JPH0968565A - Automatic phase correcting device for nuclear magnetic resonance spectrum - Google Patents

Abstract

PROBLEM TO BE SOLVED: To automatically correct phase shift. SOLUTION: This device has a first phase correcting means 7 for correcting a phase shift by measurement delay, a phase shift by frequency filter, and a phase shift by off resonance, and a second phase correcting means 8 for correcting the constant term of the phase shift. The fist phase correcting means corrects each phase shift to direct observation axis in multi-dimensional nuclear magnetic resonance spectrum to correct the phase shift by measurement delay and the phase shift by off-resonance to indirect observation axis, and the second phase correcting means corrects the phase shift only to indirect observation axis. According to such a structure, the phase shift can be automatically corrected without depending on the eyes of an analyst, or his personal perception or experience.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a nuclear magnetic resonance spectrum automatic phase correction apparatus for correcting a phase shift included in a nuclear magnetic resonance spectrum.

In an NMR (Nuclear Magnetic Resonance) apparatus, a sample to be measured is placed in a static magnetic field, and a high frequency magnetic field having a resonance frequency is radiated in a pulsed manner via a transmitting / receiving coil placed around the sample. As a result, the resonance signal induced in the transmission / reception coil is extracted as a free induction attenuation signal (FID signal). By Fourier transforming this FID signal, N
An MR spectrum is obtained. A one-dimensional (1D) NMR spectrum is represented with the absorption intensity on the vertical axis and the frequency or magnetic field on the horizontal axis.

Multi-dimensional NMR measurement For example, in the two-dimensional NMR measurement, as shown in FIG.
It is performed by irradiating the sample after the on period) t1. The FID signal detected as a result of pulse irradiation is a detection period (detection period).
period) t2 and detected and stored. This measurement is t1
Is changed stepwise and is repeated M times a predetermined number of times. Then, as shown in FIG. 2, the two-dimensional NMR spectrum data S (is obtained by subjecting the aggregate data A (t2, t1) of M FID signals obtained by a series of measurements to the double Fourier transform for t2, t1. F2, F1) is obtained.

The F2 axis of the two-dimensional NMR spectrum shown in FIG. 2 is the axis obtained by Fourier transforming the t2 axis and is called the direct observation axis. The F1 axis is the axis obtained by Fourier transforming the t1 axis and is called the indirect observation axis. .

Although the NMR measurement is performed as described above, it is unavoidable that the obtained NMR spectrum contains a phase shift due to various factors. This phase shift exists not only in the one-dimensional NMR spectrum but also in all observation axes of the two-dimensional or higher-dimensional NMR spectrum. In order to obtain a complete absorption spectrum that can be used for spectrum analysis, it is necessary to correct such a phase shift for all observation axes. For example, in a one-dimensional NMR spectrum, a correction coefficient (first-order term) is given based on the shape of the signal, and the phase shift is corrected by data processing based on the coefficient.

[0006]

However, it is not easy to manually determine the coefficient and perform the phase correction while confirming the spectrum with human eyes as an analyst. Therefore, it requires personal intuition, knowledge, and familiarity.
There is a problem of individual differences. There is also a problem that the correction accuracy cannot be increased by the correction based on the first-order term. Therefore, it has long been desired to correct the phase shifts of multidimensional NMR spectra by computer software without human intervention.

SUMMARY OF THE INVENTION The present invention has been made to solve the above problems, and an object of the present invention is to provide an automatic phase correction apparatus for a nuclear magnetic resonance spectrum which can automatically correct a phase shift. .

[0008]

To this end, the present invention is an automatic phase correction method of a nuclear magnetic resonance spectrum for correcting a phase shift included in the nuclear magnetic resonance spectrum, wherein a frequency ω obtained by measurement is used as a variable. The first phase correction step for correcting the phase shift φd due to the measurement delay, the phase shift φf due to the frequency filter, and the phase shift φo due to off-resonance for the nuclear magnetic resonance spectrum data S (ω) A second phase correction step for correcting the phase shift φc due to the phase difference between the high-frequency carrier wave used for measurement and the detection reference wave for the nuclear magnetic resonance spectrum data corrected It is characterized by.

Further, the automatic nuclear magnetic resonance spectrum phase correcting apparatus for correcting the phase shift included in the nuclear magnetic resonance spectrum of the present invention has the nuclear magnetic resonance spectrum data S (with the frequency ω obtained by the measurement as a variable. ω), the phase shift due to the measurement delay φd, the phase shift due to the frequency filter φf, and the phase shift due to off-resonance φo
And a phase based on the phase difference between the high-frequency carrier wave used for measurement and the detection reference wave with respect to the nuclear magnetic resonance spectrum data corrected by the first correction means. It is characterized in that it is provided with a second phase correcting means for correcting the shift φc.

[0010]

Before explaining the embodiment of the present invention, the phase shift will be described in detail. First, the FID signal and the NMR spectrum are defined as mathematical expressions. FID signal F (t)
Is observed as the sum of signals (waves) that have a phase shift at t = 0 and decay exponentially.

[0011]

[Equation 1] Here, N is the number of signals (waves), Ij is the intensity of the signal j at t = 0, τj is the relaxation constant of the signal j, ωj is the angular frequency of the signal j, and Φj is the phase shift of the signal j at t = 0. Is.

The spectrum S (ω) is obtained by Fourier transforming the equation (1) at t = 0 to T under the condition in which the FID is completely attenuated.

[0013]

[Equation 2] Here, the part Ij {...} is the spectral component of the signal j with no phase shift. Φ j is the phase shift of the signal j, but since the phase shift is a function of frequency, the spectrum is eventually expressed by the following equation.

[0014]

(Equation 3) Here, S ′ (ω) is the true spectrum without phase shift, and the remaining part exp {iΦ (ω)} is the phase shift component.

The above is a study on the one-dimensional NMR spectrum, but the phase shift in the multi-dimensional NMR spectrum is Becomes Here, N is the number of dimensions, i _n is the imaginary number of an axis, and ω
_n is the frequency of some axis.

Looking at, for example, two-dimensional NMR, the phase shifts Φ _F2 (ω) and Φ _F1 (ω) of the respective axes in the direct observation axis F2 and the indirect observation axis F1 are generally Φ _F2 (ω) = Po _F2 + P1 _F2 · ω + P2 _F2 · ω ² + ……… Φ _F1 (ω) = Po _F1 + P1 _F1 · ω + P2 _F1 · ω ² + ……… (5) can be expressed by a polynomial. Where Po, P1, P2,
Is a coefficient of 0th order, 1st order, 2nd order, ... And ω is an angular frequency. If each coefficient of the above equation is obtained, a correction calculation can be performed on the NMR spectrum data to cancel the phase shift.

Here, the present inventor examined the factors of the phase shift included in the NMR spectrum, and as a result, arranged the factors of the phase shift into the following four.

The first factor is the delay in starting the measurement of the FID signal. In the NMR measurement, as shown in FIG. 4, after the pulse irradiation is completed, wait until the distortion at the tail of the pulse becomes small compared to the intensity of the FID signal, and then the FI
The D signal is detected.

The second factor is the frequency filter inserted in the detection circuit. This filter has a phase characteristic, and various frequency components included in the FID signal are affected by this phase characteristic.

The third factor is the off-resonance effect within the pulse period. While the excitation pulse is being applied, the nuclear spins not in the just resonance state (in the off resonance state) are subjected to an effective high frequency magnetic field tilted in the rotating coordinate system. As a result, the phase shift is included in the signal component from the nuclear spin that is not in the just resonance state. Just resonance occurs only in the nuclear spin having a precession motion frequency equal to the frequency of the carrier wave of the pulse.

The fourth factor is the phase difference between the detection reference wave and the carrier wave of the high frequency pulse at the time of detection for detecting the FID signal.

In the case of two-dimensional NMR, the phase shifts due to the above four factors do not occur equally on the F2 axis and the F1 axis. That is, as shown in the table below, the phase shift on the F2 axis is caused by four factors: measurement delay, frequency filter, off-resonance effect, and phase difference between carrier wave and reference wave. On the other hand, the phase shift on the F1 axis is due to two factors: measurement delay and off-resonance effect.

Factors F2 axis F1 axis measurement delay ○ ○ Frequency filter ○ Off-resonance effect ○ ○ Phase difference between carrier wave and reference wave ○ Table 1 Of these factors, measurement delay time, frequency filter,
The off-resonance effect causes only higher order phase shifts as a function of the frequency of the observation axis. In addition, the phase difference between the carrier wave and the reference wave causes a 0th-order phase shift that does not depend on the frequency. Considering these points, the equation (5) can be replaced by the following equation.

[0024] _{Φ F2 (ω F2) = φd} F2 (ω F2) + φf F2 (ω F2) + φo F2 (ω F2) + φc F2 (ω F2) Φ F1 (ω F1) = φd F1 (ω F1) + φo _F1 (ω _F1 ) (6) In equation (6), φd, φf, φo, and φc are the phase shifts caused by the measurement delay, the filter, the off-resonance effect, and the phase difference between the carrier wave and the reference wave. Are shown respectively.

The present invention is characterized in that the phase shifts due to these four factors are divided into a direct observation axis and an indirect observation axis and are appropriately corrected.

[0026]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described below with reference to the drawings. FIG. 3 is a diagram showing an embodiment of an automatic phase correction device for a nuclear magnetic resonance spectrum according to the present invention. In FIG. 3, the NMR measurement unit 1 includes a magnet that generates a static magnetic field, and an NMR probe that houses a sample and a transmission / reception coil arranged around the sample. The sample is irradiated with a predetermined pulse train generated by the pulse output unit 2 via the transmission / reception coil. As a result, the FID signal induced in the transmission / reception coil is the FID detection unit 3 provided with the frequency filter.
Taken out. The extracted FID signal is AD
It is sent to the storage unit 5 via the converter 4 and stored therein. The Fourier transform unit 6 obtains NMR spectrum data by Fourier transforming the FID signal stored in the storage unit 5. The obtained NMR spectrum data is stored in the storage unit 6. The first phase correction unit 7 corrects the phase shift due to the measurement delay when the FID signal is detected for the direct observation axis and the indirect observation axis for the NMR spectrum data stored in the storage unit 5, and the frequency for the direct observation axis. The phase shift is corrected by the filter, and the phase shift is corrected by off-resonance for the direct observation axis and the indirect observation axis. The second phase correction unit 8 obtains and corrects the phase shift caused by the phase difference between the detection reference wave and the carrier wave with respect to the direct observation axis. The observation control unit 9 controls the pulse output unit 2, the FID detection unit 3, the AD conversion unit 4, the Fourier transform unit 6, the first phase correction unit 7, and the second phase correction unit 8. As information for correcting the phase shift, information on the pulse train used for the measurement, information on the pulse width and the observation frequency width, the measurement delay information of the FID detection unit 3, the FID
Information on the filter type and frequency characteristic of the frequency filter in the detection unit 3 is supplied to the first phase correction unit 7.

Next, the operation procedure will be described based on the flow chart shown in FIG. 4 by taking the two-dimensional NMR measurement as an example. First, in step S10, the initial value t1o of t1, the change step Δt of t1, and the number of measurements M are set by the operator, and the current number of measurements N is set to 1. In the next step S11, a pulse train consisting of two pulses generated from the pulse output section 2 at a time t1 (= t1o + N · Δt) as shown in FIG. Is irradiated. Next step S12
In, the FID signal FID1 induced in the transmission / reception coil due to the resonance of the observation nucleus in the sample is detected by the detection unit 3 directly with respect to the observation axis (time axis) t2. Next, in step 13, the obtained FID signal is stored in the NMR data storage unit 5, which is a computer memory, via the AD converter 4. In step S14, it is determined whether N is equal to M, and if not, step S
At 15, N = N + 1 is set and the process returns to step S11.

In this way, until time N = M, time t
While changing 1 in steps, the above steps S11 to S13
Is repeated M times. At the time when N = M and the measurement of M times is completed, the storage unit 5 stores M pieces of F as shown in FIG.
Aggregate data A (t2, t1) in which ID signals are arranged in order of t1 is stored.

After the measurement of M times is completed, the aggregate data A (t2, t1) stored in the storage unit 5 is t2, t1 by the arithmetic unit 6.
The two-dimensional spectral data S (F2, F1) is obtained by performing the double Fourier transform on (S1)
6).

The obtained two-dimensional spectral data S (F2,
For F1), the phase correction by the first correction unit 7 (step 17) and the phase correction by the second correction unit 8 (step 1)
8) is carried out sequentially, so that a pure absorption spectrum is obtained. The step 17 is composed of a step 17-1 for correcting the phase shift φf due to the frequency filter, a step 17-2 for correcting the phase shift φd due to the measurement delay, and a step 17-3 for correcting the phase shift φo due to the off-resonance effect. It On the other hand, step 18 is a phase shift φc due to the phase difference between the detection reference wave and the carrier wave.
Is corrected. Hereinafter, the correction of each phase shift φf, φd, φo by the first correction unit 7 and the correction of the phase shift φc by the second correction unit 8 will be described in detail. [17-1] Correction of Phase Shift φf by Frequency Filter The frequency filter is created based on the design formula in the frequency space, and this design formula is stored in the phase correction unit 7 in advance. Taking a 4-pole Butterworth filter as an analog frequency filter as an example, its design formula is as follows.

[0031]

(Equation 4) Here, Ω _k and Q _k are design constants of the filter, and ω c is a cutoff frequency. The quadrature phase detection method usually used in recent NMR apparatuses allows only angular frequency components in the range of -ωc to ω to pass.

Tf (ω) in the equation (7) is a frequency filter function, and the intensity characteristic of | Tf (ω) | and Tf (ω) / |
It has a phase characteristic of Tf (ω) |.

The following relationship holds between the true spectrum S '(ω) and the spectrum S (ω) passed through the filter. S (ω) = Tf (ω) × S ′ (ω) = {Tf (ω) / | Tf (ω) |} × | Tf (ω) | × S ′ (ω) ... (8) {} is Since it is a term that causes a phase shift, the following equation is derived when compared with the equation (2).

Exp {iφf (ω)} = Tf (ω) / | Tf (ω) | (9) Since Tf (ω) in the equation (9) can be calculated from the equation (6), an arbitrary frequency filter can be calculated. The phase shift at the angular frequency is numerically obtained by the equation (9). Phase shift φ
In order to correct f (ω), it is necessary to rotate the spectrum value S (ω) at the angular frequency ω by −φf (ω), and therefore S1 (ω) = S (ω) [ cos {−φf (ω)} + isin {−φf (ω)} = S (ω) [cos {φf (ω)} − isin {φf (ω)}] (10) Correct the phase shift φf (ω) The obtained spectrum S1 (ω) can be obtained.

In summary, in step 17-1, (6)
The phase shift φf at an arbitrary angular frequency in the observation frequency range of the direct observation axis F2 is simulated based on the filter design equation and the equation (9), and the obtained φf is used to measure based on the equation (10). Obtained spectrum S
(Ω) is corrected.

As the frequency filter, a digital filter is used in combination with an analog filter or is used alone. Even when the digital filter is used alone, the phase shift can be simulated based on the design formula in exactly the same manner as described above, and the obtained φ f is used to obtain the spectrum S.
(Ω) can be corrected. Even when both are used together,
By synthesizing the phase shifts based on the respective design formulas, the phase shifts when used in combination may be simulated. [17-2] Correction of phase shift φd due to measurement delay As described above, a delay time is required between the time origin of the FID signal and the start of detection. If the delay time from the time origin of the FID signal to the start of detection is td and this is reflected in the equation (1),

[0037]

(Equation 5) Becomes The spectrum obtained by Fourier transforming this is

[0038]

(Equation 6) Becomes In Expression (12), ωj td is the phase shift due to the measurement delay time of the signal j. Equation (12) shows that the phase shift due to the measurement delay time depends on the angular frequency of each signal. To completely correct this phase shift, the individual signals must be separated and their phase shifts corrected independently. This signal separation requires an iterative method such as the least squares method, which requires a long calculation time.
Fortunately, the NMR signal is sharp, so it is assumed that there is no problem in replacing ω = ωj. Based on this assumption, the phase shift φd (ω) due to the measurement delay time can be expressed as φd (ω) = ωtd (13). Since td is known as a measurement condition, the phase shift φd (ω) can be numerically obtained. In fact, φd
(ω) is obtained for both F2 and F1 axes, and correction is made for each axis. As the value of td necessary for obtaining φd (ω), the actual measurement delay time can be used for the F2 axis and the initial value of the expansion time t1 can be used for the F1 axis.

In order to correct the obtained phase shifts φd (ω) on the F2 axis and the F1 axis, the spectrum S1 (ω) whose phase shift is corrected by the frequency filter is further rotated by −φd (ω). There is a need. Therefore, the spectrum S2 (ω) in which the phase shift φd (ω) is corrected can be obtained by performing the calculation of S2 (ω) = S1 (ω) {cos (ωtd) −isin (ωtd)} (14) it can.

In short, in step 17-2, the information on the delay time at the time of measurement (for example, the delay time for the F2 axis and the initial value of the development time t1 for the F1 axis) given by the analyst is used, and (13) Based on the equation, the phase shift φd is calculated for the entire observation frequency range, and the calculated φd
Is used to correct the spectrum based on equation (14). [17-3] Phase shift φo due to off-resonance effect
Correction of (ω) As mentioned above, while the excitation pulse is applied, the nuclear spins that are not in the just resonance state (in the off resonance state) are subjected to the effective high frequency magnetic field inclined in the rotating coordinate system. . When a high-frequency pulse of time width τp is applied,
Nuclear spins not in just resonance cause precession due to the inclined effective magnetic field. As a result, the nuclear spins that are not in just resonance have an offset frequency Ω (a frequency used in NMR at Ω = − {ω / 2π} × with respect to an angular frequency).
Has a relationship of Freq. Freq is the observation frequency range. ) Dependent phase shift φo (ω). The phase shift due to this off-resonance effect is

[0041]

(Equation 7) There is a relationship. here,

[0042]

(Equation 8) It is. 90 ° in equations (15), (16) and (17)
Since the pulse width τ 90 and the effective pulse width τ p are known constants, the phase shift φo (ω) is a function of angular frequency. In order to correct the phase shift φo (ω) due to the off-resonance effect, the spectrum S2 (ω) corrected for the phase shift due to the measurement delay time needs to be further rotated by −φo (ω). ω) = S2 (ω) [cos {φo (ω)} − isin {φo (ω)}] (18) The spectrum S3 in which the phase shift φo (ω) due to the off-resonance effect is corrected by performing the calculation (ω) can be obtained. In calculating equation (18), use cos {φo (ω)} and sin {φo (ω)} calculated by equations (15) and (16) without calculating φo (ω). be able to.

Therefore, in step 17-3, based on the information (information such as pulse width) of the pulse sequence used for the measurement given by the analyst, based on the equations (15), (16) and (17). With respect to the F2 and F1 axes, φo is obtained over the observation frequency range, and the obtained φo is used to correct the spectrum based on the equation (18). [18] Correction of phase shift φc (ω) due to the phase difference between the detection reference wave and carrier wave φf, by the correction of [17-1], [17-2], and [17-3] described above,
In the spectrum S3 (ω) in which φd and φo are corrected, only the common phase shift φc remains over the entire observation frequency with respect to the direct observation axis F2.

FIG. 5A is a conceptual diagram in which the locus of the spectrum intensity in the vicinity of one peak (signal) of the NMR spectrum is drawn as a three-dimensional curve L on the frequency-complex space (r, i, ω). is there. Since the magnetization does not resonate in the frequency region away from the peak position ω p, the curve L is on the ω axis as shown in FIG. Then, due to the resonance of the magnetization when passing the peak position ω p, the curve L
Rotates once on the i-r plane passing through ω = ω p. Therefore, when the curve L is projected on the i-r plane (complex plane), FIG.
It becomes circular as shown in (b). In addition, the curve L is ω-r
When projected onto a plane, the spectrum has a normal spectrum with the frequency ω as the horizontal axis, and the spectrum has a pure absorption waveform as shown in FIG. 5D.

At this time, if there is a phase difference between the detection reference wave and the carrier wave, as shown in FIG. 5C, the circle on which the curve L is projected rotates about the ω axis by an angle φc corresponding to the phase difference. Then, what is projected on the ω-r plane shows a peak waveform distorted by the phase shift as shown in FIG.

Rotation angle φ of the circle shown in FIG. 5 (c)
Once c is obtained, the phase S-corrected spectrum S4 (ω) can be obtained by the following arithmetic processing for rotating the entire spectrum by φc in the opposite direction. S4 (ω) = S3 (ω) {cos (φc) −isin (φc)} (19) This φc is shown by enclosing it with a broken line in the discrete data forming the circle in FIG. 5 (c). Origin (i = 0, r =
This can be obtained by selecting only the data including 0) and existing in the region in the vicinity thereof, examining the dispersion direction of the selected data, and determining the slope of the tangent line m of the circle at the origin. The data of the NMR spectrum acquired by the measurement is composed of a large number of data points at predetermined unit frequency intervals, but the data included in the above-mentioned region near the origin is:
It is not the data of the peak portion of the spectrum but the data of the portion without the peak and the tail portion of the peak of the spectrum.

FIG. 6 is a flow chart showing a procedure for carrying out the correction based on such an idea. In FIG. 6, steps 1 and 2 are the steps of selecting the data points on the skirt and the baseline of the signal, and step 3 is the step of finding and correcting φc based on the selected data points.

First, in the procedure 1, the outer product of the vector from the data point i-1 to i and the vector from i to i + 1 in the complex space is considered, and the data point having a positive outer product is selected. Since the contribution of noise is small in the portion where the signal component is dominant, the outer product has a negative value. On the other hand, noise is conspicuous at the tail of the signal and the part of the baseline, and the outer product is either positive or negative. Therefore, if the data points whose outer product is positive are selected, the data points of the signal tail and the baseline are selected.

In the case of multidimensional NMR spectrum data, a plurality of slice data (one-dimensional NMR spectrum data) in the direction of the direct observation axis in which a signal exists is extracted and connected, and the one-dimensional spectrum data obtained by the connection is described above. The data is selected by the cross product.

In the determination by the outer product in the procedure 1, there is a possibility that the data points of the peaks and the overlapping portions of the peaks will be extracted. These data points are noisy for the work in procedure 3. Therefore, in procedure 2, only the data points that are sure to form the signal tail and the baseline are selected. Specifically, for the data points selected in step 1, 1) the average AV and the standard deviation SD of the vector length from the data points i-1 to i are obtained. 2) And
Only data points i whose lengths from the data points i-1 to i and the vectors from i to i + 1 are smaller than AV + 3SD are selected. 3) 1) and 2) are repeated until there are no more data points to be discarded.

FIG. 7 is a diagram showing a process of selecting data points in the procedure 1 and the procedure 2. Procedure 1 in FIG.
All 32,768 points of the raw data before performing are plotted in the i-r plane. In FIG. 7B, the data points of 5435 points remaining after the end of procedure 1 are i-
It is plotted on the r-plane. In FIG. 7C, the procedure 2
The remaining 4661 data points are plotted on the i-r plane in the middle of. In FIG. 7 (d),
After the procedure 2, the remaining 4147 data points are i
-Plotted on the r-plane.

By the procedure 1 and the procedure 2 described above, the data points which are surely the data points forming the tail and the baseline of the signal are selected. Then, in the final procedure 3, the computer performs the determination of φc using the data points selected in the procedures 1 and 2 and the correction calculation processing of the spectrum based on the equation (19) using the obtained φc. . The determination of φc can be performed by a method such as principal component analysis.

FIG. 8 shows an example of an NMR spectrum obtained when the analyst manually gives the 0th and 1st order coefficients to correct the phase and when the automatic phase correction is performed by the present invention. These spectra are water spectra obtained by integrating the frequencies of the carrier wave and the detection reference wave while shifting the frequencies.
In the conventional case of FIG. 8A, since the coefficients are given by focusing on the vicinity of the center of the spectrum, it is conspicuous that the phase shifts at both ends of the spectrum are not corrected. On the other hand, in the spectrum of FIG. 8B obtained by the automatic phase correction according to the present invention, it can be seen that the phase correction is correctly performed over the entire spectrum.

FIG. 9A shows strychnine.
The standard one-dimensional spectrum of ¹ H-NMR measured with respect to (1) and (b) of the same figure respectively show the spectra obtained by subjecting it to automatic phase correction.

In FIG. 10A, the same sample was measured.
Standard one-dimensional spectrum of ¹³ C-NMR, same figure (b)
Respectively show spectra obtained by automatic phase correction according to the present invention.

In FIG. 11A, the same sample was measured.
¹³ C-NMR DEPT135 spectrum, and FIG. 11B shows the spectrum obtained by subjecting it to automatic phase correction according to the present invention.

Each of FIGS. 9 to 11 has a structure according to the present invention.
It shows that the phase correction is correctly performed over the entire region of the dimensional spectrum.

FIG. 12A shows the strychnine (strychn).
ine) was obtained by two-dimensional NMR measurement of DQF-
The COZY spectrum is shown in FIG. 4B, which is the spectrum obtained by automatic phase correction according to the present invention.

FIG. 13A shows a NOESY spectrum obtained by two-dimensional NMR measurement for the same sample, and FIG. 13B shows a spectrum obtained by automatically phase-correcting the NOESY spectrum according to the present invention.

FIG. 14 (a) shows the HSQC spectrum of the same sample obtained by two-dimensional NMR measurement, and FIG. 14 (b) shows the spectrum obtained by automatic phase correction according to the present invention.

12-14, the F2 axis, F1
It shows that the phase correction is accurately performed over the entire area of both axes.

The present invention is not limited to the above embodiment, but various modifications can be made. For example, the correction by the measurement delay, the correction by the frequency filter, and the correction by the off-resonance may be performed in any order, or the procedure may be performed first for only the direct observation axis and then for the indirect observation axis.

Further, the following method is also conceivable for extracting the data points on the skirt of the signal and the baseline when the phase shift caused by the phase difference between the detection reference wave and the carrier wave is corrected. Calculate the mean intensity (y ◆) and standard deviation (σ) and remove data points that fall outside y ◆ + 3σ. The average value (y ◆) and standard deviation (σ) are calculated again for the remaining data points, and the data points that deviate from y ◆ + 3σ are excluded. This operation is repeated until there are no or extremely few data points to be excluded, and the remaining data points are determined as the data points on the tail of the signal and the baseline.

[0064]

As is apparent from the above description, according to the present invention, the phase shift due to the measurement delay, the phase shift due to the frequency filter and the phase shift due to the off-resonance are corrected, and further the constant term of the phase shift is corrected. Therefore, a complete absorption spectrum of a two-dimensional or more-dimensional NMR spectrum can be automatically obtained. Further, since a high-order polynomial with respect to the frequency can be used, even the signal at the end of the spectrum can be phase-corrected neatly.

[Brief description of drawings]

FIG. 1 is a diagram showing examples of pulse trains and FID signals used in two-dimensional NMR measurement.

FIG. 2 is a diagram showing a calculation process for obtaining a two-dimensional NMR spectrum.

FIG. 3 is a diagram showing one embodiment of an automatic phase correction device for a nuclear magnetic resonance spectrum according to the present invention.

FIG. 4 is a flow chart for explaining the operation of the NMR apparatus.

FIG. 5 is a diagram for explaining a phase shift of an NMR spectrum.

FIG. 6 is a flowchart showing an example of a procedure for correcting φc.

FIG. 7 is a diagram showing a process of selecting signal tails and baseline data.

FIG. 8 is a diagram showing an example of an NMR spectrum obtained when an analyst manually gives a coefficient to correct the phase and when the analyzer performs the automatic phase correction.

FIG. 9 is a diagram showing a ¹ H-NMR spectrum measured for strychnine and a spectrum obtained by subjecting it to automatic phase correction according to the present invention.

FIG. 10 is a view showing a standard spectrum of ¹³ C-NMR measured for strychnine and a spectrum obtained by subjecting it to automatic phase correction according to the present invention.

FIG. 11 is a diagram showing a ¹³ C-NMR DEPT135 spectrum measured for strychnine and a spectrum obtained by subjecting it to automatic phase correction according to the present invention.

FIG. 12 is a diagram showing a DQF-COSY spectrum obtained by two-dimensional NMR measurement of strychnine and a spectrum obtained by subjecting it to automatic phase correction.

FIG. 13 is a diagram showing a NOESY spectrum obtained by two-dimensional NMR measurement of strychnine and a spectrum obtained by automatically phase-correcting the NOESY spectrum.

FIG. 14 is a diagram showing an HSQC spectrum obtained by two-dimensional NMR measurement of strychnine and a spectrum obtained by automatically phase-correcting the HSQC spectrum according to the present invention.

[Explanation of symbols]

 1 ... NMR measurement unit 2 ... Pulse output unit 3 ... FID detection unit 4 ... A / D conversion unit 5 ... Fourier transformation unit 6 ... NMR data storage unit 7 ... First phase correction unit 8 ... Second phase correction unit 9 ... NMR observation control unit

Claims (7)

[Claims] 1. An automatic phase correction device for a nuclear magnetic resonance spectrum for correcting a phase shift included in a nuclear magnetic resonance spectrum, wherein the nuclear magnetic resonance spectrum data S (ω) has a frequency ω obtained by measurement as a variable. ) For correcting the phase shift φd due to the measurement delay, the phase shift φf due to the frequency filter, and the phase shift φo due to the off-resonance, and the nucleus corrected by the first phase correcting means. The nuclear magnetic resonance spectrum of the present invention is characterized in that the magnetic resonance spectrum data is provided with a second phase correcting means for correcting the phase shift φc due to the phase difference between the high frequency carrier wave used for measurement and the detection reference wave. Automatic phase correction device. 2. The nuclear magnetic resonance spectrum data S
(Ω) is multidimensional nuclear magnetic resonance spectrum data having a direct observation axis and an indirect observation axis. The phase shift φd due to measurement delay and the phase shift φo due to off-resonance are corrected for the direct observation axis and the indirect observation axis. , The phase shift φf due to the frequency filter and the phase shift φc due to the phase difference between the high-frequency carrier wave used for measurement and the detected reference wave.
2. The automatic phase correction apparatus for nuclear magnetic resonance spectrum according to claim 1, wherein the correction is performed only on the direct observation axis. 3. The correction of the phase shift φd due to the measurement delay is S (ω) {cos (ωtd) − based on the delay time td given according to the pulse sequence used for the measurement.
3. The automatic phase correction apparatus for the nuclear magnetic resonance spectrum according to claim 1, wherein the automatic phase correction apparatus is performed by the calculation of isin (ωtd)}. 4. The correction of the phase shift φf by the frequency filter is based on the design formula of the frequency filter used for the measurement, and the phase shift φf is over the observed frequency range.
Is calculated, and S (ω) [cos {φf is calculated based on the calculated φf.
(ω)}-isin {φf (ω)}]. The automatic phase correction apparatus for nuclear magnetic resonance spectrum according to any one of claims 1 to 3, wherein 5. The phase shift φ due to the off-resonance
The correction of o is performed by S (ω) using φo calculated based on the pulse width and effective pulse width of the pulse used for measurement.
The nuclear magnetic resonance spectrum automatic phase correction apparatus according to any one of claims 1 to 4, wherein the automatic phase correction apparatus for nuclear magnetic resonance spectrum is performed by a calculation of [cos {φo (ω)}-isin {φo (ω)}]. 6. The correction of the phase shift φc due to the phase difference between the high-frequency carrier wave and the detection reference wave is performed from the nuclear magnetic resonance spectrum data S (ω) to the data at the tail of the nuclear magnetic resonance signal and the portion at the baseline. The step of selecting the data, the step of determining φc by determining the direction of dispersion of the data based on the selected data, and the determined φ
6. The method according to claim 1, wherein the calculation is carried out by the step of calculating S (ω) {cos (φc) −isin (φc)} using c.
5. An automatic phase correction device for nuclear magnetic resonance spectrum according to any one of 1. 7. The nuclear magnetic resonance spectrum data S
The step of selecting the data of the skirt portion of the nuclear magnetic resonance signal and the data of the baseline portion from (ω) includes the vector from data point i-1 to i and the vector from i to i + 1 for any data point i. 7. The automatic phase correction apparatus for a nuclear magnetic resonance spectrum according to claim 6, wherein a data point having a positive vector cross product is selected.