse portion 33 is not straight.

[0149] In the present embodiment, the first portion and the second portion of the reverse portion 33 form a right angle, but generally any angle may be formed.

[0150] The inlet inner magnetizing device 11 comprises or is part of an inlet inner solenoid 11 which surrounds the first portion of the portion 33 .

[0151] The device 11 generates a magnetic field in the first portion of the portion 33 which is parallel to Z and to the direction of extension of the first portion of the portion 33 .

[0152] The chamber 2 comprises means for powering the solenoid 11 by direct current.

[0153] The exit internal magnetization device 12 comprises or is a permanent magnet and / or a Helmholtz coil, or a group of permanent magnets 12 and / or a group of Helmholtz coils 12, which frames a part of the second part of the portion 33 and is arranged to emit a magnetic field perpendicular to the part of the portion 33 it frames.

[0154] The device 12 generates a magnetic field in the second portion of the portion 33 which is parallel to Z and perpendicular to the direction of extension of the second portion of the portion 33 .

[0155] Thus, when the flow of solution 1 flows through portion 33, the magnetic field 6 reverses in the Z direction.

[0156] Note that Figure 8Among the variants not shown, there are: - Not straight part 33 - an entrance internal magnetizing device 11 comprising or being a permanent magnet and / or a Helmholtz coil, or a set of permanent magnets and / or a set of Helmholtz coils 11, said permanent magnets and / or Helmholtz coils, or a set of permanent magnets and / or a set of Helmholtz coils 11 framing a portion of a first part of the portion 33 and being arranged to emit in said first part of the portion 33 a magnetic field perpendicular to said portion of the portion 33 which it frames, - an outlet internal magnetizing device 12 , which comprises or is an outlet internal solenoid 12 , which surrounds a part of the second part of the portion 33 and generates a magnetic field in the second part of the portion 33 parallel to Z and parallel to the extension direction of the second part of the portion 33 .

[0157] Now refer to Figures 1 to 9 A fourth embodiment of a hyperpolarisation device 400 according to the invention is described comprising a fourth embodiment of a reversal chamber 2 according to the invention, which will be described only with respect to their differences from the previously described third embodiment of the chamber 2 and the apparatus 300.

[0158] Reference Fig. 9 , so note that Figure 8 Among the variations, there are: - Straight section 33 - entrance internal magnetizing means 11 comprising or being a permanent magnet and / or a Helmholtz coil, or a set of permanent magnets and / or a set of Helmholtz coils 11, framing a portion of a first part of the portion 33 and arranged to emit in the portion 33 a magnetic field perpendicular to the portion of the portion 33 that it frames, - an outlet internal magnetizing device 12 comprising or being a permanent magnet and / or a Helmholtz coil, or a set of permanent magnets and / or a set of Helmholtz coils (or a plurality of coils) 12, said permanent magnet and / or Helmholtz coil, or a set of permanent magnets and / or a set of Helmholtz coils (or a plurality of coils) 12 framing a portion of the second portion of the portion 33 and being arranged to emit in the portion 33 a magnetic field perpendicular to said portion of the portion 33 which it frames, said magnetic field being directed opposite to the field of the device 11.

[0159] Also note that for Figures 8 to 10 : - The device according to the invention comprises an inlet intermediate magnetizing means 81 (at the Fig. 9 , Fig.10 In the case of Figure 8 In a variation, means 11 and 12 should be in reverse order), and / or - The device according to the invention comprises an outlet intermediate magnetizing means 82 (at the outlet of the chamber 2) between the outlet of the chamber 2 and said (or at least one) internal magnetizing means 12 Figure 8 , Fig. 9 , Fig.10 In the case of Each of the devices 81 and 82 surrounds or frames at least a portion of the portion 33 or extends along at least a portion of the portion 33.

[0160] Each of the devices 81 and 82 includes a solenoid.

[0161] The intermediate magnetizing device 81 is arranged to maintain an entrance intermediate magnetic field (constant in time) in the conduit 3 between the magnetic field of the device 41 in the conduit 3 and the magnetic field of the device 11 (one or more) in the portion 33, which entrance intermediate magnetic field is parallel to the extension direction of the conduit 3 through the entrance of the chamber 2.

[0162] The intermediate magnetizing device 82 is arranged to maintain an exit intermediate magnetic field (constant in time) in the conduit 3 between the magnetic field of the device 42 in the conduit 3 and the magnetic field of the device 12 (one or more) in the portion 33, the exit intermediate magnetic field being parallel to the extension direction of the conduit 3 through the outlet of the chamber 2.

[0163] The function of devices 81 and 82 is to ensure that the orientation of the field to which the spin is subjected is constant. Figure 8 , 9 There is a risk that the success of the polarization transfer method of the device according to the invention of 10 will be too dependent on the orientation of the shield 5 in space and relative to the ambient magnetic field.

[0164] If the change in the orientation of the field through 90° in space (and therefore in time) is slow enough (adiabatic), then this change is not a problem. As an example of an adiabatic condition, we can give [Formula 6]

[0165] where α is the angle of the field B(t) at time t and γ is the ratio of the weaker of the two spins. As a numerical expression, this gives: [Formula 7]

[0166] It should be noted that just referring to Figures 1 to 10Each of the described embodiments of the device according to the invention or of the chamber according to the invention does not comprise a device for emitting microwaves (ie electromagnetic radiation having a frequency greater than 1 GHz or between 1 GHz and 300 GHz) in the chamber and / or in the portion 2 .

[0167] Now refer to Figures 1 to 10 A fifth embodiment of a hyperpolarisation device 500 according to the invention is described comprising a fifth embodiment of a reversal chamber 2 according to the invention, which will be described only with respect to their differences from the previously described first embodiment of the chamber 2 and the apparatus 100.

[0168] Reference Fig.10 , so we notice that we can have: - Straight section 33 - the entrance internal magnetizing means 11 comprises or is a permanent magnet and / or a Helmholtz coil, or a set of permanent magnets and / or a set of Helmholtz coils 11, which frame a part of the first part of the portion 33 or extend along a part of the first part of the portion 33 and are arranged to emit a magnetic field parallel to the part of the conduit 33 that it frames, - an outlet internal magnetizing device 12, comprising or being a permanent magnet and / or a Helmholtz coil, or a set of permanent magnets and / or a set of Helmholtz coils 12, said permanent magnets and / or Helmholtz coils, or a set of permanent magnets and / or a set of Helmholtz coils 12 framing a portion of the second portion of the portion 33 or extending along a portion of the second portion of the portion 33, and being arranged to emit a magnetic field parallel to said portion of the conduit 33 which it frames.

[0169] Now refer to Figures 1 to 10 Different embodiments of the method according to the invention are described which are carried out in different embodiments of the hyperpolarization device 100 , 200 , 300 , 400 , 500 according to the invention.

[0170] In all the apparatuses 100, 200, 300, 400 and 500, the hyperpolarization method comprises supplying a solution 1 in a liquid state, the solution 1 comprising: ○ A first type of nuclear spin (e.g., a hydrogen nucleus) with a first gyroscopic ratio and hyperpolarized 1 H) and ○ A second type of nuclear spin with a second gyroscopic ratio that is not hyperpolarized (e.g., a carbon nucleus 13 C. Nitrogen nucleus 15 N or phosphorus nucleus 31 P); In one or more molecules of solution 1, two types of nuclear spins are coupled via scalar spin coupling, also referred to by those skilled in the art as "J coupling." This coupling is a persistent coupling (without chemical exchange).

[0171] The solution 1 is supplied to the inversion chamber 2 so that it flows in the form of a stream of the solution 1 in the conduit 3 , a portion of which is referred to as the inversion portion 33 , passing through the inversion chamber 2 .

[0172] The inversion chamber 2 comprises its inlet through which the flow of solution 1 enters, and its outlet through which the flow of solution 1 exits.

[0173] The reversal chamber 2 includes a magnetic shielding body 5 surrounding the reversal portion 33 , and the magnetic shielding body 5 isolates the reversal portion 33 from the ambient magnetic field around the magnetic shielding body 5 .

[0174] In the devices 100, 200, 300, 400 and 500, the method according to the invention also comprises generating a reversal magnetic field 6 in the portion 33 by means of at least one magnetizing device, referred to as at least one internal magnetizing device 11, 12, at least one magnetizing device being at least partially located inside the magnetic shield 5 and surrounding or framing at least a portion of the reversal portion 33 or extending along at least a portion of the reversal portion 33, the main component of which is preferably reversed only once in the Z direction and while passing through the interior of the reversal portion 33, in order to transfer the hyperpolarization from the first type of nuclear spins to the second type of nuclear spins inside the reversal portion 33 during the flow of the solution 1 from the inlet of the chamber 2 to the outlet of the chamber 2 in the reversal portion 33 at a non-zero speed (i.e. without bringing the solution 1 to rest in the reversal portion 33). This is a "crossing-avoided" transfer, the probability of which can be calculated using the Landau-Zener theory.

[0175] As seen above, the inverted portion 33 may or may not be straight.

[0176] The main component of the reversal field 6 in the Z direction may be perpendicular or parallel to the direction of the flow of the solution 1 in the portion 33 (or even at an oblique angle in some variations). The Z direction is constant, and the direction of the flow of the solution 1 in the portion 33 may change, for example, through a bend, curve or turn in the portion 33.

[0177] In case of device 100 or 500: - each internal magnetization device 11, 12 generates a magnetic field which is constant in time and opposite to the magnetic field of the other internal magnetization device, the sum of the magnetic fields of these two internal magnetization devices being reversed in the interior 71 of the reversal portion 33, preferably in the center, - The two internal magnetization devices 11, 12 are driven by currents i rotating in opposite directions. 1power is supplied, and their leakage magnetic fields are opposite.

[0178] In order to obtain the ideal distribution of the field 6, the preferred solution is to use internal magnetizing means 11 and 12 (or 110 and 120) that are symmetrical (with respect to a plane 71 perpendicular to the preferably straight portion 33) and that face the inside of the shield 5 and that surround or extend along the portion 33, just as for the devices 100, 200 and 500.

[0179] In the case of device 200: - Two sets (110, 120) of internal solenoids are rotated in opposite directions by current i 1 power supply, and their leakage magnetic fields are opposite, The method optionally comprises a variable resistor 23 of the shunt bridge 20 which is adjusted via a regulating interface in order to adjust or optimize the reversal profile of the reversal magnetic field 6 .

[0180] In the case of devices 100, 200, 300, 400 and 500: - Supplying solution 1 to inversion chamber 2 comprises: o preferably supplying solution 1 from a dynamic nuclear polarization DNP device (18) (preferably dDNP) connected to conduit 3, and / or o supplying the solution 1 from any other device 18 capable of producing and / or supplying a solution comprising two types of nuclear spins, - a corresponding inlet external magnetizing device 41 or an outlet external magnetizing device 42 maintains an inlet magnetic field at the inlet of the inversion chamber 2 or an outlet magnetic field at the outlet of the inversion chamber 2 in the conduit 3, respectively, - Two external magnetizing devices 41, 42 are driven by currents i rotating in opposite directions. z powered by.

[0181] - the method preferably comprises purifying the solution 1 downstream of the chamber 2 (ie between the chamber 2 and the device 19) by means of a purification device (for example one or several purification matrices), The method further comprises supplying the solution 1 to a nuclear magnetic resonance (NMR) spectrometer 19 or a magnetic resonance imaging (MRI) device 19 via the conduit 3 after the solution 1 has passed through the inversion chamber.

[0182] The method may, for example, include detecting prostate cancer by MRI. 13 Hyperpolarization of C metabolites, either for drug screening by nuclear magnetic resonance (NMR), for studying chemical or biological dynamics and metabolomics by NMR, for protein / ligand interactions, e.g. in the context of drug screening, etc. 13 C (or 1H nuclei are coupled to other nuclei with low magnetic gyrometry ratios) by hyperpolarization of metabolites.

[0183] For example, transfer was achieved under the following experimental conditions: - Hyperpolarization device used: Device 100 - Conduit 3 upstream and downstream of chamber 2: Teflon capillary with an outer diameter of 3.2 mm and an inner diameter of 1.6 mm (circular cross section), around which a 0.5 mm copper wire (solenoid 51 or 52) is wound and attached. A current of 2 A supplied by a laboratory power supply flows through the copper wire (solenoid 51 or 52), generating a magnetic field of about 4 mT in the capillary upstream and downstream of chamber 2.

[0184] - Composition of solution 1 at the inlet of chamber 2: 100 pL of DNP sample (composition: 0.43 M 13 C-Sodium formate, 0.44M [3- 13 C]-Sodium pyruvate, 0.44 M [2- 13 C]-Sodium pyruvate, 0.45M[l- 13 C]-Sodium pyruvate and 50 mM TEMPOL were dissolved in a 1:3:6 H 2 O:D 2 O:Ds-glycerol v / v / v, where 1 The H spins have been hyperpolarized in a dDNP polarizer 18 at 1.2 K and 7.05 T. 1 The H polarization is about 50%. 13 C polarization (in 1 H spin polarization was obtained during the process) and then reduced to 0% by a series of RF pulses before dissolution (to ensure liquid state after dissolution and transfer) 13 C polarization comes entirely from 1 H transfer). The sample was dissolved in 5 mL of D 2 O and heated to 9 bar and 175 ° C, and then transferred within 1.8 s with the help of a fast transfer and injection system (see, e.g., Ceillier et al., "An automated system for fast transfer and injection of hyperpolarized solutions," Journal of Magnetic Resonance Open Volumes 8-9, December 2021, 100017) to an NMR tube placed in a benchtop NMR spectrometer operating at 1.88 Tesla (in Figure 1 The speed of the solution during the transfer process is ≈5 m.s -1The conduit that enables the transfer of the solution from the polarizer to the benchtop spectrometer passes through the inversion chamber and is placed as close as possible to the outlet of the dDNP polarizer (to minimize 1 H polarization loss).

[0185] - All solenoids 11, 12 are made of copper wire with a diameter of 0.5 mm, a coil diameter of 12 mm, 112 turns, a solenoid length of 7.3 cm, a spacing of 10.4 cm, and a current i of 0.05 amperes. 1 powered by - All solenoids 41, 42 are made of copper wire, the wire diameter is 0.5 mm, the coil diameter is 1.8 cm, 107 turns, the solenoid length is 70 cm and is powered by a current i of 1 ampere 2 powered by - All solenoids 51, 52 are made of copper wire, the wire diameter is 0.5mm, the coil diameter is 3.2cm, >2000 turns, the solenoid length is >100cm and powered by a current of 2 amps - Support 8 is made of 3D printing resin (transparent resin) which includes slots for placing the copper wires in the most precise way possible, - Support 9 is made of 3D printing resin (transparent resin) which includes slots for placing the copper wires in the most precise way possible, - The conduits 3, 33 are made of a 3D printed support with a square hole (side length 4 mm) passing through it, through which a capillary 3, 33 (or conduit) with an outer diameter (circular cross section) of 3.2 mm and an inner diameter of 1.6 mm (circular cross section) passes, - Shield 5 is made of μ-type metal, consisting of 4 concentric layers approximately 1 mm thick and 32.6 cm long along axis S (MS-1L, Twinleaf) - The distance D, 13, is 7.3 cm.

[0186] The obtained field Figure 4 shown.

[0187] The following table lists the four molecules present in the solution at the end of the experiment. 13 C polarization. The experiment was repeated twice ("Inversion #1", "Inversion #2"). In addition, two control experiments were performed: - During the "No Inversion #1" experiment, the solution passed through the inversion chamber, but the coil was connected so that the magnetic field was not reversed (the magnetic field was reduced to the order of μT and then increased again) - During the “No Inversion #2” experiment, the solution did not pass through the inversion chamber.

[0188] .

[0189] For a given magnetic field distribution in the reversal chamber and a given velocity of the solution, numerical simulations of the spin dynamics predict that for 13 C-formate molecules and [3- 13 C]-pyruvate molecule, 1 H 13 The polarization transfer of C should be complete. On the other hand, for [2- 13 C]-pyruvate and [1- 13 For [C]-pyruvate molecules, the transfer should be almost zero due to their too weak J coupling (for the given field distribution). Our experimental results confirm these predictions.

[0190] Two control experiments show that there is a non-zero transfer even without a field reversal. This is probably due to a transfer in the liquid due to the nuclear Overhauser effect (NOE). This transfer does not occur in [2- 13 C]-pyruvate and [1- 13 C]-pyruvate molecule, because 1 H and 13 The distance between the nuclear spins of C is too large.

[0191] The implementation details of the device 200 differ from those of the device 100 in that: - All solenoids 11, 12 are made of copper wire, the wire diameter is 0.5mm, the coil diameter is 4cm, 62 turns, and the solenoid length is 3cm - The current source 21 at the combined input of the shunt bridge 20 is 13 C formate provides 4000μA or 1- 13 C-pyruvate provides a current I of 30 μA, - Group 110 includes 12 solenoids 11 and 12 shunts 20 (number is Figure 6 The number shown in the figure is greater), - Group 120 includes 12 solenoids 12 and 12 shunts 20 (number is Figure 6 The number shown in the figure is greater), - Each solenoid 11 or 12 is associated with its shunt bridge 20 having a resistance R 1 and R 2 , by the current i 1 =I(R 2 / (R 1 +R 2 ))Flowing - Each R 1 / R 2 The two pairs are different, so that each part of the solenoid 11 or 12 can provide an optimal magnetic field 6.2 , each resistor has a value of 1000 ohms by default, and for R 1 , each resistor has a value that increases toward the center of portion 33 (for group 110, the resistance of bridge 20 increases from left to right, and for group 120, the resistance of bridge 20 increases from right to left). Typically, for group 110, for 12 bridges 20 from left to right and for group 120, for 12 bridges 20 from right to left, each resistor R 1 The values ​​are 4 ohms, 20 ohms, 44 ohms, 70 ohms, 90 ohms, 125 ohms, 166 ohms, 220 ohms, 302 ohms, 454 ohms, 768 ohms, and 2000 ohms respectively.

[0192] The method according to the invention is applicable to molecules having a J coupling (such as [2- 13 C]-pyruvate or [1- 13 C]-pyruvate) solution 1.

[0193] The method according to the invention is applicable to molecules having strong J coupling ([3- 13 C]-pyruvate, J = 125 Hz) 1, or other molecules of greater interest for in vivo applications, such as [2- 13 C]-pyruvate or [1- 13 C]-pyruvate, with couplings of approximately 1.3 and 6.2 Hz, respectively, being more efficient when the shield is longer (about 1 m in length).

[0194] Of course, the invention is not limited to the examples that have just been described and various adjustments may be made to these examples without departing from the scope of the invention.

[0195] The inverted portion 33 may be of any shape, straight, curved, or a combination of curved (one or more) and / or straight (one or more) shapes.

[0196] Of course, the different features, shapes, variations and embodiments of the present invention can be associated with each other in various combinations, as long as they are not mutually incompatible or mutually exclusive. In particular, all variations and embodiments described above can be combined with each other.

Claims

1. A hyperpolarization method, comprising supplying a liquid solution (1), wherein the liquid solution comprises: ○ a first type of nuclear spin having a first gyroscopic ratio and being hyperpolarized, and ○ a second type of nuclear spin having a second gyroscopic ratio; In one or more molecules of the solution (1), two types of nuclear spins are coupled via scalar spin coupling, The solution (1) is supplied to the inversion chamber (2) so that the solution (1) flows in the form of a stream of solution in a conduit (3), a portion of which, called the inversion portion (33), passes through the inversion chamber (2); The inversion chamber (2) comprises an inlet through which the flow of the solution enters, and an outlet through which the flow of the solution leaves; The reversal chamber (2) comprises a magnetic shielding body (5) surrounding the reversal portion (33), so that the reversal portion (33) is isolated from the environmental magnetic field around the magnetic shielding body (5); The method further comprises: - generating a reversal magnetic field (6) by at least one magnetizing device, referred to as at least one internal magnetizing device (11, 12), located at least partially inside the magnetic shield (5), the main component of which is in the Z direction and is reversed when passing through the interior of the reversal portion (33), so as to transfer hyperpolarization from the first type of nuclear spins to the second type of nuclear spins inside the reversal portion (33) during the flow of the solution at a non-zero speed in the reversal portion (33) from the inlet of the chamber to the outlet of the chamber.

2. The method according to claim 1, characterized in that The at least one internal magnetizing device (11, 12) comprises a pair of internal magnetizing devices (11, 12) at least partially located inside the magnetic shielding body (5), and the pair of internal magnetizing devices at least partially surround or frame the reversal portion (33) or extend along the reversal portion (33). Each internal magnetization device (11, 12) generates a magnetic field that is constant in time and opposite to the magnetic field of the other internal magnetization device, and the sum of the magnetic fields of the two internal magnetization devices reverses inside (71) the reversal part (33), preferably in the center of the reversal part (33).

3. The method according to claim 1, characterized in that The at least one internal magnetizing device (11, 12) comprises a plurality of internal solenoids (11, 12) at least partially located inside the magnetic shield (5), the plurality of internal solenoids at least partially surrounding the reversing portion (33) and connected via a shunt bridge (20), the plurality of internal solenoids (11, 12) being divided into two groups (110, 120) of internal solenoids, the two groups of internal solenoids being powered by currents with opposite rotation directions and the leakage magnetic fields of the two groups of internal solenoids being opposite.

4. The method according to claim 3, characterized in that There is no separation space between the two sets (110, 120) of internal solenoids (11, 12).

5. The method according to any one of claims 3 to 4, characterized in that The shunt bridge (20) comprises a variable resistor (23) adjustable via an adjustment interface, and the method comprises changing the resistance (23) of the shunt bridge (20) via the interface to adjust or optimize the reversal distribution of the reversal magnetic field (6).

6. The method according to any one of the preceding claims, characterized in that It also includes a magnetizing device, which is at least partially located outside the magnetic shielding body (5) and is called an entrance external magnetizing device (41), and the entrance external magnetizing device extends at least to the entrance of the reversal chamber (2), and a magnetizing device, which is at least partially located outside the magnetic shielding body (5) and is called an exit external magnetizing device (42), and the exit external magnetizing device extends at least to the exit of the reversal chamber (2), each external magnetizing device maintaining an entrance magnetic field at the entrance of the reversal chamber (2) and an exit magnetic field at the exit of the reversal chamber (2) in the conduit (3).

7. The method according to claim 6, characterized in that Each outer magnetization device (41, 42) at least partially surrounds or frames the at least one inner magnetization device (11, 12) or extends along the at least one inner magnetization device (11, 12).

8. The method according to claim 6 or 7, characterized in that: Each external magnetizing device comprises or is an external solenoid, each external solenoid (41, 42) surrounds the conduit (3) and is carried around the conduit (3) by an external support (8), the external support: - on the side of the conduit (3), without contact with the conduit, and - On the side of each external solenoid (41, 42), a protrusion arranged to receive and position the turns of each external solenoid (41, 42).

9. The method according to any one of the preceding claims, characterized in that The at least one internal magnetizing device is at least one internal solenoid, each internal solenoid (11, 12) at least partially surrounding the reversing portion (33), being at least partially carried by the reversing portion (33) via an internal support (9), the internal support: - on the conduit (3) side, in contact with said conduit (3), and - On the side of each internal solenoid (11, 12), a protrusion arranged to receive and position the turns of each internal solenoid (11, 12) along said conduit (3).

10. The method according to any one of the preceding claims, characterized in that Supplying 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).

11. The method according to any one of the preceding claims, characterized in that The inverted portion (33) and / or the conduit is a capillary tube, the largest dimension of which perpendicular to the flow of the solution (1) is less than 5 mm.

12. The method according to any one of the preceding claims, characterized in that In the reversal portion (33), the absolute value of the reversal magnetic field (6) along the Z direction is at least 0 mT to 0.1 mT.

13. A hyperpolarization device, comprising a reversal chamber, the reversal chamber (2) comprising: - an inlet arranged for a flow of a liquid solution 1 comprising: ○ a first type of nuclear spin having a first gyroscopic ratio and being hyperpolarized, and ○ A second type of nuclear spin having a second magnetic gyroscopic ratio, in one or more molecules of the solution (1), the two types of nuclear spins are coupled via scalar spin coupling, The liquid solution enters the chamber (2) through the inlet; - an outlet arranged for the solution (1) to flow out of the chamber (2) through the outlet The inlet and the outlet are arranged for causing the solution (1) to flow in the form of a stream of solution in a conduit (3), a portion of the conduit, referred to as the inversion portion (33), passing through the inversion chamber (2); The chamber (2) further comprises: - a magnetic shielding body (5) surrounding the reversal portion (33), so as to isolate the reversal portion (33) from the ambient magnetic field around the magnetic shielding body (5); - at least one magnetizing device, referred to as at least one internal magnetizing device (11, 12), located at least partially inside the magnetic shield (5), and arranged to generate a reversal magnetic field (6), the main component of which is in the Z direction and which is reversed when passing through the interior of the reversal portion (33), in order to transfer hyperpolarization from the first type of nuclear spins to the second type of nuclear spins inside the reversal portion (33) during the flow of the solution at a non-zero speed in the reversal portion (33) from the inlet of the chamber to the outlet of the chamber; The hyperpolarisation device further comprises means (18) arranged for supplying the solution (1) to the inlet of the inversion chamber (2) through the conduit (3).

14. The device according to claim 13, characterized in that The device (18) is arranged to supply a solution (1) comprising a dynamic nuclear polarization DNP device (18) connected to a conduit (3).

Images