FR2735865A1 - NMR quantitative analysis appts. for non-invasive chemical qualitative and quantitative spectroscopic NMR analysis - Google Patents

Abstract

The systems receiver (30) and processor (40) are designed to detect this radio-frequency at the time of acquisition of the RMN signal from a sample and to use the signal so detected. The controlled radio-frequency signal is a sinusoidal signal whose period includes an exponential decrement and exponential increment. The signal is also shifted in frequency with respect to the natural RMN spectrum of the sample for use in spectrometry or imagery.

Description

 The present invention relates to the field of Nuclear Magnetic Resonance (NMR) analysis devices.

 NMR analysis techniques have already given rise to abundant literature.

 The power of Nuclear Magnetic Resonance Spectroscopy (S.R.M.) lies in its ability to perform qualitative and quantitative chemical analysis, non-invasively, in a perfectly defined region of the sample.

When a number of well-known conditions are fulfilled (see: Principles of Nuclear Magnetic Resonance in One and Two Dimensions, RR Ernst, G. Bodenhausen and A. Wokaun,
Oxford Science Publication, 1988, 91-157), the area of a NMR spectrum is directly proportional to the concentration of the compound that produces it. NMR thus makes it possible to measure the proportions of the different substances in the sample. This measurement is made from ratios between the surfaces of the different lines of the spectrum. The relative concentrations thus obtained are widely used.

 The main disadvantage of this method however lies in the fact that the variation of a report does not allow to conclude on its origin: a comparable evolution of the two surfaces will mask any variation.

 It is therefore essential to be able to isolate the quantitative information for each spectrum line.

 Given the mode of acquisition of a signal R.M.N., its amplitude can have variations in time for the same sample. The measurement of the concentration of each of the compounds therefore presupposes a calibrated reference signal on a known concentration.

 When possible, this signal is formed of a chemical internal reference corresponding to the spectrum R.M.N. of a substance added to the sample in known concentration, or to a part of the spectrum of the sample analyzed, when there are compounds whose concentration is known is stable.

 In a number of cases (in vivo experiment for example) this approach by internal chemical reference is not feasible. The reference signal must then be obtained from a R.M.N acquisition. different, shifted in time or in space with respect to the acquisition of R. M. N. on the sample.

 In this context, three methods for obtaining a reference line in R. M.N. spectroscopy have already been proposed and are currently used. These methods are the following: calibration using the peak of the internal water volume e, xplore, calibration by simulation with a phantom, calibration by symmetrical phantom.

A general description of these three methods can be found in the following documents
1-A. Buchli, P. Boesiger. Comparison of methods for the determination of absolute metabolite concentrations in human muscles by 31p MRS. I \ Iagn. Reson. Met; 30: 552-558 (93).

 2-R. Buchli, E. Martin, P. Boesiger. In vivo concentration determination of absolute metabolite concentrations in human brain by 31p MRS. NADIR Biomed .; 7: 225-230 (94).

a) Calibration by internal water concentration
Because it is not always possible to find in the spectrum a compound of known and constant concentration, Thulborn and Ackerman [3] proposed to consider the signal of the internal water to the volume explored as a standard for the calculation of concentrations. This method requires that test tubes be placed in the center of the antenna, for the calibration of the radio frequency pulses. Thus, starting from the signal of the phosphorus metabolite and water internal to the volume, the concentration of the phosphorus metabolite with the relation [3 1Pmetab] = (Smetab / Swater). ['Hstand] .WC.CpH where [31Pmétab] is the concentration of the phosphorus metabolite
[1Hstalld] is the concentration of pure water (111 mmol / dm3)
WC is the relative proportion of water tissue
CPH is the relative sensitivity between 1H and 31P obtained in vitro
with the help of a phantom calibration:
signal 1H / signal 31P (mmol / dm3) Smetab is the signal of the metabolite, and 5water is the signal of water.

 The main advantage of this method is to always be applicable. On the other hand, it is of long implementation (in particular for phosphorus manipulations), and imposes identical sensitivity and calibration for the two scanned volumes. This method, although giving only very approximate results [4-7], remains nevertheless the most used currently.

 3-K.R. Thulborn, J.J.H. Ackerman, Asbolute molar concentrations by NMR in inhomogeneous B1. A scheme for analysis of in vivo metabolites. J. Nlagn. Reson .; 55: 357-371 (83).

4P. Christiansen, O. Henriksen, M. Stubgaard, P. Gideon and
HBW Larsson. In vivo quantification of brain metabolites by 1H MRS

using water as an internal standard. Magn. Reson. Imaging, 11: 107-118 (93).

 5-P.B. Barker, B.J. Soher, S.J. Blackband, J.C. Chatham, V.P.

 Mathesvs and R. N. Bryan. Quantification of proton N.M.R. Spectra of the human brain using an internal concentration reference.

 NhIR Biomed; 6: 89-94 (93).

6-PB Toft, P. Christiansen, O. Pryds, HC Lou O. Henriksen,
T1, T2> and concentrations of brain metabolites in neonates and adolescents with 1H MR spectroscopy, J. Mage. Reson. Imaging; 4: 1-5 1994.

 7-P.B. Barber, S.J. Blackband, J.C. Chatham, B.J. Soher, M.A.

Samphilipo, C. A. Magee, J. D. Hilton, J. D. Strandberg and J. H. Anderson.

Quantitative proton sprectroscopy and histology of a canine brain tumor model. Magn. Reson. Med .; 30: 458-464 (93).

b) Calibration by simulation by a ghost
For this method, a phantom is used as an external homonuclear reference. In vitro calibration should best simulate the in vivo experiment. Both acquisitions must be made under the same operating conditions, and have similar loads for the antenna. For this, the charge of the phantom is adjusted by stepwise displacement of a bottle of saline near the antenna, until a similar agreement.

In the context of, for example, phosphorus acquisitions, the expression of the concentration of the [3I-Pmetab] metabolite is given by the relation [31 Pmetab] = (Smetab / Sstand). [31 Pstand] where [Smetab] = metabolite signal
[ancd = water signal internal to the explored volume
[3lPstand] = concentration of the phantom calibration solution.

 The biggest problem with this method is the risk of making the two necessary acquisitions with different loads. A very good approach to the charge in vivo is indeed essential, otherwise there will be very different amounts of signal. Nevertheless, this method remains fairly used, and gives good results [8-12].

8-PR Luyten, JP Groen, JWAH Vermeulen and JA den
Hollander. Experimental approaches to image localized human 31p NMR

 spectroscopy. Magn. Reson. Med. : 11: 1-21 (89).

 9-P.A. Bottomley, C.J. Hardy and P.B. Roemer. Phosphate metabolite imaging and concentration in human heart by nuclear magnetic resonance. Magn. Reson. Med; 14: 425-434 (90).

DJ Meyerhoff, GS Karczmar, GB Matson, MD Bobska
MW Weiner. Non-invasive quantitation of human liver metabolites using mage-guided 31P magnetic resonance spectroscopy. NMR Biomed .; 3: 17-27 (90).

 II-E. of Bisschop, R. Luypaert, G. Annaert, J. Coremans and M.

Osteaux. Absolute quantification of 31 p liver metabolites in rats using an external reference and a surface spoiling magnetic field gradient. NMR Biomed; ; 5: 341-346 (92).

 12-J. Hennig, H. Pfister, T. Ernst and D. Ott. Direct absolute quantification of metabolites in the human brain with in vivo localized proton spectroscopy. NMR Biomed; 5: 193-199 (92).

c) Symmetrical phantom calibration:
In this method, the sample and the phantom are placed in two identical areas of the antenna from the point of view of sensitivity (symmetrical with respect to the center of the antenna). Tissue and phantom signals are collected simultaneously. This obviously assumes an identical sensitivity on both sides.

 Metabolite concentrations are also calculated with the previous equation.

 This is the simplest method to implement and the fastest (one acquisition). In addition, it does not require precise optimization of radio frequency pulses. Its main drawback, which makes it a little used method, is the clutter it imposes. In particular, this method is inapplicable in the context of many manipulations, such as, for example, the study of anoxoischemic lesions in the preterm or term neonate.

 Of all the methods currently available, none is really unanimous. The choice of the method is dictated by parameters such as: useful diameter of the magnet, examination time, technical and operational constraints.

 It is now an object of the present invention to improve the known NMR analysis means.

 This object is achieved according to the present invention by means of a nuclear magnetic resonance analysis device, characterized in that it comprises electronic means capable of generating a controlled radiofrequency signal having the characteristics of an NMR signal and that the means Receivers and device processing are adapted to detect this radio frequency signal during the acquisition of the NMR signal of the sample and use the radiofrequency signal thus detected.

 Thus, in the context of the present invention, the reference signal does not correspond to an NMR signal generated by a sample or a phantom, following an excitation, but corresponds to the radiofrequency signal itself generated by the electronic means.

 As will be explained below, this reference signal can be used in the context of the present invention to perform a quantitative analysis by spectroscopy, or in the context of imaging. This reference signal can also be used to selectively suppress at least one peak of the NMR signal generated by a sample.

 Other characteristics, objects and advantages of the present invention will appear on reading the detailed description which follows, and with reference to the accompanying drawings given by way of non-limiting example and in which - Figure 1 represents a general schematic view of an RNM analysis device according to the present invention, - Figure 2 schematically illustrates the generation of a radiofrequency signal having the characteristics of an RNM signal by analog multiplication, - Figure 3 represents a phosphor spectrum of the thenar muscle. Human Figure illustrating an example of in vivo application of the present invention, - Figure 4 shows the same spectrum at different successive times to illustrate a kinetics of effort-recovery on the thenar muscle, - Figure 5 represents a general view. , in the form of functional blocks, of an electronic radiofrequency signal generating module having the characteristics of a FIG. 6 represents the diagram of an exemplary embodiment of such a module, and FIG. 7 represents timing diagrams of the signals at different points of the circuits of FIGS. 5 and 6.

 FIG. 1 shows schematically an NMR analysis device according to the present invention.

 FIG. 1 shows the known general structure of an NMR analysis device comprising a Faraday cage 10, means 20 generating a polarization magnetic field, for example formed of a permanent magnet, means 30 , generally formed of a transmitter / receiver winding assembly, capable of generating a radiofrequency field whose magnetic field is able to excite a sample and to detect the NMR signal generated in response by this sample, as well as electronic means 40 adapted to generate the radiofrequency signal applied to the coil 30, and detect the NMR signal received by the latter and process this signal obtained.

 As indicated above, according to a main feature of the present invention, the analysis device further comprises electronic means 100 capable of generating a controlled radiofrequency signal having the characteristics of an NMR signal and the receiving means 30 and The processing circuit 40 of the device is adapted to detect this radio frequency signal during the acquisition of the NMR signal of the sample and to use the radiofrequency signal thus detected.

By "radiofrequency signal having the characteristics of an NMR signal" is meant a radiofrequency signal whose frequency, power and evolution parameters are comparable to those of a signal
NMR generated by a sample.

 More specifically, in the context of the present invention, the controlled radiofrequency signal is a sinusoidal signal whose peak-to-peak amplitude exponentially evolves.

 It can be a single frequency signal or multi-frequency continuous or not.

 In addition, the peak-to-peak evolution of this radio frequency signal may comprise a growth period and / or an exponential decay period.

 Preferably, as shown diagrammatically in FIG. 2, the radiofrequency signal having the characteristics of an NMR signal is generated by analog multiplication of the two signals: on the one hand, a low frequency signal 102 evolving exponentially, and on the other hand a high frequency sinusoidal signal 104 (mono or multifrequency).

 The high-frequency sinusoidal signal 104 is preferably at the resonance frequency of the nucleus in question, and of controlled amplitude and phase.

 The exponentially decreasing low frequency signal 102 may be made, for example, from charging and discharging a capacitor through a resistive network.

 However, the invention is not limited to this particular provision. In practice, the signal 102 evolving exponentially can be obtained by any equivalent means, for example digital means based on memories and converters.

The discharge voltage across a capacitor is a signal of the form
Vc (t) = V0.et/T where Vc (t) = voltage across the capacitor
V0 = initial charge
T = RC = time constant of the circuit
This signal, which varies exponentially, multiplied by a high frequency signal 104, makes it possible to obtain a sinusoidal signal 106, decreasing exponentially, which can then be compared with a true NMR signal, with the equation Myy (t) = MXy (O). ) .et / T2.ebt where MXy (t) = value of the transverse magnetization
Mxy (O) = value of initial transverse magnetization
T2 = constant characteristic of the medium
w = radiofrequency pulse
The means 100 in accordance with the present invention thus make it possible to manufacture a signal that combines all the characteristics of a real NMR signal. However, all the characteristics of the signal 106 are simply adjustable: frequency position of the created line, amplitude, phase, time constant of the decay, ...

 The inventors have verified using the configuration shown in FIG. 1 the ease of modifying the parameters of the line thus created. Several acquisitions have been made by varying the following parameters - frequency of the reference line (the inventors have shown that the recovery of one of the lines of the natural spectrum of a sample can be avoided), - amplitude of the reference line (which allows to adapt the amplitude of the reference line to the amplitude of the signal coming from the sample, for use with any application), and - phase of the reference line (the reference line can thus to be phased at the same time as the natural spectrum).

 In practice, the controlled radiofrequency signal 106 can be generated by means of a transmitting antenna 110 located in the environment of the NMR analysis device, either inside the Faraday cage 10.

 The transmitting antenna 110 is connected to the electronic module 100 via a link 112. Similarly, the generating means 30 of the radio frequency excitation signal are connected to the electronic means 40 via a link 32.

 The aforementioned links 32 and 112 preferably pass through the Faraday cage 10 at a filter box 114.

 The inventors have carried out various tests using the NMR analysis device according to the present invention, including in vivo studies.

 FIG. 3 shows a phosphor spectrum of the thenar muscle of man with superimposition of an electronic reference peak corresponding to the above-mentioned controlled radiofrequency signal 106.

Specifically, in Figure 3, there is shown the following peaks 1. Inorganic phosphate (Pi); 2. Phosphocreatine (Pcr); 3. there
ATP, 4.a-ATP; 5. Electronic reference corresponding to the radio frequency controlled signal (identified by an arrow); 6. B-ATP.

 As indicated previously, the ratios enter the surfaces of the different natural lines 1, 2, 3, 4 and 6 of the spectrum from the sample and the reference line make it possible to determine the relative concentrations of different reagents of the sample.

 Moreover, FIG. 4 illustrates the successive spectra obtained on a thenar muscle to represent kinetics of effortrecuperation.

 More precisely, in FIG. 4, the following are successively illustrated: a) the spectrum at rest, b) the spectrum collected one minute after effort, c) the spectrum collected two minutes after effort, d) the spectrum collected three minutes after effort, and e) the spectrum collected four minutes after effort.

 The curves of FIG. 4 illustrate the stability of the electronic reference corresponding to the peak 5 targeted by an arrow.

 In the context of a particular application of the present invention, the module 100 according to the present invention is in the form of a box provided with its own power supply and which uses as a high frequency signal 104, a signal delivered by the second radio frequency chain 42 of the NMR spectrometer. Such a second radiofrequency NMR spectrometer chain is available nowadays on many NMR spectrometers. This second radiofrequency channel generates a controlled radiofrequency signal used, for example, to scramble or cancel a line of the natural spectrum of the sample by saturation.

 This second chain 42 is sometimes called decoupler.

 In addition, the means 100 generating the controlled radio frequency signal 106 preferably uses a synchronization signal present on the output 41 of the electronic means 40, a signal present on any spectrometer to trigger the opening of the receiver.

 The means capable of generating such a synchronization signal as well as the means composing a second radio frequency chain 42 or decoupler are well known to those skilled in the art, and will therefore not be described in detail later.

 Those skilled in the art may for example refer to this point in the document Technology of Nuclear Magnetic Resonance, P.D.Esser, R.E.

Johnston (Eds), The Society of Nuclear Medicine, New York, 1984, 3-14.

 The controlled radio frequency signal 106 generated by the electronic means 100 falls within the range of the natural NMR spectrum generated by a sample, preferably between 1 MHz and 1 GHz.

 The power of this controlled radio frequency signal 106 must be low so as not to interfere with the excitation field generated by the means 30. The transmitting antenna 110 is situated at a short distance from the reception means 30, typically at a distance from the order of magnitude of the wavelength of the controlled radio frequency signal 106.

However, the invention is not limited to the particular embodiment described above with reference to FIG. 1, exploiting the signal delivered by the second radio frequency chain of the spectrometer.
NMR and the synchronization signal triggering the opening of the receiver.

 In fact, more generally, the present invention can be applied to more autonomous electronic means 100 which themselves generate the high frequency signal 104. Such a variant can be used in particular on the whole body imaging systems of the hospitals.

 FIG. 5 shows the flowchart of an exemplary embodiment of the electronic means 100, in FIG. 6 a complete nonlimiting electronic diagram of such means and in FIGS. 7A to 7F, chronograms illustrating the process of FIG. development of the radiofrequency signal controlled by these circuits.

 More precisely, the timing diagrams illustrated in FIGS. 7A to 7F respectively correspond to the signals observed at the points identified by the indices A, B, C, D, E and F respectively, in FIGS. 5 and 6. FIG. 7G represents the window of FIGS. acquisition by the receiver.

According to the non-limiting illustration shown in FIGS. 5 and 6, the analog multiplication is performed by amplitude modulation of the sinusoidal signal 104 by means of a tetrode 160, for example of the type
BF991.

 The branch generating the low frequency signal of eponential evolution, initiated by the synchronization signal coming from the output 41, comprises successively a resistive divider bridge 120 ensuring an amplitude adaptation, an RC130 circuit generating an exponential evolution , an operational amplifier 140 mounted as a follower providing an impedance matching and a unit gain reversal summing stage 150 ensuring the addition of a DC component.

 It will be understood from the examination of FIGS. 5 to 7 that the triggering of the charge and the discharge of the capacitor C is ensured by the triggering signal of the spectrometer coming from the output 41.

 It is recalled, however, that the present invention is not limited to the arrangements shown in FIGS. 5 to 7.

 The radiofrequency reference signal 106 produced by the means 100 makes it possible to obtain a stable line without necessitating acquisition other than that of the sample. The line thus obtained can be placed anywhere on the natural spectrum to avoid overlapping of one of these lines. The parameters (position, area) of the reference line 5 are easily adjustable. After calibration on a standard containing a substance in known concentration, the reference line remains stable over time. Reports giving the concentrations corresponding to each of the lines can then be calculated using this perfectly stable reference line.

 Such an electronic reference that can be used for any type of manipulation, has in particular the following advantages: - obtaining the spectrum of the sample with the reference line in a single acquisition, so fast technique, - no space occupied in the magnet 20, unlike the symmetrical phantom calibration method, therefore the entire diameter of the magnet remains available, - no addition of a reference substance to the sample, which avoids any risk of chemical interaction, and - simulated line independent of the calibrations of the antenna, unlike the methods based on the use of a ghost where the biggest difficulty is to achieve the different acquisitions with the same settings.

 The inventors have carried out comparative tests with the analysis processes according to the state of the art.

 Since both methods based on the use of a phantom for calibration are recognized in the literature as being the most efficient and of equal reliability, the inventors have established these comparative tests, by comparing the results obtained with a device according to the present invention with those resulting from calibration by simulation with a phantom.

 For this, three standards were made - a standard A containing a phosphorylated compound in known concentration acting as a reference line> and - two standards B1 and B2 each containing a phosphorylated compound in known concentration acting as samples to be analyzed .

 An acquisition on standard A was performed to calibrate the electronic reference.

 The validation operation was then carried out on the basis of the following steps: 1) Acquisition on the standard B 1 with the electronic reference line and exploitation of the results, 2) Acquisition on the standard A with the same settings as the Step 1 and exploitation of the results, 3) Acquisition on the B2 standard with the electronic reference line and exploitation of the results, and 4) Acquisition on the standard A with the same settings as for the stage 3 and exploitation of the results.

For a theoretical concentration of 40mML for standard B1 is 20mMl for standard B2 the results obtained are as follows - estimation by means of the electronic reference on standard B: 40,542, a difference of 1.34%, - estimation with a symmetrical phantom on the standard B1: 42,320, a difference of 5.48%, - estimate thanks to the electronic reference on the standard B2: 19,154, a difference of 4,23%, - estimate thanks a symmetrical phantom on standard B2: 21.11, a difference of 5.26%;
The results above show a good efficiency of the two methods (maximum error of 5.48%), with however a clear advantage for the electronic reference according to the present invention.

 The errors obtained with the phantom simulation calibration method are consistent with those reported in the literature [1,2].

 The method using the electronic reference according to the present invention is also much simpler to implement since the calibration on a standard can be carried out at the beginning of the series of manipulations and allows a good approximation of the concentration of the compounds in a single acquisition. .

 The present invention also makes it possible to overcome the problems of calibration and load adjustment which are the source of the quantization errors of the methods using a standard.

 The previously described applications of the present invention are aimed at determining the relative concentration of substances in the sample.

 The present invention is not however limited to these applications.

 The present invention can indeed be used to suppress one or more lines of the natural spectrum of the sample, for example to remove the peak of water in NMR.

 Experts know that for example in proton spectrometry the peak of the water, large amplitude sometimes mask useful peaks of smaller amplitude (of the order of 10,000 times smaller).

 This also applies to peaks corresponding to other substances such as, for example, fats or solvents, for example chloroform.

 Hitherto, those skilled in the art sought to eliminate these troublesome peaks of high amplitude by saturation.

 The present invention makes it possible to suppress such peaks more finely and more reliably.

 For this purpose, in the context of the present invention, it is sufficient to detect the peak or peaks that are to be suppressed and then generate one or more controlled radio frequency signals of phases respectively opposite to the peaks to be suppressed.

 The present invention can find wide application.

 The present invention applies in fact to any type of spectrometer, in particular both horizontal magnets and vertical magnets.

 In addition, the radiofrequency reference signal can be used effectively and simply in a quality control procedure of the apparatus. It is totally independent of the radio frequency channel at the time of transmission and thus makes it possible to test very quickly the performances of the reception and amplification chain of the NMR signal. Integrated into a standard acquisition procedure, this control can be performed automatically by the equipment, permanently.

 The present invention allows access to concentrations in vivo in many applications, such as, for example, and without limitation - the assay of compounds visible in NMR, - the medical diagnosis, and - the pharmacological monitoring of the efficacy of a drug or treatment.

 The present invention may also find application in the field of nuclear magnetic resonance imaging, in particular by generating a continuous frequency band making it possible to create in the image a calibrated intensity reference area to allow, for example, the development of of contrast products and / or the measurement of the noise present in the image to allow the quantitative exploitation of the images.

 Of course, the present invention is not limited to the particular examples which have just been described but extends to any variant within its spirit.

 In particular, the present invention also applies to the electronic module capable of generating a controlled radiofrequency signal having the characteristics of an NMR signal as previously described insofar as such an electronic module can be sold separately to equip the devices. nuclear magnetic resonance analysis available today.

Claims (14)

 1. Device for nuclear magnetic resonance analysis, characterized in that it comprises electronic means (100) capable of generating a controlled radiofrequency signal having the characteristics of a signal RNIN and that the receiving means (30) and of processing (40) of the device are adapted to detect this radio frequency signal during the acquisition of the NMR signal of the sample and use the radiofrequency signal thus detected.  2. Device according to claim 1, characterized in that the controlled radio frequency signal (106) is a sinusoidal signal whose peak-to-peak amplitude evolves exponentially.  3. Device according to claim 2, characterized in that the controlled radiofrequency signal comprises an exponential decay period.  4. Device according to one of claims 2 or 3, characterized in that the controlled radio frequency signal (106) comprises an exponential growth period.  5. Device according to one of claims 1 to 4, characterized in that the controlled radiofrequency signal (106) is shifted in frequency relative to the natural RAIN spectrum of a sample for use in spectrometry and / or imaging.  6. Device according to one of claims 1 to 4, characterized in that the controlled radio frequency signal comprises at least one component whose frequency corresponds to a peak of the natural NMR spectrum of a sample and phase opposite to this peak of natural NMR spectrum, to suppress the corresponding peak.  7. Device according to claim 6, characterized in that the controlled radiofrequency signal comprises several frequency-shifted components to allow the suppression of several corresponding peaks in the natural NMR spectrum.  8. Device according to one of claims 1 to 7, characterized in that the controlled radio frequency signal (106) is generated by analog multiplication of two signals: on the one hand a low frequency signal (102) evolving exponentially, and on the other hand a high frequency sinusoidal signal (104).  9. Device according to claim 8, characterized in that the low frequency signal (102) is obtained by charging and discharging a capacitor through a resistive network.  10. Device according to one of claims 8 or 9, characterized in that the low frequency signal (102) is controlled by a synchronization signal corresponding to the trigger signal of the acquisition of the device.  11. Device according to one of claims 8 to 10, characterized in that the high frequency sinusoidal signal (104) corresponds to the signal generated by a second radiofrequency channel (42) of the device NMR.  12. Device according to one of claims 1 to 11, characterized in that the controlled radiofrequency signal is generated by a transmitting antenna (110) located in the environment of the analysis device (RMN).  13. Device according to claim 12, characterized in that the transmitting antenna (110) is located inside a cage of Faraday (10).  14. Electronic module capable of generating a controlled radiofrequency signal having the characteristics of a signal (NMR) for the implementation of a device according to one of claims 1 to 13.