EP2649464A1

EP2649464A1 - Method for characterizing a solid sample by nmr spectrometry, and apparatus for implementing said method

Info

Publication number: EP2649464A1
Application number: EP11802677.2A
Authority: EP
Inventors: Denis Grenier; Hervé Saint-Jalmes
Original assignee: Centre National de la Recherche Scientifique CNRS; Universite de Rennes 1
Current assignee: Centre National de la Recherche Scientifique CNRS; Universite de Rennes 1
Priority date: 2010-12-06
Filing date: 2011-12-06
Publication date: 2013-10-16
Also published as: US9733325B2; WO2012076545A1; US20130328562A1; FR2968408A1; FR2968408B1

Abstract

The invention relates to a method for characterizing a sample (2) by means of a nuclear magnetic resonance spectrometer in which an effective field (Beff) is generated, wherein said field has an effective vector (I) and results from a static magnetic field (B0) and a radiofrequency magnetic field (B1), characterized in that the effective vector (I) rotates relative to a terrestrial reference frame. The invention also relates to an apparatus (1) for implementing the method.

Description

SAMPLE CHARACTERIZATION METHOD BY NMR SPECTROMETRY WITH ACQUISITION DURING THE GENERATION OF A MAGNETIC FIELD

RADIO FREQUENCY

Technical area

5

The invention relates to the field of methods for characterizing an object (material, biological sample or entire biological system in vivo or in vitro) using a Nuclear Magnetic Resonance spectrometer. The invention also relates to the field of nuclear magnetic resonance spectrometry apparatus for acquiring the magnetization of an object as defined above.

State of the art

In order to be able to study an object in Nuclear Magnetic Resonance (NMR) spectrometry, it may be necessary to suppress or limit the influence of certain interactions occurring between the atoms composing the object to be studied, for example the dipole interaction and / or quadrupole between the nuclei of the atoms.

The removal of these interactions between nuclei is usually done by averaging.

For a liquid, such as water contained in the vast majority of biological tissues, the molecules move and undergo rotations randomly in all directions (so-called

25 Brownian motion). This Brownian motion is fast enough that, on average, the dipole interactions undergone by the atoms are considered as null or relatively weak.

This is why NMR spectrometry is relatively simple to set up for the study of liquid objects.

On the other hand, NMR spectrometry for the study of a solid object is only possible under the condition of placing this object in circumstances which make it possible to recreate artificially the averaging effect of interactions so that from the point of view of NMR, the object can be likened to a liquid.

Indeed, in a solid, the Brownian motion is not fast enough for the dipole and / or quadrupole interactions perceived by the nuclei to be zero on average.

In particular, the non-zero dipolar interaction will allow the nuclei of the constituent atoms of the solid to interact with each other and to distribute their spin in all directions. The vector sum (magnetization) of the spins is then zero.

The cancellation of the magnetization occurs all the more quickly as the dipolar interaction is strong. Often, the dipolar interaction is strong enough that the magnetization vanishes too quickly to be used (measured).

The dipolar and quadrupole interactions between two atomic nuclei are proportional to 1 -3.cos ² (0), where Θ is an angle formed by an applied static magnetic field and a vector connecting the centers of the two nuclei. Thus, to cancel the effects of these interactions, it suffices that the average of 1 -3.cos ² (0) can be considered as zero. If the angle Θ is, on average, equal to 0 _m = arccos (3 ^"1/2 ) or n-arccos (3 ^{" 1/2} ) (ie approximately 54.74 °) then the average of 1 -3. cos ² (0) is zero. This angle 0 _m is called magic angle (Magic Angle). In order to obtain the 0 _m average for the angle θ, the solid material is rapidly rotated around an axis forming an angle θ _m with the vector of the static magnetic field necessary for NMR spectrometry. The faster the rotation, the more efficient the averaging effect of the interactions, and the closer the behavior of a liquid sample is to the measurement resolution. The measurement is carried out in a terrestrial reference which is that of the laboratory.

This technique of spectroscopy adapted to the solids is called technique of "magic angle rotation" and more commonly in English "Magic Angle Spinning" (MAS). A major disadvantage of this process is the need to rotate the object. In the context of the suppression of the dipole interaction, in order to obtain a sufficient resolution, the rotation is carried out at a frequency between 1 Hz and 40 kHz. It is therefore not possible to use this method in vivo, to study, for example, human subjects.

In addition, these speeds of rotation even at a frequency of 40 kHz are sometimes still too slow for the quadrupole interaction possibly present in the object can be considered averaged to zero.

A second method, known from document US 2008/0 116 889, makes it possible to dispense with the need for the rotation of the solid material to be studied in order to "suppress" the dipolar interaction.

In this second method, it is the main magnetic field (normally static) in which is placed the material (equivalent to the static magnetic field of the preceding method) which undergoes a rotation. The rotation of the main magnetic field is obtained by rotating magnets. The rotation of the main magnetic field then creates the necessary condition for the average of 1 -3.cos ² (0) to be zero.

The major disadvantage of this process is the need to rotate magnets of high mass. Indeed, in a conventional NMR spectrometer, the magnet, whether superconductive or resistive, for generating the static magnetic field, is characterized by a mass of several hundred kilograms or even several tons. It is understood that, even at frequencies of only a few hertz, rotating parts of several tons implies a very important and expensive technological change of current NMR spectrometers.

Another technique called Magic Echo Pulse Sandwich (MEPS) technique can be used on objects solid without requiring the use of moving parts. The latter technique is based on the fact that, in addition to the static magnetic field B ₀ , a radio frequency field B ₁ is applied _; the field perceived by the atoms is an effective field B _eff whose geometric characteristics are given by the equation: where VT is the frequency of the radiofrequency field Βτ applied, B ₀ = B ₀ z, and y is the gyromagnetic ratio of the studied nucleus expressed in Ηζ · Τ ¹ (γ = 2.68 · 10 ⁸ rad-Hz / T and y = - ^ -).

2 · π

When the frequency v _1; on which the _BI field is applied, is equal to y ^■ B _Q (resonance frequency of atoms considered), the effective field B _eff perceived by the atoms is equal to the radio frequency field B ^ It can be shown that under these conditions , the dipolar interaction perceived by the atoms is -1 / 2 times the dipolar interaction they perceive in the absence of the radio frequency field Bi. The principle of MEPS allows to cancel the dipole interaction at a given moment. For this purpose, during part of the measurement, the atoms are allowed to evolve freely for a duration τ, during which time they are subjected to a dipolar interaction of value H _d . Then subjected to these atoms for a time 2τ, a radiofrequency field B applied to the frequency _Ï y ^■ _Q B so that they are subjected during that duration 2τ to a dipolar interaction value -1/2 _H. Under these conditions, at time 3τ, the magnetization is totally freed from the dipolar interaction (that is to say that on all the atoms, the influence of the dipolar interaction is zero, as if the magnetization had not undergone any dipolar interaction). It is at this moment 3τ that the signal is acquired.

This technique has the advantage of "artificially" rotating the effective field seen by the atoms thanks to the magnetic field effective B _e ff created. It also has the advantage of recreating the conditions for zeroing the dipolar and quadrupole interaction.

By cons, this condition is realized only at time 3τ; a single point of the signal then verifies the zero dipolar interaction condition. However, if the dipole and quadrupole interactions are important, measurements made a few microseconds around the time 3τ may already be too tainted by the dipolar and / or quadrupole interactions to be exploitable.

Thus, with this technique, to acquire a totally freed signal from the dipolar interaction, it is necessary to perform a point-by-point acquisition of this signal for different values of the duration τ and verifying that, for each point acquired at the instant 3τ , the condition of evolution, in which the atoms are in free evolution (ie subjected to H _d ) during a duration τ and in evolution imposed by the static field B ₀ (ie subjected to -1 / 2 H _d ) during a duration 2τ, be filled.

The acquisition of a signal for a solid sample is therefore point by point with this technique. It is therefore much slower (from one hundred to one thousand orders) than that using MAS. Presentation

An object of the invention is to allow NMR spectrometry of solid objects, or with solid parts, quickly and non-destructively.

For this, the invention proposes a method for characterizing a sample by means of a Nuclear Magnetic Resonance spectrometer comprising an enclosure in which the sample is placed, a static magnetic field generator, a radio frequency magnetic field generator, and at least one sensor, the method comprising the following steps: generating in the enclosure, by the static magnetic field generator, a static magnetic field according to a static vector;

generating in the chamber and for a predetermined duration, by the radiofrequency magnetic field generator, a radiofrequency magnetic field according to a radiofrequency vector;

characterized in that the method further comprises the step of acquiring, by at least one sensor, a magnetization of the sample during the determined duration; and

in that an effective vector, to which the magnetization of the sample is subjected during the determined duration, is rotatable with respect to a terrestrial reference for the determined duration, the effective vector resulting from the static and radiofrequency magnetic fields, and the sample being fixed in relation to the terrestrial reference.

An advantage of this method is that it is not necessary to rotate the sample or to rotate the static magnetic field (equivalent to the main magnetic field). Thus, it is possible to make in vivo studies of objects (for example animals, see humans) without requiring modification of the enclosure housing one or more magnets that generate the static magnetic field.

Another advantage of this method is that the sample is placed under conditions for which the dipolar interaction is zero for each atom (and not only its influence on the entire sample) and this throughout the duration of the acquisition.

Other optional and non-limiting features are:

the radiofrequency magnetic field is modulated so that the effective field applied to the sample has its effective vector given by B _eff = and defining an angle (0 _m )

approximately 54.74 ° with the static vector, being a frequency close to the Larmor frequency v ₀ due to the static magnetic field, this frequency V 1 being due to the radiofrequency magnetic field;

the effective vector is rotating in a plane orthogonal to the static vector;

the effective vector is rotated in a plane orthogonal to the static vector at the Larmor frequency; and

the magnetization of the sample is acquired by at least two sensors; a first sensor positioned to acquire collinear magnetic signals to the static vector, having a frequency close to the effective frequency, and at least one second sensor positioned to acquire magnetic signals collinear with the plane orthogonal to the static vector, having a frequency close to the frequency of Larmor.

The invention also proposes a Nuclear Magnetic Resonance spectrometry apparatus for acquiring a magnetization of a sample comprising:

a fixed sample support relative to a terrestrial reference during the operation of the apparatus;

an enclosure in which the sample holder is placed; a static magnetic field generator for generating a magnetic field in the enclosure along a static vector; a radiofrequency magnetic field generator for generating a radiofrequency magnetic field in the enclosure according to a radiofrequency vector for a predetermined period;

characterized in that the apparatus further comprises at least one sensor for measuring the magnetization of the sample for the determined duration.

Other optional and non-limiting features are:

the radiofrequency magnetic field generator comprises at least two magnets or coils each generating a magnetic field radiofrequency so that the effective magnetic field, resulting from the two radiofrequency magnetic fields of the magnets or coils and the static magnetic field, has an effective vector rotating with respect to the terrestrial reference;

a first sensor is placed along the static vector and adjusted to acquire signals at frequencies close to an effective frequency resulting from an effective magnetic field applied to the sample such that:

V! being a frequency close to the Larmor frequency due to the static magnetic field, the frequency being due to the radiofrequency magnetic field, and B ₀ = B ₀ z; and

^V ef _f = y - B _eff ,

y being the gyromagnetic ratio characteristic of a nucleus of a studied atom;

two second sensors are placed in a plane orthogonal to the static vector and adapted to acquire a signal at a Larmor frequency due to the static magnetic field with:

v ₀ = y · B ₀ ,

being the gyromagnetic ratio characteristic of a nucleus of a studied atom;

the static magnetic field generator, the radiofrequency magnetic field generator and the sensor or sensors are fixed relative to the terrestrial reference during operation of the apparatus.

Presentation of drawings

Other characteristics, objects and advantages will appear on reading the detailed description which follows, with reference to the drawings given for illustrative and non-limiting purposes, among which: FIGS. 1 a to 1c are detailed representations of the effects of the magnetic fields normally used in NMR spectrometry on the magnetic moments of atomic nucleus spin studied;

Figure 2 is a schematic representation of a phenol molecule taken as an example in the "Principle of NMR spectrometry" part of the description;

Figure 3 is a schematic representation of an apparatus according to one embodiment of the invention;

Figure 4 is a schematic representation of a particular embodiment of the apparatus of Figure 3;

Figure 5 schematically shows an example of implementation of the method of the invention;

FIG. 6 is a timing diagram showing the magnetic fields generated (at the top the radiofrequency magnetic field and at the bottom the static magnetic field) as well as the acquisition step during the implementation of the method of FIG. 5;

Figure 7 illustrates the decoupling of the "butterfly" type surface antenna and the linear volumetric coil;

FIG. 8 illustrates an acquisition step in the form of a chronogram accompanied by the form of the acquired signals; and

Figure 9 shows the various references and their relationship during the implementation of the present invention.

detailed description

Principle of NMR spectrometry

Hereinafter is described the conventional method of signal acquisition in NMR spectrometry.

In general, Nuclear Magnetic Resonance spectrometry (NMR spectrometry) consists of acquiring a signal proportional to the sum of the magnetic spin moments of the atoms of an element. contained in an object placed in a magnetic field, for example ¹ H hydrogen atoms (this spectrometry is then called proton NMR), deuterium ( ² H), carbon 13 ( ¹³ C), etc. A magnetic spin moment is conventionally represented as a vector having a direction, a meaning and a norm. Each atom considered has a magnetic moment of spin. The vector sum of the magnetic spin moments of a material is called its magnetization.

In the absence of an applied magnetic field, the magnetic moments of spin of the studied atoms are randomly oriented in space. The magnetization is then zero on average.

The magnetic field in which the material is placed consists of a static magnetic field with respect to a terrestrial reference frame which is that of the laboratory, and a radiofrequency magnetic field. The static magnetic field is applied to the sample continuously throughout the experiment. The radiofrequency magnetic field is pulsed (i.e., briefly for a specified duration). The magnetization of the object is measured in the absence of radiofrequency field.

FIGS. 1a to 1c illustrate the known technique of NMR which consists of generating a static magnetic field B ₀ according to a static vector B _Q in a continuous manner in an enclosure 11 in which is placed an object 2 of the studied material, to generate a radiofrequency magnetic field Βτ in the form of a radiofrequency pulse following a radio frequency vector β ₁ for a determined duration T in the enclosure A2, and acquiring the magnetization M of the sample A1 after a predetermined period of change. The amplitude of the static magnetic field B ₀ is of the order of Tesla while that of the radio frequency magnetic field is at most of the order of milliTesla.

FIG. 1a shows the influence of the static magnetic field B ₀ on the magnetic spin moments of the atoms (represented by vectors S originating from a common point in space). Under the action of the static magnetic field B ₀ , the angle that each of the magnetic spin moments S of the atoms with the static vector B _{0 makes} is fixed and these magnetic spin S moments make a precessional movement around the static vector B ₀ . The link between the intensity of the static field B ₀ and the rotation frequency v ₀ of the magnetizations is given by the relation:

v ₀ = y · B ₀ ^;

called the gyromagnetic ratio of the nucleus considered expressed in Hz-T ¹ .

It can be shown that under these conditions the vector sum of all the magnetic moments of spin S is then no longer zero on average. This sum of magnetic moments of spin S gives the magnetization M of the material which is on average non-zero and according to the direction and the direction of the static vector B _Q.

FIG. 1b shows the influence of the radiofrequency magnetic field B _i (represented by the radiofrequency vector β ₁ , usually chosen orthogonal to the static vector B ₀ ).

Under the action of the radio frequency magnetic field B _1; the magnetization M of the material rotates around the radiofrequency vector B whose angle is proportional to the intensity and the determined duration T of the generation of the radio frequency magnetic field Bi. Usually, the duration T is chosen so that the angle of rotation is 90 ° (TT / 2) OR 180 ° (TT). Illustratively, has been shown in Figure 1b a rotation of 90 °.

The magnetization M actually effects a precession around the static vector B ₀ during the rotation of 90 ° or 180 °. FIG. 1c shows the evolution of the magnetization M of the material after the determined duration T, while the static magnetic field B ₀ continues to be generated and while the radiofrequency magnetic field is no longer generated.

As soon as the radiofrequency magnetic field B _i is no longer applied in the enclosure 11, the magnetization M will return to the equilibrium state by loss of energy. This return to the state of equilibrium is done according to a precession movement (see arrow F in FIG. 1c) at a frequency specific to each of the magnetic moments of spin S composing the object. The frequency of the magnetic signal generated by the return to the equilibrium state of an atom is not the same for the same element if it can be in different electronic environments. For example, the phenol comprises six hydrogen atoms H _a , H _b , H _c , H _d , but the magnetic S spin moments of each of the atoms will not all return to the equilibrium state at the same frequency . There are four groups of hydrogen atoms (see Figure 2): the hydrogen atom H _has connected to the oxygen atom 0, the hydrogen atoms H in the so-called "ortho" position, the atoms of hydrogen H _c in the so-called "meta" position and the hydrogen atom H _d in the so-called "para" position. Each group sees its magnetic spin S moment return to steady state at a different frequency than the other groups because their electronic environments are different. Nevertheless, these differences are minimal. They can still be distinctly detected. The total acquired signal is then a sum of the magnetic signals at various frequencies. A Fourier transform makes it possible to highlight these different frequencies, thus forming an NMR spectrum of the sample.

Hereinafter, for illustrative purposes only, proton NMR spectrometry (i.e., ¹ H hydrogen) will be taken as an example. This does not limit the invention to the proton NMR spectrometry alone, but the skilled person will readily adapt the following description to the NMR spectrometry of other atoms.

For magnetic fields, B represents the vector of the magnetic field and B represents the amplitude of the associated vector and also refers to the magnetic field.

Apparatus

With reference to FIGS. 3 and 4, an NMR spectrometry apparatus 1 for acquiring a magnetization of a sample is hereinafter described.

The NMR spectrometry apparatus 1 comprises a sample support 12 for receiving the sample 2. The support 12 is intended to remain fixed with respect to a terrestrial reference system during the operation of the apparatus 1.

The apparatus 1 also comprises an enclosure 11 in which the sample support 12 is placed. This enclosure 11 forms a volume in which magnetic fields will be generated.

The apparatus 1 further comprises a static magnetic field generator 13 for the generation of a static magnetic field B ₀ in the static vector enclosure B ₀ . The static magnetic field generator 13 is capable of generating a static magnetic field B ₀ of magnitude of the Tesla order, typically between 0.1 T and 16 T. This static magnetic field B ₀ makes it possible to make the vector sum of the magnetic moments of spin S of the non-zero hydrogen atoms in the direction of the static vector B ₀ without, however, making the magnetic spin moments S individually collinear with the static vector B _Q. The sum of the magnetic moments of spin S is the macroscopic magnetization M, which is collinear with the static vector B _Q and of the same direction. The magnetic moments of spin S form with this static vector B ₀ fixed angles and make a precession movement around the static vector B ₀ at the rotation frequency v ₀ .

The apparatus also includes a 14 RF magnetic field generator for generating an RF magnetic field _Bi in the enclosure 11 vector radiofrequency June _1. The static magnetic field generator 13 is capable of generating a radiofrequency magnetic field of amplitude between a few microteslas (μΤ) and a few milliteslas (mT), typically between 1 μΤ and 1 mT, which corresponds to frequencies between approximately 40 Hz and 40 kHz for the proton. The radiofrequency magnetic field Βτ is generated, for a determined duration T, in the form of a pulse applied to the radiofrequency frequency v ^. The radio frequency field B _i is modulated so that the resultant of the static magnetic fields B ₀ and radiofrequency B _As seen by the rotating atoms (see Fig. 9, where the lab mark is labeled (x, y, z), the rotating mark (x ', y', z ') at the pulsation about the z axis, and the effective reference (Xeff, Veff, z _e ff) in rotation at the pulse oo _e ff around the axis of the effective field z _eff , z _eff being offset from the magic angle with respect to the z axis of the reference mark turning). This resultant is called effective field B _e ff of effective vector B _eff and defined by:

with y the gyromagnetic ratio of the studied nucleus and the frequency vector v., collinear with the static vector B _Q.

The radiofrequency magnetic field Βτ thus makes it possible to turn the magnetization M around the effective vector B _eff .

The apparatus 1 comprises at least one sensor 15, 16 for acquiring the magnetization M of the sample during the generation of the field magnetic radio frequency Bi. This acquisition is made during the determined period T.

The apparatus 1 further comprises an actuator 17 for controlling the generation of the radiofrequency field Βτ sinusoidally.

When the amplitude of the radiofrequency field Βτ as well as its frequency of application verify the relation:

0 _M being the magic angle, the dipole and quadrupole interactions perceived by the object are zero on average and the acquisition of the signal during the application of the radiofrequency field Β of amplitude and frequency defined above allows for to overcome the need to rotate the sample or the generator 13 of static magnetic field. Thus, it is possible to study samples regardless of their state (especially solid, but also liquid, gaseous, or even a mixture thereof), or even to study the tissues of an animal or a human being in vivo.

The rotation frequency of the magnetization M (due to the effective rotating field B _e ff) can be raised to a high value (greater than the hundred kilohertz and possibly reach the megahertz) compared to the prior art of MAS which is confined a few tens of kilohertz.

In one embodiment, the radiofrequency magnetic field generator 14 is composed of a single magnet or coil. The actuator 17 then controls the radiofrequency magnetic field generator 14 for the generation of a sinusoidally modulated radiofrequency field afin to rotate the effective field B _e ff. In another embodiment, the radiofrequency magnetic field generator 14 may comprise at least two magnets or coils 141, 142 (see FIG. 4) each generating a partial radiofrequency magnetic field. This makes it possible to obtain a BT radio frequency field whose amplitude is more intense. The actuator 17 then controls the generation of the partial radiofrequency magnetic fields by the two coils 141, 142, so that the effective field B _e ff resulting from the two partial radiofrequency magnetic fields of the coils 141,

142 and the static magnetic field B ₀ has an effective vector B _eff rotating around the static vector B ₀ during the determined duration T.

Partial radiofrequency magnetic fields are, for example, modulated sinusoidally and in phase quadrature with respect to each other (which amounts to having a partial radiofrequency magnetic field modulated by a sine function and the other by a cosine function).

During the application of the radio frequency field B _1; whose frequency V! and the amplitude Β _Ϊ satisfy the condition:

the magnetic moments of spin S and thus the resulting magnetization are animated by a precession movement around the efficient vector defined by

This precession movement takes place at the frequency v _eff = y ^■ B _eff . The effective vector B _eff of the effective field B _e ff is itself in rotation around the static vector B _Q at the Larmor frequency v ₀ = y · B ₀ . When the precession frequency around the effective field B _e ff is sufficiently large (ie of the same order as the frequencies used in the MAS techniques, greater than a few hertz), an averaging of the dipolar and possibly quadrupole interaction present in the object is got.

The virtual rotation frequency v _eff responsible averaging dipolar interactions and quadrupole being simply controlled by the intensity of the radiofrequency field B _Ï applied it is neither the sample nor the static field B ₀ which must be rotated and tilted at the magic angle 0 _m but only the effective field B _eff , the latter operation being performed by appropriately selecting the frequency and amplitude of the radio frequency field B ^ It is simple to give B _i amplitudes ranging from a few μΤ to mT, these amplitude generating a virtual rotation frequency v _e ff ranging from a few Hz to several tens of kHz.

Thus, all parts of the apparatus 1 remain stationary during operation. This does not induce any mechanical wear of the device 1 and greatly limits the risk of breakdowns or mishandling.

A first sensor 15 may be placed according to the static vector B _Q and be set to detect frequencies around the effective frequency v _e ff. The effective frequency v _e ff is due to the effective magnetic field B _e ff seen by the sample 2. The effective magnetic field B _e ff results from the combination of static magnetic fields B ₀ , and radiofrequency B _Ï (without taking into account the electronic environment of the hydrogen atom), and has for formula, the following relation:

(

BB _< + \ B, 0

V The frequency Vi is the frequency of application of the field B _1; it is a frequency close to the Larmor frequency of the studied nucleus v ₀ = y · ₀ .

The following relation gives the effective frequency v _e ff:

v _eff = y - B _eff .

Thus, the first sensor 15 makes it possible to acquire signals having frequencies close to the effective frequency v _e ff which correspond to the signals resulting from the precessional movement of the S magnetic spin moments of the hydrogen atoms of the sample 2 around the effective B _eff field.

Two second sensors 16 may be placed in a plane orthogonal to the static vector B ₀ and adapted to acquire signals at the Larmor frequency v ₀ .

The one or more sensors 15, 16 are decoupled from the generator (s) 14; 141, 142 radiofrequency magnetic field B This decoupling can be performed geometrically or electronically. An example is described below.

The use of the first and second sensors 15, 16 makes it possible to acquire the variations of the magnetization M according to the three dimensions of the space in the reference frame of the laboratory.

In general, the configuration of the sensors can be chosen from the following:

a single sensor for acquiring signals at a frequency close to or equal to the frequency of Larmor v ₀ ;

two orthogonal sensors for acquiring signals at a frequency close to or equal to the frequency of Larmor v ₀ ;

two sensors, one for acquiring signals at a frequency close to or equal to the Larmor frequency v ₀ and one for acquiring signals at a frequency close to or equal to the effective frequency v _e ff;

three sensors, two of which to acquire signals at a frequency close to or equal to the frequency of Larmor v ₀ and one for acquire signals at a frequency close to or equal to the effective frequency v _e ff.

Process

With reference to FIGS. 5 and 6, a method of characterizing a sample using an NMR spectrometry apparatus described above is described below.

Prior to the process, a sample 2 is placed on the support 12 of the 1 NMR apparatus inside the chamber 11.

The method comprises a generation step E1 in the chamber 11 of the apparatus 1, by the static magnetic field generator 13, a static magnetic field B ₀ of static vector B ₀ collinear with a unit vector z.

The method also comprises a step E2 of generating in the chamber 11, by the radiofrequency magnetic field generator 14, a radiofrequency magnetic field Βτ radiofrequency vector β ₁ . The radiofrequency magnetic field Β _Ϊ is generated, for a determined duration T, in the form of a pulse I.

The amplitude Β _Ϊ of the radiofrequency magnetic field Β _Ϊ of frequency V! is given by the relation:

0 _m being the magic angle.

The radiofrequency magnetic field Βτ is, during the determined duration T, modulated so that an effective field B _e ff VU by the atoms of the object results from the static magnetic fields B ₀ and radiofrequency B _1; and effective vector B _eff rotating with respect to a terrestrial reference, such that: The effective vector B _{e {{} of the effective field B _e ff is animated by a precession movement around the static vector B ₀ at the frequency v ₀ . The radiofrequency field B _i was chosen so that the effective vector B _eff forms a magic angle of 0 _m of 54.74 ° with the static vector B ₀ .

The radiofrequency magnetic field B _i may comprise only one sinusoidally modulated component. In this case, only the effective vector B _eff revolves with respect to a terrestrial reference.

The radio frequency magnetic field Βτ may also comprise two modulated components sinusoidally and in quadrature phase.

In this second case, the radiofrequency vectors B ^ and effective B _{eff are} rotated relative to a terrestrial reference.

The application of the effective field B _e ff, forming the magic angle 0 _m with the static field B ₀ , eliminates the need to physically rotate the sample 2 or the generator 13 static magnetic field. Thus, it is possible to study samples regardless of their state (especially solid, but also liquid, gaseous, or even a mixture thereof), or even study the tissues of an animal or a living human being.

In addition, the rotation frequency of the magnetization M (due to the effective field B _e ff rotating and proportional to the effective frequency v _e ff) can be raised to a high value, which can exceed megahertz, compared to the prior art which is limited to a few tens of kilohertz.

The experimenter chooses the virtual rotation speed, proportional to the effective frequency v _e ff, that he wants to impose on the sample. Once this effective rotation speed has been chosen (between a few hertz and the megahertz), the amplitude of the radiofrequency field Βτ as well as its frequency V i are found by solving the system of equation:

with B ₀ , B _eff and y known.

The method also comprises an acquisition step E3, by at least one sensor 15, 16, of a magnetization M of the sample 2. This acquisition step E3 is carried out during the determined duration T and lasts a period of time. acquisition T _has included in the determined duration T (see Figure 6).

For example, two decoupled antennas (or coils) are used: a first antenna 14 is a linear volumetric coil (for example a Rapidbiomedical model V-HLS-047) for the emission of the radiofrequency magnetic field and a second 15 is an antenna. Surface-type ^{^"butterfly"} for reception.

The decoupling of the two coils 14, 15 is performed in two steps. Firstly, an _optimum rotation of angle α is applied to the plane of the throttle antenna in order to make the throttle antenna as parallel as possible to the radiofrequency vector β ₁ generated by the transmitting antenna 14. This minimizes the flow of the radio frequency magnetic field B1 through the two loops of the butterfly antenna to a residual flow. Then, the butterfly antenna is moved in translation inside the transmitting antenna 14. By taking advantage of the non-uniform nature of the radio frequency magnetic field B _1; it is possible to find a position in which the difference in flux between the two loops 151, 152 of the throttle antenna 15 can cancel the residual flow.

Moreover, in this case, the sample 2 can be positioned inside a first loop 151 of the butterfly antenna (see FIG. 7). Thus, the flux produced by the magnetization of the sample is maximum in the first loop 151 and almost zero in the second loop 152.

Thus, thanks to this method, one can dispense with the need to perform point-to-point measurements imposed in the MEPS technique. The acquisition step E3 may comprise the substep of acquisition E31 of magnetic signals having a frequency close to the effective frequency v _e ff. This low-frequency signal provides information on the evolution over time of the magnetizations along the axis of the static field B ₀ .

The acquisition step E3 may also comprise the substep of acquisition E32 of magnetic signals having a frequency close to the frequency of Larmor v ₀ . This step makes it possible to follow the evolution of the signal over time in the plane perpendicular to the static vector

The signals collected by the sensors 15, 16 can then be filtered E4 to eliminate spurious signals from the generators 13, 14; 13, 141, 142 of magnetic fields.

The collected signals are then processed E5 to reconstruct a three-dimensional signal describing over time the evolution of the magnetization

M of the sample 2. The three-dimensional signal can be in the form of a quaternionic signal, that is to say in the form of a signal of which each point is put in the form a + ib + jc + kd with a, b, c, real d and i ² = j ² = k ² = ijk = -1. At each instant t of the acquisition, the three-dimensional signal can be described in spherical coordinates by three parameters (p, θ, cp) corresponding to the amplitude, latitude and colatitude of the signal. Finally, a demodulation step E6 may be performed on the three-dimensional signal to represent it in the terrestrial frame according to a fixed reference.

FIG. 8 illustrates a timing diagram showing the acquisition of the signals during the emission of the radio frequency magnetic field B. According to this particular timing diagram, the acquisition is triggered before the radiofrequency magnetic field Βτ is applied and the acquisition ends after the radiofrequency magnetic field is cut off.

Figure 8 also shows the two acquired signals. The first at the top corresponds to the real part of the transverse magnetization while the second at the bottom corresponds to the complex part of this magnetization. These two oscillating and observable signals persist for a time of more than 300 ms, which is a relatively long time in the field of NMR acquisition. When the radiofrequency magnetic field is cut off, the observed signal disappears in only about twenty milliseconds.

Claims

claims

1. A method of characterizing a sample (2) by means of a Nuclear Magnetic Resonance spectrometer comprising an enclosure (1 1) in which the sample (2) is placed, a static magnetic field generator (13) (B ₀ ), a radiofrequency magnetic field generator (14), and at least one sensor (15, 16), the method comprising the steps of:

(a) generating (E1) in the chamber (1 1), by the static magnetic field generator (13), a static magnetic field (B ₀ ) according to a static vector (B ₀ );

(b) generating (E2) in the enclosure (1 1) and for a predetermined duration (T), by the radiofrequency magnetic field generator (14), a radiofrequency magnetic field (B ^ according to a radiofrequency vector (β ₁ );

characterized in that it further comprises the step (c) of acquisition

(E3), by at least one sensor (15, 16), a magnetization (M) of the sample (2) during all or part of the determined duration (T); and in that an effective vector (B _eff ), to which the magnetization (M) of the sample (2) is subjected during the determined duration (T), is rotating with respect to a terrestrial reference system during the determined duration ( T), the effective vector (B _eff ) resulting from static magnetic fields (B ₀ ) and radiofrequency (B ^, and the sample (2) being fixed relative to the terrestrial reference frame.

2. Method according to claim 1, wherein the radiofrequency magnetic field (Bi) is chosen so that the effective field (B _eff ) applied to the sample has its effective vector (B _eff ), given by B _eff = and defining an angle (0 _m )

approximately 54.74 ° with the static vector (B ₀ ),

VT being a frequency close to the frequency of Larmor v ₀ due to the static magnetic field (B ₀ ), this frequency VT being due to the radio frequency magnetic field (B ^.

3. Method according to one of claims 1 and 2, wherein the effective vector (B _eff ) is rotating in a plane orthogonal to the static vector (B ₀ ).

4. Method according to claims 2 and 3, wherein the effective vector (β.,) Is rotating in a plane orthogonal to the static vector (B ₀ ) at the frequency of Larmor (v ₀ ).

5. Method according to claim 4, wherein the acquisition (E3) of the magnetization (M) of the sample (2) is performed by at least two sensors (15, 16); a first sensor (15) arranged to acquire collinear magnetic signals to the static vector (B ₀ ), having a frequency close to the effective frequency (v _e ff), and at least one second sensor (16) positioned so as to acquiring collinear magnetic signals in the plane orthogonal to the static vector (B _Q ), having a frequency close to the Larmor frequency (v ₀ ).

6. Apparatus (1) for nuclear magnetic resonance spectrometry for acquiring a magnetization (M) of a sample (2) comprising:

a fixed sample support (12) with respect to a terrestrial reference system during operation of the apparatus (1); an enclosure (1 1) in which the sample holder (12) is placed;

a static magnetic field generator (13) for generating a static magnetic field (B ₀ ) in the enclosure (1 1) according to a static vector (B ₀ ); a radiofrequency magnetic field generator (14) for generating a radiofrequency magnetic field (B ^ in the enclosure according to a radiofrequency vector

(B ^) for a fixed period (T);

characterized in that the apparatus (1) further comprises at least one sensor (15, 16) for measuring the magnetization (M) of the sample (2) for the determined duration (T).

7. Apparatus (1) according to claim 6, wherein the radiofrequency magnetic field generator (14) comprises at least two coils (141, 142) each generating a radiofrequency magnetic field so that the effective magnetic field (B _e ff) total resulting from the two radiofrequency magnetic fields of the coils (141, 142) and the static magnetic field (B ₀ ) have an effective vector (B _eff ) rotating with respect to the terrestrial reference.

8. Apparatus (1) according to one of claims 6 and 7, wherein a first sensor (15) is placed according to the static vector (β ₀ ) and set to acquire signals at frequencies close to a frequency effective (v _e ff) resulting from an effective magnetic field (B _e ff) applied to the sample (2) such that:

VT being a frequency close to the Larmor frequency (v ₀ ) due to the static magnetic field (B ₀ ), the frequency being due to the radiofrequency magnetic field (B i) and y being the characteristic gyromagnetic ratio of a nucleus of a studied atom.

9. Apparatus (1) according to one of claims 6 to 8, wherein two second sensors (16) are placed in a plane orthogonal to the static vector (B ₀ ) and adapted to acquire a signal at a frequency of

Larmor (v ₀ ) due to the static magnetic field (B ₀ ) with:

v ₀ = y · ₀ ,

y being the characteristic gyromagnetic ratio of a nucleus of a studied atom.

Apparatus (1) according to one of claims 6 to 9, wherein the static magnetic field generator (13), the radiofrequency magnetic field generator (14) and the at least one sensor (15, 16) are fixed by report to the terrestrial reference system during the operation of the device (1).