WO2006080417A1

WO2006080417A1 - Somatic measurement device and method thereof

Info

Publication number: WO2006080417A1
Application number: PCT/JP2006/301278
Authority: WO
Inventors: Hideo Utsumi
Original assignee: Kyushu University, National University Corporation
Priority date: 2005-01-28
Filing date: 2006-01-27
Publication date: 2006-08-03
Also published as: JP2006204551A

Abstract

[PROBLEMS] To provide a somatic measurement device and method for obtaining a somatic tissue image by utilizing various magnetic resonances such as an electronic spin resonance and a nuclear magnetic resonance. [MEANS FOR SOLVING PROBLEMS] A somatic measurement device includes first magnetic field generation means for generating a magnetic field of a predetermined size, second magnetic field generation means for generating a magnetic field greater than the magnetic field of the first magnetic field generation means, measurement object moving means for moving a somatic object to be measured between the first and the second magnetic field generation means in synchronization with irradiation of an RF pulse, and measurement means for measuring a tissue image in the somatic object to be measured according tot he signal detected according to the RF pulse.

Description

Specification

Biological measuring device and method

Technical field

The present invention relates to a living body measurement apparatus for obtaining a tissue image of a living body using various magnetic resonances such as electron spin resonance and nuclear magnetic resonance.

Background art

[0002] The number of patient reserves related to oxidative stress in Japan is now estimated to be in the millions. Here, the oxidative stress is caused by the fact that the living body cannot sufficiently process the active oxygen generated by the endogenous or exogenous cause of the living body. Oxidative stress is known to be involved in many pathologies and aging such as cancer, lifestyle-related diseases, post-ischemic reperfusion injury, and inflammation.

In recent years, attention has been focused on the relationship between oxidative stress and free radicals such as active oxygen and active nitrogen species. If excessive generation of active oxygen 'free radicals occurs, the generation and elimination of the active oxygen in the living body will be lost, resulting in a state of oxidative stress. Reactive oxygen 'free radicals cause various diseases by damaging lipids, nucleic acids, proteins and carbohydrates.

[0004] Oxidative stress is thought to be involved in some form of almost all diseases. However, the basis is mostly indirect, and there is no clear evidence as to whether active oxygen production is the primary cause of the disease or whether it is secondarily related to the progression of the disorder. . What kind of reactive oxygen force in the living body When, where, how, what, and what reacts, it becomes possible to perform non-invasive image analysis in oxidative stress model animals. It can be useful information for elucidation of kinetics and development of anti-acidic drugs.

[0005] As an apparatus for detecting free radicals, there is an ESR imaging apparatus (ESRI). ESR (Electr on Spin Resonance) is an abbreviation for electron spin resonance, and the magnetic moment of the free radical's unpaired electron spin is observed by electromagnetic resonance absorption. Equipment. By using this ESR spectrometer, which is an improved ESR spectrometer for living organisms, radicals can be measured while alive in the entire experimental animal. It is possible to analyze the image of the cloth.

[0006] The inventors have been involved in the development of a drug with the mechanism of anti-acidic action, and at the development stage, the biometric ESR / spin probe method was used for anti-cerebral ischemia in reperfusion injury model rats. We have succeeded in clarifying the oxidative expression. It was also clarified that anti-ulcer drugs inhibit the formation of wrinkles in the gastric cavity in gastric ulcer model rats. In addition, biomedical ESR's spin probe method, such as Kampo medicine for gastric ulcers, is very useful as a method for evaluating the in vivo effects of antioxidant drugs.

[0007] That is, the development of a living body measuring apparatus capable of detecting such free radicals is directly related to the health and welfare of the people, and has great social significance. In addition, this research makes it possible to evaluate and create new antioxidant drugs, and its economic ripple effects are immeasurable.

Patent Document 1: Japanese Patent No. 3117847

Disclosure of the invention

Problems to be solved by the invention

[0008] By the way, in the conventional method described above, only free radicals can be seen, and therefore there is a problem that the site for producing active oxygen / free radicals' tissue cannot be specified. To solve this problem, there is an ESRI 'MRI fusion type magnetic resonance imaging analyzer that can superimpose an MRI image of an organ on an active oxygen' free radical image (ESRI). When this device is used, the in vivo behavior of the probe applied by various routes can be imaged.

[0009] A nuclear 'electron double resonance device (PEDRI) is also effective in analyzing the dynamics of free radicals. PEDRI shifts the electron spin of a living body by ESR irradiation and causes an energy transition to a nuclear spin. Then, by performing MRI measurements, the nuclear spin Boltzmann distribution can be enhanced by a maximum (theoretical value) of 330 times that of the normal nuclear spin Boltzmann distribution. In other words, the sensitivity can be increased by 330 times (theoretical value) compared to normal MRI measurement. As a result of application to an ulcerative colitis model, it has been found that it is very useful for image analysis of redox behavior in oxidative stress diseases.

[0010] However, in general, such a PEDRI or ERSIZMRI combined measurement apparatus has a problem that the resolution of the obtained image is low. In other words, the equipment under development in the United States In each case, the external magnetic field of the MRI is several tens of mT (millitesla) (Dr. Zweier; Ohio State University, Dr. Halpern; According to Dr. Lurie's proposal from Aberdeen University, UK, which has obtained a basic MRI patent, it is 500 mT (millitesla) (however, the sample size is about 10 mm). This is because the sensitivity and resolution of magnetic resonance depend on the magnitude of the external magnetic field, while all conventional devices use a single magnetic field generator and convert the external magnetic field to the Field Cycle method (Dr 丄This is due to the fact that the external magnetic field of the MR I device cannot be increased because urie is conducting a US patent.

[0011] The inventors have also been developing equipment for several years with reference to this Field Cycle method. Due to the limitations of sensitivity and resolution described above, it is possible to perform more accurate analysis using conventional equipment. It came to the conclusion that there is a limit.

Therefore, an object of the present invention is to provide a composite that can dramatically improve the sensitivity and resolution of electron spin resonance and magnetic resonance compared to a conventional biological measurement apparatus without using the Field Cycle method. It is providing a type | mold biological measurement apparatus.

Means for solving the problem

[0013] In order to solve the above-described problem, according to the present invention, a first magnetic field generating means for generating a magnetic field of a predetermined magnitude and a magnetic field larger than the magnetic field of the first magnetic resonance means are generated. A second magnetic field generating means to be moved, a measurement object moving means for moving the measurement target living body between the first and second magnetic field generating apparatuses in synchronization with the irradiation of the RF pulse, and the RF pulse according to There is provided a living body measurement apparatus comprising: a measuring unit that measures a tissue image in a living body to be measured based on a detected signal.

[0014] According to one embodiment, the second magnetic resonance means is for generating a magnetic field of at least 1 Tesla and exciting nuclear magnetic resonance. The first magnetic field generating means is for exciting electron spin resonance.

[0015] Further, the measurement object moving means is not limited to a short time, but preferably within 1 second, the movement of the measurement object between the first and second magnetic field generation means. It is preferably configured to complete within 0.7 seconds.

[0016] According to such a configuration, compared to a conventional biological measurement apparatus using the Field Cycle method. In addition, it is possible to obtain a composite biological measuring apparatus capable of dramatically improving the sensitivity and resolution of electron spin resonance and magnetic resonance.

That is, as a result of preliminary experiments by the inventors, the relaxation time of biological water molecules after electron spin excitation is close to 1 second, and electron spin excitation and MRI for ESR are performed in the same external magnetic field. It became clear that there was no need. Based on this new knowledge, we made a prototype and experimented with an external MRI magnetic field and an ESR external magnetic field, and found that the MRI external magnetic field was increased to 1 Tesla or more, and the ESR magnetic field was increased. It has been shown that high-sensitivity and high-resolution images can be obtained by moving experimental animals within 1 second (for example, about 0.5 seconds) between (8 millitesla). The present invention has been completed as a technique.

[0018] According to such a configuration, the second external magnetic field generation means is used as an ESRI external magnetic field generation apparatus and a PEDRI electron spin excitation apparatus, and the first external magnetic field generation means is used as an MRI and PEDRI It can be used as an external magnetic field generator. Therefore, the time-change image of radical amount can be obtained by PEDRI and the qualitative change image can be obtained by spectrum 'space 4D ESRIZMRI, and the magnetic field by the second external magnetic field generation means can be increased, so high sensitivity' high resolution You will get an image. Furthermore, as mentioned above, since the electronic spin excitation device in PEDRI and the external magnetic field generator and resonator in ESRI can be shared, it is possible to obtain a highly effective device with a simple configuration through integration. Can do.

[0019] Further, according to a further embodiment of the present invention, the measurement means applies a plurality of probes having different in-vivo localization in a measurement target living body, and separates microscopic voids separated through a cell membrane. The tissue image between them is separated and image analysis is performed simultaneously. In this case, the plurality of probes having different in vivo localizations are -troxyl compounds labeled with different markers (preferably N 14 and N 15).

[0020] According to such a configuration, it is possible to simultaneously analyze the nanospace in the living body.

[0021] According to another embodiment of the present invention, a first magnetic field generating means for generating a magnetic field of a predetermined magnitude, and a first magnetic field for generating a magnetic field larger than the magnetic field of the first magnetic resonance means. Measurement object movement process to move the measurement target living body between the two magnetic field generation means in synchronization with the irradiation of the RF pulse and measurement based on the signal detected according to the RF pulse. And a measuring step for measuring a tissue image in the target living body.

[0022] In addition, a step of applying a plurality of -troxi probes with different in-vivo localizations labeled with N14 and N15 in a measurement target living body, and two magnetic fields having different sizes in the measurement target There is also provided a biological measurement method comprising the steps of: applying and simultaneously measuring different tissue images in the measurement target living body based on a signal detected based on the label.

[0023] According to such a configuration, it is possible to obtain a method for standardizing kinetic analysis including 'redox metabolism' and brain function evaluation by applying and optimizing to various oxidative stress state models and cerebral dysfunction models such as schizophrenia. it can. In other words, it is possible to greatly contribute to the elucidation of active oxygen dynamics in the development of oxidative stress diseases and the development of anti-acidic drugs.

[0024] Other features and remarkable effects not described above of the present invention can be clearly understood by those skilled in the art from the section of the best mode described below.

BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, embodiments of the present invention will be described with reference to the drawings.

FIG. 1 is a schematic configuration diagram showing a living body measuring apparatus 1 of the present invention, and FIG. 2 is a perspective view of the living body measuring apparatus 1.

[0027] This apparatus basically includes a first external magnetic field generator 2 for low magnetic fields (for example, ESRIZPEDRI in this embodiment) and a second external magnetic field generator for high magnetic fields (for example, MRIZPEDRI in this embodiment). The magnetic field generator 3 is connected.

[0028] For convenience of description, the second external magnetic field generator 3 will be described from the second external magnetic field generator 3. The second external magnetic field generator 3 is supported by the support base 4 and the support base 4 and has a large-diameter cylindrical shape. A housing 5 having an outer shape and a cylindrical superconducting magnet 6 that is installed inside one end of the housing 5 and generates a static magnetic field in an inner diameter portion 8 of the housing 5 are provided. Further, a magnetic field gradient coil 7 is installed on the inner diameter surface of the housing 5, and a magnetic field gradient of a predetermined scale corresponding to a predetermined MR pulse case is generated in a predetermined number of times in the generated static magnetic field. It is supposed to be. This second external magnetic field generator 3 provides an external static magnetic field for MRIZPEDR I. On the other hand, the first external magnetic field generator 2 has an electromagnet 11, a magnetic field gradient coil 12, and a magnetic field sweep coil 13 disposed concentrically with the other end of the housing 5. To do. This first external magnetic field generator 2 provides an external static magnetic field of ESR and an excitation magnetic field in PEDRI in the inner diameter portion 15 of the electromagnet 11.

[0030] The first and second external magnetic field generators 2 and 3 are arranged so that their central axes coincide with each other, and cylindrical inner first RF coils 16 (resonance) are provided in the inner diameter portions 8 and 15 thereof. And a second RF coil 17 are provided on the concentric axes. The first and second RF coils 16 and 17 form a radio frequency (RF) high frequency (microwave) magnetic field in a direction perpendicular to the static magnetic field.

In addition, a linear moving device 19 is installed between the first and second external magnetic field generators 2 and 3 along the central axes of the first and second RF coils 16 and 17. Yes. The linear moving device 19 includes a guide 20 installed on the central axis and a measurement target living body holding unit 21 slidably provided on the guide 20. The linear moving device 19 is driven by, for example, a linear motor. In this case, as shown in FIG. 3, the stator 22 provided in the guide 20 and also having a permanent magnet force, and the support It comprises a mover 23 which is provided on the part side and also has an electromagnetic magnet force and also has an electromagnet force arranged in the longitudinal direction. By switching the polarity of the mover 23 at a predetermined cycle, it can be driven and stopped.

The control of this device will be described. First, the first external magnetic field generation device 2 is connected to the control unit 27 via the first static magnetic field generation driver 25. The first static magnetic field generation driver 25 is connected to a power source (not shown) for supplying power to the air core coil type electromagnet 11, the magnetic field gradient coil 12, and the magnetic field sweep coil 13, and the control unit 27 The air core coil type electromagnet 11, the magnetic field gradient coil 12, and the magnetic field sweep coil 13 are controlled by an instruction from. According to this embodiment, the force is not limited to this. For example, the strength of the static magnetic field generated by the first external magnetic field generator 2 is 8 mT, the gap width is 15 cm, the three-dimensional gradient magnetic field is 100 mTZm, and the magnetic field sweep coil. The strength of 13 magnetic fields is 2mTZs.

The second external magnetic field generation device 3 is connected to the control unit 27 via a second static magnetic field generation driver 26. The second static magnetic field generation driver 26 includes the superconducting magnet 6 and a magnetic field gradient. A power supply (not shown) for supplying power to the distribution coil 7 is connected, and the superconducting magnet 6 and the magnetic field gradient coil 7 are driven by an instruction to the control unit 27. According to this embodiment, the strength of the static magnetic field generated by the second external magnetic field generator 3 is 2T (tesla), the gap width is 20 cm, and the force is a three-dimensional gradient magnetic field lOmTZm. . As will be described in detail later, the strength of this static magnetic field is 70 times that of the current PEDRI, which can improve the sensitivity by about 100 times.

In addition, the first and second RF coils 16 and 17 are connected to the control unit 27 via an RF coil driver 28 and a detection signal receiving unit 29. The RF coil driver 28 is connected to a power source (not shown) for supplying power to the RF coils 16 and 17, and drives the RF coils 16 and 17 in accordance with a sequence commanded by the control unit 27. . A high frequency pulse is applied to the RF coils 16, 17, and a high frequency magnetic field is applied to the measurement target on the holding unit 21. The electron spin resonance signal Z magnetic resonance signal received by the RF coils 16, 17 is received by the detection signal receiving unit 29 and passed to the control unit 27.

[0035] Here, although not limited to this, the spatial resolution and imaging time of ESRI measurement are the space within lmm in the spectral space 3D image and 4D image when FOV is lcm. The resolution can be acquired within 1 minute in 3 dimensions and within 10 minutes in 4 dimensions.

The linear drive device 19 is connected to the control unit 27 via a linear drive device driver 30. The linear drive device 19 moves the measurement object between the first external magnetic field generation device 2 and the second external magnetic field generation device 3, and follows the sequence commanded from the control unit 27 in accordance with the RF coil. The measurement target is driven at a timing synchronized with the application of the high-frequency magnetic field by 16 and 17. The drive time from the first external magnetic field generator 2 to the second external magnetic field generator 3 is preferably within 1 second, more preferably within 0.7 seconds, and in this embodiment it is 0. Set to 5 seconds.

On the other hand, the control unit 27 includes a measurement sequence processing unit 31, a PEDRI measurement processing unit 32, and an ESRIZMRI measurement processing unit 33. The measurement sequence processing unit 31 supplies power to the first and second external magnetic field generators 2 and 3 and the first and second RF coils 16 and 17. A sequence and a measurement sequence in the first and second RF coils 16 and 17 to control the apparatus. The PEDRI measurement processing unit 32 and the ESRIZMRI measurement processing unit 33 perform image processing based on the electron spin resonance signal and the magnetic resonance signal obtained according to the measurement sequence, and display the result on the monitor 35.

[0038] Further, in this embodiment, this image processing is performed by synthesizing a plurality of -troxyl probes having different in-vivo localizations (for example, different membrane permeabilities), and combining them with N14 and N15, respectively. Labeling makes it possible to separate and analyze images of minute spaces via binding to cell membranes (thickness nanometers) or receptors.

Note that the control unit 27 described above actually has a computer system power, and the processing units 31 to 33 also have a computer software program power stored in a hard disk or the like. These computer software programs are appropriately called and executed by the CPU to function as components of the present invention!

Next, the operation of this apparatus will be described.

First, a small animal to be measured, such as a mouse, is placed on the holding unit 21 of the linear moving device 19. In this example, a spatial image analysis is performed on a brain function in a redox metabolism abnormality due to an oxidative stress disease or schizophrenia in a measurement target.

[0042] In addition, a probe agent derivatized with -troxyl radical labeled with N14 or N15 is introduced into this mouse. In this example, multiple probes with different biolocalizations (eg, different membrane permeability) are labeled with N14 and N15, via binding to cell membranes (thickness nanometers) or receptors. Enables separation and simultaneous image analysis of minute spaces.

That is, in order to perform image analysis with a high-sensitivity / high-resolution apparatus as in this embodiment, it is essential to develop a contrast agent with higher sensitivity / high selectivity. As one element for obtaining a high-sensitivity image, a method of narrowing the spectral line width of the contrast agent itself can be considered. The line width of the contrast agent can be reduced by reducing the proton localization of the unpaired electron density of the contrast agent itself. On the other hand, in order to trace the radical reaction in vivo, it is necessary to synthesize a -troxyl spin probe contrast agent having a redox potential corresponding to the redox potential of each radical species. Therefore, molecular design is performed using the theoretical calculation scientific methods frequently used by pharmaceutical manufacturers, and the unpaired electron density (acid-reduction potential) of the new contrast agent is calculated. By conducting organic chemical synthesis based on the design and verifying the biochemical reactivity of the contrast agent, we have developed the most suitable contrast agent for tracking in vivo free radical reactions.

In this embodiment, about 10 types of -troxyl probes having substituents having various properties were newly synthesized using a molecular design technique utilizing a computer. These include, but are not limited to: a) intravascular half-life of 20 minutes or longer, b) high retention probe with intracellular retention of 5 minutes or longer, c) cell membrane directional probe, d) blood brain Includes barrier-passing probes. Furthermore, in order to double the sensitivity, a probe agent synthesized so that the resonance absorption line width is within 0.5 gauss (commercially available nitroxyl probe is 1.0 gauss or more) was used.

Next, the linear drive device 19 is driven, and the measurement object is positioned in the first RF coil 16 in the static magnetic field 8 by the first external magnetic field generation device 2. Next, high frequency is radiated from the first RF coil 16 and the sweep coil 13 is driven to sweep the magnetostatic field at high speed. As a result, unpaired electrons in the measurement object absorb high frequency, and the electron spin is resonantly excited. The ESR signal is received by the detection signal receiving unit 29 due to the reflection of the microwave.

[0046] When the ESR measurement in the first external magnetic field generator 2 is completed, the linear drive device 19 is driven, and within 0.7 seconds, in this example 0.5 seconds, the measurement target is set in the second external magnetic field. Move to generator 3. As a result, the object to be measured is placed in a very strong static magnetic field of 1T or more, in this example 2T. As a result, the resonantly excited electron spin causes a nuclear spin energy transition. Next, the detection signal receiving unit 29 receives a signal that can also obtain a measurement target force by high-frequency irradiation using the second RF coil 17.

The signal received by the detection signal receiving unit 29 in this way is received by the control unit 27 and processed by the measurement processing units 32 and 33. The ESRIZMRI measurement processing unit 33 synthesizes an image obtained by superimposing an ERS image and an MRI image from the ERS signal obtained from the first RF coil 16 and the MRI signal obtained from the second RF coil 17. . In addition, the PEDRI measurement processing unit 32 synthesizes an image showing the nuclear spin distribution by processing the signal obtained from the second RF coil 17. [0048] According to such a configuration, it is possible to obtain a biological measurement apparatus with extremely high sensitivity and high resolution.

[0049] That is, as described above, the inventors have conducted preliminary experiments that the relaxation time of biological water molecules after electron spin excitation is nearly 1 second, and it is necessary to perform electron spin excitation and MRI in the same external magnetic field. Based on this new knowledge, we have completed a device that separates the external magnetic field for MRI and the external magnetic field for ESR. Since the external magnetic field for MRI and the external magnetic field for ESR are independent, the external magnetic field for MRI can be made very large to obtain higher sensitivity and spatial resolution. In this embodiment, the magnitude of the magnetic field of the first external static magnetic field generator for MRI is 2 Tesla, and the measurement target is moved between ESR magnetic fields (8 millitesla) in about 0.5 seconds. . According to such a configuration and method, an ESRZMRI superimposed image with higher sensitivity and higher resolution can be obtained without using the Field Cycle method.

[0050] According to such a configuration, the second external magnetic field generator 3 is used as an MRI and PEDRI external magnetic field generator, and the first external magnetic field generator 2 is used as an ESRI external magnetic field generator and PEDRI. PEDRI can also be fused. As described above, the external magnetic field of the MRI can be increased, so that a highly sensitive and high resolution PEDRI image can be obtained.

[0051] In other words, the time-change image of the radical amount can be obtained by PEDRI, the qualitative change image can be obtained by spectrum 'space 4D ESRI / MRI, and the magnetic field by the second external magnetic field generator 3 can be increased. High sensitivity and high resolution images can be obtained. Furthermore, as described above, since the electron spin excitation device in PEDRI and the external magnetic field generator and resonator in ESRI can be shared, a compact device with a very small installation area can be obtained by integration. be able to.

[0052] Furthermore, according to a further embodiment of the present invention, the PEDRI measurement processing unit 32 and the ESRIZMRI measurement processing unit 33 apply a plurality of probes having different in-vivo localizations within a measurement target. In addition, a tissue image of a minute space separated through a cell membrane is separated and simultaneously analyzed. According to such a configuration, it is possible to simultaneously analyze the nanospace in the living body. [0053] It should be noted that the present invention is not limited to the above-described embodiment, and various modifications can be made without departing from the scope of the invention.

For example, in the above embodiment, the electromagnet 11 of the first external magnetic field generator and the superconducting magnet 6 of the second external magnetic field generator are provided separately in the horizontal direction. It is not limited to. As shown in FIG. 4, a superconducting magnet 6 ′ for generating a high magnetic field is provided over the entire length of the housing 5, and the electromagnet 11 is used for demagnetization to reduce the magnetic field for the first external magnetic field device. You may comprise. That is, in this case, the low magnetic field generated by the first external magnetic field generator 2 is generated by the superconducting magnet 6 ′ and the electromagnet 11 ′.

[0055] In the above embodiment, the living body measurement apparatus is ESRIZMRIZPEDRI, but is not limited thereto. The present invention can be applied to any apparatus that moves a sample between different external magnetic field generators.

Brief Description of Drawings

FIG. 1 is a schematic configuration diagram showing an embodiment of the present invention.

[Fig. 2] Same perspective view.

FIG. 3 is a longitudinal sectional view showing the same linear movement mechanism.

FIG. 4 is a schematic configuration diagram showing another embodiment.

Explanation of symbols

1 ·· -Biometric device

2 '' First external magnetic field generation means

3 '' First external magnetic field generator

4 ... Support base

5 ...-No, Uzing

6 ... 'Superconducting magnet

7. Magnetic field gradient coil

8 ... Inside the inner diameter

11… Electromagnet

12… Magnetic field gradient coil IB "magnetic field sweep coil

IS -... inside the inner diameter

16 · “First RF coil

17 ··· Second RF coil

19 · Linear movement device

20 · "Guide

1 ... Holding part

2 ... Stator

3 ... Mover

5 · '' · First static magnetic field generation driver 6 · '' · Second static magnetic field generation driver 7 ·· Control unit

8 ... RF coil driver

9 • Detection signal receiver

0-Linear drive driver 1 ... 'Measurement sequence processor 2 · PEDRI measurement processor 3 · MRI measurement processor

5 ... 'Monitor

Claims

The scope of the claims

[1] first magnetic field generating means for generating a magnetic field of a predetermined magnitude;

A second magnetic field generating means for generating a magnetic field larger than the magnetic field of the first magnetic field generating means;

A measurement object moving means for moving the measurement target living body between the first and second magnetic field generation means in synchronization with the irradiation of the RF pulse;

Measuring means for measuring a tissue image in a measurement target living body based on a signal detected according to the RF pulse;

A living body measurement apparatus characterized by comprising:

[2] In the biological measurement device according to claim 1,

The living body measuring apparatus, wherein the second magnetic field generating means is for generating a magnetic field of at least 1 Tesla and exciting nuclear magnetic resonance.

[3] In the biological measurement device according to claim 1,

The measuring means includes

A living body measuring apparatus characterized by applying a plurality of probes having different in vivo localities in a measurement target living body, separating different living body tissue images, and simultaneously performing image analysis.

[4] In the biological measurement device according to claim 3,

The biological measurement apparatus, wherein the plurality of probes having different in vivo localizations are label compounds labeled with different markers.

[5] In the biological measurement device according to claim 4,

The biological measurement apparatus, wherein the plurality of probes having different in vivo localizations are -troxyl compounds labeled with N14 and N15.

[6] An object to be measured between a first magnetic field generating means for generating a magnetic field of a predetermined magnitude and a second magnetic field generating means for generating a magnetic field larger than the magnetic field of the first magnetic resonance means. A measurement object moving process for moving the organism in synchronization with the irradiation of the RF pulse,

A measurement process for measuring a tissue image in a measurement target living body based on a signal detected according to the RF pulse;

A biological measurement method characterized by comprising:

[7] In the biological measurement method according to claim 6,

The biological measurement method, wherein the second magnetic field generating means is for generating a magnetic field of at least 1 Tesla and exciting nuclear magnetic resonance.

[8] In the biological measurement method according to claim 6,

The measurement step includes

A living body measuring method characterized by applying a plurality of probes having different in vivo localization in a living body to be measured, separating different living body tissue images, and simultaneously performing image analysis.

[9] In the biological measurement method according to claim 8,

The biological measurement method, wherein the plurality of probes having different in-vivo localizations are label compounds labeled with different markers.

[10] In the biological measurement method according to claim 9,

The biological measurement method, wherein the plurality of probes having different in vivo localizations are -troxyl compounds labeled with N14 and N15.

[11] A step of applying a plurality of -troxy probes labeled with N14 and N15 and having different in-vivo localizations in a measurement target body;

Applying two magnetic fields of different sizes to the measurement object;

A step of simultaneously measuring different tissue images in a living body to be measured based on a signal detected based on the label;

A biological measurement method characterized by comprising:

[12] The biological measurement method according to claim 11, wherein

The step of applying two magnetic fields having different sizes further includes a measurement object moving step of moving the measurement object between two magnetic field generators.