JPH0430859B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION "Field of Industrial Application" The present invention relates to a nuclear magnetic resonance tomographic image forming apparatus that obtains a tomographic image of a subject using nuclear magnetic resonance.

"Prior Art" First, we will discuss the main conventional method (imaging method) of obtaining tomographic images using nuclear magnetic resonance (NMR). The currently used imaging method is the projection reconstruction method.
and the 2D-FT method (spin warp method). The projection reconstruction method places the object in a homogeneous static magnetic field _H0 ,
While applying a linear gradient magnetic field Gz whose magnetic field strength changes in the z direction in the same direction as this static magnetic field,
RF pulse (high frequency electromagnetic field) called 90° pulse
Add. The 90° pulse is made into a pulse by amplitude modulating a high frequency electromagnetic field with a constant frequency ω ₀ . Through this process, the nuclear spin that satisfies ω ₀ = r (H ₀ + GzZ) at position Z on the z-axis in a plane perpendicular to the z-axis is tilted by 90°, resulting in a rotational coordinate system that moves at ω _0. It will point in the y′-axis direction. r is the gyromagnetic ratio. This plane becomes the slice plane of the tomographic image,
This process is called excitation of the slice plane. In the above example, the xy plane becomes the slice plane because a gradient magnetic field is applied in the z direction, but by selecting the direction of the gradient magnetic field, any plane can be used as the slice plane. Select the slice plane as shown in Figure 1.
A 180° pulse is applied after a time τ from the 90° pulse.
The 180° pulse is an RF pulse similar to the 90° pulse, but it rotates the nuclear spins by twice the angle as the 90° pulse. Due to the action of the 180° pulse, a phenomenon called a spin echo occurs that generates a free induction decay signal of angular frequency ω ₀ at time 2τ. This spin
Collect echo signals (free induction decay signals) as data. However, at this time, a gradient magnetic field G in the θ direction is added by combining the gradient magnetic field G _x in the x direction and the gradient magnetic field G _y in the y direction. Assuming that the position in the θ direction is S, frequency analysis of the collected data yields an angular frequency distribution given by ω=r(H ₀ +G〓S). This distribution is a projected image of the subject in the θ direction. Therefore, by changing θ little by little and making one rotation (360°), image reconstruction can be performed from these projection data by back projection processing.

Next, we will discuss the 2D-FT method (Spin Warp method). There are several variations of the 2D-FT method, but the pulse sequence of a typical one is shown in Figure 2.
The difference between this method and the projection reconstruction method is that after selectively exciting the slice plane, gradient magnetic field pulses are applied in the y direction to provide phase encoding in the y direction.
Collect data while applying a constant x-gradient magnetic field (readout gradient), adjust the amount of phase encoding by varying the amplitude of the y-gradient magnetic field pulse, collect data repeatedly, and read out the collected data. The point is to obtain an image by performing a two-dimensional Fourier transform on the image.

The projection reconstruction method and 2D-FT method described above each obtain information according to the density of nuclear spins.

A pulse sequence in which an inversion pulse (e.g., 180° pulse) is added before the 90° pulse for slice selection in these projection reconstruction methods and 2D-FT methods, as shown in Figure 3A, is called an IR sequence. The image obtained is called an IR image (inverted recovery image). The signal intensity of this IR image (I _IR is I _IR = I ₀ (1-2e ^{- Td/T1} ), which is influenced by the longitudinal relaxation time T ₁ value of the nuclear spin. Here, I ₀ is the signal strength at equilibrium, and Td is the waiting time between the inversion pulse and the slice selection pulse.

A saturation recovery method is also used to obtain a signal related to the longitudinal relaxation time T ₁ . In this method, a slice selection pulse (90° pulse) is repeatedly applied and the nuclear spin echo signal generated immediately after is detected.The signal intensity I _SR is: I _SR = I ₀ (1-e ^-Tr/TI ) It is. Tr is the repetition period of the slice selection pulse. If the repetition time Tr is sufficiently longer than T ₁ , the second term can be ignored, and it can be considered that I _SR ≒ I _0. Therefore, the IR image signal I _IR and the saturated recovery image can be calculated by the pulse sequence shown in Figure 3B. (SR image) signal I _SR is obtained, and by calculating T ₁ = −Td / log _e (I _SR − I _IR /2I _SR ) for each pixel, the
An image of T ₁ value can be obtained.

“Problems to be solved by the invention” Conventional nuclear spin density images, T ₁ (longitudinal relaxation time) images,
In IR (inversion recovery) images, there is a small difference between normal cells in humans and animals and tumors such as cancer, making it difficult to distinguish between these at an early stage and making quantitative diagnosis difficult.

On the other hand, NMR glass tubes containing normal rat liver tissue and tumor tissue were incubated at 25°C with TSP (3-tritriple liver tissue).
An experiment has been reported in which an aromatic amino acid residue with a chemical shift of 7.13 ppm in the resonance frequency was mainly excited as a reference (methylsilyl propionate), and the cross-relaxation time T _IS was measured by adding a sampling pulse.
According to this report, the relationships between the reciprocals of the cross relaxation time T _IS and the longitudinal relaxation time T ₁ and the water content of the tissue are as shown in FIGS. 4A and B, respectively. In these figures, the horizontal axis indicates the dry weight after evaporating water relative to the original weight, and the one scale on the vertical axis is as shown in Figure 4A.
has twice the weight as in FIG. 4B. From these figures, it is understood that the difference between normal tissue and tumor tissue is about twice as large for 1/T _IS as compared to 1/T ₁ .

Cross-relaxation is a process in which a high-energy level nuclear spin transfers energy to a low-energy level nuclear spin due to dipolar interaction between two nuclear spins, causing relaxation. It is thought that this is likely to occur.

On the other hand, when a nuclear spin absorbs electromagnetic waves and later emits electromagnetic waves, there is a phenomenon in which the emitted signal strength and T ₁ value change due to dipole interaction or polar exchange with another nuclear spin. This is called the nuclear Overhauser effect. Cross-relaxation is also closely related to the nuclear Overhauser effect, and the reason why the cross-relaxation time T _IS becomes longer in tumor tissues is thought to be due to the weakening of the dipolar interaction between water and biopolymers.

``Means for Solving the Problems'' According to the present invention, a high frequency electromagnetic field is applied to a subject placed in a static magnetic field to create a nuclear overlap between protons of biopolymers of the subject and protons of water. The Hauser effect is generated, and then a high-frequency electromagnetic field is irradiated to the specimen to excite the nuclear spins of protons in the specimen, and the nuclear magnetic resonance signal of the excited nuclear spins is detected to detect the nuclei in the specimen. A cross-relaxation influenced image is created corresponding to the magnetic resonance signal. Cross-relaxation influenced images or cross-relaxation time images allow for example to distinguish between normal cells and tumors more clearly than traditional _T1 images. To selectively cause the nuclear Overhauser effect, for example, give two 90° pulses and select the pulse interval so that the phase difference between the free precession of the two nuclear spins is 2π. , or selectively saturate specific nuclear spins.

``Example'' As described above, when obtaining a two-dimensional cross-relaxation time image, in the present invention, a high-frequency electromagnetic field is applied to the subject before exciting the nuclear spins on the slice plane to selectively apply the overhauser to the nuclear spins. produce an effect. This Overhauser effect (NOE:
A pulse sequence for selectively causing the Nuclear Overhauser effect is shown in FIG. In this sequence, the first 90° pulse and the second 90° pulse do not select the slice plane. third
Only the 90° pulse selects the slice plane.
Regarding the frequency axis (chemical shift direction), the first
Both the second and third are non-selective. By the first 90° pulse, all the spins of the target nucleus are
It falls in the y′ direction. Free precession is performed during the time t ₁ until the next second 90° pulse. Figure 6 depicts this movement as a model. For example, when the spin of a water proton is I and the spin of a proton of an amino acid residue in a biopolymer is S, there is a chemical shift difference of δ between these spins I and S. By the first 90° pulse, the axes of the spins I and S are set in the y' direction as shown in Figure 6A, and the phase difference during the free precession of these nuclear spins I and S during time _t1 . Δφ will occur as Δφ=2π(ν _I −ν _S )t ₁ =2πδt ₁ . ν _I is the resonance frequency of the nuclear spin I, and ν _S is the resonance frequency of the nuclear spin S. If t ₁ is determined so that this Δφ becomes π, that is, the state shown in Figure 6B is applied, and the next 90° pulse is applied, the nuclear spin I becomes as shown in Figures 6C and D. Perform pure vertical relaxation. On the other hand, when Δφ is 2π (Fig. 7B), the equations expressing the relaxation of nuclear spins I and S are as follows, dI _(t) /dt = ρ _I (I ₀ −I _{(t )} ) +σ _IS (S ₀ −S _(t) ) dS _(t) /dt = ρ _S (S ₀ −S _(t) )+σ _SI (I ₀ −I _(t) ) Signal I _(t) , S _{( t)} , the equilibrium state signals I ₀ and S ₀ are S _(t)
≠S ₀ , so in the case of internuclear cross-relaxation, 1/T _IS =σ _IS ≠0, so σ _IS (S ₀ −S _(t) ) is the relaxation of nuclear spin I dI _(t) /dt greatly affects. ρ _I is the reciprocal of the longitudinal relaxation time of the nuclear spin I, ρ _S is the reciprocal of the longitudinal relaxation time of the nuclear spin S, and σ is the cross-relaxation rate. Figure 7 shows the model.

When looking specifically at the cross-relaxation between amino acid residues and water, for example, the -
Assuming that the difference in chemical shift between 2.45 ppm and the 4.7 ppm peak of water is 7 ppm, when the static magnetic field is 3000 Gauss, the resonance frequency is 12.75 MHz, so Δφ = 2π × (12.75 × 10 ⁶ ) × (7 × 10 ^-6 ) × t ₁ ≡2π, t ₁ = 1 [msec] Also, if the static magnetic field is 1 Tesla (10,000 Gauss),
It is sufficient to set t ₁ =3.4 [msec]. like this time t ₁
By selecting , a nuclear Overhauser effect can be selectively obtained between the two selected nuclear spins I and S. That is, in FIG. 5, the nuclear Overhauser effect occurs after the second 90° pulse.

In a two-component system, when the interaction between the nuclear spins I and S is relatively weak, the relationship between the mixing time τm (Fig. 5) and the signal intensity is determined as follows. When the interaction is relatively weak, the relaxation components are expressed as λ ₁ and
If λ ₂ , σ=σ _IS =σ _SI λ ₁ = 1/2 [(ρ _I + ρ _S ) + √( _I − _S ) ² +4 ² ] λ ₂ = 1/2 [(ρ _I + ρ _S ) − √( _I − _S ) ² +4 ² ] The signal strength is I(τm)=I ₀ [1−2(ρ ₁ −λ ₂ )/λ ₁ −λ ₂ e ⁻ 〓 ₁ ^Tm −2(λ ₁ − ρ ₁ )/λ ₁ −λ ₂ e ⁻ 〓 ₁ ^Tm ] +S ₀ [−2σ/λ ₁ −λ ₂ e ⁻ 〓 ₁ ^Tm +2σ/λ ₁ −λ ₂ e ⁻ 〓 ₂ ^Tm ]. Here, the second term on the right side is the main term for cross relaxation. The dependence of this second term on the mixing time τ _n is shown in FIG.

Figure 5 shows the case where the value of _t1 is set to Δφ=π and the case where the value of Δφ=2π is set for at least three different values of this mixing time τ _n where the second term is sufficiently large. As shown in Figure 2, spin echoes are obtained using a normal method (2D-FT method in this example), and using these images, the cross-relaxation sum velocity σ is obtained for each pixel using the least squares estimation method to obtain an image of σ.

Note that, similar to the technique used in conventional imaging methods, a gradient magnetic field pulse called a spoiling pulse is applied after the second 90° pulse, as shown in Figure 5, to remove the transverse magnetization component of the spins. You may also erase it to obtain a clearer image.

Next, in order to make it less susceptible to magnetic field inhomogeneity and transverse relaxation, the following can be done. The pulse sequence is shown in FIG. The behavior of the nuclear spin at this time is shown in FIG. first
When a 90° pulse is applied, the spin I of water protons and the spin S of protons of amino acid residues are flipped to point in the y' direction (Fig. 10A), and during the following period of τ ₁ , spin I , S undergoes free precession and the first
As shown in Figure 0B, it faces in a different direction, and transverse relaxation and transverse relaxation due to the gradient magnetic field G _x occur. If a 180° pulse is applied in the y' direction, the spin distribution will become as shown in FIG. 10C. Due to this 180° pulse, the spins S and I begin to focus again, creating a gradient magnetic field.
If G _x is at a symmetrical position with respect to the 180° pulse, spin echoes will occur at positions τ ₁ from the 180° pulse. However, by shifting the position of the gradient magnetic field, it is possible to freely shift the echo caused by the convergence of phase variations caused by the gradient magnetic field. That is, if ν ₀ is the Larmor frequency and δ is the chemical shift, then if the gradient magnetic field is set so that 2πν ₀ · δ (τ ₁ − τ ₂ ) = π, then at the time τ ₂ from the 180° pulse, as shown in Fig. 10. A spin distribution as shown in D can be obtained. Of course, it is also possible to make the spins I and S coincide in the y' direction so that τ ₁ =τ ₂ , that is, it is also possible to provide a phase difference of 0 or π between these spins I and S.

If a second 90° pulse is applied under these conditions, the first
As shown in Figure 0E, spins I and S can be directed in opposite directions, or conversely, can be directed in the same -z' direction. After this, the interactions between water protons and amino acid residue protons are imaged by causing longitudinal relaxation and cross-relaxation during a waiting time of τ _n and performing data convergence using a conventional imaging method. I can do it.

As a specific example, water and 7ppm in a magnetic field of 5000 Gauss
When emphasizing the interaction between _{an amino acid and water that has a chemical shift difference of , the phase difference π τ 1 −τ 2 = 1 / (} ν ₀ It is sufficient to apply a gradient magnetic field under the conditions of δ) = 6.8 msec and a phase difference of 2π.

In the above, longitudinal relaxation or cross-relaxation was obtained by setting the phase difference between the free precession of the two components of transverse spin to π or 2π. However, by selectively irradiating specific chemical shift components with a high-frequency magnetic field, we It is also possible to cause the Overhauser effect to cause cross-relaxation.
For example, by selectively irradiating amino acid residues with a high-frequency electromagnetic field (saturation selection pulse) with a frequency that differs by the amount of the chemical shift, the magnetization is directly saturated (the number of high-energy spins and low-energy spins is equalized). ) Immediately after the irradiation is turned off, a gradient magnetic field and a slice-selective high-frequency pulse are applied to selectively excite the slice plane, and thereafter imaging data is collected using phase encoding and projection reconstruction methods. In order to change the contrast of the image, it may be used in combination with a sequence such as a spin echo method, a saturation recovery method, an inversion recovery method, or the like. An example of the pulse sequence is shown in FIG. The relationship between the irradiation time τ of the relaxation selection pulse and the obtained spin A signal intensity is expressed as
Shown in Figure 2. When a selective saturation pulse is applied, the spin S of the amino acid residue is quickly saturated and its magnetization becomes 0, but the spin I of the water proton is due to the nuclear Overhauser effect between the spin S of the proton of the amino acid residue. The equilibrium value I ^∞ is slowly approached by the cross relaxation based on

The equilibrium value is dI ^∞ /dt=ρ ₁ (I ₀ −I ^∞ )+σS ₀ =0, so I ^∞ =I ₀ +σ/ρ ₁ S ₀ . In the case of biopolymers, if σ<0 and a negative Overhauser effect occurs, I ^∞ <I ₀ .

The irradiation time τ of the selective saturation pulse and the signal intensity can be approximated as follows.

I(τ)=I ^∞ + (I ₀ −I ^∞ )e ^- 〓 ^/T1* 1/T ₁ ^* = 1/T ₁ + 1/T _IS However, in this case, water protons and amino acid residue protons are strongly mutual. , and that they follow the same relaxation equation.

Therefore, the image data obtained by the above pulse sequence in which protons S of amino acid residues are selectively irradiated reflects the cross relaxation time T _IS . By capturing at least three images of this image data while changing the value of τ, I ₀ , I ^∞ , and T ₁ ^* can be determined for each pixel using the least squares estimation method. or,
If the image data of the longitudinal relaxation time T ₁ is obtained by another method, the cross-relaxation image of T _IS can be obtained from 1/T ₁ ^* −1/T ₁ =1/T _IS .

The apparatus for obtaining an image within a selected plane of a situation affected (or unaffected) by the cross-relaxation of nuclear spins is constructed with hardware similar to a conventional nuclear magnetic resonance tomography apparatus. FIG. 13 shows an example. Main electromagnet 11 that generates the main static magnetic field layer H ₀ , each gradient magnetic field G _x , G y , G z in the x, _y , and _z directions
A gradient magnetic field creating coil 12 that generates a magnetic field, and a transmitting/receiving coil 13 that transmits and receives high frequency electromagnetic waves are provided at the position where the subject is placed. A current is supplied to the main electromagnet 11 from an electromagnet power supply 14, a timing waveform is amplified by a gradient magnetic field current amplifier 15, and the amplified current is selectively supplied to each gradient magnetic field generating coil 12 as a current. A timing frequency is set for the synthesizer 16, and the timing pulse is applied from the synthesizer 16 to the transmitter 17, and the high frequency pulse is applied to the transmitting/receiving coil 13 through matching and transmitting/receiving switch 18. The spin echo signal detected by the transmitter/receiver coil 13 is matched and received by the receiver 19 through the transmitter/receiver switch 18, amplified and detected, and the received output is taken into the computer 22 through the timing controller 21. The computer 22 supplies a timing waveform to the gradient magnetic field amplifier 15, sets a timing frequency to the synthesizer 16, etc. through the control unit 21.

Although the above has described an apparatus for obtaining two-dimensional tomographic images affected by cross-relaxation, this apparatus can also be extended to three dimensions. That is, by using a non-slice-selecting 90° pulse instead of a slice-selecting 90° pulse and imaging while applying phase encoding in two directions, it is possible to obtain a three-dimensional image affected by cross-relaxation. can.

"Effects of the Invention" As described above, according to the present invention, it is possible to display as an image the state of cross-relaxation of nuclear spins between protons of a biopolymer and protons of water in a selected slice plane of a subject. For example, normal tissue and tumor tissue can be better distinguished from each other than when the state of longitudinal relaxation is displayed as an image, and the early detection and progress of cancer can be accurately determined.

[Brief explanation of drawings]

Figure 1 shows the pulse sequence of the projection reconstruction method, Figure 2 shows the pulse sequence of the two-dimensional Fourier method (spin warp method), and Figure 3 shows the pulse sequence of the two-dimensional Fourier method (spin warp method).
Figures A and B show the pulse sequences of the inversion recovery image and the longitudinal relaxation time (T ₁ ) image, respectively; Figures 4A and B are the longitudinal relaxation time (T ₁ ) and cross-relaxation time of rat liver tissue, respectively. Figure 5 shows the pulse sequence of two 90° pulses plus a spoiling pulse to produce the nuclear Overhauser effect using the device according to the invention _. Figures 6 and 7
Each figure shows a model of the behavior of the spin at that time, Figure 8 shows the relationship between the mixing time τ _n and the main cross-relaxation term, and Figure 9 shows the relationship between the two 90° pulses. A diagram showing a pulse sequence in which a ゜ pulse and an echo position movement gradient pulse are added, Figure 10 is a diagram depicting the behavior of spins at that time, and Figure 11 is an Overhauser pulse sequence that selectively saturates and pushes specific nuclear spins. FIG. 12 is a diagram showing the pulse sequence of the imaging method that produces the effect, FIG. 12 is a diagram showing the relationship between the irradiation time τ and signal intensity, and FIG. 13 is a block diagram showing the configuration of the apparatus of the present invention. .

Claims (1)

[Claims] 1. A means for generating a static magnetic field; and a means for applying a high-frequency electromagnetic field to a subject placed in the static magnetic field to create a nuclear overlap between protons of a biopolymer of the subject and protons of water. means for producing a Hauser effect; and means for irradiating the subject with a high-frequency electromagnetic field to excite nuclear spins of protons in the subject after producing the nuclear Overhauser effect in the nuclear spin of the subject; A nuclear magnetic resonance tomographic image forming apparatus comprising: means for detecting the nuclear magnetic resonance signal; and means for creating an image affected by cross relaxation in response to the nuclear magnetic resonance signal in the subject. .