FR2672688A1 - METHOD FOR EXCITTING AN NMR SPECTROMETER FOR SUPPRESSING THE SOLVENT SIGNAL. - Google Patents

Abstract

According to the invention, a sequence of two pulses (I1, I2) having a time duration (t) with rising fronts separated from the time duration (T), the duration (t) being extended and the interval (T-t) being shortened, is applied according to the amplitude of the applied field. Application to NMR spectrometry.

Description

METHOD FOR EXCITTING A SPECTROMETER
NMR FOR THE SUPPRESSION OF THE SOLVENT SIGNAL
DESCRIPTION
The subject of the present invention is a method of excitation of a nuclear magnetic resonance spectrometer allowing the suppression of the solvent signal.

 It finds an application in fields as diverse as Chemistry, Biochemistry, Neurobiophysics, Biophysics, BioLogy, BiomedicaL, etc ...

 The technique of nuclear magnetic resonance (NMR for short) is well known today.

It constitutes a remarkable tool for the study of
Condensed matter. However, it is not without faults when it comes to analyzing compounds dissolved in very low concentration in a solvent also comprising spin nuclei. This is the case, for example, for substances in aqueous solution where the protons of water saturate the various measurement equipment.

Many methods have been developed to attenuate or even eliminate the part of the signal corresponding to the contribution of the solvent and leave only the signal linked to the solute. These methods are called "removal of the solvent signal" (or
SSS for short).

They consist in applying to the solution a series of radiofrequency field pulses including
The number, the duration and the separation determine an excitation spectrum without line at the resonant frequency of the solvent. We thus know a sequence called "2-1-4" giving good results. It is described in the article by AG REDFIELD et al., Published in the journal "Journal of Magnetic Resonance", vol. 19, p. 114 (1975).

However, this technique has a drawback linked to the existence of a phase shift in the measurement signal, phase shift which depends on the frequency and which causes an undulation of the baseline of the NMR spectrum obtained. This phenomenon was described in an article by Pierre PLATEAU, Christian DUMAS and Maurice GUERON entitled "Solvent-Peak Suppressed NMR:
Correction of Baseline Distortion and Use of
Strong-PuLse Excitation ", published in the journal" Journal of Magnetic Resonance, vol. 54, 46-53, (1983), pp. 46-53.

To remedy this drawback, iL has been proposed in this article, as well as in an article by Pierre PLATEAU and Maurice GUERON entitled "Exchangeable Proton NMS without BaseLine Distorsion, Using
New Strong PuLse Sequences "published in the journal" The
JournaL of the American ChemicaL Society ", 1982, 104, pp. 7310-7311, to use a particular excitation consisting of two intense and brief impulses, at the resonant frequency of the solvent and out of phase with one another in 1800 .

FIG. 1 appended thus shows two pulses Il and I2, of duration t0, the rising edges of which are separated from Duration Tg, the interval between pulses thus being T0-t0. We must understand that these rectangular pulses represent the envelope of a radiofrequency pulse, the negative sign of
The impulse I2 symbolically representing a radiofrequency impulse of phase opposite to that of
the pulse I1.

 This excitation sequence is called "Jump and Return" (or jump and return) or JR for short, for reasons which will appear better in connection with FIG. 2.

 This figure 2 represents, on the top line, an Oxyz trirectangle reference frame, making it possible to identify the orientation of the various nuclear spins.

This referential is not fixed but rotates around the Oz axis at a speed which is that of the precession of the spins of the solvent when a static Hst field is applied, parallel to Oz. In the rotating reference, a static field appears which opposes Hst and compensates it exactly for the spins of the solvent. Consequently, in this reference, the orientation of the spins of the solvent is fixed in the absence of a radiofrequency field. During the radiofrequency excitation, the spins of the solvent revolve around the radiofrequency field that is assumed along the Ox axis of this same referent. Still on Figure 2,
The bottom line shows The JR excitation sequence.

According to this known art, and as always in
NMR, the solution to be analyzed is continuously subjected to the static magnetic field Hst directed along Oz, which has the effect of creating a polarization of the solvent and solute nuclear spins) Along this field (therefore along the Oz axis) (strong line). A first radiofrequency magnetic field (Hrf) 1 is applied to the solution perpendicular to the static field and directed along Ox; this field can be generated by a winding of axis perpendicular to Oz. This
field has a frequency equal to the frequency W of resonance of the solvent, a very large amplitude and a phase which determines the axis Ox above. This first radiofrequency field (Hrf) 1 is maintained for a duration t0 to constitute the first pulse. excitation ion I1; this pulse has the effect of switching all nuclear spins from 'in / 2.

These spins are therefore aligned along the axis Oy.

 This first phase is illustrated in column A of FIG. 2.

The solution is then left, for a time interval T0-t0, under the sole effect of the static magnetic field Hst, which has the effect of allowing all the spins around the static field to pre-stop.
Hst in The equatorial plane xOy. The spins linked to the solvent precess at the frequency W and the spins linked to the solute at Their own relative frequency w counted relative to W. The spins of the solvent therefore remain directed according to Oy, by hypothesis, and the spins of the solute gradually present angular offset
0 relative to the solvent spins. This is what is represented in column B where we see the orientation of the spins in the xOy plane.

 A second radiofrequency magnetic field (Hrf) 2 is then applied with the same direction, amplitude and frequency characteristics as the field (Hrf) 1 but of opposite phase; this second field (Hrf) 2 is maintained for the same duration t0 to constitute a second excitation pulse I2, which has the effect of switching the spins of I2 back; this brings back the spins of the solvent according to Oz, that is to say parallel to the static magnetic field Hst and brings back all the spins of the solute in the plane xOz.

 This is shown schematically in column C.

 Thus, this excitation sequence has the overall effect, by the mechanism of jump of magnetization and return ("Jump and Return") to angularly separate the spins, those of the solvent remaining aligned according to Oz on the static field Hast, those of the solute being offset from Oz by a certain angular deviationo (.

For a certain relative frequency wmax,
The angular offset in the xOy equatorial plane is / 2 and, after the second pulse, the corresponding spins are aligned along Ox.

 After this excitation sequence, it will be possible to detect an electrical signal induced by the precession of the spins of the solute around the static field Hst, this signal being devoid of component linked to the solvent.

In addition, this signal will present a maximum for the spins furthest from the direction of the static field, which is the case for spins whose frequency has been designated by Wmax.

 It will remain to process this electrical signal to obtain the NMR spectrum of the solute. This treatment is not part of the invention.

As all the spins of the solute are initially in the xOz plane, their projections on the transverse xOy plane are all confused with the axis
Ox. However, it is this transverse component of the spins which is capable of inducing an electrical signal in a winding for detecting a transverse axis. The phases of the various induced electrical signals will therefore all be the same, whatever the frequency w. We have therefore remedied the disadvantages of the prior art which introduced a phase shift.

 If this method has a certain advantage, it nevertheless suffers from a disadvantage in certain cases. Indeed, it requires that the two radiofrequency fields applied according to Ox in the form of pulses are of large amplitude. If this is not the case, we will not find exactly the spins in the xOz plane at the end of the excitation sequence and we will observe a substantially linear phase shift as a function of the frequency. Furthermore, the frequency for which the measurement signal is maximum will no longer be quite the frequency Wmax obtained when the excitation amplitude is very large.

 The finite nature of the amplitude of the excitation field therefore causes a double fault, one of phase and the other of amplitude, affecting the electrical measurement signal.

 The object of the present invention is precisely to remedy these drawbacks.

 To this end, it takes account of the amplitude of the radiofrequency fields applied to adjust the duration of the pulses and the interval between them.

As will be understood better below, the duration t of the pulses is lengthened compared to the valid theoretical duration t0 When the amplitude is very large and the duration Tt of the interval is shortened compared to The theoretical duration T0-t0 .

The invention thus improves the technique
JR by allowing the use of radiofrequency fields of limited amplitude, which is more in line with practice.

 More specifically, the present invention relates to a method of excitation of an NMR spectrometer with suppression of the solvent signal, which is of the type JR mentioned above and which is characterized by the fact that the duration t of the two radiofrequency field pulses is such that the two tiltings of the magnetization resulting from these pulses are greater than Iri 2 by a first quantity and the duration Tt of the interval between pulses is such that the angular offset of the spins of the solute by relative frequency wmax with respect to the spins of the solvent during The interval between pulses is less than lY / 2 of a second quantity, so that at the end of the excitation, all the spins of the solute are located in the same plane defined by the static magnetic field Hst and the direction of application of the radiofrequency field, which minimizes any phase error in the sampled electrical signal, those of the spins of the solute which have the fr relative equation Wmax being still angularly offset by at / 2 with respect to the static magnetic field and leading to a signal maximum, which minimizes any amplitude error in the sampled electrical signal.

 These two differences (t-t0) on the one hand, and (T-To) on the other hand, are preferably expressed as a function of the same parameter p equal to the ratio t0 / T0 between the duration t0 of a radio frequency field pulse which would be capable of causing a tilting equal to 1tl2 and the duration To which corresponds to an angular offset equal to t / 2 for the relative frequency Wmax leading to a maximum of signal (wmax (To-to) = # 2 ).

 According to a first variant, the duration t of the pulses corresponds substantially to a tilting of the magnetization close to (lY / 2) + p and the duration Tt of the interval corresponds substantially to an angular offset close to C? R / 2) -2p.

According to another variant, the duration t of the pulses corresponds to a tilting of the magnetization close to (072) / (1-2p />) and the duration Tt of the interval between the pulses is such that the angular offset cZ is close to (t / 2) S1-p / 3-pt / (1-2Rrp) 3
Any other combination is possible depending on
The desired result: phase shift strictly zero or less than a certain threshold, shift of the frequency of the maximum signal strictly zero or less than a threshold.

 Finally, in a spin echo embodiment, the duration t of the pulses is chosen such that the tilting of the magnetization is equal to (# / 2) / (1- (2 / #) p-q).

In any case, the characteristics and advantages of the invention will appear better in the light of the description which follows. This description relates to exemplary embodiments given by way of explanation and in no way limitative and it refers to the attached drawings on which
- Figure 1, already described, illustrates a
known excitation sequence, of the type
JR,
FIG. 2, already described, illustrates the
physical phenomena involved in
The known excitation of FIG. 1,
- Figure 3 illustrates the origin of the faults
of the known process and shows how The
method of the invention corrects these defects,
- Figure 4 shows a sequence of excita
tion according to the invention,
- Figure 5 shows the amp variations
study of the electrical signal taken in function
tion of the relative frequency (w / wmax)
for different parameter values
P,
- Figure 6 shows the phase variations
of the electrical signal taken as a function
relative frequency (W / wmax) for
different values of the parameter p.

 In the description which follows, we will take as parameter p describing the amplitude of the radiofrequency field, the ratio between the duration t0 of a pulse which would cause a tilting of 972 of the magnetization of the solvent and the interval Tg corresponding to a precession of> / 2 for the frequency wmax, knowing that this interval is counted between the two front edges of the pulses. Thus, when the power of the field (or, if you want, its amplitude), is infinitely large, t0 is zero and the parameter p is also zero. The parameter p increases when the field is no longer infinitely large. At most p is equal to 1, when t0 is equal to Tg. The parameter p is therefore between O and 1, depending on the more or less weak power of the radiofrequency field applied.

 According to conventional considerations, the duration t0 is equal to t / 2gHrf where vt is The gyromagnetic ratio in question and Tg is equal to t / (2wmax).

 FIG. 3 illustrates the origin of the phase shift and of the amplitude error observed when the amplitude of the excitation radiofrequency field is low and the means of remedying this double defect according to the invention.

 The following description is a first order approximation on p. It always refers to a mobile Oxyz reference frame around the static field Hst directed along Oz and rotating at the frequency W of precession of the nuclear spins of the solvent. The radiofrequency field at frequency W, which constitutes the excitation, is assumed to be applied, as in the prior art, by circulation of a current in a winding with an axis perpendicular to Oz. The precession frequency w of the nuclear spins of the solute is counted from the precession frequency W of the nuclear spins of the solvent.

 The path followed by the spins in the mobile Oxyz coordinate system is represented by the dotted line when it comes to the prior art JR and in solid line when it is a question of the invention.

When the first field (Hrf) 1 is applied according to Ox, the resulting magnetic field, composed with the residual static field directed according to Oz, is directed according to a direction OE1 making an angle p with Ox
(if (Hrf) l were infinite, the resulting field would be directed according to Ox). The application of the first pulse I1 switches the magnetization, not around Ox but around OE1 so that the spins are found in the xOy plane, with a direction making an angle -p with Oy (and no longer the along Oy).

The solute spins precession in
the xOy plane (relative to the spins of the solvent which are directed along Oy).

When the second pulse I2 is applied, with an opposite phase (the field is therefore directed along -Ox), the magnetic result is directed according to
the direction opposite to OE2 which makes an angle -p with
Ox. It is around this direction OE2 that the magnetization switches back (and not rigorously around
Ox).

 If, after the second pulse, the magnetization proper to the solvent has resumed its direction Oz, the spins I of the solute, which are at the relative frequency wmax and which, normally, should have been aligned according to Ox have, in reality, exceeded the xOz plane and are found appreciably in the meridian -p compared to xOz.

 The phase of the spins (or if one wants the phase of the electrical signals that their precession will generate in the detection winding), represented by the projection of the spins in the transverse plane xOy, is therefore not zero. It is -p for spins such as I and it depends linearly on the frequency, in the form -pw / wmax.

 The spins which will lead to a maximum signal are Spins such as J which end their movement in the xOy equatorial plane. Just before the application of the second pulse they had the -p phase. They had therefore undergone an angular offset of precession iÙ2-p-p between the two pulses, while spins such as I had precession of @ 2-p.

 The frequency w 'max (corresponding to the maximum of the signal) is therefore linked to the theoretical frequency Wmax by the relation (W'max-wmax) / wmax = -P (4 / # - l) / (l-p).

 The use of fields with finite amplitude to carry out the excitation thus introduces not only a phase shift proportional to p but also a shift in frequency of the maximum of signal, proportional to p / (1-p).

 FIG. 3 also shows how the invention remedies this double defect. The strong line symbolically shows the path taken by the spins in the excitation process of the invention.

 The pulse sequence (I1 of duration t, interval T, I2 of duration t) is shown in Figure 4.

 According to the invention, the first pulse I1 is elongated. which switches the magnetization under the xOy plane. The tilt angle is substantially p + 5t12 (instead of / 2). The spins of the solute corresponding to wmax then precession in a horizontal plane located under the equatorial plane. The interval T between pulses is shortened so that the angular deviation due to precession is reduced.

After the second pulse, the spins I corresponding to wmax find themselves aligned according to Ox.

 This qualitative description of the invention makes it possible to understand that it is necessary to lengthen t to give the tilting a value greater than # / 2 and, on the contrary, decrease T to reduce the precession below> / 2. Considerations and theoretical calculations which would go beyond the scope of this description recommend a duration t equal to to / (1-2ptit-) and an interval T equal to T0 (1-p / 3).

 But other practical values are possible around these theoretical values.

 Figures 5 and 6 show the results obtained for different values of p, therefore for different amplitudes of the field used. FIG. 5 illustrates the relative amplitude of the electrical measurement signal, plotted on the ordinate as a function of the relative frequency w / wmax for different values of p (p = O / 0.1 / 0.2 / 0.3 / 0, 4). Figure 6 shows the phase of the electrical signal, always as a function of w / wmax for the same values of p.

 In these diagrams, i I was assumed that the duration t of the pulses was to / (1-2p / t) and the duration T of the interval Tg (p-p / 3).

 It can be seen in FIG. 5 that the amplitude variation with w is substantially independent of p over a very wide frequency range, which makes it easy to program the compensation for this variation.

 Figure 6 shows that the phase is almost flat.

 In these FIGS. 5 and 6, the dotted curves correspond to the prior art JR with pulses (t0, To) with a parameter p equal to 0.4.

By comparison with the curves in solid line, one sees how much the regularity of the amplitude is improved and the phase shift reduced thanks to the invention.

 The invention is not limited to the free spin precession mechanism but can also be applied to the so-called spin echo technique. In this case, the width t of the pulses is modified by the introduction of a coefficient q linked to the time delay between echo and excitation pulse.

We will take as pulse width The value t '
t '= t0 (1-2p / -q).

 When the parameter q is much less than 1, the echo appears after a time qT0 after the end of the second pulse.

Claims (5)

 1. Process. excitation of a nuclear magnetic resonance spectrometer allowing the removal of the solvent signal, this process consisting in applying to a solution subjected to a static magnetic field (hast) a radiofrequency magnetic field (Hrf) at the frequency (W) of resonance of the solvent of the solution, this field being applied perpendicular to the static field (hast) in two rectan glar pulses of duration (t) of amplitude (Hrf) and of opposite phases, the rising edges of these pulses being s .pares.es of a duration (T), these pulses causing two opposite tiltings of the magnetization of the solution, the interval (Tt) between two pulses causing a relative angular shift of the nuclear spins of the solute by with respect to the nuclear spins of the solvent, said nuclear spins of the solvent finding, after this excitation, their initial direction parallel to the static magnetic field (hast) and The nuclear spins of the solute being offset angytically from the nuclear spins of the solvent by an amount which depends on the duration (Tt) of the interval between pulses and on their relative frequency of resistance (w), an electrical signal being able then to be taken which will result from the precession of the only nuclear spins of the solute around the static magnetic field (Hst), Which signal will present a maximum amplitude for those of the spins of the solute whose Relative frequency of resonance (wmax) is such that at The end of the excitation their angular offset with respect to the magnetic ~ static field was # / 2, this process being characterized by the fact that the duration  (t) of the two radiofrequency field pulses is such that the two tiltings of the magnetization are greater than # / 2 by a first quantity and that The duration (Tt) of the interval between pulses is such that the angular offset of the spins of the solute of relative frequency (wmax) with respect to the spins of the solvent during the interval between pulses is less than t / 2 by a second quantity , so that at the end of the excitation, all the spins of the solute are located in the same plane defined by the static magnetic field (Hst) and the directipn of application of the radiofrequency field (Ox), which minimizes any phase error in the drawn electrical sign fl, those of the spins of the solute which have the relative frequency (wmax) being still angularly offset by  by comparison with the static magnetic field and leading to a maximum signal, which minimizes any amplitude error in the electrical signal sampled.  2. Method according to claim 1, character ized. By the fact that two differences (t-t0) on the one hand, and (T-To) on the other hand, are expressed as a function of the same parameter (p) equal to the ratio (to / To) between the duration (to) of an amplitude radiofrequency field pulse (Hrf) which would be capable of causing a tilting equal to t / Z, and The duration (To) which corresponds to an angular offset (&alpha;) equal to # / 2 for the relative frequency (wmax) leading to a maximum signal.  3. Method according to claim 2, characterized in that the duration (t) of the pulses corresponds substantially to a tilting of the magnetization close to (# / 2) + p and that the duration (Tt) of the interval corresponds substantially at an angular offset (x) close to (w2) -2p.  4. Method according to claim 2, characterized in that the duration (t) of the pulses corresponds to a tilting of the magnetization close to (# / 2) / (1-2p / #) and in that the duration (Tt) of the interval between the pulses is such that the angular offset (c <) is close to (# / 2) [1-p / 3-pt / (1-2 / # p)].  5. Method according to claim 2, characterized in that, to obtain an operation in spin echo, the duration (t) of the pulses is chosen such that the tilting of the magnetization is equal to # / 2) / (1 - (2 / #) pq).