JP2009162587A - Measuring instrument and measurement method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide techniques for stably acquiring a local echo signal arising from a protic solvent in a sample using NMR method, and further, for measuring the amount of the protic solvent with high accuracy. <P>SOLUTION: This instrument for measuring a local echo signal, arising from the protic solvent at a specific point in the sample by using the nuclear magnetic resonance method, is equipped with a static magnetic field applying part for applying a static magnetic field to the sample, a static magnetic field intensity control part for controlling the intensity of the magnetic field applied to the sample, and an RF coil for applying a vibrating magnetic field for excitation, to a part of the sample, while acquiring an echo signal corresponding to the magnetic field for excitation. A static magnetic field intensity control means causes the applying part to thereto apply a static magnetic field of a prescribed gradient magnetic field strength variation ΔG, expressed by means of an expression: 400≥D [m]×ΔG [gauss/m]×γ [Hz/T]×10<SP>-4</SP>[T/gauss]×τ [sec]≥4, using the inside diameter D of the RF coil, the magnetic field strength variation ΔG, the nuclear magnetogyric ratio γ of the protic solvent, and an excitation interval τ. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a measuring device and a measuring method for measuring an echo signal generated from a protic solvent using a nuclear magnetic resonance method, a measuring device for calculating the amount of a protic solvent using the intensity of the measured echo signal, and It relates to the measurement method.

With regard to this type of technology, the following Patent Document 1 discloses a technology for measuring a local echo signal generated from a protic solvent at a specific location in a sample, and a technology for measuring the amount of the protic solvent using this. The ones described are known. This document describes an invention relating to a measuring device that applies an RF pulse locally to a specific location in a sample by a small RF coil and obtains an echo signal corresponding thereto. In this apparatus, the amount of protic solvent is measured by calculating a T ₂ relaxation time constant based on the acquired echo signal. According to this technique, it is said that the local protic solvent amount at a specific location in a substance can be measured in a relatively short time by using the NMR measurement result.

In the measurement of the echo signal and the measurement of the amount of the protic solvent using the conventional nuclear magnetic resonance method exemplified above, any method such as a magnetic field application device (permanent magnet, electromagnet, superconducting magnet) is used for the small RF coil. However, it is possible to obtain an echo signal generated from the sample by applying an excitation oscillating magnetic field by the coil while applying a uniform static magnetic field.
Conventionally, in order to apply a uniform static magnetic field as much as possible to a sufficient region including the winding diameter of the RF coil, a passive shim such as an iron piece or an active shim such as a shim coil is used, resulting from the sample itself or a building. A technique for canceling the disturbance of the static magnetic field is used (see, for example, Non-Patent Document 1 below). Note that the time constant representing the attenuation rate of the FID signal due to the disturbance of the static magnetic field caused by the sample itself is referred to as T ₂ ^* relaxation time constant.
A shim coil refers to a coil that is arranged around an RF coil and forms a desired magnetic field distribution by passing a current. In the conventional NMR measurement, a measurer adjusts the current applied to the shim coil for adjusting the static magnetic field while watching the FID signal so that the uniformity of the static magnetic field is maximized.

  In addition, as a related technology using shim coils, a gradient magnetic field that loads a gradient magnetic field much smaller than a static magnetic field applied by a permanent magnet to decipher spatial information from received echo signals and limit the spatial position. A coil is known (see Non-Patent Document 2 below).

JP 2007-121037 A "MRI Lecture MRI Learning from the Basics", Educational Committee, Japan Magnetic Resonance Medical Society, pp 112-113 (published first on August 1, 2001) “MRI Lecture Power Text From Basic Theory to High-Speed Imaging”, Medical Science International, pp 28-29 (issued June 1, 1999)

In the measurement of protic solvents using the conventional nuclear magnetic resonance method (NMR method), the relative uniformity of the static magnetic field provided by the permanent magnet can be obtained by localizing the measurement region using a small RF coil. It has been considered that the variation in measurement value is improved and the stability of measurement is improved. The reason for this is that if the uniformity of the static magnetic field applied to the measurement area is improved, the phase of the magnetization vector in the sample will be aligned, and a stronger free induction decay (FID) signal or echo compared to noise. This is because it has been considered that the signal can be acquired, and as a result, the signal intensity is stabilized and the stability of the measurement amount is improved.
However, as a result of studies by the present inventors, it is not always possible to adjust the uniformity of the static magnetic field to the maximum as in a conventional NMR apparatus, and a good measurement result is obtained. When measuring the organic solvent, it became clear that stable measurement values could not be obtained by improving the uniformity of the static magnetic field.

Specifically, in the conventional measurement of the echo signal, the FID signal acquired by the RF coil interferes with the echo signal, and the intensity of the acquired echo signal is unstable. There has been a problem that the value of the T ₂ relaxation time constant calculated based on the intensity of the echo signal varies greatly.

  The present invention has been made in view of the above problems, and can stably acquire a local echo signal generated from a protic solvent in a sample using an NMR method, and can accurately determine the amount of the protic solvent. The technology to measure is provided.

  According to the study by the present inventors in solving the above problems, the cause of the instability of the echo signal is that when the magnetization vector of protons in the sample is excited with a small RF coil, the excitation intensity distribution is spatially uniform. Therefore, it is considered that the FID signal appears strong and long after irradiation with the excitation pulse, and this interferes with an echo signal necessary as a measurement value.

  FIG. 56 is an example of a distribution diagram of the magnetic field intensity Hz (xp, yp, zp) in the z direction of the oscillating magnetic field intensity when a single-turn small surface coil is used as an example of a small RF coil. As shown in the figure, it can be seen that the oscillating magnetic field strength is spatially nonuniform in the small surface coil. As a result of this non-uniformity, the magnetization vector in the sample is not excited to 180 ° in all regions even when irradiated with the 180 ° excitation pulse, and the FID signal is strong and long after irradiation with the 180 ° excitation pulse. It is thought that it is done. This is the difference between the RF coil used in the conventional large NMR apparatus and the small surface coil.

  On the other hand, FIG. 57 is a conceptual diagram showing a FID signal observed when a sample is measured with a small RF coil using a pulse sequence of the conventional CPMG method, and a state in which an FID signal and an echo signal interfere with each other. . As described above, when the decay time of the FID signal that appears after irradiation of the 180 ° excitation pulse becomes long, a corresponding echo signal is generated before both are sufficiently attenuated, and both interfere with each other.

  Thus, when the measurement region of the RF coil is small, the uniformity of the static magnetic field is remarkably increased as compared with the conventional large-scale NMR measurement for a human body or the like. As a result, the decay time of the FID signal after the excitation pulse irradiation becomes long, and the next excitation pulse is irradiated before the FID signal sufficiently attenuates, so that interference occurs in the echo signal.

  Then, the inventors of the present invention adjust the static magnetic field applied to the RF coil so as to give an appropriate non-uniformity so that the FID signal does not interfere with the echo signal. I came up with the knowledge that acquisition would be possible.

That is, as shown in the conceptual diagram of the present invention in FIG. 1, in order to stably acquire the echo signal while avoiding interference between the FID signal and the echo signal, the static magnetic field applied to the sample is intentionally nonuniform. Thus, the FID signal may be attenuated quickly. The more uniform the static magnetic field, the faster the FID signal decays and the shorter the T ₂ ^* relaxation time constant. As shown in the figure, interference between the FID signal and the echo signal can be avoided by sufficiently attenuating the FID signal after irradiation of the 90 ° excitation pulse and the 180 ° excitation pulse at regular intervals. That is, the present invention has been made on the basis of the technical idea of improving the stability of echo signal and proton measurement by applying a static magnetic field formed intentionally inhomogeneously to a sample.

From the above, the measuring device of the present invention is
An apparatus for measuring a local echo signal generated from a protic solvent at a specific location in a sample using a nuclear magnetic resonance method,
A static magnetic field applying means for applying a static magnetic field to the sample;
Static magnetic field strength control means for controlling the strength of the static magnetic field applied to the sample;
An RF coil that applies an excitation oscillating magnetic field to a part of the sample and acquires an echo signal corresponding to the excitation oscillating magnetic field;
With
The static magnetic field strength control means includes an inner diameter (D [m]) of the RF coil, a gradient magnetic field strength variation (ΔG [gauss / m]), and a nuclear magnetorotation ratio (γ [Hz / T] of the protic solvent. ), And applying the static magnetic field of the predetermined gradient magnetic field intensity change amount (ΔG) represented by the following formula (3) from the static magnetic field applying means using the excitation interval (τ [sec]). To do.
400 ≧ D [m] · ΔG [gauss / m] · γ [Hz / T] · 10 ⁻⁴ [T / gauss] · τ [sec] ≧ 4 (3)

  The measuring device of the present invention may further include a solvent amount calculating means for calculating the amount of the protic solvent at a specific location of the sample from the intensity of the acquired echo signal.

Moreover, the measurement method of the present invention includes
A method of measuring a local echo signal generated from a protic solvent at a specific location in a sample using a nuclear magnetic resonance method,
RF coil inner diameter (D [m]), gradient magnetic field strength change (ΔG [gauss / m]), nuclear magnetic rotation ratio (γ [Hz / T]) of the protic solvent, excitation Applying a static magnetic field of the predetermined gradient magnetic field strength change amount (ΔG) expressed by the above formula (3) using the interval (τ [sec]), the RF coil is used to apply a part of the sample. A measurement step of applying an oscillating magnetic field for excitation once or a plurality of times and measuring an echo signal corresponding to the oscillating magnetic field for excitation;
including.

Further, in the measurement method of the present invention, from the intensity of one or a plurality of echo signals measured in the measurement step, a calculation step of calculating the amount of the protic solvent at a specific location of the sample,
May be further included.

Here, in the present specification, the static magnetic field may not be a completely stable magnetic field as long as it is a temporally stable magnetic field capable of stably acquiring a nuclear magnetic resonance signal. There may be some variation within the range.
In particular, the gradient magnetic field controlled by the static magnetic field intensity control means does not necessarily have to be loaded with a stable intensity during the entire measurement time during the application of the oscillating magnetic field for excitation by the RF coil and the acquisition of the echo signal. It may vary within the range. Specifically, the FID signal may be attenuated by applying the predetermined gradient magnetic field only during the application of the 180 ° excitation pulse and for a predetermined time before and after that.

  The excitation interval τ is the time from the 90 ° excitation pulse to the next 180 ° excitation pulse. The time from the application of the 180 ° excitation pulse to the peak of the corresponding echo signal is also equal to the excitation interval τ.

  In the present specification, the protic solvent refers to a solvent that dissociates itself and generates protons. Examples of the protic solvent include water, alcohols such as methanol and ethanol, carboxylic acids such as acetic acid, phenol, and liquid ammonia. Of these, water and alcohols can more stably measure the amount of solvent according to the present invention.

  According to the measurement apparatus and the measurement method of the present invention, by applying a predetermined gradient strength to the static magnetic field applied to a sample containing a protic solvent, attenuation of the FID signal after excitation pulse irradiation is promoted. For this reason, the echo signal corresponding to the excitation pulse and the FID signal do not interfere with each other. As a result, the echo signal is stably acquired, and the amount of the protic solvent calculated based on the intensity of the echo signal is obtained with high accuracy.

  First, an overview of the method of the present invention, in which a local echo signal generated from a protic solvent at a specific location in a sample is measured using an NMR method, and the amount of the protic solvent is measured based on the measured echo signal Will be explained.

  In the measurement method of the present embodiment, first, with respect to the sample, the inner diameter of the RF coil (D [m]), the gradient magnetic field strength change amount (ΔG [gauss / m]), the nuclear magnetic rotation ratio (γ of the protic solvent) [Hz / T]) and excitation interval (τ [sec]) using an RF coil while applying a static magnetic field of a predetermined gradient magnetic field strength change amount (ΔG) represented by the above formula (3). An excitation vibration magnetic field is applied to a part of the sample once or a plurality of times, and a measurement step is performed to measure an echo signal corresponding to the excitation vibration magnetic field.

  Then, in the measurement method of the present embodiment, a calculation step for calculating the amount of the protic solvent at a specific location of the sample is performed from the intensity of one or a plurality of echo signals measured in the measurement step.

Next, the measurement method of this embodiment will be described in detail.
The measurement method of the present embodiment measures a local echo signal generated from a protic solvent at a specific location of a sample using a nuclear magnetic resonance (NMR) method. In the NMR method, the motion of nuclear magnetization can be detected as an NMR signal by the spin resonance phenomenon of a nucleus placed in a static magnetic field.
As an RF coil that applies an oscillating magnetic field for excitation and acquires an echo signal, a small surface coil in which a conducting wire is wound in a plane smaller than a static magnetic field region or a sample in a plane is used. In contrast, local NMR measurement is possible. Therefore, in the following embodiments, a small surface coil is used as the RF coil.

Here, water will be exemplified as the protic solvent, that is, a method for measuring the amount of water in the sample will be described. Note that the moisture amount measurement mode according to the present embodiment may be referred to as a first measurement mode.
FIG. 2 is a flowchart showing an outline of moisture content measurement.

<Measurement step>
First, a sample containing moisture is placed in a space where a permanent magnet is placed, and a static magnetic field is applied to the sample (S102). The static magnetic field applied in the present embodiment is a gradient magnetic field, and the attenuation of the FID signal is promoted by controlling the static magnetic field nonuniformly by such a gradient. The meaning of the above formula (3) indicating a suitable gradient magnetic field strength (D · ΔG [gauss]) and gradient magnetic field strength change amount (ΔG [gauss / m]) will be described later.

  In this state, the excitation oscillating magnetic field (high frequency pulse) is sequentially applied to the sample through the RF coil a plurality of times, and the corresponding NMR signals (echo signals) are acquired (S104).

<Calculation step>
Next, a T ₂ relaxation time constant is calculated from this echo signal (S106). Then, the local water content in the sample is measured from the obtained T ₂ relaxation time constant (S108). Specifically, test data indicating the correlation between the amount of water in the sample and the T ₂ relaxation time constant is acquired in advance, and from this test data and the calculated T ₂ relaxation time constant, It is possible to determine the local water content at a specific location. The format of the test data is various. For example, a conversion table in which the T ₂ relaxation time constant and the amount of water are associated in a table format, or a function representing an approximate curve obtained by the least square method or the like may be used.

Hereinafter, step 104 to step 108 will be specifically described.
(I) Step 104 (Application of excitation high-frequency pulse and acquisition of NMR signal)
The excitation high frequency pulse in step 104 is preferably a pulse sequence composed of a plurality of pulses, and an echo signal group corresponding to the pulse sequence is acquired. By doing so, the T ₂ relaxation time constant can be accurately obtained.

The pulse sequence preferably includes the following (a), (b) and (c) (see FIG. 1).
(A): 90 ° pulse, and
(B): 180 ° pulse applied after the excitation interval τ has elapsed from the pulse of (a),
(C): n 180 ° pulses (n is a natural number) that starts after 2τ has elapsed from the pulse of (b) and is continuously applied at intervals of time 2τ.

  By applying the excitation oscillating magnetic field according to the pulse sequences (a) to (c) above, the phase of the echo signal converges, and the measurement error due to the non-uniform magnetic field caused by the sample or the measurement device is effectively reduced. The In addition, since the variation in the phase of the corresponding echo signal can be suppressed, the amount of moisture can be obtained more accurately.

  A hydrogen nucleus placed in a static magnetic field has a net magnetization vector in a direction along the static magnetic field (for convenience, the Z direction), and an RF wave having a specific frequency (referred to as a resonance frequency) is transmitted along the Z axis. By irradiating from the outside in the X-axis direction perpendicular to the magnetic field, the magnetization vector is tilted in the positive direction of the Y-axis, and a nuclear magnetic resonance signal (referred to as NMR signal) can be observed. At this time, the excitation pulse in the X-axis direction irradiated to acquire the maximum intensity NMR signal is referred to as a 90 ° pulse. Then, after the magnetization vector is tilted in the positive direction of the Y axis by the 90 ° pulse, a 180 ° excitation pulse is irradiated from the outside in the “Y axis direction” after τ time, and the magnetization vector is set to “Y axis as the symmetry axis”. "Invert. As a result, after 2τ time, the magnetization vector converges on the “positive direction” of the Y axis, and an NMR signal having a large amplitude is observed.

  Further, in (c) above, after 3τ time has elapsed from the 90 ° pulse irradiation, the magnetization vector is irradiated with the 180 ° excitation pulse from the outside in the “Y-axis direction” and again on the “positive direction” of the Y-axis. After convergence, an echo signal having a large amplitude is observed after the elapse of 4τ. Further, irradiation with 180 ° pulses is continued at the same 2τ interval.

(Ii) Step 106 (calculation of T ₂ relaxation time constant)
The T ₂ relaxation time constant can be measured by, for example, the method described in Patent Document 1. Specifically, by fitting a plurality of echo signal groups (2τ, 4τ, 6τ,...) On the T ₂ attenuation curve acquired in step 104 with an exponential function, the above equation (A) is obtained. T ₂ relaxation time constant can be determined.

In the pulse sequence of (a) to (c) above, if the 90 ° pulse is set to the first phase and the 180 ° pulse is set to the second phase shifted by 90 ° from the first phase, the T ₂ relaxation time constant and the sample It is possible to stably acquire a clear correlation with the amount of moisture in the medium. The CPMG method is an example of a method for providing such a pulse sequence. As way of giving the T ₂ relaxation time constant used to measure the T ₂ relaxation time constant, Hahn echo method is known. Any of these may be used in the present invention, but the peak intensity of the even-numbered echo signals of 2τ, 4τ, 6τ,... Is extracted by the CPMG method, and fitted with an exponential function to reduce T ₂ (lateral). It is good to calculate the time constant. Thereby, even when there is non-uniformity of the static magnetic field and non-uniformity of the excitation pulse intensity irradiated by the RF coil, there is an advantage that it can be compensated and an accurate T ₂ relaxation time constant can be measured.

(Iii) Step 108 (calculation of water content)
Returning to FIG. 2, in step 108, the water content is calculated from the T ₂ relaxation time constant. The amount of water in the sample and the T ₂ relaxation time constant have a positive correlation, and the T ₂ relaxation time constant increases as the amount of water increases. Since this correlation varies depending on the type and form of the sample, it is preferable to prepare test data for a sample of the same type as the measurement target sample whose moisture concentration is known. That is, the water content of the relationship between water content and the T ₂ relaxation time constant was measured for a plurality of known standard samples, and stored in the storage device in advance for data of a calibration curve representing this relationship as a table or a function Keep it. At the time of measurement, the stored test data is retrieved and acquired, and the moisture content in the sample can be calculated from this and the measured value of the calculated T ₂ relaxation time constant.

Note that, in the calculation step, in the measurement method according to the present embodiment in which the echo signal can be stably measured, the moisture content may be directly obtained from the intensity of the echo signal without calculating the T ₂ relaxation time constant. In other words, step 106 is optional in the calculation step.
When obtaining the moisture content in the sample from the echo signal intensity, it is preferable to measure in advance test data indicating the correlation between the moisture content in the sample and the echo signal intensity and store it in a storage device. At the time of measurement, the stored test data can be called up and acquired, and the local water content at a specific location in the sample can be obtained from this and the calculated echo signal intensity.
When the moisture content in the sample is directly converted from the echo signal intensity without using the T ₂ relaxation time constant, if the S / N ratio of the echo signal is good, the moisture content is obtained from only one echo signal. It is also possible to ask for it.

  Thereafter, the result is output (S110). By performing the above procedure (step 104 to step 110) via a small RF coil, the local water content in the sample can be grasped.

<Setting of gradient magnetic field strength change amount (ΔG [gauss / m])>
The above formula (3), which is a preferable range of the static magnetic field (gradient magnetic field) applied to the sample in the measurement apparatus and measurement method of the present invention, is listed below.
400 ≧ D [m] · ΔG [gauss / m] · γ [Hz / T] · 10 ⁻⁴ [T / gauss] · τ [sec] ≧ 4

Here, the nuclear gyromagnetic ratio (γ [Hz / T]) of the protic solvent is a constant unique to the nuclide, and in the case of the protic solvent ( ¹ H) to be measured, 42.6 · 10 ⁶ [Hz / T].
The excitation interval (τ [sec]) can be arbitrarily set by the measurer. When a solution is a measurement target as in the present embodiment, τ is preferably 0.1 msec or more and 100 msec or less. If τ is excessively large, the excited magnetization vector is dispersed too much, resulting in insufficient convergence, and the intensity of the acquired echo signal is reduced. On the other hand, if τ is too small, the number of excitation pulses to be irradiated in a short time increases and the load on the apparatus increases, and the load on the measuring apparatus such as extraction processing and arithmetic processing for a large number of echo signals becomes excessive.
Hereinafter, in this embodiment, τ = 10 ⁻² [sec] = 10 [msec] unless otherwise specified.

Returning to FIG. 1, the meaning of the lower limit (right side) of the above equation (3) will be described. In FIG. 1, the excitation interval τ from the 90 ° pulse irradiation to the 180 ° pulse irradiation also corresponds to the time from the 180 ° pulse irradiation until the intensity of the echo signal corresponding to this becomes the highest.
Here, paying attention to the 180 ° excitation pulse (1), the FID signal that appears at the time of irradiation (time τ) has a time of τ / 2 after the pulse irradiation as shown in FIG. When attenuated to substantially zero intensity (by 5τ), it is believed that interference with the corresponding echo signal is better avoided. The echo signal is generated at around time 1.5τ, and the intensity peaks at time 2τ.

FIG. 3 is a conceptual diagram of the phase difference of the nuclear magnetization vectors. The thick line shows the intensity distribution of the small surface coil and the static magnetic field H applied to the inside thereof. The static magnetic field is given as a gradient magnetic field. The means for forming the gradient magnetic field is not particularly limited, but here the gradient magnetic field is formed by the sum of the static magnetic field H ₀ applied by the permanent magnet and the constant gradient magnetic field applied by the gradient coil. Shall.
In the measurement region inside the winding diameter of the small surface coil, a phase is generated in the nuclear magnetization vector due to the difference in the magnetic field strength, thereby promoting the attenuation of the FID signal. Specifically, it is considered that the nuclear magnetization vector is sufficiently dispersed by giving a phase of at least 2π [rad] at the position of the inner diameter D (radius D / 2) farthest from the coil center. Therefore, at both ends of the diameter where the phase within the coil has the largest difference, at least ± 2π [rad], that is, 4π [rad], is mutually phased during the time of τ / 2 when the FID signal is desired to be sufficiently attenuated. By giving non-uniformity to the static magnetic field so that they are shifted, good attenuation of the FID signal can be obtained.

On the other hand, the nuclear gyromagnetic ratio of proton ¹ H is γ [Hz / T] = γ · 10 ⁻⁴ [(gauss · sec) ⁻¹ ] = 42.6 · 10 ² [(gauss · sec) ⁻¹ ]. . Therefore, the rotational angular frequency Δω obtained by multiplying this by the gradient magnetic field strength D · ΔG [gauss] is
Δω = D · ΔG · 2π · γ · 10 ⁻⁴ [rad / sec] (4)
It is expressed. This rotational angular frequency Δω is a difference in rotational angular frequency of the nuclear magnetization vector under a condition in which a difference in static magnetic field strength is applied between both ends of the coil inner diameter D serving as a measurement region.

When the nuclear magnetization vector having this rotational angular frequency generates a phase difference of at least 4π [rad] at both ends of the coil during time τ / 2 [sec], the FID signal is sufficiently attenuated as described above. Because it is thought that
D · ΔG · 2π · γ · 10 ⁻⁴ · τ / 2 ≧ 4π (5)
It is established.

When the above equation (5) is transformed,
D · ΔG [gauss] · γ [Hz / T] · 10 ⁻⁴ [T / gauss] · τ [sec] ≧ 4 (6)
This is the right side of the above equation (3).

A preferable lower limit value of the gradient magnetic field strength (D · ΔG) in the measurement is determined from the above equation (6), the nuclear magnetic rotation ratio (γ) of proton ¹ H and the excitation interval (τ) set by the operator. The

Specifically, when τ = 10 ⁻² [sec], in the measurement of the echo signal of the protic solvent and the calculation of the amount of the protic solvent based thereon, D · ΔG ≧ 0.094 from the above equation (6). ≒ 0.1 [gauss] (7)
It becomes.
Therefore, a lower limit value of a range of a suitable gradient magnetic field intensity change amount (ΔG [gauss / m]) to be applied to the sample is determined according to the inner diameter (D [m]) of the small surface coil used for measurement.

  On the other hand, when the gradient magnetic field strength of the static magnetic field applied to the small surface coil is increased, the attenuation of the FID signal is further promoted to reduce the variation of the measured echo signal, but the dispersion of the magnetization vector phase is increased. The absolute value of the measured echo signal also becomes smaller. This is because the water molecules being measured move randomly in the sample due to Brownian motion and move to different static magnetic field regions, so that the phase convergence function of the spin echo does not work sufficiently. It is. Therefore, when the gradient magnetic field strength is excessive, for example, when measuring the time change of the amount of protic solvent, the error weight with respect to the absolute value of the measurement value becomes high, so the change amount must be accurately tracked. It becomes difficult.

  Specifically, if the value is up to about 100 times the lower limit obtained by the above formula (6), the absolute value of the measured echo signal is not excessively small, and the time change of the protic solvent is practical. Can be calculated at various levels. Thereby, the left side of the above equation (3) is determined.

In the present embodiment where the excitation interval τ = 10 ⁻² [sec],
10 [gauss] ≧ D · ΔG (8)
Is set.
Therefore, from the above formulas (7) and (8), the preferred range of the gradient magnetic field strength of the static magnetic field applied to the sample from the static magnetic field application unit 150 in this embodiment is
10 ≧ D · ΔG [gauss] ≧ 0.1 (9)
Is set.

In the above formula (3), the upper limit value of the left side is set to 50 times the lower limit value of the right side, that is, 200 ≧ D [m] · ΔG [gauss / m] · γ [Hz / T] · 10 ⁻⁴ [T / Gauss] · τ [sec] (10)
In particular, when measuring a change in the amount of the protic solvent with time, an error in the measurement value can be suppressed to a practical level.

<About measuring device>
FIG. 4 is a hardware configuration diagram illustrating an example of a schematic configuration of the measurement apparatus 10 of the present embodiment. FIG. 5 is a functional block diagram of the measuring apparatus 10 of the present embodiment.
Each component of the measuring device 10 is realized by an arbitrary combination of hardware and software, centering on a CPU, a memory, a program that implements the components shown in FIG. It will be understood by those skilled in the art that there are various modifications to the implementation method and apparatus.
Note that a part of FIG. 4 shows functional units instead of hardware units.

The measuring device 10 is a device that measures a local echo signal generated from a protic solvent at a specific location in a sample using a nuclear magnetic resonance method. The measuring apparatus 10 includes a static magnetic field application unit 150 that applies a static magnetic field H ₀ to the sample 115 and a static magnetic field intensity control unit (control unit) 307 that controls the strength of the static magnetic field H ₀ applied to the sample 115. And. In addition, the measurement apparatus 10 includes a small RF coil 114 that applies an excitation oscillating magnetic field (180 ° pulse) to a part of the sample 115 and acquires an echo signal corresponding to the excitation oscillating magnetic field.
In the measurement apparatus 10, the control unit 307 causes the static magnetic field application unit 150 to apply a static magnetic field having a predetermined gradient magnetic field strength change amount (ΔG) expressed by the above formula (9) to the sample 115.

In addition, the measurement apparatus 10 of the present embodiment further includes a solvent amount calculation unit (calculation unit) 130 that calculates the amount of the protic solvent at a specific location of the sample 115 from the intensity of the acquired echo signal.
The computing unit 130 calculates a local water content in the sample based on the acquired echo signal. As described above, the processing method in the specific calculation step (see FIG. 2) can be roughly divided into two methods. One is a method in which the T ₂ relaxation time constant is calculated from the intensity of the echo signal, and this value is converted into the amount of water, and the other is a method in which the intensity of the echo signal is directly converted into the amount of water.

  According to the measuring apparatus 10 of the present embodiment, it is possible to evaluate the permeation characteristics of the protic solvent in the solid polymer electrolyte membrane (PEM). More specifically, the measuring device 10 can be used as a device for evaluating the crossover characteristics of a solid polymer electrolyte membrane of a fuel cell.

Hereinafter, the configuration of the measuring apparatus 10 will be described in detail.
The measuring apparatus 10 includes an RF oscillator 102, a modulator 104, an RF amplifier 106, a preamplifier 112, a detector, in addition to the small RF coil 114, the permanent magnet 113, the static magnetic field adjustment shim coil 151, the control unit 307, and the calculation unit 130 described above. 301, an A / D converter 118, a switch unit 161, a time measuring unit 128, a sequence table 127, an operation signal receiving unit 129, a data receiving unit 131, a current driving power source 159, a storage unit 305, an output unit 135, and the like.

The sample 115 has a configuration in which a protic solvent (water in this embodiment) is held in a sample to be measured. The sample constituting the sample 115 can be in various forms such as a film, a solid such as a massive substance, a liquid, a gel such as a jelly-like substance such as an agar gel. In the case of a membranous substance, the measurement result of the local protic solvent amount can be stably obtained. In particular, when a film having a property of retaining moisture in the film, such as a solid electrolyte film, is used as a sample, the measurement result can be obtained more stably.
The sample mounting table 116 is a table on which the sample 115 is mounted, and a sample having a predetermined shape and material can be used.

  The static magnetic field application unit 150 of the present embodiment is a combination of a permanent magnet 113 that is a uniform magnetic field application unit and a static magnetic field adjustment shim coil 151 that is a gradient magnetic field application unit. The permanent magnet 113 forms a uniform static magnetic field over the entire sample 115, and the static magnetic field adjusting shim coil 151 forms a gradient magnetic field. Therefore, a static gradient magnetic field is applied to the sample 115 by combining both.

  There are various arrangement modes of the static magnetic field adjustment shim coil 151. For example, the static magnetic field adjustment shim coil 151 may be arranged apart from the small RF coil 114 or may be a planar coil provided in the same plane as the small RF coil 114. Alternatively, as shown in FIGS. 4 and 5, a pair of gradient magnetic field application coils may be arranged with the small RF coil 114 interposed therebetween. Alternatively, these configurations may be arbitrarily combined.

  In the present embodiment, the planar shape of the pair of gradient magnetic field application coils may be approximately a half-moon shape, and the half-moon strings may be arranged to face each other toward the small RF coil 114 side. By doing so, high-accuracy local measurement can be performed while saving space. In this specification, “substantially meniscus” means that a pair of planar coils has a string-like linear region, and a gradient magnetic field that is inclined in a direction perpendicular to the linear region is applied to the sample by arranging them in opposition to each other. If the gradient magnetic field can be applied, the planar shape of the moon shape of the coil may be larger or smaller than half a month.

In the measurement apparatus 10 according to the present embodiment, the static magnetic field intensity control unit (control unit 307) performs static measurement in preparation for performing measurement of the protic solvent in another measurement mode in a state where a uniform magnetic field is applied as described later. The gradient strength of the static magnetic field applied from the magnetic field application unit 150 may be switched to substantially zero.
However, the static magnetic field application unit 150 according to the present invention is not necessarily configured using a coil as described above, and may be configured only by a permanent magnet.

The static magnetic field application unit 150 may be any means that can controllably give a predetermined non-uniformity to the static magnetic field applied to the sample 115, such as a method of passing a current through the coil, a magnetic material or the like in the static magnetic field. There is a way to insert. Therefore, the static magnetic field application unit 150 may intentionally disturb the uniformity of the static magnetic field generated by the magnetic pole surface, for example, by locally and discretely attaching a low magnetic permeability material to the magnetic pole surface of the permanent magnet 113. Good.
Hereinafter, in the present embodiment and the following examples, a case where a static magnetic field adjusting shim coil 151 (gradient magnetic field coil) is used as a method for making the static magnetic field non-uniform will be described as an example. Although the gradient coil has a simple configuration, the static magnetic field inhomogeneity can be easily adjusted by an electric current.

The small RF coil 114 is smaller than the sample 115. Specifically, it is preferably 1/2 or less, more preferably 1/10 or less of the size of the entire sample. With such a size, the amount of water molecules in the sample 115 can be accurately measured in a short time.
The size of the sample can be, for example, a projected area when the sample is placed, and the exclusive area of the small RF coil 114 is preferably ½ or less of the projected area, more preferably 1 / 10 or less. The size of the small RF coil 114 is preferably set to a diameter of 0.01 mm or more and 100 mm or less, for example.

As the small RF coil 114, for example, a planar spiral coil as shown in FIG. 6 can be used. By using such a planar coil, the measurement area can be limited. The measurement area of the spiral coil (small RF coil) has a width of about the coil diameter and a depth of about 1/5 to 1/2 of the coil diameter.
FIG. 7 is a diagram showing a state in which a small surface coil installed in a cell is connected to an LC resonance circuit.
In addition, unlike a normal solenoid type coil, the small surface coil has a planar shape, and therefore, as shown in FIG. 8, an NMR signal can be acquired simply by pressing on a planar sample.

The oscillating magnetic field (exciting oscillating magnetic field) applied by the small RF coil 114 is generated by the RF pulse generator 210.
The RF pulse generation unit 210 includes the functions of the RF oscillator 102, the modulator 104, the RF amplifier 106, and the control unit 307.

First, the control unit 307 determines the frequency of the oscillating magnetic field for excitation so as to synchronize with the spin resonance frequency of the protic solvent in the static magnetic field in which the sample 115 is placed.
The RF oscillator 102 transmits a signal having the determined frequency.
The modulator 104 modulates the signal transmitted from the RF oscillator 102 into a pulse shape to generate RF pulses (90 ° pulse and 180 ° pulse).
The RF amplifier 106 amplifies the RF pulse and sends it to the small RF coil 114.
The small RF coil 114 applies such an RF pulse to a specific portion of the sample 115 placed on the sample placing table 116.

  Note that a sequence table 127 and a timer unit 128 are connected to the control unit 307. The sequence table 127 stores high-frequency pulse sequence data when the moisture content is measured. Specifically, a timing diagram in which a time for generating a high-frequency pulse for measuring the amount of moisture in the sample 115 and an interval between the time and the intensity of the high-frequency pulse generated by the modulator 104 based on the timing diagram are shown. Is remembered. The control unit 307 generates a pulse for excitation according to the sequence table 127 while measuring the pulse generation time by the timer unit 128.

The application of the oscillating magnetic field for excitation and the acquisition of the NMR signal as described above can be realized by an LC circuit including the small RF coil 114. An example of such an LC circuit is shown in FIG.
In the nuclear magnetic resonance (NMR) method, the atomic number density and the spin relaxation time constant can be measured by detecting the movement of nuclear magnetization as an NMR signal by the spin resonance phenomenon of a nucleus placed in a magnetic field. The spin resonance frequency in a magnetic field of 1 [Tesla] is about 43 MHz, and an LC resonance circuit as shown in the figure is used to selectively detect the frequency band with high sensitivity.

A corresponding nuclear magnetic resonance signal (echo signal) is generated from the sample 115 to which the RF pulse is applied by the small RF coil 114. The small RF coil 114 acquires this and sends it to the NMR signal detector 220.
The NMR signal detection unit 220 includes a preamplifier 112 that amplifies an echo signal, a detector 301 that detects a nuclear magnetic resonance signal based on the frequency of an excitation oscillating magnetic field, and an A / D converter 118.
In the detector 301, the acquired echo signal is detected based on the fundamental wave of the RF oscillator, as in Patent Document 1 described above. The echo signal is A / D converted by the A / D converter 118 and sent to the arithmetic unit 130.

Further, the small RF coil 114, the RF pulse generation unit 210, and the NMR signal detection unit 220 are connected via a switch unit 161 (indicated by a symbol x in □ in FIG. 4).
The switch unit 161 is connected to the first state in which the small RF coil 114 and the RF pulse generation unit 210 (RF amplifier 106) are connected, and to the small RF coil 114 and the NMR signal detection unit 220 (detector 301). The transmission / reception changeover switch for switching the second state.
In the case of the measuring apparatus 10 that acquires an NMR signal using a small surface coil, it is preferable to use a transmission / reception changeover switch because the received NMR signal is weak.

When transmitting the excitation pulse amplified by the RF amplifier 106 (RF power-amp in FIG. 4) to the small RF coil 114, the switch unit 161 separates the reception preamplifier 112 (same pre-amp) and makes a large signal. Protect from voltage. Further, when receiving the NMR signal after excitation, the switch unit 161 blocks the noise generated by the large amplification transistor leaking from the RF amplifier 106 from being transmitted to the preamplifier 112.
Further, the spin resonance frequency in a magnetic field of 1 Tesla is about 43 MHz (this frequency band is referred to as Radio frequency), and in order to selectively detect the frequency band with high sensitivity, LC resonance as shown in FIG. A circuit is used.

<About Shim Coil for Static Magnetic Field Adjustment>
A static magnetic field adjusting shim coil (Gradient Coil) 151 is arranged so that a gradient magnetic field can be applied to the sample 115. Specifically, in the present embodiment, as schematically shown in FIG. 9, the static magnetic field adjusting shim coil 151 is disposed so as to face each axis with the small RF coil 114 interposed therebetween. More specifically, the static magnetic field adjustment shim coil 151 includes a Z-direction gradient magnetic field coil (Gz coil) 154, a Y-direction gradient magnetic field coil (Gy coil) 153, and an X-direction gradient magnetic field coil (Gx coil: FIG. (Not shown). The direction of each axis corresponds to the orthogonal coordinates shown in FIG. It is assumed that the small RF coil 114 is placed in the ZX plane with the coil center as the coordinate origin. It is assumed that the static magnetic field H ₀ of the permanent magnet 113 is applied in the Z direction.
The Gz coil 154 is a loop coil having a winding surface in the XY plane, and is arranged with the small RF coil 114 sandwiched in the ± Z direction. A desired gradient magnetic field can be applied to the small RF coil 114 in the Z direction by adjusting the energization amount to each Gz coil 154.
Each of the Gy coils 153 (153a to 153d) is a half-moon shaped coil arranged in the first to fourth quadrants of the YZ plane, and a linear portion corresponding to the string extends in the X direction. A desired gradient magnetic field can be applied to the small RF coil 114 in the Y direction by adjusting the energization amount to the Gy coils 153a to 153d arranged in each quadrant.
The Gx coil has the same configuration as the Gy coil, and can be arranged at a position obtained by rotating them by 90 degrees around the Z axis.
The shape of each static magnetic field adjusting shim coil 151 (Gx coil, Gy coil, Gz coil) is not limited to the above, and various shapes can be adopted.
A shielding shield (not shown) is provided between the small RF coil 114 and the static magnetic field adjustment shim coil 151. This shielding shield prevents noise from the static magnetic field adjustment shim coil 151 from affecting the small RF coil 114. The shielding shield has a thickness that prevents noise from passing and allows a magnetic field to pass.

  The measuring apparatus 10 according to the present embodiment applies a gradient magnetic field of the gradient magnetic field intensity change amount (ΔG) defined by the above formula (9) to the sample 115 using the static magnetic field adjustment shim coil 151.

  The control unit 307 controls the strength of the static magnetic field applied to the sample 115 by controlling the supply of current to the static magnetic field adjustment shim coil 151 via the current drive power source 159 constituted by a transformer, a transistor, and the like. Functions as a static magnetic field intensity control unit.

The echo signal acquired by the small RF coil 114 and A / D converted by the A / D converter 118 is acquired by the data reception unit 131 and sent to the calculation unit 130.
The calculation unit 130 calculates the amount of the protic solvent based on the echo signal intensity and the test data stored in the storage unit 305. That is, the calculation unit 130 functions as the moisture amount calculation unit 132.
In addition, the calculation unit 130 calculates a T ₂ (CPMG) value based on the echo signal as described later. Further, the water content calculation unit 132 may calculate the amount of the protic solvent from the calculated T ₂ (CPMG) value and the test data.

  The water content data calculated by the calculation unit 130 is output from the output unit 135. The specific output unit 135 is not limited, and may be a display device, a semiconductor memory device, or another output device.

The present invention is not limited to the above-described embodiment, and includes various modifications and improvements as long as the object of the present invention is achieved.
Here, if the NMR method is used, not only the amount of the protic solvent but also other characteristic values of a specific portion in the protic solvent can be measured. In this specification, the measurement of such other characteristic values is referred to as a second measurement mode. Examples of the characteristic value to be measured include mobility of the protic solvent, current flowing through the solvent, and permeation characteristics of the protic solvent in the solid polymer electrolyte membrane.

The mobility of the protic solvent refers to a physical property value indicating the ease of movement of the protic solvent in the sample. Such physical property values include parameters such as self-diffusion coefficient and mobility (movement speed).
That is, the measurement apparatus 10 of the present embodiment further includes a mobility calculation unit that calculates the mobility of the protic solvent in the sample 115 based on the echo signal acquired by the small RF coil 114, and the mobility is such. A calculation part is good also as calculating the mobility of the specific location in the sample 115 based on the information of the measured echo signal. The function of the mobility calculation unit can be realized by the calculation unit 130.

In measuring the mobility, as in the measurement of the amount of protic solvent, if the static magnetic field applied to the sample 115 is a gradient magnetic field, the non-uniformity is increased for a certain period of time. Good.
Therefore, in the measurement apparatus 10 of this embodiment, when the mobility is measured in the second measurement mode by switching to the first measurement mode (protic solvent amount measurement), the gradient magnetic field is applied by the static magnetic field adjustment shim coil 151. Subsequently, it is performed in a state where the small RF coil 114 is applied. However, in the mobility measurement, the gradient magnetic field intensity change amount (ΔG) is adjusted again to a state suitable for this, and the gradient magnetic field that is applied for a certain period of time can be applied.

On the other hand, for example, when measuring the current, the difference (frequency shift amount) between the frequency of the echo signal and the frequency of the 180 ° excitation pulse can be calculated, and the current value can be calculated from the difference.
That is, the measurement apparatus 10 of the present embodiment may further include a frequency shift amount calculation unit that calculates a difference between the frequency of the excitation oscillating magnetic field and the frequency of the echo signal. The function of the frequency shift amount calculation means can be realized by the calculation unit 130.

  Here, when measuring the current of the protic solvent, the higher the uniformity of the static magnetic field applied to the sample, the smaller the variation in the frequency shift amount, and the more stable the measured value. The reason is that as the uniformity of the static magnetic field is higher, the FID signal and the spin echo signal can be acquired over a longer period of time, and the frequency change amount can be observed over a longer period of time, thereby improving the calculation accuracy of the change rate. It is to do.

  Therefore, in the present invention, when measuring the current of the protic solvent, it is preferable that the gradient magnetic field applied by the static magnetic field adjusting shim coil 151 is substantially zero in strength. That is, in the measurement apparatus 10 of the present embodiment, when the current is measured in the second measurement mode by switching to the first measurement mode (protic solvent amount measurement), the magnetic field output of the static magnetic field adjustment shim coil 151 is adjusted. The gradient magnetic field strength applied to the sample 115 by the static magnetic field application unit 150 may be set to substantially zero. Such adjustment of the magnetic field output is realized by the control unit 307. The measurement mode can be switched by the control unit 307 based on an operator switching command through the operation signal receiving unit 129. That is, the control unit 307 functions as a switching unit that switches between the first measurement mode and the second measurement mode.

  Note that the gradient magnetic field strength here is substantially zero means that the static magnetic field non-uniformity inherent in the permanent magnet 113 to which the static magnetic field is applied, the sample 115 whose magnetic susceptibility is not zero, This means that the magnetic field gradient is equal to or less than the magnetic field gradient generated due to the non-uniformity of the magnetic field newly formed by inserting the small RF coil 114 or the like into the magnetic field.

In the case of measuring the permeation characteristics of a protic solvent, from a sample containing two or more kinds of protic solvents such as alcohols and water, obtain a spectrum of a chemical shift value indicating only one protic solvent, The ratio of the one protic solvent amount at a specific location in the membrane can be calculated.
That is, in the measurement apparatus 10 of the present embodiment, the sample includes two or more types of protic solvents, and a spectrum for acquiring a chemical shift value spectrum indicating only one protic solvent based on the acquired echo signal. An acquisition means and a permeation characteristic calculation means for calculating the ratio of the one protic solvent amount at a specific location in the membrane based on the intensity of the spectrum may be provided. The functions of the spectrum acquisition unit and the transmission characteristic calculation unit can be realized by the calculation unit 130.

  In the measurement of the permeation characteristics of the protic solvent in the membrane, the more uniform the static magnetic field, the shorter the FID signal that can be observed and the lower the frequency resolution in spectral analysis. The magnetic field is preferably uniform. This is because, for example, when separation of CH and OH spectra of alcohols is required, the separation of the spectra becomes difficult if the static magnetic field is not uniform.

  Therefore, in the present invention, when measuring the permeation characteristics of the protic solvent, it is preferable that the gradient magnetic field strength applied by the static magnetic field adjusting shim coil 151 is substantially zero. That is, similarly to the current measurement, in the measurement apparatus 10 of the present embodiment, when the transmission characteristic is measured in the second measurement mode by switching to the first measurement mode (protic solvent amount measurement), the static magnetic field application unit 150 is used. The gradient magnetic field strength applied to the sample 115 may be substantially zero.

  That is, the measurement apparatus 10 of the present embodiment determines the amount of the protic solvent from the intensity of the echo signal acquired in a state where the static magnetic field application unit 150 applies a gradient magnetic field having a predetermined gradient magnetic field strength change amount (ΔG) to the sample. Switching between the first measurement mode to be calculated and the second measurement mode to measure other characteristic values of the protic solvent from the intensity of the echo signal acquired when the gradient of the static magnetic field is substantially zero A switching means may be further provided.

  As described above, in the present invention, in addition to the amount of the protic solvent, it is possible to measure the mobility, current, permeation characteristics, etc. of the protic solvent in a multifaceted manner. It becomes possible to grasp. In particular, when the present invention is applied to measurement of a solid electrolyte membrane of a fuel cell, it is possible to accurately grasp the current in the power generation state and the presence state of the protic solvent.

  Hereinafter, the echo signal measurement technique and the protic solvent amount measurement technique according to the present invention will be described in more detail with reference to Examples and Comparative Examples.

[Experiment 1]
NMR measurement was performed by the CPMG method using the measurement apparatus 10 illustrated in FIGS. 4 and 5.
As shown in FIG. 6, the small RF coil 114 is formed by winding a conductive wire having a wire diameter of 50 μm in a substantially concentric manner three times, and the inner diameter D = 0.91 mm and the outer diameter = 1.3 mm of the coil portion (inductance portion) of the resonance circuit. A small surface coil was used.

As the sample 115, a polymer electrolyte membrane containing water was used. Specifically, as shown in FIG. 10, a cell with a flow channel capable of flowing gas and water around the solid polymer electrolyte membrane was manufactured and used. The width of the flow path is 1.0 mm and the depth is 1.0 mm. Water was supplied to one side of the solid polymer electrolyte membrane, and the other side was dried with nitrogen gas and held for a long time to obtain a steady state in which the supply of water to the polymer electrolyte membrane and evaporation were balanced.
FIG. 11 is a diagram illustrating an example of a configuration of a cell with a flow path.
The two cells were face to face, and a polymer electrolyte membrane was sandwiched between them. As the solid polymer electrolyte membrane, a polymer membrane having a size of 15 mm × 15 mm and a thickness of 500 μm (trade name Flemion, manufactured by Asahi Glass Co., Ltd.) was used. No catalyst is used on the surface of the polymer electrolyte membrane.

  Nitrogen gas was supplied to the upper channel of the cell at 50 [ml / min], and water was supplied to the lower channel. The small RF coil 114 is embedded in the cell on the gas side, and is pressed against the surface of the polymer electrolyte membrane from the gas supply side. In this example, the cell temperature was 20 ° C.

  As Comparative Example 1 (Case 1), Example 1 (Case 2), and Example 2 (Case 3), there are three current values that flow through the shim coil 151 for static magnetic field adjustment, and thereby the uniformity (non-uniformity) of the static magnetic field. CPMG measurement was performed while changing. In the CPMG method, the time (τ) from the 90 ° excitation pulse to the next 180 ° excitation pulse was set to 10 msec. Similarly, the time from the 180 ° excitation pulse to the peak of the echo signal was also set to 10 msec.

Table 1 below shows the dial reading of the current value passed through the shim coil [a. u. ]showed that. In this example and comparative example, according to (X, Y, Z) of the Cartesian coordinate system, shim coils (GX-coil, GY-coil, GZ-coil) for static magnetic field adjustment are provided on each of three orthogonal space axes. Arranged. By applying each current I _G to each shim coil, a linear static magnetic field whose gradient G is proportional to I _G can be applied with the geometric center of the shim coil as the origin.

The magnetic field received by the sample 115 is a value obtained by adding the linear static magnetic field H _G by the static magnetic field adjusting shim coil 151 and the static magnetic field H ₀ by the permanent magnet 113. For example, in the case of a shim coil GX-coil in the X direction, assuming that the position of the sample is x [m], the static magnetic field H [gauss] received by the sample is
H = H ₀ + H _G
H _G = G _X (x−x ₀ ) (11)
It becomes.

x ₀ [m] is the center position of the shim coil, and G _X is the gradient [gauss / m] of the static magnetic field applied by the shim coil GX-coil in the x direction. In the measurement apparatus 10 used in the present Examples and Comparative Examples, the current I _G to be supplied to the shim coil is expressed by using the readings dial. The current I _G and the dial reading are in a directly proportional relationship, and the current I _G and the gradient of the static magnetic field are in a directly proportional relationship.

In this example (comparative example), the proportionality coefficient was calculated as 208. By using such a proportionality coefficient, the gradient G _X [gauss / m] of the applied static magnetic field can be found from the dial reading of the current passed through the GX-coil. The relationship is as follows.
G _X = 208 × (Dial reading) (12)
This relationship is the same for all three shim coils (GX-coil, GY-coil, GZ-coil).

Comparative Example 1 (Case 1) is a case where the current flowing through the shim coil is adjusted so that the observed FID signal is the longest. Such a current is referred to as “sim current dial reading that maximizes T ₂ ^* ”. Case 1 is “when the static magnetic field is in the most uniform state” in the measurement region of the sample being measured, and this is used as a reference for the static magnetic field applied to the sample. The reason why the dial reading is not zero in this case is that the permanent magnet to which the static magnetic field is applied originally has a non-uniform static magnetic field, or a sample or coil with a non-zero magnetic susceptibility is inserted into the magnetic field. This is because the newly formed magnetic field causes non-uniformity of the static magnetic field, and the static magnetic field is uniformly adjusted by flowing a current through the shim coil so as to correct the non-uniformity. Therefore, the reading value of the dial of Case 1 is set as a reference value for “when the static magnetic field is uniform”. The increase / decrease (change amount) from the reference value corresponds to the change amount ΔG of the gradient magnetic field strength further added by the static magnetic field adjustment shim coil 151.

  Example 1 (Case 2) and Example 2 (Case 3) are “when the static magnetic field is not uniform”. In Example 2, non-uniformity of the static magnetic field is increased by increasing the gradient magnetic field strength as compared with Example 1. The numerical value in () in the table indicates the amount of increase / decrease from the value of Case1.

In Table 2 below, X, Y, Z given by each shim coil (GX-coil, GY-coil, GZ-coil) calculated from the above formula (12) based on the values in parentheses in Table 1 The gradient magnetic field strengths ΔG _x , ΔG _y , ΔG _{z in the direction} and the change amount ΔG [gauss / m] of the gradient magnetic field strength as their combined vector are shown. This ΔG indicates the amount of increase / decrease of how much gradient magnetic field strength is applied from Case 1 as a reference. Since the shim coil has three axes, the evaluation value of the change amount ΔG of the gradient magnetic field strength obtained by integrating the three gradient magnetic field strengths was calculated as the square root of the square sum of the gradient magnetic field strengths (ΔG _X , ΔG _Y , ΔG _Z ).
The value of the gradient magnetic field strength D · ΔG [gauss] obtained by multiplying this by the inner diameter (D = 0.91 · 10 ⁻³ m) of the small RF coil 114 is shown in the same table. In Examples 1 and 2, the above formula (9) is satisfied.

  The NMR measurement conditions were a 90 ° excitation pulse repetition time (TR) of 10 seconds, a 90 ° excitation pulse dummy count of 4, an NMR signal integration count of 1, and a resonance frequency of 43.37 MHz.

  Hereinafter, each measurement result of Comparative Example 1 (Case 1), Example 1 (Case 2), and Example 2 (Case 3), and a calculation result based thereon will be described in order.

(About Comparative Example 1)
The waveform of the NMR signal acquired under the Case 1 conditions is shown in FIGS. FIG. 5A shows the whole measured NMR signal, and FIG. 4B shows an enlarged portion of 0 to 100 msec in FIG.

  In the case of Comparative Example 1, the FID signal after the 90 ° excitation pulse is long and the τ = 10 msec until the next 180 ° excitation pulse (1) is irradiated as seen in FIG. There was almost no decay in the meantime. For this reason, the echo signal to be observed interferes with the FID signal and cannot be recognized as a clear mountain-shaped echo signal. In this case, the FID signal and the echo signal are not simply overlapped, but the motion of the magnetization vector itself interferes and does not interfere when the next 180 ° excitation pulse (2) is irradiated. It can be said that it causes the motion of a completely different magnetization vector. As a result, the acquired echo signal is considered to be unstable.

From the acquired NMR signal, only the “even-numbered echo signal intensity” was extracted and logarithmically plotted. Based on this plotter, linear approximation was performed by the least square method, and the T ₂ (CPMG) relaxation time constant (T ₂ (CPMG) value) was calculated from the gradient of the straight line. For the calculation of the T ₂ (CPMG) value, the method described in Patent Document 1 can be used.

FIG. 13 is a diagram showing the transition of the relationship between the number of experiments and the T ₂ (CPMG) value calculated by repeating measurement under the conditions of Comparative Example 1 16 times. From the figure, it can be seen that the T ₂ (CPMG) value calculated in Comparative Example 1 (Case 1) varies greatly. This is evaluated quantitatively.

The obtained 16 T ₂ (CPMG) values were statistically analyzed to determine the standard deviation of the T ₂ (CPMG) value and its coefficient of variation (= the standard deviation divided by the average value). This is shown in Table 3 below.
In addition, the average value of the second, fourth, and sixth echo signal intensities obtained by the CPMG method (each time average value of the echo signal intensity) was calculated for 16 times. The table shows the standard deviation and the coefficient of variation regarding the variation of the average value for each time. In addition, what averaged each time the average value of echo signal intensity over the frequency | count of experiment further is hereafter called "average echo signal intensity." In the present invention, the expression “echo signal intensity” means the average echo signal intensity.
In addition, from the irradiation of the second, fourth, and sixth 180 ° excitation pulses (2), (4), and (6) (see FIG. 1 for the 180 ° excitation pulse (2)), τ / 3≈3. Similarly, the average value of the three FID signal intensities observed at the respective time points after 5 msec (average value of each FID signal intensity at τ / 3 o'clock) was calculated for 16 times. The standard deviation and the coefficient of variation regarding the variation of the average value of each FID signal intensity are shown in the same table. In addition, what averaged each time average value of the FID signal strength at τ / 3 time over the number of experiments is hereinafter referred to as “average FID signal strength at τ / 3 time”. In the present invention, when expressed as FID signal intensity or free induction decay signal intensity without any notice, it means the average FID signal intensity at τ / 3.
Further, the table shows an average of the ratio of the average value of each echo signal intensity and the average value of the FID signal intensity at τ / 3 time over the number of experiments (hereinafter referred to as “echo”). "Signal strength / average of FID signal strength").
In the same table, the results of measurement and calculation in the same manner for Example 1 (Case 2) and Example 2 (Case 3) are also shown together.

Information for investigating the cause of the large variation in the T ₂ (CPMG) value includes the strength of the echo signal, the strength of the FID signal after irradiation of the excitation pulse, and the clarity of the echo signal strength.

FIG. 14 is a diagram showing how the average value of the echo signal intensity changes every time the number of experiments.
From the figure, it can be seen that in the first comparative example, the average value itself of the echo signal intensity varies. Originally, the echo signal of the steady state polymer electrolyte membrane (sample 115) should be constant, and such a dramatic increase or decrease is not observed.

Therefore, the average value of the signal strengths of the three FID signals observed after 3.5 msec from the irradiation of the three 180 ° excitation pulses (2), (4), and (6) (the FID signal strength of τ / 3 o'clock). Each time average value) was plotted. Here, 3.5 msec is approximately one third of 10 msec (= τ) at which the echo signal peaks after irradiation of the 180 ° excitation pulse as described above.
This time is a safer side than τ / 2 [sec] set when the above equation (5) is derived, that is, a time in which interference between the FID signal and the echo signal can be sufficiently avoided.

  That is, if the FID signal is attenuated during the time of about τ / 2, the influence of the FID signal is avoided when measuring the peak intensity of the echo signal, and further the FID signal is attenuated within the time of about τ / 3. Then, it is considered that interference with the FID signal does not occur over the entire echo signal generated thereafter.

Therefore, for Case 1 of Comparative Example 1, the average signal strength of the FID signal was calculated when 3.5 msec had elapsed since each irradiation of the second, fourth, and sixth 180 ° excitation pulses.
FIG. 15 is a diagram illustrating how the average signal intensity changes for each number of experiments.
In addition, Table 3 shows the standard deviation and coefficient of variation of the FID signal intensity when this calculation is repeated 16 times.

  Comparing FIGS. 14 and 15, it can be seen that the FID signal intensity and the echo signal intensity are approximately the same. It can also be seen that the FID signal also increases and decreases in synchronization with the increase and decrease of the echo signal. Whether or not the echo signal intensity can be clearly identified without being buried in the FID signal is represented by a ratio between the echo signal intensity in FIG. 14 and the FID signal intensity in FIG.

  FIG. 16 shows how the ratio of each time average value of echo signal intensity and each time average value of FID signal intensity at τ / 3 changes for each number of experiments. The average value of the ratios (echo signal intensity / FID signal intensity average) was calculated to be 1.27 as described in Table 3 above.

(About Example 1)
The measurement results and calculation results for Case 2 in which the gradient magnetic field strength change amount ΔG is increased to 270 [gauss / m] and a certain degree of nonuniformity is given to the static magnetic field applied to the sample 115 are shown below. The measurement method and calculation method are the same as those in the first comparative example.

  The waveforms of the NMR signals acquired under the Case 2 conditions are shown in FIGS. FIG. 5A shows the whole measured NMR signal, and FIG. 4B shows an enlarged portion of 0 to 100 msec in FIG.

Similar to Case 1, measurement under the Case 2 conditions was repeated 16 times.
FIG. 18 is a diagram showing the relationship between the number of experiments and the T ₂ (CPMG) value. Further, the obtained T ₂ (CPMG) values for 16 times were statistically analyzed to determine the standard deviation of the T ₂ (CPMG) value and its coefficient of variation (= the value obtained by dividing the standard deviation by the average value). These are shown in Table 3 above.

From the figure and the calculation result, that the standard deviation and coefficient of variation of the first embodiment variation of T ₂ (CPMG) values as compared with Comparative Example 1 is reduced, T ₂ (CPMG) values are reduced I understand. This is because a static magnetic field having a predetermined gradient magnetic field strength change amount is applied to the sample 115 by the static magnetic field adjusting shim coil 151.

Further, the intensity of the measured echo signal, the intensity of the FID signal after 3.5 msec of the excitation pulse irradiation, and the ratio of the echo signal to the FID signal (clarity of the echo signal) are the same as in Case 1 above. It was calculated over 16 times.
19A, 19B, and 19C show the calculation results. FIG. 4A shows the transition of the average value of the echo signal intensity for each number of experiments. FIG. 5B shows the transition of the average value of the FID signal intensity at τ / 3 for each number of experiments. FIG. 4C shows the transition for each number of experiments regarding the ratio between the average value of the echo signal intensity and the average value of the FID signal intensity at τ / 3.

From these results, in Example 1 (Case 2), compared with Comparative Example 1 (Case 1), the intensity of the FID signal after τ / 3 (3.5 msec) after irradiation with the excitation pulse is reduced, and the echo signal It can be seen that the ratio of the FID signal to the FID signal has increased and the T ₂ (CPMG) value has become stable.

(About Example 2)
The measurement results and calculation results for Case 3 in which the gradient magnetic field strength change amount ΔG is increased to 532 [gauss / m] and the static magnetic field applied to the sample 115 is sufficiently nonuniform are shown below. The measurement method and the calculation method are the same as those in Comparative Example 1 and Example 1.

  The waveforms of NMR signals acquired under the Case 3 conditions are shown in FIGS. 20 (a) and 20 (b). FIG. 5A shows the whole measured NMR signal, and FIG. 4B shows an enlarged portion of 0 to 100 msec in FIG. From this figure, it can be seen that the NMR signal acquired under the condition of Case 3 does not interfere with the FID signal and the echo signal, and the echo signal has a mountain shape with a clear peak.

Similar to Case 1, measurement under the Case 3 conditions was repeated 16 times.
FIG. 21 is a diagram showing the relationship between the number of experiments and the T ₂ (CPMG) value. Further, the obtained T ₂ (CPMG) values for 16 times were statistically analyzed to determine the standard deviation of the T ₂ (CPMG) value and its coefficient of variation (= the value obtained by dividing the standard deviation by the average value). These are shown in Table 3 above.

From the figure and the calculation result, that the standard deviation and coefficient of variation of the second embodiment variation of T ₂ (CPMG) values as compared with Comparative Example 1 is reduced, T ₂ (CPMG) values are reduced I understand. In the second embodiment, a higher gradient magnetic field strength (D · ΔG) is applied to the small RF coil 114 within the range of the above formula (9) than in the first embodiment, thereby causing more variation in T ₂ (CPMG) value. You can see that it was suppressed.

  Further, the intensity of the measured echo signal, the intensity of the FID signal after 3.5 msec of the excitation pulse irradiation, and the ratio of the echo signal to the FID signal (clarity of the echo signal) are expressed as Cases 1 and 2 above. Similarly, calculation was performed 16 times. The calculation results are shown in FIGS. 22 (a), (b), and (c). FIG. 4A shows the transition of the average value of the echo signal intensity for each number of experiments. FIG. 5B shows the transition of the average value of the FID signal intensity at τ / 3 for each number of experiments. FIG. 4C shows the transition for each number of experiments related to the ratio between the average value of the echo signal intensity and the average value of the FID signal intensity at τ / 3.

  The echo signal intensity may be measured only for the second echo, but the S / N ratio is obtained by averaging the signal intensities of the even-numbered echoes such as the second, fourth and sixth as described above. Can be improved.

From these results, in Example 2 (Case 3), compared to Comparative Example 1 (Case 1), the strength of the FID signal after lapse of τ / 3 (3.5 msec) after irradiation of the 180 ° excitation pulse is noise. The average of the echo signal strength / FID signal strength is increased to about 10. Thereby, it can be seen that the T ₂ (CPMG) value was stably stabilized.

One of the indexes indicating that the T ₂ (CPMG) value can be stably measured is the standard deviation of the T ₂ (CPMG) value shown in Table 3 above. If the standard deviation is large, the T ₂ (CPMG) value varies greatly, and if it is small, the T ₂ (CPMG) value can be measured stably.

In FIG. 23, the vertical axis represents the standard deviation of the T ₂ (CPMG) value and the horizontal axis represents the gradient magnetic field strength (D · ΔG [gauss]). Cases 1, 2, and 3 are plotted in order from the left. ing. From the figure, it can be seen that the greater the D · ΔG, the more stably the T ₂ (CPMG) value can be measured.

Based on the T ₂ (CPMG) value obtained by measuring the sample 115 (polymer electrolyte) by the CPMG method and the average value of the second, fourth and sixth echo signal intensities, the water content in the polymer electrolyte membrane To calculate, the relationship of FIGS. 24A and 24B may be used. This is the relationship when Flemion is used as the polymer electrolyte membrane and measurement is performed in an environment of 22 to 23 ° C. The figure (a) is a figure of a calibration curve (test data) showing the relation between the water content and the T ₂ (CPMG) value, and the figure (b) is a figure showing the relation between the water content and the echo signal intensity. is there. The water content is a value obtained by calculating the mass of the contained water based on the dried polymer electrolyte membrane.

24, the water content in the sample 115, the T ₂ (CPMG) value, and the echo signal intensity are positively correlated and have a substantially linear relationship.
Therefore, by using such a calibration curve as a calibration curve, the water content in the sample 115 can be obtained from the calculated T ₂ (CPMG) value or the measured echo signal intensity.

  At this time, when the echo signal intensity is stably measured repeatedly at the same intensity, the stability and reproducibility of the moisture content measurement is improved.

Here, the “intensity ratio between the echo signal and the FID signal” is used as another index for evaluating the appropriate nonuniformity of the static magnetic field that enables stable measurement of the T ₂ (CPMG) value. be able to.
Specifically, the non-uniformity of the static magnetic field may be increased so that the “average of echo signal intensity / FID signal intensity” shown in Table 3 is 5 or more, preferably 10 or more.
Thus, by monitoring the intensity ratio between the echo signal and the FID signal instead of the stability of the T ₂ (CPMG) value, statistical processing based on several times of measurement data becomes unnecessary, and the protic solvent The quantity can be measured quickly. The non-uniformity of the static magnetic field applied by the static magnetic field application unit 150 is adjusted by adjusting the current value flowing from the current drive power source 159 to the static magnetic field adjustment shim coil 151 while monitoring the intensity ratio. This is because it can be determined in real time within the range.

[Experiment 2]
The protic solvent was changed from water contained in the polymer electrolyte membrane to a water sample, and echo signals were measured in the same manner as in Experiment 1 above, and the T ₂ (CPMG) value and the amount of protic solvent were calculated.
The water sample is made by punching out a 0.50 mm thick acrylic plate into a 18 mm x 18 mm rectangular shape to form a frame, adhering a 0.12 mm thick cover glass on both sides to form a sealed container, and enclosing the water in it. Configured.

In this experiment, two kinds of small RF coils 114 having different inner diameters D are used. One is a small surface coil with an inner diameter of 0.60 mm and five turns (hereinafter sometimes referred to as “inner diameter 0.60 mm, five turns coil”), and the other is a small surface coil with an inner diameter of 1.30 mm and ten turns. (Hereinafter, it may be referred to as an “inner diameter 1.30 mm 10-turn coil”). A polyurethane coated copper wire having a diameter of 0.04 mm was used for both windings.
The former photograph is shown in FIG. 25 (a), and the latter photograph is shown in FIG. 25 (b).

  The small RF coils 114 shown in FIGS. 11A and 11B were respectively installed in the cell shown in FIG. 11, and NMR measurement was performed with a water sample interposed therebetween.

<In the case of an inner diameter 0.60 mm 5-coil>
First, the case where an inner diameter 0.60 mm 5-turn coil is used as the small RF coil 114 will be described. The experiment was performed in 5 cases of Case 4 to 8 shown in Table 4 below.
Table 4 below shows the dial reading of the current passed through the shim coil [a. u. ] Is shown. Table 5 below shows the amount of change ΔG [gauss / m] of the gradient magnetic field strength given by each shim coil (GX-coil, GY-coil, GZ-coil) calculated using the above equation (12). . The value of the gradient magnetic field strength D · ΔG [gauss] obtained by multiplying this by the inner diameter (D = 0.60 · 10 ⁻³ m) of the small RF coil 114 is shown.

  In Case 4, a gradient magnetic field is not applied to the water sample, and Cases 5 to 8 are applied. However, in Case 5, the current flowing through the shim coil is suppressed, and a static magnetic field having a gradient magnetic field strength lower than the lower limit of the above formula (9) is applied. Cases 6 to 8 were values satisfying the above formula (9).

  The NMR measurement conditions were such that the 90 ° excitation pulse repetition time (TR) was 20 seconds, the 90 ° excitation pulse dummy count was 4, the NMR signal integration count was 1, and the resonance frequency was 43.24 MHz.

(Comparative Example 2)
FIGS. 26A and 26B show waveforms of NMR signals acquired under the Case 4 conditions. FIG. 5A shows the whole measured NMR signal, and FIG. 4B shows an enlarged portion of 0 to 100 msec in FIG.

  In the case of Comparative Example 2, the FID signal after the 90 ° excitation pulse is long, as seen in FIG. 5B, and is slightly attenuated during 10 msec until the next 180 ° excitation pulse is irradiated. But not. Therefore, the echo signal to be observed interferes with the FID signal and is not a clear mountain-shaped echo signal.

From the acquired NMR signal, only the “even-numbered echo signal intensity” was extracted and logarithmically plotted. Based on this plot, a straight line approximation was performed by the least square method, and a T ₂ (CPMG) value was calculated from the slope of the straight line. FIG. 27 is a diagram showing the relationship between the number of experiments and the T ₂ (CPMG) value by repeating the same measurement 15 times.

Table 6 below shows a statistical analysis of the T ₂ (CPMG) values obtained in this way, and the standard deviation and coefficient of variation (= value obtained by dividing the standard deviation by the average value). is there. The table shows the echo signal intensity (average echo signal intensity) further averaged over 15 times and the coefficient of variation of each average value of the echo signal intensity. In addition, for each time average value of the FID signal intensity at τ / 3 time, the average intensity over 15 times (average FID signal intensity at τ / 3 time) and its variation coefficient are shown. Further, an average value of 15 times (echo signal intensity / average of FID signal intensity) relating to a ratio between each time average value of the echo signal intensity and each time average value of the FID signal intensity at τ / 3 is shown.

From FIG. 27 and Table 6 above, it can be seen that the T ₂ (CPMG) values of Comparative Example 2 (Case 4) vary greatly. Similarly, the standard deviation of T ₂ (CPMG) value and its coefficient of variation are also very large values.

Similarly to Comparative Example 1, FIG. 28A shows the transition of the number of experiments for each average value of the echo signal intensity measured under the conditions of Comparative Example 2 for each number of experiments. Also, the transition for each number of experiments regarding the average value of the FID signal intensity at τ / 3 is shown in FIG. FIG. 4C shows the transition of the echo signal intensity at each time with respect to the ratio (clarity of the echo signal) between the average value of the echo signal intensity and the average value of the FID signal intensity at τ / 3.
From FIG. 6 and Table 6 above, it can be seen that in the case of Comparative Example 2, the variation coefficient of the echo signal intensity is large, and the average of the echo signal intensity / FID signal intensity is a very low value of 2.33.

(About Example 3)
A small RF coil 114 is a 0.60 mm inner diameter five-turn coil, and the amount of change ΔG in the gradient magnetic field intensity from Case 4 is 297 [gauss / m], the coil inner diameter D [m] and ΔG [gauss / m]. Product D · ΔG was increased to 0.178 [gauss], and the uniformity of the static magnetic field was increased to measure the echo signal.
At this time, the FID signal observed after the 90 ° excitation pulse is completely attenuated before the irradiation of the 180 ° excitation pulse. Similarly, the FID signal after the 180 ° excitation pulse interferes with the echo signal. There are no conditions. FIG. 29 shows a signal acquired under this condition. The T ₂ ^* relaxation time constant of the FID signal is about 3 msec. The figure (a) has shown the whole measured NMR signal, and the figure (b) has expanded and shown only 0-100 msec of the figure (a).

  From FIG. 5B, it can be seen that the FID signal after the 90 ° excitation pulse and the FID signal after the 180 ° excitation pulse are acquired under the condition that they rapidly attenuate and do not interfere with the echo signal. In this case, the echo signal can be clearly recognized.

Similarly to Case 4, measurement of the water sample under the condition of Case 6 was repeated 15 times using a 0.60 mm inner diameter coil, and the transition of the relationship between the number of experiments and T ₂ (CPMG) value is shown in FIG. . These 15 T ₂ (CPMG) values obtained were statistically analyzed, and the standard deviation of the T ₂ (CPMG) value and its coefficient of variation (= the standard deviation divided by the average value) were also obtained. This is shown in Table 6 above.

From FIG. 30 and Table 6, if Case 4 and 6 are compared, the variation in the T ₂ (CPMG) value of Case 6 is greatly reduced, and the coefficient of variation of the T ₂ (CPMG) value is reduced to about 3.3%. You can see that This shows that the T ₂ (CPMG) value can be measured very stably.
As in Case 4, the transition of the average value of the echo signal intensity measured for each case of the water sample using the 0.60 mm 5 inner diameter coil under the condition of Case 6, the transition of the average value of the FID signal intensity at τ / 3 time, and 31 (a), (b), and (c) show the transition of the ratio (clarity of echo signal) of each time average value of echo signal intensity to each time average value of FID signal intensity at τ / 3. Show.

Similarly to Case 4, the above-mentioned Table 6 shows the average value of each echo signal intensity and its variation coefficient, the average value of each FID signal intensity at τ / 3 and its coefficient of variation, and the echo signal intensity / FID signal intensity. Averaged. From these, in Case 6, each time average value of the FID signal intensity at τ / 3 decreases to almost the noise level, and the average of the echo signal intensity / FID signal intensity increases to about 7.13.
Thus, it can be said that the T ₂ (CPMG) value measured under the condition of Case 6 is more stable than that of Case 4.

  As shown in Tables 4 and 5 above, the inhomogeneity of the static magnetic field is sequentially increased, and the evaluation value of the change amount ΔG of the gradient magnetic field strength, or the coil inner diameter D [m] and ΔG [gauss / m When the product D · ΔG with the above was sequentially increased (Case 5, 7, 8) was also measured. In these cases, the statistical values were calculated by measuring 15 times in the same manner as in Cases 4 and 6. The measurement results are summarized in Table 6.

The standard deviation of the T ₂ (CPMG) value representing the stability of the measurement when T ₂ (CPMG) measurement of a water sample was performed using the 0.60 mm 5-coil coil shown in Table 6 as a small RF coil 114 FIGS. 32A and 32B are diagrams in which the coefficient of variation is plotted as a function of D · ΔG (for the horizontal axis).

From Table 6 and FIGS. 32 (a) and 32 (b), in order to reduce the variation in T ₂ (CPMG) value to about several percent and perform stable measurement, D · ΔG is approximately 0. It can be seen that the static magnetic field in the small RF coil 114 may be made non-uniform so as to be 10 [gauss] or more, preferably 0.15 [gauss] or more. This indicates the validity of the above formula (9), and by extension, the validity of the above formula (3).

As described above, in the measurement apparatus and the measurement method of the present embodiment, when the excitation interval τ = 10 msec and the nuclear magnetic rotation ratio γ = 42.6 MHz / T of proton ¹ H,
D · ΔG ≧ 0.15 (13)
It can be said that it is preferable.

And based on the above formula (13), the above general formula (3) is rewritten to define more preferable lower limit values of D · ΔG, γ, τ.
D [m] · ΔG [gauss / m] · γ [Hz / T] · 10 ⁻⁴ [T / gauss] · τ [sec] ≧ 6 (14)
Is guided.

<In the case of an inner diameter 1.30 mm 10-winding coil>
Next, the case where a 10-turn coil with an inner diameter of 1.30 mm is used as the small RF coil 114 will be described. The experiment was performed in 6 cases of Cases 9 to 14 shown in Table 7 below.

Table 7 below shows the dial reading of the current passed through the shim coil [a. u. ] Is shown. Table 8 below shows gradient magnetic field strengths ΔG _x and ΔG in the X, Y, and Z directions given by the respective shim coils (GX-coil, GY-coil, GZ-coil) calculated using the above equation (12). _y, and .DELTA.G _z, the variation of the gradient magnetic field strength as their composite vector ΔG [gauss / m] illustrated. Further, the value of the gradient magnetic field strength D · ΔG [gauss] obtained by multiplying this by the inner diameter (D) of the small RF coil 114 is shown.

In Case 9 (Comparative Example 4), a gradient magnetic field is not applied to the water sample, and Cases 10 to 14 are applied. However, in Case 10 (Comparative Example 5), the current flowing through the shim coil is suppressed, and a static magnetic field having a gradient magnetic field strength lower than the lower limit of the above formula (9) is applied. Cases 11 to 14 (Examples 6 to 9) were set to satisfy the above formula (9).
For Cases 12 to 14, the gradient magnetic field intensity exceeded the lower limit of the above formula (13) and satisfied the above formula (14).

As shown in Tables 7 and 8 above, the inhomogeneity of the static magnetic field is sequentially increased, and the evaluation value of the change amount ΔG of the gradient magnetic field strength, that is, the gradient magnetic field strength D · ΔG is sequentially increased Cases 9 to 14) were measured. The NMR measurement conditions were a 90 ° excitation pulse repetition time (TR) of 20 seconds, a 90 ° excitation pulse dummy count of 4, an NMR signal integration count of 1, and a resonance frequency of 43.21 MHz.
Statistical analysis of 15 T ₂ (CPMG) values obtained by measuring a water sample with a 10-coil coil with an inner diameter of 1.30 mm, and the standard deviation of the T ₂ (CPMG) value and its coefficient of variation (= standard deviation) (Value divided by average value). This is shown in Table 9 below. In the table, in addition to the average echo signal intensity and the coefficient of variation of the echo signal intensity each time, the average value (average FID signal at τ / 3 time) of the FID signal intensity at each time of τ / 3 time. (Intensity) and coefficient of variation, as well as the average of echo signal intensity / FID signal intensity.

The standard deviation and coefficient of variation of the T ₂ (CPMG) value representing the stability of measurement when T ₂ (CPMG) measurement of a water sample was performed using the 1.30 mm 10-turn coil shown in Table 9 above, FIGS. 33 (a) and 33 (b) are diagrams plotted as a function of ΔG (for the horizontal axis). This figure also shows the results for a coil with an inner diameter of 0.60 mm.
From Table 9 and FIGS. 9A and 9B, in order to reduce the variation in T ₂ (CPMG) value to about several percent and perform stable measurement, D · ΔG is approximately 0. .10 [gauss] or more, that is, Examples 6 to 9 are preferable, and 0.15 [gauss] or more, that is, Examples 7 to 9, so that the static magnetic field applied to the small RF coil 114 is made non-uniform. I know it ’s good.
The value of 0.15 [gauss] is the same for both a small surface coil having an inner diameter D of 0.60 mm and a small surface coil of 1.30 mm.

In Experiments 1 and 2 described above, three coils with inner diameters of 0.60, 0.90, and 1.30 mm were used as small surface coils, and CPMG measurement was performed using PEM and water as the sample, and T ₂ (CPMG) The measurement stability of the value was shown. As a common index, the gradient magnetic field strength change amount ΔG [gauss / m] or the gradient magnetic field strength D · ΔG [gauss] obtained by multiplying this by the coil inner diameter D [m] is effective as shown in FIG. Shown in a) and (b).

In FIG. 34 (a), the standard deviation of the T ₂ (CPMG) value is substantially the same for the three coils. Even if the sample is different between PEM and water, it is almost the same. From this, it can be considered that the gradient magnetic field strength change amount ΔG and the gradient magnetic field strength D · ΔG give an evaluation value capable of stably measuring the amount of the protic solvent.
Further, in the relationship between the gradient magnetic field strength D · ΔG and the variation coefficient of the T ₂ (CPMG) value shown in FIG. 34B, the same tendency is shown for PEM and water. In addition, since the average value of T ₂ (CPMG) value of PEM is as small as about 2 to 3 times that of water, the coefficient of variation obtained by dividing the standard deviation by the average value is larger in PEM. If the averages of both T ₂ (CPMG) values are approximately the same, it is assumed that the coefficient of variation further matches.

[Experiment 3]
As an example of the protic solvent, an alcohol aqueous solution was used as a sample, and an experiment similar to the above was performed.
Specifically, a 60 [vol%] aqueous methanol solution was used as a sample, and the relationship between the static magnetic field inhomogeneity and measurement variation was determined.

A 60 [vol%] aqueous methanol solution was sealed in an airtight container in which cover glasses were bonded to both surfaces of an acrylic plate in the same manner as in Experiment 2.
In this experiment, as in Experiment 2, a polyurethane-coated copper wire having an inner diameter of 0.60 mm and a wire diameter of 0.04 mm and an inner diameter of 0.60 mm and a 5-winding coil were used as the small RF coil 114 (see FIG. 25A).
FIG. 35 is a diagram showing a state in which such a small RF coil 114 is installed in the center of the cell and a methanol aqueous solution sample is placed thereon. At the time of measurement, the sample was sandwiched between the opposing cells, and the coil and the sample were brought into contact with each other.

In this measurement, measurement was performed under seven magnetic field conditions of Cases 15 to 21 shown in Table 10 below. Table 10 below shows the dial reading [a. u. ] Is shown. Table 11 below shows gradient magnetic field strengths ΔG _x and ΔG _{y in} the X, Y, and Z directions given by the respective shim coils (GX-coil, GY-coil, GZ-coil) calculated using the above equation (12). , ΔG _z and the gradient magnetic field strength variation ΔG [gauss / m] as a combined vector thereof. The value of the gradient magnetic field strength D · ΔG [gauss] obtained by multiplying this by the inner diameter (D = 0.60 · 10 ⁻³ m) of the small RF coil 114 is shown.

  In Case 15 (Comparative Example 6), a gradient magnetic field is not applied to the methanol aqueous solution sample, and this is applied to Cases 16-21. However, in Case 16 (Comparative Example 7), the current flowing through the shim coil is suppressed, and a static magnetic field having a gradient magnetic field strength lower than the lower limit of the above formula (9) is applied. Cases 17 to 21 (Examples 10 to 14) were set to satisfy the above formula (9). Case 18 is a case in which a static magnetic field having a gradient magnetic field strength substantially coincident with the lower limit value of the above equation (13) is applied. Cases 19 to 21 exceed this, and the gradient magnetic field strength sufficiently satisfies the above equation (14). This is the case.

  The NMR measurement conditions were a 90 ° excitation pulse repetition time (TR) of 20 seconds, a 90 ° excitation pulse dummy count of 4, an NMR signal integration count of 1, and a resonance frequency of 43.28 MHz. The sample temperature was 19.0 ° C.

(Comparative Example 6)
FIG. 36 shows the waveform of an FID signal obtained by obtaining a methanol aqueous solution sample under the condition of Case 15 with an inner diameter 0.60 mm 5-winding coil.

The aqueous methanol solution contains CH and OH, and the difference in resonance frequency between them is several ppm.
Here, it can be seen from the FID signal in FIG. 36 that the NMR signal has a beat, and the NMR signal does not form a monotonically decaying curve as obtained with water. From the figure, the beat width of the NMR signal is about 15 msec, which is about 67 Hz when converted into a frequency. 67 Hz is 1.5 ppm with respect to the resonance frequency of 43.3 MHz of ¹ H in this apparatus. That is, it can be said that the figure shows a waveform in a state where FID signals of different resonance frequencies originating from CH and OH are mixed.

The relationship between the T ₂ (CPMG) value measured in such a case, its variation, and the gradient magnetic field strength D · ΔG was experimentally determined.

  FIG. 37 shows an NMR signal when a methanol aqueous solution sample is obtained by the CPMG method under a magnetic field condition of Case 15 using a 0.60 mm 5-winding coil as the small RF coil 114. FIG. 2A shows the whole measured NMR signal, and FIG. 2B shows only the 0 to 100 msec portion in an enlarged manner.

  When measured under the Case 15 condition, as shown in FIG. 37 (b), the FID signal after the 90-degree excitation pulse appears for a long time with a beat, and the next 180 ° excitation pulse is irradiated. It is not fully attenuated during τ = 10 msec. For this reason, the second echo signal to be observed that appears in the vicinity of 52.5 msec in the figure is in a state of being affected by interference with the FID signal.

Next, only the even-numbered echo signal intensity was extracted from the acquired NMR signal and logarithmically plotted. Based on this plot, a straight line approximation was performed by the least square method, and a T ₂ (CPMG) value was calculated from the slope of the straight line.

The same measurement was repeated 16 times, and the transition of the relationship between the number of experiments and the T ₂ (CPMG) value is shown in FIG.
The obtained 16 T ₂ (CPMG) values were statistically analyzed to determine the standard deviation of the T ₂ (CPMG) value and its coefficient of variation (= the standard deviation divided by the average value). This is shown in Table 12 below. The table shows the average echo signal intensity, the coefficient of variation of the average value of each echo signal intensity, the average value of each time of the FID signal intensity at τ / 3 and its coefficient of variation, and the average of the echo signal intensity / FID signal intensity. Is also described.

From FIG. 38 and Table 12 above, it can be seen that the T ₂ (CPMG) values of Case 15 vary greatly. Similarly, the standard deviation of T ₂ (CPMG) value and its coefficient of variation are also large values.
Transition of each time average value of echo signal intensity measured under Case 15 conditions, transition of each time average value of FID signal intensity at τ / 3 time, and each time average value of echo signal intensity and FID signal strength at τ / 3 time The transition of the ratio (clarity of echo signal) with the average value of each time was calculated in the same manner as in Comparative Example 2 (Case 4). The results are shown in FIGS. 39 (a), (b) and (c).

  In Case 15, it can be seen from Table 12 that the coefficient of variation of the echo signal intensity is large and the average of the echo signal intensity / FID signal intensity is a low value of 3.52.

(About Example 12)
In Case 19, the gradient magnetic field strength change amount ΔG is set to 299.0 [gauss / m] and the gradient magnetic field strength D · ΔG = 0.179 [gauss] from Case 15, and the echo signal is increased by increasing the non-uniformity of the static magnetic field. It is measured. At this time, the FID signal observed after the 90 ° excitation pulse is completely attenuated before the irradiation of the 180 ° excitation pulse. Similarly, the FID signal after the 180 ° excitation pulse interferes with the echo signal. There are no conditions. A signal acquired under this condition is shown in FIG. The T ₂ ^* relaxation time constant of the FID signal is about 3 msec. The figure (a) has shown the whole of the measured NMR signal, and the figure (b) has expanded and shown the 0-100 msec part.

  From FIG. 40 (b), it can be seen that the FID signal after the 90 ° excitation pulse and the FID signal after the 180 ° excitation pulse are quickly attenuated and acquired under conditions that do not interfere with the echo signal. In this case, the echo signal can be clearly recognized.

Similarly to Case 15, a methanol aqueous solution sample was repeatedly measured 16 times under the condition of Case 19 using a 0.60 mm inner diameter 5-winding coil, and the relationship between the number of experiments and the T ₂ (CPMG) value is shown in FIG. The obtained 16 T ₂ (CPMG) values were statistically analyzed, and the standard deviation of the T ₂ (CPMG) value and its coefficient of variation (= the standard deviation divided by the average value) were also obtained. This is shown in Table 12 above.

41 and Table 12 above, comparing Cases 15 and 19, the variation in the T ₂ (CPMG) value of Case 19 is greatly reduced, and the variation coefficient of the T ₂ (CPMG) value is about 4.6%. It turns out that it has decreased. This shows that the T ₂ (CPMG) value can be measured very stably.

  Similar to Case 15, the transition of the average value of each echo signal intensity measured for a methanol aqueous solution sample under the condition of Case 19 using a 0.60 mm inner diameter 5-coil, the transition of the average value of each time of the FID signal intensity at τ / 3, and 42 (a), (b) and (c) show the transition of the ratio (clarity of echo signal) between the average value of each echo signal intensity and the average value of each FID signal intensity at τ / 3. Show.

Also, as in Case 15, the average of the average value of each echo signal intensity for 16 times (average echo signal intensity) and its coefficient of variation, the average of the average value of each time of FID signal intensity at τ / 3 o'clock for 16 times and its The coefficient of variation and the average of echo signal intensity / FID signal intensity were calculated. The results are shown in Table 12 above. From these, Case 19 is irradiated with a 180 ° excitation pulse, the intensity of the FID signal after lapse of τ / 3 decreases to almost the noise level, and the ratio of the echo signal to the FID signal increases to about 6.5. ing. Accordingly, it can be said that the T ₂ (CPMG) value measured under the condition of Case 19 is more stable than that of Case 15.

  As shown in Tables 10, 11, and 12, the static magnetic field inhomogeneity is gradually increased, and the evaluation value of the gradient magnetic field strength change amount ΔG and the gradient magnetic field strengths D · ΔG are sequentially increased (Case 16). The measurement of ˜18, 20, 21) was similarly performed. Also in these cases, the statistical value was calculated by measuring 16 times similarly to Cases 15 and 19. The measurement results are also summarized in Table 12 above.

43 (a) and 43 (b) are plotted with the standard deviation or coefficient of variation of the T ₂ (CPMG) value on the vertical axis and the gradient magnetic field strength D · ΔG on the horizontal axis using the results of Table 12 above. is there.
From these results, in order to reduce the variation of the T ₂ (CPMG) value to about several percent and perform stable measurement, the gradient magnetic field strength D · ΔG is about 0.10 [gauss] or more. Examples 10 to 14 are preferable, and about 0.15 [gauss] or more, that is, Examples 11 to 14 are more preferable.

As described above, in Experiments 1 to 3, the inner diameter of the small surface coil was changed in three ways: 0.60 mm, 0.91 mm, and 1.30 mm, and the sample was PEM, water, and a 60 [vol%] aqueous methanol solution. Instead, CPMG measurement was performed and the measurement stability of T ₂ (CPMG) value was shown.

These results are shown in FIGS. 44 (a) and 44 (b).
From FIG. 44 (a), the relationship between the standard deviation of the T ₂ (CPMG) value and D · ΔG is almost the same in any experimental results in which the sample of the protic solvent is different from PEM, water, and aqueous methanol solution. Become. Thus, it is considered that the gradient magnetic field strength change amount ΔG and the gradient magnetic field strength D · ΔG provide an evaluation value that can stably measure the echo signal and the amount of the protic solvent. That is, it can be seen that the general formula (3) defines conditions under which the echo signal measurement and the solvent amount measurement for the protic solvent are stably performed. Specifically, in the above experimental results where γ = 42.6 MHz and τ = 10 msec, the variation in T ₂ (CPMG) value is practical when D · ΔG [gauss] is 0.1 or more. Is significantly suppressed. An inflection point exists at D · ΔG≈0.15 [gauss], and when a gradient higher than this is applied, the standard deviation of the T ₂ (CPMG) value becomes almost a noise level and does not vary.

Also, in the relationship between the gradient magnetic field strength D · ΔG and the coefficient of variation of the T ₂ (CPMG) value shown in FIG. 44 (b), the same tendency is shown when the inner diameter D of the protic solvent and the small RF coil is changed. ing. In particular, it can be seen that the results of Experiment 3 using an alcoholic solvent and the results of Experiment 2 using a water sample agree very well.

  From the above, when performing echo signal measurement or protic solvent amount measurement of the protic solvent according to the present invention, it is preferable to satisfy the above general formula (3), and the lower limit value particularly satisfies the above formula (14). It can be said that it is preferable.

In measuring the amount of protic solvent (for example, water content) in a sample according to the present invention, based on the method of converting the intensity of the acquired echo signal into the water content and the T ₂ relaxation time constant calculated from the intensity of the echo signal. There is a method to obtain the water content.
In the former case, it is necessary to measure the absolute value of the echo signal intensity. In order to convert the moisture content, the echo signal intensity may be verified using a standard sample, and the relationship between the two may be associated in advance.
On the other hand, in the latter case, the absolute value of the echo signal intensity is unnecessary, and it is only necessary that the echo signal is relatively measured, that is, the T ₂ (CPMG) value is obtained from the way the echo signal is attenuated. There is. In other words, when the water content is calculated from the echo signal intensity, stable acquisition of the echo signal without variation is required.

  FIG. 45A shows the standard deviation of the echo signal intensity measured by changing the gradient magnetic field intensity D · ΔG based on the results of Experiments 1 to 3 relating to the present invention. It can be seen that in all cases, the standard deviation (variation) of the echo signal intensity decreases as the gradient magnetic field intensity increases.

FIG. 4B shows the coefficient of variation of the echo signal intensity measured by changing the gradient magnetic field intensity D · ΔG. Again, in all cases, the variation coefficient of the echo signal intensity decreases as the gradient magnetic field intensity increases. In particular, when the sample is water and an alcohol aqueous solution (methanol aqueous solution), the coefficient of variation of the echo signal intensity takes almost the same value. When the gradient magnetic field strength D · ΔG is 0.15 [gauss] or more, that is, when the above equation (14) is satisfied, the variation coefficient is 0.05 or less and the echo signal is stably measured. I can say that.
Note that if the average value of the echo signal intensity of the PEM is about the same as that of water, it is estimated that the coefficient of variation further matches.

  Next, by applying a uniform static magnetic field to the sample 115 by the static magnetic field application unit 150, the current ground flowing in the copper plate is calculated from the frequency shift amount of the NMR signal from the water sample placed adjacent to the copper plate. The result of the experiment measured stably will be described.

[Experiment 4]
When calculating the amount of current flowing through the copper plate from the frequency shift amount of the NMR signal, it was examined how the uniformity of the static magnetic field affects the variation in the measured value.
The shape of the echo signal varies depending on whether the uniformity of the static magnetic field is high or low. FIG. 46 is a schematic diagram showing how the shape of an echo signal observed using a small surface coil changes with the uniformity of a static magnetic field. The echo signal in this figure is a “spin echo signal without interference” observed when a sequence in which a gradient magnetic field is applied before and after the 180 ° excitation pulse to rapidly attenuate the FID signal is used.

  When the uniformity of the static magnetic field is high, a strong echo signal is observed for a long time immediately after the application of the gradient magnetic field after the 180 ° excitation pulse is completed. On the other hand, when the uniformity of the static magnetic field is low, an echo signal is observed in the Mt. Fuji type around the time when the phase converges (the position where the time is 15 msec in the figure), and the time when the echo signal is observed is Shorter. The reason for this is that if the static magnetic field is uniform, the phase of the magnetization vector will not be dispersed, and the phase will converge quickly by irradiation of the 180 ° excitation pulse, and this state will be maintained for a very long time. If it is not uniform, the dispersion of the phase of the magnetization vector occurs violently, and the phase converges only before and after the phase convergence time (in the figure, the time is 15 msec).

  In current measurement, the amount of phase change that progresses during a certain period of time is calculated as a “gradient” (frequency shift amount) based on the Real component and Imaginary component of the observed echo signal. For this reason, the longer the time that the echo signal can be observed, the larger the phase change amount, that is, the gradient (frequency shift amount), and the variation included in the phase change amount is reduced, thereby improving the measurement accuracy. . This conceptual diagram is shown in FIG. White circles in the figure represent measured data, and straight lines represent linear approximation of the data.

  As shown in this figure, when both of the measurement data are scattered to the same extent (when the noise level is the same), the uniformity of the static magnetic field is higher and the longer the echo signal can be observed, Variation can be suppressed, and a measurement result with smaller measurement variation can be obtained.

If this is expressed by an equation, it is expressed by the following equation (15).
(Phase change amount) = (Measured phase) / (Measurement time) = {(True value of phase) + (Phase variation due to noise)} / (Measurement time) (15)

  Here, when the “variation in phase due to noise” is the same, the “variation in phase variation” can be reduced as the “measurement time” becomes longer. From the above equation (15), it can be seen that it is better to use measurement data observed for a long time in order to obtain a stable measurement value with a small measurement variation.

  In this experiment, the time during which a significant echo signal can be observed was changed by changing the uniformity of the static magnetic field. This experiment examined how much the variation in the measurement of the frequency shift changes with the observation time of the echo signal.

In the present measurement, the above-described 0.60 mm 5-winding coil was used as the small RF coil 114.
The water sample used in Experiment 2 was used.

  FIG. 48 (a) shows a photograph of a copper plate and a small surface coil installed thereon. The copper plate through which current flows was 0.05 mm thick and 10 mm wide. A current was passed through the copper plate in the direction shown in the figure. A 1 mm hole was formed in the copper plate, and the coil was covered with polyimide tape (thickness 30 μm) through the hole and the small-surface coil conductor was fixed. The copper plate and the coil were attached to the cell with a polyimide tape (thickness 30 μm).

  As shown in FIG. 2B, the water sample was placed on a copper plate and a coil. Another cell was placed on the water sample and pinched, and the water sample was fixed by tightening. The coil is pressed against the water sample.

This sample was measured with two cases shown in Table 13. In the same table, the dial reading of the current passed through the shim coil is given, and in Table 14, X given by each shim coil (GX-coil, GY-coil, GZ-coil) calculated using the above equation (12), The gradient magnetic field strengths ΔG _x , ΔG _y , ΔG _{z in the} Y and Z directions, and the change amount ΔG [gauss / m] of the gradient magnetic field strength as a combined vector thereof, and the coil inner diameters D [m] and ΔG [gauss] / M] is a product D · ΔG.

  The NMR signal was measured by setting the interval between the 90 ° excitation pulse and the 180 ° excitation pulse to 5 msec and setting the echo time to 10 msec. In this sequence, a gradient magnetic field was applied for 1 msec before and after the 180 ° excitation pulse so that the FID signals immediately after the 90 ° and 180 ° excitation pulses did not interfere with the echo signal. Further, a gradient magnetic field was applied again at 10 msec irradiated with a 180 ° excitation pulse, and the magnetization vector was dispersed for the next measurement.

  The NMR measurement conditions were a 90 ° excitation pulse repetition time (TR) of 20 seconds, a 90 ° excitation pulse dummy count of 2, an NMR signal integration count of 1, and a resonance frequency of 43.39 MHz.

<Current measurement at Case 22>
The measurement result when the static magnetic field is uniform is shown. An echo signal when the current I flowing through the copper plate is zero is shown in FIG. The NMR signal is detected by a phase sensitive detection method, and two signals of a real part and an imaginary part are acquired. In FIG. 2A, they are expressed as Real and Imag, respectively. The 90 ° excitation pulse is applied at time = 5 msec. “Power” in the figure is the signal intensity calculated from the real part and the imaginary part, and this form represents the form of the echo signal. It can be seen that when the static magnetic field is uniform, the shape of the echo signal is very flat, and a significant echo signal is observed from time = about 12 msec to about 20 msec.

The phase difference ΔΦ [rad] of the NMR signal is calculated by taking tan ⁻¹ (Re / Img) based on the real part Re and the imaginary part Img. The phase reference is a reference wave from an oscillator included in the NMR apparatus, and this frequency is adjusted in advance to the resonance frequency of the NMR signal. The phase difference between the reference wave (phase Φ ₀ ) that does not change with time and the measured NMR signal is ΔΦ. The relationship between the real part, the imaginary part, and the phase difference ΔΦ is shown in FIG. (It is a general conceptual diagram of real axis, imaginary axis and phase in mathematics.)

FIG. 4C shows the phase difference ΔΦ calculated by taking tan ⁻¹ (Re / Img) of FIG. However, in this figure, only the period from 12.5 msec to 19.5 msec during which the echo signal is observed is shown.

  From FIG. 6C, when the phase difference ΔΦ is substantially constant in time (straight line) and the current I is zero, the NMR signal is rotated with a constant phase difference from the reference wave. I understand.

Next, an echo signal measured when the current I is 0.40 [A] is shown in FIG. 50A, and a phase difference ΔΦ calculated based on the echo signal is shown in FIG. The pulse sequence is the same as when the current I is zero.
In the echo signal in FIG. 49A, unlike in FIG. 49A, it can be seen that the real part and imaginary part of the NMR signal vibrate and the frequency is shifted from the reference wave. In the area of the echo signal, the real part (Real) comes first, and the imaginary part (Imag) vibrates thereafter.

FIG. 50B shows the phase difference ΔΦ calculated by taking tan ⁻¹ (Re / Img) of FIG. In this figure, it can be seen that as time elapses, the phase difference ΔΦ decreases (straight-down straight line), and the phase of the NMR signal delays with time from the reference wave. Originally, the phase difference ΔΦ seems to be a straight line with a downward slope that monotonously decreases with time, but the phase is expressed in the range of 2π from −π to + π, and thus exceeds that range. And appear as discontinuous lines shifted by 2π. This is the reason for discontinuous transition from −π to + π at time = 13 msec, 14.2 msec, 15.9 msec, 17.3 msec, and 18.8 msec.

The phase difference ΔΦ of the NMR signal that changes during 1 msec is defined as “a frequency shift amount Δω [rad / msec] of the NMR signal”.
This frequency shift amount Δω [rad / msec] corresponds to “inclination of phase difference ΔΦ” in FIGS. 49C and 50B. Based on the graph of each phase difference ΔΦ, linear approximation was performed by the least square method, and the frequency shift amount Δω was calculated from the gradient. In the case of Case 22, 6 msec from 13 msec to 19 msec is a time during which an echo signal is significantly observed compared to noise, and the variation in the phase difference ΔΦ between them is small. Using the phase difference data at 112 points during this 6 msec, calculation of linear approximation was performed.
In order to statistically analyze the variation in the frequency shift amount obtained by this method, measurement was performed seven times under the same conditions, and the frequency shift amount was calculated by the same calculation method. Moreover, the electric current value which flows through a copper plate was changed into 0.0 [A], 0.1 [A], and 0.2 [A], and it measured 7 times similarly. The results of these seven measurements are shown in FIG.

  Table 15 shows the statistical value of the frequency shift amount obtained under the Case 22 conditions. This table also shows the data interval when the frequency shift amount is linearly approximated, and the number of data points used.

  From the table, the variation coefficient in Case 22 is 3.3% when 0.10 [A] is energized with a small frequency shift, and 0.8% when 0.40 [A] is energized with a large frequency shift. It was. From this result, it can be said that the variation in the measurement amount is small and the measurement value is stable.

<Current measurement in Case 23>
Experiments were conducted on how the variation in frequency shift changes when the T ₂ ^* relaxation time constant is shortened to some extent and the static magnetic field is intentionally made nonuniform. Under the conditions of Case 23 in Tables 13 and 14, the same measurement as in Case 22 was performed. The measurement results are shown.

  FIG. 52 (a) shows an echo signal when the current I flowing through the copper plate is zero. From this figure, when the static magnetic field is not uniform, the echo signal becomes Mt. Fuji and becomes shorter. The time during which a significant echo signal for noise is observed is from time = about 13.5 msec to about 16.5 msec.

FIG. 4B shows the phase difference ΔΦ calculated by taking tan ⁻¹ (Re / Img) of FIG. However, in this figure, only the period from 12.5 msec to 19.5 msec during which the echo signal is observed is shown. From this figure, it can be seen that the interval in which the variation due to noise is small and the phase difference ΔΦ is stably obtained is from about 14 msec to about 16 msec. In Case 23, linear approximation was performed using this section.

  Next, FIG. 53A shows an echo signal measured when the current I is 0.40 [A], and FIG. 5B shows a phase difference ΔΦ calculated based on the echo signal. The pulse sequence is the same as when the current I is zero.

  Similarly to the relationship between FIG. 49A and FIG. 50A, in the echo signal of FIG. 53A, the real part and the imaginary part of the NMR signal oscillate and the frequency is the reference wave as compared with FIG. You can see how it is off.

FIG. 53B shows the phase difference ΔΦ calculated by taking tan ⁻¹ (Re / Img) of FIG. In this figure, it can be seen that as time elapses, the phase difference ΔΦ decreases (straight-down straight line), and the phase of the NMR signal delays with time from the reference wave. In this case, the time for discontinuously shifting from −π to + π is seen at time = 14.2 msec and 15.9 msec.

  Similar to Case 22, linear approximation was performed by the method of least squares based on the respective phase difference ΔΦ graphs of FIGS. 52 (b) and 53 (b), and the frequency shift amount Δω was calculated from the gradient. In the case of Case 23, a period of about 2 msec from about 14 msec to about 16 msec is a time during which an echo signal is significantly observed as compared with noise. Therefore, linear approximation calculation was performed using 112 phase difference data for 1.8 msec between time = 14.16 msec and 15.96 msec.

  In the same manner as in Table 15, in order to statistically analyze the variation in the frequency shift amount, measurement was performed seven times under the same conditions, and the frequency shift amount was calculated by the same calculation method. Further, the current value passed through the copper plate was changed to 0.0 [A], 0.1 [A], 0.2 [A], and 0.4 [A], and the measurement was performed seven times in the same manner. The results of the seven measurements are shown in FIG.

  Table 16 shows the statistical value of the frequency shift amount obtained under the Case 23 conditions. This table also shows the data interval when the frequency shift amount is linearly approximated, and the number of data points used. The number of data points used is the same as in Table 15.

  In order to compare the influence of the difference between the conditions of Cases 22 and 23 on the variation in the frequency shift amount as a graph, the standard deviations and the values of the coefficient of variation described in Tables 15 and 16 are shown in FIGS. 55 (a) and 55 (b). It was shown to.

The following can be seen from the results of this experiment. The frequency shift amount calculated from the NMR signal measured under the Case 22 condition with high static magnetic field uniformity is smaller in variation than the Case 23 condition with low static magnetic field uniformity. As a result, it can be said that the higher the uniformity of the static magnetic field, the more stable the frequency shift amount can be measured.
Further, the frequency shift amount and the amount of current flowing through the copper plate are in a directly proportional relationship, and the amount of current flowing through the copper plate can be more stably estimated because the frequency shift amount can be stably measured.

  Therefore, by changing the output of the static magnetic field adjusting shim coil 151 and switching the static magnetic field applied to the sample 115 and the small RF coil 114 between the gradient magnetic field and the uniform magnetic field as in the above embodiment, the protic solvent in the sample is changed. It is possible to stably measure the amount and the amount of current. In addition, as another example of measurement using a static magnetic field as a uniform magnetic field, the above spectrum analysis of alcohols can be exemplified.

It is a conceptual diagram of the measuring method of the echo signal by this invention. It is a flowchart which shows the outline | summary of a moisture content measurement. It is a conceptual diagram of the phase difference of a nuclear magnetization vector. It is a hardware block diagram which shows an example of schematic structure of a measuring device. It is a functional block diagram of a measuring device. It is a figure which shows an example of a small RF coil. It is a figure which shows a mode that the small surface coil installed in the cell was connected to LC resonance circuit. It is a figure which shows an example of LC circuit with a small surface circuit. It is a schematic diagram which shows the shim coil for static magnetic field adjustment. It is a layout diagram of a polymer electrolyte sandwiched between cells with a flow path, a small surface coil, supplied nitrogen gas and water. It is a figure which shows an example of a structure of a cell with a flow path. 6 is a diagram showing a waveform of an NMR signal in Comparative Example 1. FIG. It is a diagram showing a change in the T ₂ (CPMG) value in Comparative Example 1. 6 is a diagram illustrating a transition of an average value of second, fourth, and sixth echo signal intensities in Comparative Example 1. FIG. It is a figure which shows transition of the average FID signal strength at the time of (tau) / 3 progress from 180 degree pulse irradiation in the comparative example 1. FIG. It is a figure which shows transition of ratio of the average value of echo signal intensity | strength at the time of (tau) / 3 progress from 180 degree pulse irradiation in the comparative example 1, and the average value of FID signal intensity | strength. FIG. 3 is a diagram showing a waveform of an NMR signal in Example 1. It is a diagram showing a change in the T ₂ (CPMG) values in Example 1. (A) is a figure which shows transition of each time average value of the echo signal strength in Example 1. FIG. (B) is a figure which shows transition of each time average value of the FID signal strength at the time of (tau) / 3 in Example 1. FIG. (C) is a figure which shows transition of ratio of each time average value of echo signal strength in Example 1, and each time average value of FID signal strength at the time of τ / 3. FIG. 6 is a diagram showing a waveform of an NMR signal in Example 2. It is a diagram showing a change in the T ₂ (CPMG) values in the second embodiment. (A) is a figure which shows transition of each time average value of the echo signal strength in Example 2. FIG. (B) is a figure which shows transition of each time average value of FID signal strength at the time of (tau) / 3 in Example 2. FIG. (C) is a figure which shows transition of ratio of each time average value of echo signal strength in Example 2, and each time average value of FID signal strength at the time of τ / 3. Is a diagram showing the relationship between the standard deviation of the gradient field strength _{(D · ΔG) T 2 (} CPMG) values. (A) is a calibration curve showing the relationship between the water content and the T ₂ (CPMG) value, and (b) is a diagram showing the relationship between the water content and the echo signal intensity. (A) is a figure which shows an inner diameter 0.60mm5 winding coil, (b) is a figure which shows an inner diameter 1.30mm10 winding coil. 6 is a diagram showing a waveform of an NMR signal in Comparative Example 2. FIG. It is a diagram showing a change in the T ₂ (CPMG) value in Comparative Example 2. (A) is a figure which shows transition of each time average value of the echo signal strength in the comparative example 2. FIG. (B) is a figure which shows transition of each time average value of the FID signal strength at the time of (tau) / 3 in the comparative example 2. FIG. (C) is a figure which shows transition of ratio of each time average value of echo signal strength in Comparative Example 2, and each time average value of FID signal strength at τ / 3. FIG. 6 is a diagram showing a waveform of an NMR signal in Example 3. It is a diagram showing a change in the T ₂ (CPMG) values in Example 3. (A) is a figure which shows transition of each time average value of the echo signal intensity | strength in Example 3. FIG. (B) is a figure which shows transition of each time average value of FID signal strength at the time of (tau) / 3 in Example 3. FIG. (C) is a figure which shows transition of ratio of each time average value of echo signal strength in Example 3, and each time average value of FID signal strength at the time of τ / 3. (A) is a figure which shows the relationship between the gradient magnetic field strength (D * ΔG) and the standard deviation of the T ₂ (CPMG) value, and (b) is the gradient magnetic field intensity (D · ΔG) and the T ₂ (CPMG) value. It is a figure which shows the relationship with the coefficient of variation. In Experiment 2, it is a diagram showing the relationship between the standard deviation or coefficient of variation of the gradient magnetic field strength (D · .DELTA.G) and T ₂ (CPMG) values in the case of changing the inner diameter D of the small-sized RF coils. In Experiment 1 and 2 is a diagram showing the relationship between the standard deviation or coefficient of variation of the gradient magnetic field strength (D · .DELTA.G) and T ₂ (CPMG) values in the case of changing the inner diameter D of the small-sized RF coils. It is a figure which shows a mode that the small aqueous solution coil was installed in the cell center, and the methanol aqueous solution sample was set | placed on it. It is a figure which shows the waveform of the FID signal in the comparative example 6. It is a figure which shows the waveform of the NMR signal in the comparative example 6. It is a diagram showing a change in the T ₂ (CPMG) values in Comparative Example 6. (A) is a figure which shows transition of each time average value of the echo signal strength in the comparative example 6. FIG. (B) is a figure which shows transition of each time average value of the FID signal strength at the time of (tau) / 3 in the comparative example 6. FIG. (C) is a figure which shows transition of ratio of each time average value of the echo signal strength in Comparative Example 6, and each time average value of the FID signal strength at τ / 3. FIG. 10 is a diagram showing a waveform of an NMR signal in Example 12. It is a diagram showing a change in the T ₂ (CPMG) values in Example 12. (A) is a figure which shows transition of each time average value of the echo signal intensity | strength in Example 12. FIG. (B) is a figure which shows transition of each time average value of FID signal strength at the time of (tau) / 3 in Example 12. FIG. (C) is a figure which shows transition of ratio of each time average value of echo signal strength in Example 12, and each time average value of FID signal strength at τ / 3. (A) is a figure which shows the relationship between the gradient magnetic field strength (D * ΔG) and the standard deviation of the T ₂ (CPMG) value, and (b) is the gradient magnetic field intensity (D · ΔG) and the T ₂ (CPMG) value. It is a figure which shows the relationship with the coefficient of variation. The figure which shows the relationship between the standard deviation or variation coefficient of gradient magnetic field strength (D * ΔG) and T ₂ (CPMG) value when changing the inner diameter D of the small RF coil and the protic solvent sample in Experiments 1 to 3 It is. It is a figure which shows the relationship between the standard deviation or variation coefficient of the gradient magnetic field intensity (D * ΔG) and the echo signal intensity when the inner diameter D of the small RF coil and the protic solvent sample are changed in Experiments 1 to 3. It is the schematic of the level of static magnetic field uniformity, and the shape of the echo signal observed with a small surface coil, (a) shows the case where static magnetic field uniformity is high, (b) shows the case where static magnetic field uniformity is low. FIG. It is a conceptual diagram of the level of static magnetic field uniformity and the method of suppressing the dispersion | variation in measurement data, (a) is a figure which shows a case where static magnetic field uniformity is high, (b) is a case where static magnetic field uniformity is low. (A) is a figure which shows the small surface coil affixed on the copper plate, (b) is a figure which shows the water sample put on the copper plate and the coil. (A) is a figure which shows the echo signal acquired when the electric current I sent through the copper plate in Case22 is zero, (b) is a figure which shows the relationship between real part and imaginary part, and phase difference (DELTA) (phi), (c) These are figures which show the time passage of the phase difference ΔΦ of the echo signal acquired when the current I passed through the copper plate is zero. (A) is a figure which shows the echo signal acquired when the electric current I sent through the copper plate in Case22 was 0.40 [A], and (b) when the electric current I passed through the copper plate was 0.40 [A]. It is a figure which shows the time passage of phase difference (DELTA) (PHI) of the acquired echo signal. It is a figure which shows transition for every frequency | count of experiment of the frequency shift amount obtained on the conditions of Case22. (A) is a figure which shows the echo signal acquired when the electric current I sent through the copper plate in Case23 is zero, (b) is the time of phase difference ΔΦ of the echo signal acquired when the electric current I passed through the copper plate is zero It is a figure which shows progress. (A) is a figure which shows the echo signal acquired when the electric current I sent through the copper plate in Case23 is 0.40 [A], and (b) when the electric current I passed through the copper plate is 0.40 [A]. It is a figure which shows the time passage of phase difference (DELTA) (PHI) of the acquired echo signal. It is a figure which shows transition for every frequency | count of experiment of the frequency shift amount obtained on the conditions of Case23. (A) is a figure which shows the standard deviation of the frequency shift amount measured on the conditions of Case22 and 23, (b) is a figure which shows the variation coefficient of the frequency shift amount measured on the conditions of Case22 and 23. It is a distribution map which shows an example of the magnetic field intensity Hz (xp, yp, zp) of the z direction of the oscillating magnetic field intensity at the time of using the small surface coil of 1 turn. It is a conceptual diagram which shows a mode that the FID signal observed by the conventional CPMG method, and the FID signal and the echo signal interfere.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 Measuring apparatus 102 RF oscillator 104 Modulator 106 RF amplifier 112 Preamplifier 113 Permanent magnet 114 Small RF coil 115 Sample 116 Sample mounting stand 118 A / D converter 127 Sequence table 128 Time measuring unit 129 Operation signal receiving unit 130 Solvent amount calculation unit ( Calculation unit)
131 Data reception unit 132 Moisture amount calculation unit 135 Output unit 150 Static magnetic field application unit 151 Static magnetic field adjustment shim coil 159 Current drive power supply 161 Switch unit 210 RF pulse generation unit 220 NMR signal detection unit 301 Detector 305 Storage unit 307 Static magnetic field Strength control unit (control unit)

Claims (17)

An apparatus for measuring a local echo signal generated from a protic solvent at a specific location in a sample using a nuclear magnetic resonance method,
A static magnetic field applying means for applying a static magnetic field to the sample;
Static magnetic field strength control means for controlling the strength of the static magnetic field applied to the sample;
An RF coil that applies an excitation oscillating magnetic field to a part of the sample and acquires an echo signal corresponding to the excitation oscillating magnetic field;
With
The static magnetic field strength control means includes an inner diameter (D [m]) of the RF coil, a gradient magnetic field strength variation (ΔG [gauss / m]), and a nuclear magnetorotation ratio (γ [Hz / T] of the protic solvent. ), And applying the static magnetic field of the predetermined gradient magnetic field strength change amount (ΔG) represented by the following formula (1) from the static magnetic field applying means using the excitation interval (τ [sec]). A measuring device.
400 ≧ D [m] · ΔG [gauss / m] · γ [Hz / T] · 10 ⁻⁴ [T / gauss] · τ [sec] ≧ 4 (1)   The intensity of an echo signal corresponding to the excitation oscillating magnetic field is at least five times the intensity of the free induction decay signal when τ / 3 has elapsed since the application of the excitation oscillating magnetic field. 1. The measuring device according to 1.   The measurement apparatus according to claim 1, wherein the excitation interval (τ) is 0.1 msec or more and 100 msec or less.   The static magnetic field applying means includes both a permanent magnet that applies a uniform static magnetic field inside the RF coil and a static magnetic field adjustment shim coil that imparts a gradient to the static magnetic field applied by the permanent magnet. The measuring device according to any one of claims 1 to 3.   The measuring apparatus according to claim 4, wherein at least three sets of the static magnetic field adjustment shim coils are provided, and the gradient is given to each of three orthogonal axes. 6. The measuring device according to claim 1, wherein an inner diameter (D) of the RF coil is 0.01 · 10 ^{−3 to} 100 · 10 ⁻³ [m].   The measuring apparatus according to claim 1, further comprising a solvent amount calculating unit that calculates an amount of the protic solvent at a specific portion of the sample from the intensity of the acquired echo signal. . The solvent amount calculating means calculates a T ₂ relaxation time constant from the intensity of the acquired echo signal, and calculates the amount of the protic solvent at a specific location of the sample from the calculated T ₂ relaxation time constant. The measuring device according to claim 7 to calculate.   The measuring device according to claim 7 or 8, wherein the protic solvent is water or alcohols.   10. The static magnetic field strength control means can switch the gradient strength of the static magnetic field applied by the static magnetic field application means to the predetermined gradient magnetic field strength change amount (ΔG) or substantially zero. The measuring apparatus in any one of. A first measurement mode in which the static magnetic field applying means calculates the amount of the protic solvent from the intensity of the echo signal acquired in a state where the static magnetic field having the predetermined gradient magnetic field strength variation (ΔG) is applied to the sample; ,
The apparatus further comprises switching means for switching between a second measurement mode for measuring another characteristic value of the protic solvent from the intensity of an echo signal acquired in a state where the gradient intensity of the static magnetic field is substantially zero. 10. The measuring device according to 10. A method of measuring a local echo signal generated from a protic solvent at a specific location in a sample using a nuclear magnetic resonance method,
RF coil inner diameter (D [m]), gradient magnetic field strength change (ΔG [gauss / m]), nuclear magnetic rotation ratio (γ [Hz / T]) of the protic solvent, excitation While applying a static magnetic field having a predetermined gradient magnetic field strength change amount (ΔG) represented by the following formula (2) using an interval (τ [sec]), a part of the sample is applied using the RF coil. A measurement step of applying an oscillating magnetic field for excitation once or a plurality of times and measuring an echo signal corresponding to the oscillating magnetic field for excitation;
Measuring method including
400 ≧ D [m] · ΔG [gauss / m] · γ [Hz / T] · 10 ⁻⁴ [T / gauss] · τ [sec] ≧ 4 (2)   The intensity of an echo signal corresponding to the excitation oscillating magnetic field is at least five times the intensity of the free induction decay signal when τ / 3 has elapsed since the application of the excitation oscillating magnetic field. 12. The measuring method according to 12. A calculation step for calculating the amount of the protic solvent at a specific location of the sample from the intensity of one or a plurality of the echo signals measured in the measurement step,
The measurement method according to claim 12, further comprising: The calculating step comprises:
Obtaining calibration data indicating the correlation between the amount of protic solvent in the sample and the intensity of the echo signal;
Calculating the amount of the protic solvent from the test data and the intensity of the acquired echo signal;
The measurement method according to claim 14, comprising: The calculating step comprises:
Calculating a T ₂ relaxation time constant from the intensity of the measured echo signal;
Obtaining test data indicating the correlation between the amount of protic solvent in the sample and the T ₂ relaxation time constant, and from the test data and the calculated T ₂ relaxation time constant, at a specific location of the sample Calculating the amount of protic solvent;
The measurement method according to claim 14, comprising: In the measuring method in any one of Claim 14 to 16,
A switching step of switching the gradient strength of the static magnetic field applied to the sample from the predetermined gradient magnetic field strength change amount (ΔG) to substantially zero;
While the intensity of the gradient of the static magnetic field is substantially zero, the excitation vibration magnetic field is applied to a part of the sample one or more times using the RF coil, and the excitation vibration A second measurement step for measuring an echo signal corresponding to the magnetic field;
From the intensity of one or a plurality of the echo signals measured in the second measurement step, a second calculation step of calculating other characteristic values of the protic solvent at a specific location of the sample;
The measurement method characterized by further including.